FitSugar

Chewing Gum Fights Stress?

FitSugar — Mon, 05 Jan 2009 03:00:00 -0800

My favorite candy, chewing gum, not only fights heartburn, but it looks like it may also help conquer stress. Chomping on a piece of gum, and may I add that the gum should definitely be sugar-free, was found to decrease levels of the stress hormone cortisol by 17 percent. In recent laboratory tests, chewing gum also increased alertness and improved performance. It sounds like a winning combination but might be a bit more complicated than unwrapping a stick of gum.

While working your jaw, chewing gum may increase the flow of blood to your brain helping you think more clearly, but it can also tire out the muscles of the jaw and lead to overuse injuries of the joint, like TMJ. For full disclosure, I should mention that the study on gum for stress release was funded by gum maker Wrigley, who is "committed to advancing and sharing scientific research that explores the benefits of chewing gum." While I thoroughly enjoy chewing gum, I think I will also stick to my free and injury-free stress reduction technique, breathing. How about you?

Source

Kristen Wants to Quit Smoking, Do It Too!

FitSugar — Fri, 13 Nov 2009 04:30:06 -0800

Kristen Stewart made the first step in kicking her cigarette habit - admitting to Entertainment Weekly that she's ready to give it up, saying, "I'm going to stop smoking. I'm not such a good smoker, anyway. It's not in my bones. I'm gonna drop it." More power to the gorgeous Twilight star, and here's hoping she sticks with it. Now, if you're out to ditch your own smoking habit, read on to kick-start your plan to quit.

Get Support - If you're ready to quit, whether or not you have friends that are smokers, make your decision known. Spreading the word that you're quitting will let your friends and family know that you'll need support. If you're having a tough day, reach out to friends. Instead of caving for a cigarette break, invite a friend for a long walk, a movie, or a workout class. Having the support of your loved ones who back your decision to quit will help give you a united front against your bad habit.

Don't Underestimate the Power of the Patch (or Gum) - Forms of nicotine replacement therapy have been shown to double your chances of quitting smoking, and can help you fight the urge to light up when you're facing nicotine withdrawal, reducing your feelings of depression and restlessness.

For more ways to help you quit, read more.

Find Another Way to Relieve Stress - Since smoking can often be a way to unwind, you'll have to find a healthier outlet to relieve stress. Combat stress with an alternative that's good for the body like a yoga class, soothing massage, or aromatherapy. Natural herbal supplements like lavender, valerian, and passionflower can aid with feelings of anxiousness and help ease tension. Short bouts of exercise can help relieve cravings, too.

Don't Drink - Alcohol and smoking are social activities that seem to go hand in hand. Plus, since alcohol naturally lowers our inhibitions, it can be harder to resist the temptation of a smoke when you're out drinking. So, when you're trying to quit, it's probably best to avoid the bar scene altogether.

Get Your Fill of Fruits and Veggies - Since many smokers fear gaining weight when they quit, many choose to diet while they're trying to give it up. But it's not a great idea to limit your food intake or choices, which can leave you feeling even more irritable while you're working to quit. Instead, think of quitting in a healthier way - focus on how eliminating the toxins from cigarettes will help to purify your body, and choose healthy fruits and veggies to fill you up. You might even try juicing your servings of fruit and vegetables. The nutrient-rich juice can help to curb cravings and can even help flush toxins from the body.

Stress

FitSugar — Wed, 08 Oct 2008 17:35:26 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Some people are pre-programmed for a heightened response to stress by conditions in the womb. Pregnant women under stress who eat a diet high in protein and low in carbohydrates have babies with higher cortisol levels. Later on, these levels increase in response to stress.
The impact of stress on the heart and circulation system is becoming more clear. Stress causes the body to release inflammatory markers that may worsen heart and circulatory diseases as well as inflammatory disease, such as rheumatoid arthritis. High levels of inflammatory markers are associated with increased risk of heart attack and stroke. Extreme stress can also produce a condition that mimics a heart attack, but is reversible. People under severe stress can experience irregular heart beats that make them susceptible to sudden cardiac death.
Stress also increases the risk of developing type 2 diabetes in women.
Traumatic stress has long been known to cause amnesia, emotional numbness, nightmares, and memory problems. Now it is known that traumatic emotional stress can cause permanent changes in the brain that interfere with the normal way information is accepted, coded, and retrieved.
The good news is that our physical response to stress is increasingly understood. Knowing what occurs at the cellular level may help researchers find more ways to counteract the detrimental physical and emotional effects of stress.

Introduction

Stress affects most people in some way. Acute (sudden, short-term) stress leads to rapid changes throughout the body. Almost all body systems (the heart and blood vessels, the immune system, the lungs, the digestive system, the sensory organs, and brain) gear up to meet the perceived danger.

These stresses could prove beneficial in a critical, life-or-death situation. Over time, however, repeated stressful situations put a strain on the body that may contribute to physical and psychological problems. Chronic (long-term) stress can have real health consequences and should be addressed like any other health concern.

Fortunately, research is showing that lifestyle changes and stress-reduction techniques can help people learn to manage their stress.

People can experience stress from external or internal factors.

External stressors include adverse physical conditions (such as pain or hot or cold temperatures) or stressful psychological environments (such as poor working conditions or abusive relationships). Humans, like animals, can also experience external stressors.
Internal stressors can also be physical (infections, inflammation) or psychological (such as intense worry about a harmful event that may or may not occur). As far as anyone can tell, internal psychological stressors are rare or absent in most animals except humans.

Stressors can also be defined as short-term (acute) or long-term (chronic).

Acute Stress. Acute stress is the reaction to an immediate threat, commonly known as the fight or flight response. The threat can be any situation that is perceived, even subconsciously or falsely, as a danger.

Common acute stressors include:

Noise (which can trigger a stress response even during sleep)
Crowding
Isolation
Hunger
Danger
Infection
High technology effects (playing video games, frequently ringing mobile phones)
Imagining a threat or remembering a dangerous event

Under most circumstances, once the acute threat has passed, levels of stress hormones return to normal. This is called the relaxation response.

Chronic Stress. Frequently, modern life poses ongoing stressful situations that are not short-lived. The urge to act (to fight or flee) must therefore be controlled. Stress, then, becomes chronic.

Common chronic stressors include:

On-going highly pressured work
Long-term relationship problems
Loneliness
Persistent financial worries

The Body's Response

The best way to envision the effect of acute stress is to imagine yourself in a primitive situation, such as being chased by a bear.

In response to seeing the bear, a part of the brain called the hypothalamic-pituitary-adrenal (HPA) system is activated.

Release of Steroid Hormones and the Stress Hormone Cortisol. The HPA systems trigger the production and release of steroid hormones (glucocorticoids), including the primary stress hormone cortisol. Cortisol is very important in organizing systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with the bear.

Release of Catecholamines. The HPA system also releases certain neurotransmitters (chemical messengers) called catecholamines, particularly those known as dopamine, norepinephrine, and epinephrine (also called adrenaline).

Catecholamines activate an area inside the brain called the amygdala, which appears to trigger an emotional response to a stressful event. In the case of the bear, this emotion is most likely fear.

Release of Neuropeptide S. The brain releases neuropeptide S, a small protein that modulates stress by decreasing sleep and increasing alertness and a sense of anxiety. This gives the person a sense of urgency to run away from the bear.

Effects on Long- and Short-Term Memory. During the stressful event, catecholamines also suppress activity in areas at the front of the brain concerned with short-term memory, concentration, inhibition, and rational thought. This sequence of mental events allows a person to react quickly, either to fight the bear or to flee from it. It also interferes with the ability to handle difficult social or intellectual tasks and behaviors during that time.

On the other hand, neurotransmitters at the same time signal the hippocampus (a nearby area in the brain) to store the emotionally loaded experience in long-term memory. In primitive times, this brain action would have been essential for survival, since long-lasting memories of dangerous stimuli (such as the large bear) would be critical for avoiding such threats in the future.

The stress response also affects the heart, lungs, and circulation:

As the bear comes closer, the heart rate and blood pressure increase instantaneously.
Breathing becomes rapid, and the lungs take in more oxygen.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen throughout the body. Blood flow may actually increase 300 - 400%, priming the muscles, lungs, and brain for added demands.

The effect on the immune system from confrontation with the bear is similar to organizing a defensive line of soldiers to potentially critical areas. The steroid hormones reduce the activity in parts of the immune system, so that specific infection fighters (including important white blood cells) or other immune molecules can be repositioned. These immune-boosting troops are sent to the body's front lines where injury or infection is most likely to occur, such as the skin and the lymph nodes.

As the bear gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The stress effect moves blood flow away from the skin to support the heart and muscle tissues. This also reduces blood loss in the event that the bear causes a wound. The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

Stress shuts down digestive activity, a nonessential body function during short-term periods of hard physical work or crisis.

Once the threat has passed and the effect has not been harmful (for example, the bear has not wounded the human), the stress hormones return to normal. This is known as the relaxation response. In turn, the body's systems also return to normal.

Complications

In prehistoric times, the physical changes in response to stress were an essential adaptation for meeting natural threats. Even in the modern world, the stress response can be an asset for raising levels of performance during critical events, such as a sports activity, an important meeting, or in situations of actual danger or crisis.

If stress becomes persistent and low-level, however, all parts of the body's stress apparatus (the brain, heart, lungs, vessels, and muscles) become chronically over- or under-activated. Such chronic stress may produce physical or psychological damage over time. Acute stress can also be harmful in certain situations, particularly in individuals with preexisting heart conditions.

Studies suggest that the inability to adapt to stress is associated with the onset of depression or anxiety. In one study, two-thirds of subjects who experienced a stressful situation had nearly 6 times the risk of developing depression within that month.

Some evidence suggests that repeated release of stress hormones produces hyperactivity in the hypothalamic-pituitary-adrenal (HPA) system, and disrupts normal levels of serotonin, the nerve chemical that is critical for feelings of well-being. Some people appear to be more at risk for an overactive HPA system under stress, including those with the personality traits that cause perfectionism. Certainly, on a more obvious level, stress reduces the quality of life by reducing feelings of pleasure and accomplishment. In addition, relationships are often threatened in times of stress.

The full impact of mental stress on heart disease is just coming to light, but the underlying mechanisms are not always clear. Stress can certainly influence the activity of the heart when it activates the automatic part of the nervous system that affects many organs, including the heart. Such actions and others could theoretically affect the heart badly in several ways:

Sudden stress increases the pumping action and rate of the heart, while at the same time causing the arteries to constrict (narrow). This restricts blood flow to the heart. A 2002 study suggested that such actions may be responsible for some cases of acute stress that have been associated with a higher risk for serious heart problems. These problems include heart rhythm abnormalities and heart attacks, and even death in people with heart disease.
Emotional effects of stress alter the heart rhythms, which could pose a risk for serious arrhythmias (rhythm abnormalities) in people with existing heart rhythm disturbances.
Stress causes blood to become stickier (possibly in preparation of potential injury), increasing the likelihood of an artery-clogging blood clot.
Stress appears to impair the clearance of fat molecules in the body, raising blood-cholesterol levels, at least temporarily.
Stress that leads to depression appears to be associated with increased intima-medial thickness, a measure of the arteries that signifies worsening blood vessel disease.
Chronic stress may lead to the production of immune factors called cytokines, although study results vary widely. Cytokines produce an inflammatory response that is now believed to be responsible for damaging the arteries. Such damage contributes to heart disease. New studies indicate that some people under stress may have increased levels of C-reactive protein (CRP), a risk marker for heart attack. Each 1 mg/L increase in CRP has been linked to a 20% increased risk of myocaridal ischemia, a condition that signals poor blood flow to the heart muscle.
Stress causes the body to release inflammatory markers into the bloodstream. These markers may worsen heart disease or increase the risk of heart attack or stroke.
Studies have reported an association between stress and high blood pressure, which may be more pronounced in men than in women. According to some evidence, people who regularly experience sudden spikes in blood pressure (caused by mental stress) may, over time, develop injuries in the inner lining of their blood vessels. In one 20-year study, for example, men who periodically measured highest on the stress scale were twice as likely to have high blood pressure as those with normal stress.

Evidence is still needed to confirm any clear-cut relationship between stress and heart disease. For example, a 2002 study in Scotland found no greater risk for actual heart disease or heart events even in men who reported higher mental stress. In fact, higher stress was associated with fewer heart events. Men with high stress levels did tend to complain of chest pain and to go to the hospital for it more often than those with lower stress. They also went to the hospital more often.

Evidence links stress to heart disease in men, particularly in work situations where they lack control. The association between stress and heart problems in women is weaker, and there is some evidence that the ways women cope with stress may be more heart-protective. In one study, men were more apt than women to use alcohol or eat less healthily in response to stress, which might account for their higher heart risks from stress. Different stressors may affect genders differently. In one study, work stress was associated with a higher risk for heart disease in men, but marital stress -- not work stress -- was associated with more severe heart disease in women with existing heart problems.

A condition called stress cardiomyopathy (or Takotsubo cardiomyopathy) is widely recognized. In this disease, intense emotional or physical stress causes severe but reversible heart dysfunction. The patient experiences chest pain, and EKGs and echocardiograms indicate a heart attack, but further tests show no underlying obstructive coronary artery disease.

Acute emotional stress can create abnormal heartbeats. MRI studies show that asymmetric brain activity may play a role in making a stressed heart susceptible to ventricular arrhythmias by creating electrical instability. In some patients, this can cause sudden cardiac death.

Psychological stress is also recognized as a possible cause of acute coronary syndrome (ACS), a collection of symptoms that signify heart attack or approaching heart attack. In one study of men who suffered ACS at work or up to 2 hours after work, many of the men were found to have anger and negative emotions. A 2007 review of studies on blood qualities, coagulation, fibrinolysis, and platelet reactivity found that high levels of psychological stress are associated with harmful changes to the blood. The research suggests that stress has the potential to trigger ACS, particularly in patients with heart disease. The studies also suggest that the risk is greatest immediately after the stressful incident, rather than during it.

Stress Reduction and Heart Disease. Studies suggest that treatments that reduce psychological distress improve long-term outlook in people with heart disease, including after a heart attack. Evidence indicates that stress management programs may reduce the risk of heart attacks by up to 75% in people with heart disease. Specific stress management techniques may help some problems but not others. For example, acupuncture in one study helped people with heart failure but had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure.

One survey revealed that men who had a more intense response to stressful situations, such as waiting in line or problems at work, were more likely to have strokes than those who did not report such distress. In some people, prolonged or frequent mental stress causes an exaggerated increase in blood pressure.

Chronic stress affects the immune system in complicated ways, and may have various results.

Susceptibility to Infections. Chronic stress appears to blunt the immune system's response to infections, and may even impair a person's response to immunizations. Several studies have shown that people under chronic stress have low white blood cell counts and are vulnerable to colds. Once a person catches a cold or flu, stress can make symptoms worse. People who carry the herpes virus or HIV may be more susceptible to viral activation following exposure to stress. Even more serious, some research has found that HIV-infected men with high stress levels progress more rapidly to AIDS when compared to those with lower stress levels.

Inflammatory Response. Some evidence suggests that chronic stress triggers an over-production of certain immune factors called cytokines. In excess levels, these chemicals can have very damaging effects. A recent study found that students unable to cope with stress had high levels of TNF-alpha, an inflammatory cytokine. Such findings may partly explain the association between chronic stress and numerous diseases, including heart disease and asthma.

Whether or not stress causes or aggravates cancer is not entirely clear. One study reported no association between stressful life events and recurrence in women who had been treated for breast cancer. Nevertheless, some animal studies suggest that lack of control over stress (not simply stress itself) had negative effects on immune function and contributed to tumor growth.

That being said, a 2007 study found that stress activates a gene that may cause metastatic cancer, as measured by increasing levels of the marker AGR2.

Although stress reduction techniques have no effect on survival rates, studies show that they are very helpful in improving a cancer patient's quality of life. Stress is also known to be one cause of hyponatremia (low plasma sodium levels) in cancer patients. Fortunately, this imbalance can be corrected with drugs called AVP-receptor agonists, developed for use in heart failure.

The brain and intestines are strongly related, and are controlled by many of the same hormones and parts of the nervous system. Indeed, some research suggests that the gut itself has features of a primitive brain. It is not surprising then that prolonged stress can disrupt the digestive system, irritating the large intestine and causing diarrhea, constipation, cramping, and bloating. Excessive production of digestive acids in the stomach may cause a painful burning.

Irritable Bowel Syndrome. Irritable bowel syndrome (or spastic colon) is strongly related to stress. With this condition, the large intestine becomes irritated, and its muscular contractions are spastic rather than smooth and wave-like. The abdomen is bloated, and the patient experiences cramping and alternating periods of constipation and diarrhea. Sleep disturbances due to stress can make irritable bowel syndrome even worse.

Peptic Ulcers. It is now well-established that most peptic ulcers are either caused by the H. pylori bacteria or the use of nonsteroidal anti-inflammatory (NSAID) medications (such as aspirin and ibuprofen). Nevertheless, studies still suggest that stress may predispose someone to ulcers, or sustain existing ulcers. Some experts estimate that social and psychological factors play some contributing role in 30 - 60% of peptic ulcer cases, whether they are caused by H. pylori or NSAIDs. In any case, some experts believe that the anecdotal relationship between stress and ulcers is so strong that attention to psychological factors is still warranted.

Inflammatory Bowel Disease. Although stress is not a cause of inflammatory bowel disease (Crohn's disease or ulcerative colitis), there are reports of an association between stress and symptom flare-ups. One study, for example, found that while short-term (over the previous month) stress did not significantly exacerbate ulcerative colitis symptoms, long-term perceived stress tripled the rate of flare-ups compared to patients who did not report feelings of stress.

Stress can have varying effects on eating problems and weight.

Weight Gain. Often stress is related to weight gain and obesity. Many people develop cravings for salt, fat, and sugar to counteract tension. As a result, they gain weight. Weight gain can occur even with a healthy diet, however, in some people exposed to stress. In addition, the weight gained is often abdominal fat, a predictor of diabetes and heart problems.

The release of cortisol, a major stress hormone, appears to encourage abdominal fat and may be the primary connection between stress and weight gain. Cortisol is a glucocorticoid. These hormones, along with insulin, appear to be responsible for stress-related food cravings. A 2005 study showed that hormonally induced cravings for "comfort foods" may have a biological benefit for managing stress. Eating comfort foods appears to reduce the negative hormonal and behavioral changes associated with stress, which might lessen the impact of stress on an individual. Carbohydrates in particular have been found to significantly increase levels of tryptophan and large neutral amino acids. This produces serotonin, which improves mood and performance under stress.

A 2007 study proposes a "reward-based stress eating" model. In this theory, stress and tasty, high-calorie foods cause the brain to make chemicals called endogenous opioids. These neurotransmitters help protect against the harmful effects of stress by slowing activity of a brain process called the hypothalamic-pituitary-adrenal (HPA) axis, thus weakening the stress response. Repeated stimulation of the reward pathways through stress-induced HPA stimulation, eating tasty food, or both, may lead to changes in the brain that cause compulsive overeating.

Weight Loss. Some people suffer a loss of appetite and lose weight during periods of stress. In rare cases, stress may trigger hyperactivity of the thyroid gland, stimulating appetite but causing the body to burn up calories at a faster than normal rate.

Eating Disorders. Chronically elevated levels of stress chemicals have been observed in patients with anorexia and bulimia. Some studies, however, have not found any strong link between stress and eating disorders. More work is needed to determine if changes in stress hormones are a cause or result of eating disorders.

Chronic stress has been associated with the development of insulin resistance, a condition in which the body is unable to use insulin effectively to regulate glucose (blood sugar). Insulin resistance is a primary factor in diabetes. In the Healthy Women Study, a large population of healthy women was studied for 15 years. Very stressful life events and severe depression greatly increased the risk of developing insulin resistance.

In another study of more than 33,000 Swedish workers, the development of type 2 diabetes was strongly correlated with work stress and low emotional support. However, the effect was seen in women, but not in men.

Stress can also exacerbate existing diabetes by impairing the patient's ability to manage the disease effectively.

Researchers are attempting to find the relationship between pain and emotion, but the area is complicated by many factors, including effects of personality types, fear of pain, and stress itself. A recent study suggests that chronic pain may impair the action of neutrophils, thereby weakening the immune response.

Muscular and Joint Pain. Stress may intensify chronic pain caused by arthritis and other conditions. According to a study on patients with rheumatoid arthritis, however, stress management techniques do not appear to have much effect on arthritic pain. Psychological distress also plays a significant role in the severity of back pain. Some studies have clearly associated job dissatisfaction and depression to back problems, although it is still unclear if stress is a direct cause of the back pain.

Headaches. Tension-type headaches are highly associated with stress and stressful events. Sometimes the headache does not start until long after the stressful event has ended. Additionally, stress can contribute to the development of headaches or cause headaches to occur more often.

Some research suggests that people who suffer from tension-type headaches may have some biological predisposition for translating stress into muscle contractions. Among the wide range of possible migraine triggers is emotional stress (although the headaches often erupt after the stress has eased). One study suggested that women with migraines tend to have personalities that over-respond to stressful situations.

The tensions of unresolved stress frequently cause insomnia, generally keeping the stressed person awake or causing awakening in the middle of the night or early morning. This appears to be due to the fact that stress causes physiological arousal during non-rapid eye movement (NREM) sleep.

Sexual Function. Stress can lead to diminished sexual desire and an inability to achieve orgasm in women. Stress response can cause androgen levels to drop, causing temporary impotence in men. Part of the stress response involves the release of brain chemicals that constrict the smooth muscles of the penis and its arteries. This constriction reduces the blood flow into and increases the blood flow out of the penis, which can prevent erection.

Premenstrual Syndrome. Some studies indicate that the stress response in women with premenstrual syndrome may be more intense than in those without the syndrome.

Fertility. Stress may even affect fertility. Stress hormones have an impact on the hypothalamus gland, which produces reproductive hormones. Severely elevated cortisol levels can even shut down menstruation. One small study reported a significantly higher incidence of pregnancy loss in women who had both high stress and prolonged menstrual cycles. Another reported that women with stressful jobs had shorter periods than women with low-stress jobs.

Effects on Pregnancy. Old wives' tales about a pregnant woman's emotions affecting her baby may have some credence. Stress may cause physiologic alterations, such as increased adrenal hormone levels or resistance in the arteries, which may interfere with normal blood flow to the placenta. Maternal stress during pregnancy has been linked to a higher risk for miscarriage, lower birth weights, and increased incidence of premature births. Some evidence also suggests that stress experienced by expectant mothers can even influence the way in which the baby's brain and nervous system will react to stressful events. Indeed, one study found a higher rate of crying and low attention in infants of mothers who had been stressed during pregnancy.

Menopause. A drop in estrogen levels during perimenopause and menopause may be responsible for changes in mood precipitated by stress. Estrogen replacement therapy can soften this response to stressful events.

Stress affects the brain, particularly memory, but the effects vary widely depending on whether the stress is acute or chronic.

Effect of Acute Stress on Memory and Concentration. Studies indicate that the immediate effect of acute stress impairs short-term memory, particularly verbal memory. On the plus side, high levels of stress hormone during short-term stress have been associated with enhanced memory storage and greater concentration on immediate events. The difference in effect may be due to how cortisol impacts glucocorticoid receptors in the hippocampus and prefrontal cortex. In a study of 20 men and 20 women, those whose cortisol levels increased in response to unpleasant, emotionally arousing photos had less memory recall later than those whose cortisol levels did not rise.

Effect of Chronic Stress on Memory. If stress becomes chronic, sufferers often experience loss of concentration at work and home, and they may become inefficient and accident-prone. In children, the physiologic responses to chronic stress can clearly inhibit learning. Chronic stress in older people may play an even more important role in memory loss than the aging process. In one study, for example, older adults with low stress hormone levels tested as well as younger adults in cognitive tests; those with higher stress levels tested 20 - 50% lower.

Studies have connected long-term exposure to excess amounts of cortisol (a major stress hormone) to shrinking of the hippocampus, the brain’s memory center. For example, two studies reported that groups who suffered from post-traumatic stress disorder (Vietnam veterans and women who suffered from sexual abuse) displayed up to 8% shrinking of the hippocampus. It is not yet known if this shrinking is reversible.

Allergies. Stress has been related to skin allergies. Some research suggests that stress, not indoor pollutants, may actually be a cause of the so-called sick-building syndrome. Sick-building syndrome produces allergy-like symptoms, such as eczema, headaches, asthma, and sinus problems, in office workers.

Compulsive Hoarding. People with obsessive-compulsive disorder (OCD) and compulsive hoarding are far more likely to have experienced a traumatically stressful event than people with OCD who are not hoarders. Hoarders who have experienced traumatic events have significantly more severe hoarding than those who have not been traumatized. The strongest association with traumatic stress is found in the clutter factor of compulsive hoarding, rather than in difficulty discarding objects.

Chronic Fatigue. Stress increases the risk of developing chronic fatigue syndrome, although studies suggest that high levels of emotional instability may genetically predispose someone to the syndrome.

Skin Disorders. Stress plays a role in worsening numerous skin conditions, including hives, psoriasis, acne, rosacea, and eczema, and is one of the most common causes of eczema. Unexplained itching may also be caused by stress. Evidence suggests that experiencing the stress of a traumatic event (parental divorce or separation, or a severe disease in a family member) before age 2 increases the risk of developing eczema.

Unexplained Hair Loss (Alopecia Areata). Alopecia areata is hair loss that occurs in localized (individual) patches. The cause is unknown, but stress is suspected as a player in this condition. For example, hair loss often occurs during periods of intense stress, such as mourning.

Teeth and Gums. Stress has now been implicated in increasing the risk for periodontal disease, which is disease in the gums that can cause tooth loss.

People under chronic stress often turn to alcohol abuse or tobacco use for relief. The damage these self-destructive habits cause under ordinary circumstances is compounded by the physiological effects of stress itself. Many people also resort to abnormal eating patterns or passive activities, such as watching television. The results of a national survey, released in February 2006, show that: "Americans engage in unhealthy behaviors such as comfort eating, poor diet choices, smoking and inactivity to help deal with stress."

Alcohol affects receptors in the brain that reduce stress. Lack of nicotine increases stress in smokers, which creates a cycle of dependency on smoking. One study indicated that nicotine has calming effects in women but not in men. In fact, in the study, smoking increased aggression in men.

The cycle is self-perpetuating: a sedentary routine, an unhealthy diet, alcohol abuse, and smoking all promote heart disease. They also interfere with sleep patterns, and lead to increased rather than reduced tension levels. Drinking four or five cups of coffee, for example, can cause changes in blood pressure and stress hormone levels similar to those produced by chronic stress. Animal fats, simple sugars, and salt are known contributors to health problems.

Conditions with Similar Symptoms

The physical symptoms of anxiety disorders mirror many symptoms of stress, including:

A fast heart rate
Rapid, shallow breathing
Increased muscle tension

Anxiety is an emotional disorder, however, and is characterized by feelings of apprehension, uncertainty, fear, or panic. Unlike stress, the triggers for anxiety are not necessarily or even usually associated with specific stressful or threatening conditions. Some individuals with anxiety disorders have numerous physical complaints, such as headaches, gastrointestinal disturbances, dizziness, and chest pain. Severe cases of anxiety disorders are debilitating, and interfere with career, family, and social spheres.

Depression can be a disabling condition, and, like anxiety disorders, may result from chronic stress. A 2005 study of Canadian workers found that individuals with a high level of work-related stress are more than twice as likely to experience a major depressive episode, compared with people under less stress. Evidence also suggests that certain people may be genetically susceptible to depression after stressful life events. Depression also mimics some of the symptoms of stress, including changes in appetite, sleep patterns, and concentration. Serious depression, however, is distinguished from stress by feelings of sadness, hopelessness, loss of interest in life, and, sometimes, thoughts of suicide. Acute depression is also accompanied by significant changes in the patient's functioning. Professional therapy may be needed in order to determine if depression is caused by stress, or if it is the primary problem.

Post-traumatic stress disorder (PTSD) is a reaction to a very traumatic event, and it is actually classified as an anxiety disorder. The event that brings on PTSD is usually outside the norm of human experience, such as intense combat or sexual assault. The patient struggles to forget the traumatic event and frequently develops emotional numbness and event-related amnesia. Often, however, there is a mental flashback, and the patient re-experiences the painful circumstance in the form of dreams and disturbing thoughts and memories. These thoughts and dreams resemble or recall the trauma. Other symptoms may include lack of pleasure in formerly enjoyed activities, hopelessness, irritability, mood swings, sleep problems, inability to concentrate, and an excessive startle-response to noise.

Treatment

Perhaps the best general approach for treating stress can be found in the elegant passage by Reinhold Niebuhr, "Grant me the courage to change the things I can change, the serenity to accept the things I can't change, and the wisdom to know the difference." The process of learning to control stress is life-long, and will not only contribute to better health, but a greater ability to succeed in one's own agenda.

Stress can be a factor in a variety of physical and emotional illnesses, which should be professionally treated. Many stress symptoms are mild and can be managed by over-the-counter medications (for example, aspirin, acetaminophen, or ibuprofen for tension headaches; antacids, anti-diarrhea medications, or laxatives for mild stomach distress). A physician should be consulted, however, for physical symptoms that are out of the ordinary, particularly those that get worse or wake a person up at night. A mental health professional should be consulted for unmanageable acute stress or for severe anxiety or depression. Often short-term therapy can resolve stress-related emotional problems.

In choosing specific strategies for treating stress, several factors should be considered.

No single method is always successful: A combination of approaches is generally most effective.
What works for one person does not necessarily work for someone else.
Stress can be positive as well as negative. Appropriate and controllable stress provides interest and excitement and motivates the individual to greater achievement. A lack of stress may lead to boredom and depression.

Stress may play a part in making people vulnerable to illness. A physician or psychologist should be consulted if there are any indications of accompanying medical or psychological conditions, such as heart symptoms, significant pain, anxiety, or depression.

People often succeed in relieving stress for the short term. However, they go back to previous ways of stressful thinking and behaving because of outside pressure, long-held beliefs, or habits. The following are some obstacles to managing stress:

The fight or flight urge: The very idea of relaxation can feel threatening, because it is perceived as letting down one's guard. For example, an over-demanding boss may put a subordinate into a psychological state of fighting-readiness, even though there is no safe opportunity for the subordinate to fight back or express anger. Stress builds up, but the worker has the illusion, even subconsciously, that the stress itself is providing safety or preparedness. For this reason, the employee does nothing to correct the condition.
Many people are afraid of being perceived as selfish if they engage in stress-reducing activities that benefit only themselves. The truth is that self-sacrifice (in the form of not reducing one’s stress) may be inappropriate and even damaging, if the person making the sacrifice is unhappy, angry, or physically unwell.
Some people believe that certain emotional responses to stress, such as anger, are natural and unchangeable features of personality. Research has shown, however, that with cognitive behavioral therapy, individuals can be taught to change their emotional reactions to stressful events.

It is essential to remember that reducing stress and staying relaxed clears the mind, so it can begin appropriate actions to get rid of the stress-ridden conditions.

Although treating stress cannot cure medical problems, stress management can be a very important part of medical treatment. Specific stress reduction approaches may benefit different medical problems. For example, acupuncture in one study helped reduce harmful heart muscle actions in people with heart failure, but it had no effect on blood pressure. Relaxation methods, on the other hand, may help people with high blood pressure. Stress reduction may improve well-being and quality of life for many patients who are experiencing stress because of severe or chronic medical conditions.

Important Note: Never use stress reduction techniques as the only treatment, or in place of proven treatments, for any medical condition.

Risk Factors

At some point in their lives virtually everyone will experience stressful events or situations that overwhelm their natural coping mechanisms. In one poll, 89% of respondents indicated that they had experienced serious stress in their lives. Some people are simply biologically prone to stress. Many outside factors influence susceptibility as well.

Conditions Most Likely To Produce Stress-Related Health Problems. Conditions that are most likely to be associated with stress and negative physical effects include the following:

An accumulation of persistent stressful situations, particularly those that a person cannot easily control (for example, high-pressured work plus an unhappy relationship)
Persistent stress following a severe acute response to a traumatic event (such as an automobile accident)
Acute stress accompanying serious illness, such as heart disease

Factors That Influence the Response to Stress. People respond to stress differently, depending on different factors:

Early nurturing: Abusive behavior towards children may cause long-term abnormalities in the hypothalamus-pituitary system, which regulates stress.
Personality traits: Certain people have personality traits that cause them to over-respond to stressful events.
Genetic factors: Some people have genetic factors that affect stress, such as having a more or less efficient relaxation response. One study found a genetic abnormality in serotonin regulation that was connected with a heightened reaction of heart rates and blood pressure in response to stress. (Serotonin is a brain chemical involved with feelings of well-being.)
Immune regulated diseases: Certain diseases that are associated with immune abnormalities (such as rheumatoid arthritis or eczema) may actually weaken a response to stress.
The length and quality of stressors: Naturally, the longer the duration and more intense the stressors, the more harmful the effects.

Individuals at Higher Risk for Stress. Studies indicate that the following people are more vulnerable to the effects of stress than others:

Older adults: As people age, achieving a relaxation response after a stressful event becomes more difficult. Aging may simply wear out the systems in the brain that respond to stress, so that they become inefficient. The elderly, too, are very often exposed to major stressors such as medical problems, the loss of a spouse and friends, a change in a living situation, and financial worries. No one is immune to stress, however, and it may simply go unnoticed in the very young and old.
Women in general and working mothers specifically: Working mothers, regardless of whether they are married or single, face higher stress levels and possibly adverse health effects, most likely because they bear a greater and more diffuse work load than men or other women. This has been observed in women in the U.S. and in Europe. Such stress may also have a domino and harmful effect on their children. It is not clear, however, if stress has the same adverse effects on women's hearts as it does on men's.
Less educated individuals.
Divorced or widowed individuals: Numerous studies indicate that unmarried people generally do not live as long as their married contemporaries.
Anyone experiencing financial strain, particularly long-term unemployed and those without health insurance.
People who are isolated or lonely.
People who are targets of racial or sexual discrimination.
People who live in cities.

Children are frequent victims of stress because they are often unable to communicate their feelings accurately. They also have trouble communicating their responses to events over which they have no control. Certain physical symptoms, notably repeated abdominal pain without a known cause, may be indicators of stress in children.

Various conditions can affect their susceptibility to stress.

Low Birth Weight. One study reported that low birth weight and slow growth up until age 7 was related to stress in adulthood.

Parental Stress. Parental stress, especially in mothers, is a particularly powerful source of stress in children, even more important than poverty or overcrowding. In a 2002 study, for example, young children of mothers who were highly stressed (particularly if they were depressed) tended to be at high risk for developing stress-related problems. This was especially true if the mothers were stressed during both the child's infancy and early years. Some evidence even supports the old idea that stress during pregnancy can have adverse effects on the infant's mood and behavior. Older children with stressed mothers may become aggressive and anti-social. One study suggested that stress-reduction techniques in parents may improve their children's behavior.

Gender Differences in Adolescent Stress. Adolescent boys and girls experience equal amounts of stress, but the source and effects may differ. Girls tend to become stressed from interpersonal situations, and stress is more likely to lead to depression in girls than in boys. For boys, however, specific events, such as changing schools or getting poor grades, appear to be the major sources of stress.

A report issued in October 2006 by the American Academy of Pediatrics recommends more unstructured play time for children. The report notes that today’s overscheduled, hurried lifestyle that many children experience is a source of stress and anxiety in some children.

In a 1999 study of 46,000 workers, health care costs were 147% higher in workers who were stressed or depressed than in others who were not. Furthermore, according to one survey, 40% of American workers describe their jobs as very stressful, making job-related stress an important and preventable health hazard.

Several studies are now suggesting that job-related stress is as great a threat to health as smoking or not exercising. Stress impairs concentration, causes sleeplessness, and increases the risk for illness, back problems, accidents, and lost time from work. Work stress can lead to harassment or even violence while on the job. At its most extreme, chronic stress places a burden on the heart and circulation that in some cases may be fatal. The Japanese even have a word for sudden death due to overwork, karoushi.

Not all work stress is harmful. However, studies suggest the following job-related stressors may increase people's -- particularly men's -- health risks:

Having no say in decisions that affect one's responsibilities
Unrelenting and unreasonable performance demands
Lack of effective communication and conflict-resolution methods among workers and employers
Lack of job security
Night-shift work, long hours, or both
Too much time spent away from home and family
Wages not matching levels of responsibility

Reducing Stress on the Job. Many institutions within the current culture, while paying lip service to stress reduction, put intense pressure on individuals to behave in ways that increase tension. Yet, there are numerous effective management tools and techniques available to reduce stress. Furthermore, treatment for work-related stress has proven benefits for both the employee and employer. In one study, at the end of 2 years, a company that instituted a stress management program saved nearly $150,000 in workers compensations costs (the cost of the program was only $6,000). Other studies have reported specific health benefits resulting from workplace stress-management programs. In one of the studies, workers with hypertension experienced reduced blood pressure after even a brief (16-hour) program that helped them manage stress behaviorally.

In general, however, few workplaces offer stress management programs, and it is usually up to the employee to find their own ways to reduce stress. Here are some suggestions:

Seek out someone in the Human Resources department or a sympathetic manager and communicate concerns about job stress. Work with them in a non-confrontational way to improve working conditions, letting them know that productivity can be improved if some of the pressure is off.
Establish or reinforce a network of friends at work and at home.
Restructure priorities and eliminate unnecessary tasks.
Learn to focus on positive outcomes.
If the job is unendurable, plan and execute a career change. Send out resumes or work on transfers within the company.
If this isn't possible, be sure to schedule daily pleasant activities and physical exercise during free time.

It may be helpful to keep in mind that bosses are also victimized by the same stressful conditions they are imposing. For example, in one study of male managers in three Swedish companies, those who worked in a bureaucracy had greater stress-related heart risks than those who worked in companies with social supports.

Caregivers of Family Members. Studies show that caregivers of physically or mentally disabled family members are at risk for chronic stress. One study reported that overall mortality rates were over 60% higher in caregivers who were under constant stress. Spouses caring for a disabled partner are particularly vulnerable to a range of stress-related health threats, including influenza, depression, heart disease, and even poorer survival rates. Caring for a spouse with even minor disabilities can induce severe stress.

Specific risk factors that put caregivers at higher risk for severe stress, or stress-related illnesses, include:

Caregiving wives: Some studies suggest that wives experience significantly greater stress from caregiving than husbands do.
Having a low income.
Being African-American: African-American people tend to be in poorer physical health, and have lower incomes, than Caucasians. They therefore face greater stress as caregivers to their spouses than their white counterparts.
Living alone with the patient.
Helping a highly dependent patient.
Having a difficult relationship with the patient.

Intervention programs that are aimed at helping the caregiver approach the situation positively can reduce stress, and help the caregiver maintain a positive attitude. A 2002 program also demonstrated that moderate-intensity exercise was very helpful in reducing stress and improving sleep in caregivers.

Health Professional Caregivers. Caregiving among the health professionals is also a high risk factor for stress. One study, for example, found that registered nurses with low job control, high job demands, and low work-related social support experienced very dramatic health declines, both physically and emotionally.

People who are less emotionally stable or have high anxiety levels tend to experience specific events as more stressful than others. Some doctors describe an exaggerated negative response to stress as "catastrophizing" the event (turning it into a catastrophe). Nevertheless, a 2003 study of patients with anxiety disorder did not find any differences in actual physical response to stress (heart rate, blood pressure, release of stress hormones) compared to people without anxiety.

The lack of an established network of family and friends predisposes one to stress disorders and stress-related health problems, including heart disease and infections. A study, meanwhile, reported that older people who maintain active relationships with their adult children are buffered against the adverse health effects of chronic stress-inducing situations, such as low income or lower social class. Another study suggested this may be because people who live alone are unable to discuss negative feelings as a means to relieve their stress.

Studies of people who remain happy and healthy despite many life stresses conclude that most have very good networks of social support. One study indicated that support even from strangers reduced blood pressure surges in people undergoing a stressful event. Many studies suggest that having a pet helps reduce medical problems aggravated by stress, including heart disease and high blood pressure.

Lifestyle Changes

A healthy lifestyle is an essential companion to any stress-reduction program. General health and stress resistance can be enhanced by regular exercise, a diet rich in a variety of whole grains, vegetables, and fruits, and by avoiding excessive alcohol, caffeine, and tobacco.

Of interest, a 2003 study suggested that fish oil, which has been associated with a lower risk for heart disease and stroke, may blunt some of the harmful effects of mental stress on the heart.

In one study, high doses of vitamin C reduced stress levels and blood pressure. The doses given were higher than the recommended upper limit of 2,000 mg per day. High doses may cause headaches and diarrhea. Long-term use increases risk for kidney stones and has other adverse effects in specific individuals.

Exercise in combination with stress management techniques is extremely important for many reasons:

Exercise is an effective distraction from stressful events.
Exercise may directly blunt the harmful effects of stress on blood pressure and the heart (exercise protects the heart in any case).

Usually, a varied exercise regime is more interesting, and thus easier to stick to. Start slowly. Strenuous exercise in people who are not used to it can be very dangerous and any exercise program should be discussed with a physician. In addition, half of all people who begin a vigorous training regime drop out within a year. The key is to find activities that are exciting, challenging, and satisfying. The following are some suggestions:

Sign up for aerobics classes at a gym.
Brisk walking is an excellent aerobic exercise that is free and available to nearly anyone. Even short brisk walks can relieve bouts of stress.
Swimming is an ideal exercise for many stressed people, including pregnant women, individuals with musculoskeletal problems, and those who suffer exercise-induced asthma.
Yoga or Tai Chi can be very effective, combining many of the benefits of breathing, muscle relaxation, and meditation while toning and stretching the muscles. The benefits of yoga may be considerable. Numerous studies have found it beneficial for many conditions in which stress is an important factor, such as anxiety, headaches, high blood pressure, and asthma. It also elevates mood and improves concentration and the ability to focus.

As in other areas of stress management, making a plan and executing it successfully develops feelings of mastery and control, which are very beneficial in and of themselves. Start small. Just 10 minutes of exercise three times a week can build a good base for novices. Gradually build up the length of these every-other-day sessions to 30 minutes or more.

Cognitive-behavioral techniques (CBT) are among the most effective ways of reducing stress. A 2005 study found that CBT training can have a long-term impact one’s ability to cope with stress. In the study, participants received CBT training and were exposed to a stressful situation 4 months later. The participants who had received CBT training had significantly less stress-induced cortisol responses compared with individuals who had received no stress management training. This effect was observed in both men and women, although the CBT had a greater effect on men. CBT may be particularly helpful when the source of stress is chronic pain or a chronic disease. In fact, in a study of patients with HIV, CBT was more helpful than support groups for improving well-being and quality-of-life.

A typical CBT approach includes identifying sources of stress, restructuring priorities, changing one's response to stress, and finding methods for managing and reducing stress.

Identifying Sources of Stress. One key component in most CBT approaches is a diary that keeps an informal inventory of daily events and activities. While this exercise might itself seem stress producing (and yet one more chore), it need not be done in painstaking detail. A few words accompanying a time and date are usually enough to serve as reminders of significant events or activities.

The first step is to note activities that put a strain on energy and time, trigger anger or anxiety, or precipitate a negative physical response (such as a sour stomach or headache).

Also note positive experiences, such as those that are mentally or physically refreshing or produce a sense of accomplishment.

After a week or two, try to identify two or three events or activities that have been significantly upsetting or overwhelming.

Questioning the Sources of Stress. Individuals should then ask themselves the following questions:

Do these stressful activities meet my goals or someone else's?
Have I taken on tasks that I can reasonably accomplish?
Which tasks are under my control and which ones aren't?

Restructuring Priorities: Adding Stress Reducing Activities. The next step is to attempt to shift the balance from stress-producing to stress-reducing activities. Eliminating stress is rarely practical or feasible, but there are many ways to reduce its impact.

Consider as many relief options as possible. Examples include:

Listen to music. Music is an effective stress reducer in both healthy individuals and people with health problems. In one study, for example, students who listened to a well-known gentle classical piece of music during a stressful task had reduced feelings of anxiety, heart rate, and blood pressure.
Take long weekends or, ideally, vacations.
If the source of stress is in the home, plan times away, even if it is only an hour or two a week.
Replace unnecessary time-consuming chores with pleasurable or interesting activities.
Make time for recreation. This is as essential as paying bills or shopping for groceries.
Own a pet. In a study of people with high blood pressure, pet owners had much lower blood pressure increase in response to stress than non-owners. Note that owning a pet was beneficial only for people who like animals to begin with.

Discuss Feelings. The concept of communication and letting your feelings out has been so excessively promoted and parodied that it has nearly lost its value as good psychological advice. Nevertheless, feelings of anger or frustration that are not expressed in an acceptable way may lead to hostility, a sense of helplessness, and depression.

Expressing feelings does not mean venting frustration on waiters and subordinates, boring friends with emotional minutia, or wallowing in self-pity. In fact, because blood pressure may spike when certain chronically hostile individuals become angry, some therapists strongly advise that just talking, not simply venting anger, is the best approach, especially for these people.

The primary goal is to explain and assert one's needs to a trusted individual in as positive a way as possible. Direct communication may not even be necessary. Writing in a journal, writing a poem, or composing a letter that is never mailed may be sufficient.

Expressing one's feelings solves only half of the communication puzzle. Learning to listen, empathize, and respond to others with understanding is just as important for maintaining the strong relationships necessary for emotional fulfillment and reduced stress.

Keep Perspective and Look for the Positive. Reversing negative ideas and learning to focus on positive outcomes helps reduce tension and achieve goals. The following steps, using an example of a person who is alarmed at the prospect of giving a speech, may be useful:

First, identify the worst possible outcomes (forgetting the speech, stumbling over words, humiliation, audience contempt).
Rate the likelihood of these bad outcomes happening (probably very low or that speaker wouldn't have been selected in the first place).
Envision a favorable result (a well-rounded, articulate presentation with rewarding applause).
Develop a specific plan to achieve the positive outcome (preparing in front of a mirror, using a video camera or tape recorder, relaxation exercises).
Try to recall previous situations that initially seemed negative but ended well.

Use Humor. Research has shown that humor is a very effective mechanism for coping with acute stress. Keeping a sense of humor during difficult situations is a common recommendation from stress management experts. Laughter not only releases the tension of pent-up feelings and helps keep perspective, but it appears to have actual physical effects that reduce stress hormone levels. It is not uncommon for people to recall laughing intensely even during tragic events, such as the death of a loved one, and to remember this laughter as helping them to endure the emotional pain.

Relaxation Methods. Since stress is here to stay, everyone needs to develop methods to promote the relaxation response, the natural unwinding of the stress response. Relaxation lowers blood pressure, respiration, and pulse rates, releases muscle tension, and eases emotional strains. This response is highly individualized, but there are certain approaches that seem to work.

Combinations are probably best. For example, in a study of children and adolescents with adjustment disorder and depression, a combination of yoga, a brief massage, and progressive muscle relaxation effectively reduced both feelings of anxiety and stress hormone levels. A 2005 study of organ transplant recipients showed that training in meditation and gentle yoga led to significant improvements in quality of sleep and lessened anxiety and depression.

No one should expect a total resolution of stress from these approaches, but if done regularly, these programs can be very effective.

Acupuncture. Some evidence suggests that acupuncture may also be helpful. It might even improve some physical factors associated with stress and health problems. For example, in a study of heart failure patients, acupuncture improved stress-related heart muscle activity, which could be an important benefit in these patients. However, acupuncture had no effect on stress-related blood pressure or heart rate.

Hypnosis. Hypnosis may also benefit some people with severe stress. In one study of patients with irritable bowel, stress reduction by hypnosis correlated with improvement in many bowel symptoms.


