FitSugar

The Leanest Cuts of Meats Revealed

FitSugar — Tue, 06 Nov 2007 15:30:00 -0800

Sick of chicken yet? You're not alone, but how does someone who's trying to watch her calories and fat intake pick a lean type of meat? I found a basic breakdown on the leanest meat choices on Yahoo and I thought it would be helpful in deciding which meat meets your needs. Here are the highlights:

Bison: We hope you’re ready to expand your dinner horizons because bison (aka buffalo) is the big winner. (Deer and elk are right on its hooves, er, heels.) Believe it or not, bison has slightly less fat and fewer calories (2 grams and 122 calories per 3-ounce serving) than skinless light meat chicken (3g and 144 cals). Plus, it’s a terrific source of protein (24g) and iron. The taste? Similar to beef, though slightly sweeter and richer.

Bonus: With bison (wild game, too), you aren't exposed to the cancer-linked growth hormones and antibiotics administered to farm-raised cows.

Beef and Veal: Beef and veal are skinniest when they’re loin or round cuts, such as beef bottom sirloin (6g fat, 150 cals) and top round veal (3g, 128 cals). Avoid veal cutlets and breast meat.

Pork: Choose leg cuts, such as ham, or loin, as in boneless sirloin pork chops or top loin chops (both have about 7g fat and 170 cals).

Lamb: Try cuts from the shank half of the leg (if labels aren’t clear, ask the butcher). Well-trimmed shank-half cuts have 5-6 grams fat and about 155 calories per serving.

Fit's Tip: Meat is generally higher in cholesterol and saturated fat than chicken, fish or vegetables, so use the choices above for those times when you just need some red meat.

Source

Cookbook Review: Almost Meatless

FitSugar — Mon, 27 Apr 2009 08:00:00 -0700

Studies on health and the health of the environment continue pointing to the fact that eating less meat is beneficial. It is from the perspective that you can reduce both your carbon footprint and your long term health by cutting back on your carnivorous ways that the authors of Almost Meatless ($22.50) penned their new cookbook. A collaboration between a former vegan, Joy Manning, and a committed meat eater, Tara Mataraza Desmond, this cookbook is full of recipes that include meat, fish, and poultry in the ingredient list. The meat, however, is not central to the dishes and is used more like a spice for flavor, texture, and color.

The cookbook is divided into sections by animal proteins, including chicken, seafood, eggs, beef, and pork. The amount of meat in these recipes is small, often hovering around four ounces to create a final dish containing four to six servings. The photos of the dishes are inspiring, but I would love a shot of every dish - I am very visually motivated when it comes to experimenting with new recipes. There are many tempting dishes to make like Almond Gnocchi with Lamb Ragu and Sweet Potato Chorizo Mole. I cooked up the shrimp fried rice and everyone in my house plus two guests loved it, and I look forward to trying more recipes from this book. The authors provide great cooking and shopping tips - like how to freeze bacon so you can use a slice when needed. Yes, cooking with just a piece of bacon still packs a powerful tasty punch. The only problem I have with this cookbook - there are no nutritional breakdowns of the recipes. I believe that cooks interested in using less meat are also going to want to know the calories, protein, and fat per serving.

To check out the tasty fried rice recipe read more.

Shrimp and Pineapple Fried Rice
Almost Meatless by Joy Manning and Tara Mataraza Desmond

Ingredients

1 large pineapple, cut in half length wise
2 tablespoons vegetable oil
1/2 small onion, but into 1/4 inch dice (about 1/2 cup)
2 cloves, garlic minced (about 1 tablespoon)
1 (1-inch) piece of ginger, peeled and minced
1 small red bell pepper, but into 1/4 inch dice, about (half a cup)
1 cup shopped sugar snap or snow peas
1 Thai chile, seeded and thinly sliced
2 tablespoons soy sauce
2 teaspoons fish sauce
4 cups cold cooked brown or white rice
1/2 shrimp, peeled, deveined, and cute into 1/4-inch pieces

Directions

Make two bowls form the pineapple halves by arcing out the center, leaving the bottom intact and leaving about a 1/2-inch-think border along the sides. Cut the carved out pineapple into small chunks, discarding the pieces of the tough center core. Set the pineapple shells and he chunks aside.
Coat a wok or a large sautée pan with the oil and set over medium-high heat. Once the oils shimmering but not smoking, add onion, garlic, ginger, bell peppers, peas, and chili. Stir-fry for about 2 minutes.
Add the soy sauce, fish sauce, and rice, tossing to incorporate with the other ingredients.
Add the shrimp, cooking just until done, for about two minutes.
Remove from the heat and stir in the pineapple chunks. Spoon the rice into the carved out pineapple halves and serve.