*Deep Breathing Exercises.* During stress, breathing becomes shallow and rapid. Taking a deep breath is an automatic and effective technique for winding down. Deep breathing exercises consciously intensify this natural physiologic reaction and can be very useful during a stressful situation, or for maintaining a relaxed state during the day.	Inhale through the nose slowly and deeply to the count of 10. Make sure that the stomach and abdomen expand, but the chest does not rise. Exhale through the nose, slowly and completely, also to the count of 10. To help quiet the mind, concentrate fully on breathing and counting through each cycle. Repeat five to 10 times, and make a habit of doing the exercise several times each day, even when not feeling stressed.
*Muscle Relaxation.* Muscle relaxation techniques, often combined with deep breathing, are simple to learn and very useful for getting to sleep. In the beginning it is useful to have a friend or partner check for tension by lifting an arm and dropping it. The arm should fall freely. Practice makes the exercise much more effective and produces relaxation much more rapidly. Small studies have reported beneficial effects on blood pressure in patients with high blood pressure who use this technique.	After lying down in a comfortable position without crossing the limbs, concentrate on each part of the body. Maintain a slow, deep breathing pattern throughout this exercise. Tense each muscle as tightly as possible for a count of five to 10, and then release it completely. Experience the muscle as totally relaxed and lead-heavy. Begin with the top of the head and progress downward to focus on all the muscles in the body. Be sure to include the forehead, ears, eyes, mouth, neck, shoulders, arms and hands, fingers, chest, belly, thighs, calves, and feet. Once the external review is complete, imagine tensing and releasing internal muscles.
*Meditation.* Meditation, used for many years in Eastern cultures, is now widely accepted in this country as a relaxation technique. The goal of all meditative procedures, both religious and therapeutic, is to quiet the mind (essentially, to relax thought). Small studies have suggested that regular meditation can benefit the heart and help reduce blood pressure. Better research is needed, however, to confirm such claims. Some recommend meditating for no longer than 20 minutes in the morning after awakening and then again in early evening before dinner. Even once a day is helpful. Note: Meditating before going to bed may cause some people to wake up in the middle of the night, alert and unable to return to sleep. New practitioners should understand that it can be difficult to quiet the mind, and should not be discouraged by lack of immediate results. Several techniques are available. A few are discussed here. The only potential risks from meditating are in people with psychosis, in whom meditating may trigger a psychotic event.	Mindfulness Meditation. Mindfulness is a common practice that focuses on breathing. It employs the basic technique used in other forms of meditation. Sit upright with the spine straight, either cross-legged or sitting on a firm chair with both feet on the floor, uncrossed. With the eyes closed or gently looking a few feet ahead, observe the exhalation of the breath. As the mind wanders, simply note it as a fact and returns to the "out" breath. It may be helpful to imagine your thoughts as clouds dissipating away. Transcendental Meditation (TM). TM uses a mantra (a word that has a specific chanting sound but no meaning). The person meditating repeats the word silently, letting thoughts come and go. In one study, TM was as effective as exercise in elevating mood. Mini-Meditation. The method involves heightening awareness of the immediate surrounding environment. Choose a routine activity when alone. For example: While washing dishes, concentrate on the feel of the water and dishes. Allow the mind to wander to any immediate sensory experience (sounds outside the window, smells from the stove, colors in the room). If the mind begins to think about the past or future, or fills with unformed thoughts or worries, redirect it gently back. This redirection of brain activity from your thoughts and worries to your senses disrupts the stress response and prompts relaxation. It also helps promote an emotional and sensual appreciation of simple pleasures already present in a person's life.
*Biofeedback.* Biofeedback is a technique that measures bodily functions, like breathing, heart rate, blood pressure, skin temperature, and muscle tension. By watching these measurements, you can learn how to alter these functions by relaxing or holding pleasant images in your mind.	During biofeedback, electric leads are taped to a subject's head. The person is encouraged to relax using methods such as those described above. Brain waves are measured and an audible signal is emitted when alpha waves are detected, a frequency which coincides with a state of deep relaxation. By repeating the process, subjects associate the sound with the relaxed state and learn to achieve relaxation by themselves.
*Massage Therapy.* A 2005 report that reviewed data from multiple studies showed that massage therapy decreases cortisol levels. Another 2005 study showed that massage from a stable romantic partner can reduce physiological responses to a subsequent stressful event. In the study, women who received instructed shoulder-neck-massage from their partners before being exposed to stress had lowered cortisol responses, and smaller heart rate increases after the stressful event. Interestingly, massage was more beneficial than receiving social support from the partner, indicating the power of physical touch in managing stress. Several massage therapies are available.	Many massage techniques are available, such as the following: Swedish massage is the standard massage technique. It uses long smooth strokes, and kneading and tapping of the muscles. Shiatsu applies intense pressure to the same points targeted in acupuncture. It can be painful, but people report deep relaxation afterward. Reflexology manipulates acupuncture points in the hands and feet.

Some people who experience chronic stress seek herbal or natural remedies. It should be strongly noted, however, that just as with standard drugs, so-called natural remedies can cause problems, sometimes serious ones.

Probiotics. Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria. They do so through various mechanisms, such as excreting certain acids (for example, lactate, acetate) that inhibit harmful bacteria. They may also compete with them for nutrients. Stress reduces levels of these bacteria. Research even suggests that probiotics may help maintain remission in patients with IBD. In one small study, people suffering from stress and exhaustion significantly reduced their stress symptoms and gastrointestinal complaints when they took a probiotic supplement for 6 months. The specific bacteria that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics include the lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.

Aromatherapy. The smell of lavender has long been associated with a calming effect. In a Japanese study, 14 women who were put in a room with a lavender scent experienced reduced mental stress. Several aromatherapies are now used for relaxation. Use caution, however, as some of the exotic plant extracts in these formulas have been associated with a wide range of skin allergies.

Valerian. Valerian is an herb that has sedative qualities and may reduce stress and associated physical effects. This herb is on the FDA's list of generally safe products. Of note, however, the herb's effects could be dangerously increased if it is used with standard sedatives. Other interactions and long-term side effects are unknown. Side effects include vivid dreams. High doses of valerian can cause blurred vision, excitability, and changes in heart rhythm.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, however, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been numerous reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Special Warning on Kava. Kava has been commonly used to reduce anxiety and stress. It is now highly associated with liver injury and even liver failure in a few cases. Experts now strongly warn against its use.

People seeking relief from stress should be wary of things that promise a quick cure, or plans that include the purchase of expensive treatments. These treatments may be useless and sometimes even dangerous.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.nami.org -- National Alliance for the Mentally Ill
www.nmha.org -- National Mental Health Association
www.amtamassage.org -- American Massage Therapy Association
www.cognitivetherapynyc.com -- American Institute for Cognitive Therapy
www.aabt.org -- Association for the Advancement of Behavior Therapy
www.healthyminds.org -- The American Psychiatric Association
www.naswdc.org -- The National Association of Social Workers
www.aacap.org -- American Academy of Child and Adolescent Psychiatry
www.stress.org -- The American Institute of Stress

References

Ginsburg KR and the Committee on Communications and Committee on Psychosocial Aspects of Child and Family Health. Clinical Report: The Importance of Play in Promoting Healthy Child Development and Maintaining Strong Parent-ChildBonds.Last accessed on 17 October, 2006.

Dallman MF, Pecoraro NC, la Fleur SE. Chronic stress and comfort foods: self-medication and abdominal obesity. Brain Behav Immun. 2005;19:275-280.

Wang J. Work stress as a risk factor for major depressive episode(s). Psychol Med. 2005;35:865-871.

Hammerfald K, Grau M, et al. Persistent effects of cognitive-behavioral stress management on cortisol responses to acute stress in healthy subjects-A randomized controlled trial. Psychoneuroendocrinology. 2005 Sep 22; epub ahead of print.

Kreitzer MJ, Gross CR, Ye X, et al. Longitudinal impact of mindfulness meditation on illness burden in solid-organ transplant recipients. Prog Transplant. 2005;15:166-172.

Field T, Hernandez-Reif M, Diego M, et al. Cortisol decreases and serotonin and dopamine increase following massage therapy. Int J Neurosci. 2005;115:1397-1413.

Ditzen B, Neumann I, Bodenmann G, et al. Romantic Partner Interaction Reduces Endocrine and Autonomic Stress Responses in Women. New Research Abstracts, Annual Meeting of the American Psychiatric Association. Washington, D.C. 2005. Abstract NR140.

Review Date:
10/16/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial policy, editorial process and privacy policy. A.D.A.M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

A.D.A.M. Copyright

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2009 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.

adam.com

Periodontal disease

FitSugar — Wed, 08 Oct 2008 17:35:31 -0700

In This Report

Highlights
Introduction
Symptoms
Causes
Risk Factors
Complications
Prevention
Diagnosis
Treatment
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Symptoms of Periodontal Disease

Symptoms of periodontal disease include red and swollen gums, persistent bad breath, and gum recession and loose teeth. Smoking, certain types of illnesses (diabetes), older age, and other factors increase the risk for periodontal disease. If you have periodontal disease, your dentist may refer you to a periodontist, a dentist who specializes in treating this condition.

Practice Good Dental Hygiene

Consistent good dental hygiene can help prevent gingivitis and periodontitis. The American Dental Association recommends that everyone:

Brush twice daily with a fluoride toothpaste (be sure to replace toothbrushes every 3 - 4 months).
Clean between the teeth with floss or an interdental cleaner.
Eat a well-balanced diet and limit between meal snacks.
Have regular visits with a dentist for teeth cleaning and oral examinations.

Mouthwashes

In 2007, the American Dental Association stated that antimicrobial mouthwashes may provide additional oral health benefits for preventing and reducing gingivitis and plaque. However, they are not a substitute for daily brushing and flossing.

Research

Intensive treatment of periodontal disease may help reduce inflammation and improve blood flow throughout the body, according to a small study published in 2007 in the New England Journal of Medicine. In the study of patients with severe periodontitis, intensive treatment ultimately resulted in improved endothelial function. Poor endothelial function is associated with increased risk for atherosclerosis and heart disease. Researchers are investigating the connection between periodontal disease and heart disease, and whether treatment of periodontal disease can reduce heart disease risk.

Introduction

Periodontal disease refers to a group of problems that arise in the sulcus, the gap between the gum and the tooth.

The part of the mouth that consists of the gum and supporting structures is called the periodontium. It is made up of the following parts:

Gum (gingiva). When healthy, the gingiva is pale pink, firm, and does not move. It has a smooth or speckled texture. The gingival tissue between teeth is shaped like a wedge.
The space between the gum and tooth, called the sulcus
Root surface (the cementum)
Connective tissue
Bone. The crest of the supporting bone, which can be viewed on x-rays, is normally 2 mm below the point where the crown of the tooth meets the root (the cementoenamel junction).

The structure of the tooth includes dentin, pulp and other tissues, blood vessels, and nerves imbedded in the bony jaw. Above the gum line, the tooth is protected by the hard enamel covering.

Periodontal diseases are generally divided into two groups:

Gingivitis, which causes lesions (wounds) that affect the gums
Periodontitis, which damages the bone and connective tissue that supports the teeth

The process starts with bacteria. Even in healthy mouths, the sulcus is teeming with bacteria, but they tend to be harmless varieties. Periodontal disease develops usually because of two events in the oral cavity: an increase in bacteria quantity and a change in balance of bacterial types from harmless to disease-causing bacteria. These harmful bacteria increase in mass and thickness until they form a film called plaque.

Click the icon to see an image of plaque and damaged gum tissue.

In healthy mouths, plaque itself actually provides some barrier against outside bacterial invasion. When it accumulates to excessive levels, however, plaque sticks to the surfaces of the teeth and adjacent gums and causes cellular injury, with subsequent swelling, redness, and heat.

When plaque is allowed to remain in the periodontal area, it transforms into calculus (commonly known as tartar ). This material has a rock-like consistency and grabs onto the tooth surface. It is much more difficult to remove than plaque, which is a soft mass.

The most important component leading to the disease process, however, is the body's persistent immune response to the bacterial plaque. Specific immune factors are released that cause inflammation and damage that eventually destroys the support structures and bone and can lead to tooth loss.

Gingivitis is an inflammation of the gingiva, or gums. Is nearly always chronic, but an acute form infrequently occurs.

Chronic Gingivitis. Ordinary chronic gingivitis affects over 90% of the population. It is characterized by tender, red, swollen gums that bleed easily and may be responsible for bad breath (halitosis) in some cases. Treatment is very effective if initiated early in the course of gingivitis. Without good management, however, the problem can progress.

Periodontitis is characterized by the following:

Gum inflammation, with redness and bleeding.
Deep pockets (greater than 3 mm in depth) form between the gum and the tooth.
Loose teeth, caused by loss of connective tissue structures and bone.

Gingivitis precedes periodontitis, although it doesn't always lead to this more severe condition. In fact, some experts believe it is an entirely different disease. There are different categories of periodontal disease, including:

Chronic Periodontitis. Chronic periodontitis (also referred to as adult periodontitis) may begin in adolescence as a slowly progressing disease that becomes clinically significant in the mid-30s and continues throughout life. Some experts question whether it is a chronic, unrelenting condition and instead suggest that it waxes and wanes depending on the response of the immune system.

Aggressive Periodontitis. Aggressive periodontitis (also referred to as early onset periodontitis) often occurs in young people. It is subdivided according to whether it begins before or after puberty. Immune deficiencies and a genetic link have been shown to be possible factors for all types of aggressive periodontitis. If the condition is localized and treated, the outlook is positive. People with severe and widespread aggressive periodontitis are at high risk for tooth loss.

Periodontitis that occurs before puberty is very rare. It begins with the eruption of primary teeth in the first year and causes severe inflammation and bone and tooth loss.
Juvenile periodontitis begins at puberty and is defined by severe bone loss around the first molars and incisors. It is more common in girls than in boys. The clinical signs -- such as inflammation, bleeding, and heavy plaque accumulation -- are not present in this relatively rare disease. The treatment is the same as in chronic periodontitis.
Rapidly progressive periodontitis occurs in the early 20s to mid-30s. Severe inflammation and rapid bone and connective tissue loss occur, and tooth loss is possible within a year of onset.

Disease-Related Periodontitis. Periodontitis can also be associated with a number of systemic diseases, including type 1 diabetes, Down syndrome, AIDS, and several rare disorders of white blood cells.

Acute Necrotizing Periodontal Disease. Acute necrotizing periodontal disease is an acute infection in the gums. It is characterized by:

Black, dead tissue (necrosis)
Spontaneous bleeding
Rapid onset of pain
Bad odor
Blunted gum tissue (tissue is normally cone-shaped)

Stress, poor diet, smoking, and viral infections are predisposing factors for this acute necrotizing periodontal disease.

Symptoms

In general, symptoms progress over time and include:

Red and Swollen Gums
Gum Bleeding. Bleeding of the gums, even during brushing, is a sign of inflammation and the major marker of periodontal disease. One exception is juvenile periodontitis, in which symptoms are mild or even absent. It should be noted that the gums of smokers with periodontal disease tend to bleed less than nonsmokers.
Bad Breath. Debris and bacteria can cause a bad taste in the mouth and persistent bad breath.
Gum Recession and Loose Teeth. As the disease advances the gums recede, and supporting structure of bone is lost. Teeth loosen, sometimes causing a change in the way the upper and lower teeth fit together when biting down or a change in the fit of partial dentures.

Abnormally bulging, protruding, or swollen gums are a possible sign of disease.

Click the icon to see an image of recessed gums.

Abscesses. Deepening periodontal pockets between the gums and bone can become blocked by tartar or food particles. Infection-fighting white blood cells become trapped and die. Pus forms, and an abscess develops. Abscesses can destroy both gum and tooth tissue, cause nearby teeth to become loose and painful, and may cause fever and swollen lymph nodes.

Click the icon to see an image of a tooth abscess.

Pain is usually not a symptom, which partly explains why the disease may become advanced before treatment is sought and why some patients avoid treatment even after periodontitis is diagnosed.

Causes

Periodontal disease is marked by bacterial overgrowth. However, a persistent immune response to chronic infections in the mouth is believed to play a major role in gum destruction.

In the healthy mouth, more than 350 species of microorganisms have been found. Periodontal infections are linked to fewer than 5% of these species. Healthy and disease-causing bacteria can generally be grouped into two categories:

The harmless or helpful bacteria are usually known as gram positive aerobic bacteria.
In periodontal disease, the bacterial balance shifts over to gram negative anaerobic bacteria. Inflammatory disease and injury cannot develop without these bacteria.

Following are some of the bacteria most implicated in periodontal disease and bone loss:

Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. These two bacteria appear to be particularly likely to cause aggressive periodontal disease. Both P. gingivalis and A. actinomycetemcomitans, along with multiple deep pockets in the gum, are associated with resistance to standard treatments for gum disease. P. gingivalis may double the risk for serious gum disease. P. gingivalis produces enzymes, such as one called arginine-specific cysteine proteinase, which may be the specific destructive factors that disrupt the immune system and lead to subsequent periodontal connective tissue destruction.
Bacteroides forsythus is also strongly linked to periodontal disease.
Other bacteria associated with periodontal disease are Treponema denticola, T. socranskii, and P. intermedia. These bacteria, together with P. gingivalis, are frequently present at the same sites, and are associated with deep periodontal pockets.

Some bacteria are related to gingivitis, but not plaque development. They include various streptococcal species.

Evidence now suggests that periodontal disease is an autoimmune disorder, in which immune factors in the body attack the person's own cells and tissue -- in this case, those in the gum. It appears to work as follows:

The bacteria that form plaque and tartar release toxins that stimulate the immune system to overproduce powerful infection-fighting factors called cytokines.
Ordinarily, cytokines are important for healing. In excess, however, they can cause inflammation and severe damage. Cytokines of particular importance in periodontal disease are known as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta, which are very active in the mouth, and are important in causing destructive inflammation.
In addition, white blood cells produced by the immune response to bacteria also release a family of enzymes called matrix metalloproteinases (MMPs), which break down connective tissue.

Studies suggest that this inflammatory response may have damaging effects not only in the gums but also in organs throughout the body, including the heart.

Certain herpes viruses (herpes simplex and varicella-zoster virus, the cause of chickenpox and shingles) are known causes of gingivitis. Other herpes viruses (cytomegalovirus and Epstein-Barr) may also play a role in the onset or progression of some types of periodontal disease, including aggressive and severe chronic periodontal disease. All herpes viruses go through an active phase followed by a latent phase and possibly reactivation.

Some experts theorize that these viruses may cause periodontal disease in different ways, including release of tissue-destructive cytokines, overgrowth of periodontal bacteria, suppressing immune factors, and initiation of other disease processes that lead to cell death.

Risk Factors

More than 75% of American adults have some form of gum disease, but according to a major survey, only 60% have any significant knowledge about the problem. Gum inflammation and ulcers are common, and not all people with these problems develop periodontal disease. Still, about 30% of people are genetically susceptible to periodontal disease. Other factors also put individuals at higher risk.

Lack of Oral Hygiene. Lack of oral hygiene encourages bacterial buildup and plaque formation.

Sugar and Acid. The bacteria that cause periodontal disease thrive in acidic environments. Therefore, eating sugars and other foods that increase the acidity in the mouth increase bacterial counts.

Poorly Contoured Restorations. Poorly contoured restorations (fillings or crowns) that provide traps for debris and plaque can also contribute to its formation.

Anatomical Tooth Abnormalities. Abnormal tooth structure can increase the risk.

Wisdom Teeth. Wisdom teeth, also called third molars, can be a major breeding ground for the bacteria that cause periodontal disease. In fact, for patients in their 20s, periodontal disease is most likely to occur around the wisdom teeth. Research suggests that periodontitis can occur in wisdom teeth that have broken through the gum as well as teeth that are impacted (buried). Periodontal disease can also be present even in patients with wisdom teeth who do not have any symptoms. Experts recommend that adolescents and young adults with wisdom teeth should have a dentist check for signs of periodontal disease

Children and Adolescents. Gingivitis, in varying degrees, is nearly a universal finding in children and adolescents. In rare genetic cases, children and adolescents are subject to destructive forms of the disease. Researchers have also observed some of the organisms seen in periodontal disease in young children without signs of gum problems. Healthy children, however, do not generally harbor two primary periodontal bacteria, P. gingivalis and T. denticola. The disease is also uncommon in teenagers.

Adults. One survey reported that 3.6% of adults between the ages of 18 - 34 had periodontal disease. As people age, the risk for periodontal disease increases. Over half of American adults have gingivitis surrounding 3 - 4 teeth, and 30% have significant periodontal disease surrounding 3 - 4 teeth. In a study of people over 70 years old, 86% had at least moderate periodontitis and over a quarter of them had lost their teeth.

About three-quarters of periodontal office visits are made by women, even though women tend to take better care of their teeth than men. Female hormones affect the gums, and women are particularly susceptible to periodontal problems. Hormone-influenced gingivitis appears in some adolescents, in some pregnant women, and is occasionally a side effect of birth control medication.

Before Menstruation. Gingivitis may flare up in some women a few days before they menstruate, when progesterone levels are high. Gum inflammation may also occur during ovulation. Progesterone dilates blood vessels causing inflammation, and blocks the repair of collagen, the structural protein that supports the gums.

Pregnancy. Hormonal changes during pregnancy can aggravate existing gingivitis, which typically worsens around the second month and reaches a peak in the eighth month. Pregnancy does not cause gum disease, and simple preventive oral hygiene can help maintain healthy gums. Any pregnancy-related gingivitis usually resolves within a few months of delivery. Because periodontal disease can increase the risk for low-weight infants and cause other complications, it is important for pregnant women to see a dentist.

Oral Contraceptives. Some studies report that oral contraceptives containing the synthetic progesterone desogestrel (but not dienogest, another common progesterone) increase the risk for periodontal disease.

Menopause. Estrogen deficiency after menopause reduces bone mineral density, which can lead to bone loss. Bone loss is associated with both periodontal disease and osteoporosis. Bone loss in the alveolar bone (which holds the tooth in place) may be a major predictor of tooth loss in postmenopausal women. Periodontal disease is the main cause of alveolar bone loss. During menopause, some women may also develop a rare condition called menopausal gingivostomatitis, in which the gums are dry, shiny, and bleed easily. Women may also experience abnormal tastes and sensations (such as salty, spicy, acidic, burning) in the mouth.

Periodontal disease often occurs in members of the same family. Genetics, intimacy, hygiene, or a mixture of factors may be responsible. Studies have found that children of parents with periodontitis are 12 times more likely to have the bacteria thought to be responsible for causing plaque and, eventually, periodontal disease.

Genetic Factors. Genetic factors may play the critical role in half the cases of periodontal disease. Up to 30% of the population may have some genetic susceptibility to periodontal disease. For example, some people with severe periodontal disease have genetic factors that affect the immune factor interleukin-1 (IL-1), a cytokine involved in the inflammatory response. Such individuals are up to 20 times more likely to develop advanced periodontitis than those without these genetic factors. Early onset and rapidly progressive periodontal disease also have strong genetic components.

Intimacy. Intimate partners and spouses of people with periodontal disease may also be at risk. Researchers have found that the bacteria P. gingivalis may be contagious after exposure to an infected person over a long period of time. There is no risk from short exposure such as after a fast kiss or when sharing an eating utensil.

Smoking is the single major preventable risk factor for periodontal disease. The habit can cause bone loss and gum recession even in the absence of periodontal disease. A number of studies indicate that smoking and nicotine increase inflammation by reducing oxygen in gum tissue and triggering an over-production of immune factors called cytokines (specifically ones called interleukins). In excess, cytokines are harmful to cells and tissue.

Furthermore, when nicotine combines with oral bacteria, such as P. gingivalis, the effect produces even greater levels of cytokines and eventually leads to periodontal connective tissue breakdown. Studies suggest that smokers are 11 times more likely than nonsmokers to harbor the bacteria that cause periodontal disease and four times more likely to have advanced periodontal disease. In one study more than 40% of smokers lost their teeth by the end of their lives.

The risk of periodontal disease increases with the number of cigarettes smoked per day. Smoking cigars and pipes carries the same risks as smoking cigarettes. Exposure to secondhand smoke is also associated with a 50 - 60% increased risk for developing periodontal disease, according to one study. Fortunately, when smokers quit, their periodontal health gradually recovers to a state comparable to that of nonsmokers.

Diabetes. Much evidence exists on the link between type 1 and 2 diabetes and periodontal disease. Diabetes causes changes in blood vessels, and high levels of specific inflammatory chemicals such as interleukins, that significantly increase the chances of periodontal disease. High levels of triglycerides (which are common in type 2 diabetes) also appear to impair periodontal health. Obesity, common in people with type 2 diabetes, may also predispose a person to gum disease. Controlling both type 1 and 2 diabetes may help reduce periodontal problems. For children with diabetes, good oral hygiene should begin at a young age. A 2006 study suggested that gum problems can start as early as 6 years of age in children with diabetes.

Osteoporosis and Osteonecrosis. Osteoporosis (loss of bone density) has been associated with periodontal disease in postmenopausal women. There have also been a few reports of osteonecrosis (bone decay) of the jaw in patients who take oral bisphosphonate drugs such as alendronate (Fosamax). Symptoms of osteonecrosis of the jaw include loose teeth, exposed jawbone, pain or swelling in the jaw, gum infections, and poor healing of the gums. As a precaution, the American Dental Association (ADA) recommends that patients who are prescribed bisphosphonate drugs get a thorough dental exam before beginning drug therapy, or as soon as possible after beginning therapy. The ADA also recommends that patients who take oral bisphosphonate drugs should discuss with their dentists any potential risks from dental procedures (such as extractions and implants) that involve the jawbone. In any case, be sure to inform your dentist if you are taking a bisphosphonate drug.

Osteoporosis is a condition marked by progressive loss of bone density, thinning of bone tissue, and increased risk of fractures. Osteoporosis may result from disease, dietary or hormonal deficiency, or advanced age. Regular exercise and vitamin and mineral supplements can reduce and may even reverse loss of bone density.

Giving intravenous bisphosphonates to patients being treated for bone cancer, or other cancers that have spread to the bone, increases their risk for developing osteonecrosis by 1 - 10%. Patients who take oral bisphosphonate drugs also have a slight risk, but 94% of osteonecrosis of the jaw cases involve patients who received bisphosphonates intravenously. If possible, see a dentist for a complete oral exam before beginning bisphosphonate therapy. In any case, be sure to inform your dentist if you are receiving intravenous bisphosphonates. Your dentist or oral surgeon may need to take special precautions when performing dental surgery

Herpes-Related Gingivitis. Herpes virus is a common cause of gingivitis in children and has become increasingly common in adults. It typically starts out with a purplish color and "boggy" sensation in the gums. Multiple blisters may form across the mucus membranes in the mouth and gums, followed by ulcers. They usually resolve in 7 - 14 days.

HIV-Associated Gingivitis. HIV-associated gingivitis has been reported in 15 - 50% of patients with HIV or AIDS. HIV-positive individuals harbor larger numbers of periodontal bacteria (candida albicans, P. gingivalis, black-pigmented anaerobic rods, and A. actinomycetemcomitans) than people without HIV. Severe pain is characteristic, along with odor, spontaneous bleeding, ulcers, and swollen, bright red gums. The inflammation never recedes, but halitosis and acute episodes can be managed by conventional cleaning treatments. Its severest form, known as necrotizing stomatitis, can be diagnostic for AIDS. In addition to bleeding, the gums in the front of the mouth are a yellowish-gray color, and bone thrusts out.

Autoimmune Diseases. Autoimmune conditions (Crohn's disease, multiple sclerosis, rheumatoid arthritis, lupus erythematosus, CREST syndrome) have been associated with a higher incidence of periodontal disease. Some research suggests that periodontal disease may even play some causal role. For example, one study suggested that P. gingivalis, one of the major bacteria in periodontal disease, was associated with destructive processes in the brain leading to multiple sclerosis. Still, more research is needed to determine a definitive association between these diseases.

Other Diseases. People with tuberculosis, syphilis, Wegener's granulomatosis, amyloidosis, and many genetic disorders are also at higher risk for periodontitis.

Vitamin C helps the body repair and maintain connective tissue, and its antioxidant effects are important in the presence of tissue-destroying oxidants in periodontal disease. Research indicates that vitamin C deficiency contributes to periodontal disease. A study of more than 12,000 adults found that people who consumed less than the recommended daily allowance of vitamin C, 60 mg (about one orange) were 1.5 times more likely to develop severe gingivitis than those who consumed more than 180 mg each day. Vitamin C levels are especially depleted in smokers. Eating citrus fruits high in vitamin C (such as grapefruit) may be helpful for patients with periodontitis.

Click the icon to see an image of the benefits of vitamin C.

Click the icon to see an image of the sources of vitamin C.

Dental disease is most likely to affect the poor. Children and the elderly suffer the worst oral care, and ethnic minorities follow. In the United States, the lack of access to dental insurance is a contributing factor. In a survey of residents of five states (Arizona, California, Hawaii, Oregon, and Wisconsin), the rate of total tooth loss was less than 20%. In three states (Kentucky, Louisiana, and West Virginia) it was greater than 40%.

Gingival overgrowth can be a side effect of nearly 20 different drugs, most commonly phenytoin (Dilantin), cyclosporine (Sandimmune), and a short-acting form of the calcium channel blocker nifedipine (Procardia).

Several other conditions can also cause gum inflammation, and some have been associated with periodontal disease. They include:

Mouth breathing
Psychologic stress. Stress can affect the immune system. Some studies suggest that stress can influence the development of chronic inflammatory diseases, like periodontitis.
Alcohol abuse. One study reported a higher incidence of periodontal disease, tooth decay, and possibly precancerous areas in patients who abuse alcohol.
Canker sores (aphthous ulcers)

Click the icon to see an image of a canker sore.

Self-injury in psychologically disturbed patients
Hereditary gingival fibromatosis. A rare genetic disease associated with both gum overgrowth and hairiness. It is often associated with gingivitis and periodontal disease.
Desquamative gingivitis. With this condition the outer layer of the gum tissue desquamates (peels away), exposing an acutely red surface. It usually occurs as a result of an allergic reaction or of skin diseases such as lichen planus, benign mucous membrane pemphigoid, bullous pemphigoid, and pemphigus vulgaris. (Bacteria may also play a role in this gum disease.) This condition generally resolves when the underlying problem is treated. It is fairly common in middle-aged women.

Complications

The ultimate outcome of uncontrolled periodontal disease is tooth loss. As the destructive factors cause the breakdown of bone and connective tissue, teeth lose their anchor.

A much less severe but nevertheless distressing problem caused by periodontal disease is bad breath, although coatings on the tongue may contribute more to bad breath than periodontal disease.

Studies have reported that people who have heart disease have a 1.5 - 4 times increased risk for periodontal disease. (The risk is highest for patients with extensive gum disease, bleeding from every tooth.) Acute coronary syndrome, high blood pressure (hypertension), and high cholesterol have also been associated with periodontal disease.

Periodontal disease has also been linked to stroke and coronary artery disease (CAD). The more severe the periodontitis, the greater the risk for heart problems. Many experts, however, are still not sure whether periodontal disease is a risk factor for stroke or a marker that reflects various risk factors common to both conditions.

A stroke is caused by a loss of blood circulation to areas of the brain. The blockage usually occurs when a clot or piece of atherosclerotic plaque breaks away from another area of the body and lodges within the blood vessels of the brain.

Recent evidence suggests that the inflammatory response may be the common element. This is an over-reaction of the immune system that causes injury to tissues in the body. A common link between patients with heart conditions and periodontal disease may be elevated levels of C-reactive protein (CRP), a marker for the inflammatory response. Some experts believe that immune factors causing this response are released into the bloodstream during periodontal disease and cause injury in the arteries supplying blood to the heart.

Other evidence suggests that the periodontal disease bacteria themselves -- particularly P. gingivalis, T. denticola, T. forsythia, and streptococci species -- may be the main culprit. In 2005, results from the NIH-sponsored Oral Infections and Vascular Disease Epidemiology Study (INVEST) determined an association between cardiovascular disease and the bacteria that cause periodontal disease. In this study, higher levels of periodontal bacteria were associated with thicker carotid arteries (a predictor of heart attack and stroke), regardless of C-reactive protein levels. While this study's findings are an important advance in understanding the relationship between periodontal and heart disease, it is still not clear if periodontal disease actually causes heart disease. Researchers hope that future results from INVEST will clarify this issue.

Experts are still not sure if treating gum disease can reduce the risks of heart disease and improve health outcomes for patients with periodontal disease and vascular heart problems. Studies have been mixed, but research is ongoing.

Diabetes is not only a risk factor for periodontal disease -- periodontal disease itself can worsen diabetes. Some evidence suggests that the bacteria that causes periodontal disease may enter the bloodstream and activate cytokines (damaging immune system factors), which then destroy cells in the pancreas where insulin is produced. Some studies indicate that treating periodontal disease can reduce the need for insulin and improve blood sugar control in some people with diabetes.

Bacteria that reproduce in the mouth can also be carried into the airways in the throat and lungs, increasing the risks for respiratory diseases and worsening chronic lung conditions, such as emphysema.

Click the icon to see an image of emphysema.

Many studies strongly indicate that bacterial infections that cause moderate-to-severe periodontal disease in pregnant women can increase the risk for premature delivery and low birth weight infants. The more severe the infection, the greater the risk to the baby. Research indicates that bacteria from gum disease and tooth decay may trigger the same factors in the immune system as genital and urinary tract infections. These biologic substances, called prostaglandins and tumor necrosis factor, produce inflammation in the cervix and uterus that can cause premature dilation and contractions. Research also suggests that periodontal disease increases the risk for preeclampsia, a life-threatening disorder that occurs in mid- to late pregnancy and is characterized by high blood pressure.

Experts recommend that women have a periodontal examination before becoming pregnant or as soon as possible thereafter. Because women with diabetes are at higher risk for periodontal disease, it is especially important that they see a dentist early in pregnancy. Experts are still not sure if treating periodontal disease can improve birth outcomes. A 2006 study in the New England Journal of Medicine indicated that the treatment does not affect pre-term birth or birth weight. However, the researchers reported that periodontal treatment is definitely safe for pregnant women.

Prevention

Healthy habits and good oral hygiene are critical in preventing gum disease. Regular and effective tooth brushing and mouth washing, however, are effective only above and slightly below the gum line. Once periodontal disease develops, more intensive treatments are needed.

It is important to reduce both the quantity and, in particular, the frequency of sugar intake. Avoid snacks and drinks with sugar (other than natural sugars found in fruits and vegetables). Eat sugar-containing foods with meals, ideally followed by brushing. Since fruit juices can also cause tooth erosion in children, parents should emphasize milk and water.

Smoking may play a significant role in over half the cases of chronic periodontal disease, according to research published in 2000. For smokers, quitting is one of the most important steps toward regaining periodontal health.

Fluoride treatment in children has helped to account for the decline in periodontal disease in adults. Because fluoride prevents decay, back molars, which keep the teeth in place, are spared, and are thus less vulnerable to bacteria. Even before teeth first erupt, babies' gums should be wiped clean with a bit of gauze bearing a dab of fluoride toothpaste. Supplementation with fluoride tablets or drops may be recommended for children 6 months or older who drink unfluoridated water or who are at risk for dental problems. A prescription from the child's pediatrician or dentist is required.

Some dentists recommend a fluoride gel for adult patients who are still at risk for tooth decay or sensitivity, but extra fluoride is generally not necessary for adults who use fluoride toothpaste.

Periodontitis is a silent disease. People with the disease rarely experience pain and may not be aware of the problem. A periodontal examination by a general dentist once or twice a year should reveal any incipient or progressive problems. A full mouth series of x-rays is advised every 2 - 3 years. This will alert the dentist to early bone loss and other disorders of the oral cavity.

Dentists now often perform Periodontal Screening and Recording (PSR) using a probe to measure gum pockets. Previously performed only by periodontists, this procedure is now encouraged as part of a regular dental examination. The dentist will identify any areas where deep pocketing has occurred, where the health of the gingiva appears compromised, and where there is undue mobility of teeth. It is the general dentist's responsibility to identify periodontal disease and inform the patient. If the condition is severe, the dentist may want to refer the patient to a periodontist.

Correct tooth brushing, mouth cleansing, and flossing should be everyone's defense against periodontal disease. (However, good hygiene is probably not sufficient to prevent periodontal disease in many people. Regular visits to a dentist are extremely important, especially for high-risk individuals.)

Brushing Guidelines. The following are some recommendations for brushing:

Use a dry brush. One study reported that when people brushed their teeth without toothpaste first, using a soft dry brush, their plaque deposits were reduced by 67%, and gum bleeding dropped by 50%.
No brush of any size, shape, or gimmick is effective if it is incorrectly positioned in the mouth. Place the brush where the gum meets the tooth, with bristles resting along each tooth at a 45-degree angle.
Begin by dry brushing the inside the bottom row of teeth, then the inner top teeth, and last the outer surfaces.
Wiggle the brush back and forth so the bristles extend under the gum line.
Scrub the broad, biting surfaces of the back teeth.
Dry brushing should take about a minute and a half.
A paste is then applied, and the teeth should again be brushed in the same way.
The tongue should be scrubbed for a total of about 30 seconds. A tongue scraper used with an anti-bacterial mouthwash (such as Listerine) is more effective than a toothbrush in removing bacteria.
Rinse the toothbrush thoroughly and then tap it on the edge of the sink at least five times to get rid of debris.
Flossing should finish the process. A mouthwash may also be used.

If brushing after each meal is not possible, rinsing the mouth with water after eating can reduce bacteria by 30%.

Toothbrushes. A vast assortment of brushes of varying sizes and shapes are available, and each manufacturer makes its claim for the benefits of a particular brush. Look for the American Dental Association (ADA) seal on both electric and regular brushes.

In spite of the wide variety of nonelectric toothbrushes, both in shape and bristle design, a study of eight brands found no significant differences in effectiveness among them.

Electric toothbrushes, particularly those with a stationary grip and revolving tufts of bristles, can be advantageous for some people with physical disabilities. Electric toothbrushes with heads that move back and forth up to 4,200 times a minute remove significantly more plaque than ordinary brushes. Even more high-tech brushes are now available that use sound waves to remove plaque.

In general, studies have reported no differences between electric and manual toothbrushes in their ability to remove plaque. (One study showed considerable improvement in groups using sonic toothbrushes, particularly in those with moderate periodontal disease.) Experts recommend, however, that if a regular toothbrush works, it isn't necessary to buy an expensive electric one.

For individuals with average dexterity, a four- or five-rowed, soft, nylon-bristled toothbrush is sufficient. The most important factor in buying any toothbrush, electric or manual, is to choose one with a soft head. Soft bristles get into crevices easier and do not irritate the gums, thereby reducing the risk of exposing teeth below the gum line compared to hard brushes.

Experts generally recommend replacing toothbrushes every 1 - 3 months. Not only do they become breeding grounds for bacteria, but the worn bristles are less effective at removing plaque.

Toothpaste. The object of a good toothpaste is to reduce the development of plaque and eliminate periodontal-causing microorganisms without destroying the organisms that are important for a healthy mouth. All brands should show ADA approval. Even a good toothpaste, however, cannot be delivered past 3 mm below the gum line, where periodontitis develops.

Toothpastes are a combination of abrasives, binders, colors, detergents, flavors, fluoride, humectants, preservatives, and artificial sweeteners. Avoid highly abrasive toothpastes, especially for individuals whose gums have receded.

Ingredients contained in toothpastes may include:

Fluoride. Most commercial toothpastes contain fluoride, which both strengthens tooth enamel against decay and enhances remineralization of the enamel. Fluoride also inhibits acid-loving bacteria, especially after eating, when the mouth is more acidic. This antibacterial activity may help control plaque.
Triclosan. Triclosan is an anti-bacterial substance that may help reduce mild gingivitis.
Metal salts. Metal salts, such as stannous and zinc, serve mostly as anti-bacterial substances in toothpastes. Stannous fluoride gel toothpastes do not reduce plaque, however, even though they have some effect against the bacteria that cause it, but slightly reduce gingivitis.
Peroxide and baking soda. Toothpastes with these ingredients claim to have a whitening action, but while they may help remove stains there is little evidence they whiten the actual color of the teeth. In addition, these substances appear to offer no benefits against gum disease.
Antibacterial sugar substitutes (xylitol), and detergents (delmopinol)

Mouthwashes. The American Dental Association recommends (in addition to daily brushing and flossing) antimicrobial mouthwash to help prevent and reduce plaque and gingivitis, and fluoride mouthwashes to help provide additional protection against tooth decay.

Chlorhexidine (Peridex or PerioGard) is an antimicrobial mouthwash available by prescription only. It reduces plaque by 55% and gingivitis by 30 - 45%. Patients should rinse for 1 minute twice daily. They should wait at least 30 minutes (and preferably 2 hours) between brushing and rinsing since chlorhexidine can be inactivated by certain compounds in toothpastes. It has a bitter taste. It also binds to tannins, which are in tea, coffee, and red wine, so it has tendency to stain teeth in people who drink these beverages. Studies are mixed as to its effectiveness for preventing or reducing periodontal disease.
Listerine is another antimicrobial mouthwash. It is composed of essential oils and is available over the counter. It reduces plaque and gingivitis, when used for 30 seconds twice a day. It leaves a burning sensation in the mouth that most people better tolerate after a few days of use. The usual regimen is to rinse twice a day. (Listerine PocketPaks, which are strips that dissolve on the tongue, have no proven effects on plague and gingivitis.)
Mouthwashes containing cetylpyridinium (Scope, Cepacol) have moderate antimicrobial effect on plaque, but only if they are used an hour after brushing. None are as effective as Listerine or chlorhexidine, but they may still have some value for people who cannot tolerate the other mouthwashes.
Mouthwashes containing stannous fluoride and amine fluoride (Meridol) are moderately effective, but are also not as effective as effective as Listerine or chlorhexidine.
Fluoride mouthwashes (Act) are helpful in preventing cavities.
Mouthwashes that contain alcohol are dangerous for children and should be kept away from them.

Flossing. The use of dental floss, either waxed or unwaxed, is critical in cleaning between the teeth where the toothbrush bristles cannot reach. In spite of this, nearly two-thirds of people do not floss.

To floss correctly, the following steps may be helpful:

Break off about 18 inches of floss and wind most of it around the middle finger of one hand and the rest around the other middle finger.
Hold the floss between the thumbs and forefingers and gently guide and rub it back and forth between the teeth.
When it reaches the gum line, the floss should be curved around each tooth and slid gently back and forth against the gum.
Finally, rub gently up and down against the tooth. Repeat with each tooth, including the outside of the back teeth.
If, on repeated flossing attempts, the floss becomes shredded or cannot be removed easily from between the teeth, a rough crown or overhanging filling may be the cause. In such cases, the restoration should be redone. Such areas create spaces for the collection of food debris, plaque, and calculus.

Here are some tips in choosing the right floss or flossing device:

Use a floss that does not shred or break.
Avoid a very thin floss, which can cut the gum if brought down with too much force or not guided along the side of the tooth.
A floss threader is an invaluable aid for the person who has bridgework. Made of plastic, it looks like a needle with a huge eye, or loop. A piece of floss is threaded into the loop, which can then be inserted between the bridge and the gum. The floss that is carried through with it can then be used to clean underneath the false tooth or teeth and along the sides of the abutting teeth.
Another handy device for cleaning under bridges is a Proxabrush, which is an interdental cleaner. This is a tiny narrow brush that can be worked in between the natural teeth and around the attached false tooth or teeth.
Special toothpicks such as Stim-U-Dent may be effective for wide spaces between teeth but should never replace flossing. Standard toothpicks should never be used for regular hygiene.
Electronic products, such as water piks, are also helpful. These devices are expensive but may improve flossing compliance.

Producing Saliva and Drinking Water. Saliva is important for diluting the toxins created by plaque. Drinking at least 7 glasses of water a day helps reduce inflammation in the mouth by producing more saliva. Increasing water intake is particularly important as one ages, when less saliva is produced.

Diagnosis

The dental practitioner typically performs a number of procedures to determine a diagnosis of periodontal disease.

The dentist will first take a medical history to reveal any past or present periodontal problems, any underlying diseases that might be contributing to the problem, and any medications the patient is taking. After noting the general state of oral hygiene, the dentist may ask about the quality of home dental care.

Inspection of the Gum Area. The dentist inspects the color and shape of gingival tissue on the cheek (buccal) side and the tongue (lingual) side of every tooth and compares these qualities to the healthy ideal. Redness, puffiness, and bleeding upon probing indicate inflammation. If the gum formation between teeth is blunt and not pointed, acute necrotizing periodontal disease may be indicated.

Periodontal Screening and Recording (PSR). PSR is a painless procedure used to measure and determine the severity of periodontal disease:

The dentist uses a mirror and a periodontal probe, a fine instrument calibrated in millimeters (mm), which is used to measure pocket depth. (A new automatic probing device may prove to be even more sensitive and accurate than the standard manual probe that most dentists use.)
The probe is held along the length of the tooth with the tip placed in the pocket. The tip of the probe will then touch the point where the connective tissue attaches to the tooth.
The dentist will "walk" the probe to six specified points on each tooth, three on the buccal (cheek) and three on the lingual (tongue) sides. The dentist measures the depth of the probe at each point.
Pocket depths greater than 3 mm indicate disease.

These measurements help determine the condition of the connective tissue and amount of gingival overgrowth or recession. PSR appears to be even more reliable than x-rays in diagnosing gum disease.

Testing Tooth Movement. Tooth mobility is determined by pushing each tooth between two instrument handles and observing any movement. Mobility is a strong indicator of bone support loss.

X-rays. X-rays are taken to show any loss of bone structure supporting the teeth. Eighteen x-rays make up the full mouth series necessary for diagnosis.

Treatment

Studies support the effectiveness of active treatment combined with a strict maintenance program for patients with periodontal disease. In one study, for example, people with periodontal disease who were inconsistent in caring for their gums after treatment had 5.6 times the risk for tooth loss as those who were very vigilant.

Some dentists have reported a success rate of 85% when professional treatment and good home maintenance are combined. Treatment helps nonsmokers more than smokers, particularly when pockets are deep and persistent. Some studies suggest that periodontal treatment in people with type 2 diabetes helps improve blood sugar levels. Whether treatment will help reduce other health risks, including heart attack and stroke, is unknown.

Treatment Goals. Once periodontal disease has been identified, the goals of treatment are:

To arrest and control the progress of the disease
To leave the periodontal tissues in an easily maintainable state
If possible, to restore the supporting structures, which include bone, gum tissue, and ligaments

Treatment Phases. To achieve these goals, there are various approaches:

Initial cleaning, scaling, and curettage
Surgery -- if needed for reducing deep pockets that remain underneath the gum after extensive cleaning sessions
Low-dose oral or topical antibiotics
Maintenance

After the active treatment is completed and the mouth is in a relative state of health, the patient should have regular cleanings lasting 45 minutes to 1 hour, approximately every 3 months. These may be done by the dental hygienist, the periodontist, or the general dentist. The patient may alternate between them. Home care, of course, must be continued.

Antibiotics Before Treatment. In cases where the individual has a mitral valve prolapse or history of rheumatic heart disease, pretreatment with an appropriate antibiotic is required before any dental work, including cleaning. This is necessary to prevent the possibility of bacterial endocarditis, which can be life threatening.

Scaling, polishing, and sometimes curettage are used to manage periodontal disease. They are usually accomplished in a series of three to four visits spaced about a week apart. (Patients might ask their dentist about the gas nitrous oxide, which is helpful for many patients and may reduce the visits to a single one.) The dental hygienist or practitioner generally uses both ultrasonic and manual instruments to remove calculus.

Calculus above the gum is easily seen. The dental professional usually detects calculus below the gum by careful probing with an instrument.
The hygienist or dentist may use an ultrasonic instrument for removal of the more accessible calculus. This probe-like device vibrates at a frequency range higher than is audible to the human ear. Some people with low tolerance for the ultrasonic probe may wish to request nitrous oxide.
A spray of water is used with ultrasound to prevent overheating and to flush out the debris that is dislodged.
The dental professional will scrape the plaque from above and below the gum line (called scaling). When the probe contacts the rock-like calculus, deposits fracture off the tooth fairly efficiently.
The hygienist or dentist will then smooth the rough spots on the tooth. Smoothing the surface helps remove bacteria that collect there (root planing) and also helps the gums reattach.
Polishing is the finishing procedure. It uses a rubber cup with an abrasive paste to remove plaque and stains on the crown portion of the tooth. It produces a smooth surface, making it temporarily harder for plaque to adhere.

After the cleaning procedure, the dentist will check the pocket depths around the teeth after the cleaning process has been completed. Further treatment needs are determined by the results of these initial sessions:

If the cleaning processes have reduced inflammation, observation only is needed.
If an abscess is present, surgery may be required.

Finally, the dental hygienist or practitioner should offer thorough instructions on home care to insure the removal of bacteria on a daily basis. This includes proper use of the toothbrush, paste, mouth rinses, floss, floss threaders, and proxabrushes. Home care can effectively eliminate the plaque above the gums and down to 2 mm below the gums.

Gingival curettage removes the soft tissue lining of the periodontal pockets in order to completely eliminate bacteria and diseased tissue. It may be used along with scaling and root planing, but achieves a deeper and more complete cleaning. Evidence indicates, however, that it does not contribute any additional benefits beyond simple scaling and planing.

Surgery allows access for deep cleaning of the root surface, removal of diseased tissue, and repositioning and shaping of the bones, gum, and tissues supporting the teeth. Surgical procedures vary depending on the individual diagnosis and needs of the patient. The basic procedure is known as open flap curettage. It involves:

The periodontal surgeon lifts, or flaps, the gums away from the tooth and surrounding bone.
The diseased root surfaces are cleaned and curetted (scraped) to remove deposits.
Gum tissue is replaced into positions to minimize pocket depth.
The periodontist may also contour the remaining bone and attempt to regenerate lost bone and gingival attachment through bone grafts and guided tissue regeneration or the use of enamel matrix protein derivatives.

There is some debate about whether this procedure is any more effective in preventing disease progression than non-surgical therapies, such as low-dose doxycycline, short-term antibiotics, or antibiotic gels. Some studies have reported that although surgical treatment reduced pocket depth more than non-surgical therapies for at least a year after the procedure, benefits from surgery do not persist beyond 5 years, except in very deep pockets.

Postsurgery Pain and Discomfort. Post-surgery discomfort is usually managed easily with over-the-counter medications such as ibuprofen. If discomfort is severe, stronger analgesics may be prescribed. Some patients experience sensitivity to hot or cold temperatures from exposed roots. These problems can be managed with topical fluoride treatments or, in severe cases, with dental restoration.

Guided Tissue Regeneration. A more advanced technique, called guided tissue regeneration, is used to stimulate bone and gum tissue growth:

First, the root surfaces and diseased bone are meticulously cleaned out. Preventing bacterial contamination is very important. The more residual bacteria, the greater the chance that the treatment will fail.
A specialized piece of fabric is sewn around the tooth to cover the crater in the bone left after the cleaning. It is either absorbable or nonabsorbable. (Some studies report highly beneficial results with new absorbable materials, including those coated with the antibiotic doxycycline.)
The gum is then sewn over the fabric. The fabric prevents the gum tissue from growing down into the bone defect and allows the bone and the attachment to the root to regenerate.
After 4 - 6 weeks, the nonabsorbable fabric must be removed using a minor surgical procedure. The absorbable membrane may be left in. In general, there is little difference in outcome between absorbable and nonabsorbable procedures. The absorbable fabric may not be as effective as standard grafts if gum tissue is thin, although newer materials may prove to produce better results.

Bone Grafting. In some cases of severe bone loss, the surgeon may attempt to encourage regrowth and restoration of bone tissue that has been lost through the disease process. This involves bone grafting:

The surgeon places bone graft material into the defect.
The material may be either bone from the same patient or a substance called decalcified freeze-dried bone allografts (DFDBA) which is obtained from a donor.
This material then stimulates new bone growth in the area.

Enamel Matrix Protein Derivative. Amelogenin is a derivative of a major protein in the structure (the matrix) of enamel that helps stimulate gum tissue growth. A gel containing amelogenin (Emdogain) is applied during surgery and forms a coat over the roots of the teeth. The gel itself dissolves after 2 days, leaving the active substance behind. Studies report that it is safe and may significantly reduce the effects of periodontal disease. One study suggested that the benefits, as indicated by bone attachment, can persist for at least 4 years. (Results were similar to guided tissue regeneration.)

Gum grafting techniques can also be very useful for improving the looks of the gum as well as adding support to the teeth. During this procedure, the periodontist takes gum tissue from the palate or another donor source to cover the exposed root in order to even the gum line and reduce sensitivity. Other procedures are available to improve the look of the gums and teeth. The gum line can be sculpted to improve uneven or excess gums and to cover exposed roots as gums recede.

Periodontists report that they are achieving great success with tooth implants in patients who have lost teeth due to periodontal disease. The average cost for a single implant is high, however, and one implant requires 5 - 7 months for completion.

Medications

Antibiotics are often used in combination with surgery, curettage, or alone to eliminate or prevent disease-causing bacteria after periodontal procedures. They are being investigated in oral forms as well as in topical forms that are applied directly to the gum. Increasingly, dental professionals are finding that local application of antibiotics is more effective than periodontal surgery alone. They may even prove to be an alternative to surgery.

Some experts are concerned, however, that long-term use of antibiotics increases the risk of bacterial resistance to these drugs, which is a growing health problem in general. Of some encouragement was a 2000 review, which indicated that low-dose antibiotics do not increase the risk of bacterial resistance. However, long-term studies are still needed

Antibiotics given orally and at standard doses have some limited applications for periodontal disease. They are typically given for an acute infection. Long-term use of antibiotics is advised for the control of juvenile periodontitis, refractory periodontitis, rapidly progressing periodontitis, and prepubertal periodontitis. Specific antibiotics used in periodontal disease include:

Tetracycline antibiotics -- which include tetracycline hydrochloride, doxycycline, and minocycline -- are the primary drugs used. They not only have anti-bacterial actions but also reduce inflammation and help block collagenase, the protein that destroys connective tissue and bone, even in low doses. In fact, these two actions seem to contribute most to periodontal protection, rather than their antibacterial properties. Short-term use of standard-dose doxycycline (a 10-day treatment) is used for treating acute periodontal infections and for eliminating inflammation. Topical application and long-term use of these antibiotics are showing particular promise.
Some macrolide antibiotics (roxithromycin) may have actions against inflammation and growth involved in periodontal disease.
Some quinolone antibiotics (moxifloxacin, ciprofloxacin) may specifically target A. actinomycetemcomitans, an important bacteria in periodontal disease.
Metronidazole (Flagyl) in combination with tetracycline or amoxicillin (a penicillin) may be used for severe and chronic periodontal disease.

There is growing bacterial resistance to many of these antibiotics, such as roxithromycin and metronidazole, therefore limiting their use in periodontal disease. One study indicated, however, that 3 months after antibiotic administration, the percentage of bacteria that could be eliminated with standard antibiotics returned to normal.

Topical application of antibiotics to the gum surface does not affect the entire body like oral antibiotics do, and they are preferred whenever possible. Studies suggest that, in combination with scaling and planing, any of these approaches are very effective for periodontal health.

Several different topical applications are showing promise, including:

Atridox is a doxycycline gel that conforms to the gum surface and then solidifies. Over the next few days, it releases the antibiotics.
Elyzol is a gel or strip applied to the gum that is composed of metronidazole. It has unique actions that are effective against parasites as well as bacteria. Studies suggest that Atridox, which contains doxycycline, may be more effective than Elyzol. (In one study, however, the doxycycline gel worked faster, but metronidazole achieved a greater bacterial reduction.)
PerioChip is a chip that is placed into the gum pocket after scaling. Over time, it slowly releases chlorhexidine, a powerful bacteria-killing antiseptic. Early studies report benefits in reducing pocket depths, but it is still not known whether these improvements are sustained.
Minocycline microspheres (Arestin) contain antibiotics in tiny capsules, which are applied to the gums after scaling and planing. Studies report that they are more effective in reducing pocket depth and bone loss than standard periodontal maintenance. Patients obtain these benefits regardless of their smoking status, age gender, or extent of the periodontal disease.
Actisite is a thin strip similar to dental floss, which is treated with tetracycline hydrochloride. The treated thread is temporarily inserted between the tooth and gum. (Using multiple strips may be more beneficial than using a single strip.) This was one of the first topical applications of antibiotics. Other topical approaches are being increasingly used.

Subantimicrobial Dose Doxycycline (Periostat). Subantimicrobial dose doxycycline (SDD) is a term used for a treatment that uses very low doses (20 mg) of doxycycline (Periostat). Although doxycycline is a tetracycline antibiotic, the doses used are too low to affect bacteria. However, at these dose levels, the drug blocks matrix metalloproteinases (MMPs) -- enzymes that destroy the connective tissues holding the teeth. Periostat is taken twice a day for months. There is some concern that such long-term use may pose a risk for the development of antibiotic-resistant bacteria or other, still unknown, adverse effects. The doses used in this treatment, however, are too low to have any effect on bacteria, so some experts believe this risk is very low. In fact, several 12-month studies report significant improvements in tooth attachment and pocket depth with no increased incidence of side effects. [Taking a common nonsteroidal anti-inflammatory drug, such as aspirin or ibuprofen (Advil) along with doxycycline, may enhance the effectiveness of this treatment.]

Chemically Modified Tetracyclines. Other tetracyclines are being developed that inhibit MMPs but have no antibiotic properties, which would, theoretically, avoid possible long-term problems with antibiotic resistance.

Other Treatments

Nonsteroidal Anti-inflammatory Drugs (NSAIDs). NSAIDs are drugs that block factors that cause inflammation and pain.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), indomethacin (Indocin).

These drugs are used not only for relieving pain in periodontal disease but also for slowing the disease process. NSAIDs block inflammatory enzymes triggered by cytokines, which are important immune factors in periodontal disease. A number of NSAIDs have been investigated and have been shown to reduce gingivitis and slow progression of periodontal disease.

In one study, long-term use of oral flurbiprofen (Ansaid) resulted in significantly lower bone loss, although disease progression returned when the drug was stopped.

Investigators are also studying rinses, creams, and other topical forms of NSAIDs. For example, a cream containing ketoprofen appears to reduce bone loss. (Ketoprofen is of particular interest because it blocks not only COX-2 but also another pathway involved in the disease process.)

Warning about NSAIDs: Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding.

Gels containing growth factors -- including substances called recombinant human (rh), platelet-derived growth factor-BB (PDGF-BB), and (rh) insulin-like growth factor-I (IGF-I) -- are showing promise for restoring bone.

Research is underway to find a vaccine against periodontal disease. To date, animal studies show promise, but an effective vaccine for people is years away.

Researchers are investigating the use of photodynamic therapy (PDT) as an alternative to antibiotic drugs. PDT destroys periodontal bacteria by applying photosensitive drugs to oral regions and exposing the drug-treated area to a light or laser. Research appears promising but is still in its preliminary stages.

Resources

www.nidcr.nih.gov -- National Institute of Dental and Craniofacial Research
www.perio.org -- American Academy of Periodontology
www.ada.org -- American Dental Association
www.aaoms.org -- American Association of Oral and Maxillofacial Surgeons

References

Amaliya , Timmerman MF, Abbas F, Loos BG, Van der Weijden GA, Van Winkelhoff AJ, et al. Java project on periodontal diseases: the relationship between vitamin C and the severity of periodontitis. J Clin Periodontol. 2007 Apr;34(4):299-304.

de Oliveira RR, Schwartz-Filho HO, Novaes AB Jr, Taba M Jr. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: a preliminary randomized controlled clinical study. J Periodontol. 2007 Jun;78(6):965-73.

Kolahi J, Soolari A. Rinsing with chlorhexidine gluconate solution after brushing and flossing teeth: a systematic review of effectiveness. Quintessence Int. 2006 Sep;37(:605-12.

Persson GR, Yeates J, Persson RE, Hirschi-Imfeld R, Weibel M, Kiyak HA. The impact of a low-frequency chlorhexidine rinsing schedule on the subgingival microbiota (the TEETH clinical trial). J Periodontol. 2007 Sep;78(9):1751-8.

Staudte H, Sigusch BW, Glockmann E. Grapefruit consumption improves vitamin C status in periodontitis patients. Br Dent J. 2005 Aug 27;199(4):213-7, discussion 210.

Review Date:
1/26/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Eating disorders

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Risk Factors
Causes
Complications of Bulimia...
Complications of Anorexia...
Symptoms
Diagnosis
Treatment
Treatment for Bulimia
Treatment for Anorexia
Therapy
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Eating Disorders Overview

Eating disorders typically occur among young women.
Bulimia nervosa involves a pattern of bingeing and purging. Many people with bulimia nervosa also suffer from depression.
Anorexia nervosa involves a pattern of self-starvation. Patients often have an accompanying anxiety disorder (such as obsessive compulsive disorder) or depression. Patients who have anorexia and depression have a high risk for suicide. Some studies estimate that anorexia nervosa has the highest death rate of any psychiatric disorder.

Treatment of Bulimia Nervosa

Bulimia nervosa is treated with a combination of psychotherapy and medication. Cognitive behavioral therapy, which is given along with nutritional counseling, is the preferred psychotherapeutic approach. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), are the first choice for drug therapy.

Treatment of Anorexia Nervosa

Unlike bulimia nervosa, anorexia nervosa does not respond as well to drug treatment, although SSRIs are sometimes used as an adjunct to psychotherapy. Therapy that includes the entire family -- not just the patient -- is an important part of the treatment process, as is nutritional education. Patients who are severely underweight and who have other physical risks may need to be hospitalized while weight is restored. Recovery is a long process that can take 5 - 6 years to achieve.

Introduction

Eating disorders are behavioral issues brought on by a complex interplay of factors, which may include emotional and personality disorders, family pressures, a possible genetic or biologic susceptibility, and a culture in which there is an overabundance of food and an obsession with thinness. There are four general categories of eating disorders:

Bulimia nervosa
Anorexia nervosa
Binge eating
Eating disorders not otherwise specified

These are not new disorders. Although anorexia nervosa was first defined as a medical problem in the late 1800s, descriptions of self-starvation have been found even in medieval writings.

Bulimia nervosa is more common than anorexia, and it usually begins early in adolescence. It is characterized by cycles of bingeing and purging, and typically takes the following pattern:

Bulimia is often triggered when young women attempt restrictive diets, fail, and react by binge eating. (Binge eating involves consuming larger than normal amounts of food within a 2-hour period.)
In response to the binges, patients compensate, usually by purging, vomiting, using enemas, or taking laxatives, diet pills, or drugs to reduce fluids.
Patients then revert to severe dieting, excessive exercise, or both. (Some patients with bulimia follow bingeing only with fasting and exercise. They are then considered to have non-purging bulimia.)
The cycle then swings back to bingeing and then to purging again.
Some studies have reported that patients with bulimia average about 14 episodes of binge-purging per week. To be diagnosed with bulimia, however, a patient must binge and purge at least twice a week for 3 months. (Some experts believe that going through the cycle only once a week is sufficient for a diagnosis.)
In some cases, the condition progresses to anorexia. Most people with bulimia, however, have a normal to high-normal body weight, although it may fluctuate by more than 10 pounds because of the binge-purge cycle.

Young people who occasionally force vomiting after eating too much are not considered bulimic, and most of the time this occasional unhealthy behavior does not continue beyond youth.

The term "anorexia" literally means absence of appetite. Anorexia nervosa involves an aversion to food that leads to a state of starvation and emaciation. It is a very serious illness that some experts believe is an entirely different condition from bulimia and should be not be diagnosed as a simple eating disorder.

Facts associated with anorexia nervosa:

At least 15% to as much as 60% of normal body weight is lost.
The patient with anorexia nervosa has an intense fear of gaining weight, even when severely underweight.
Individuals with anorexia nervosa have a distorted image of their own weight or shape and deny the serious health consequences of their low weight.
Women with anorexia nervosa miss at least three consecutive menstrual periods. (Some experts believe women can be anorexic without this occurrence.)

Patients with this condition are often characterized as anorexia restrictors or anorexic bulimic patients. Each type is equally prevalent.

Anorexia restrictors reduce their weight by severe dieting.
Anorexic bulimic patients maintain emaciation by purging. Although both types are serious, the bulimic type, which imposes additional stress on an undernourished body, is the more damaging.

Severe anorexia is common in the elderly, who may experience weight loss because of social isolation, impaired gastrointestinal function, or loss of certain chemicals related to the feeding drive. Such age-related anorexia, however, is not synonymous with anorexia nervosa, a psychologic disorder.

Bingeing without purging is characterized as compulsive overeating (binge eating) with the absence of bulimic behaviors, such as vomiting or laxative abuse (used to eliminate calories). Binge eating usually leads to becoming overweight.

To be diagnosed as a binge eater, a person typically has the following characteristics:

Bingeing at least twice a week for 6 months
Consuming 5,000 - 15,000 calories in one sitting
Eating three meals a day plus frequent snacks
Overeating continually throughout the day, rather than consuming large amounts of food during binges

Since binge eating disorder is generally associated with weight gain, it will not be further discussed in this report. [For more information, see In-Depth Report #53: Weight control and diet.]

A fourth category called eating disorders not otherwise specified (NOS) has been established to define eating disorders not specifically defined as anorexia or bulimia. This category includes:

Infrequent binge-purge episodes (occurring less than twice a week or having such behavior for less than months)
Repeated chewing and spitting without swallowing large amounts of food
Normal weight and anorexic behavior

Such patients tend to be older at diagnosis. Although less serious than other eating disorders, these patients still face similar health problems, including a higher risk for fractures and other conditions.

Risk Factors

Many factors contribute to the risk of developing an eating disorder. In the United States, about 7 million women and 1 million men suffer from eating disorders.

Eating disorders occur most often in adolescents and young adults. However, new research finds that they are increasingly prevalent among young children. Eating disorders are more difficult to identify in young children because they are rarely suspected.

Studies indicate that eating disorders occur predominantly among girls and women. About 90 - 95% of patients with anorexia nervosa, and about 80% of patients with bulimia nervosa, are female.

Most studies of individuals with eating disorders have been conducted using Caucasian middle-class females. Studies now indicate, however, that minority populations (including Hispanic Americans and African-Americans) are increasingly affected.

Living in any economically developed nation on any continent appears to pose a risk for eating disorders. Within nations, eating disorders can affect people of all socioeconomic levels.

People with eating disorders tend to share similar personality and behavioral traits, including low self-esteem, dependency, and problems with self-direction. Specific psychiatric personality disorders may put people at higher risk for eating disorders.

Avoidant Personalities. Some studies indicate that many patients with anorexia nervosa have avoidant personalities. This personality disorder is characterized by:

Being a perfectionist
Being emotionally and sexually inhibited
Having less of a fantasy life than people with bulimia or those without an eating disorder
Being perceived as always being "good," not being rebellious
Being terrified of being ridiculed or criticized or of feeling humiliated

People with anorexia are extremely sensitive to failure, and any criticism, no matter how slight, reinforces their own belief that they are "no good".

Obsessive-Compulsive Personality. Obsessive-compulsive personality defines certain character traits (being a perfectionist, morally rigid, or preoccupied with rules and order). This personality disorder has been strongly associated with a higher risk for anorexia. These traits should not be confused with the anxiety disorder called obsessive-compulsive disorder (OCD), although they may increase the risk for this disorder.

Borderline Personalities. Borderline Personality Disorder (BPD) is associated with self-destructive and impulsive behaviors. People with BPD tend to have other co-existing mental health problems, including eating disorders.

Narcissistic Personalities. Studies have also found that people with bulimia or anorexia are often highly narcissistic and tend to:

Have an inability to soothe oneself
Have an inability to empathize with others
Have a need for admiration
Be hypersensitive to criticism or defeat

Many patients with eating disorders experience depression and anxiety disorders. Depression, anxiety, or both is also common in families of patients with eating disorders. It is not clear if emotional disorders, particularly obsessive-compulsive disorder (OCD), cause the eating disorders, increase susceptibility to them, or share common biologic cause.

Obsessive-Compulsive Disorder (OCD). Obsessive-compulsive disorder is an anxiety disorder that occurs in up to two thirds of patients with anorexia and up to one third of patients with bulimia. In fact, some experts believe that eating disorders are variants of OCD. Obsessions are recurrent or persistent mental images, thoughts, or ideas, which may result in compulsive behaviors (repetitive, rigid, and self-prescribed routines) that are intended to prevent the manifestation of the obsession. Women with anorexia and OCD may become obsessed with exercise, dieting, and food. They often develop compulsive rituals (weighing every bit of food, cutting it into tiny pieces, or putting it into tiny containers). The presence of OCD with either anorexia or bulimia does not, however, appear to have any influence on whether a patient improves or not.

Obsessive-compulsive disorder is an anxiety disorder characterized by an inability to resist or stop continuous, abnormal thoughts or fears combined with ritualistic, repetitive, and involuntary defense behavior.

Other Anxiety Disorders. A number of other anxiety disorders have been associated with both bulimia and anorexia, including:

Phobias. Phobias often precede the onset of the eating disorder. Social phobias, in which a person is fearful about being humiliated in public, are common in both types of eating disorders.
Panic Disorder. Panic disorder often follows the onset of an eating disorder. It is characterized by periodic attacks of anxiety or terror (panic attacks).
Post-Traumatic Stress Disorder. Many women with serious eating disorders report a past traumatic event, and many exhibit symptoms of post-traumatic stress disorder (PTSD) -- an anxiety disorder that occurs in response to life-threatening circumstances.

Depression. Depression is common in people with eating disorders, for both anorexia and bulimia. Major depression is unlikely to be a cause of eating disorders, however, because treating and relieving depression rarely cures an eating disorder. In addition, depression often improves after anorexic patients begin to gain weight.

Extreme eating disorder behaviors, including use of diet pills, laxatives, diuretics, and vomiting, are reported more often in overweight teenagers. Researchers are working on strategies for preventing the development of eating disorders among overweight adolescents. A 2006 study that targeted overweight college-age women reported success with an Internet-based cognitive behavioral therapy program that helped these women become more comfortable with their body weight and shape. The program also included information on the risks of eating disorders, and education on healthy eating and weight maintenance.

Body Dysmorphic Disorder. Body dysmorphic disorder (BDD) involves a distorted view of one's body that is caused by social, psychologic, or possibly biologic factors. It is often associated with anorexia or bulimia, but it can also occur without any eating disorder. People with this disorder commonly suffer from emotional disorders, including obsessive-compulsive disorder and depression. As part of obsessive thinking, some people with BDD may obsess about a perceived deformity in one area of their body, and may repeatedly seek cosmetic surgery to "correct" it. People with BDD are also at higher risk for suicidal thinking and attempts. Some evidence suggests that treatment with fluoxetine (Prozac), a common antidepressant known as an SSRI helps reduce this problem, even in people without an eating disorder.

Muscle Dysmorphia. Experts are also increasingly reporting a disorder in which people have distorted body images involving their muscles. It tends to occur in men who perceive themselves as being "puny," which results in excessive body building, preoccupation with diet, and social problems. Such individuals are prone to eating disorders and other unhealthy behaviors, including the use of anabolic steroids.

Highly competitive athletes are often perfectionists, a trait common among people with eating disorders.

Female Athletes. Excessive exercise is associated with many cases of anorexia (and, to a lesser degree, bulimia). In young female athletes, anorexia postpones puberty, allowing them to retain a muscular boyish shape without the normal accumulation of fatty tissues in breasts and hips that may blunt their competitive edge. Many coaches and teachers compound the problem by overstressing calorie counting and loss of body fat.

In response, people who are vulnerable to such criticism may lose excessive weight, which has been known to be deadly even for famous athletes. The term "female athlete triad" in fact, is now a common and serious disorder facing young female athletes and dancers and describes the combined presence of the following problems:

Eating disorders, including anorexia
Amenorrhea (absence or irregular menstruation)
Osteoporosis (bone loss, which appears to be related to low weight)

Male Athletes. Male wrestlers and lightweight rowers are also at risk for excessive dieting. One-third of high school wrestlers use a method called weight-cutting for rapid weight loss. This process involves food restriction and fluid depletion by using steam rooms, saunas, laxatives, and diuretics. Although male athletes are more apt to resume normal eating patterns once competition ends, studies show that the body fat levels of many wrestlers are still well below their peers during off-season and are often as low as 3% during wrestling season.

Men and Women in the Military. Studies also show a higher-than-average risk for eating disorders in men and women in the military. A study of eating behavior on one Army base reported that 8% of the women had an eating disorder, compared to 1 - 3% in the civilian female population.

In general, vegetarianism, with careful planning, is a healthy practice for both adults and adolescents. Studies report, however, that vegetarianism in adolescence may be a risk factor for eating disorders in both males and females. Vegetarian teens have been found to be twice as likely to diet frequently, four times as likely to intensively diet, and eight times as likely to use laxatives as their non-vegetarian peers.

These studies do not mean that being a vegetarian equates with having an eating disorder. They do suggest, however, that parents with children who suddenly become vegetarians should be sure that their children are eating a balanced meal with sufficient protein, calories, and important minerals, such as calcium. Parents also might suspect anorexic behavior in their child under certain conditions:

If the child has stopped eating meat only to avoid fat rather than from other motives, such as love of animals or to improve health.
If the vegetarian diet coincides with rapid weight loss.
If the child avoids important vegetable products because of calories (such as whole grains) or because of fats and oils (such as tofu, nuts, and dairy products).

Eating disorders may be more common in teenagers with chronic illness, such as diabetes or asthma. Some recent research suggests an endocrinological link between obesity, diabetes, and eating disorders.

Diabetes. Eating disorders are particularly serious problems for people with either type 1 or type 2 diabetes.

Binge eating (without purging) is most common in type 2 diabetes and, in fact, the obesity it causes may even trigger this diabetes in some people.
Both bulimia and anorexia are common in type 1 diabetes. A 2005 study indicated that as many as 25% of young women with type 1 diabetes may develop abnormal eating habits, and that the combination of diabetes and an eating disorder can have serious health consequences in the women's future. Diabetic women often omit or underuse insulin in order to control weight. If such patients develop anorexia, their extremely low weight may appear to control the diabetes for a while. Eventually, however, if they fail to take insulin and continue to lose weight, these patients develop life-threatening complications.

Click the icon to see an image of type 1 diabetes.

There is a greater risk for eating disorders and other emotional problems for girls who undergo early puberty, when the pressures experienced by all adolescents are intensified by experiencing, possibly alone, these early physical changes, including normal increased body fat. One interesting study reported that:

Before puberty, girls ate quantities of food appropriate to their body weight, were satisfied with their bodies, and noted their depression increased with lower food intake.
After puberty, girls ate about three-quarters of the recommended calorie intake, had a worse body self-image, and noted their depression increased with higher food intake.

This study reported on girls without eating disorders, but it certainly suggests patterns that can lead to eating problems, particularly in girls who go through puberty early. Other studies also indicate that girls who start menstruating at a younger age are more likely to develop eating disorders.

Causes

There is no single cause for eating disorders. Although concerns about weight and body shape play a role in all eating disorders, the actual cause of these disorders appear to result from many factors, including cultural and family pressures and emotional and personality disorders. Genetics and biologic factors may also play a role.

Negative influences within the family may play a major role in triggering and perpetuating eating disorders. Some studies have produced the following observations and theories regarding family influence.

Insecure Infancy. Some experts theorize that parents who fail to provide a safe and secure foundation in infancy may foster eating disorders. In such cases, children experience so-called insecure attachments. They are more likely to have greater weight concerns and lower self-esteem than are those with secure attachments.
Parental Behaviors. Poor parenting by both mothers and fathers has been implicated in eating disorders. One study found that 40% of 9- and 10-year-old girls trying to lose weight generally with the urging of their mothers. Some studies have found that mothers of anorexics tend to be over-involved in their child's life, while mothers of people with bulimia are critical and detached. Overly critical fathers, brothers, or both may play a factor in the development of anorexia in both girls and boys.
Family Meals. How often a family eats together may influence whether a child develops an eating disorder. A study published in the Journal of Adolescent Health found that young girls who ate 3 - 4 meals per week with their families were about half as likely to engage in extreme weight control behaviors as girls who ate family meals less often.
Family History of Addictions or Emotional Disorders. Studies report that people with either anorexia or bulimia are more likely to have parents with alcoholism or substance abuse than are those in the general population. Parents of people with bulimia appear to be more likely to have psychiatric disorders than parents of patients with anorexia.
History of Abuse. Women with eating disorders, particularly bulimia, appear to have a higher incidence of sexual abuse. Studies have reported sexual abuse rates as high as 35% in women with bulimia.
Family History of Obesity. People with bulimia are more likely than average to have an obese parent or to have been overweight themselves during childhood.

At least one study has reported that the most positive way for parents to influence their children's eating habits and to prevent weight problems and eating disorders is to have healthy eating habits themselves.

Anorexia is eight times more common in people who have relatives with the disorder, and some experts estimate that genetic factors are the root cause of many cases of eating disorders. Twins had a tendency to share specific eating disorders (anorexia nervosa, bulimia nervosa, and obesity). Researchers have identified specific chromosomes that may be associated with bulimia and anorexia. In particular, regions on chromosome 10 have been linked to bulimia as well as obesity. Some evidence has also reported an association with genetic factors responsible for serotonin, the brain chemical involved with both well-being and appetite. Researchers have also pinpointed certain proteins such as brain-derived neurotrophic factor (BDNF). This protein may influence an individual's susceptibility to developing an eating disorder.

The approach to food in Western countries is extremely problematic. Enough food is produced in the U.S. to supply 3,800 calories every day to each man, woman, and child, far more than any single person needs to sustain life. Obesity is a global epidemic, and few people living in this over-fed and sedentary culture eat a meal guiltlessly.

One interesting anthropologic study reported the following observations:

During historical periods or in cultures where women are financially dependent and marital ties are stronger, the standard is toward being curvaceous, possibly reflecting a cultural or economic need for greater reproduction.
During periods or in cultures where female independence has been possible, the standard of female attractiveness tends toward thinness.

The response of the media to the cultural drive for thinness and the overproduction of food both likely play major roles in triggering obesity and eating disorders.

On the one hand, advertisers heavily market weight-reduction programs and present anorexic young models as the paradigm of sexual desirability.
Clothes are designed and displayed for thin bodies in spite of the fact that few women could wear them successfully.
On the other hand, the media floods the public with attractive ads for consuming foods, especially "junk" foods.

Hormonal abnormalities are common in eating disorders and include chemical abnormalities in the thyroid, the reproductive regions, and areas related to stress, well-being, and appetite. Many of these chemical changes are certainly a result of malnutrition or other aspects of eating disorders, but they also may play a role in perpetuating or even creating susceptibility to the disorders.

The primary setting of many of these abnormalities originate in a small area of the brain called the limbic system. A specific system called hypothalamic-pituitary-adrenal axis (HPA) may be particularly important in eating disorders. It originates in the following regions in the brain:

Hypothalamus. The hypothalamus is a small structure that plays a role in controlling our behavior, such as eating, sexual behavior and sleeping, and regulates body temperature, emotions, secretion of hormones, and movement.

Click the icon to see an image of the hypothalamus.

The pituitary gland. The pituitary gland is involved in controlling thyroid functions, the adrenal glands, growth, and sexual maturation.
Amygdala. This small almond-like structure lies deep in the brain and is associated with regulation and control of major emotional activities, including anxiety, depression, aggression, and affection.

Click the icon to see an image of the brain-thyroid link.

Stress Hormones. The HPA systems trigger the production and release of stress hormones called glucocorticoids, including the primary stress hormone cortisol. Chronically elevated levels of stress chemicals have been observed in patients with anorexia and bulimia. Cortisol is very important in marshaling systems throughout the body (including the heart, lungs, circulation, metabolism, immune systems, and skin) to deal quickly with any threat.

Release of Neurotransmitters. The HPA system also releases certain neurotransmitters (chemical messengers) that regulate stress, mood, and appetite and are being heavily investigated for a possible role in eating disorders. Abnormalities in the activities of three of them, serotonin, norepinephrine, and dopamine, are of particular interest. Serotonin is involved with well-being, anxiety, and appetite (among other traits), and norepinephrine is a stress hormone. Dopamine is involved in reward-seeking behavior. Recent research suggests that people with anorexia have increased activity in the brain's dopamine receptors. This overactivity may explain why people with anorexia do not experience a sense of pleasure from food and other typical comforts.

Ghrelin. High levels of ghrelin, a hormone that increases the feeling of hunger and slows metabolism, have been noted in patients with anorexia and bulimia.

Low-Leptin Levels. Leptin is a hormone that appears to trigger the hypothalamus to stimulate appetite, and low levels have been observed in people with anorexia and bulimia.

Low Reproductive Hormones. The hypothalamic-pituitary system is also responsible for the production of important reproductive hormones that are severely depleted in anorexics. Although most experts believe that these reproductive abnormalities are a result of anorexia, others have reported that in 30 - 50% of people with anorexia, menstrual disturbances occurred before severe malnutrition set in and remained a problem long after weight gain, indicating that hypothalamic-pituitary abnormalities precede the eating disorder itself.

In some cases, infection has been associated with anorexia. In such cases, immune factors released to fight these infections may cause inflammation and injury in the areas of the brain that affect appetite and behavior.

Streptococcal Infection. The bacteria responsible for strep throat and rheumatic fever -- called group A beta-hemolytic streptococcal (GABHS) -- is now a suspect in some cases of anorexia. Some children who have been infected with these bacteria develop a syndrome that includes obsessive-compulsive disorder (OCD), tics, and anorexia nervosa. The syndrome is called PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus). More research is needed to confirm this as an actual cause of anorexia and to determine if it may be treatable with antibiotics.

Epstein Barr Virus. Epstein Barr, the virus that causes mononucleosis, has also been associated with the development of anorexia.

Click the icon to see an image of infectious mononucleosis.

Complications of Bulimia

Most studies report that patients who have bulimia without severe weight loss have a much better outlook than patients with anorexia. Some studies have suggested that 60 - 80% of bulimic patients are in remission within 3 months of treatment. However, relapse is common, and over half of women with bulimia continue to battle disordered eating habits for years. In one study, bulimia itself persisted in 10 - 25% of patients after treatment.

Many medical problems are directly associated with bulimic behavior, including:

Tooth erosion, cavities, and gum problems
Water retention, swelling, and abdominal bloating
Acute stomach distress
Fluid loss with low potassium levels (due to excessive vomiting or laxative use; can lead to extreme weakness, near paralysis, or lethal heart rhythms)
Irregular periods
Swallowing problems and esophagus damage

Forced vomiting causes repetitive assaults on the esophagus (the food pipe) from forced vomiting. It is not clear, however, if swallowing problems are common.

The esophagus connects the nose and mouth with the stomach. The epiglottis folds over the trachea when a swallow occurs, to prevent the swallowed substance from being inhaled into the lungs. When a person is unable to swallow because of illness or coma, a tube may be inserted either through the mouth or nose, past the epiglottis, through the esophagus and into the stomach. Nutrients pass directly through the tube into the stomach.

Rupture of the esophagus, or food pipe
Weakened rectal walls (rare, but serious condition that requires surgery)

Click the icon to see an image of the rectum.

A number of self-destructive behaviors occur with bulimia:

Smoking. Many teenage girls with eating disorders smoke because it is thought to help prevent weight gain.
Impulsive Behaviors. Women with bulimia are at higher-than-average risk for dangerous impulsive behaviors, such as sexual promiscuity, self-cutting, and kleptomania. Some studies have reported such behaviors in half of those with bulimia.
Alcohol and Substance Abuse. An estimated 30 - 70% of patients with bulimia abuse alcohol, drugs, or both. This rate is higher than that of the general population and for people with anorexia. However, this higher rate of substance abuse may be a distortion because studies are conducted only on diagnosed patients. Bulimia tends not to get diagnosed. And reports of bulimia in the community (where the incidence of the eating disorder is higher than statistics suggest) indicate that substance abuse is actually lower than in people with anorexia.

Women with bulimia frequently abuse over-the-counter medications, such as laxatives, appetite suppressants, diuretics, and drugs that induce vomiting (ipecac). None of these drugs is without risk. For example, ipecac poisonings have been reported, and some people become dependent on laxatives for normal bowel functioning. Diet pills, even herbal and over-the-counter medications, can be hazardous, particularly if they are abused.

Complications of Anorexia

Anorexia nervosa is a very serious illness that has a wide range of effects on the body and mind. It is also associated with other problems, ranging from frequent flus and general poor health to life-threatening conditions. Some experts believe that it should not be approached as a simple eating disorder but as a serious condition requiring staging according to severity.

At this time, no treatment program for anorexia nervosa is completely effective. Recovery rates vary between 23 - 50%, and relapses range from 4 - 27%. Recovery takes an average of 5 - 6 years from the time of diagnosis. Up to 30% of patients do not recover.

Even after treatment and weight gain, many patients continue to display characteristics of the disorder, including perfectionism and a drive for thinness, which could keep them at risk for recurrence.

Some research suggests that anorexia nervosa has the highest death rate of any psychiatric disorder. According to different studies, the risk for early death is higher for people with the following conditions or characteristics:

Being younger
Having bulimia anorexia (twice as high in this group than in the anorexic-restrictor types)
Being severely low in weight at the time of treatment
Being sick for more than 6 years
Having been previously obese
Having an accompanying severe psychological disorder including personality disorders

One of the most serious effects of anorexia is hormonal changes, which can have severe health consequences.

Reproductive hormones, including estrogen and dehydroepiandrosterone (DHEA), are lower. Estrogen is important for healthy hearts and bones. DHEA, a weak male hormone, may also be important for bone health and for other functions.
Thyroid hormones are lower.
Stress hormones are higher.
Growth hormones are lower. Children and adolescents with anorexia may experience retarded growth.

The result of many of these hormonal abnormalities in women is long-term, irregular or absent menstruation (amenorrhea). This can occur early on in anorexia, even before severe weight loss. Over time this causes infertility, bone loss, and other problems. Low weight alone may not be sufficient to cause amenorrhea. Extreme fasting and purging behaviors may play an even stronger role in hormonal disturbance.

Adolescents with eating behaviors associated with anorexia (fasting, frequent exercise to lose weight, and self-induced vomiting) are at high risk for anxiety and depression in young adulthood. Alcohol and drug abuse are more common in patients with anorexia. Suicide has been estimated to account for as many as half the deaths in anorexia with studies showing up to a fifth of anorexic patients attempting suicide.

Heart disease is the most common medical cause of death in people with severe anorexia. The effects of anorexia on the heart are:

Dangerous heart rhythms, including slow rhythms known as bradycardia, may develop. Such abnormalities can show up even in teenagers with anorexia.

Bradycardia is a slowness of the heartbeat, usually at a rate under 60 beats per minute (normal resting rate is 60 - 100 beats per minute).

Blood flow is reduced
Blood pressure may drop
The heart muscles starve, losing size
Cholesterol levels tend to rise

Click the icon to see an image of cholesterol.

A primary danger to the heart is from abnormalities in the balance of minerals, such as potassium, calcium, magnesium, and phosphate, which are normally dissolved in the body's fluid. The dehydration and starvation that occurs with anorexia can reduce fluid and mineral levels and produce a condition known as electrolyte imbalance. Electrolytes (calcium and potassium) are critical for maintaining the electric currents necessary for a normal heartbeat. An imbalance in these electrolytes can be very serious and even life threatening unless fluids and minerals are replaced. Heart problems are a particular risk when anorexia is compounded by bulimia and the use of ipecac, a drug that causes vomiting.

After treatment and an increase in weight, estrogen levels are usually restored and periods resume. In severe anorexia, however, even after treatment, normal menstruation never returns in 25% of such patients.

If a woman with anorexia becomes pregnant before regaining normal weight, she faces a higher risk for miscarriage, cesarean section, and for having an infant with low birth weight or birth defects. She is also at higher risk for postpartum depression.
Women with anorexia who seek fertility treatments have lower chances for success.

Most pregnant women with a history of eating disorders have healthy pregnancies. However, some studies suggest that they may face higher risks for a number of complications, including cesarean sections, postpartum depression, miscarriages, complicated deliveries, and premature birth. Many studies indicate that babies born to mothers with eating disorders have a higher risk for low birth weight. However, an encouraging 2006 study reported that mothers with a history of anorexia nervosa do not have a higher risk for pregnancy complications or poor birth outcomes.

Almost 90% of women with anorexia experience osteopenia (loss of bone minerals), and 40% have osteoporosis (more advanced loss of bone density). Up to two-thirds of children and adolescent girls with anorexia fail to develop strong bones during their critical growing period. Boys with anorexia also suffer from stunted growth. The less the patient weighs, the more severe the bone loss. Women with anorexia who also binge-purge face an even higher risk for bone loss.

Bone loss in women is mainly due to low estrogen levels that occur with anorexia. Other biologic factors in anorexia also may contribute to bone loss, including high levels of stress hormones (which impair bone growth) and low levels of calcium, certain growth factors, and DHEA (a weak male hormone). Weight gain, unfortunately, does not completely restore bone. Only achieving regular menstruation as soon as possible can protect against permanent bone loss. The longer the eating disorder persists the more likely the bone loss will be permanent.

Testosterone levels decline in boys as they lose weight, which also can affect their bone density. In young boys with anorexia, weight restoration produces some catch-up growth, but it may not produce full growth.

People with severe anorexia may suffer nerve damage that affects the brain and other parts of the body. The following nerve-related conditions have been reported:

Seizures
Disordered thinking
Numbness or odd nerve sensations in the hands or feet (peripheral neuropathy)

Brain scans indicate that parts of the brain undergo structural changes and abnormal activity during anorexic states. Some of these changes return to normal after weight gain, but there is evidence that some damage may be permanent. Still, the extent of the neurologic problems is unclear.

Anemia is a common result of anorexia and starvation. In one study, 38% of anorexic participants had anemia. A particularly serious blood problem is pernicious anemia, which can be caused by severely low levels of vitamin B12. If anorexia becomes extreme, the bone marrow dramatically reduces its production of blood cells, a life-threatening condition called pancytopenia.

Bloating and constipation are both very common problems in people with anorexia.

In very late anorexia, the organs simply fail. The main warning sign is high blood levels of liver enzymes, which require immediate administration of calories.

Eating disorders are very serious for young people with type 1 diabetes. A study of over 2,000 women found that bulimia, or a combination of bulimia and anorexia, was more common among women with type 1 diabetes.

The complications of eating disorders that affect all patients are even more dangerous in this group of patients. Low blood sugar, for example, is a danger for anyone with anorexia, but it is a particularly dangerous risk for those with diabetes. If patients do not take their insulin, high blood sugar, which is also very dangerous, can occur. Unfortunately, patients with eating disorders may skip or reduce their daily insulin in order to decrease their intake of calories. Extremely high blood sugar levels can cause diabetic ketoacidosis, a condition in which acidic chemicals (ketones) accumulate in the body. This condition can lead to coma and death.

Symptoms

Possibly the most bewildering symptom of eating disorders is the distorted body image (body dysmorphia ). Although people typically associate distorted body image with severe anorexia, one study indicated that distortion may be more prevalent in people with bulimia. People with bulimia were more likely than those with anorexia to overestimate their size. There was also a greater disparity between what they wanted to look like and what they believed they looked like.

People with bulimia nearly always practice it in secret, and, although they may be underweight, they are not always anorexic. Symptoms or signs of bulimia may, therefore, be very subtle and go unnoticed. They may include:

Evidence of discarded packaging for laxatives, diet pills, emetics (drugs that induce vomiting), or diuretics (medications that reduce fluids)
Regularly going to the bathroom right after meals
Suddenly eating large amounts of food or buying large quantities that disappear right away
Compulsive exercising
Broken blood vessels in the eyes (from the strain of vomiting)
Pouch-like appearance to the corners of the mouth due to swollen salivary glands (occurs within days of vomiting in about 8% of people with bulimia)
Dry mouth
Tooth cavities, diseased gums, and irreversible enamel erosion from excessive acid
Rashes and pimples
Small cuts and calluses across the tops of finger joints due to self-induced vomiting

Weight Loss. The primary symptom of anorexia is major weight loss from excessive and continuous dieting, which may either be restrictive dieting or binge-eating and purging.

Other symptoms of anorexia may include:

Infrequent or absent menstrual periods
Compulsive exercising coupled with excessive thinness
Refusal to eat in front of others
Ritualistic eating, including cutting food into small pieces
Hypersensitivity to cold -- some women wear several layers of clothing to both keep warm and hide their thinness
Yellowish skin, especially on the palms of the hands and soles of the feet -- from eating too many vitamin A-rich vegetables such as carrots
Dry skin covered with fine hair
Thin scalp hair
Cold or swollen feet and hands
Stomach problems, including bloating after eating
Confused or slowed thinking
Poor memory or judgment

Diagnosis

The first step towards a diagnosis is to admit the existence of an eating disorder. Often, the patient needs to be compelled by a parent or others to see a doctor because the patient may deny and resist the problem. Some patients may even self-diagnose their condition as an allergy to carbohydrates, because after being on a restricted diet, eating carbohydrates can produce gastrointestinal problems, dizziness, weakness, and palpitations. This may lead such people to restrict carbohydrates even more severely.

It is often extremely difficult for parents as well as the patient to admit that a problem is present. For example, because food is such an intrinsic part of the mother-child relationship, a child's eating disorder might seem like a terrible parental failure. Parents may have their own emotional issues with weight gain and loss and perceive no problem with having a "thin" child.

It is recommended that a supportive companion be present during part of the initial medical interview to offer additional information on the patient's eating history and to help offset any resistance or denial the patient may express.

Various questionnaires are available for assessing patients. The Eating Disorders Examination (EDE), which is an interview of the patient by the doctor, and the self-reported Eating Disorders Examination-Questionnaire (EDE-Q) are both considered valid tests for assessing eating disorder diagnosis and determining specific features of the individual’s condition (such as vomiting or laxative use).

Another test is called the SCOFF questionnaire. It is proving to be very reliable in accurately identifying both very young and adult patients who meet the full criteria for anorexia or bulimia nervosa. (It may not be as accurate in people who do not meet the full criteria.)

SCOFF Questionnaire

Do you make yourself Sick because you feel uncomfortably full?

Do you worry you have lost Control over how much you eat?

Have you recently lost more than One stone 's worth of weight (14 pounds) in a 3-month period?

Do you believe yourself to be Fat when others say you are too thin?

Would you say that Food dominates your life?

Answering yes to two of these questions is a strong indicator of an eating disorder.

In spite of the prevalence of bulimia, a majority of doctors have never diagnosed bulimia in a patient. Younger and female doctors are more likely to detect bulimia. A doctor should make a diagnosis of bulimia if there are at least two bulimic episodes per week for 3 months. Because people with bulimia tend to have complications with their teeth and gums, dentists could play a crucial role in identifying and diagnosing bulimia.

Generally, an observation of physical symptoms and a personal history will quickly confirm the diagnosis of anorexia. The standard criteria for diagnosing anorexia nervosa are:

The patient's refusal to maintain a body weight normal for age and height
Intense fear of becoming fat even though underweight
A distorted self-image that results in diminished self-confidence
Denial of the seriousness of emaciation and starvation
The loss of menstrual function for at least 3 months

The doctor then categorizes the anorexia further:

Restricting (severe dieting only)
Anorexia bulimia (binge-purge behavior)

Because the disorder rarely shows up in men, doctors may not be on the lookout for it in male patients, even if they show classic symptoms of anorexia. Doctors should be very aware of these symptoms in anyone, particularly in athletes and dancers.

Once a diagnosis is made, doctors should immediately check for any serious complications of starvation. They should also rule out other medical disorders that might be causing the anorexia. Tests should include:

A complete blood count
Tests for electrolyte imbalances (low potassium levels mean the disorder is more likely to be accompanied by the binge-purge syndrome)
Test for protein levels
An electrocardiogram and a chest x-ray
Tests for liver, kidney, and thyroid problems
A bone density test

Treatment

Treatment goals for eating disorders include:

Restore normal weight for anorexia nervosa
Reduce, and hopefully stop, binge eating and purging for bulimia nervosa
Treat physical complications and any associated psychiatric disorders
Teach patients proper nutritional habits and how to develop healthy eating patterns and meal plans
Change patients’ dysfunctional thoughts about the eating disorder
Improve self-control, self-esteem, and behavior
Provide family counseling
Prevent relapse

The first major difficulty in treating eating disorders is resistance by everyone involved:

The anorexic patient often believes that the emaciation is normal and even attractive.
The bulimic patient may feel that purging is the only way to prevent obesity.
Even worse, the anorexic condition may be encouraged by friends who envy thinness or by dance or athletic coaches who encourage low body fat.
The family itself may deny the problem and be obstructive or manipulative, adding to the difficulties of treatment.

It is very important that the patient and any close friends and relatives be informed about the serious potential of these conditions and the importance of receiving immediate help.

A multidisciplinary team approach with consistent support and counseling is essential for long-term recovery from all severe eating disorders. Depending on the severity and type of disorder, team members may include:

Doctors specializing in relevant medical complications
Dietitians
Cognitive-behavioral therapists
Psychotherapists
Nurses

All should be skilled in treating eating disorders. Studies have found that people treated by such specialists have a lower mortality rate than those treated only as psychiatric patients.

Patients may drop out of programs if they have unrealistic expectations of being "cured" simply through the therapists' insights. Before a program begins, the following possibilities should be made clear:

The process is painful and requires hard work on the part of the patient and family.
A number of therapeutic methods are likely to be tried until the patient succeeds in overcoming these difficult disorders.
Relapse is common but should not be greeted with despair. (In one study, about 90% of bulimic patients responded to treatments after 6 years.)

Although the outcome for bulimics is generally more favorable than for anorexics, long-term studies are showing recovery in most people treated for anorexia.

Psychotherapies. Eating disorders are nearly always treated with some form of psychiatric or psychologic treatment. Depending on the problem, certain psychologic approaches may work better than others.

Medications. Various medications may be helpful for patients depending on the type of eating disorder, psychiatric state, and severity of the condition.

Nutritional Rehabilitation. Nutritional counseling can help patients regain weight and learn normal expectations concerning hunger and eating patterns.

The patient’s condition, social circumstances, and health insurance coverage determine the type of treatment facility -- inpatient hospitalization, residential hospitalization, partial hospitalization, or outpatient care. Weight is not the sole determining factor. The patient’s overall physical condition, psychological state, behavior patterns, and family support are all factors. Patients and their families should discuss with their doctors the various options available and how structured and intense the treatment should be.