Serves 4

Make it family friendly by leaving out the Thai chili. Just sautée the chili separately and add to adult plates depending on desired spiciness.

Print recipe with images | without images

Fit For March: Must Haves

FitSugar — Mon, 02 Mar 2009 05:30:00 -0800

The month of March comes in like a lion, bringing with it St. Patrick's Day and the first day of Spring. I for one am keeping my fingers crossed that it does really go out like a lamb. Here are a few items that will help keep you fit during the wild month of March. Start the slideshow to see my March must haves.

Source

View Slideshow ›

Condom application - series

FitSugar — Wed, 08 Oct 2008 17:35:45 -0700

Back

HEALTH GUIDE REFERENCE FROM A.D.A.M

Condoms are made of latex rubber, polyurethane or lamb intestines. One of the benefits of condoms is the ability to block sexually transmitted diseases. Latex condoms are best.

Review Date:
12/31/2007
Reviewed By:
Harvey Simon, MD, 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

Kidney stones

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Research:

Patients who have the most common type of gastric bypass surgery, the Roux-en-Y, are at increased risk for kidney stones, beginning 6 months after surgery, according to a study published in 2006.

Causes of Kidney Stones:

Calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of this imbalance is unknown.
Having acidic urine or too much uric acid in the body leads to the formation of uric acid stones.
Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes.
Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Treatments:

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 - 3 days.
Certain medications can prevent recurrence of stones in people who are at high risk.
Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. The shock waves are delivered from outside the body.
Surgery may be necessary if the stone or stones are too big to pass, and cannot be broken down through ESWL.
A change of diet and increased drinking of fluids, especially water, will help prevent a recurrence.

Introduction

Kidney stones are hard, solid rocks that form in the urinary tract. In many cases, the stones are very small and can pass out of the body without any problems. However, if a stone (even a small one) blocks the flow of urine, excruciating pain may result, and prompt medical treatment may be needed.

The process of urination begins in the kidneys. The kidneys filter out fluids and waste from the body, producing urine. The two kidneys are located deep behind the abdominal organs, below the ribs and toward the middle of the back.

Each kidney contains over a million nephrons. These are the tiny filtration units of the kidney.
Each nephron is composed of a tiny group of blood vessels (a glomerulus) enclosed in a funnel-like structure called Bowman's capsule.
Each glomerulus filters waste products, water, and salts out of the liquid part of the blood (plasma) that has entered the kidney.
About 1% of the plasma is converted into urine. The rest returns into the blood to prevent dehydration. Urine is primarily made of acids, urea, and creatinine (nitrogen compounds).
Urine passes from Bowman's capsule into tiny tubules, which lead to large collecting tubes in the center of the kidney. As the urine passes through this network, it becomes more concentrated.
Urine then flows from the kidney through thin tubes called ureters into the bladder.
The bladder's stretchy walls expand to store the incoming urine until it leaves the body through a tube called the urethra.

The kidneys are responsible for removing wastes from the body, regulating electrolyte balance and blood pressure, and stimulating red blood cell production.

Click the icon to see an image of the urinary tract.

Occasionally, various salts build up on the inside surfaces of the kidney and form crystals. Eventually these crystals become large enough to form stones in the kidney, a condition called nephrolithiasis. Kidney stones (renal calculi) may also form in the ureter or the bladder. Combinations of minerals and other chemicals, some derived from a person's diet, make up the salts in these stones.

Click the icon to see an image of the kidney stones.

Calcium Stones. About 70 - 90% of all kidney stones are made of calcium, usually combined with oxalate, or oxalic acid. A number of common vegetables, fruits, and grains contain oxalate.

About 6% of calcium stones are made of calcium phosphate (called brushite).

Uric Acid Stones. Uric acid is responsible for close to 10% of kidney stones. It is the breakdown product of purines, nitrogen compounds found in our bodies and in certain foods. The breakdown of purines to uric acid occurs in the liver, and from there uric acid enters the bloodstream, most of it passing into the kidneys. From the kidneys, uric acid leaves the body in the urine. Often, uric acid stones occur with calcium stones.

Struvite Stones. Struvite stones are made of magnesium ammonium phosphate. They are almost always associated with certain urinary tract infections. Worldwide, they make up to 30% of all kidney stones. In the United States, however, less than 15% of all stones are struvite. Most struvite stones occur in women. The rate of these stones may be declining in America, perhaps because of better control of urinary tract infections.

Cystine Stones. A build-up of the amino acid cystine, a building block of protein, causes 1% of kidney stones in adults and up to 8% of stones in children. The tendency to form these stones is inherited. Cystine stones are marked by rapid growth and recurrence, which, if not treated promptly, can eventually lead to kidney failure.