Treatment for Bulimia

Some experts recommend a stepped approach for patients with bulimia, which follow specific stages depending on the severity and response to initial treatments:

Support groups. This is the least expensive approach and may be helpful for patients who have mild conditions with no health consequences.
Cognitive-behavioral therapy (CBT) along with nutritional therapy is the preferred first treatment for bulimia that does not respond to support groups.
Drugs. The drugs used for bulimia are typically antidepressants known as selective serotonin-reuptake inhibitors (SSRIs). A combination of CBT and SSRIs is very effective if CBT alone is not helpful.

Patients with bulimia rarely need hospitalization except under the following circumstances:

Binge-purge cycles have led to anorexia
Drugs are needed for withdrawal from purging
Major depression is present

Psychologic Therapy. Cognitive-behavioral therapy (CBT) is the first-line of therapy for most patients with bulimia and is successful in about 60% of cases. Patients who do not respond to CBT tend to be less committed to the treatment, are more preoccupied with their symptoms, and have ritualized eating behaviors. Interpersonal therapy may be tried if CBT fails. Some studies have found that bulimic patients respond well to self-help CBT with a CD-ROM or manual. These methods, the research found, reduced the incidence of both binging and vomiting. Patients who do not respond to CBT may wish to try interpersonal therapy (also known as “talk therapy’), where therapists help patients explore how social and family relationships may affect their eating disorder.

Antidepressants. The most common antidepressants prescribed for bulimia are selective serotonin reuptake inhibitors (SSRIs) such as:

Fluoxetine (Prozac)
Sertraline (Zoloft)
Paroxetine (Paxil)
Fluvoxamine (Luvox)

Studies are mixed, however, on whether SSRIs offer an additional advantage in reducing binge-eating compared to CBT. Fluoxetine has been approved for bulimia and is considered the drug of choice, although some studies suggest that other SSRIs work just as well.

Antidepressants may increase the risks for suicidal thoughts and actions during the first few months of treatment. In particular, adolescents and young adults should be carefully monitored during this time period for any changes in behavior.

Topiramate. The antiepileptic drug topiramate (Topamax) has been shown in studies to reduce bingeing and purging episodes in patients with bulimia. However, due to this drug’s risk for serious side effects, topiramate should be used only if other medication has failed. In addition, because people tend to lose weight while taking topiramate, it should not be used by patients who have low or even normal body weight.

Treatment for Anorexia

Treatment goals for patients with anorexia require a team approach. Doctors should immediately check and treat any medical problems related to the condition, such as bone loss, imbalances in important electrolytes, and any hormonal deficiencies, including thyroid and reproductive hormones. Nutrition rehabilitation and psychotherapy also plays an important part in anorexia therapy.

Many moderately to severely ill anorexic patients require hospitalization when:

Weight loss continues even with outpatient treatment
Weight is 30% below ideal body weight
Depression is severe or the patient is suicidal
There are symptoms of medical complications (disturbed heart rate, low potassium levels, altered mental status, low blood pressure, severe sensations of cold)

When severe metabolic or medical problems occur, patients with anorexia may need to be hospitalized either voluntarily or involuntarily. A variety of partial hospitalization or day care programs are also available.

Duration of Inpatient Treatment. For people with severe anorexia, many experts believe that 10 - 12 weeks of hospitalization with full nutritional support are required to reach ideal body weight. Check to see how many days your insurance company allows for inpatient treatment. Many rarely cover more than 15 days in the hospital. It is particularly important for women with both diabetes and anorexia to achieve 100% of ideal weight before being released.

The body mass index (BMI) is the measurement of body fat. It is derived by multiplying a person's weight in pounds by 703 and then dividing it twice by the height in inches.

A healthy BMI for women over age 20 is 19 - 24.
Those over 24 are considered to be at risk for health problems related to obesity.
Those under 17.5 are considered to be at risk for health problems related to anorexia. (However, young teenagers can have lower BMIs without necessarily being anorexic.)

For example, a woman who is 5'5" and weighs 125 pounds has a healthy BMI of 21. A woman at the same height who weighs 90 pounds would have a dangerously low BMI of 15.

Nutritional intervention is essential. Weight gain is associated with fewer symptoms of anorexia and with improvements in both physical and mental function. Restoring good nutrition can help reduce bone loss, and raising the level of energy available to the body by balancing food intake and exercise can normalize hormonal function. Restoring weight is also essential before the patient can fully benefit from additional psychotherapeutic treatments.

Goals for Weight Gain and Good Nutrition. A weight-gain goal of 2 - 3 pounds a week for hospitalized patients, and 0.5 - 1 pound a week for outpatients, is strongly encouraged. Patients typically begin with a calorie count as low as 1,000 - 1,600 calories a day, which is then gradually increased to 2,000 - 3,500 calories a day. Patients may initially experience intensified anxiety and depressive symptoms, as well as fluid retention, in response to weight gain. These symptoms decrease as the weight is maintained.

Tubal Feedings. Feeding tubes that pass through the nose to the stomach are not commonly used, since many experts believe they discourage a return to normal eating habits and because many patients interpret their use as punishing forced feeding. However, for patients who are at significant risk or for those who refuse to eat, tube feeding through the nose or through a tube inserted through the abdomen into the stomach can help with weight gain and improve the nutritional status of the patient. One method is to administer such feedings only at nighttime, with the patient eating normally during the day.

Intravenous Feedings. Intravenous feedings may be needed in life-threatening situations. This involves inserting a needle into the vein and infusing fluids containing nutrients directly into the bloodstream. Intravenous feedings must be administered carefully. When given at home, no more than the prescribed amount should be used. Overzealous administration of glucose solutions can trigger the so-called refeeding syndrome, in which phosphate levels drop severely and cause a condition called hypophosphatemia. Emergency symptoms include irritability, muscle weakness, bleeding from the mouth, disturbed heart rhythms, seizures, and coma.

The role of exercise in recovery is complex, since, for those with anorexia, excessive exercise is often a component of the original disorder. However, very controlled exercise regimens may be used as both a reward for developing good eating habits and as a way to reduce the stomach and intestinal distress that accompanies recovery. Exercise should not be performed if severe medical problems still exist and if the patient has not gained significant weight. The goal of exercise should be on improving physical fitness and health, not on burning off calories.

Psychologic Therapies Used in Anorexia. Family therapy is an important component of anorexia treatment, especially for children and adolescents. Adults usually begin with motivational psychotherapy that provides an empathetic setting and rewards positive efforts towards weight gain. After weight is restored, cognitive behavioral therapy techniques are helpful.

Antidepressants. Studies have not reported many benefits for treating anorexia nervosa with selective serotonin reuptake inhibitors (SSRIs), the antidepressants that are often useful for patients with bulimia. A few studies suggest that these drugs could be useful for people with anorexia nervosa who also have obsessive-compulsive disorder (OCD).

Doctors hoped that SSRIs could help prevent relapse in patients who have successfully restored their body weight. However, in a well-designed study in the Journal of the American Medical Association there was no difference in the time to relapse between patients who received fluoxetine (Prozac) and those who received placebo.

Nutritional Supplements. Calcium and vitamin D supplements are often recommended. Some studies have reported that zinc supplements may help patients gain weight.

Therapy

Eating disorders are nearly always treated with some form of psychiatric or psychologic treatment. Depending on the problem, different psychologic approaches may work better than others.

Cognitive-behavioral therapy (CBT) works on the principle that a pattern of false thinking and belief about one's body can be recognized objectively and altered, thereby changing the response and eliminating the unhealthy reaction to food. One approach for bulimia is the following:

Over a period of 4 - 6 months the patient builds up to eating 3 meals a day, including foods that the patient has previously avoided.
During this period, the patient monitors and records the daily dietary intake along with any habitual unhealthy reactions and negative thoughts toward eating while they are occurring.
The patient also records any relapses (binges or purging). Such lapses are reported objectively and without self-criticism and judgment.
The patient discusses the responses with a cognitive therapist at regular sessions. Eventually the patient is able to discover the false attitudes about body image and the unattainable perfectionism that underlies the opposition to food and health.
Once these habits are recognized, food choices are broadened, and the patient begins to challenge any entrenched and automatic ideas and responses. The patient then replaces them with a set of realistic beliefs along with actions based on reasonable self-expectations.

Interpersonal therapy deals with depression or anxiety that might underlie the eating disorders along with social factors that influence eating behavior. This therapy does not deal with weight, food, or body image at all.

The goals are the following:

To express feelings
To discover how to tolerate uncertainty and change
To develop a strong sense of individuality and independence
To address any relevant sexual issues or traumatic or abusive event in the past that might be a contributor of the eating disorder

Studies generally report that interpersonal therapy is not as effective as cognitive therapy for bulimia and binge eating, but may be useful for some patients with anorexia. The skill of the therapist plays a strong role in its success.

Because of the major role family attitudes play in eating disorders, one of the first steps in treating the patient with early-onset anorexia is to also treat the family. Family therapy can be useful for both younger and older patients.

If the patient is hospitalized, experts recommend that family therapy start after the patient has gained weight, but before discharge. It should usually continue after the patient has left the hospital.

The feelings of intense guilt and anxiety that caregivers experience are probably similar to those produced by living with a person who is suicidal. An over-involved parent may even support the patient's eating disorder for various reasons:

Some parents may be afraid of releasing some underlying anger or grief directed at the patient.
Other parents may identify with the goal of thinness and not even perceive that their child is unhealthily underweight.

In such cases, it is extremely important that the family members fully understand the danger of this disorder and that they are collaborating in their child's illness, or even death, by encouraging this state.

Resources

www.nimh.nih.gov -- National Institute of Mental Health
www.anad.org -- National Association of Anorexia Nervosa and Associated Disorders
www.aedweb.org -- Academy for Eating Disorders
www.nationaleatingdisorders.org -- Eating Disorders Awareness and Prevention
www.eatright.org -- American Dietetic Association
www.aabt.org -- Association for Behaviorial and Cognitive Therapies
www.psych.org -- The American Psychiatric Association
www.aacap.org -- American Academy of Child and Adolescent Psychiatry

References

American Psychiatric Association. Treatment of patients with eating disorders, third edition. American Psychiatric Association. Am J Psychiatry. 2006 Jul;163(7 Suppl):4-54.

Berkman ND, Lohr KN, Bulik CM. Outcomes of eating disorders: a systematic review of the literature. Int J Eat Disord. 2007 May;40(4):293-309.

Bulik CM, Berkman ND, Brownley KA, Sedway JA, Lohr KN. Anorexia nervosa treatment: a systematic review of randomized controlled trials. Int J Eat Disord. 2007 May;40(4):310-20.

Morris J, Twaddle S. Anorexia nervosa. BMJ. 2007 Apr 28;334(7599):894-8.

Signorini A, De Filippo E, Panico S, De Caprio C, Pasanisi F, Contaldo F. Long-term mortality in anorexia nervosa: a report after an 8-year follow-up and a review of the most recent literature. Eur J Clin Nutr. 2007 Jan;61(1):119-22. Epub 2006 Aug 2.

Schmidt U, Lee S, Beecham J, et al. A randomized controlled trial of family therapy and cognitive behavior therapy guided self-care for adolescents with bulimia nervosa and related disorders. Am J Psychiatry. 2007 Apr;164(4):591-8.

Review Date:
12/31/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Systemic lupus erythematosus

FitSugar — Wed, 08 Oct 2008 17:35:17 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Treatment for Cutaneous and...
Treatment for Severe SLE...
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Systematic Lupus Erythematosus (SLE)

SLE is an autoimmune disease that causes a chronic inflammatory condition. The inflammation triggered by SLE affects many organs in the body, including skin, joints, kidneys, lung, and nervous system. Women, especially African-American and Asian women, are at highest risk for developing SLE.

Symptoms and Diagnosis

Not all patients with SLE experience the same symptoms. The most common symptoms are joint pain, skin rash, and fever. Symptoms can develop slowly or appear suddenly. Many patients with SLE have “flares,” in which symptoms suddenly worsen and then disappear for long periods of time. Diagnosing SLE is complicated because symptoms vary widely and can resemble other conditions. A doctor will base an SLE diagnosis on certain specific criteria including symptom history and the results of blood tests for antinuclear antibodies.

Treatment

No drug can cure SLE, but many different drugs can help control symptoms and relieve discomfort. The choice of drugs depends on the severity of the condition as well as other factors. Patients with mild SLE may be helped by nonsteroidal anti-inflammatory drugs (NSAIDs) while patients with more severe SLE may require corticosteroids or immunosuppressants. Researchers are working to develop new drugs and treatments for SLE.

Living with SLE

Patients can make lifestyle changes to help cope with SLE. These include:

Avoid excessive sunlight exposure, and wear sunscreen (ultraviolet light is the one of the main triggers of flares).
Get plenty of rest (fatigue is another common SLE symptom).
Engage in regular light-to-moderate exercise to help fight fatigue and heart disease, and to keep joints flexible.

Introduction

Systemic lupus erythematosus (SLE) is a chronic, often life-long, autoimmune disease. It can be mild to severe, and affects mostly women. SLE may affect various parts of the body, but it most often manifests in the skin, joints, blood, and kidneys. SLE was first described in 1828. Its very name helps define the disease:

Systemic is used because the disease can affect organs and tissue throughout the body.
Lupus is Latin for wolf. It refers to the rash that extends across the bridge of the nose and upper cheekbones and was thought to resemble a wolf bite.
Erythematosus is from the Greek word for red and refers to the color of the rash.

Lupus has many different symptoms. Common ones include:

Fatigue
Joint pain or swelling
Skin rashes

Causes

Systemic lupus erythematosus is a complex disorder that occurs as a consequence of a number of independent processes and factors.

Environmental factors, such as viruses, exposure to chemicals, or sunlight trigger inflammatory or immune activity. This immune activation may begin as an appropriate response to an unwanted "invader." But, because of a combination of genetic factors, an individual with lupus develops an ongoing immune response that does not shut itself off appropriately. This leads to waxing and waning flares of inflammation that can involve various organs of the body, depending on specific features of this self-perpetuating immune response in individual patients.

The exact combination of genes that predispose individuals to SLE may differ somewhat from patient to patient, but probably share certain common features which tend to impair the ability of the body to get rid of immune-triggering particles and which tend to prolong or increase the degree of immune responsiveness to these triggers.

A major characteristic of lupus is that it is an autoimmune response in which immune factors, called autoantibodies, attack the person's own cells. Some autoantibodies are normal in a well-balanced immune system, and serve various roles to help the body dispose of wastes, protect from infectious invaders, and to keep blood vessels clear. In healthy people, autoantibodies tend to be well-regulated and well "masked," or covered up, until needed. Therefore, it is probably the high activity and high detectability of autoantibodies that makes lupus unique, not the fact that they exist.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to fight any infections.
In the process, the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting any bleeding blood vessels and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has special factors that control and limit this inflammatory process.

The Infection Fighters. B cells and T cells are two important components of the immune system that play a role in the inflammation associated with lupus. Both B cells and T cells belong to a family of immune cells called lymphocytes. Lymphocytes help fight infection.

B cells and T cells are involved in the immune system's response to infection. Antigens are foreign bodies (such as bacteria and viruses) that stimulate the immune system to produce autoantibodies. When a T cell recognizes an antigen it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

For reasons that are still not completely understood, both the T cells and B cells become overactive in lupus patients. In lupus, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal range of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

Autoantibodies. In the majority of patients with SLE, antinuclear antibodies (ANA) are detectable. Such autoantibodies may be present in individuals up to 7 years prior to their developing symptoms of lupus. Some subtypes of ANA are found in lupus patients and only rarely in people without lupus. These include:

Anti-ds DNA. An autoantibody called anti-double stranded DNA (anti-ds DNA) may play an important role in some lupus patients.
Anti-Sm antibodies. This antibody is found most often in lupus patients of African descent and is almost never detected in people without lupus.
Anti-Ro (SSA) and Anti-La (SSB)
Antiphospholipid antibodies

Cytokines. Most immune cells secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for maintaining the balance of the body during immune responses, including:

Infections
Injuries
Tissue repair
Blood clotting
Clearing of debris from inflamed blood vessels
Other aspects of healing.

If overproduced, however, they can cause serious damage, including dangerous levels of inflammation and cellular injury. Specific cytokines called interferons and interleukins play a critical role in SLE by regulating the secretion of autoantibodies by B cells.

Complement. Another immune factor of high interest in SLE is the complement system. This is comprised of more than 30 proteins and is important for defending and regulating the immune response. Inherited deficiencies in certain complement components (C1q, C1r, C1s, C4, and C2) have long been associated with SLE.

Researchers estimated that 20 - 100 different genetic factors may be involved in the alterations of the immune system set point that could make a person susceptible to SLE.

Research published in 2003 identified a particular set of genes, now commonly called the "interferon signature," that is activated by interferon in patients with severe lupus. This discovery may help doctors identify patients at particular risk for severe disease before they develop symptoms.
A genetic risk factor for lupus in African-American women has been identified.
Other research has identified defects in genes that regulate apoptosis, the natural process by which cells self-destruct.
An abnormal gene identified in some patients with SLE promotes the build-up of immune complexes that can cause kidney damage. HLA (human leukocyte antigen) is a protein that presents antigens to T cells by holding them up from the surface of macrophages or other antigen-presenting cells. Among the types of HLA associated with lupus are HLA-DR2, -DR3, -A1, -B8, and DMA-0104.

In genetically susceptible people, there are various external factors that can provoke an immune response. Possible SLE triggers include colds, fatigue, stress, chemicals, sunlight, and certain drugs.

Viruses. Blood tests reveal that patients with SLE are more likely to have been exposed to certain viruses than the general population. These viruses include the Epstein-Barr virus (the cause of mononucleosis), cytomegalovirus, and parvovirus-B1.

Results from a 2005 study, conducted by researchers at the National Institute of Environmental Health Sciences, suggested a strong association between Epstein-Barr virus (EBV) and increased risk of lupus, particularly for African-Americans. The association was not as strong for whites, but increased with age (patients over 50 years of age had four times higher risk).

The researchers also observed that a genetic variation in CTLA-4, a protein that helps regulate T cell immune system response, appeared to modify the risk of lupus associated with EBV-IgA antibodies. Therefore, an individual’s CTLA-4 genotype could determine the immune system’s responsiveness in fighting repeat episodes of EBV infection.

Click the icon to see an image of mononucleosis.

Some research suggests that different viruses may imprint specific types of SLE. For instance cytomegalovirus may affect blood vessels and cause problems such as Raynaud's phenomenon or blood abnormalities, but may not affect the kidney as much. These are speculations, however, and not a proven association.

Sunlight. Ultraviolet (UV) rays found in sunlight are important SLE triggers. When they bombard the skin, they can alter the structure of DNA in cells below the surface. The immune system may perceive these altered skin cells as foreign and trigger an autoimmune response against them. UV light is categorized as UVB or UVA depending on the length of the wave.

UVB are short waves (280 - 320 nm). The shorter the wavelengths, the more damage they do.
UVA are longer waves (320 - 400 nm). Some research suggests that UVA wavelengths in the longest range, known as UVA1 (340 - 400 nm), may actually repair DNA and normalize immune responses.

Chemicals. Clusters of SLE cases have occurred in populations with high exposure to certain chemicals. Chlorinated pesticides and crystalline silica are two suspects. A number of other chemicals are under investigation. However, it is very difficult to determine a causal role for any specific chemicals. (Silicone breast implants have been under intense scrutiny as a possible trigger of autoimmune diseases, including SLE. The weight of evidence to date, however, finds no support for this concern.) Some drugs have been associated with a temporary lupus syndrome (drug-induced lupus), which resolves when these drugs are stopped.

Hormones. Cytokines, major immune factors that are active in SLE, are directly affected by sex hormones. In general, estrogen enhances antibody production, and testosterone reduces antibody production, although their exact role in SLE may be more complicated than that since there are various ways in which each hormone might influence various immune cells. Women with SLE may have lower levels of several active male hormones (androgens), and some men who are affected by SLE may also have abnormal androgen levels.

Premature menopause, and its accompanying symptoms (such as hot flashes), is common in women with SLE. Hormone replacement therapy (HRT), which is used to relieve these symptoms, increases the risk for blood clots and heart problems. It is not clear whether HRT triggers SLE flares. Women should discuss with their doctors whether HRT is an appropriate and safe choice. Guidelines recommend that women who take HRT use the lowest possible dose for the shortest possible time. Women with SLE who have active disease, antiphospholipid antibodies, or a history of blood clots or heart disease should not use HRT.

Oral Contraceptives. Female patients with lupus used to be cautioned against taking oral contraceptives (OCs) due to the possibility that estrogen could trigger lupus flare-ups. However, recent evidence indicates that OCs are safe, at least for women with inactive or stable lupus. Women who have been newly diagnosed with lupus should avoid OCs. Lupus can cause complications in its early stages. For this reason, women should wait until the disease reaches a stable state before taking OCs. In addition, women who have a history of, or who are at high risk for, blood clots (particularly women with antiphospholipid syndrome) should not use OCs. The estrogen in OCs increases the risk for blood clots.

Risk Factors

The number of people diagnosed with lupus has more than tripled over the past four decades. Some experts believe this may simply indicate a greater degree of doctor training in recognizing the syndrome.

About 90% of lupus patients are women, most diagnosed when they are in their childbearing ages. Hormones may be an explanation. After menopause, women are only 2.5 times as likely as men to contract SLE. Flares also become somewhat less common after menopause in women who have chronic SLE.

African-Americans are three to four times more likely to develop the disease than Caucasians and to have severe complications. Hispanics and Asians are also more susceptible to the disease.

A family history plays a strong role in SLE. A brother or sister of a patient with the disorder has 20 times the risk as someone without an immediate family member with SLE.

The disease is rare in childhood. When it does occur, it is often associated with thrombotic thrombocytopenia purpura, a condition resulting from abnormally low levels of blood platelets. SLE in children may also be caused by certain medications, including minocycline and zafirlukast.

Rheumatoid Arthritis. Studies have investigated the relationship among hormones, SLE, and rheumatoid arthritis, another autoimmune disease. Higher levels of estrogen are associated with SLE, while lower levels are associated with rheumatoid arthritis. Some research suggests that some patients, in fact, progress from one disease to the other, and that such transitions occur during major hormonal shifts, such as the onset of menopause or pregnancy.

Rheumatoid arthritis is a systemic autoimmune disease that initially attacks the lining, or synovium, of the joints.

Many prescription drugs can cause lupus-like skin symptoms. In one study, the most common drugs causing these symptoms were high blood pressure (hypertension) medications, including hydrochlorothiazide, angiotensin-converting-enzyme inhibitors, and calcium-channel blockers. About 40 different drugs have been linked to lupus onset. Anyone diagnosed with cutaneous lupus erythematosus should be sure to tell their doctors all the medications (including herbs and supplements) that they are taking.

Smoking. Smoking may be a risk factor for triggering SLE and can increase the risk for skin and kidney problems in women who have the disease.

Symptoms

SLE symptoms may develop slowly over months or years, or they may appear suddenly. Symptoms tend to be worse during winter months, perhaps because prolonged exposure to sunlight in the summer causes a gradual build-up of factors that trigger symptoms months later.

The most common symptom is joint pain, which occurs in about 90% of patients with SLE. Characteristics of this symptom vary widely:

It is often accompanied by swelling and redness.
It can last from hours to months.
It may be mild or severe.
It can occur in one joint, move from one to another, or flare erratically.
Pain often occurs in the morning and improves during the day, only to return later when the patient tires.
The joints most affected are fingers, wrists, elbows, knees, and ankles. (Joints in the spine and neck are not affected.)

Children may experience these symptoms as growing pains, and, in all patients, they may be the only symptoms for many years.

Fever occurs in 90% of patients with SLE and is usually caused by the inflammatory process of the disease, not by infection. It is low-grade except during an acute lupus crisis.

Three-quarters of patients with SLE have skin inflammation and skin lesions (ulcers, rashes, or other injured areas). About half of these lesions are photosensitive; that is, they are aggravated by ultraviolet (UV) radiation from sunlight, even from light coming through a window. (UV radiation may even trigger systemic flares in patients with SLE.)

A number of different skin conditions have been described in patients with SLE.

Discoid Lupus Erythematosus. About 20% of patients have discoid lesions. In such cases, the condition is often known as discoid lupus erythematosus (DLE). Patients with this condition may have the following skin abnormalities:

Discoid means coin-shaped, so these lesions are round and raised. They are also scaly. Untreated, the margins gradually extend outward as the center dries out and shrivels, causing severe scarring. If discoid lesions appear on the scalp, they can plug hair follicles and cause irreversible hair loss. Discoid lesions can also appear on the upper body.

Lupus, discoid -- view of lesions on the chest: This close-up picture of the neck clearly shows the typical rounded appearance of discoid lupus. The whitish appearance is caused by scaling. The two dark spots are biopsy sites and are not part of the disease.

A butterfly-shaped rash across the face may accompany this condition. This rash causes little scarring, although spidery, branching lines of swollen capillaries (the tiniest blood vessels) may appear.

Click the icon to see an image of systemic lupus erythematosus.

Most patients with this condition have only a limited skin disorder. In only about 10% of cases does discoid lupus develop into full-blown SLE.

Subacute Cutaneous Lupus Erythematosus. Subacute cutaneous lupus erythematosus (SCLE) can cause skin lesions on parts of the body that are exposed to sunlight. These lesions do not cause scarring.

Vasculitis. Patients with SLE sometimes develop inflammation in the blood vessels (vasculitis) that may have the following effects on the skin:

Red welts may form across large areas of the body.
Sometimes deep red bumps may appear, particularly on the leg, where they may ulcerate.
In some people, reddish-purple lesions appear on the pads of fingers and toes or near the nails of fingers and toes.
Lesions caused by vasculitis may ulcerate or blister if they erupt on mucous membranes in the mouth, nose, or vagina and can be painful if they occur on the throat.
Vasulitis can attack blood vessels in almost any other organ, including the brain, the heart, and the gastrointestinal tract.

Click the icon to see an image of vasculitis.

Other symptoms include:

Fatigue
Loss of appetite, nausea, and weight loss
Chest pain
Bruising
Menstrual irregularities
Thought and concentration disturbances
Personality changes
Sleep disorders, such as restless legs syndrome and sleep apnea
Dryness of the eyes and mouth
Brittle hair or hair loss

Hair loss or breakage may also occur in about half of patients with SLE during severe flares or after pregnancy or severe illness. In such cases, hair grows back.

Raynaud's phenomenon is a condition in which cold or stress can cause spasms in impaired blood vessels, resulting in pain in fingers and toes. It occurs as part of the inflammatory response in blood vessels, which can narrow them and reduce circulation. In extreme cases, gangrene can result.

Click the icon to see an image of Raynaud's phenomenon.

A number of conditions may resemble SLE:

Scleroderma: Hardening of the skin caused by overproduction of collagen
Multiple sclerosis: Fatigue, heaviness or clumsiness in the arms and legs
Rheumatoid arthritis: Inflammation of the lining of the joints
Sjögren syndrome: Characterized by dry eyes and dry mouth
Mixed connective tissue disorder: Similar to SLE, but milder
Myositis: Inflammation and degeneration of muscle tissues
Rosacea: Flushed face with pus-filled blisters
Seborrheic dermatitis: Sores on lips and nose
Lichen planus: Swollen rash that itches, typically on scalp, arms, legs, or in the mouth
Dermatomyositis: Bluish-red skin eruptions on face and upper body
Lyme disease: Bulls-eye rash, joint inflammation, and flu-like symptoms

Complications

Systemic lupus erythematosus (SLE) is one of the most serious rheumatic diseases. According to a 2002 government study, the annual number of deaths has risen from 879 - 1,406 since 1979. About a third of these deaths occur in people aged 15 - 44 years, mostly women. Such numbers may be underestimates, since SLE can affect so many organs that a cause of death in some people with SLE may not be directly attributed to the condition. A primary cause of death among patients with lupus is atherosclerosis, a disease of the coronary blood vessels resulting from accelerated buildup of plaque.

SLE is unpredictable and varies greatly form one individual to the next. Severity also appears to differ among ethnic groups and countries. In European and North American patients with SLE for example, overall 5-year survival rates are 93 - 95%, while in Asia or Africa they are considerable lower (60 - 70%). Other research indicates that African-American and Hispanic American patients suffer greater organ damage than Caucasian patients. Genetic factors appear to have some influence on specific effects of SLE on organ damage among ethnic groups. However, the poorer outlook among minority groups and in underdeveloped nations is probably due to less access to good health care.

Mild SLE. About 20 - 30% of cases are mild. For many of these patients, the only symptoms may be the skin rashes of discoid lupus erythematosus (DLE) or subacute cutaneous lupus erythematosus (SCLE) with or without joint aches. The number and intensity of symptoms in mild cases often decrease over time, as does the likelihood of major organ involvement. These skin conditions, however, are not absolute insurance against more severe disease, and patients with mild SLE should be tested for organ involvement.

Widespread SLE. Most commonly, SLE is a chronic, life-long disease, alternating between periods of symptom relapse, (called flares), and remission. The disease may begin in any of the various systems of the body and progress unpredictably to others. The following are typical patterns:

Symptom relapses, or flares, occur on the average of two or three times a year.
Between flares, most patients with SLE function at about 90% of normal capacity.

The degree of severity depends on different factors:

Severity of the inflammatory response
Frequency of episodes
The degree of organ or system involvement

Vital organs or systems, such as lungs, kidneys, nervous system, joints skin, and others are affected in 50 - 75% of patients with SLE. Infections followed by kidney failure are the chief causes of death in patients with SLE.

Because of more effective and aggressive treatment, the prognosis for SLE has improved markedly over the past two decades. Long-term progress of the disease is affected greatly by treatment in the initial acute phase of the disease, so a speedy and accurate diagnosis is all-important. The 10-year survival rate with treatment is now 85 - 95%, and many people have a normal life span. SLE that develops later in life is generally less serious than SLE that strikes in childhood.

Almost 85% of patients with SLE experience problems associated with abnormalities in the blood.

Anemia. About half of patients with SLE are anemic. Causes include:

Iron deficiencies resulting from excessive menstruation
Iron deficiencies from gastro-intestinal bleeding caused by some of the treatments
A specific anemia called hemolytic anemia, which destroys red blood cells
Anemia of chronic disease

Hemolytic anemia can occur with very high levels of the anticardiolipin antibody. It can be chronic or develop suddenly and be severely (acute).

Antiphospholipid Syndrome. Between 34 - 42% of patients with SLE have antiphospholipid syndrome (APS). This is a specific set of conditions related to the presence of autoantibodies called lupus anticoagulant and anticardiolipin. These autoantibodies react against fat molecules called phospholipids, and so are called antiphospholipids. Their actions have complex effects that include causing narrowing and abnormalities of blood vessels.

Patients who have APS have a very incidence of blood clots, which most often occur in the deep veins in the legs (32%). Blood clotting, in turn, puts patients at higher risk for stroke (13%) and pulmonary embolism (clots in the lungs) (9%).

This picture shows a red and swollen thigh and leg caused by a blood clot (thrombus) in the deep veins in the groin (iliofemoral veins). Such a clot prevents normal return of blood from the leg to the heart.

About 22% of patients have thrombocytopenia -- a reduction in blood platelets that can cause bleeding.
The effects on blood vessels have also been associated with confusion, headaches, and seizures. Leg ulcers can also develop.
Patients with APS who become pregnant have a high incidence of pregnancy loss, especially in the late term.

Not all patients with APS carry both of the autoantibodies, and they can also wax and wane and so have varying effects. APS also occurs without lupus in about half of patients with the syndrome.

Thrombocytopenia. In thrombocytopenia, antibodies attack blood platelets. In such cases, blood clotting is impaired, which causes bruising and bleeding from the skin, nose, gums, or intestines. (This condition can also occur in APS, but it is not considered to be one of the standard features of the syndrome.)

Neutropenia. Neutropenia is a drop in the number of white blood cells. Patients with SLE often neutropenia, but the condition is usually harmless unless the reductions are so severe that they leave the patient vulnerable to infections.

Acute Lupus Hemophagocyte Syndrome. A rare blood complication of SLE that occurs primarily in Asians is called acute lupus hemophagocytic syndrome. It is generally of short duration and characterized by fever and a sudden drop in blood cells and platelets.

Lymphomas. Patients with SLE and other autoimmune disorders have a greater risk for developing lymph system cancers such as Hodgkin’s disease and non-Hodgkin’s lymphoma (NHL). A 2005 study reported that patients with SLE were over seven times more likely to develop NHL than healthy patients.

Heart disease is a primary cause of death in lupus patients. The immune response in SLE can cause inflammation and other damaging effects that can cause significant injury to the arteries and tissues associated with the circulation and the heart. In addition, SLE treatments (particularly corticosteroids) affect cholesterol, weight, and other factors that can also affect the heart. For decades, experts questioned the extent to which the drugs used to treat SLE contributed to the high rate of atherosclerosis in such patients. Numerous studies now suggest that something about the disease process itself, possibly the chronic inflammation of the blood vessels, probably lies at the root of this dangerous problem. In any event, patients with SLE, have a higher chance for the following conditions, which put them at risk for heart attack or stroke:

Atherosclerosis, or plaque buildup in the arteries
Increased stiffness in the arteries
Unhealthy cholesterol and lipid (fatty molecules) levels
High blood pressure, most likely because of kidney injury and corticosteroid treatments
Congestive heart failure
Pericarditis, an inflammation of the tissue surrounding the heart (occurs in about 30% of patients)
Myocarditis, an inflammation of the heart muscle itself (rare)

Click the icon to see an image of pericarditis.

Abnormalities in the valves of the heart (rare)
Blood clots

The risk for cardiovascular disease, heart attack, and stroke is much higher than average in younger women with SLE. The risks decline as such women age.

SLE affects the lungs in about 60% of patients:

Recurrent inflammation of the membrane lining the lung (pleurisy) is the most common problem.
In some cases, fluid accumulates, a condition called pleural effusion, and can cause stabbing localized pain that worsens when coughing, sneezing, laughing, or taking a deep breath.
Inflammation of the lung itself in SLE is called lupus pneumonitis. It can be caused by infections or by the SLE inflammatory process. Symptoms are the same in both cases: fever, chest pain, labored breathing, and coughing. Rarely, lupus pneumonitis becomes chronic and causes scarring in the lungs, which reduces their ability to deliver oxygen to the blood.
A very serious and also rare condition called pulmonary hypertension occurs when high pressure develops in the vessels supplying blood to the lungs.

Click the icon to see an image of primary pulmonary hypertension.

The kidneys are a crucial battleground in SLE because it is here that the debris left over from the immune attacks is most likely to be deposited. About 50% of patients with SLE exhibit inflammation of the kidneys (called lupus nephritis).This condition occurs in different forms and can vary widely in severity.

Click the icon to see an image of the kidney.

Proliferative nephritis is a serious variant of lupus nephritis. It occurs when the inflammatory process causes widespread damage and scarring in the blood vessels of the kidneys, which filters waste products, water, and salts out of the blood. The condition is associated with high blood pressure and kidney deterioration.
Membranous lupus nephritis is another variant that is often associated with a good outlook. In some cases, however, if the kidney is persistently exposed to high protein levels, the disorder can progress to fatal end-stage kidney (renal) disease.

Serious complications occur eventually in about 30% of patients. If kidney injury develops, it almost always occurs within 10 years of the onset of SLE, rarely after that.

Nearly all patients with SLE report some symptoms relating to problems that occur in the central nervous system (CNS), which includes the spinal cord and the brain. Most of these symptoms are minor and some, such as headache, may be related to depression rather than the disease itself. CNS involvement is more likely to occur in the first year, usually during flare-ups in other organs. Symptoms vary widely and may be indistinguishable from psychiatric or neurologic disorders or from the side effects of some medications used for SLE. Central nervous system symptoms are usually mild, but there is little effective treatment available for them. CNS symptoms get worse as the disease progresses.

The most serious CNS disorder is inflammation of the blood vessels in the brain, which occurs in 10% of patients with SLE. Fever, seizures, psychosis, and even coma can occur. Other CNS side effects include:

Irritability
Emotional disorders (anxiety, depression)
Mild impairment of concentration and memory
Migraine and tension headaches
Problems with the reflex systems, sensation, vision, hearing, and motor control

Infections are a common complication and a major cause of death in all stages of SLE. The immune system is indeed overactive in SLE, but it is also abnormal and reduces the ability to fight infections. Patients are not only prone to the ordinary streptococcal and staphylococcal infections, but they are also susceptible to fungal and parasitic infections (called opportunistic infections), which are common in people with weakened immune systems. They also face an increased risk for herpes, salmonella, and yeast infections. Corticosteroid and immunosuppressants, treatments used for SLE, also increase the risk for infections, thereby compounding the problem.

About 45% of patients with SLE suffer gastrointestinal problems, including nausea, weight loss, mild abdominal pain, and diarrhea. Severe inflammation of the intestinal tract occurs in less than 5% of patients and causes acute cramping, vomiting, diarrhea, and, rarely, intestinal perforation, which can be life-threatening. Fluid retention and swelling can cause intestinal obstruction, which is much less serious but causes the same type of severe pain. Inflammation of the pancreas can be caused by the disease and by corticosteroid therapy.

Arthritis caused by SLE almost never leads to destruction or deformity of joints. The inflammatory process can, however, damage muscles and cause weakness. Patients with SLE also commonly experience reductions in bone mass density (osteoporosis) and have a higher risk for fractures, whether or not they are taking corticosteroids (which can increase the risk for osteoporosis). Women who have SLE should have regular bone mineral density scans to monitor bone health.

Click the icon to see an image of osteoporosis.

Inflamed blood vessels in the eye can reduce blood supply to the retina, resulting in degeneration of nerve cells and a risk of hemorrhage in the retina. The most common symptoms are cotton-wool-like spots on the retina. In about 5% of patients sudden temporary blindness may occur.

In one study, 40% of patients with SLE quit work within 4 years of diagnosis, and many had to modify their work conditions. Significant factors that predicted job loss included high physical demands from the work itself, a more severe condition at the time of diagnosis, and lower educational levels. People with lower income jobs were at particular risk for leaving them.

Women with lupus who conceive face high-risk pregnancies. It is important for women to understand the potential complications and plan accordingly. The most important advice is to avoid becoming pregnant when lupus is active.

Research suggests that the following factors predict a successful pregnancy:

Disease state at time of conception. Experts strongly recommend that women wait to conceive until their disease state has been inactive for at least 6 months.
Kidney (renal) function. Women should make sure that their kidney function is evaluated prior to conception. Poor kidney function can worsen high blood pressure and cause excess protein in the urine. These complications increase the risk for preeclampsia and miscarriage.
Lupus-related antibodies. Antiphospholipid and anticardiolipin antibodies can increase the risks for preeclampsia, miscarriage, and stillbirths. Anti-SSA and anti-SSB antibodies can increase the risk for neonatal lupus erythematosus, a condition that can cause skin rash and liver and heart damage to the newborn baby. Levels of these antibodies should be tested at the start of pregnancy. Certain medications (aspirin, heparin) and tests (fetal heart monitoring) may be needed to ensure a safe pregnancy.
Medication use during pregnancy. Women with active disease may need to take low-dose corticosteroids, but women with inactive disease should avoid these drugs. Steroids appear to pose a low risk for birth defects, but can increase a pregnant woman’s risks for gestational diabetes, high blood pressure, infection, and osteoporosis. For patients who need immunosuppressive therapy, azathioprine (Imuran) is an option. Methotrexate (Rheumatrex) and cyclophosphamide (Cytoxan) should not be taken during pregnancy.

Pregnancy Risks

Women with lupus are 20 times more likely to die during pregnancy than women without the disease. The risk for maternal death is due to the following serious conditions that can develop during pregnancy:

Miscarriages. About 25% of lupus pregnancies result in miscarriage. The risk is highest for patients with antiphospholipid antibodies, active kidney disease, or high blood pressure.
Blood clots. Women with lupus have a 6 times greater risk for developing deep vein thrombosis (blood clots) than women without the disease.
Clotting complications. Low blood platelet count and anemia are also risks. Women with lupus are 3 times more likely to need a transfusion during pregnancy than women without lupus.
Infections. Blood infections (sepsis), pneumonia, and urinary tract infections are more common in pregnant women with lupus.
Preeclampsia. Women with lupus are three times more likely than healthy women to develop preeclampsia (pregnancy-related high blood pressure), which can be potentially life threatening.

Birth Complications

Pre-term birth. Women with lupus are 2.5 times more likely to have pre-term labor than women without lupus. Pre-term labor increases the risk for giving birth to low-weight babies.
Stillbirths. A 2005 study reported that the risk of still births was 10 times greater for women who had not yet been diagnosed with lupus, and 4 times greater for women with diagnosed lupus, compared with healthy women. This suggests that lupus may have a pre-disease state.
Caesarean section. Thirty-seven percent of women with lupus require a C-section compared with 22% of women without the disease.

Despite these obstacles, many women with lupus have healthy pregnancies and deliver healthy babies. To increase the odds of a successful pregnancy, it is important for women to plan carefully before becoming pregnant. Be sure to find knowledgeable doctors with whom you can communicate and trust. Experts recommend that pregnant women with lupus assemble an interdisciplinary health care team that includes a rheumatologist, high-risk obstetrician, and (for patients with kidney disease) a nephrologist.

Diagnosis

No single test can confirm or rule out SLE. A number of tests are required before SLE can be diagnosed definitively. The first symptoms of SLE can resemble one of many syndromes or disorders, including rheumatoid arthritis, Still's disease, rheumatic fever, Lyme disease, multiple sclerosis, thrombotic thrombocytopenia purpura, cryoglobulinemia, Weber-Christian disease, viral infections, vasculitis, psychosis, and other conditions. Other autoimmune disorders, such as Sjögren syndrome or scleroderma, may even be present at the same time as SLE.

1. Characteristic rash across the cheek

2. Discoid lesion rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

6. Inflammation of membranes in the lungs, the heart, or the abdomen

7. Evidence of kidney disease

8. Evidence of severe neurologic disease

9. Blood disorders, including low red and white blood cell and platelet counts

10. Immunologic abnormalities

11. Positive antinuclear antibody (ANA)

Note: A patient must experienced four of the criteria before a doctor can classify the condition as SLE. These criteria, proposed by the American College of Rheumatology, are not to be relied upon solely for diagnosis, however.

Methods for measuring the antibodies involved with SLE vary, and the range of results can be bewildering. Repeat tests may be needed.

Antinuclear Antibodies (ANAs). A primary test for SLE checks for antinuclear antibodies (ANA), which attack the cell nucleus.

High levels of ANA are found in more than 98% of patients with SLE. A number of other conditions, however, also cause high levels of ANA, so a positive test is not a definite diagnosis for SLE:

Antinuclear antibodies may be strongly present in other autoimmune diseases (such as scleroderma, Sjögren syndrome, or rheumatoid arthritis).
They also may be weakly present in about 20 - 40% of healthy women.
Some drugs can also produce positive antibody tests, including hydralazine, procainamide, isoniazid, and chlorpromazine.

A negative ANA test makes a diagnosis of SLE unlikely but not impossible. High or low concentrations of ANA also do not necessarily indicate the severity of the disease, since antibodies tend to come and go in patients with SLE.

In general, the ANA test is considered a screening test:

If SLE symptoms are present and the ANA test is positive, other tests for SLE will be administered.
If SLE symptoms are not present and the test is positive, the doctor will look for other causes, or the results will be ignored if the patient is feeling healthy.

ANA Subtypes. In some cases, doctors may test for specific ANA subtypes.

Anti-double stranded DNA (Anti-ds DNA) is usually found only in patients with SLE. It may play an important role in injury to blood vessels found in SLE, and high levels often indicate kidney involvement. Anti-ds DNA levels tend to fluctuate over time and may even disappear.
Anti-Sm antibodies are also usually found only with SLE. They are more constant and are more likely to be detected in African-American patients. Although the antibody is not usually seen in lupus patients, its confirmed presence almost always indicates SLE.
When the ANA is negative but the diagnosis is still strongly suspected, a test for anti-Ro (also called anti-SSA) and anti-La (also called anti-SSB) antibodies may identify patients with a rare condition called ANA negative, Ro lupus. These autoantibodies may be involved in the sun-sensitive rashes experienced by patients with SLE and are also found in association with neonatal lupus syndrome, in which a pregnant mother's antibodies cross the placenta and cause inflammation in the developing child's skin or heart.

Antibodies to SR Proteins. An advance in diagnosing SLE has been the detection of antibodies to molecules called SR proteins, which are carried by most patients. The test accurately detects lupus in 50 - 70% of patients who test positive for these antibodies.

Antiphospholipid Antibodies. In patients with SLE in whom blood abnormalities are suspected, tests may be able to detect the presence of the two major antiphospholipid antibodies:

A quarter to a half of patients with SLE may have these antibodies. They attack blood-clotting regulator proteins that stick to phospholipids, fatty compounds found in cell membranes throughout the body. Antiphospholipid antibodies increase the risks for blood clots and may be responsible for narrowing of (and irregularities in) blood vessels. Antiphospholipid antibodies are linked with miscarriages and other pregnancy complications, strokes, heart attacks and blood clots in almost any part of the body, including kidneys, legs, lungs, and eyes.
The test for the lupus anticoagulant antibody measures the time it takes blood to clot. A longer than normal blood clotting time indicates a higher chance for clotting in the body and, therefore, the presence of lupus anticoagulant.
An ELISA test (enzyme-linked immunosorbent assay) is performed to detect the anticardiolipin antibody.

As with the ANA, these antibodies also have a tendency to appear and disappear in a single patient. Patients who have these autoantibodies as well as blood clotting problems or frequent miscarriage are diagnosed with antiphospholipid syndrome (APS), which often occurs in SLE but can also develop independently.

Complement. Blood tests of patients with SLE often show low levels of serum complement, a protein in the blood that aids the body's infection fighters. Individual proteins are termed by the letter "C" followed by a number. Common complement tests measure C3, C4, C1q, and CH50. There is some evidence that complete deficiencies of C1q may be a key factor in the inability of the immune system to contain the autoimmunity process. Complement levels are especially low if there is kidney involvement or other disease activity.

LE Cell Tests. The first blood test ever used for SLE called LE (lupus erythematosus) cell test is positive in only about half of patients with SLE and is no longer used that often.

Blood Count. White and red blood cell and platelet counts are usually lower than normal and, depending on severity, are used to determine complications, such as anemia or infection.

Click the icon to see an image of the formed elements of blood.

If a skin rash is present, the doctor may take a biopsy (a tissue sample) from the margin of a skin lesion. A test known as a lupus band detects antibodies known as immunoglobulin G (IgG), which are located just below the outer layer of the tissue sample. They are present in about 80% of patients with active SLE and in 30 - 40% of those with inactive disease. The biopsy will not differentiate between systemic and discoid lupus, but it can rule out other diseases. Tests for other antibodies will rule out or confirm discoid lupus and subacute cutaneous lupus.

Kidney Damage and Lupus Nephritis. Kidney damage in patients already diagnosed with SLE may be detected from the following tests:

Blood tests that measure creatinine, a protein metabolized in muscles and excreted in the urine. High levels suggest kidney damage, although it can also be present with normal creative levels.
Tests for detecting anti-ds DNA antibodies and complement. High levels of anti-ds DNA and low levels of complement C3 suggest kidney damage. (It should be noted, however, that some patients with severe kidney damage show low levels of anti-ds DNA.) Testing for anti-C1q antibodies now appears to be an even more reliable indicator of lupus nephritis.
Urine analysis. Urine analyses should be performed at 4- to 6-month intervals to check for signs of kidney involvement.
A kidney biopsy. This may be performed to determine if lupus nephritis is present when less invasive tests indicate kidney involvement. It is not absolutely accurate but it helps determine treatment. Electron microscopy (very high-powered electronic microscopes) may be especially important in obtaining critical information on the degree of kidney damage.

Lung and Heart Involvement. A chest x-ray may be performed to check lung and heart function. An electrocardiogram and an echocardiogram are administered if heart disease is suspected.

Click the icon to see an image of an electrocardiogram.

Central Nervous System Complications. SLE occurring in the central nervous system (CNS) can be difficult to diagnose because its symptoms are easily confused with other psychiatric and neurologic conditions.

Tests of the cerebrospinal fluid (CSF) for elevated levels of autoantibodies are the most reliable ways to detect CNS complications caused by a faulty immune system.
Additional tests, including electroencephalograms (EEGs), magnetic resonance imaging (MRI), computed tomography (CT), or x-rays may be useful when blood vessel blockage in the brain is suspected.
If the doctor suspects that CNS symptoms are caused by infection, especially for patients who are receiving immunosuppressant therapy, a lumbar puncture should be performed.

Osteoporosis. To detect early osteoporosis in patients with SLE whose disease has lasted more than 3.5 years, experts recommend an imaging test called dual energy x-ray absorptiometry (DEXA) to measure bone mineral density.