Xanthine Stones. Other kidney stones are composed of xanthine, a nitrogen compound. These stones are extremely uncommon and usually occur as a result of a rare genetic disorder.

Click the icon to see an animation about kidney stones.

Causes

The key process in the development of kidney stones is supersaturation.

The urine carries salts, including calcium oxalate, uric acid, cystine, or xanthine.
These salts can become extremely concentrated if there is not enough urine, or if unusually high amounts of crystal-forming salts are present.
When salt concentration levels reach the point at which they no longer dissolve, these salts form crystals.

Different factors may be involved in either reducing urine amount, or increasing the levels of the salts.

Deficiencies in Protective Factors. Normally, urine contains substances that may protect against stone formation, including:

Magnesium
Citrate
Pyrophosphate
Enzymes

These substances:

Allow salt in the urine to be at higher-than-normal concentrations without forming crystals
Prevent crystal formation
Coat the crystals and prevent them from sticking to the surface of kidney tubes

Not having enough of these protective substances can cause stones.

Changes in the Acidity of the Urine. Changes in the acid balance of the urine can affect stone formation.

Uric acid and cystine stones mainly form in acidic urine.
Calcium phosphate and struvite stones increase in alkaline urine.

Factors that Bind Crystals to the Kidney Tubules. Researchers are studying the cells lining the kidney tubules in order to understand how and why early crystals bind to the tubes long enough to form stones. Under investigation are elevated levels of substances that either cause crystals to stick to the tubes or deficiencies in those that prevent them from sticking.

In general, calcium stones form when there is an imbalance in the urine substances that promote and block the formation of stones. Often, the cause of calcium stones is not known, and the condition is then called idiopathic nephrolithiasis. Research suggests that nearly all stones result from problems in the breakdown and absorption of calcium and oxalate. Genetic factors may play a role in about half of these cases. A number of medical conditions and drugs can also affect digestion and intestinal absorption.

Excess Calcium in the Urine (Hypercalciuria). Hypercalciuria (too much calcium in the urine) is responsible for as much as 70% of calcium-containing stones. A number of conditions may produce hypercalciuria. Many are due to genetic factors, but most cases are idiopathic (due to unknown causes).

The following can lead to hypercalciuria and calcium stones:

Too much calcium absorption in the intestines: In most of these conditions, genetic factors lead to increased calcium absorption in the intestine. Researchers are investigating a possible defective gene that regulates calcitriol, a form of vitamin D, which, in excess levels, may increase intestinal absorption of calcium.
Excessive chloride: Chloride has a negative charge, and calcium has a positive one, so they balance each other in the body. Excess chloride may lead to excess calcium. A gene known as CLCN5, which regulates chloride in the urine, is defective in many patients with calcium stones.
Renal calcium leak: In this condition, the filtering processes in the kidney fail, causing an increase of calcium in the urine.
Excessive sodium: High urinary levels of sodium result in increased levels of calcium. Certain defects in the kidney tubules transport system, which cause imbalances in sodium and phosphate, can lead to high calcium levels in the urine. A diet high in salt can also produce this effect.

Excess Oxalate in the Urine (Hyperoxaluria). Oxalate is the most common stone-forming compound. Excessive oxalate in the urine (hyperoxaluria) is responsible for up to 60% of calcium stones and is a more common cause of stones than too much calcium in the urine.

Hyperoxaluria can be either primary or secondary.

Primary hyperoxaluria is an inherited disorder in which too much oxalate in the urine is the main problem.
Secondary hyperoxaluria results from specific conditions that cause high levels of urinary oxalate.

Secondary hyperoxaluria is usually caused by too much dietary oxalates (found in a number of common vegetables, fruits, and grains) or by problems in the body's breakdown of oxalates. Such defects may be due to various factors:

Severe vitamin B6 deficiencies (usually due to genetic disorders)
Deficiencies in Oxalobacter formigene, an intestinal bacteria that breaks down oxalate
Short bowel syndrome, a condition that makes the intestines unable to properly absorb fat and nutrients; calcium may bind to unabsorbed fat instead of oxalates, which causes a buildup of oxalate
Androgens (male hormones)

Female hormones (estrogens) actually lower the risk of hyperoxaluria. Estrogen may help prevent the formation of calcium oxalate stones by keeping urine alkaline, and raising protective citrate levels.

A study published in 2006 found that patients who undergo the most common gastric type of bypass surgery, the Roux-en-Y, were at increased risk for calcium oxalate kidney stones, beginning 6 months after surgery. The study found that patients who underwent the procedure developed hyperoxaluria, and the condition was common 12 months after surgery. The authors also noted an increased number of kidney stone incidents in this patient group.

Excessive Calcium in the Bloodstream (Hypercalcemia). Hypercalcemia generally occurs when bones break down and release too much calcium into the bloodstream. This is a process called resorption. It can occur from a number of different diseases and events:

Hyperparathyroidism: Overactive parathyroid glands cause about 5% of calcium stones. People with this disorder have at least a 20% chance of developing kidney stones. Women are more likely to have this disorder than men.
Immobilization: Lack of movement can lead to kidney stones.
Renal tubular acidosis: This disorder causes acidic and alkaline imbalance. Renal tubular acidosis not only increases calcium levels in the bloodstream but also reduces protective citrate levels.

Hyperuricosuria is a condition of high levels of uric acid in urine. It occurs in between 15 - 20% of people (mostly men) with calcium oxalate stones. Urate, the salt formed from uric acid, creates the center of a crystal (nidus), around which calcium oxalate crystals form and grow. Such stones tend to be severe and recurrent. They appear to be strongly related to a high intake of protein. (Hyperuricosuria also plays a major role in some uric acid stones.)

Low Urine Levels of Citrate (Hypocitraturia). Citrate is the main substance in the body that is responsible for removing excess calcium. It also blocks the process that turns calcium crystals into stones. Low levels of citrate in the urine (hypocitraturia) is a significant risk factor for calcium stones. In addition, hypocitraturia also increases the risk for uric acid stones. This condition most likely contributes to about a third of all kidney stones.

Many conditions can reduce citrate levels. Some causes include:

Renal tubular acidosis
Potassium or magnesium deficiency
Urinary tract infection
Kidney failure
Chronic diarrhea

Often, however, the cause of hypocitraturia-related stones is unknown.

Low Levels of Other Stone-Blocking Compounds. Several other compounds in the urine, including magnesium and pyrophosphate, also prevent the formation of calcium stones. If any of these compounds are lacking, stones may develop.

Nanobacteria Infection. Nanobacteria are tiny infectious organisms that can pass from the blood into urine. They coat themselves with mineral deposits that resemble the composition of kidney stones. Cells infected with these bacteria develop mineral deposits on the inside and outside. Researchers believe that nanobacteria may form the cores of the kidney stones in many people.

Human body tissues, certain foods, and certain alcoholic drinks contain substances called purines. Purine-containing foods include dried beans, peas, and liver. When the body breaks down purines, it produces uric acid. The presence of a certain level of uric acid in the body is normal.

The following conditions are usually seen in patients with uric acid stones:

Too much acid in the urine for a long period (the most important cause of uric acid stones)
Lower than normal amounts of urine produced.
Hyperuricosuria, a metabolic disorder that leads to high levels of uric acid in the urine

Note: Hyperuricosuria can also trigger calcium stones. Therefore, a combination of calcium and uric acid stones may be present in patients with hyperuricosuria.

A number of conditions and other factors may contribute to, or cause, uric acid stones:

Gout: Uric acid and other kidney stones develop in up to 25% of patients with primary gout, a painful form of arthritis that occurs when uric acid in the blood forms crystals in one or more joints.
Diabetes: New research has shown that people with type 2 diabetes have highly acidic urine that can lead to kidney stones, particularly uric acid stones. The findings were published in the May 2006 Journal of the American Society of Nephrology.
Insulin resistance: People with insulin resistance are at an increased risk for uric acid stones. The reason is unknown but may be related to the transport of certain salts through the kidneys. This transport changes in patients with insulin resistance.
Kidney abnormalities: Kidney problems that reduce the production of ammonia, particularly in people with diabetes or insulin resistance, may lead to uric acid stones.
Genetic factors: Genetic factors can increase a person's risk for uric acid stones.
Hypocitraturia: Hypocitraturia is a low amount of citrate in the urine.
Diet: Eating too much animal protein increases the risk of forming uric acid stones.

Other risk factors include:

Certain medications (chemotherapy drugs, diuretics, and salicylates)
Binge drinking
Not eating for long periods of time (fasting)
Lead poisoning
Blood cancers (leukemia, multiple myeloma, and lymphomas)
Some rare types of anemia (low levels of red blood cells in the blood)
Chronic diarrhea

Struvite stones are almost always caused by urinary tract infections due to bacteria that produce certain enzymes. These enzymes raise the concentration of ammonia in the urine. Ammonia makes up the crystals that form struvite stones. The stone-promoting bacteria are usually Proteus, but may also include Pseudomonas, Klebsiella, Providencia, Serratia, and staphylococci. Women are twice as likely to have struvite stones as men.

Other stones, including cystine and xanthine stones, are usually due to genetic abnormalities.

Causes of Cystine Stones. Cystine stones develop from genetic defects that cause abnormal transport of amino acids in the kidney and gastrointestinal system leading to a build-up of cystine, one of these amino acids. Researchers have identified two genes responsible for this condition: SLC3A1 and CLC7A9.