Treatment

No treatment cures systemic lupus erythematosus, but many therapies can suppress symptoms and relieve discomfort. Treatment of SLE varies depending on the extent and severity of the disease.

Only three drugs are FDA-approved for the treatment of lupus:

Prednisone
Aspirin
Hydroxychloroquine

However, none of these drugs are the current standard of care. In everyday practice, numerous other drugs are commonly used. Researchers are conducting numerous clinical studies and drug investigations. Genetic research in lupus is progressing very rapidly, and hopefully new drugs will be approved in the future. There are also different drugs available to treat some of the conditions associated with lupus.

Less intensive treatments may be effective for symptoms of mild lupus. They include:

Creams and sunblocks for rashes
Nonsteroidal anti-inflammatory drugs for fever, arthritis, and headache
Antimalarial drugs for pleurisy, mild kidney involvement, and inflammation of the tissue surrounding the heart

More aggressive treatment is needed if there is serious disease progression, as evidenced by:

Hemolytic anemia
Low platelet count with an accompanying rash (thrombocytopenia purpura)
Major involvement in the lungs or heart
Significant kidney damage
Acute inflammation of the small blood vessels in the extremities or gastrointestinal tract
Severe central nervous system symptoms

The primary approach to treating severe SLE is to suppress the immune factors, most often first with corticosteroids and other immunosuppressant drugs. Investigational drugs and procedures are also showing promise.

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspects of SLE. They are discussed elsewhere in this report.

Treatment for Cutaneous and Mild SLE

Creams. Steroid creams are often used for skin lesions. However, many patients with discoid lupus do not respond to steroids, particularly if they have eruptions that are caused by sun sensitivity. A cream derived from vitamin A (Tegison) may help some lesions that do not clear up with steroid creams.

Sun Protection. Sun protection is essential. Patients should always use sunblock creams (not just sunscreens) and always wear hats and clothing made of tightly woven fabrics.

Common NSAIDs. NSAIDs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs.

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin, Advil), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil).

For people with lupus, NSAIDs may help relieve:

Joint pain and swelling
Muscle pain

Side Effects. Regular, long-term use of NSAIDs can cause ulcers and gastrointestinal bleeding, which can lead to anemia. To avoid these problems, it’s best to take NSAIDs with food or immediately after a meal. Long-term use of NSAIDs (with the exception of aspirin) can also increase the risk for heart attack and stroke.

Other NSAID side effects may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Patients who have kidney problems associated with lupus (lupus nephritis) should be especially cautious about using NSAIDs. Experts recommend that patients with lupus who take NSAIDs on a regular basis should have their liver and kidney function tested every 3 - 4 months.

An ulcer is a crater-like lesion on the skin or mucous membrane caused by an inflammatory, infectious, or malignant condition. Patients can take certain medicines to suppress the acid in the stomach causing the erosion of the stomach lining. Endoscopic therapy can be used to stop bleeding from the ulcer.

Long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) is the second most common cause of ulcers. Ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are more likely to bleed than those caused by the bacteria Helicobacter pylori.

Those at high risk for bleeding include people over age 60, anyone with a history of ulcers or gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

A doctor may prescribe antimalarial drugs for discoid lupus (skin sores) or mild lupus when skin problems and joint pains are the predominant symptoms:

Hydroxychloroquine (Plaquenil) is the most common antimalarial drug used for lupus. This drug is effective as maintenance therapy to reduce flares in patients with mild or inactive disease. Hydroxychloroquine may help protect against blood clots in people with antiphospholipid syndrome, high cholesterol levels, and bone loss.
Other antimalarial drugs include chloroquine (Aralen) or quinacrine (Atabrine).

Treatment may start initially with high doses in order to accumulate high levels of the drug in the bloodstream. It is not known exactly why antimalarials work. Some researchers believe they inhibit the immune response, and others think they interfere specifically with inflammation.

A 2006 study suggested that anti-malarial drugs work best in patients who have genetic predispositions to certain types of immune-fighting proteins. The study found that patients who had genetic variations causing abnormally high levels of tumor necrosis alpha (TNF-alpha) and abnormally low levels of interleukin-10 (IL-10) responded best to these drugs.

Side Effects. Side effects of antimalarials may include:

Skin rash
Change in skin color (yellow in the case of quinacrine)
Gastrointestinal problems
Headache
Hair loss
Muscle aches
Eye damage

The most serious is damage to the retina, although this is very uncommon at low doses. Eye damage after taking hydroxychloroquine is reversible when caught in time and treated, but it is not reversible if the damage develops after taking chloroquine. An eye exam is advisable about every 6 months.

Antimalarials may also be used in combination with other anti-SLE drugs, including immunosuppressants and corticosteroids. It should be noted that smoking significantly reduces the effectiveness of antimalarial drugs.

Treatment for Severe SLE

Severe SLE is treated with corticosteroids, also called steroids, which suppress the inflammatory process. Steroids can help relieve many of the complications and symptoms, including anemia and kidney involvement.

Oral prednisone (Deltasone, Orasone) is usually prescribed. Other drugs include methylprednisolone (Medrol, Solumedrol), hydrocortisone, and dexamethasone (Decadron).

Some people need to take oral prednisone for only a short time; others may require it for a long duration. An intravenous administration of methylprednisolone using "pulse" therapy for 3 days is proving useful for flare-ups in the joints. Combinations with other drugs, particularly immunosuppressants, may be beneficial.

Regimens vary widely, depending on the severity and location of the disease. Most patients with SLE can eventually function without prednisone, although some may have to choose between the long-term toxicity of corticosteroids and the complications of active disease.

Side Effects of Long-Term Oral Corticosteroids. Unfortunately, serious and even life-threatening complications have been associated with long-term steroid use. The bone-thinning condition osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, alendronate etidronate, risedronate, or hormone replacement therapy in post-menopausal women. Vitamin C and E may help reduce the risk of cataracts.

Other side effects associated with prolonged use of oral steroids include:

Cataracts
Glaucoma
Diabetes
Fluid retention
Susceptibility to infections
Weight gain
High blood pressure
Acne
Excess hair growth
Wasting of the muscles
Menstrual irregularities
Irritability
Insomnia
Psychosis

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. A few cases of severe adrenal insufficiency have occurred when patients switched from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctors measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Drugs known as immunosuppressants are often used, either alone or with corticosteroids for very active SLE, particularly when kidney or neurologic involvement or acute blood vessel inflammation is present. These drugs suppress the immune system by damaging cells that grow rapidly, including those that produce antibodies. About a third of patients take immunosuppressants at some point in the course of the disease.

Specific Immunosuppressants. The most common immunosuppressants are:

Cyclophosphamide (Cytoxan) used to be considered the gold standard of treatment for lupus kidney disease (lupus nephritis). Cyclophosphamide is given intravenously and is sometimes used in combination with corticosteroids or other drugs. It has been used for lupus since the 1970s. Side effects are very severe and include nausea, vomiting, hair loss, infertility, and infections.
Mycophenolate mofetil (CellCept) is now becoming the new standard. Many recent studies have shown that CellCept works better than cyclophosphamide and causes far fewer severe side effects (diarrhea is the main side effect). Unlike cyclophosphamide, it is taken by mouth. Most doctors now recommend CellCept as a first-line treatment for newly diagnosed patients with mild or moderate lupus kidney disease. It may not be appropriate for patients with kidney failure or rapidly progressing kidney disease.
Azathioprine (Imuran) has the lowest toxicity, but is less effective than other immunosuppressants.
Cyclosporine (Sandimmune) has been used for years, mostly for SLE associated with kidney involvement. High blood pressure is common, however, with this drug.

The most frequent side effects of immunosuppressants include:

Stomach and intestinal problems
Skin rash
Mouth sores
Hair loss

Serious side effects of immunosuppressants include:

Low blood cell counts
Anemia
Menstrual irregularity
Early menopause
Ovarian failure
Infertility
Herpes zoster (shingles)
Liver and bladder toxicity
Increased risk of cancer

In general, immunosuppressants should not be used alone unless corticosteroids are ineffective or inappropriate. Grapefruit juice has an enzyme that may enhance the effects of some immunosuppressants.

Monoclonal Antibodies (MAbs). A MAb is a laboratory-made protein that targets specific immune cells, such as B cells. B cell over-activation has been identified as a key component of the lupus disease process. Promising MAbs in development for SLE treatment include:

Epratuzumab is being investigated for treatment of moderate-to-severe lupus. It is currently in Phase III trials.
Belimumab (Lymphostat-B) is also in Phase III trials.
Rituximab (Rituxan), a lymphoma cancer and rheumatoid arthritis drug, has shown good results in early trials in improving lupus symptoms. Researchers think it may affect how T cells and B cells interact. However, in December 2006 the FDA warned of several cases of progressive multifocal leukoencephalopathy (PML) in patients with lupus who took this drug. PML is a life-threatening brain infection. Some patients developed PML as late as 12 months after their last dose of rituximab. Two patients with lupus died from PML.

Intravenous Immunoglobulins. Intravenous immunoglobulins (IVIG) are sometimes used for patients who have not responded to other SLE treatments. Immunoglobulins are antibodies produced by immune system B-lymphocyte cells. IVIG is a blood product that contains these antibodies.

Dehydroepiandrosterone (DHEA). Dehydroepiandrosterone (DHEA) is a natural steroid hormone that is produced by the adrenal glands and converted into estrogen and androgen. The synthetic equivalent of DHEA, prasterone (Prestara), is being investigated as a potential treatment for SLE. Several clinical trials have indicated promising, although mixed, results for prasterone’s effect on preventing bone mineral density loss in women who take prednisone. Prasterone is still in the drug development stage and it is not clear when, or if, it will be commercially available.

Autologous Stem Cell Transplantation. Some patients with severe lupus have achieved at least short-term remission after undergoing autologous transplantation of stem cells and high-dose drug therapy to suppress the damaging immune factors. Stem cells are the early forms for all blood cells in the body. An autologous transplant is one in which marrow or blood cells used are the patient's own. (The advantage to an autologous transplant is that the patient's own cells are not at risk for rejection by the immune system.)

The procedure first removes the cells from the patient, who then receives high-dose immunotherapy. The stem cells are then reintroduced. Early results of small studies are encouraging, especially for treatment of antiphospholipid syndrome. Evidence suggests that these re-introduced stem cells do not repeat the original autoimmune errors. A 2006 study in the Journal of the American Medical Association indicated that autologous stem cell transplantation can help boost the immune system and lead to remission. Patients in the study had severe lupus that was resistant to standard treatments. Results were long-lasting. Researchers calculated that patients had a 50% chance of remaining disease-free after 5 years.

UVA-1 Phototherapy. A promising treatment uses ultraviolet A-1 (UVA-1) radiation, long UVA wave lengths that do not promote sunburn and may actually block inflammatory immune factors. Small studies have suggested that UVA-1 phototherapy may have some benefits for lowering disease activity in SLE.

Plasmapheresis. Plasmapheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves first taking blood from the patient. The plasma, which contains the inflammatory antibodies and other immunologically active substances, is discarded and replaced with other fluids. The blood is then returned. Plasmapheresis is not useful for routine management of patients but may have some benefits for patients who do not respond to standard treatments or in specific cases, such as lupus patients with hemolytic anemia.


Infections, Inflammation, or Hypertension in the Lungs	Preventive Measures. Immunizations with inactive viruses and preventive antibiotics should be considered for patients with SLE who are at high risk for infection. Treating Infections. Lung infections need to be treated aggressively with antibiotics. However, antibiotic drugs such as penicillin or the sulfa drugs may cause sensitivity rashes that can be confused with SLE rash. Treating Lung Inflammation. While inflammation of the lung (pneumonitis) resembles pneumonia, it is not an infection but is a result of the autoimmune process. This condition needs to be treated with corticosteroids or immunosuppressants, but only if the doctor is sure infection is not present. Treating Pulmonary Hypertension. Pulmonary hypertension is very serious. Drugs known as prostacylins -- which include epoprostenol, iloprost, and treprostinil -- are standard drugs. Bosentan (Tracleer) is the first oral drug approved for pulmonary hypertension. An inhaled iloprost formulation (Ventavis) was approved in 2004. Sildenafil (Viagra, Revatio) may also be used for this condition. Lung transplantation may be required.
Bleeding and Clotting Disorders	Antiphospholipid Syndrome and Clotting Disorders. Hydroxychloroquine or aspirin may help prevent blood clots in women with antiphospholipid syndrome (APS). (Aspirin does not appear to be protective in men who carry the autoantibodies responsible for APS.) In patients who have experienced blood clots, treatment with the anticoagulant warfarin (Coumadin) is advisable. This blood-thinning drug may be needed lifelong. Scientists are investigating other treatment options, including autologous stem cell transplantation. The procedure has shown promise in studies for treating lupus-associated APS, but it is still experimental. Excess Bleeding from Thrombocytopenia (Drop in Blood Platelets). Treatments that may be effective for thrombocytopenia include combinations of a corticosteroid and either danazol (a male hormone) or the antimalarial hydroxychloroquine. Immunosuppressants or intravenous immunoglobulin IgG may be helpful in some patients. Surgical removal of the spleen may be advisable if bleeding disorders are a serious problem, but this option should be considered carefully, because the spleen provides one line of defense against infection. (Abnormal spleen function, in any case, appears to be fairly common in SLE.)
Kidney Disease	Drugs. Mycophenolate mofetil (CellCept), a newer drug, can help treat kidney disease associated with SLE and has fewer side effects than other immunosuppressants. It is taken by mouth. Recent studies suggest that it works better than cyclophosphamide. CellCept may be best for patients with mild-to-moderate lupus kidney disease and may not be appropriate for patients with advanced kidney disease. Intravenous cyclophosphamide is the most effective drug at this time for proliferative lupus nephritis, and, in combination with a steroid, has been shown to control advanced kidney disease in 60 - 90% of patients. It has severe side effects, including nausea, vomiting, hair loss, and infertility. Steroids are also useful for treating active kidney disease and for managing milder forms of nephritis. Procedures. Kidney transplant or dialysis should be considered for patients with SLE with severe kidney damage. For unknown reasons, SLE does not generally recur in the transplanted kidneys. Studies are conflicting, however, over whether SLE transplant patients have higher organ-rejection rates than other kidney-transplant recipients. Both transplantation and dialysis have potentially serious complications. Plasmapheresis. It is not clear if plasmapheresis is beneficial for SLE kidney disease.
Osteoporosis	Treatments for osteoporosis include calcium, vitamin D, bisphosphonates, parathyroid hormone, and selective estrogen-receptor modulators (SERMs). [For more information, see In-Depth Report #18: Osteoporosis.]
Heart Disease	The need for aggressive treatment of high blood pressure often accompanies kidney disease. SLE is also accompanied by high cholesterol levels, which requires diet changes and drug therapies. [For more information, see In-Depth Reports #3: Coronary artery disease; #14: High blood pressure; #23: Cholesterol; and #43: Heart healthy diet.]

The spleen is an organ that helps produce and maintain red blood cells. It also aids the body's immune system by producing white blood cells that destroy harmful substances in the body. Removal of the spleen makes a person more susceptible to infection.

Click the icon to see an illustrated series detailing kidney transplant.

Lifestyle Changes

People with SLE should try to maintain a healthy and active lifestyle. Light-to-moderate exercise, interspersed with rest periods, is good for the heart, helps fight depression and fatigue, and can help keep joints flexible.

Patients should minimize their exposure to crowds or people with contagious illnesses. Careful hygiene, including dental hygiene, is also important.

It is very important that patients with SLE avoid excessive exposure to sunlight. Simple preventive measures include avoiding overexposure to ultraviolet rays and wearing protective clothing and sunblocks. There is some concern that allergy shots may cause flare ups in certain cases. Patients who may benefit from them should discuss risks and benefits with an SLE specialist. In general, patients with SLE should use only hypoallergenic cosmetics or hair products.

Chronic stress has profound physical effects and influences the progression of SLE. Getting adequate rest of at least 8 hours and possibly napping during the day may be helpful. Maintaining social relationships and healthy activities may also help prevent the depression and anxiety associated with the disease.

Resources

www.lupus.org -- Lupus Foundation of America
www.lupusny.org -- SLE Foundation of America
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.lupusresearchinstitute.org -- Lupus Research Institute

References

Bernatsky S, Ramsey-Goldman R, Isenberg D, Rahman A, Dooley MA, Sibley J, et al. Hodgkin's lymphoma in systemic lupus erythematosus. Rheumatology (Oxford). 2007 May;46(5):830-2. Epub 2007 Jan 25.

Crosbie D, Black C, McIntyre L, Royle PL, Thomas S. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114.

D'Cruz DP, Khamashta MA, Hughes GR. Systemic lupus erythematosus. Lancet. 2007 Feb 17;369(9561):587-96.

Dörner T, Kaufmann J, Wegener WA, Teoh N, Goldenberg DM, Burmester GR. Initial clinical trial of epratuzumab (humanized anti-CD22 antibody) for immunotherapy of systemic lupus erythematosus. Arthritis Res Ther. 2006;8(3):R74. Epub 2006 Apr 21.

Gompel A, Piette JC. Systemic lupus erythematosus and hormone replacement therapy. Menopause Int. 2007 Jun;13(2):65-70.

Harel-Meir M, Sherer Y, Shoenfeld Y. Tobacco smoking and autoimmune rheumatic diseases. Nat Clin Pract Rheumatol. 2007 Dec;3(12):707-15.

Khamashta MA. Systemic lupus erythematosus and pregnancy. Best Pract Res Clin Rheumatol. 2006 Aug;20(4):685-94.

Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Curr Opin Rheumatol. 2007 Jan;19(1):49-54.

Kocis P. Prasterone. Am J Health Syst Pharm. 2006 Nov 15;63(22):2201-10. Lane NE. Therapy Insight: osteoporosis and osteonecrosis in systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Oct;2(10):562-9.

Mackillop LH, Germain SJ, Nelson-Piercy C. Systemic lupus erythematosus. BMJ. 2007 Nov 3;335(7626):933-6.

Mease PJ, Ginzler EM, Gluck OS, Schiff M, Goldman A, Greenwald M, et al. Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy. J Rheumatol. 2005 Apr;32(4):616-21.

Sabahi R, Anolik JH. B-cell-targeted therapy for systemic lupus erythematosus. Drugs. 2006;66(15):1933-48.

Sánchez-Guerrero J, González-Pérez M, Durand-Carbajal M, Lara-Reyes P, Jiménez-Santana L, Romero-Díaz J, et al. Menopause hormonal therapy in women with systemic lupus erythematosus. Arthritis Rheum. 2007 Sep;56(9):3070-9.

Vigna-Perez M, Hernández-Castro B, Paredes-Saharopulos O, Portales-Pérez D, Baranda L, Abud-Mendoza C, et al. Clinical and immunological effects of Rituximab in patients with lupus nephritis refractory to conventional therapy: a pilot study. Arthritis Res Ther. 2006;8(3):R83. Epub 2006 May 5.

Walsh M, James M, Jayne D, Tonelli M, Manns BJ, Hemmelgarn BR. Mycophenolate mofetil for induction therapy of lupus nephritis: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2007 Sep;2(5):968-75. Epub 2007 Aug 8.

Walsh M, Jayne D. Rituximab in the treatment of anti-neutrophil cytoplasm antibody associated vasculitis and systemic lupus erythematosus: past, present and future. Kidney Int. 2007 Sep;72(6):676-82. Epub 2007 Jul 4.

Review Date:
1/21/2008
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Rheumatoid arthritis

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Complications
Diagnosis
Treatment
Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Treatment Approaches

Patients with rheumatoid arthritis who do not respond to single-drug therapy often do better when a combination of drugs is used, indicates a review of 23 clinical trials published in 2007 in the Annals of Internal Medicine. However, the researchers were unable to determine which combinations of drugs work best or which individual drugs are more effective than others.
Combination drug treatment is now becoming a standard approach to treating rheumatoid arthritis while it is still in its early stages. Another 2007 Annals of Internal Medicine study indicated that initial combination therapies slow progression of joint damage more rapidly than single-drug therapy but, after several years, all treatment strategies produce benefits.

Fish Oil for Joint Pain

The omega-3 fatty acids found in fish oil may have anti-inflammatory properties that can help relieve joint pain, indicates a 2007 review in Pain. The researchers found that taking omega-3 fatty acids for 3 - 4 months helped reduce joint pain intensity, minutes of morning stiffness, the number of painful or tender joints, and consumption of non-steroidal anti-inflammatory drugs (NSAIDs). Salmon, mackerel, and herring are types of fish that are particularly high in these fatty acids. Fish oil can also be taken through dietary supplements, but these can interact with some types of prescription medications and may not be safe or appropriate for all patients. (Check with your doctor before taking these or any other supplements.)

Introduction

Rheumatoid arthritis (RA) is a chronic disease in which various joints in the body are inflamed, leading to swelling, pain, stiffness, and the possible loss of function.

Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints affected is usually symmetrical, involves the hands and other joints, and is worse in the morning. Rheumatoid arthritis is a systemic (body-wide) disease, involving other body organs, whereas osteoarthritis is limited to the joints. Both forms of arthritis can be crippling.

The process probably develops in the following way:

The disease process leading to rheumatoid arthritis begins in the synovium, the membrane that surrounds a joint and creates a protective sac.
This sac is filled with lubricating liquid called the synovial fluid. In addition to cushioning joints, this fluid supplies nutrients and oxygen to cartilage, a slippery tissue that coats the ends of bones.
Cartilage is composed primarily of collagen, the structural protein in the body, which forms a mesh to give support and flexibility to joints.
In rheumatoid arthritis, an abnormal immune system produces destructive molecules that cause continuous inflammation of the synovium. Collagen is gradually destroyed, narrowing the joint space and eventually damaging bone.
If the disease develops into a form called progressive rheumatoid arthritis, destruction to the cartilage accelerates. Fluid and immune system cells accumulate in the synovium to produce a pannus, a growth composed of thickened synovial tissue.
The pannus produces more enzymes that destroy nearby cartilage, aggravating the area and attracting more inflammatory white cells, thereby perpetuating the process.

This inflammatory process not only affects cartilage and bones but can also harm organs in other parts of the body.

Click the icon to see an image of rheumatoid arthritis.

Causes

Although much has been learned about the process leading to rheumatoid arthritis, researchers have yet to uncover all the factors that lead to this devastating disease. One prevalent theory is that a combination of factors triggers rheumatoid arthritis, including an abnormal autoimmune response, genetic susceptibility, and some environmental or biologic trigger, such as a viral infection or hormonal changes.

The Normal Immune System Response. The inflammatory process is a byproduct of the activity of the body's immune system, which fights infection and heals wounds and injuries:

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign proteins, such as a virus.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight any infections.
In the process the surrounding area becomes inflamed and some healthy tissue is injured. The immune system is then called upon to repair wounds by clotting off any bleeding blood vessel and initiating fiber-like patches to the tissue.
Under normal conditions, the immune system has other special factors that control and limit this inflammatory process.

The Infection Fighters. Two important components of the immune system that play a role in the inflammation associated with rheumatoid arthritis are B cells and T cells, both of which belong to a family of immune cells called lymphocytes.

When macrophages recognize foreign particles entering the bloodstream, they are programmed to ingest them, split them into pieces, and bring specific sections of them (antigens) into contact with the surface of the T cell. These antigens are placed within specialized proteins on the surface of the T cell that signal to a T cell and begin a process of immune system inspection. This process involves the interaction of several proteins on B cells and T cells, which seem to signal back and forth.

If the T cell recognizes an antigen as "non-self," it will produce chemicals (cytokines) that cause B cells to multiply and release many immune proteins (antibodies). These antibodies circulate widely in the bloodstream, recognizing the foreign particles and triggering inflammation in order to rid the body of the invasion. T cells can be further categorized as killer T cells or helper T cells. Killer T cells directly attack antigens, such as viruses and tumor cells. Helper T cells recognize antigens that are presented to them by macrophages (or other specialized cells), and can stimulate B cells to mount various kinds of attacks on the antigen. They also produce chemicals (cytokines) that can have a more direct role in the inflammatory process.

For reasons that are still not completely understood, both the T cells and the B cells become overactive in patients with RA. In an immune response it is normal for the antibody response to change over time, particularly if the first antibodies that are made do not eliminate the invading particles. Little by little, the types of antibodies being made undergo changes in an attempt to achieve better recognition and a stronger inflammatory response against a recalcitrant invader. In RA, a complex interaction between activated immune cells and an impaired antigen-elimination process leads to a greater than normal repertoire of what the antibodies recognize. Eventually, antibodies are made that recognize more of the body's own tissues in a stronger or more persistent manner than is healthy, and inflammatory responses are mounted in these tissues.

An antigen is a substance that can provoke an immune response. Typically antigens are substances not usually found in the body.

Cytokines. Cytokines are very important in the destructive process of rheumatoid arthritis, particularly those known as interleukins (ILs) -- notably IL1 and IL6 -- and tumor necrosis factor (TNF). TNF is now known to be the major cause of joint damage and various systemic manifestations of RA, including weight loss.

Leukocytes. The leukocytes, the other major white blood cells in the body, are also spurred into action by the over-zealous T cells. Leukocytes stimulate the production of key players in the inflammatory process, including leukotrienes, prostaglandins, and nitric oxide.

The Hypothalamic-Pituitary-Adrenal Axis and Stress Hormones. Some research suggests that abnormalities in the hypothalamic-pituitary-adrenal axis (HPA axis) may contribute to RA. The HPA system includes two parts of the brain (the hypothalamus and the pituitary) and the adrenal gland.

Click the icon to see an image of the adrenal glands.

The HPA axis regulates a person's response to stress, which includes the release of cortisol (an important stress hormones) and DHEA (a weak male hormone). The cytokines interleukin-6 and TNF-alpha normally stimulate a surge in these hormones, which then block further release of the cytokines. Research suggests, however, that in RA, a defective HPA axis responds to the cytokines with a lower-than-normal release of cortisol and DHEA. Without a strong stress response, the cytokine levels remain high and become destructive, causing inflammation.

Genetic factors play some role in RA, but are clearly not the only important factor. The presence of certain genetic mutations, however, may worsen the disease process. It should be pointed out that defective genes not only can be inherited but they may be changed and mutated by environmental or other factors. More research is needed to determine the specific genetic contributions to this disease.

HLA. HLA (human leukocyte antigen) is a genetically regulated molecule that traps part of antigens and presents them on the surface of cells for destruction by antibodies and T cells. It is designed to recognize self- from non-self cells. A number of HLA genetic forms called HLA-DRB1 alleles are referred to as the RA-shared epitope because of their association with rheumatoid arthritis. These genetic factors do not cause RA, but they may make the disease more severe once it has developed. Genetic variations in the HLA region may also predict drug treatment response to etanercept and the disease-modifying anti-rheumatic drug methotrexate.

Lack of Corticotropin-Releasing Hormone. Some people with RA may have a genetic deficiency of a hormone known as corticotropin-releasing hormone (CRH), which produces corticosteroids, hormones that suppress the inflammatory process.

Infections. Although many bacteria and viruses have been studied, no single organism has been proven to be the primary trigger for the autoimmune response and subsequent damaging inflammation. Higher than average levels of antibodies that react with the common intestinal bacteria E. coli have appeared in the synovial fluid of people with RA. Some experts think they may stimulate the immune system to prolong RA once the disease has been triggered by some other initial infection. Other potential triggers include Mycoplasma, parvovirus B19, retroviruses, mycobacteria, and Epstein-Barr virus.

Chemicals. A number of chemicals are being investigated as triggers of rheumatoid arthritis, but it is very difficult to determine causal effects of any specific trigger.

Risk Factors

Rheumatoid arthritis (RA) is an ancient disease. The condition has been identified in skeletons thousands of years old. According to the Arthritis Foundation, RA affects an estimated 2.1 million Americans.

Although the disease can occur at any age from childhood to old age, it usually starts in young adulthood, with onset peaking between the ages of 20 - 45. Still, about 50,000 children may be afflicted with juvenile rheumatoid arthritis.

Women are more likely to have RA than men. (The risk for women is slightly lower if they have been pregnant.) Women are also at higher risk for the severe type 2 rheumatoid arthritis.

Some people may inherit genes that make them susceptible to RA, but a family history of RA does not appear to increase an individual's risk.

Other factors may place certain susceptible individuals at higher risk for developing RA:

Heavy long-term smoking is a very strong risk factor for RA, particularly in patients without a family history of the disease.
Women who have a shorter fertility time (and so lower levels of reproductive hormones) may be at higher risk.
History of blood transfusions.

Most studies have not found any association between silicone breast implants and rheumatoid arthritis or other autoimmune disease (except possibly Sjögren syndrome).

Reports from a Dutch study suggest that hay fever sufferers have a reduced risk of developing rheumatoid arthritis, and, conversely, arthritis patients are less likely to have hay fever.

Symptoms

The hallmark symptom of rheumatoid arthritis is morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis, for instance, usually clears up within half an hour.) Even after remaining motionless for a few moments, the body can stiffen. Movement becomes easier again after loosening up.

Swelling and pain in the joints must occur for at least 6 weeks before a diagnosis of rheumatoid arthritis is considered. The inflamed joints are usually swollen and often feel warm and "boggy" when touched. The pain often occurs symmetrically but may be more severe on one side of the body, depending on which hand the person uses more often.

Although rheumatoid arthritis almost always develops in the wrists and knuckles, the knees and joints of the ball of the foot are often affected as well. Indeed, many joints may be involved, including those in the cervical spine, shoulders, elbows, tips, temporomandibular joint (jaw), and even joints between very small bones in the inner ear. Rheumatoid arthritis does not usually show up in the fingertips, where osteoarthritis is common, but joints at the base of the fingers are often painful.

In about 20% of people with RA, inflammation of small blood vessels can cause nodules, or lumps, under the skin. They are about the size of a pea or slightly larger, and are often located near the elbow, although they can show up anywhere. Nodules can occur throughout the course of the disease. Rarely, nodules may become sore and infected, particularly if they are in locations where stress occurs, such as the ankles. On rare occasions, nodules can reflect the presence of rheumatoid vasculitis, a condition that can affect blood vessels in the lungs, kidneys, or other organs.

Fluid may accumulate, particularly in the ankles. In rare cases, the joint sac behind the knee accumulates fluid and forms what is known as a Baker cyst. This cyst feels like a tumor and sometimes extends down the back of the calf causing pain.

Symptoms such as fatigue, weight loss, and fever may accompany early rheumatoid arthritis. Some people describe them as being similar to those of a cold or flu except, of course, RA symptoms can last for years.

In children, juvenile rheumatoid arthritis, also known as Still's disease, is usually preceded by high fever and shaking chills along with pain and swelling in many joints. A pink skin rash may be present.

Complications

Rheumatoid arthritis is not fatal, but complications of the disease may shorten survival by a few years in some individuals. Although type 2 rheumatoid arthritis is progressive and there is no cure, over time the disease becomes less aggressive, and symptoms may even improve.

Treatments for RA are increasingly effective in slowing this debilitating disease, and some may even prevent initial destruction by aggressively reducing inflammation. If bone and ligament destruction and any deformities have occurred, however, the effects are permanent. It is essential, therefore, to seek a doctor's help as soon as symptoms develop. Side effects of the treatments often contribute to the severity of the disease.

Affected joints can become deformed, and the performance of even ordinary tasks may be very difficult or impossible. According to one survey, 70% of patients with rheumatoid arthritis feel the disease prevents them from living a fully productive life. A 2000 study found that about one-third of people with RA stop working within 5 years of onset of the disease.

Rheumatoid arthritis can affect other parts of the body as well as the joints. Some patients with severe disease may then be at higher risk for complications, such as the following:

Peripheral Neuropathy. This condition affects the nerves, most often those in the hands and feet. It can result in tingling, numbness, or burning.
Muscle problems. Many patients have weakness of the muscles.
Anemia. People with RA may develop anemia, which involves a decrease in the production of red blood cells.
Scleritis and Episcleritis. This is an inflammation of the blood vessels in the eye that can result in corneal damage. Symptoms include redness of the eye and a gritty sensation.
Infections. Patients with RA have a higher risk for infections, particularly from some of the immune-suppressing drugs (corticosteroids, anti-tumor necrosis factors, disease modifying drugs) that they take.
Skin Problems. Skin problems are common, particularly on the fingers and under the nails. Some patients develop severe skin complications that include rash, ulcers, blisters (which may bleed in some cases), lumps under the skin, and other problems. Severe skin disease can reflects a more serious case of RA in general.
Osteoporosis. Osteoporosis, a disorder in which bone density decreases, is more common than average in postmenopausal women with RA. The hipbone is particularly affected. The risk for osteoporosis also appears to be higher than average in men with RA who are over 60 years old.
Lung Disease. Patients with RA are susceptible to chronic lung diseases, including interstitial fibrosis, pulmonary hypertension, and other problems. Both rheumatoid arthritis itself and some treatments may cause this damage.
Kidney. Although rheumatoid arthritis only rarely involves the kidney, many of the drugs used to treat it can damage kidneys.
Vasculitis. Vasculitis involves autoimmune inflammatory abnormalities in very small vessels and can affect many organs in the body. Manifestations of vasculitis include mouth ulcers, nerve disorders, rapid worsening of the lungs, inflammation of coronary arteries, and inflammation of the arteries supplying blood to the intestines.
Heart Disease. Inflammation of the heart muscle itself in the sac around the heart can cause many problems. Mounting evidence suggests that RA can increase the risk for heart disease, possibly because of the inflammatory response in RA, which may also injure arteries and heart muscle tissue. Some studies have reported that people with RA are 30 - 50% more likely to suffer heart vessel blockages and 60 - 70% more likely to die as result than people without RA.
Lymphoma and Other Cancers. Research suggests that patients with RA are four times more likely than healthy patients to develop non-Hodgkin’s lymphoma. There has also been concern that some RA treatments may increase the risk for lymphoma. Studies from 2006 indicate that RA’s chronic inflammatory process may play a role in the development of lymphoma. Researchers found that patients with very severe and long-term RA had a substantially increased risk of developing lymphoma. Other 2006 research suggests that RA drugs, such as biologic response modifiers, do not increase lymphoma risk, although they do increase skin cancer risk.
Periodontal Disease. People with RA may be twice as likely as non-arthritic individuals to have periodontal disease. Chronic inflammation and immune dysfunction are central to both diseases.
Pregnancy. Women with RA have an increased risk for premature delivery. They are also three times more likely than healthy women to develop hypertension during the last trimester of pregnancy.

Juvenile rheumatoid arthritis often resolves before adulthood. Patients who experience arthritis in only a few joints do better than those with more widespread (systemic) disease, which is very difficult to treat. Although it can be very serious, very few people die from this condition.

MAS. Macrophage activation syndrome (MAS) is a life-threatening complication of this disorder and requires immediate treatment with high-dose steroids and cyclosporin A. Parents should be aware of symptoms, which include persistent fever, weakness, drowsiness, and lethargy.

Diagnosis

Rheumatoid arthritis can be difficult to diagnose. Many other conditions resemble it and its symptoms can develop insidiously. Blood tests and x-rays may show normal results for months after the onset of joint pain. Even after rheumatoid arthritis has been diagnosed, it is extremely important to determine whether the course of the disease is benign (type 1) or aggressive (type 2) in order to treat the problem appropriately.

Specific findings or presentation more likely to suggest the diagnosis of rheumatoid arthritis include morning stiffness, involvement of three joints at the same time, involvement of both sides of the body, subcutaneous nodules, positive rheumatoid factor, changes in x-rays.

Various blood tests may be used to help diagnose RA, determine its severity, and detect complications of the disease.

Rheumatoid Factor. In RA, antibodies that collect in the synovium of the joint are known as rheumatoid factor. In about 80% of cases of RA, blood tests reveal rheumatoid factor. It can also show up in blood tests of people with other diseases. However, when it appears in patients with arthritic pain on both sides of the body, it is a strong indicator of type 2 RA. The presence of rheumatoid factor plus evidence of bone damage on x-rays also suggests a significant chance for progressive joint damage.

Erythrocyte Sedimentation Rate Test. An erythrocyte sedimentation rate (ESR or sed rate) measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the patient's blood. The higher the sed rate the greater the inflammation. In addition to rheumatoid arthritis, the sed rate can be high in many conditions ranging from infection to inflammation to tumors. The test is used, then, not for diagnosis, but to help determine how serious the condition is.

C-Reactive Protein. High levels of C-reactive protein (CRP) are also indicators of active inflammation. However, because obesity also increases CRP levels, the doctor should consider a patient’s body mass index when evaluating CRP levels during RA diagnosis.

Anti-CCP Antibody Test. The presence of antibodies to cyclic citrullinated peptides (CCP) can identify RA years before symptoms develop. In combination with the test for rheumatoid factor, the CCP antibody test is the best predictor of which patients will go on to develop severe RA. Used in Europe, the test is now beginning to be used somewhat more commonly in the U.S. U.S. laboratories have not yet developed consistent standards for interpreting the test, however.

Tests for Anemia. Anemia is a common complication. Blood tests are needed often to determine the amount of red blood cells (hemoglobin and hematocrit) and iron (soluble transferrin receptor and serum ferritin) in the blood.

Analyzing the synovial fluid might prove to be helpful in detecting markers of joint destruction, but this is not commonly performed. Some investigational examples include the following:

An enzyme called MMP-3 (matrix metalloproteinase 3) is involved with the degradation of cartilage. Its presence in synovial fluid is strongly associated with progressive joint destruction in patients with chronic RA.
High levels urocortin, a member of the peptide family involved in the stress response, may also be a major player in the RA inflammation.

X-Rays. X-rays generally have not been helpful to detect the presence of early rheumatoid arthritis because they cannot show images of soft tissue. The use of a technique known as dual energy x-ray absorptiometry, however, may be useful in detecting early bone loss in rheumatoid arthritis (2 - 27 months after onset). Evidence of damage on x-rays along with elevated rheumatoid factor is a significant predictor for progressive joint destruction.

Ultrasound. Special ultrasound techniques called power Doppler ultrasonography (PDUS) or quantitative ultrasound (QUS) may be helpful in RA. PDUS may be reliable for monitoring inflammatory activity in the joint. QUS, which is used for osteoporosis, can detect bone loss in fingers, which may prove to be a good indicator of early RA.

Magnetic Resonance Imaging. Specially designed magnetic resonance imaging (MRI) equipment called extremity MRI may be able detect bone erosions in the hands of RA patients where x-rays cannot. Further evaluation is necessary.

Symptoms of rheumatoid arthritis can be mimicked by things as benign as a bad mattress or as serious as cancer. A number of rare genetic diseases attack the joints. Physical injuries, infections, and poor circulation are among the many problems that can cause aches and pains. It would be impossible to discuss in this report the dozens of all conditions with symptoms of joint aches and pains.

Osteoarthritis. Osteoarthritis requires some special mention because it is the most common form of arthritis. It differs from RA in several important respects.

Osteoarthritis usually occurs in older people.
It is located in only one or a few joints. (In fact, osteoarthritis is probably most often confused with rheumatoid arthritis if it affects multiple joints in the body.)
The joints are less inflamed.
Progression of pain is almost always gradual.

Gout. Gout also causes swelling and severe pain in a joint, although most commonly starting in one joint. It is particularly difficult to distinguish chronic gout in older people from rheumatoid arthritis, however, since gout in this population can occur in a number of joints. A proper diagnosis can be made with a detailed medical history, laboratory tests, and detection in the affected joint of a salt called monosodium urate (MSU), which identifies gout.


Disease	Specific Subtypes
Osteoarthritis
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Crystal Induced Arthritis	Gout and pseudogout
Other Rheumatic Autoimmune Diseases	Systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis), Behcet's disease
Other Diseases	Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Treatment

The treatment of rheumatoid arthritis involves medications and lifestyle changes.

Many drugs are used for managing the pain and slowing the progression of rheumatoid arthritis, but none completely cure the disease. Some experts believe that no single drug will ever cure rheumatoid arthritis because of the many factors that affect the disease at various times. The goals of drug treatment for rheumatoid arthritis include:

Reduce inflammation
Prevent damage to the bones and ligaments of the joint
Preserve movement
To be as inexpensive and as free from side effects as possible over the long-term

The drug categories used for RA include:

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the least potent drugs used for RA. These drugs relieve pain by reducing inflammation, but do not affect the course of the disease.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are the main drugs used for treating rheumatoid arthritis. They slow the progression of the disease. They are much more effective than NSAIDs but also have more side effects. Methotrexate (Rheumatrex, Trexall) is the most widely used of these drugs.
Biologic Response Modifiers (also known as Biologic DMARDs) are often prescribed to patients who have failed to respond to DMARDs. They may be used alone or in combination with DMARDs such as methotrexate. They modify or block destructive immune factors such as tumor-necrosis factor (TNF). Current anti-TNF drugs include infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). Other biologic response modifiers include the interleukin-1 antagonist anakinra (Kineret), the T cell co-stimulation modulator abatacept (Orencia), and rituximab (Rituxan), which targets CD20-positive B cells.
Corticosteroids, or steroids, are powerful anti-inflammatory drugs that are used to quickly reduce inflammation. These drugs include prednisone and prednisolone.

The question of how early and how aggressively to treat RA has been the subject of great debate. Among patients with RA, some will go into remission and remain in remission for the length of their lives even in the absence of treatment, while others will go on to develop active, sometimes severe RA.

Current practice has moved towards treating the disease aggressively while it is in its early stages to help prevent it from reaching a more severe and chronic state. Studies have found less joint damage in patients with early, aggressive treatment, particularly with the use of DMARDs and TNF modifiers in combination with methotrexate. Intensive early dosing of methotrexate may help slow progression of rheumatoid arthritis. Early combination therapy with DMARDs and corticosteroids is also showing good results.

During the first year of treatment, combination therapy appears to reduce the progression of joint deterioration more rapidly and effectively than single drug treatment. In addition, patients who have not been helped by one drug often benefit from a combination of drugs. However, over a longer period of time, it is not clear whether a drug combination approach offers many advantages over single drugs. It is also not certain which combination of drugs works best. Depending on your particular health condition, and how you respond to the drugs prescribed, your doctor may try various treatment strategies.

Medications

Two-thirds of people with RA rank pain as their primary reason for seeking professional help. The most common pain relievers for RA are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil). In 2004, a new NSAID, meloxicam (Mobic) was approved in the U.S. for the management and treatment of rheumatoid arthritis.

Studies suggest that the best times for taking an NSAID may be after the evening meal and then again on awakening. RA symptoms increase gradually during the night, reaching their greatest severity at the time of awakening. Taking NSAIDs with food can reduce stomach discomfort, although it may slow down the pain-relieving effect.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same warning label used for the COX-2 inhibitor celecoxib (Celebrex). This "black box" warning, the FDA's strongest warning, emphasizes the increased risks for cardiovascular events and gastrointestinal bleeding associated with these drugs’ use. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions. In December 2006, the FDA proposed even stronger labeling changes to highlight these drugs’ risk for liver damage as well as alcohol and drug interactions.

Long-term, regular use of NSAIDs can increase the risk for heart attack, especially for people who have a heart condition. Long-term use of NSAIDs is also the second most common cause of ulcers and gastrointestinal bleeding. To reduce the risks associated with NSAIDs, take the lowest dose possible for pain relief.

Other possible side effects of NSAIDs may include:

Upset stomach
Dyspepsia (burning, bloated feeling in pit of stomach)
Drowsiness
Skin bruising
High blood pressure
Fluid retention
Headache
Rash
Reduced kidney function

Long-term use of NSAIDs is the second most common cause of ulcers. Ulcers caused by NSAIDs are more likely to bleed than those caused by the bacteria Helicobacter pylori.

NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Those at high risk for bleeding include people over age 60, anyone with a history of ulcers of gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

Proton-pump inhibitor (PPI) drugs may help prevent and heal ulcers caused by NSAIDs. PPIs include omeprazole (Prilosec), esomeprazole (Nexium), and lansoprazole (Prevacid).

COX-2 Inhibitors (Coxibs). Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of heart problems, skin rashes, and other adverse effects, the FDA re-evaluated the risks and benefits of this drug class. This lead to the removal of rofecoxib (Vioxx) and valdecoxib (Bextra) from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor whether the drug is appropriate and safe for them. In December 2006, the FDA approved celecoxib for the relief of symptoms of juvenile rheumatoid arthritis in patients ages 2 years and older.

Disease-modifying anti-rheumatic drugs (DMARDs) are the standard treatments for RA. They are used either alone or in combination with newer biologic DMARDs.

DMARDs do not have any common properties other than their ability to slow down the progression of rheumatoid arthritis. Many were used for other diseases and were found accidentally to help RA. DMARDs include:

Methotrexate (considered to be the current standard of care)
Leflunomide
Hydroxychloroquine
Sulfasalazine
Gold
Minocycline
Azathioprine
Cyclosporine

Unfortunately, all DMARDs tend to lose effectiveness over time, even methotrexate. Patients rarely use one drug for more than 2 years. Combining DMARDs with each other or with drugs in other categories offers the best approach for many patients. The addition of a corticosteroid to any combination may also be helpful.

All DMARDs may produce stomach and intestinal side effects, and, over the long-term, each poses some risk for rare but serious reactions. (In some cases, however, they may be less harmful than long-term NSAID treatment.)

Methotrexate. Methotrexate (Rheumatrex, Trexall) acts as an anti-inflammatory drug and is now the most frequently used DMARD, particularly for severe disease. It has a faster mode of action than other DMARDs, (it starts working within 3 - 6 weeks), and its effectiveness as a well proven in studies.

Even this drug loses effectiveness, however, when used alone. It may be more effective when used in combination with other DMARDs or other drugs. Recent studies have focused on combining methotrexate with various biological response modifier drugs, especially for treatment of patients with early aggressive arthritis. The combination appears to work better than single drug therapy.

About 20% of patients withdraw from methotrexate because of its side effects. They include nausea and vomiting, rash, mild hair loss, headache, mouth sores, and muscle aches. Methotrexate reduces levels of folic acid (folate) in the body, which can lead to some of these side effects. Doctors may prescribe folic acid supplements to prevent side effects. However, some research suggests that folic acid may interfere with methotrexate’s effectiveness.

Methotrexate is usually given as pills. Patients who need higher doses can take it as an injection. Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:

Kidney and liver damage. People at particular risk for liver damage from methotrexate include those with diabetes, obesity, and alcoholism.
Increased risk for infections
Lung disease occurs in up to 5% of people. People who have poor lung function are most at risk.
The drug increases the risk for birth defects and should not be taken by pregnant women. However, methotrexate will not harm a woman’s chance for future healthy pregnancy.

Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. It has the following benefits:

It slows disease progression as early as 6 months into treatment.
Comparison studies with methotrexate report a better quality of life with leflunomide, including more energy, greater vitality, and fewer emotional side effects. (Studies comparing their risk for serious adverse effects are mixed. One, for example, showed fewer problems with leflunomide, while another reported identical rates.)

The combination of methotrexate and leflunomide (which has different effects on the immune system) is very effective compared to either drug alone. (This combination poses a risk for liver toxicity and requires monitoring.)

Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury. Everyone taking leflunomide should be monitored regularly, including blood tests for liver function, and anyone with liver problems should not take this drug. Monitoring of serum concentrations of the most active metabolite of leflunomide may help predict treatment response.

Hydroxychloroquine. Hydroxychloroquine (Plaquenil) was originally used for preventing malaria and is now also used for mild, slowly progressive arthritis. It can help relieve pain and improve mobility. It has one of the least toxic profiles of the DMARDs. The downside is that this drug can take up to 6 months to achieve full benefit. It also does not appear to slow disease progression. One study concluded that joint erosion after 2 years was worse than with no DMARD at all.

As with all DMARDs, gastrointestinal complaints are fairly common. This drug used to be associated with eye and vision problems, but with current lower doses this side effect is rare. If vision problems occur, it is usually with people taking very high doses, those with kidney disease, or those over 60 years of age. Still, you should have regular eye exams while taking this drug and notify your doctor if you experience any sudden changes in vision.

Sulfasalazine. Sulfasalazine (Azulfidine) was developed in the 1930s for treating rheumatoid arthritis, but fell into disfavor when gold treatment emerged. It has regained popularity, however, and is now used for both adult and juvenile RA. It works best when the disease is confined to the joints. Symptom relief occurs within 1 - 3 months.

Side effects are common, particularly stomach and intestinal distress, which usually occur early in the course of treatment. (However, serious gastrointestinal side effects, such as stomach ulcers, occur less frequently with sulfasalazine than with NSAIDs.) A coated-tablet form may help reduce side effects. Other side effects include skin rash and headache. Sulfasalazine increases sensitivity to sunlight. Be sure to wear sunscreen (SPF 15 or higher) while taking this drug. People with intestinal or urinary obstructions or who have allergies to sulfa drugs or salicylates should not take sulfasalazine.