Causes of Xanthine Stones. In some cases, xanthine stones may develop in patients being treated with allopurinol for gout.

Risk Factors

Kidney stones are one of the most common disorders of the urinary tract. They are an ancient health problem. Evidence of kidney stones has been found in an Egyptian mummy estimated to be more than 7,000 years old.

An estimated 1.3 million Americans seek medical help for kidney stones each year. At this time, studies suggest kidney stones affect over 5% of Americans and that the rate has increased since the 1970s, perhaps because of increases in animal and dietary protein intake.

Men. The risk of kidney stones increases in a man's 40s and continues to rise until age 70. Caucasian men are at higher risk than other groups.

Women. The risk of kidney stones peaks in a woman's 50s. In younger women, stones are more likely to develop during the late stages of pregnancy. Pregnant women tend to have a higher calcium intake, but their kidneys do no handle the calcium as well as they did prior to pregnancy. Kidney stones are still a rare occurrence during pregnancy, however, affecting only 1 in 1,500 pregnancies.

Risk Factors in Children. Stones in the urinary tract in children are usually due to genetic factors. Most of the time, the cause is too much calcium in the urine (hypercalciuria). Deformities in the urinary tract pose a significant risk for kidney stones in children. Children with low birth weight who need to be fed intravenously are also at risk for stones.

Obesity and weight gain are both associated with an increased risk of kidney stones.

Men who weigh more than 220 lbs are 44% more likely to develop kidney stones than men who weigh less than 150 lbs.
Women who are obese are 90% more likely to develop kidney stones than women with a lower body mass index (BMI).

Higher BMIs and larger waist circumferences are both risk factors for kidney stones. Researchers think that there may be a link between fat tissue, insulin resistance, and urine composition. People with larger body sizes may excrete more calcium and uric acid, which increase the risk of kidney stone formation.

A family history of kidney stones increases one's risk for the condition. Researchers are looking into markers or other factors that might predict kidney stones in relatives, although none has yet been clearly identified. One report found that among the siblings of patients with calcium stones, sisters with higher urinary calcium levels and more acidic urine were more likely to develop stones. Brothers with high urinary calcium, low urinary potassium, and older age were more likely to have the problem. A family history of gout may also make a person vulnerable to stones.

According to a 2003 study of American ethnic groups, Caucasians have the highest incidence of kidney stones (5.9%) followed by Mexican Americans (2.6%). African-Americans have the lowest risk (1.7%).

Dietary factors, minerals in local water, or both may contribute to geographic differences that have been observed in the occurrence of kidney stones. Studies have reported the highest occurrence of kidney stones in the southern region of the United States and the lowest in the west. One study suggested that the higher risk may be due to a higher rate of high blood pressure in the southern states and certain dietary habits, particularly lower intake of magnesium and low use of calcium supplements.

Specific Foods. In general, certain foods increase the risk for stones only in people who have genetic or medical vulnerability. People whose diets are high in animal protein and low in fiber and fluids may be at higher risk for stones. A number of foods contain oxalic acid, but there is no proof that such foods make any major contribution to calcium oxalate stones in people without other risk factors. However, several studies have shown that increasing dietary calcium and restricting salt, animal protein, and foods rich in oxalate can help prevent calcium oxalate stones from returning.

Stress. One study reported that people who had a major, stressful life experience were more likely to develop stones than those who had not. Some experts speculate that this increased risk may be due to a hormone called vasopressin, which is released in response to stress. Vasopressin also increases the concentration of urine.

Sleep Position. Sleeping in the same position consistently may influence risk. A 2001 study reported that in people who had a history of kidney stones, recurrences tended to occur on the same side that people slept on. An earlier study suggested that people who had kidney stones were more apt to sleep on their stomachs. Movement during sleep did not appear to affect the risk.

Being Bedridden. Any medical or physical condition that keeps a person in bed or immobile increases blood levels of calcium from bone breakdown, thereby posing a risk for stone formation.

Gout. Patients with gout are at a high risk of uric acid stones. These patients have very acidic urine, and a 2002 study suggested that the two disorders may have a common source.

High Blood Pressure. Persons with high blood pressure are up to three times more likely to develop kidney stones. It is not entirely clear whether having high blood pressure increases the risk for a stone, whether stones lead to high blood pressure, or if there is an action linking both.

Inflammatory Bowel Disease: Crohn's disease and ulcerative colitis cause problems in absorption of substances in the intestines. These problems significantly increase the risk for kidney stones, particularly in men.

Urinary Tract Infections (UTIs): Urinary tract infections are almost always the cause of struvite stones.

Hyperparathyroidism: The parathyroid glands regulate calcium levels in the body through the parathyroid hormone. In hyperparathyroidism, one or more of these glands makes too much parathyroid hormone. Some people with hyperparathyroidism develop kidney stones. Surgery to remove the hyperactive parathyroid gland in such patients reduces the risk for stone formation, but the risk still remains high for some time after surgery.

Other Medical Conditions. Kidney disease, chronic diarrhea, certain cancers (such as leukemia and lymphoma), and sarcoidosis put people at higher risk for stones.

AIDS medications. Over 10% of persons with AIDS who take the medicine indinavir develop stones. The risk is even higher in patients with AIDS who also have hepatitis B, hepatitis C, or hemophilia, as well as those who are very thin or who take the antibiotic combination TMP-SMX. In one study of persons with AIDS who took a combination of indinavir, zidovudine, and lamivudine, 36% developed kidney stones.

Other Drugs. Kidney stones are a rare side effect of thyroid hormones and loop diuretics (drugs that increase urination). In fact, diuretics are also used to prevent calcium stones. Certain cancer chemotherapies can also cause kidney stones. Long-term use of medications, such as antacids, which change the acidic content of urine, may increase the risk for kidney stones.

Symptoms

In many cases, kidney stones do not produce symptoms. However, if a stone becomes stuck in the ureter (the thin tube between the bladder and the kidney), symptoms can be very severe. Often, they vary depending on the stone's location and its progress.

Kidney stone attacks tend to be most common late at night or in the early morning, possibly because of minimal urine output or constriction of the ureters during the early morning hours. Kidney stone attacks are least common during the late afternoon

Pain usually begins abruptly on one side and then usually continues as intense, constant pain. (In some cases it persists for a few minutes, disappears, and then returns after about 10 minutes.)
The patient cannot become comfortable and usually stands, sits, paces, or reclines in a vain search for a position that will bring relief.
If the stone is in the kidney or upper urinary tract, the pain usually starts in one flank area (to the side of the back near the waist). It typically moves to the groin as the stone passes down.
If the stone is too large to pass easily, the pain follows the muscle contractions in the wall of the ureter as they try to squeeze the stone along into the bladder.
Nausea and vomiting may occur.
Blood in the urine may be present.
As the stone passes down the ureter closer to the bladder, a person may feel the need to urinate more often or a burning sensation during urination.
If fever and chills accompany any of these symptoms, an infection may be present.

The size of the stone does not necessarily predict the severity of the pain; a very tiny crystal with sharp edges can cause intense pain while a larger round stone may not be as distressing. Struvite stones can often occur without symptoms.

Diagnosis

The doctor will perform a physical exam. This includes pressing against abdominal areas for tender locations that might indicate the presence of the stone.

The patient's age is a significant factor. Kidney stones that occur in children and young patients are more apt to result from inherited problems that cause cystine, xanthine, or, in some cases, calcium oxalate stones. In adult patients, calcium stones are most common.

A medical history may help predict which crystal has formed the stone. The doctor will need to know the following:

Any previous kidney stone attacks
Histories of cancer, sarcoidosis, or small bowel disease
Any medications being taken, including non-prescription substances, particularly high doses of vitamins D or C and calcium-containing antacids

Many conditions can cause symptoms similar to kidney stones. Usually the diagnosis is easily made because of the specific nature of the symptoms, but it is not always clear. Urinary tract infections can cause similar, but usually less intense, pain. In fact, infection may be present with a kidney stone. Other causes of pain that may mimic kidney stones include:

Gallstones
Diverticulitis (infection or irritation of abnormal pockets in the intestines)
Intestinal blockage
Blood clots
Irritable bowel syndrome
Appendicitis
Stomach ulcers
Hiatal hernia (when the upper part of the stomach bulges into the chest, through an opening in the diaphragm)
Pancreatitis (inflammation of the pancreas)
Hepatitis
Pelvic inflammatory disease
Inflammatory bowel disease (Crohn's and colitis)
Heart attack

Various imaging techniques are helpful in determining the presence of kidney stones. The best approach uses spiral (or helical) computed tomography scans. If it is not available, the patient will need ultrasound or standard x-rays. If no stones show up, but the patient has severe pain that suggests the presence of kidney stones, the next step is an intravenous pyelogram.

X-Rays. A standard x-ray of the kidneys, ureters, and bladder may be a good first step for identifying many stones, since many are visible on x-rays. Calcium stones can be identified on x-rays by their white color. Cystine crystals can also show up on x-rays.

Spiral (or Helical) Computed Tomography. A type of computed tomography (CT) scan, called a spiral or helical CT scan, is currently the best method for diagnosing stones in either the kidneys or the ureters. This test is fast, does not require instruments or foreign chemicals to enter the body, and provides detailed accurate images of even very small stones. If stones are not present, a spiral CT scan can often identify other causes of pain in the kidney area. It is better than x-rays, ultrasound, and intravenous pyelogram -- the previous standard test for detecting kidney stones. Experts hope spiral CT will eventually be able to identify the chemicals present in a stone.