Gold. Gold has been a long-standing DMARD for rheumatoid arthritis, although its use has decreased with the development of disease modifying and biologic drugs. Gold is usually administered in an injected form because the oral form, auranofin (Ridaura), is much less effective. There are two injectable forms of gold: Gold sodium thiomalate (Myochrysine) and aurothioglucose (Solganal). It can take 3 - 6 months before injections have an effect on RA symptoms.

Gold injections cause mouth sores in about a third of patients. Skin side effects include itching and rash, which can be severe in some patients. . The most serious side effects of gold injections, while rare, are kidney damage and decreased white blood cell count. Gold injections are not usually given to pregnant women. It is not definite that gold causes birth defects but doctors generally recommend that women use birth control while receiving this drug.

Minocycline. Minocycline (Minocin) is a tetracycline antibiotic that is usually prescribed for patients with mild RA. It can take 2 - 3 months before symptoms begin to improve and up to a year for full benefit. Side effects include upset stomach, dizziness, and skin rash. Long-term use of minocycline can cause changes in skin color, but this side effect usually disappears once the medication is stopped. Minocycline can cause yeast infections in women. Minocycline increases sensitivity to sunlight and patients should be sure to wear sunscreen. In rare cases, minocycline can affect the kidneys and liver.

Azathioprine. Azathioprine (Imuran) suppresses immune system activity. It takes 6 - 8 weeks for early symptom improvement and up to 12 weeks for full benefit. Azathioprine can cause serious problems with the gastrointestinal tract. About 10 - 15% of patients experience nausea and vomiting, often accompanied by stomach pain and diarrhea. (Taking the medication twice daily, instead of once daily, or taking it after eating may help avoid this problem.) Azathioprine can also cause problems with liver function and pancreas gland inflammation, and can reduce white blood cell count.

Cyclosporine. Like azathioprine, cyclosporine (Sandimmune, Neoral) is an immunosuppressant. It is used for people with RA who have not responded to other drugs. It can take a week before symptoms improve and up to 3 months for full benefit. The most serious and common side effects of cyclosporine are high blood pressure and kidney function problems. While kidney function usually improves once the drug is stopped, mild-to-moderate high blood pressure may continue. Cyclosporine can also cause gout or worsen gout in people who have this condition.

Other common side effects include headache, nausea, vomiting, stomach pain and upset, and swelling of hands and feet. About 10% of patients who take cyclosporine develop tremors, increased hair growth, muscle cramps, and numbing or tingling in hands and feet (neuropathy). Swelling of the gums is also common. Patients should practice good dental hygiene, including regular brushing and flossing.

Biologic response modifiers are drugs made from living cells. These drugs target specific components of the immune system that contribute to the joint inflammation and damage that are part of the rheumatoid arthritis disease process.

Currently approved biologic response modifiers include:

Etanercept (Enbrel). Etanercept is an anti-tumor necrosis factor (anti-TNF) drug. Approved in 1998, etanercept was the first biologic response modifier drug for treatment of rheumatoid arthritis. It is also approved for juvenile RA and psoriatic arthritis.
Infliximab (Remicade). Approved in 1999, infliximab is also an anti-TNF drug. It is used in combination with methotrexate.
Adalimumab (Humira). Adalimumab is another anti-TNF drug. First approved in 2002 as a second-line treatment for RA, adalimumab received additional approvals in 2005 as a first-line treatment for RA and psoriatic arthritis. It is used alone or in combination with methotrexate or other DMARDs. It is also showing promising results in clinical trials for juvenile rheumatoid arthritis.
Anakinra (Kineret). Approved in 2001, anakinra targets interleukin-1 (IL-1), another type of immune factor.
Abatacept (Orencia). Approved in 2005 for adults with moderate-to-severe RA who have not responded to DMARD or anti-TNF drugs. Abatacept is known as a T cell co-stimulation modulator. It blocks T cell activation. It is used alone or in combination with other DMARDs aside from anti-TNF drugs.
Rituximab (Rituxan). Approved in 2006, rituximab targets CD20-positive B cells and blocks their activation. It is used in combination with methotrexate for patients with moderate-to-severe RA who have not responded to anti-TNF therapies.

Some of these drugs are used as first-line treatments for RA. Others are used for patients who have not responded to DMARDs or other types of treatment. Depending on the specific drug, they may be used alone or in combination with the DMARD methotrexate. However, biologic response modifiers are not used in combination with each other, as they can lead to serious infections.

As with other rheumatoid arthritis drugs, these drugs do not cure the disease but can help slow progression and joint damage. In recent clinical trials, some patients have achieved remission using methotrexate in combination with infliximab, adalimumab, or rituximab.

Side Effects and Complications. Etanercept, adalimumab, and anakinra are given by injection and may cause pain at the injection site. To prevent injection reactions, patients are sometimes pretreated with betamethasone, a corticosteroid drug, but some research suggests that the steroid does little good. Infliximab, abatacept and rituximab are given by intravenous infusion. Common infusion reactions include headache, nausea, and flu-like symptoms. Because biologic response modifiers affect the immune system, patients who take these drugs have an increased risk for infections.

Other risks associated with these drugs include:

Anti-TNF drugs (etanercept, infliximab, adalimumab) have been associated with sepsis, pneumonia, and tuberculosis; non-melanoma skin cancer, lymphoma, and other malignancies; lupus; heart failure; blood disorders (including aplastic anemia); palmoplantar psoriasis; lung disease; and liver damage.
Anakinra may cause a sudden drop in white blood cells (leukopenia) that increases the risk for infections.
Abatacept should be used cautiously in patients with chronic obstructive pulmonary disorder (COPD) as it may increase the risk for respiratory complications.
Rituximab has been associated with cases of a rare and deadly brain infection called progressive multifocal leukoencephalopathy (PML). It also may cause hepatitis B reactivation, viral infections, and heart rhythm disturbances and other heart problems.

Corticosteroids work rapidly to control inflammation and pain. Long-time use, however, can have severe adverse effects. Still, they are often used under the following conditions:

Oral corticosteroids, such as prednisolone and prednisone (Deltasone, Orasone), are most often used in combination with DMARDs, which significantly enhances the benefits of DMARDs.
Oral corticosteroids are sometimes used in early stage-RA for patients who cannot tolerate NSAIDs. Studies, in fact, suggest that low-dose corticosteroids may significantly slow joint pain when it is the first drug administered and then used for 2 years. (Even low-dose oral steroids have adverse effects on bone density, blood sugar, and weight.)
Higher doses of corticosteroids are used for flareups of vasculitis and severe reactions to medications.
Corticosteroids may also be used during pregnancy to avoid exposure to more toxic drugs.
Daily, low-dose corticosteroids are also needed in some patients to control their rheumatoid arthritis symptoms.
Corticosteroids are sometimes injected directly into joints for relief of flare-ups when only one or a few joints are affected. Experts suggest no more than three or four injections into a specific joint a year. Steroid injections in the joints may be a safe and effective treatment for juvenile rheumatoid arthritis and reduce the need for oral medication.
Corticosteroid pulse therapy (intravenous administration) may work as well as DMARDs.

Side Effects of Oral Corticosteroids. Serious side effects are associated with long-term use of oral steroids. (Low doses may reduce these risks, but they do not eliminate them.) Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, or bisphosphonates (alendronate etidronate, risedronate). Other adverse effects include cataracts, glaucoma, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and, rarely, psychosis. Recent research suggests that prednisone can increase the risk of developing non-melanoma skin cancer.

Withdrawal from Long-Term Use of Oral Corticosteroids. Long-term use of oral steroid medications suppresses secretion of natural steroid hormones by the adrenal glands. After withdrawal from these drugs, this so-called adrenal suppression persists and it can take the body a while (sometimes up to a year) to regain its ability to produce natural steroids again. There have been a few cases of severe adrenal insufficiency that occurred when switching from oral to inhaled steroids, which, in rare cases, has resulted in death.

No one should stop taking any steroids without consulting a doctor first, and if steroids are withdrawn, regular follow-up monitoring is necessary. Patients should discuss with their doctor measures for preventing adrenal insufficiency during withdrawal, particularly during stressful times, when the risk increases.

Biologic Drugs. For many years, therapeutic treatment of rheumatoid arthritis focused on T cell mediation. New research is now examining the role of B cells, which become overactive in autoimmune disease, and how B cell depletion may help to reduce disease activity. Other areas of intense research include interleukin receptor antagonists, which target cytokines involved in the inflammatory process.

Many of the current investigational drugs are monoclonal antibodies (MAbs), biologic drugs that are designed to target specific receptors. Promising candidates in late-stage research include tocilizumab (Actemra), golimumab, denosumab, ocrelizumab, ofatumumab, and certolizumab.

Statins. Some research suggests that compounds derived from statins, the highly regarded cholesterol-lowering drugs, may suppress the inflammation responsible for RA damage.

Stem cell transplantation. Stem cells are the early versions of mature, specialized blood cells. Investigators are reporting that transplantation of donated hemopoietic stem cells, which mature into various blood cells, has induced remission in a few children with severe juvenile rheumatoid arthritis. The procedure is promising in select cases, but it can be highly toxic. More studies are needed to determine risks and benefits for RA patients.

Plasmapheresis. A device called the Prosorba column is used to remove inflammatory antibodies from the patient's blood. Small, short-term studies have shown that this therapy may slow or even halt the progression of the disease in a third to a half of patients. Side effects from the Prosorba column may include anemia, fatigue, itching, fever, a drop in blood pressure, and nausea. Nearly all patients experience an immediate flare-up of joint pain that lasts a few days. Some patients develop infection from the catheter used to remove blood. Long-term studies are needed.

Surgery

Certain surgical techniques may be helpful for people with severe deformities or disabilities.

Arthroscopy. Arthroscopy is performed to clean out bone and cartilage fragments that cause pain and inflammation. It is usually performed on the knee, but it also may be done on the hip:

The surgeon makes a small incision and injects a sterile solution to make the joint swell for easier viewing.
A lighted tube, called an arthroscope (which enables the surgeon to view the joint), is then inserted through another small incision.
Through a third incision, the surgeon trims, shaves, or stitches the damaged tissue. (Arthroscopy is most successful when the removal of cartilage only, and not bone, is involved.)

In many cases, the procedure can be done using local anesthetic, and the patient can go home within a day. In the case of knee operations, patients can resume mild activity in a couple of days, but full recovery can take up to 3 months.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed, the surgeon may choose to perform osteotomy:

The knee is opened.
A debridement (removal of damaged tissue) is performed in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.

The procedure is best used in heavier adults who are under 60 years old.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in some cases of limited damage in the knee. It is intended to relieve pain and preserve function as long as possible before a total knee replacement is necessary. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which should preserve more movement than a total knee replacement. The procedure is not widely available and is somewhat controversial, since the implants may not be as reliable as those in total knee replacement.

Synovectomy. Synovectomy is a procedure whereby the diseased joint lining is removed. It is used when more conservative measures fail, particularly in the wrist. Studies are suggesting, however, that with the use of lasers for the procedure, eventually synovectomy may prove to be an alternative to DMARD treatments in reducing symptoms and achieving long-term remission.

Joint Replacement Surgery. Eventually, even after these procedures, rheumatoid arthritis may progress to the point that normal functioning is impossible. In such cases, artificial (prosthetic) replacement joint implants may be considered for knees, hips, or other joints. The prosthesis is usually made of a chromium alloy and plastic and may be attached to the adjoining bones using a cement, polymethyl methacrylate, or the prosthesis may be composed of a porous material that allows bone to grow into and eventually adhere to the device.

Although this procedure has usually been performed in people over 60, implants are now lasting 20 years and more and younger patients with severe disability are finding them useful. Uncemented arthroplasty using porous material is showing particularly good results. Studies on hip replacement, for example, now report that after 10 years, 5% of patients require reoperation and 12% of patients report some pain.

Lifestyle Changes

It is important to maintain a balance between rest (which will reduce inflammation) and exercise (which will relieve stiffness and weakness). Studies have suggested that even as little as 3 hours of physical therapy over 6 weeks will help people with RA, and that these benefits are sustained.

The goal of exercise is to:

Maintain a wide range of motion
Increase strength, endurance, and mobility
Improve general health
Promote well-being

In general, doctors recommend the following approaches:

Start with the easiest exercises, stretching and tensing of the joints without movement.
Next attempt mild strength training. (One study found that people with RA who exercised with machines that use compressed air for gentle resistance experienced less pain and increased muscle tone.)
The next step is to try aerobic exercises. These include walking, dancing, or swimming, particularly in heated pools. Avoid heavy impact exercises, such as running, downhill skiing, and jumping.
Tai chi, which uses graceful slow sweeping movements, is an excellent method for combining stretching and range-of-motion exercises with relaxation techniques. It is of particularly value for elderly RA patients who report significantly less pain after practicing this technique.

While traditional guidelines have restricted RA patients to only gentle exercise, recent research suggests that more intense exercise may not only be safe, but may actually produce greater muscle strength and overall functioning. Common sense is the best guide:

If exercise is causing sharp pain, stop immediately.
If lesser aches and pains continue for more than 2 hours afterwards, try a lighter exercise program for a while.
Using large joints instead of small ones for ordinary tasks can help relieve pressure, for instance, closing a door with the hip or pushing buttons with the palm of the hand.

Many patients with RA try dietary approaches, such as fasting, vegan diets, or eliminating specific foods, that seem to worsen RA symptoms. There is little scientific evidence to support these approaches but some patients report anecdotally that they are helpful.

In recent years, a number of studies have suggested that the omega-3 fatty acids contained in fish oil may have anti-inflammatory properties useful for RA joint pain relief. The best source of fish oil is through increased consumption of fatty fish such as salmon, mackerel, and herring. Fish oil supplements are another option, but they may interact with certain medications. If you are thinking of trying fish oil supplements, talk to your doctor first.

Various ointments, including Ben Gay and capsaicin (a cream that use the active ingredient in chilli peppers), may help soothe painful joints.

Orthotic devices are specialized braces and splints that support and help align joints. Many such devices made from a variety of light materials are available and can be very helpful when worn properly.

A number of specially designed appliances and devices are available to ease daily activities.

Although the influence of stress or emotions on the progression of RA is not fully known, having a history of major depression that persists or reoccurs seems to increase the pain, disability, and fatigue. Stress management alone cannot reduce pain, but it may be very helpful in helping people deal with their condition.

One study found that people with RA reported significant clinical improvement after writing about their pain, stress, or other traumatic experiences. Writing for 20 minutes, just a few days a week, resulted in improvement that lasted for months. One study found that spirituality (defined as "a belief in a power outside oneself and one's own existence," as opposed to the practice of any specific religion) is associated with better health, happiness and well-being among RA patients. (Spiritual healing does not appear to offer any advantages.)

People often turn to alternative therapies or nontraditional remedies to relieve the pain of rheumatoid arthritis. Some alternative procedures, such as acupuncture, massage, relaxation techniques, biofeedback, and hypnosis, are not harmful and may be a useful adjunct to standard treatments.

In a small study, acupuncture reduced pain by a third in 73% of patients, and more than half reported at least a 50% improvement in pain. Patients also reduced their use of pain medications. Research presented at the 2006 American College of Rheumatology annual meeting suggested that both electroacupuncture and traditional acupuncture may help reduce joint tenderness.
Balneotherapy, also known as hydrotherapy or spa therapy, is an ancient form of therapy that involves mineral baths to soothe pain, and some patients have reported relief using such baths.
The NIH is conducting clinical trials to examine whether relaxation response, tai chi, stress management, and cognitive-behavioral therapy can help patients with RA feel better.

Herbal remedies used for RA include boswellia, equisetum arvense (horsetail), devil's claw, borage seed oil, and many others. To date, no evidence supports their efficacy.

Researchers are currently conducting studies in animals to determine if supplements extracted from the turmeric spice can help prevent joint inflammation. The U.S. National Institutes of Health is also conducting a clinical trial to compare the clinical effects of the Chinese herb Tripterygium wilfordii Hook F (TwHF) with the pharmaceutical drug sulfasalazine. TwHF is traditionally used in Chinese medicine for its anti-inflammatory properties.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.niams.nih.gov -- The National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation
www.fda.gov/cder/drug/infopage/cox2 -- FDA information on COX-2 inhibitors and NSAIDs
www.clinicaltrials.gov -- Find a clinical trial

References

Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006 Nov;10(42):iii-iv, xi-xiii, 1-229.

Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, et al. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Ann Intern Med. 2007 Nov 19 [Epub ahead of print]

Firestein GS. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii2-22.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM,, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):406-15.

Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1.

Harris ED Jr. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005. O’Dell JR. In: Goldman, ed. Cecil Medicine. 23rd ed. Saunders; 2007.

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007 Dec 1;370(9602):1861-74.

Smolen JS, Keystone EC, Emery P, Breedveld FC, Betteridge N, Burmester GR,. et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 Feb; 66(2): 143-50.

A.D.A.M. Copyright

adam.com

Herpes simplex

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Symptoms
Transmission
Risk Factors
Complications
Diagnosis
Similar Conditions
Home Remedies and Preventio...
Treatment for Genital Herpe...
Treatment for Oral Herpes...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Herpes Diagnosis

In 2006, the U.S. Centers for Disease Control (CDC) released updated guidelines for diagnosis and management of sexually transmitted diseases.

For diagnosis of genital herpes, the CDC recommends the use of both skin and blood tests.
Blood (or type-specific serologic) tests must be able to detect antibodies to glycoprotein G (gG). According to the CDC, gG serologic tests are much more accurate than other types of blood tests and are the only ones that should be used. These blood tests can help determine whether genital herpes is caused by herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2).
Although HSV-1 has traditionally been the main cause of oral herpes, and HSV-2 the main cause of genital herpes, HSV-1 is now causing up to 50% of all cases of genital herpes. Prognosis may vary depending on the type of virus involved.

Herpes Treatment

Acyclovir (Zovirax), famiciclovir (Famvir), and valacyclovir (Valtrex) are used for episodic treatment (when herpes outbreaks occur) or suppressive treatment (preventing outbreaks). Valacyclovir may be a particularly good choice for reducing the risk of herpes transmission among heterosexual couples when only one partner is infected with HSV-2.
According to a 2007 review of studies involving over 6,000 patients, these drugs are very effective in reducing herpes recurrences.

Herpes and HIV

Treatment of HSV-2 can help reduce HIV levels in women who are infected with both viruses, indicates a study published in 2007 in the New England Journal of Medicine. In the trial, women who received twice-daily valacyclovir therapy for 12 weeks had reduced genital-track shedding of HIV and blood HIV levels compared to women who received placebo. Researchers are now focusing on the major question: Whether treatment of genital herpes can help prevent HIV transmission.

Introduction

Herpes simplex virus (HSV) commonly causes infections of the skin and mucous membranes. Sometimes it can cause more serious infections in other parts of the body. HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years.

Herpes simplex is part of a group of other herpes viruses that include human herpesvirus 8 (the cause of Kaposi's sarcoma) and herpes zoster (the virus responsible for shingles and chicken pox). They differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which is derived from a Greek word meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive state for some indeterminate time.

There are two forms of the herpes simplex virus:

Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)

These viruses are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule has been to assume that HSV-1 infections occur in the oral cavity (mouth) and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted. It is now widely accepted, however, that either type can be found in either area and at other sites. In fact, HSV-1 is now responsible for up to half of all new cases of genital herpes.

For infection to occur, the following conditions must apply:

The herpes simplex virus passes moves through bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores.
The virus must have direct access to the noninfected person through injuries in their skin or mucus surfaces (such as in the mouth or genital area).

When herpes simplex virus enters the body, the infection process typically takes place as follows:

The virus enters vulnerable cells in the lower layers of skin tissue and tries to reproduce in the cell nuclei. Scientists are close to decoding the genetic structure of herpes simples virus and to discovering how the virus works its way into specific cells. The virus may have specially shaped proteins called cell adhesion molecules that can allow the virus to enter healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of the virus and help the infection move from cell to cell.
Even after it has entered the cells, the virus never causes symptoms in most cases.
However, if the virus destroys the host cells when it multiplies, inflammation and fluid-filled blisters or ulcers appear. Once the fluid is absorbed, scabs form, and the blisters disappear without scarring.
After the first time they multiply, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends (the dorsal root ganglia).
Here, the virus lives in an inactive (latent) form. The virus does not multiply, but both the host cells and the virus survive.
At unpredictable times, the virus begins multiplying again. It then goes through a period called shedding. During those times, the virus can be passed into bodily fluids and infect other people. Unfortunately, a third to half of the times shedding occurs without any symptoms at all.
Eventually, the symptoms return in most cases, causing a new outbreak of blisters and sores.

This close-up view of early herpes outbreak shows small, grouped blisters (vesicles) and lots of inflammation (erythema).

Symptoms

Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new herpes simplex virus 2 (HSV-2) infections and about a third of new herpes simplex virus 1 (HSV-1) infections do not produce symptoms.

Skin Eruptions and Pain. Skin eruptions will appear 2 - 12 days after the initial exposure to the virus.

The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters -- the characteristic herpes virus lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
When the crust falls off, the lesions are no longer contagious. (Rarely, the virus may still be active in nearby tissue.)
Once the virus gains entry to a site in the body, it can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in the first (primary) virus attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome).

Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually go away within a week.
Lymph glands near the site may be swollen as well.

It may be especially important to identify a first (primary) infection -- if possible -- and to treat it as soon as possible. Some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that time, the virus does not produce symptoms and cannot be transmitted to other people.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus multiples and can be transmitted through fluids and infect other people. This occurs during an outbreak. However, in a third to half of cases shedding occurs without any symptoms at all (asymptomatic). One study reported that about 40% of all people infected with herpes simplex virus (HSV) had sheeding of the virus without symptoms more than 5% of the time. (Other evidence suggests shedding occurs much more often -- 9 - 28% of the time.) About half of shedding episodes without symptoms happen within a few days before or after an outbreak and can last about 1.5 days. Asymptomatic shedding is much more common with herpes simplex virus 2 (HSV-2) than with herpes simplex virus 1 (HSV-1).

Symptoms of Recurrence. Herpes simplex nearly always recurs. The site on the body and the type of virus influence how often it comes back. The virus usually takes the following course:

Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also have a headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as few as 2 hours or as many as 2 days, steps when the blisters develop. About 25% of the time, recurrence does not go beyond the prodrome stage.
Outbreak. Recurrent outbreaks of herpes simplex virus (HSV) feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they typically heal in 6 - 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but several different factors may be involved. These include sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, and emotional stress. Some studies link recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Oral herpes can be provoked within about 3 days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot kill the virus completely.

Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 1 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by herpes simplex virus 2 (HSV-2), although the rate of simplex virus 1 (HSV-1) genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. While there is no difference in treatment, there can be a difference in disease course. Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area 3 - 14 days after exposure to the virus. If there is a long time between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has already produced antibodies to the virus. These kinds of first infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop symptoms such as flu-like discomfort and fever. The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men:

In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as many as 6 weeks.
Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, people have four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes:

HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some have them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

Patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.


Location and type	Symptoms	Treatments
*Eye (ocular herpetic infection).* Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. The incidence has been highest in children, although it is increasing in older individuals.	Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks. Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers. Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).	Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate-to-severe inflammation. Procedures. Patients with ocular HSV may also need debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. The patient may wear a patch or soft contact lens afterward. Patients with HSV who show scarring in the cornea may need surgery. In rare cases, a corneal transplant may be necessary.
*Brain (HSV encephalitis).* Usually HSV-1, although HSV-2 is typically the cause in newborns. In about 25% of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About a third of cases occur in people under 20 years old, half over age 50, and the balance between ages 20 -50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.
*Finger (herpetic whitlow)*. One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% of cases, and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2 - 3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit. Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir, or foscarnet in patients resistant to acyclovir.
Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
*Other skin areas (herpetic erythema multiforme).* May follow any form of recurrent HSV. Is relatively rare.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.	Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).
Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Click the icon to see an image of herpetic esophagitis.

Transmission

To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through broken skin or a mucous membrane, such as inside the mouth or on the genital area. Each virus can be carried in bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores. The risk for infection is highest with direct contact of blisters or sores during an outbreak.

Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus cannot be transmitted to another person. However, at some point, it often begins to multiply again without causing symptoms (called shedding ). During shedding, the virus can infect other people through exchange of bodily fluids.

Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.

Oral herpes (usually HSV-1) has been detected in both the saliva and blood of patients with active oral infections. It is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. The virus, however, can also enter through the anus, skin, and other areas.

People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests about one-third of all herpes simplex virus 2 (HSV-2) infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.

In the past, genital herpes was mostly caused by HSV-2, but herpes simplex virus 1 (HSV-1) genital infection is increasing, most likely to due to oral sex. Shedding of genital HSV-1 is less common than with HSV-2, but transmission obviously still occurs, as evidenced by the rising prevalence of genital HSV-1. In fact, a person who carries both HSV-1 and HSV-2 poses a greater risk for sexually transmitting HSV-2 than a person who carries only HSV-2. A person who is infected with only HSV-1 has some protection against being infected by HSV-2.

Risk Factors

Everyone is at risk for herpes simplex virus. According to the latest U.S. data from 1999 - 2004, 57.7% of Americans ages 14 – 49 are infected with herpes simplex virus 1 (HSV-1). About 17% of Americans in the same age range test positive for herpes simplex virus 2 (HSV-2). Infection rates for both viruses have declined since the late 1980s. However, infection is lifelong.

Oral herpes is usually caused by HSV-1. The highest incidence of first infection occurs between 6 months and 3 years of age. The incidence in children varies among regions and countries, with the highest rates occurring in crowded and unsanitary regions. Studies suggest that by age 5 more than a third of children in low-income areas are infected compared to 20% of children in middle-income areas. However, by the time children in middle-income areas reach their 30s, about 60% have become infected with HSV-1. After age 40, socioeconomic differences in infection rates become even less pronounced.

The number of Americans with genital herpes increased by 30% from the late 1970s through the early 1990s. However, recent surveys indicate that prevalence is decreasing. A 2006 study in the Journal of the American Medical Association found that among Americans age 14 - 49, the prevalence of herpes simplex virus 2 (HSV-2) decreased by 19% from 1988 - 2004. The decrease was greatest among teenagers age 14 - 19.

The prevalence of herpes virus simplex 1 (HSV-1) also declined, but the percentage of genital herpes infections caused by HSV-1 more than tripled. Among people infected with HSV-1, but not HSV-2, 1.8% were diagnosed with genital herpes from 1999 to 2004 compared with 0.4% from 1988 to 1994. (HSV-2 still causes the majority of genital herpes infections.)

Although the prevalence of genital herpes is declining in the United States, it still remains in epidemic proportions. According to the U.S. Centers for Disease Control and Prevention, at least 45 million Americans age 12 and over have had genital herpes. About 1 in 5 teenagers and adults are infected with genital herpes.

Gender. Anyone who is sexually active is at risk for genital herpes. Studies indicate that around 22% of Americans are infected with HSV-2, with the risk higher in women (26%) than in men (18%). Men, however, have twice as many recurrent infections as women.

Women have an 80 - 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 4 times more likely to be infected than men. In one study of sexually active American teenagers, 15% of the females had evidence of being infected with HSV-2, compared to none of the males. Having a drinking problem greatly increased the likelihood of infection in these young women.

Ethnicity. Although African-Americans are more likely to test positive for HSV-2, Caucasians have a higher risk for active genital symptoms. Over the past few years, the greatest increase in HSV-2 has occurred in Caucasian teenagers.

Compromised Immune Systems. People with compromised immune systems, notably patients with HIV, are at very high risk for HSV-2. Between 68 - 81% of patients with HIV are infected with HSV-2. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and transplant patients.

The following are examples of people who are at particularly risk for specific forms of herpes.

Health care providers, including doctors, nurses, and dentists. This group is at higher than average risk for herpetic whitlow, herpes that occurs in the fingers.
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing. These individuals are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores and usually affects the head or eyes.

Complications

The severity of symptoms depends on where and how the virus enters the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the herpes infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with herpes is also common during pregnancy.

However, although about 1 million pregnancies occur each year in women who have been infected with HSV-2, complications occur in fewer than 4 in 1,000 infected pregnant women.

Approach to the Pregnant Herpes Patient. The approach to a pregnant woman who has been infected by either HSV-1 or HSV-2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study, the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be virus-free, and the newborn must still be tested.)
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at 3 - 5-day intervals prior to delivery to determine whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, a vaginal delivery can be performed and the newborn is examined and cultured after delivery.

Some doctors now recommend anti-viral medication for pregnant women who are infected with HSV-2. Recent studies indicate that acyclovir (Zovirax) or valacyclovir (Valtrex) can help reduce the recurrence of genital herpes and the need for Cesarean sections. Women begin to take the drug on a daily basis beginning in the 36th week of pregnancy (last trimester).

Although 25 - 30% of pregnant women in the U.S. and Europe have a history of herpes simplex virus (HSV-2) infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 - 20,000 births, depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes and a first infection that is acquired early in the pregnancy pose a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are:

During a first infection, the virus is shed for longer periods, and more viral particles are excreted.
An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Infants may acquire congenital herpes from a mother with an active herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not help systemic herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Herpes infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of herpes in the newborn.

Localized infection affects the skin, eyes, and mucous membranes. Herpes simplex virus 1 (HSV-1) usually causes this temporary. However, in some cases, most often herpes simplex virus 2 (HSV-2) infections, later complications develop in 5 - 10% of infants. If untreated, the virus may lead to very severe complications, notably disseminated or central nervous system infection.
Disseminated disease can affect internal organs, such as the liver, lungs, and adrenal glands. It is fatal in up to 80% of newborns if left untreated, and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal, and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications. These may include:

Acute infection in the mother at delivery
Prematurity
Seizures in the infant
Disseminated intravascular coagulopathy, a blood-clotting disorder that can occur in response to infection

Factors that Indicate a Lower Risk for Severe Complications. These may include:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. However, antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first 6 months.

Tests for the Newborn at Risk for Herpes. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 - 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of Herpes in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Doctors and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within 5 - 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
The other half of infected infants develop no lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Doctors should suspect infection in any infant with fever, irritability, lethargy, or poor feeding at 1 week of age.

Treatment of Herpes in the Newborn. If doctors suspect herpes virus infection in a newborn, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 - 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term acyclovir by mouth to newborns following the initial infection will improve the outcome.

Herpes Encephalitis. Each year in the U.S., herpes accounts for 2,100 cases of encephalitis, a rare but extremely serious brain disease. Herpes simplex virus 1 (HSV-1) is usually the cause, except in newborns. In about 70% of cases of infant herpes encephalitis, the disease occurs when a latent herpes simplex virus 2 (HSV-2) is activated. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have both significantly improved survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from herpes encephalitis depends on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within 2 days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk than men for herpes meningitis. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for up to a week, although recurrences have been reported.

Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein that is critical in the development of Alzheimer's disease.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that go away in a few days.

Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of cases of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture, resulting in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks.Rarely, it can lead to a viral infection. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of patients with herpes, 82% felt depressed, and 75% were worried about rejection. Over 25% had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes simplex is particularly devastating when it occurs in immunocompromised patients and, unfortunately, coinfection is common. People infected with herpes have a three-fold increased risk for contracting HIV. Furthermore, studies have reported that 68 - 81% of patients with HIV are also infected with herpes simplex virus 2 (HSV-2).

Patients with HIV are particularly vulnerable to complications. When a person has both viruses, there appears to be a synergy between them, with each virus increasing the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be transmitted to sexual partners. In addition, episodes of herpes recurrence increase, at least temporarily, HIV viral load. An important 2007 study in the New England Journal of Medicine indicated that treatment of HSV-2 with valacyclovir can help reduce plasma and genital levels of HIV in women who are infected with both viruses. Researchers are continuing to investigate whether treatment of HSV-2 may help reduce the risk of HIV transmission.

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including:

Pneumonia
Inflammation of the esophagus
Encephalitis (inflammation of the brain)
Destruction of the adrenal glands
Disseminated herpes (spread of infection throughout the body)
Liver damage, including hepatitis

Hepatitis caused by primary or recurrent herpes can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications, or even a liver transplant, when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Several conditions have been linked to herpes infections, although the association has not been substantiated in most cases.

Arthritis, usually in a single joint, has been sporadically reported as a result of herpes infection.
People with herpes simplex virus 2 (HSV-2) may be more likely to get sexually transmitted hepatitis C.
Some evidence suggests that herpes simplex virus 1 (HSV-1) may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
Some studies have reported associations between herpes simplex and heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Diagnosis

The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, some patients who carry the virus may not have visible genital lesions. Laboratory tests are essential for confirming herpes diagnosis. These tests include virologic tests (which examine samples of skin taken from the lesion) and serologic tests (blood tests that detect antibodies).

In its 2006 guidelines for sexually transmitted diseases, the U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases.

According to the CDC, up to 50% of first-episode cases of genital herpes are now caused by herpes simplex virus 1 (HSV-1). However, recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than herpes simplex virus 2 (HSV-2). It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations.

Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 3 days of appearance. The viruses, if present, will reproduce in this fluid sample but may take 1 - 10 days to do so. If infection is severe, testing technology can shorten this period to 24 hours, but speeding up the timeframe during this test may make the results even less accurate. Viral cultures are very accurate if lesions are still in the clear blister stage, but they do not work as well for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Polymerase chain reaction (PCR) tests are much more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis (see below). PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures and is not FDA-approved for testing genital specimens. However, because PCR is highly accurate, many labs have used it for herpes testing.

An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and microscopically examined for the virus. Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies) indicate herpes infection. The test is quick but accurate 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.

Serologic (blood) tests can identify antibodies that are specific to the virus and its type, herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.

Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:

Glycoprotein gG-1 is associated with HSV-1
Glycoprotein gG-2 is associated with HSV-2

Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.

Serologic tests are most accurate when administered 12 - 16 weeks after exposure to the virus. Recommended tests include:

HerpeSelect. This includes two tests: ELISA (enzyme-linked immunosorbent assay) or Immunoblot. They are both highly accurate in detecting both types of herpes simplex virus. Samples need to be sent to a lab, so results take longer than the in-office Biokit test.
Biokit HSV-2 (also marketed as SureVue HSV-2). This test detects HSV-2 only. Its major advantages are that it requires only a finger prick and results are provided in less than 10 minutes. It is very accurate, although slightly less so than the other tests. It is also less expensive.
Western Blot Test. This is the gold standard for researchers with accuracy rates of 99%. It is costly and time consuming, however, and is not as widely available as the other tests.

False-negative (testing negative when herpes infection is actually present) results can occur if tests are done in the early stages of infection. False-positive results (testing positive when herpes infection is not actually present) can also occur, although more rarely than false-negative. Your doctor may recommend that you have the test repeated.

Experts recommend serologic herpes tests especially for:

People who have had recurrent genital symptoms but no negative herpes viral cultures
Confirming infection in people who have visible symptoms of genital herpes
Determining if the partner of someone diagnosed with genital herpes has acquired herpes
People who have multiple sex partners and who need to be tested for different types of STDs

At this time, doctors do not recommend screening for HSV-1 or HSV-2 in the general population.

It make take a number of test to diagnose herpes encephalitis.

Imaging Tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography or magnetic resonance imaging scans may be used to differentiate encephalitis from other conditions.

Brain Biopsy. Brain biopsy is the most reliable method of diagnosing herpes encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain.

Polymerase Chain Reaction (PCR). The polymerase chain reaction (PCR) assay looks for tiny pieces of the DNA of the virus, and then replicates them millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of herpes encephalitis in most cases, eliminating the need for biopsies. The CDC recommends PCR for diagnosing herpes central nervous system infections.

Similar Conditions

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal in 2 weeks without treatment.

Canker sores (Aphthous ulcers) are very common. Typically, they are a shallow ulcer with a white or whitish/yellow base surrounded by a reddish border. This ulcer is seen in an individual with AIDS and is located in front and just below the bottom teeth.

Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly those with impaired immune systems.

Click the icon to see an image of thrush.

Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.

Conditions that may be confused with herpes simplex virus 2 (HSV-2) include bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Simple corneal scratches can cause the same pain as herpetic infection, but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Stevens-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

Click the icon to see an image of the shingles.

Click the icon to see an image of chickenpox.

Home Remedies and Prevention

Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.

Several simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Keep blisters or sores clean and dry with cornstarch or similar product. (Women should not use talcum powder because it may increase their risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Avoid tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain on urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of herpes simplex virus 1 (HSV-1).
Avoid sex during both outbreaks and prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen. Never give children aspirin.

In one study, stress management techniques developed using cognitive-behavioral methods not only were effective in reducing depression in those with hepres simplex virus 2 (HSV-2) but blood test results also revealed lower levels of HSV-2 antibodies, a possible sign of decreased viral activity. In any case, reducing stress using relaxation techniques does no harm.

Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:

Echinacea (Echinacea purpurea )
Siberian ginseng (Eleutherococcus senticosus )
Aloe (Aloe vera )
Bee products that contain propolis, a tree resin collected by bees
Lysine
Zinc

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following are special concerns for people taking natural remedies for herpes simplex:

Echinacea can lower white blood cell levels when taken for long periods of time. This herb can also interfere with drugs that are used to treat immune system disorders.
Siberian ginseng can raise blood pressure levels.
Bee products (like propolis) can cause allergic reactions in people who are allergic to bee stings.
Do not take Lysine with certain types of antibiotics.
'Taking zinc in large amounts (more than 200 mg/day) can cause stomach upset.

Infected people should take several steps to avoid transmitting the virus to others. It is almost impossible to defend against the transmission of oral herpes simplex virus 1 (HSV-1) since it can be transmitted by very casual contact.

Preventing Transmission During an Outbreak. When an outbreak of herpes occurs, the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands and nails after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to 2 hours on cloth and for 4 hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.

Preventing Sexually Transmitted Disease. Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. Condoms are also important during oral sex, as an increasing number of new genital herpes cases are due to HSV-1, particularly among younger people.

The use of condoms for preventing the transmission of herpes simplex virus 2 (HSV-2) is not foolproof. Even a small tear can permit passage of the virus. However, studies show that regular condom use can significantly reduce the risk of HSV-2 infection.

Condoms made of latex are less likely to slip or break than those made of polyurethane. “Natural” condoms made from animal skin do not protect against HSV infection because herpes viruses can pass through them.

Women appear to be better protected than men are by male condoms. The reason may be that men shed HSV-2 from the skin of the penis, which is covered by the condom. However, in women the virus is often shed from skin areas around the genital area, which can have contact to skin areas in the male outside the condom.

The female condom is another option for infected women or partners of infected men. The female condom covers a large area and is an effective barrier to sexually transmitted viruses.

Note on Lubricants and Spermicides. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used. Oil-based lubricants (petroleum jelly, body lotions, cooking oil) can weaken latex.

Some condoms come prelubricated with sperm-killing substances called spermicides, which are no longer recommended. The standard active ingredient in spermicides is nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9 does not provide any additional protection against sexually transmitted diseases (STDs). It can cause yeast and urinary tract infections in women. In addition, it can cause irritation around the genital areas, which makes it easier for herpes and other STDs to be transmitted. In fact, research indicates that it actually increases the risk for HIV in women.

Treatment for Genital Herpes

No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped, and, even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce symptoms and improve healing times.

Antiviral drugs called nucleosides or nucleotide analogues are the main drugs used to treat genital herpes. They are taken by mouth. (Acyclovir is also available as an ointment, but the oral form is much more effective.) These drugs limit herpes viral replication and its spread to other cells. They are not cures, however.

Three drugs are approved to treat genital herpes:

Acyclovir (Zovirax or generic)
Valacyclovir (Valtrex)
Famiciclovir (Famvir)

When a patient has herpes for the first time, the drug is taken several times a day for 7 -10 days. Then the drugs are used either to suppress the virus or to treat outbreaks.

To treat outbreaks, regimens depend on the medication and dosage prescribed:

Acyclovir: 400 mg three times a day for 2 days or 800 mg twice a day for 5 days
Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days
Famiciclovir: 125 mg twice a day for 5 days or 1000 mg twice a day for 1 day. (In 2006, famiclovir was approved as the first one-day treatment for recurrent genital herpes.)

To suppress outbreaks, treatment requires taking pills daily on a long-term basis. (Acyclovir and famiciclovir are taken twice a day, valacyclovir once a day.) Suppressive treatment can reduce outbreaks by 70 – 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Valacyclovir may work especially well for preventing herpes transmission among heterosexual patients when one partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, valacyclovir may not be as effective as acyclovir or famiciclovir for patients who have very frequent recurrences of herpes (more than 10 outbreaks per year).

Because the frequency of herpes recurrences often diminishes over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it. Studies suggest that daily drug therapy is safe and effective for up to 6 years with acyclovir, and up to 1 year with valacyclovir or famciclovir.

Side Effects. Nausea and headache are the most common side effects, but in general these drugs are safe. Although there is some evidence these drugs may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these medications.

Risk for Resistant Viruses. As with antibiotics, doctors are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They feel that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. However, patients who do not respond to standard regimens should be monitored for emergence of drug resistance.

Some doctors believe that developing an effective herpes vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold the potential for eliminating latent, lifelong infections.

In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) launched the Herpevac Trial for Women. The NIAID seeks to enroll 7,500 women between the ages of 18 and 30 who test negative for both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infection. The trial is being conducted at more than 40 sites in the United States and Canada. Participants are randomly assigned to receive either three doses of the experimental herpes vaccine or an investigational hepatitis A vaccine. The women will be observed for 20 months following the initial vaccination to determine if they contract genital herpes (or, for the control group, hepatitis A) during this time. The vaccine used in the trial does not contain live virus and will not itself cause infection.

The premise for the Herpevac trial is based on results from two studies published in the New England Journal of Medicine in 2002. In these studies, a glycoprotein D vaccine was effective in preventing genital herpes in women who were not infected with HSV-1 or HSV-2. For uninfected women, the risk of contracting genital herpes was reduced by nearly 75 percent. The vaccine was not useful, however, for women already infected with HSV-1 and was ineffective in men regardless of their virus status.

Treatment for Oral Herpes

Acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) -- the anti-viral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes. In addition, acyclovir is available in topical form, as is penciclovir (a related drug).

These ointments or creams help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.

Penciclovir (Denavir) heals herpes simplex virus 1 (HSV-1) sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of pain. Ideally, the patient should apply the cream within the first hour of symptoms, although benefits have also been noted with later application. It is continued for 4 consecutive days, and should be reapplied every 2 hours while awake.
Acyclovir cream (Zovirax) works best when applied early on (at the first sign of pain or tingling).
Docosanol cream (Abreva) is the only FDA-approved non-prescription ointment for oral herpes. The patient applies the cream five times a day, beginning at the first sign of tingling or pain. Studies have been mixed on the cream’s benefits.
Over-the-counter topical anesthetics may provide modest relief. They include Anbesol gel, Blistex lip ointment, Campho-phenique, Herpecin-L, Viractin, and Zilactin.

Resources

www.ashastd.org -- American Social Health Association
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/std/herpes -- Centers for Disease Control and Prevention
www.herpesdiagnosis.com -- Herpes Diagnosis
www.herpesalliance.org -- International Herpes Alliance
www.gotherpes.com -- Herpes support site
www.niaid.nih.gov/dmid/stds/herpevac -- Herpevac (herpes vaccine) clinical trial information

References

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume JC, Lechat P, Chosidow O. A meta-analysis to assess the efficacy of oral antiviral treatment to preventgenital herpes outbreaks. J Am Acad Dermatol. 2007 Aug;57(2):238-46. Epub 2007 Apr 9.

Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(:790-9.

Review Date:
9/9/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Vitamins

FitSugar — Wed, 08 Oct 2008 17:35:00 -0700

In This Report

Highlights
Introduction
Carotenoids
Phytochemicals
Healthy Foods
Dietary Health Benefits
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer

Growing evidence suggests that vitamins and micronutrients, especially from foods, may play important roles in the prevention or treatment of certain cancers:

One study found that the risk of prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose.
A diet high in cruciferous vegetables has been found to reduce the risk of kidney cancer; low consumption of cruciferous vegetables increases the risk.

On the other hand, high amounts of folic acid (a B vitamin) may be associated with colorectal cancer, and beta-carotene supplements are associated with increased lung cancer risk in smokers and people exposed to asbestos.

Macular Degeneration

In 2007, the National Eye Institute recommended that people with intermediate or advanced macular degeneration in one eye take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc.

Osteoporosis

Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it also may be effective in treating rheumatoid arthritis.

Heart Disease

Although people with high levels of homocysteine are prone to developing blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with B vitamins and folic acid does not reduce the incidence of deep vein thrombosis (DVT). A 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with folic acid and other B vitamins had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke.

Introduction

Vitamins do not share a common chemistry, but they do share certain characteristics. They are all organic nutrients that are necessary in small amounts for normal metabolism and good health. Your diet or supplements provide most vitamins. The body can manufacture only three vitamins (D, K, and the B vitamin biotin) from nondietary sources. Unlike carbohydrates, fats, and proteins, vitamins are not sources of energy. Instead, vitamins are chemical partners for the enzymes involved in the body's metabolism, cell production, tissue repair, and other vital processes.

Vitamins are either fat soluble or water soluble. The fat-soluble vitamins, which include A, D, E, and K, are absorbed by the body using processes that closely parallel the absorption of fat. They are stored in the liver and used up by the body very slowly. The water-soluble vitamins include C and the B complex vitamins. The body uses these vitamins very quickly. Excess amounts are eliminated in urine.

The Recommended Daily Allowance (RDA) for vitamins, set by the Food and Nutrition Board of the National Academy of Sciences-National Research Council, has been used for years as a guide for determining the amount of vitamins needed for a healthy diet. The RDA refers to an estimate of the average daily requirement. It is not completely adequate, however, for informing people about the amounts of vitamins they may need.

The RDA is gradually being enhanced using a new standard called the Dietary Reference Intake (DRI). The DRI is based on the following ratings, which will eventually appear on labels:

The recommended daily allowance (RDA). This is the current rating on most vitamins.
The estimated average requirement (EAR). This is the amount adequate for 50% of all people, which will be put on labels when it can be calculated.
Adequate intake (AI). This is an amount that will be used if there is insufficient data to calculate the EAR.
Tolerable upper intake level (UL). This is the maximum dose likely to be safe in nearly all individuals. It will be included on labels if this amount is known.

Food and supplement labels now typically list the Daily Value (DV). This is the percentage of the amount of a nutrient that experts believe a person needs in their daily diet. On food labels it is usually based on one serving size for a person who takes in 2,000 calories a day.

Regulation of dietary supplements by the U.S. Food and Drug Administration (FDA) is a complex issue.

Labels on vitamins and other dietary supplements now include nutrient information and list all ingredients, including identifying parts of plants from which ingredients may be taken. Unlike the labels for drugs, however, labels for vitamins and supplements may not claim to prevent or treat any specific disease. Labels for vitamins and supplements include one of the following:

Health claim -- description of how the substance may reduce the risk of a health-related condition
Nutrient claim -- description of the amount of the nutrient in the product or
Structure or function claim -- description of how the product may affect organs or systems of the body, without claiming to prevent or treat specific disease

The quality of dietary supplements depends on the manufacturer and is not ensured by FDA. The U.S. government does not require that supplements be standardized, meaning that the amounts or quality of nutrients may vary depending on the batch. So, more expensive supplements are not necessarily better than the less expensive ones. Government regulations are in the process of catching up to the boom in the supplement industry. In the meantime, some companies voluntarily adhere to rigorous quality controls, while others do not.

The U.S. Pharmacopeia (USP), an independent organization that sets quality standards for drugs, has also implemented standards for vitamins. Consumers may look for the USP label on products of companies that adhere to these standards. USP verification means the following:

What is in the bottle matches what is listed on the label.
There are no harmful levels of contaminants.
The supplement will be absorbed properly into the body.
It has been produced according to good manufacturing standards.

Before selling any supplement introduced after 1994, manufacturers must submit information as to why the product is considered safe for people. The FDA may refuse to allow it on the market if it finds the evidence insufficient. The FDA does not require manufacturers to provide any scientific evidence that dietary supplements are safe and effective before a product is sold (unlike drugs, which must be proven both safe and effective through clinical trials). If a supplement causes side effects in people once it is for sale, the government may place restrictions on the supplement or withdraw it from the market. The FDA may also withdraw products from the market if their labels are misleading or false.

About 30% of Americans take at least one vitamin or mineral supplement daily. In a large study that examined the death rates of 11,000 people, however, there was no difference in mortality rate between those who took vitamin supplements and those who didn't. Most people who have a healthy diet do not need vitamins, but there are some exceptions.

Pregnant and Breast-Feeding Women. Women who are pregnant or who are breast-feeding generally need additional vitamins. Vitamins B6, B12, and folic acid are particularly important. Women who are vegetarians must be sure to avoid deficiencies, which can harm their offspring. Folic acid reduces the risk for neural tube defects and possibly facial abnormalities, such as cleft palate. Studies also show that low folate levels during pregnancy are associated with low birth weight, a risk factor for the development of cardiovascular disease in adulthood. Multivitamins that contain folic acid also appear to be somewhat protective. A woman's best approach is to take extra folic acid plus multivitamin supplements (which have additional benefits), starting them before becomming pregnant.