Ultrasound. Ultrasound can detect clear uric acid stones and obstruction in the urinary tract. It is not useful for finding very small stones, but some research indicates that it may be a useful first diagnostic step in the emergency room to help predict the likelihood of a stone, including suspected stones in children.

Intravenous Pyelogram. With intravenous pyelogram (IVP), the doctor injects a special dye into the patient. A technician will then take x-rays as the dye enters the kidneys and travels down the urinary tract. IVP is invasive but, until recently, was the most cost-effective method for detecting stones. Where it is available, spiral CT is now preferred, since it gives a faster diagnosis, is more accurate, is safer, and is similar in cost.

In any case, IVP should not be used on patients with kidney failure. There is also a risk for an allergic reaction to standard dyes, although newer less allergenic ones are becoming available.

In the procedure intravenous pyelogram (IVP), the patient is injected with dye. X-rays are taken as the dye travels through the urinary tract. This procedure is done to confirm the presence of kidney stones, although some stones may be too small to see.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) techniques are showing promise for diagnosing urinary tract obstruction but do not yet accurately reveal small stones, or ones that do not cause a blockage. Because no radiation is involved with MRI, however, it may prove to be a good option for pregnant women.

Urine samples are required to evaluate features of the urine, including its acidity and the presence of:

Red or white blood cells
Infection
Crystals
High or low levels of chemicals that inhibit or promote stone formation

Clean-Catch Urine Sample for Culturing. After determining that a kidney stone is present, the health care provider usually gives the patient a collection kit, including filters, to try to catch the stone or gravel as it passes out. The urine may also be tested (cultured) for the presence of infection-causing organisms. A clean-catch urine sample is almost always required for culturing. To provide a clean catch, do the following:

First, wash your hands thoroughly, then wash the penis or vulva and surrounding area four times with downward strokes, using a new soapy sponge each time.
Begin urinating into the toilet and stop after a few drops.
Position the container to catch the middle portion of the urine stream. Ideally, this urine will contain only the bacteria and other evidence of the stone.
Urinate the remainder into the toilet.
Tighten the cap on the container securely, being careful not to touch the inside of the rim.

Click the icon to see an image of a calcium urine test.

Twenty-Four Hour Urine Collection. A 24-hour urine collection may be needed to measure urine volume and levels of acidity, calcium, sodium, uric acid, oxalate, citrate, and creatinine.

You should not change any of your usual eating or drinking patterns when performing this test.
Discard the first urination on the day of the test.
Afterward all urine passed over the next 24 hours is collected, including the first urination on the morning of day two.
A second 24-hour urine collection may be needed to determine if treatment is working or if the first analysis was not conclusive and the doctor suspects a less common stone, such as a cystine or xanthine stone.

Click the icon to see an image of a uric acid urine test.

Urine tests that are used to determine the specific chemical and biological factors causing the stone should be performed about 6 weeks after the attack, since the attack itself may change the levels of such substances, including calcium, phosphate, and citrate. It should be noted that calcium levels in the urine may be abnormal even in many people without stones. In addition, high urinary concentrations of calcium may pose a greater or lesser risk depending on age. (In one 2001 study, middle-aged adults with high urinary calcium concentrations had a much greater risk than older adults with high levels.)

The kidney stones obtained from the urine sample are examined under a microscope. The crystal formations are often specific enough so that the doctor is able to identify the substance causing the stone.

Calcium oxalate crystals are eight-sided, while calcium phosphate crystals tend to have irregular shapes.
Uric acid stones are sometimes described as pear-shaped or diamond-shaped.
Some struvite stones have very specific shapes commonly described as "coffin lids." Struvite crystals may also occur in a formation known as a staghorn, which can be large and damaging to the kidney.

Testing whether urine is acidic or alkaline helps to identify the specific type of stone. The levels of acidity or alkalinity in any solution, including urine, are indicated by the pH scale:

A pH value of 7.0 is neutral.
A solution with a low pH (below 7.0) is acidic. (A low pH favors uric acid and cystine stones.)
A solution with a high pH is alkaline. (A high pH favors calcium phosphate and struvite stones.)

A dipstick test for blood in the urine (called hematuria) is typically performed when patients appear in the emergency room with flank pain (the primary symptom of kidney stones). About a third of kidney stone patients, however, do not show blood in the urine, so other tests may be needed.

Blood Tests for Stone Factors. Blood and urine tests help determine what substances form the crystals. This allows the doctor to determine the appropriate treatment and preventive measures.