The human body stores several years' worth of vitamin B12, so nutritional deficiency of this vitamin is extremely rare. Although, people who follow a strict vegetarian diet and do not consume eggs or dairy products may require vitamin B12 supplements.

Pregnant women with healthy diets may have low folate levels and need to take supplements. Requirements are as follows:

The recommended daily allowance (RDA) for folic acid prior to conception and during pregnancy is 400 mcg.
During breast-feeding 260 - 280 mcg is recommended.

The following vitamins may have some value for pregnant women:

Choline, another vitamin B, is also essential for pregnant (450 mg) and nursing women (550 mg). Choline plays a key role in brain development. Not getting enough during pregnancy can lead to memory and cognitive defects in the baby. Choline supplements can also lessen the cognitive defects of prenatal alcohol exposure.
Vitamin B6 may help improve morning sickness.
Vitamin C may reduce the risk of urinary tract infections during pregnancy.
Vitamin D may help prevent preeclampsia.
One study also suggested that if pregnant women took vitamin K supplements, their infants might not need the required injection of this vitamin after birth, but supplements of vitamin K during pregnancy are not currently recommended.

Some women have low vitamin A reserves in their liver. It is important to note, however, that too much vitamin A significantly increases the risk for birth defects. Daily amounts of 10,000 IU (international units) of vitamin A in supplements and food (an amount not far above the RDA level) can pose a danger. Experts recommend that pregnant women take in no more than 8,000 IU per day and avoid eating liver.

Infants and Children. Infants who are breast-fed by healthy mothers receive enough vitamins except, in some cases, vitamins K and D. Human milk has low levels of K, and the newborn's immature intestinal tract may not produce enough of the baby's own supply. Most babies are given an injection of this vitamin at birth. Infants being breast-fed by malnourished women or those who lack sufficient exposure to sunlight may be deficient in vitamin D. In these cases, supplements of 200 - 300 IU are recommended. Formulas are required to contain sufficient vitamins and minerals. One study suggests that vitamin supplements for infants under 1 year of age may help protect them from developing type 1 diabetes later on. Beyond infancy, most American children receive all the vitamins they need from their diet unless they are living in severely deprived circumstances.

Smokers. Smoking interferes with absorption of several vitamins, importantly vitamins C and D. In one study nearly 25% of female smokers and 31% of male smokers were deficient in vitamin C. Smoking can interfere with the metabolims of vitamin D, resulting in poor muscle function. Taking high doses of antioxidant vitamins, however, may actually be harmful in smokers, especially beta carotene. Instead of taking supplements, most smokers should be sure their diets are rich in fresh fruits and vegetables and whole grains. Of course, smoking cessation is the most important intervention of all.

Click the icon to see an image of sources for vitamin C.

Alcoholics. Alcoholics often suffer from multiple vitamin deficiencies. The most dangerous deficiencies are from vitamins B1 (thiamin), folic acid, B6 (pyridoxine), B2 (riboflavin), and vitamin C. Low levels of B6 are associated with increased risk of colorectal cancer in men who drink large amounts of alcohol.

Overweight Adults. Overweight and obesity causes many problems that often result in metabolic syndrome or type 2 diabetes. Evidence suggests that isoflavones can help regulate cholesterol levels and reduce body weight and fat mass. Because some medications used to control blood sugar levels reduce folic acid and vitamin B12, some people may need vitamin supplements.

People Who Have Had Gastric Bypass Surgery. Vitamin deficiency is a recognized complication of gastric bypass surgery. Women, African-Americans of both sexes, and adults who have had laparoscopic Roux-en-Y bypass surgery are at highest risk. The deficiency is treated with water-soluble vitamin supplements.

Strict Vegetarians. Strict vegetarians need supplements of vitamin B12, unless they get enough of it from fortified cereals and other grain products.

Dieters and Vegetarians. People on weight-reduction diets with less than 1,000 calories a day should probably take a multivitamin and should also check regularly with a physician.

Vegetarians may need riboflavin, vitamin B12, and vitamin D supplements. Vegans, who do not eat dairy or eggs as well as meat, may be at further risk for vitamin A deficiencies if they do not also have plenty of dark colored fruits and vegetables. Those who eat eggs and dairy products need only watch their iron levels.

Deficiencies in vegetarian children may be particularly harmful. (One study, for example, reported that adolescents who had been on macrobiotic diets before age 6 and were deficient in vitamin B12 scored lower on psychological tests.) Pregnant and breast-feeding women who are vegetarians must be sure to have sufficient vitamins. Of special note, maternal deficiencies in vitamin B12 may cause delayed growth and neurologic problems in their newborns.

Click the icon to see an image of sources for vitamin D.

Older Adults. Deficiencies of vitamins and important minerals have been observed in almost a third of elderly people. Often their dietary habits slip and they fail to eat balanced meals regularly. Multiple drug regimens may prevent absorption of some vitamins. Elderly people, particularly if they are not exposed to sunlight, may be deficient in vitamin D. They also may have low levels of important B vitamins. (Older adults showing signs of dementia should be checked for B12 deficiencies as well as other disorders causing mental disturbances.) One study reported that the immune systems of elderly people may benefit from higher levels of vitamin E than the daily recommended dosage. It should be noted, however, that metabolism slows down as a person ages, and in elderly people it takes the liver longer to eliminate drugs and vitamins from the body. The effect of some vitamin supplements, therefore, may be intensified. Dosage levels of vitamin A, for instance, which might be harmless in a younger adult, could be toxic in an elderly patient. Nevertheless, experts are increasingly recommending extra vitamin and mineral supplements for older people.

People Who Need to Avoid Sunlight. People who need to avoid sunlight or are housebound, and whose diet is low in foods that contain vitamin D should take supplements. People with darker skin are at higher risk for deficiencies than those with whiter skin. (Note: vitamin D is toxic in high doses, and no one should exceed the recommended daily intake of vitamin D except under the direction of a physician.)


Benefits	Essential for growth, bone development, night vision, reproduction, and healthy skin.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	Vitamin A RDA and Upper Limit (when toxicity is risk) are the following: For children: 1,000 IU ages one to three (upper limit is 2,000 IU); 1,333 IU ages 4 - 8 (upper limit is 3,000 IU); and 2,000 IU for 9 - 13 (upper limit is 5,665 IU). For nonpregnant women: 2,330 IU ages 14 through adulthood. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For pregnant women: 2,500 IU for pregnant women under 18; 2,565 IU for pregnant women over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19. It should be noted that some experts recommend 8,000 IU as the upper limit during pregnancy.) Warning: Use of the topical acne medication tretinoin, a vitamin A derivative, during pregnancy can cause birth defects. For nursing women: 4,000 IU for nursing mothers under 18; 4,335 IU for nursing mothers over 19. (Upper limit is 9,335 IU for ages 14 - 18 and 10,000 IU for women over 19.) For men: 3,000 IU ages 14 - 18; 3,000 IU for ages 19 and above. (Upper limit is 10,000 IU.) Note: In determining the daily vitamin A allowance, experts also take note of provitamins, such beta carotene, that convert to vitamin A. Some experts recommend 3 - 6 mg of beta-carotene. Vitamin A is also now being measured with a new unit called the Retinol Activity Equivalent (RAE or RE). One RE is equal to 1 mcg. Retinol is the most active form of vitamin A and it is also converted in the liver from carotenoids. One RE is equal to 12 mcg of beta-carotene or 24 mcg of alpha-carotene or beta-cryptoxanthin).
Foods containing the vitamin	Animal products, such as liver, dairy products, eggs, and fish liver oil. Provitamin A carotenoids are also found in dark red, green, and yellow vegetables and fruits. Requires some dietary fat to be absorbed.
Effects of deficiencies	Skin disorders, severe diarrhea, and eye damage. In less developed countries severe deficiencies cause blindness in 250,000 children each year. Diets low in vitamin A may also increase the risk of developing cancer. Low dietary intake of vitamin A has been associated with impaired lung function in children.
People at risk for deficiencies	Preschool children and any child with inadequate intake of protein, calories, and zinc. Iron deficiency may also impair metabolism of vitamin A. People with asthma. People with serious disorders in the intestine, liver or pancreas, such as cystic fibrosis, steatorrhea, biliary obstruction, inflammatory bowel disease, cirrhosis, and others. People who have undergone Roux-en-Y gastric bypass surgery. Vegans (vegetarians who do not eat eggs and dairy). Such individuals should be sure to have plenty of deep-colored fruits and vegetables. People who abuse alcohol. It should be noted, however, that people with alcoholism may be at risk for vitamin A deficiency, but a combination of high-dose vitamin A and alcohol may cause toxic effects in the liver. Healthy adults usually have a year's store of vitamin A in the liver, so temporary nutritional deficiencies or problems with fat absorption are unlikely to cause serious vitamin A deficiency problems.
Toxicities	Very toxic when taken in high-dose supplements for long periods of time. Symptoms of overdose include dizziness, nausea, vomiting, headache, skin damage, mental disturbances, and, in women, infrequent periods. Can affect almost every part of the body, including eyes, bones, blood, skin, central nervous system, liver, and genital and urinary tracts. Severe toxicity can cause blindness and may even be life threatening. In children, chronic overdose can cause fluid on the brain and as well as adult complications. High consumption of vitamin A may also increase the risk of gastric cancer and the risk of osteoporosis and fractures in both men and women. Pregnant women who take amounts not much higher than RDA levels increase the risk for birth defects in their children. Liver damage can occur in children who take RDA-approved adult levels over prolonged periods of time or in adults who take as little as five times the RDA-approved amount for 7 - 10 years.


	B Vitamins: General Information	Vitamin B1 (thiamin)
Benefits	The B vitamins have a wide and varied range of functions in the human body. Most B vitamins are involved in the process of converting blood sugar into energy.	Essential for converting blood sugar into energy and is involved in metabolic activities in nerves, heart, and muscles and in the production of red blood cells.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)		RDA is 1.2 mg per day for men and 1.1 mg for women.
Foods containing the vitamin		Best source is pork and good sources are dried fortified cereals, oatmeal, corn, nuts, cauliflower, and sunflower seeds. Supplements for people with normal diets and health are unnecessary.
Effects of deficiencies	Deficiencies are uncommon in the U.S., but when they occur, they usually involve several B vitamins, since many of them come from the same food groups.	Severe vitamin B1 deficiency is known as beriberi. It can cause visual disturbances, paralysis, staggering, loss of sensation in the legs and feet, psychosis, and congestive heart failure.
People at risk for deficiencies	Alcohol interferes with these vitamins, and some of the physical and mental problems that alcoholics experience may be attributed to a deficiency of B vitamins. Elderly people are also at risk for deficiencies because of inadequate diets and potential interference with B-vitamin absorption by medications. Deficiencies can occur in severely malnourished people or in those receiving long-term dialysis or intravenous feeding. Vegetarians may be at risk.	See general vitamin B description.
Toxicities	Because the B vitamins are water-soluble and eliminated in the urine, toxic reactions from oral administration of most of them are extremely rare. (Exceptions are niacin and B6.) It should be noted that substances known as B15 (pangamic acid) and B17 (laetrile) are neither vitamins nor nutrients; both chemicals are highly dangerous and have no proven nutritional or health value.	No toxic effects have been reported from thiamin.


	Vitamin B2 (riboflavin)	Vitamin B3 (niacin) also known as nicotinic acid	Vitamin B5 (Pantothenic Acid)
Benefits	Important in the production of energy.	Helps break down blood sugar for energy. Acts as a vasodilator, widening blood vessels and increasing blood flow. May be prescribed for improving cholesterol levels.	Important for metabolism of fats, carbohydrates, and proteins, as well as production of steroid hormones and other important chemicals.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 1.7 mg.	DRI is 20 mg.	Adequate intake (AI) is 4 - 7 mg.
Foods containing the vitamin	Liver, dried fortified cereals, dairy products, fish. Some dark green vegetables. Supplements for people with normal diets and health are unnecessary.	Mackerel, swordfish, chicken, veal, dried fortified cereals, pork, salmon, and beef liver. Supplements are unnecessary in people with normal health and diets.	Whole grains, beans, milk, eggs, and liver. Supplements are unnecessary in people with normal health and diets.
Effects of deficiencies	Deficiencies affect the skin and mucous membranes and can cause cracks on the lips or corners of the mouth, eczema of the face and genitals, a burning sensation on the tongue, eye irritation. May contribute to anemia when iron levels are low and contribute to elevated levels of homocysteine, a heart risk factor.	Deficiency causes pellagra; symptoms can include eczema, intestinal and stomach distress, depression, headache, thinning of the hair, and excess saliva production.	Deficiency is unlikely except in company with other B vitamin deficiencies. Symptoms include abdominal distress, burning sensation in the heels, and sleep problems.
People at risk for deficiencies	See general vitamin B description.	Alcoholics and any malnourished persons.	Alcoholics and any malnourished persons.
Toxicities	Until recently, no toxic effects had been reported even from large doses of riboflavin. However, one study indicated that high consumption of vitamin B2 might increase the risk of stomach cancer. More research is needed. (In the same study, vitamins B1, B3, and B6 were protective.)	Even mildly high doses of niacin can cause hot flushing of the face and shoulders, headache, itchiness, and stomach problems. Some report heart disturbances and temporarily lowered blood pressure. Large doses may produce ulcers, gout, diabetes, and liver damage, which are usually reversed when high doses are discontinued.	Although no toxicity has been reported in humans, high dosages have caused liver damage in rats.


	Vitamin B6 (pyridoxine)	Vitamin B12 (cobalamin)
Benefits	Has an effect on over 60 proteins in the body, importantly, those that play a role in the nervous system, in red and white blood cell production, and in heart disease.	Essential for the production of blood cells, manufacturing genetic material, and for healthy functioning of the nervous system. New evidence suggests that high levels of B12 may protect against colon and rectal cancer.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 1.3 mg in adults under 50 and 1.7 mg for older men and 1.5 for older women. (Some experts recommend 3 to 6 mg for people who need heart protection.) Upper limit is 100 mg for adults.	RDA is 2.4 mcg in men and nonpregnant women, 2.6 mcg in pregnant women, and 2.8 mcg in nursing mothers.
Foods containing the vitamin	Meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.	The only natural dietary sources are animal products, including meats, dairy products, eggs, and fish (clams and oily fish are very high in B12). Like other B vitamins, however, B12 is added to commercial dried cereals.
Effects of deficiencies	Increased levels of homocysteine, associated with heart disease and possibly Alzheimer's disease. Skin problems and nervous system disorders, including impaired memory and concentration. Increased risk for kidney stones. One study found a correlation between vitamin B6 deficiency and inability to conceive or carry a child to term. In unborn children, some evidence shows that lack of vitamin B6, in addition to vitamin B12 and folic acid, may be responsible for defects such as cleft lip and palate and spina bifida. Supplementation with these vitamins is advised during pregnancy. Note: People who have been taking more than 50 mg for some time and stop suddenly are at risk for a so-called rebound deficiency. When people stop, they should taper off slowly.	Deficiencies elevate homocysteine, a possible risk factor for heart disease and Alzheimer's disease. Increased risk of bone fractures. Abnormal gaits in the elderly. May cause severe depression, memory loss, instability, disorientation, and decreased reflexes, and possibly hearing loss. Children who are deficient may experience growth failure. Deficiencies in pregnant and breast-feeding women may cause neurologic harm in their offspring. A genetic defect that causes vitamin B12 deficiencies is responsible for pernicious anemia, a serious disorder that causes rapid heart rate, shortness of breath, dizziness, weakness, and fatigue. It must be treated with injections of vitamin B12 or else neurologic damage may occur.
People at risk for deficiencies	Alcoholics and any malnourished person. In rare cases, infants are born unable to metabolize pyridoxine; in such cases, seizures or convulsions can occur and vitamin B6 must be administered.	Alcoholics and any malnourished persons. Evidence suggests deficiencies may be caused by Helicobacter pylori (H. pylori) bacteria (a cause of ulcers). Nearly 30% of patients with inflammatory bowel disease have vitamin B6 deficiency, as well as low levels of iron and vitamin D. People who take the antibiotic isoniazid, high blood pressure medication hydralazine, and the drug penicillimine are at risk for vitamin B6 deficiency. The elderly and people with Crohn’s disease and those who have undergone ileal and ileocolonic resection may have trouble absorbing natural vitamin B12 and require supplements. Some evidence shows that patients with Parkinson’s disease treated with levodopa plus dopa decarboxylase inhibitor (DDC-i) and catechol-O-methyltransferase inhibitor (COMT-i) have low levels of both vitamin B12 and folate. As a result, they need to take supplements of these vitamins. Other studies have found that patients with diabetes treated with metformin, but not roziglitazone, are at risk for low levels of vitamin B12. Vitamin B12 deficiency is also common in patients with polyneuropathy. In up to one-third of patients, vitamin B12 deficiency is the sole or major contributing cause of their neuropathy. Treatment with vitamin B12 has a high success rate in improving the symptoms. Vegetarians are at higher risk for deficiencies.
Toxicities	Very high doses can cause nerve damage with symptoms of instability and numbness in the feet and hands, which may be permanent in some cases. Of specific concern are possible adverse effects on nerve development in the offspring of pregnant women who take large doses, such as for morning sickness.	There is no evidence of toxicity with this vitamin.


	Biotin (a B vitamin)	Choline (a B vitamin)	Folate, or Folic Acid, its synthetic form (a B vitamin)
Benefits	Involved in the production of amino acid proteins and fatty acids.	Essential for fetal brain development and for learning and memory.	Important for many metabolic processes in the body. It is used in the manufacturing of neurotransmitters (chemical messengers in the brain), in protecting the heart, and for synthesizing genetic materials (DNA) in the cells. It may improve blood flow.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	There is no DRI for biotin; some experts suggest 30-100 mcg.	RDA 425 mg for nonpregnant women, 450 mg for pregnant women, and 550 mg for nursing women.	Supplements may be folate (natural) or folic acid (synthetic). Folic acid is nearly twice as potent as folate. DRI is 400 mcg (.4 mg) of folate for the general population, 600 mcg during pregnancy and 500 mcg while nursing. Women who are planning to be pregnant should certainly take 400 mcg of folic acid before conception, during pregnancy, and while nursing.
Foods containing the vitamin	Dietary sources are eggs, milk, liver, mushrooms, bananas, tomatoes, whole grains, nuts, and brewer's yeast. Also produced by bacteria in the intestines.	Peanuts, eggs, cauliflower, and meats, especially liver.	Avocado, bananas, orange juice, cold cereal, asparagus, green leafy vegetables, dried beans and peas, and yeast. Folic acid supplements are now added to commercial breads and cereals.
Effects of deficiencies	Deficiencies are almost unheard of.	Low levels during pregnancy increase risk of birth defects in newborns.	As with vitamins B6 and B12, deficiencies of folate elevate levels of homocysteine, an amino acid in the body that may increase the risk for heart disease, and possibly Alzheimer's disease. Folic acid supplements lower homocysteine levels, but with little or no impact on risk of atherosclerotic disease in the heart or in the peripheral arteries and veins. This suggests that homocysteine may be a marker of cardiovascular disease, rather than a cause. This being said, one 2007 study found that folic acid supplementation in patients with low folic acids levels substantially reduced the risk of a first stroke. Low levels during pregnancy increase risk of birth defects in newborns, and folic acid supplementation plays a key role in preventing birth defects. Folic acid deficiencies Deficiencies can also cause depression and megaloblastic anemia and impair concentration, memory, and hearing.
People at risk for deficiencies			Alcoholics, malnourished persons, people with conditions that disturb the small intestine, people taking certain drugs, particularly methotrexate. Other risk factors for deficiency: high-dose aspirin, smoking, treatment for seizures, taking oral contraceptives.
Toxicities		Excessive doses can cause intestinal problems, and there is also some concern that high doses can be carcinogenic.	Possible connection between high consumption of folate/folic acid and colorectal cancer now under exploration. Some link between high doses and central nervous system disorders, zinc deficiency, and seizures in epileptics. This risk appears to be low, but results indicate that megadoses should be avoided. High amounts in the elderly may mask symptoms of vitamin B12 deficiencies.


Benefits	Vitamin C is a water-soluble vitamin. Acts as an antioxidant (reduces harm from damaging chemical processes in the body). Essential for the production of collagen, the basic protein in bones, cartilage, tendons, and ligaments. A 2007 study found that vitamin C supplements can help prevent the development of complex regional pain syndrome following wrist fracture. Another study found that prostate cancer risk dropped as consumption of vegetables high in vitamin C, such as broccoli and bell peppers, rose. It may also protect against brochoconstriction during exercise in people with asthma. May help boost the immune system.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	DRI is 75 mg (women) and 90 mg (men). (Smokers need an additional 35 mg.)
Foods containing the vitamin	Citrus fruits and juices, papayas, hot chili peppers, bell peppers, broccoli, potatoes, dark leafy greens, kale, red cabbage, cauliflower, cantaloupe, sweet potatoes, and Brussels sprouts. Orange juice is the most important source of vitamin C in the U.S., with frozen juice being the best source of the vitamin.
Effects of deficiencies	Scurvy is the primary deficiency disease. Affects most body tissues, particularly bones, teeth, and blood vessels. Early symptoms include tiredness, weakness, irritability, weight loss, and vague muscle aches. Later symptoms are bleeding gums, wounds that won't heal, rough skin, and wasting away of the muscles. Deficiencies may contribute to periodontal disease and gallstones. Low dietary intake of vitamin C has been associated with impaired lung function in children. Low intake may also increase lead levels in the blood.
People at risk for deficiencies	Deficiency has been uncommon in the U.S., usually occurring in the elderly, alcoholics, cancer patients, and some people on severely limited diets low in fresh fruits and vegetables. Surprisingly, however, studies now suggest that as many as 16% of middle-aged Americans, with the highest risk in smokers and middle aged men, are deficient in vitamin C. High doses of aspirin taken over a long period of time can interfere with vitamin C.
Toxicities	Tolerable upper limit is 2000 mg/day. High doses may cause headaches and diarrhea. Long-term high doses may increase risk for kidney stones. Ascorbic acid increases iron absorption so people with blood disorders, such as hemochromatosis, thalassemia, or sideroblastic anemia, should avoid high doses. Large doses may also thin blood and interfere with anticoagulant medications, blood tests used in diabetes, and stool tests. Rebound scurvy can occur after abrupt withdrawal from long-term large doses. This may affect infants or pregnant women who withdraw suddenly from high doses.


Benefits	Vitamin D is actually a single term for several hormones that are stored mainly in the liver and also in fat and muscle tissue. It is essential for the absorption of calcium into the bone and for normal bone growth.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 200 IU (5 mcg) per day for children and most adults to age 50, 400 IU (10 mcg) for people between ages 50 and 60, and 600 IU over age 70. and 1000 IU (15 mcg) for those over 70. People who are housebound, do not have sufficient exposure to sunlight, or are dark-skinned individuals, as well as breast-fed infants, should take need vitamin D supplements. The maximum tolerated dose after the age of 12 months is 2,000 IU/day
How the body gets the vitamin	There are two forms of vitamin D. Vitamin D3 is made in the body from a chemical reaction to the ultraviolet radiation in sunlight. Vitamin D2 is found in a few food sources, including vitamin D fortified milk, fatty fish, egg yolk, and liver.
Effects of deficiencies	Softening of the bones caused by low levels of calcium and phosphorous (called rickets in children and osteomalacia in adults). Also increases the risk for bone-related knee problems, and hip fractures in postmenopausal women. Associated with a higher risk for prostate cancer and breast cancer risk. Evidence suggests that vitamin D deficiency may be responsible for poor muscle strength after bone fracture. The deficiency is associated with high blood pressure and diabetes, but it is unknown whether supplementation with vitamin D impacts these diseases. Studies now suggest vitamin D plays a role in age-related macular degeneration (AMD), and that drinking milk with added vitamin D can help protect against AMD.
People at risk for deficiencies	Older people, particularly if they live in the North, who are underexposed to sunlight. Obesity may also increase risk. There is some concern, in fact, that vitamin D deficiency may be a growing problem in the US among younger adults as sunscreen use becomes widespread. Individuals at highest risk for vitamin D deficiency are those who assiduously avoid the midday sun, wear protective clothing, regularly use sunscreen, and have dark skin. Exposure to sunlight for about 15 - 20 minutes at mid-morning or mid-afternoon three times a week is recommended for most people who live in temperate climates.
Toxicities	Vitamin D is very toxic in high doses. In infants, daily amounts higher than 1,000 IU can cause mental and growth retardation, kidney failure, and death. In children and adults, daily amounts over 50,000 IU can cause weakness, anorexia, vomiting, diarrhea, and mental changes. Prolonged use of megadoses can cause calcification of soft tissue and life-threatening kidney failure. Low-calcium diets and withdrawal from the vitamin can usually reverse the side effects except for kidney failure.


	Vitamin E (Tocopherol or Tocotrienol)	Vitamin K
Benefits	A fat-soluble antioxidant vitamin that helps prevent cell membrane damage and may inhibit oxidation of LDL cholesterol (a process that increases its harmful effects on arteries). Researchers once thought that vitamin E might protect against cardiovascular disease. This theory has been debunked. However, a 2007 study found that vitamin E supplementation reduced the risk of deep vein thrombosis (DVT) in women at risk for, or with a history of, DVT. Vitamin E supplements have also been shown to produce a statistically significant decrease in menopausal hot flashes. There is also early evidence that vitamin E may protect against ovarian cancer.	The most important function of vitamin K is its role in blood clotting and prevention of bleeding. As a result, the vitamin may be able to help treat hepatoma, leukemia, and hepatocellular carcinoma, a form of liver cancer. The vitamin also contributes to maintaining healthy bones and healing fractures. Vitamin K is widely used in Japan to treat osteoporosis, and studies suggest it may be effective in treating rheumatoid arthritis.
Recommended daily allowance (RDA) or dietary reference intake (DRI) (mcg = micrograms, mg = milligrams, IU = international units)	RDA is 15 mg (22 IU) for all adults, including pregnancy women. Nursing mothers need 19 mg (28 IU). (Supplements should be taken along with some oil or fat to be absorbed.) Vitamin E is composed of 8 compounds (four tocopherols and four tocotrienols). Vitamin E is most often available as supplements of dl alpha tocopherol (a synthetic form). Other vitamin E compounds may prove to be more active than the standard synthetic supplement. They include natural vitamin E, called d-alpha- or RRR-alpha-tocopherol succinate (VES). Other vitamin E compounds of interest are tocotrienol and beta and gamma tocopherol. Supplements that contain a combination of some of these forms may be most beneficial.	RDA is 60 - 65 micrograms (women) and 70 - 80 micrograms (men).
Foods containing the vitamin	Vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Tocotrienol (a possibly beneficial form) is found in natural tropical oils. Palm oil sold in the US is refined and does not contain tocotrienol.	Best dietary sources are canola oil, cruciferous vegetables, and soybean oil. Good sources are beef liver, bran, and olive oil. Also produced by bacteria in the intestines.
Effects of deficiencies	Deficiencies have not been established.	Easy bruising, bleeding. May increase the risk of hip fractures in women.
People at risk for deficiencies	Low-birth weight infants. People who eat a low-fat diet. People with medical problems that impair fat absorption, such as Crohn's disease, cystic fibrosis, steatorrhea, liver diseases (such as cirrhosis). People with abetalipoproteinemia, a rare genetic disorder that impairs fat metabolism.	Deficiency may occur in patients who have problems absorbing fats, such as those with cirrhosis, people who are on long-term antibiotic therapy, or who are taking other medications, including cholestyramine, Dilantin, and phenobarbital. Some evidence suggests that more young people may be deficient than previously believed.
Toxicities	Upper level recommended is 1,500 IU of alpha tocopherol. Large doses may cause bleeding problems, particularly in people taking anti-clotting medications. Some research now indicates that vitamin E, like other antioxidants, may have pro-oxidant and damaging effects. Although vitamin E is one of the best studied vitamins, research has yielded conflicting results, and definitive conclusions about the benefits and toxicity of vitamin E have not yet been determined. In a major 2005 study, there was no significant difference in cancer rates between people who took 400 IU of vitamin E daily and those who did not, although those who took the supplement had a higher risk of heart failure. Additional studies also link high levels of vitamin E with a slightly increased risk of heart failure and death. On the other hand, studies show that vitamin E may reduce heart problems in high-risk patients such as certain people with diabetes.	Allergic-type responses, including rash and itching, to high doses have been reported. Those who are taking Coumadin, an anticoagulant, should not take vitamin K without consulting a physician. Vitamin K deficiency can cause anorexia, lethargy, growth retardation, bone loss, soft tissue calcification, and death.

Carotenoids

Carotenoids are a group of more than 700 fat soluble nutrients that produce the colors in foods such as carrots, pumpkins, sweet potatoes, tomatoes, and other deep green, yellow, orange, and red fruits and vegetables. Many are proving to be very important for health. Beta carotene is the most widely studied carotenoid, but others are proving to be of great interest. As with some, but not all, carotenoids, beta carotene is known as a provitamin A because it converts to the vitamin in the body.

They are categorized as either xanthophylls or carotenes according to their chemical composition.

Carotenes are hydrocarbons and most are found in yellow, orange, and red vegetables. They include beta and alpha carotene and lycopene.

Beta Carotene and other Provitamin A Carotenoids. Beta carotene, alpha-carotene, and beta-cryptoxanthin are carotenes that are converted into vitamin A or retinol (the active form of vitamin A) in the body. They are found in many yellow fruits and vegetables. Beta carotene is the most widely studied carotenoid. Evidence now strongly suggests that when taken as a separate supplement it can have harmful effects.
Lycopene. Lycopene is responsible for the red color in fruits and vegetables, including tomatoes, red grapes, watermelon, and pink grapefruit. It is also found in papayas and apricots. It does not convert to vitamin A but may have important cancer fighting properties and other health benefits.
The beneficial actions of most carotenes such as those tomatoes, corn, and carrots, appear to be enhanced by cooking them, especially in oil (preferably olive, canola, or another monounsaturated oil). (Note: Cooking can also destroy certain nutrients, such as vitamin C, in these vegetables.)

Xanthophylls contain oxygen and most are found in green vegetables, such as broccoli, cabbage, and kale. They are also in yellow fruits and vegetables. Xanthophylls include lutein and zeaxanthin, which are both stored in the retina of the eye. Neither converts to vitamin A. Both are powerful antioxidants and may be very important for healthy eyes. Unlike carotenes, cooking may reduce the antioxidant activity of some xanthophylls in foods, although probably not to any significant degree.

Phytochemicals

The word phytochemicals means plant chemicals. Hundreds of phytochemicals are being studied. Many are believed to have a major positive impact on human health. Some contribute to the bright and vivid colors found in fruits and vegetables. The results of studies on specific phytochemicals are not necessarily applicable to the vegetables or fruits that harbor small concentrations of these chemicals.

Nevertheless, it is obvious that vegetables and fruits are healthful, which is probably due to some balance of phytochemicals, carotenoids, vitamins, fibers, and minerals rather than any single substance.

The benefits of individual phytochemical supplements are largely unproven. Furthermore, they are not regulated and high concentrations of some may behave like drugs and can be toxic and possibly even contribute to cancer cell growth.

Polyphenols are important phytochemicals, and flavonoids (or catechins) are members of the polyphenol family that may have significant health benefits. Laboratory studies have shown that specific flavonoids suppress tumor growth, interfere with sexual hormones, prevent blood clots, and have anti-inflammatory properties. In general, flavonoids are found in celery, cranberries, onions, kale, dark chocolate, broccoli, apples, cherries, berries, tea, red wine or purple grape juice, parsley, soybeans, tomatoes, eggplant, and thyme. Most common berries contain flavonoids and are particularly rich in potent antioxidants.

Among the important flavonoids are resveratrol, quercetin, and catechin. Evidence suggests that resveratrol (found in red wine, grapes, olive oil) may be extremely potent. In laboratory studies, it increases cell survival and has been shown to increase the life span of worms and fruit flies. Catechins are the primary flavonoids in tea and may be responsible for its possible beneficial effects. Flavonoids in dark chocolate may also be health protective.

Isoflavones, commonly known as phytoestrogens, have actions that are similar to the female hormone estrogen. A high consumption of soy, which is primarily composed of isoflavones, may reduce symptoms resulting from estrogen depletion during menopause. In a recent study, supplementation with isoflavones decreased hot flashes by 57% and night sweats by 43%, but other research is less favorable.

Lignan is another phytoestrogen and is found in the fiber layers of whole-grains, berries, some seeds, some vegetables, and a few fruits.

Isothiocyanates and related substances, indoles, are also known as mustard oils and are responsible for the sharp taste in cruciferous (also called brassica) vegetables. Such vegetables include broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy. Isothiocyanates also stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. (Cruciferous vegetables are also high in fiber, vitamin C, and selenium.)

Monoterpenes have two important phytochemicals, perillyl alcohol and limonene. They block proteins that stimulate cell growth and reproduction and are being tested for actions against cancer. Limonene is found in the peels of citrus fruits.

Organosulfurs are part of the allium family of phytochemicals. Compounds, such as allicin, may have benefits on the immune system, assist the liver in rendering carcinogens harmless, and reduce production of cholesterol in the liver. These compounds are found in garlic, leeks, onions, chives, scallions, and shallots.

Capsaicin seems to reduce levels of substance P, a compound that contributes to inflammation and the delivery of pain impulses from the central nervous system. Research suggests that it may inhibit cancer-generating substances. It is found in hot red peppers.

Sterols, which include sitosterol, stigmasterol, campesterol, and squalene, are found in vegetable oils. Sitosterol is the most studied and appears to have cholesterol-lowering effects.

Beta-sitosterols may help improve urine flow and urinary symptoms in men with enlarged prostate glands (benign prostatic hyperplasia, or BPH). A recent review study of five randomized trials (519 men) found that urinary flow and other urinary symptoms improved in men who took the herbal remedy from 4 - 26 weeks. The study’s authors cautioned that while beta-sitosterols show effectiveness in the short term, their long-term effectiveness, ability to prevent complications from BPH, and safety are not known. More research is necessary. Beta-sitosterols come from South African star grass, Hypoxis rooperi, or species of Pinus and Picea.

Healthy Foods

Evidence increasingly suggests that a varied diet, not individual food chemicals, is essential for basic health and a longer life. Such diets are rich in fresh fruits and vegetables and whole grains, and low in saturated fats.


Foods	Phytochemicals and Carotenoids	Vitamins and other valuable food components	Benefits
Apples	Flavonoids		May have activity against certain cancers (lung). Also may help maintain healthy cholesterol. May protect against asthma.
Beans	Flavonoids	Folate, iron, potassium, and zinc	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored	Ellegic Acid	Vitamin C, minerals	The anthocyanins in berries such as bilberries, blueberries, cranberries, elderberries, and others, have numerous healthful properties including anti-cancer and antioxidant effects. Bilberry (Vaccinium myrtillis) is widely used to prevent macular degeneration. Blueberries may protect the aging brain. (In one study blueberries were most effective.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, isothiocyanates, lutein, beta and alpha carotene. Note: Young sprouts of broccoli and cauliflower contain much higher levels of isothiocyanates than their mature forms.	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protective against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, beta carotene and other provitamin A carotenoids	Vitamin A (converted from carotenoids), vitamin C	Protects eyes, lungs. (Cooking carrots may increase the potency of food nutrients.)
Chocolate, dark. Note: Milk chocolate does not have benefits.	Flavonoids		Heart protective (may improve lipids and help prevent blood clotting. May have protective properties against lung cancer (not other cancers).
Eggs	Lutein	Many B vitamins, vitamin A, vitamin D	Although egg yolks are high in cholesterol, very little of it has a negative effect on people with normal levels. And the health benefits of eggs are now known to be very high. (People with diabetes or those with high cholesterol should restrict eggs, however.)
Fish, oily (mackerel, salmon, sardines)		Vitamin B3, B12. Essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Possibly protective against certain cancers, heart diseases, and infection. Heating garlic can reduce benefits. Allowing crushed fresh garlic to stand 10 minutes before heating, however, may preserve beneficial chemicals while cooking.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, Selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes, including purple grape juice, and red wine	Flavonoids, (resveratrol, quercetin and catechin)		Fight heart disease and cancer. May help lower the risk for asthma.
Nuts		Vitamin E, vitamin B1, essential fatty acids, folate	Protects the heart and may help prevent stroke.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung).
Oranges	Monoterpenes	Vitamin C, folate, potassium.	Many health benefits. Increases HDL levels.
Potatoes (Sweet)		Vitamin C, vitamin E, vitamin A	Many health benefits.
Soy. The best products are tofu, soy milk, or whole soy protein.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins.		May have effects similar to estrogen, including maintaining bone and benefiting the heart in women. May also be protective against prostate cancer and possibly other cancers. More studies are needed. Effects on breast cancer are uncertain. (Note: Soy may have different effects in men than in women. Of some concern is one study reporting more mental decline in men who consume greater amounts of tofu.)
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects lungs and brain.
Tea (Both black and green tea are beneficial. Best results associated with green tea.)	Flavonoids (primarily catechins)		Cancer fighting properties, particularly in green tea, which may be especially beneficial for smokers. Both black and green tea may protect against heart disease and stroke, although studies are mixed. Tea drinking also may help with weight control and help prevent osteoporosis.
Tomatoes	Lycopene, Flavonoids	Vitamin C, biotin, minerals	Studies link to reductions in prostate and other cancers. Infection fighters.
Note on Organic versus Inorganic Products. There is some evidence that organic produce has higher levels of antioxidants and that some agricultural chemicals may destroy flavonoids. Nevertheless, organic produce is expensive, and fruits and vegetables, no matter how they are grown, are still filled with healthful nutrients.

Dietary Health Benefits

The benefits of any dietary factors are very difficult to prove, and, to date, there is little evidence that most dietary supplements protect against major diseases in otherwise healthy people with normal eating habits. An exception is lutein, which is known to reduce the risk of macular degeneration. However, a diet naturally high in vitamins and minerals can be the best defense against many diseases. Fresh fruits and vegetables and whole grains are the primary sources of vitamins, carotenoids, and vitamins, as well as of fiber and important minerals.

Description of Oxygen-Free Radicals (Oxidants). Currently, the most important benefit claimed for vitamins A, C, E, and many of the carotenoids and phytochemicals is their role as antioxidants, which are scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful in the following way:

They can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including cancer, heart disease, cataracts, and even the aging process itself.
Oxygen-free radicals can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of atherosclerosis.

Description of Antioxidants and Warnings on High-Dose Supplements. Antioxidant vitamins (A, C, and E), carotenoids, and many phytochemicals can neutralize free radicals. Unfortunately, although it is clear that vitamins are required to prevent deficiency diseases, high doses of vitamin C, vitamin E, and beta carotene supplements may also have pro-oxidant effects, which can be harmful in patients with cancer. In these people, high doses of antioxidant vitamins may actually protect cancer cells just as they do healthy cells.

The strongest evidence on negative effects to date comes from studies reporting an increase in lung cancer and overall mortality rates among smokers who took beta carotene supplements. In determining reasons for this disturbing effect, one animal study suggested that beta carotene increased enzymes in the lungs that actually promote cancerous changes. One study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E.

Some evidence also indicates that high doses of vitamin C may speed up atherosclerosis, or hardening of the arteries. In one study, women with heart disease who took antioxidant vitamins had a higher risk for heart attack or death than those who didn't take one.

Another study also reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. Some researchers speculate that certain immune factors generate oxidants to fight bacteria. This antioxidant vitamin, then, may block that action. Research published in 2005 suggests that those who take large amounts of vitamin E (1,500 IU/day) may slightly increase their risk for heart failure and death, but this evidence is not considered conclusive. Further study is necessary.

Vitamins and Heart Protection.

Antioxidant Vitamins A, C, and E. Deficiencies in vitamins A, C, E, and beta carotene have been linked to heart disease. All of these nutrients have antioxidant effects and other properties that should benefit the heart. A study in patients with heart failure has shown that vitamin C can work with dobutamine, a powerful intravenous medication, to strengthen the heart’s ability to contract following a heart attack. In fact, a 2005 study has found that taking high doses of vitamin E is associated with an increased risk of heart failure. In 2007, the Women’s Antioxidant Cardiovascular Study failed to find that vitamins C, E, and beta carotene could reduce the risk of heart attack, stroke, need for revascularization, or cardiovascular death in women. According to the U.S. Preventive Service Task Force, evidence is insufficient to confirm or refute the benefits of supplements of any of these vitamins in protecting against heart disease.
Folate and B12 Vitamins. Deficiencies in the B vitamins folate (known also as folic acid) and B12 have been associated with elevated blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. One study, reported lower failure rates after heart surgery in patients who took folic acid and vitamins B12 and B6. And a major 2002 study suggested that lowering homocysteine levels with folic acid would reduce the risk for heart disease by 16% and stroke by 24%. However, a 2007 trial in adults with stable coronary artery disease found that lowering homocysteine levels 33% with B vitamins and folic acid had no effect on arterial inflammation, meaning that lower levels were unlikely to offer protection against heart attack or stroke. More evidence is needed to determine whether homocysteine plays a causal role in cardiovascular disease and whether the B vitamins are protective. Folate improves blood flow through the arteries, which may be important for the heart, regardless of its effect on homocysteine. Although people with high levels of homocysteine are prone to damaging blood clots in their arteries and veins, a 2007 study found that lowering homocysteine with folic acid and other B vitamins does not reduce the incidence of blood clots in the peripheral veins (deep venous thrombosis).
Niacin. Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A physician should prescribe niacin in order to ensure its safety and effectiveness. [See In-Depth Report #23, Cholesterol.]

Carotenoids and Heart Protection. Studies have reported that a diet high in fruits and vegetables containing beta carotene, lycopene, and other carotenoids may reduce the risk of heart attack. A small Finish study found that a diet high in tomatoes reduced total cholesterol and LDL ("bad") cholesterol. Diets low in lycopene (particularly from tomatoes) were associated with a significantly higher risk of heart disease and stroke.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Phytochemicals and Heart Protection. Several phytochemicals are associated with heart protection.

Flavonoids. Certain flavonoids, found in both black and green tea, dark chocolate, onions, red wine or red grape juice, and apples, appear to be strongly heart protective. In one study, people who consumed the most flavonoids in foods had a 20% lower risk for heart disease than those with low consumption. Flavonoids may protect against damage done by cholesterol and help prevent blood clots. A number of studies have now reported heart protection from the flavonoid catechin, which is found in both black and green tea. The flavonoid resveratrol, which is found in grape skin, appears to be responsible for the well-known heart protective effects in red wine and purple grape juice.
Organosulfurs. Organosulfurs found in onions and garlic have been under investigation for possible beneficial effects on cholesterol levels. One study reported an association between taking garlic capsules and significantly lower cholesterol-build up in the arteries of older women but not in older men. In the study, daily garlic supplements dramatically reduced the build-up of newly formed plaque in the arteries, while having much less effect on older, harder plaque deposits. Garlic supplements for cardiovascular disease may be most beneficial when used during earlier years among men and later years among women.
Isoflavones. Soy protein is the most studied source of isoflavones (known as phytoestrogens, or plant estrogens). Not all studies are consistent, but the majority has shown an improvement in at least one of the cholesterol components in people who consumed at least 25 grams of soy protein. A 2007 meta-analysis of all soy protein studies performed from 1990 - 2006 found that soy protein significantly decreased total cholesterol and LDL cholesterol, but had no effect on HDL or triglycerides. The effect was particularly evident in people with hypercholesterolemia. A 2007 study found that 12 weeks of soy supplement lowered total cholesterol and LDL levels in both Caucasian and African-American postmenopausal women. Soy may also reduce other heart risk factors, at least in certain populations. For example, in one 2002 study, soy was beneficial for controlling blood sugar and lowering LDL in postmenopausal women with type 2 diabetes. In a 2007 study of overweight men and postmenopausal women, soy protein reduced blood pressure and arterial stiffness. In another study, soy protein was associated with lower systolic blood pressure in men. The best sources are soy products (tofu, soy milk) or whole soy protein. Powdered soy protein that contains at least 60 mg of isoflavones may provide similar benefits.
Sterols. The plant sterols, including sitosterol, are also proving to be potent cholesterol fighters by blocking the absorption of cholesterol in the intestine. Sitostanol, a derivative of sitosterol, is being used in new margarine products to lower cholesterol levels. Sterols and stanols are now found in breads, cereals, yogurt, and fruit juices.

A healthy diet rich in fruits and vegetables and low in salt and saturated fats may significantly lower the risk for a first stroke, perhaps by helping to protect against high blood pressure -- a major risk factor for stroke.

Vitamins and Stroke Protection. The effects of antioxidant vitamins and carotenoids on stroke, dementia, or both are being studied. Studies are conflicting, however. A 2007 study of 8,171 women with cardiovascular disease reported that vitamins C, E, and beta carotene offered no protection against heart attack and stroke.

The B vitamin folate (usually in the form of folic acid) may protect against stroke. However, exactly which people benefit from this therapy has yet to be determined. Studies have suggested that people who have higher blood levels of folate have a lower than average risk for stroke. Its primary benefit in this case appears to be to reduce levels of homocysteine, an amino acid that has been strongly linked to an increased risk of coronary artery disease, stroke, and Alzheimer's disease. A 2007 meta-analysis of 8 trials found that folate supplements decreased homocysteine 20% and lowered stroke risk 18%. Interestingly, lowering homocysteine with folic acid and B vitamins had no effect on heart attack, strokes, amputations, need for dialysis, or death in patients with chronic or end-stage kidney disease.

Carotenoids and Stroke Protection. Some, but not all, studies have reported a lower risk of stroke from carotenoids, including beta carotene and lycopene.

Many fresh fruits and vegetables contain chemicals that may fight many cancers, including lung, breast, colon, and prostate cancers. Examples of important cancer fighting foods include the following:

Cruciferous vegetables (such as cabbage, Brussels sprouts, and broccoli)
Tomatoes (which contain lycopene)
Carrots (which contain alpha carotene)

Some evidence suggests that antioxidants may enhance the anticancer effects of chemotherapy. In multiple studies, patients who maintained their antioxidant levels were better able to withstand the high stress caused by chemotherapy or radiation therapy compared to those with low antioxidant levels. Antioxidant nutrients that may help reduce the side effects of chemotherapy include vitamins E and C, beta carotene, genistein and daidzein (isoflavones found in soy), and quercetin (found in red wine an purple grape juice).

Any protective effects of vitamins or specific phytochemical against cancer, however, appear to depend on the cooperative effort among them. Individual supplements of any vitamin or food chemical have not as yet shown any benefits.

Additionally, certain supplements may actually encourage tumor growth, particularly when taken in large amounts. Two 2007 studies found a connection between folate supplements and colorectal cancer. In one study, which was designed to evaluate the benefits of folic acid in patients who had previous colorectal adenomas (precancerous polyps), the researchers instead found that folic acid was associated with a higher risk of having 3 or more adenomas and noncolorectal cancers. In another study, it was noted that the downward trend in colorectal cancer diagnoses abruptly started to rise in 1996 when mandatory folate enrichment of grains within the U.S. and Canada began. Rates continue to exceed pre-1996 levels. Additionally, a large 2007 National Cancer Institute/AARP study found an increased risk of advanced and fatal prostate cancer in men who took more than 7 multivitamins a week, but no association between multivitamin use and localized prostate cancer.

High consumption of cruciferous vegetables (at least once per week) was associated with lower risk of kidney cancer, and low consumption (less than once per month) of cruciferous vegetables was associated with higher risk of kidney cancer in a multinational 2007 European study. Cruciferous vegetables also appear to offer protection against head and neck cancer resulting from chemical toxins found in cigarettes and alcohol, for example.

Vitamins and Cancer Protection. Because many cancers are thought to be initiated by the effects of oxygen-free radicals on DNA, the antioxidants A, C, and E and beta carotene have been intensively studied. A major study found that men who took selenium for 6 or 7 years reduced their risk of prostate cancer by 52%. Nevertheless, most individual supplements have not been proven to protect against cancer, and high doses may be dangerous.

A 2007 review of the diets of men exposed to asbestos found a decreased risk of prostate cancer associated with increasing intakes of vitamin C-rich vegetables, but not fruits and vegetables high in vitamin A. The chemopreventive role of silymarin (Silybum marianum), found in milk thistle extract, has been extensively studied and has shown anticancer efficacy against various cancers, especially prostate and skin, by inhibiting UVB radiation.

A review of 13 cancer registries found 416,134 cases of skin cancer and 3,776,501 cases of non-skin cancer as a first cancer. Rates from cancer registries in sunny countries (such as Australia and Spain) and less sunny countries (such as Canada and Iceland) were compared. The researchers concluded that vitamin D production in the skin decreases the risk of several solid cancers, especially stomach, colorectal, liver and gallbladder, pancreas, lung, female breast, prostate, bladder, and kidney cancers. The apparently protective effect of sun exposure against second primary cancer is more pronounced after non-melanoma skin cancers than melanoma.

Consumption of aflatoxins, a common fungus-related toxin infecting cereal grains, oil seeds, spices, tree nuts, and the milk of animals fed contaminated feed, is known to cause hepatocellular carcinoma, a deadly form of liver cancer. Rodent studies have shown that phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids may act as chemopreventive agents, dispersing aflatoxins and protecting against hepatocellular carcinoma. Human trials are planned. A similar study found that several isothiocyanates, diallyl sulfide, and polyphenolic compounds can prevent esophageal dysplasia from progressing to squamous cell carcinoma.

A review of all articles on vitamins and cancer published through February 2007 found that multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. With few exceptions, neither beta-carotene nor vitamin E had benefits for preventing cancer. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos.

A 2007 study of nearly 82,000 men and women in Sweden found that high intake of methionine was associated with reduced risk of pancreatic cancer. The same relationship was not seen with vitamin B6 or folate.

Vitamin A, C, and E. Although some studies have reported an association between low blood levels of these antioxidant vitamins and a higher risk for cancer, supplements of vitamins A, C, and E appear to have few advantages in most cases. And there are some studies finding higher cancer risks with high intakes of antioxidants. For example, a 2003 study reported a higher risk in melanoma in people with vitamin-C rich diets. Another study also reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. (Vitamin E may be protective against bladder cancer and ovarian cancer.)
Vitamin D. Some studies have suggested that certain vitamin D compounds may inhibit certain cancer cells, specifically prostate cancer, from proliferating. More research is needed. In 2007, the National Cancer Institute confirmed that ultraviolet (UV) radiation exposure may reduce the risk of developing non-Hodgkin lymphoma (NHL), but only in patients with certain variations in the D vitamin receptor gene. A second 2007 study found that variations in this gene increase the risk of diffuse large B-cell lymphoma. A 2007 prospective analysis of 31,500 women in the Women’s Health Study evaluated calcium and vitamin D intake. The researchers found a moderately lower risk of premenopausal, but not postmenopausal, breast cancer with higher intakes of total calcium and vitamin D. A 2007 review of breast cancer cases reported in Ontario, Canada, found reduced breast cancer risks were associated with increasing sun exposure in women ages 10 - 19, less evidence for associations in women ages 20 - 29, and no evidence for ages 45 - 54. Researchers concluded that sun exposure earlier in life, particularly during breast development, may be key in the connection between vitamin D exposure and breast cancer risk.
Folic acid and B12. These B vitamins convert the amino acid homocysteine to methionine, a substance that helps prevent cells from becoming malignant. Folic acid may provide some protection against cervical and colon cancer. One small study showed a reduction of lung cancer cells in smokers taking folic acid and vitamin B12, but the study was very small, of short duration, and other factors might have biased the results. Still another study reported that folic acid may reduce the risk for breast cancer among women who regularly drink alcohol. (In the study, folic acid had no other effect on breast cancer.)

In 2006, a study for the National Institutes of Health reviewed randomized trials evaluating the effectiveness and safety of multivitamin and mineral supplements in preventing cancer and chronic disease. The studies had mixed results, and some supplements reduced cancer rates in certain populations. However, the reviewers concluded that current evidence is not sufficient to determine whether multivitamin and mineral supplements may prevent cancer and chronic disease.

Carotenoids and Cancer Protection. A number of studies have reported that fruits and vegetables rich in carotenoids are associated with protection against many cancers. Lycopene, found in tomatoes, may have particular value in protection against prostate, colon, lung, and bladder cancer. A 2005 study found that in one out of four men with genetic variations that cause them to be more sensitive to oxidative stress, supplementation with selenium, vitamin E, and lycopene significantly reduces the risk of prostate cancer. Individual supplements, however, do not offer any advantage. In fact, evidence now strongly suggests that beta carotene supplements increase the risk for lung cancer in smokers and people exposed to asbestos

Phytochemicals and Cancer Protection. The following phytochemicals appear to have cancer-protecting properties.

Isothiocyanates. Isothiocyanates and sulforaphane, found in cruciferous vegetables, may block the effects of carcinogens and suppress tumor growth. In one study, for example, women with the highest consumption of cruciferous vegetables had a 24% lower risk of breast cancer than women with the lowest consumption.
Isoflavones. Isoflavones, found in soy beans and flax seed, behave like estrogen in some ways and not in others. Researchers are very interested, then, in their effects on hormone-related cancers, including breast and prostate cancers. Much research has focused on soy. In general, a number of Asian studies have reported an association between a higher intake of soy and a lower incidence of reproductive and breast cancers. The effects of phytoestrogens, however, in all women are far from settled. Some evidence suggests the genistein in soy may have properties that are protective against lung cancer. Nonfermented soy products (tofu, soy milk) also may protect against stomach cancer, while fermented soy products (miso, soy paste) appears to increase the risk.
Organosulfurs. The organosulfur compounds found in the onion and garlic family may have very potent properties in suppressing or blocking carcinogenic substances. A 2007 study found that synthetic organosulfur compounds act as selective inhibitors of growth in breast cancer cells. Studies indicate that people who regularly consume fresh or cooked garlic have about half the risk of developing stomach cancer and two thirds the risk of colorectal cancer as people who eat little or no garlic. One possible explanation for garlic's anti-cancer effect in the stomach is its antibacterial action against H. pylori, which can promote stomach cancer. Taking garlic supplements, however, did not offer these benefits.

It should be noted that studies on the health benefits of vitamins and minerals have some important limitations. Some are held to rigorous standards, while others are not. In most cases, the results of existing research are complex, as they can easily be complicated by factors such as diet, exercise, the presence of healthy or unhealthy lifestyle behaviors, environmental factors, and more.


Disease or Condition	Vitamins	Carotenoids, Phytochemicals, and Healthy Foods
Alzheimer's Disease	Vitamin E. Some reports, including a large 2002 population study, have suggested that vitamin E intake, from food or supplements, may protect against mental decline. (One study suggested that the vitamin protected only those who carried the apoE4 gene. No strong evidence to date has found any protection from antioxidant supplements.) Some studies performed since 2002 challenge this finding, while others agree with it. B Vitamins. Some studies suggest that deficiencies of the B vitamins B6, B12, and folate may be a risk factor for Alzheimer' diseases, possibly because deficiencies elevate homocysteine levels, which some research now associated with a higher risk for Alzheimer's disease. Of these, folates may offer the best protection. In 2007, researchers at Tufts-New England Medical Center reviewed all human studies on folate, vitamin B-6, vitamin B-12, and cognitive function in the elderly conducted between 1966 and November 2006. Six of 10 folate studies reported a significant association between low baseline blood folate concentrations and poor cognitive test performance; 4 of 9 folate studies found associations between low blood folate concentrations and increased prevalence of Alzheimer's disease. No association between vitamin B-6 and vitamin B-12 blood concentrations and cognitive-test performance or Alzheimer's disease was seen, and B-vitamin dietary intake was not associated with cognitive function. Although the majority of studies indicated that low blood folate concentrations predicted poorer cognitive function, data are not solid, due to variations in the way the studies were conducted and lack of agreement on what constitutes a low B-vitamin status.	According to several studies, eating plenty of darkly colored fruits and vegetables may slow brain aging. The estrogen-like properties in isoflavones are of interest in the study of Alzheimer's disease. Animal studies suggest that soy might be protective against AD, particularly in postmenopausal women. Of some concern, however, were one population and a few animal studies suggesting that soy intake may pose a risk for greater mental decline among older men. More research is needed to confirm the effects of soy on the aging brain and to determine if there are gender differences.
Infectious Disease	Studies are mixed whether vitamin supplements protect against upper respiratory infections. Large doses of vitamin C, for example, may help reduce the duration of a cold, but they do not appear to protect against one in the first place, even after exposure to a cold virus. Two studies in 2002 on multivitamins reported opposite results, with one finding fewer infections and one finding no difference. It is possible that vitamin C or multivitamin supplements may be helpful in specific people, such those who are vitamin deficient or have medical problems that impair their immune systems. A review of all studies on vitamin C and pneumonia prevention found only 1 placebo-controlled, randomized trial conducted in an English boarding school during World War II. The trial found a statistically significant (80% or greater) reduction in pneumonia incidence among boys consuming vitamin C. Two less-well-constructed trials arrived at the same conclusion. Therapeutic trials were even scarcer. Only one randomized, double-blind, placebo-controlled study of vitamin C for treatment of pneumonia was found. In this trial, elderly patients given vitamin C had lower mortality and respiratory symptom scores. However, the benefits were restricted to the sickest patients. One other trial of adults in the former Soviet Union found a dose-dependent reduction in the time to recover with two vitamin C doses. One 2007 study on vitamin D found that a single dose by mouth of this vitamin might prevent healthy individuals from activating the bacterium that causes tuberculosis in patients who harbor the infection. Studies on vitamin E specifically have been mixed. A 2002 study, in fact, reported a higher incidence and greater severity of respiratory infections in older adults who took 200 mg of vitamin E daily. However, a 2004 clinical trial conducted among elderly nursing home residents found that daily supplementation with 200 IU of vitamin E did provide protection from upper respiratory infections, especially the common cold. At present, there is not enough evidence to recommend vitamin E for infection prevention. Diarrhea is a worldwide problem, particularly in developing countries and those with poor sanitation. Taking supplements with B-complex vitamins, vitamin C, vitamin E, and selenium may reduce the risk of diarrhea, depending upon the organism that causes the disease. Meanwhile, iron supplements appear to increase the risk of infection from organisms that cause diarrhea. Vitamin A has not been shown to prevent diarrhea. Urinary tract infections (UTIs) may affect as many as 25% of pregnant women. A 2007 study found that women who took vitamin C (100 mg) for 3 months had significantly fewer UTIs than women who did not take vitamin C supplements. Rotavirus is a common cause of acute gastric pain in children under age 5. A 2007 study showed that the high amount of isoflavones found in soy-based infant formula can help prevent rotavirus infection.	Lycopene, found in tomatoes, appears to have properties that protect infection-fighting white blood cells. Saponins extracted from ginseng and allicin (found in garlic) have properties that boost the immune system. Both ginseng and garlic have long been traditionally used for their health benefits.
Asthma	Vitamin C from diet has been associated with lower risk for asthma. In one study, some people with exercise-induced asthma benefited from taking vitamin C one hour before strenuous physical activity. In a 2007 study, taking 1,500 mg supplements of vitamin C for 2 weeks helped prevent exercise-induced airway narrowing in patients with asthma.	Flavonoids found in apples and red wine may help lower the risk for asthma. Some evidence indicates that a low dietary intake of antioxidant nutrients could increase the risk for lung damage. Such nutrients should be obtained from fresh, deep green and yellow-orange fruits and vegetables. A 2007 study found low blood lycopene levels in people with asthma. Increasing lycopene- and vitamin A-rich foods may help raise lycopene levels.
Eye Disorder	Cataracts and Macular Degeneration. Oxygen-free radicals play a role in cataract formation and age related macular degeneration, the most common cause of irreversible blindness in the elderly. Bilberry (Vaccinium myrtillis), which contains powerful anthocyanins, is widely used to prevent macular degeneration. Low levels of vitamin C in the lens of the eye have been particularly strong predictors of cataracts. People with cataracts are frequently deficient in vitamin A, the carotenes, lutein, and zeaxanthin. Studies on protection against cataracts using antioxidant supplements have been mixed, including two identically conducted studies that reported opposite results. Vitamin C currently has the strongest evidence for protection, but even with this antioxidant studies are not consistent. A combination of zinc and antioxidants, including vitamin C and E, may slow the progression of macular degeneration. (Vitamin E alone does not appear to be protective.) Glaucoma. Although no evidence exists that antioxidants will prevent glaucoma, some studies reported an association between vitamin E and improved visual fields in patients with glaucoma.	Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein, lycopene, and zeaxanthin, are especially eye-protective and may help prevent cataracts and macular degeneration. The National Eye Institute in 2007 suggested that people with intermediate- or advanced macular degeneration in one eye may want to take a vitamin formula shown to reduce the risk of macular degeneration in the other eye by 25%. The formula contains vitamin C, vitamin E, beta-carotene, and zinc. They also suggest that a diet high in lutein and zeaxanthin may help reduce the risk of advanced age-related macular degeneration. Several studies report that the consumption of antioxidant-rich foods is associated with a decreased risk for cataracts. Carotenoids, especially lutein lycopene, and zeaxanthin are especially eye-protective and may help prevent cataracts and macular degeneration.
Skin Disorders and Wrinkles	Topical vitamin A (retinol) has been shown to improve fine wrinkles due to aging, by increasing glycosaminoglycan, which retains water, and increasing collagen production. One small study found that taking a combination of vitamins oral C and E supplements may help reduce sunburn reactions, although the protection is much less than from sunscreens. Taking the vitamins singly did not have any effect. In fact, a 2002 study reported that oral vitamin C had no effect on sunburn reaction. Of concern, in the same study some natural antioxidants in the body were reduced in people who took the vitamin. Also of concern are studies reporting no benefits and possibly harm from topical vitamin C in the form of ascorbyl palmitate, which is soluble in fat. One study reported that older adults had fewer wrinkles if they ate whole grains, fresh fruits and vegetables, and the use of healthy oils (such as olive oil). Diet played a role in improving skin regardless of whether the people in the study smoked or lived in sunny countries.	The following foods and phytochemicals may be especially skin protective: Both green tea and ginger appear to have properties that may provide some protection against skin cancer. Green tea skin care products are now available. The substance silymarin, found in the milk thistle family (which includes artichokes), may inhibit UVB-promoted cancers in animals. In one interesting study, eating garlic protected animals very effectively against UVB damage by interfering with urocanic acid in the skin. Whether these results may apply to humans (and what quantities of garlic might be beneficial) is still unknown.
Osteoporosis	Vitamin D. Vitamin D is the essential companion to calcium in maintaining strong bones. Supplements may be needed for people who have poor exposure to sunlight. It should be noted that diet supplies most people's need and high amounts of vitamin D can be toxic. Of interest: Taking vitamin D supplements does not prevent bone loss in post-menopausal African American women, according to research published in 2005. Further study will be needed to determine whether vitamin D prevents bone loss in women from other ethnic groups. Vitamin K. Studies suggest that vitamin K has properties that protect bone and prevent fracture. Vitamin K2 (menatetrenone), a form of vitamin K, is proving to prevent fractures in people with osteoporosis. Vitamin K affects blood clotting, and supplements are not recommended without specific physician instruction. Vitamin B12. One study reported that in people with osteoporosis and pernicious anemia, taking vitamin B12 (which is used to treat the anemia) also increased bone density. Vitamin C and E. There has been some indication of a positive association between vitamin C and E intake and bone density, although evidence proving actual benefits is weak. Note on Vitamin A. High amounts of dietary vitamin A reduces bone density and may even increase the risk for fracture in both postmenopausal women and men. (A form of vitamin A, retinoic acid, has been found to stimulate bone break down.) Beta carotene does not appear to increase risk. Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones.	Studies suggest that diets rich in fresh fruits and vegetables (which include those high in potassium and magnesium) reduce elimination of calcium from the body and help preserve bones. Studies are suggesting that isoflavones-rich soy products may actually improve bone density in postmenopausal women. A 2007 study of postmenopausal women in Italy found that 24 months of treatment with genistein plus calcium and vitamin D increased bone density, while women who took calcium and D alone lost bone density. Flavonoids and other compounds in tea may protect the bones.
Menstrual Disorders	Vitamin B6. Limited clinical evidence suggests that vitamin B6 may be beneficial in reducing premenstrual symptoms, including depression. Typically, women take 100 mg per day, although one study suggested that a lower dose (50 mg) may have the same effect. Other preliminary research indicates that women who receive the equivalent of 1,200 mg of calcium and 400 IU of vitamin D per day (through food or supplements) have a significantly lower incidence of premenstrual symptoms than women who did not. Vitamin B1. One study reported relief from menstrual pain using vitamin B1 (thiamin). Vitamin E. Several randomized controlled trials have shown that vitamin E significantly improves both physical and emotional premenstrual symptoms. One study reported that high doses of vitamin E helped reduce menstrual cramps. The doses were much higher than those recommended and could possibly increase the risk for bleeding. Although anecdotal evidence reports that vitamin E helps reduce the frequency of hot flashes for menopausal women, there is no clinical evidence to support this claim.

Resources

http://fnic.nal.usda.gov -- The Food and Nutrition Information Center
http://dietary-supplements.info.nih.gov -- Office of Dietary Supplements, National Institutes of Health
www.ars.usda.gov/ba/bhnrc/ndl -- Nutrient Data Laboratory
www.fda.gov -- Food and Drug Administration
www.eatright.org -- The American Dietetic Association
www.acsh.org -- American Council on Science and Health
www.aicr.org -- American Institute for Cancer Research
www.nutritiondata.com -- Information on vitamins and nutrients in foods
www.consumerlab.com -- Independent testing of nutritional supplements' contents and quality
www.usp.org -- US Pharmacopeia
www.herbs.org -- Herb Research Foundation

References

Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol. 2007;125(9):1225-1232.

Ambrosini GL, de Klerk NH, Fritschi L, Mackerras D, Musk B. Fruit, vegetable, vitamin A intakes, and prostate cancer risk. Prostate Cancer Prostatic Dis. 2007 May 22; [Epub ahead of print]

Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Feb 21; [Epub ahead of print]

Bermudez Y, Ahmadi S, Lowell NE, Kruk PA. Vitamin E suppresses telomerase activity in ovarian cancer cells. Cancer Detect Prev. 2007;31(2):119-28. Epub 2007 Feb 28.

Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin d deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007 ;92(9):3517-22. Epub 2007 May 29.

Clements RH, Katasani VG, Palepu R, Leeth RR, Leath TD, Roy BP, Vickers SM. Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a university hospital setting. Am Surg. 2006;72(12):1196-202.

Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9(6):562-566.

Dietary Guidelines for Americans 2005. Dept of Health and Human Services, US Dept of Agriculture. Accessed 10/3/2007.

Fischer Walker CL, Black RE. Micronutrients and diarrheal disease. Clin Infect Dis. 2007;45 Suppl 1:S73-S77.

Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE. Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study. Circulation. 2007;116(13):1497-503.

Headstrom PD, Rulyak SJ, Lee SD. Prevalence of and risk factors for vitamin B(12) deficiency in patients with Crohn's disease. Inflamm Bowel Dis. 2007 Sep 20; [Epub ahead of print]

Inderjeeth CA, Glennon D, Petta A, Soderstrom J, Boyatzis I, Tapper J.Vitamin D and muscle strength in patients with previous fractures. N Z Med J. 2007;120(1262):U2730.

Ishihara J, Otani T, Inoue M, Iwasaki M, Sasazuki S, Tsugane S; Japan Public Health Center-based Prospective Study Group. Low intake of vitamin B-6 is associated with increased risk of colorectal cancer in Japanese men. J Nutr. 2007;137(7):1808-1814.

J.G. Ray, C. Kearon, Q. Yi, P. Sheridan, and E. Lonn, for the Heart Outcomes Prevention Evaluation 2 (HOPE-2) Investigators. Randomized Trial of Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism. Ann Intern Med. 2007;146(11):761-767.

Kitchin B, Morgan SL. Not just calcium and vitamin D: other nutritional considerations in osteoporosis. Curr Rheumatol Rep. 2007;9(1):85-92.

Kune G, Watson L. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene. Nutr Cancer. 2006;56(1):11-21.

Lim MR, Huang RC, Wu A, Girardi FP, Cammisa FP Jr. Evaluation of the elderly patient with an abnormal gait. J Am Acad Orthop Surg. 2007;15(2):107-117.

Martin H, Lindblad B, Norman M. Endothelial function in newborn infants is related to folate levels and birth weight. Pediatrics. 2007;119(6):1152-1158.

Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007;16(7):1325-1329.

Nardin RA, Amick AN, Raynor EM. Vitamin B(12) and methylmalonic acid levels in patients presenting with polyneuropathy. Muscle Nerve. 2007;36(4):532-535.

Ochoa-Brust GJ, Fernández AR, Villanueva-Ruiz GJ, Velasco R, Trujillo-Hernández B, Vásquez. Daily intake of 100 mg ascorbic acid as urinary tract infection prophylactic agent during pregnancy. Acta Obstet Gynecol Scand. 2007;86(7):783-787.

Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA. Association between vitamin D and age-related macular degeneration in the Third National Health and Nutrition Examination Survey, 1988 through 1994. Arch Ophthalmol. 2007;125(5):661-669.

Pham DQ, Plakogiannis R. Vitamin E supplementation in Alzheimer’s disease, Parkinson’s disease, tardive dyskinsia, and cataract: Part 2. Ann Pharmacother. 2005;39(12): 2065-2072.

Riccioni G, Bucciarelli T, Mancini B, Di Ilio C, Della Vecchia R, D'Orazio N. Plasma lycopene and antioxidant vitamins in asthma: the PLAVA study. J Asthma. 2007;44(6):429-432.

Ronnenberg AG, Venners SA, Xu X, Chen C, Wang L, Guang W, Huang A, Wang X. Preconception B-vitamin and homocysteine status, conception, and early pregnancy loss. Am J Epidemiol. 2007;166(3):304-12. Epub 2007 May 2.

Sahin M, Tutuncu NB, Ertugrul D, Tanaci N, Guvener ND. Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus. J Diabetes Complications. 2007;21(2):118-123.

Tamori A, Habu D, Shiomi S, Kubo S, Nishiguchi S. Potential role of vitamin K(2) as a chemopreventive agent against hepatocellular carcinoma. Hepatol Res. 2007;37 Suppl 2:S303-307.

Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JMAscorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma. Respir Med. 2007;101(:1770-1778.

Triantafyllou NI, Kararizou E, Angelopoulos E, Tsounis S, Boufidou F, Evangelopoulos ME, Nikolaou C, Vassilopoulos D. The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients. Eur Neurol. 2007;58(2):96-99.

Vagianos K, Bector S, McConnell J, Bernstein CN. Nutrition assessment of patients with inflammatory bowel disease. J Parenter Enteral Nutr. 2007;31(4):311-319.

Velasquez MT, Bhathena SJ. Role of dietary soy protein in obesity. Int J Med Sci. 2007; 4(2):72-82.

Wang Y, Hodge AM, Wluka AE, English DR, Giles GG, O'sullivan R, Forbes A, Cicuttini FM. Effect of antioxidants on knee cartilage and bone in healthy, middle-aged subjects: a cross-sectional study. Arthritis Res Ther. 2007;9(4):R66 [Epub ahead of print]

Wang X, Qin X, Demirtas H, Li J, Mao G, Huo Y, Sun N, Liu L, Xu X. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007;369(9576):1876-1882.

Weingärtner J, Lotz K, Fanghänel J, Gedrange T, Bienengräber V, Proff P. Induction and Prevention of Cleft Lip, Alveolus and Palate and Neural Tube Defects with Special Consideration of B Vitamins and the Methylation Cycle. J Orofac Orthop. 2007; 68(4):266-277.

Wierzbicki AS. Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res. 2007;4(2):143-50.

Zeisel SH. The fetal origins of memory: the role of dietary choline in optimal brain development. J Pediatr. 2006;149(5 Suppl):S131-136.

Ziaei S, Kazemnejad A, Zareai M. The Effect of Vitamin E on Hot Flashes in Menopausal Women. Gynecol Obstet Invest. 2007;64(4):204-207 [Epub ahead of print]

Zollinger PE, Tuinebreijer WE, Breederveld RS, Kreis RW. Can vitamin C prevent complex regional pain syndrome in patients with wrist fractures? A randomized, controlled, multicenter dose-response study. J Bone Joint Surg Am. 2007;89(7):1424-1431.

Review Date:
10/29/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Crohn's disease

FitSugar — Wed, 08 Oct 2008 17:35:24 -0700

Overview

Signs and Symptoms
What Causes It?
Risk Factors
What to Expect at Your Provider's Office
Preventive Care
Treatment Options
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Crohn's disease is a chronic inflammatory bowel disease that causes ongoing inflammation of the intestinal tract. It is similar to ulcerative colitis, another inflammatory bowel disease. However, while ulcerative colitis usually is confined to the innermost layer of the large intestine and rectum, Crohn's disease can occur anywhere in the intestine, often in patches surrounded by healthy tissue, and can spread deeper into the tissues. Symptoms include chronic bloody or watery diarrhea, abdominal pain, fever, and loss of appetite. Symptoms tend to wax and wane, with the disease becoming active or going into remission several times during the person's lifetime.

Crohn's disease can cause intestinal obstructions, ulcers (most often in the lower part of the small intestine, the large intestine, or the rectum), fistulas (hollow passages from one part of the intestine to another), and anal fissures (a crack in the anus or the skin around the anus that can lead to infection). In addition, people with Crohn's disease are at risk of malnutrition, because their intestine cannot absorb all the needed nutrients from their diet.

Crohn's disease affects 2 - 7 out of 100,000 people and researchers believe that these numbers are growing. It develops mostly between the ages of 15 - 40, although children and older adults may also develop the condition. There is no cure for Crohn's disease. Medication and strict diets can help control the condition. Some people with the condition will require surgery to remove part of the digestive tract at some point in their lives. However, surgery does not cure the disease.

Signs and Symptoms

The most common signs and symptoms of Crohn's disease are diarrhea and abdominal pain. The symptoms can range from mild to severe.

Diarrhea (with or without blood)
Abdominal pain and bloating
Fatigue
Poor appetite
Weight loss
Fever
Nausea and vomiting
Floating stools (which is caused by poor digestion of fat)

Crohn's disease can also be associated with other medical conditions, including arthritis, osteoporosis, eye infections, blood clots, liver disease, and skin rashes.

What Causes It?

No one is sure what causes Crohn's disease. Theories include a faulty immune system response triggered by bacteria or a virus; genetics, since about a quarter of people who have Crohn's disease also have a close relative with the disease; and a diet high in saturated fat and processed foods, since Crohn's disease is more common in the developed world. It is likely that several factors may be involved in the disease.

Risk Factors

Jewish heritage (three to six times more likely than the general population)
European (particularly Scandinavian) ancestry
Family history of inflammatory bowel disease
Cigarette smoking
Living in an industrialized country (particularly an urban area)
Diet high in sugar and saturated fat and low in fruit and vegetables

What to Expect at Your Provider's Office

Your doctor will perform a thorough physical exam as well as a series of tests to diagnose Crohn's disease. Blood tests may reveal anemia (due to a significant loss of blood) and a high white blood cell count (a sign of inflammation somewhere in the body). Stool samples may indicate whether there is bleeding or infection in the colon or rectum.

The following procedures may be also helpful in distinguishing between ulcerative colitis, Crohn's disease, and other inflammatory conditions.

Colonoscopy -- A colonoscopy, in which a long, flexible, lighted tube with a camera is used to take pictures of the colon, can reveal any inflammation, bleeding, or ulcers along the entire colon wall. This procedure usually requires sedation. A sigmoidoscopy is similar but is used to examine the rectum and lower part of your colon. It can be done without sedation, but may miss inflammation higher in the colon or the small intestine.
Capsule endoscopy -- In this test, you swallow a small capsule with a camera in it, and the camera takes pictures as it passes through the length of your digestive tract. The capsule then passes out of the body through your stool. The test is generally safe, but if there is an intestinal obstruction the capsule may become trapped. Your doctor will run other tests to make sure you do not have an obstruction before using this procedure.
Barium enema -- This procedure examines the large intestine with an x-ray. It involves being given barium (a dye) as an enema, which coats the lining of your large intestine and rectum. It is generally not as reliable a test as colonoscopy.
CT scans -- This imaging technique allows your doctor to look at the entire intestine and can help locate intestinal obstructions or fistulas.

Preventive Care

Although there is no known way to prevent Crohn's disease, the condition can usually be managed with a combination of medication, diet, and lifestyle changes. Exercise can help prevent the stress and depression that often accompany Crohn's disease, and quitting smoking can reduce symptoms. Eating a diet rich in fruit and vegetables can also help lessen symptoms.

Treatment Options

The primary goal in treating Crohn's disease is to control acute flares of the disease and to maintain remission for as long as possible. The specific type of treatment often depends on how severe the symptoms are. For example, people with mild-to-moderate symptoms are usually treated with medications that reduce swelling and suppress the immune system. More severe cases may require surgery.

Many people with inflammatory bowel diseases use complementary and alternative remedies in addition to prescription medications. Preliminary studies indicate that lifestyle changes, dietary adjustments (such as eating a rich variety of fruits and vegetables and avoiding saturated fat and sugar), and specific herbs and supplements may be useful additions to treatment.

Lifestyle

Stress

Many people with Crohn's disease report that stress makes their symptoms worse. Relaxation techniques and mind-body exercises, such as yoga, tai chi, and meditation, are worth considering, particularly when used in addition to other forms of treatment. In addition, studies suggest that hypnosis may improve immune function, increase relaxation, decrease stress, and ease feelings of anxiety.

Exercise

Exercise is helpful for those with Crohn's disease, both in terms of maintaining health and reducing stress. Although exercise is considered safe for people with Crohn's disease, anyone with a chronic illness should talk to their doctor before starting a new exercise or fitness regimen. It is especially important for people with Crohn's disease to drink water before exercising and during exercise to prevent dehydration. Extreme changes in body temperature during exercise should also be avoided.

Smoking

Cigarette smoking is a risk factor for Crohn's disease and studies have shown that it may worsen symptoms. If you smoke, you should quit.

Drug Therapies

Although medications cannot cure Crohn's disease, they can reduce symptoms and help you control your condition. Sometimes, they can induce remission of the disease for a period of time. Medications commonly used to treat Crohn's disease include:

Sulfasalazine (Azulfidine) -- An older drug that reduces inflammation during acute flare-ups and is usually taken with folic acid. Side effects include abdominal discomfort, nausea, and lowered sperm count. Sulfasalazine can be effective, but newer drugs are available.
Mesalamine (Asacol, Rowasa) -- This drug reduces inflammation during acute flare-ups and helps prevent recurrences, and generally has fewer side effects that sulfasalazine.
Corticosteroids (such as budesonide, prednisone, and prednisolone) -- These drugs can reduce inflammation throughout your body but have many side effects, including acne, and an increased risk of infection, osteoporosis, high blood pressure, excessive hair growth, diabetes, and disorders of the eye including glaucoma and cataracts. Corticosteroids also suppress your body's production of the hormone cortisol and cannot be stopped abruptly. They are not for long-term use, but may be used to control flares.
Immune system suppressors -- These medications decrease inflammation by suppressing the immune system. They are sometimes used in combination with steroids to reduce the dose of the steroid medication. These drugs can take several months to work, and all may have significant side effects. Drugs include azathioprine (Imuran), methotrexate (Rheumatrex), infliximab (Remicade), and cyclosporine. Newer drugs in this class that have fewer side effects, such as adalimumab (Humira), are being tested.
Antibiotics -- Antibiotics may be prescribed to help treat fistulas and ulcers. Ciproflaxin (Cipro) and metronidazole (Flagyl) are most commonly used.
Antidiarrheal medications (such as diphenoxylate, loperamide, or psyllium) -- Medications used to treat diarrhea must be used only under medical supervision and with extreme caution. They can slow down the normal movements of the gastrointestinal tract and, in severe cases, may cause a complication known as toxic megacolon.

Surgical Procedures

Although surgery will not cure Crohn's disease, three out of four people with the condition will eventually have resections (parts of their colons removed) to close fistulas or to remove a severely damaged part of your intestine. In some cases laparoscopic surgery (which uses a smaller incision) can be done, leading to fewer complications and shorter hospital stays. Strictureplasty, in which a balloon is inserted into the intestine and expanded, is sometimes done when the intestine has become too narrow from scar tissue.

Complementary and Alternative Therapies

People with Crohn's disease often cannot absorb all the nutrients their bodies need, due to damage in the intestine, or they find it difficult to eat because of abdominal pain and nausea. Some medications may also lower needed nutrients in the body. For example, sulfasalazine reduces the body's ability to absorb folate while corticosteroids can reduce levels of calcium. Making sure that you get enough nutrients is a crucial part of treating Crohn's disease. People with significant malnourishment, severe symptoms, or those awaiting surgery may require parenteral (intravenous) nutrition.

Nutrition

Although diet cannot cause or cure Crohn's disease, some studies suggest that people who eat foods high in saturated fat and sugar or who eat processed foods may be more likely to develop the disease. Certain foods may also reduce symptoms and make recurrences of the disease less likely.

Eating fruits and vegetables, lowering fat, and eliminating sugar may reduce the risk of developing Crohn's disease. Although a low-fiber diet is one of the risk factors for developing Crohn's disease, some people with Crohn's disease find that fiber makes symptoms worse. If fiber bothers you, steam or bake your vegetables rather than eating them raw, and avoid high fiber fruits such as apples.
Certain foods may aggravate symptoms of Crohn's disease – most often, dairy products, fats, and spicy foods. People with Crohn's disease may want to avoid these foods.
Eat five or six smalls a day.
If symptoms are severe, an elemental diet may be recommended. Elemental formulas are liquid diets that contain only the basic building blocks of food and need not be broken down into smaller substances along the digestive tract. Some people find it difficult to stick to an elemental diet, but after a period of time, often other foods can be reintroduced. One study suggests that adding omega-3 fatty acids to an elemental diet may boost its nutritional content and make it more likely that people with Crohn's disease will adhere to it.

Vitamins and Minerals

Because of decreased appetite, malabsorption, chronic diarrhea, side effects of medication, and surgical removal of parts of the digestive tract, many people with Crohn's disease have vitamin and mineral deficiencies. In particular, people with Crohn's disease may lack adequate vitamin D, B12, and K, plus folic acid, calcium, and zinc. Your doctor may recommend that you take a multivitamin daily.

Zinc (25 mg), folic acid (800 mcg), vitamin B12 (800 mcg) -- These vitamins are used by the body to repair cells in the intestine. In addition, drugs such as sulfasalazine and methotrexate may case levels of folic acid in the body to drop, requiring supplementation.

Vitamin D (1,000 IU per day) -- is necessary to maintain strong bones. People with Crohn's disease, especially those who take corticosteroids, often have low levels of vitamin D and are at risk for osteoporosis.

Fish oil (2.7 g per day) -- Omega-3 fatty acids found in fish oil may help fight inflammation and reduce the chances of recurrence, but studies have been mixed. The study with the most positive results used a special type of fish oil – "enteric-coated free-fatty-acid form" – that is not sold commercially. Some researchers suggest that measuring the blood levels of different types of fatty acids may help determine if fish oil would be useful. Do not take high doses of a fish oil supplement if you take blood-thinning medication.

Saccharomyces boulardi (250 mg three times per day to 500 mg four times per day) -- One small study indicated that this type of "good" bacteria helped people with Crohn's disease reduce the incidence of diarrhea. However, other studies have shown mixed results.

N-acetyl glucosamine -- Preliminary research suggests that N-acetyl glucosamine supplements or enemas may improve symptoms of inflammatory bowel disease, but more studies are needed to know whether glucosamine would have any effect on Crohn's disease.

Glutamine (400 mg four times per day) -- is an amino acid found in the body that that helps the intestine function properly. While there is no evidence that glutamine specifically helps reduce symptoms of Crohn's disease, it may be beneficial for overall intestinal health. Glutamine is best taken on an empty stomach. Do not take glutamine is you are diabetic or have seizures.

Herbs

Because of the presence of inflammation and the nature of the disease, Crohn's disease should not be treated with herbs alone. However, herbs may be a useful complement to traditional medical treatment. Remember that herbs can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a health care provider.

The evidence for using herbs to treat Crohn's disease is mostly lacking. Among the herbs that have been used traditionally to treat inflammation within the digestive tract are:

Slippery elm (Ulmus fulva) is a demulcent (protects irritated tissues and promotes their healing). Take 60 -320 mg per day. One tsp. powder may be mixed with water and drunk three to four times a day.
Marshmallow (Althaea officinalis) is a demulcent and emollient; drink one cup of tea three times per day. To make tea, steep 2 - 5 g of dried leaf or 5 g dried root in one cup boiling water. Strain and cool. Avoid marshmallow if you have diabetes.
Cat's claw (Uncaria tomentosa, 250 mg per day) is an anti-inflammatory.
Boswellia (Boswellia serrata, 1,200 mg three times per day for up to 8 weeks) has anti-inflammatory properties, and a few small studies suggest that it may be effective in treating Crohn's disease. However, more research is needed to be sure. Bsowellia may interact with other drugs and supplements, so talk to your doctor before taking it.

Homeopathy

Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of Crohn's disease symptoms (such as diarrhea) based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type -- your physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

Mercurius -- for foul-smelling diarrhea that may have streaks of blood accompanied by a sensation of incomplete emptying. This remedy is most appropriate for individuals who tend to feel exhausted following bowel movements, experience fluctuations in body temperature, perspire frequently, and have a thirst for cold fluids.
Podophyllum -- for explosive, gushing, painless diarrhea that worsens after eating or drinking. Exhaustion often follows bowel movements, and the individuals for whom this remedy is appropriate may experience painful cramps in the lower legs and feet.
Veratrum album -- for profuse, watery diarrhea accompanied by stomach cramps, bloated abdomen, vomiting, exhaustion, and chills. The diarrhea tends to worsen as a result of eating fruit. The individual for whom this therapy is appropriate tends to crave cold liquids.

Acupuncture

Acupuncture has long been used in Traditional Chinese Medicine to treat inflammatory bowel disease. One study in Germany found that acupuncture and moxibustion were effective specifically for treating Crohn's disease. Acupuncturists treat people with inflammatory bowel disease based on an individualized assessment of the excesses and deficiencies of qi located in various meridians. Moxibustion (a technique in which the herb mugwort is burned over specific acupuncture points) is used because its effect is thought to reach deeper into the body than using needles alone.

Other Considerations

Pregnancy

Women who are in remission at the time of conception generally have normal pregnancies and healthy babies. However, women with active disease are more prone to miscarriages, spontaneous abortions, and stillbirths. Symptoms often get worse during pregnancy. For this reason, women with active Crohn's disease who are or wish to become pregnant should continue medications under the guidance of their doctor. Corticosteroids or sulfasalazine are considered relatively safe during this time.

Pregnant women should avoid high doses of vitamins. An obstetrician can provide instructions regarding taking multivitamins during pregnancy. The herbs cat's claw (Uncaria tomentosa) and turmeric (Curcuma longa) are not recommended during pregnancy or breastfeeding.

Prognosis and Complications

A number of complications can develop from Crohn's disease. Many can be successfully treated.

Narrowing of the colon, which may cause obstruction
Perforation of the colon
Abscesses (pus-filled pockets of infection) in the colon
Toxic megacolon (grossly swollen colon that may rupture)
Fistulas (abnormal hollow passages that lead from one part of the intestine to another, or to other organs)
Infection of the blood (sepsis)
Colon cancer
Nutritional problems (including weight loss and reduced muscle mass)
Joint pain and arthritis
Osteoporosis (bone loss)
Gallstones
Eye infections/inflammation
Mouth ulcers, gum inflammation, and dental cavities
Liver damage
Blood clots
Depression and anxiety
Anemia

Although there is no cure for Crohn's disease, many people with the disease lead active lives by controlling their symptoms with medication. Over time, however, Crohn's disease is less responsive to treatment. Within 10 years of diagnosis, 71% of people will need surgical removal of the affected intestine, and many experience at least one relapse in any 10-year period.

Supporting Research

Abela MB. Hypnotherapy for Crohn's disease: a promising complementary/alternative therapy. Integr Med. 2000;2(2/3):127-131.

Ammon HP. Boswellic acids in chronic inflammatory diseases. Planta Med. 2006 Oct;72(12):1100-16.

Anton PA. Stress and mind-body impact on the course of inflammatory bowel diseases. Semin Gastrointest Dis. 1999;10(1):14-19.

Ball E. Exercise guidelines for patients with inflammatory bowel disease. Gastroenterol Nurs. 1998;21(3):108-111.

Belluzzi A, Boschi S, Brignola C, Munarini A, Cariani G, Miglio F. Polyunsaturated fatty acids and inflammatory bowel disease. Am J Clin Nutr. 2000;71(suppl):339S-342S.

Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med. 1996;334(24):1557-1560.

Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn's disease. Ann Surg. 2000;231(1):38-45.

Blumenthal M, ed. Herbal Medicine. Expanded Commission E Monographs. Newton, Mass: Integrative Medicine Communications; 2000.

Bock S. Integrative medical treatment of inflammatory bowel disease. Int J Integr Med. 2000;2(5):21-29.

Brignola C, Belloli C, De Simone G, et al. Zinc supplementation restores plasma concentrations of zinc and thymulin in patients with Crohn's disease. Aliment Pharmacol Ther. 1993;7:275-280.

Chowers Y, Sela B, Holland R, Fidder H, Simoni FB, Bar-Meir S. Increased levels of homocysteine in patients with Crohn's disease are related to folate levels. Am J Gastroenterol. 2000;95(12):3498-3502.

Cosnes J, Beaugerie L, Carbonnel F, Gendre JP. Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology. 2001;120(5):1093-1099.

Dear KL, Hunter JO. Colonoscopic hydrostatic balloon dilation of Crohn's strictures. J Clin Gastroenterol. 2001;33(4):315-318.

Farmer M, Petras RE, Hunt LE, Janosky JE, Galadiuk S. The importance of diagnostic accuracy in colonic inflammatory bowel disease. Am J Gastroenterol. 2000; 95(11):3184-3188.

Favier C, Neut C, Mizon C, Cortot A, Colombel JF, Mizon J. Fecal ß-D-Galactosidase production and Bifidobacteria are decreased in Crohn's disease. Dig Dis Sci. 1997;42(4):817-822.

Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. N Engl J Med. 2000;342:1627-1632.

Geerling BJ, Badart-Smook A, Stockbrügger RW, Brummer R-JM. Comprehensive nutritional status in recently diagnosed patients with inflammatory bowel disease compared with population controls. Eur J Clin Nutr. 2000;54:514-521.

Geerling BJ, Houwelingen AC, Badart-Smook A, Stockbrügger RW, Brummer R-JM. The relation between antioxidant status and alterations in fatty acid profile in patients with Crohn disease and controls. Scand J Gastroenterol. 1999a;34:1108-1116.

Geerling BJ, Stockbrugger RW, Brummer R-JM. Nutrition and inflammatory bowel disease: an update. Scand J Gastroenterol. 1999c;34(suppl 230):95-105.

Gilman J, Shanahan F, Cashman KD. Determinants of vitamin D status in adult Crohn's disease patients, with particular emphasis on supplemental vitamin D use. Eur J Clin Nutr. 2006 Jul;60(7):889-96.

Gionchetti P, Rizzello F, Venturi A, Campieri M. Probiotics in infective diarrhea and inflammatory bowel diseases. J Gastroenterol Hepatol. 2000;15:489-493.

Gupta I, Parihar A, Malhotra P, Singh GB, Ludtke R, Safayhi H, Ammon HPT. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res. 1997;2:37-43.

Haas l, McClain C, Varilek G. Complementary and alternative medicine and gastrointestinal diseases. Curr Opin Gastroenterol. 2000;16:188-196.

Hampe J, Cuthbert A, Croucher JP, et al. Association between insertion mutation in NOD2 gene Crohn's disease in German and British populations. Lancet. 2001; 357:1925-1928.

Heuschkel RB, Menache CC, Megerian JT, Baird AE. Enteral nutrition and corticosteroids in the treatment of acute Crohn's disease in children. J Pediatr Gastroenterol Nutr. 2000;31(1):8-15.

Joachim G. The relationship between habits of food consumption and reported reactions to food in people with inflammatory bowel disease-testing the limits. Nutr Health. 1999;13(2):69-83.

Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996: 220.

Joos S, Brinkhaus B, Maluche C, Maupai N, Kohnen R, Kraehmer N, Hahn EG, Schuppan D. Acupuncture and moxibustion in the treatment of active Crohn's disease: a randomized controlled study. Digestion. 2004;69(3):131-9.

Keane J, Gershon S, Wise RP et al. Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med. 2001;345(15):1098-1104.

Kuroki F, Iida M, Tominaga M, et al. Multiple vitamin status in Crohn's disease. Dig Dis Sci. 1993;38(9):1614-1618.

Levy E, Rizwan Y, Thibault L, et al. Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease. Am J Clin Nutr. 2000;71:807-815.

Lewis JD, Fisher RL. Nutrition support in inflammatory bowel disease. Med Clin North Am. 1994;78(6):1443-1456.

Loudon CP, Corroll V, Butcher J, Rawsthorne P, Bernstein CN. The effects of physical exercise on patients with Crohn's disease. Am J Gastroenterol. 1999;94(3):697-703.

Macdonald A. Omega-3 fatty acids as adjunctive therapy in Crohn’s disease. Gastroenterol Nurs. 2006 Jul-Aug;29(4):295-301.

Malin M, Suomalainen H, Saxelin M, Isolauri E. Promotion of IgA immune response in patients with Crohn's disease by oral bacteriotherapy with Lactobacillus GG. Ann Nutr Metab. 1996;40:137-145.

Msika S, Iannelli A, Deroide G, et al. Can laparoscopy reduce hospital stay in the treatment of Crohn's disease? Dis Colon Rectum. 2001;44(11):1661-1666.

Mulder TPJ, Van Der Sluys Veer A, Verspaget HW, et al. Effect of oral zinc supplementation on metallothionein and superoxide dismutase concentrations in patients with inflammatory bowel disease. J Gastroenterol Hepatol. 1994;9:472-477.

Nielsen AA, Jorgensen LG, Nielsen JN, Eivindson M, Gronbaek H, Vind I, et al. Omega-3 fatty acids inhibit an increase of proinflammatory cytokines in patients with active Crohn's disease compared with omega-6 fatty acids. Aliment Pharmacol Ther. 2005 Dec;22(11-12):1121-8.

Philipsen-Geerling BJ, Brummer RJM. Nutrition in Crohn's disease. Curr Opin Clin Nutr Metab Care. 2000;3:305-309.

Rajapakse R, Korelitz BI. Inflammatory bowel disease during pregnancy. Current Treatment Options in Gastroenterology. 2001;4(3):245-251.

Rawsthorne P, Shanahan F, Cronin NC, et al. An international survey of the use and attitudes regarding alternative medicine by patients with inflammatory bowel disease. Am J Gastroenterol. 1999;94(5):1298-1303.

Ringel Y, Drossman DA. Psychosocial aspects of Crohn's disease. Surg Clin North Am. 2001;81(1):231-252.

Rioux JD, Daly MJ, Silverberg MS, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223-228.

Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F. Probiotics for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD004826.

Russel MG. Changes in the incidence of inflammatory bowel disease: what does it mean? Eur J Intern Med. 2000;11(4):191-196.

Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in pediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000;14:1567-1579.

Shanahan F. Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflamm Bowel Dis. 2000;6(2):107-115.

Steger GG, Mader RM, Vogelsang H, Schöfl R, Lochs H, Ferenci P. Folate absorption in Crohn's disease. Digestion. 1994;55:234-238.

Stein RB, Lichtenstein GR, Rombeau JL. Nutrition in inflammatory bowel disease. CurrOpin Clin Nutr Metab Care. 1999;2:367-371.

Szulc P, Meunier PJ. Is vitamin K deficiency a risk factor for osteoporosis in Crohn's disease? [commentary]. Lancet. 2001;357(9273):1995-1996.

Teahon K, Bjarnason I, Pearson M, Levi AJ. Ten years' experience with an elemental diet in the management of Crohn's disease. Gut. 1990;31(10):1133-1137.

Tsujikawa T, Satoh J, Katsuhiro U, et al. Clinical importance of n-3 fatty acid-rich diet and nutritional education for the maintenance of remission in Crohn's disease. Gastroenterol. 2000;35:99-104.

Ullman D. The Consumer's Guide to Homeopathy. New York, NY: Penguin Putnam; 1995: 76-77.

van Heel DA, McGovern DPB, Jewell DP. Crohn's disease: a genetic susceptibility, bacteria, and innate immunity [commentary]. Lancet. 2001;357:1902-1903.

Zachos M, Tondeur M, Griffiths AM. Enteral nutritional therapy for inducing remission of Crohn's disease (Cocrane Review). In: The Cochrane Library, 4, 2001. Oxford: Update Software.

Zurita VF, Rawls DE, Dyck WP. Nutritional support in inflammatory bowel disease. Dig Dis. 1995;13:92-107.

Review Date:
3/18/2007
Reviewed By:
Steven D. Ehrlich, N.M.D., private practice specializing in complementary and alternative medicine, Phoenix, AZ. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

adam.com