Blood tests may help determine blood levels of urea nitrogen, creatinine, calcium, phosphate, and uric acid for patients with known or suspected calcium oxalate stones. Doctors will usually schedule these tests about 6 weeks after the attack, in order to measure these substances when the stone has been passed, and the patient has been stabilized. This is particularly true in patients with recurrent stones.

Parathyroid Tests. Tests to detect parathyroid hormone levels are given if the doctor suspects hyperparathyroidism, based on other signs and symptoms.

Tests for Infection. A test result that shows a high white blood cell count might indicate infection. Such results, however, could be misleading, since the number of white blood cells could also increase in response to the extreme physical stress of a kidney stone attack.

Tests for Metabolic Problems. About half of children with stones have an identifiable metabolic disorder, which increases their risk of stone recurrence five-fold. Experts argue whether tests for metabolic disorders are routinely needed once the stone composition has been determined. Studies suggest the following:

People with recurrent calcium stones have a wide range of irregular blood or urine test results, indicating a variety of possible metabolic disorders. For example, calcium stones in middle-aged women may be due to parathyroid abnormalities.
Calcium phosphate stones most likely result from renal tubular acidosis.
People with non-calcium stones generally have identifiable metabolic disorders.
Determining the stone composition may be sufficient for treatment, and may help avoid unnecessary metabolic tests.

Treatment

When tests show there is a kidney stone, the next step is to determine treatment. The patient should be admitted to the emergency room if they have severe vomiting, fever, or symptoms of infection.

Strong opioid painkillers, such as meperidine (Demerol), are often required for a severe kidney stone attack. However, doctors will usually not give such drugs until they confirm the presence of a kidney stone on an x-ray. In some cases, powerful nonsteroidal anti-inflammatory drugs (NSAIDs) may work just as well as opioids, and they have fewer side effects. However, they do take longer to work.

In about 85% of patients, the kidney stones are small enough that they pass through normal urination, usually within 2 to 3 days. In some cases, a stone may take weeks to months to pass, although pain usually goes away before that.

The patient should drink plenty of water (two to three quarts a day) to help move the stone along, and take painkillers as needed. The doctor usually provides a collection kit with a filter and asks the patient to save any passed stones for testing.

If the stone has not passed in 2 - 3 days, the patient will need additional treatments. In some severe cases, hospitalization may be necessary.

Specific procedures vary depending on the size of the stone or complexity of the situation. Noninvasive procedures are proving to be very beneficial in eliminating stones, and have largely replaced invasive surgeries.

For small stones that are lodged in the lower part of the ureter, ureteroscopy or shock wave lithotripsy are the procedures of choice.
For larger stones, ureteroscopy, percutaneous nephrolithotomy, and shock wave lithotripsy are all potentially useful. The choice of any of these procedures depends on a number of factors, including location of the stone and the presence of any problems that caused the stone in the first place.
In some complicated cases, standard open surgical procedures (called nephrolithotomy) may be required.

See "Other Treatments" section for more information on kidney stone surgery.


Stone Type	Diet and Lifestyle	Medications	Procedures
Calcium Oxalate	Plenty of fluids. (Choose water, lemon juice. Avoid grapefruit, apple, and cranberry juice.) Limit the amount of protein and salt in the diet. Increase fiber. Limit the amount of fats in the diet, particularly in people who have short bowel syndrome. Balance normal calcium intake with potassium- and phosphate-rich foods. Limit the amount of calcium in the diet (only in people who have genetic abnormalities that cause high intestinal absorption of calcium). Limit the amount of foods high in oxalates (only in patients with rare intestinal conditions that cause hyperoxaluria).	Diuretics ("water pills"), Citrate salts, phosphates, cholestyramine.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Uric Acid	Plenty of fluids. (Choose water, blackcurrant juice. Avoid cranberry juice.) Increase calcium intake (be sure well-balanced with potassium and phosphates). Reduce protein and other foods with high-purine content.	Potassium citrate, sodium bicarbonate, allopurinol.	Lithotripsy, uteroscopy, percutaneous nephrolithotomy, open surgery.
Struvite stones	Plenty of fluids (water, cranberry juice). Reduce proteins.	Antibiotics to eliminate any infection. Acetohydroxamic acid (AHA) may be helpful in combination with antibiotics. In some cases, organic acids given through urinary tract.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.
Cystine stones	Very high fluid intake (four quarts a day). Limit the amount of protein in the diet.	Alkalizing agents (such as bicarbonate). Sometimes d-penicillamine, tiopronine, or captopril useful for lowering cystine levels.	May respond poorly to most lithotripsy procedures and require open surgery. Newer procedures may be helpful.

Medications

Diuretics. Diuretics are medicines commonly used to treat high blood pressure and other disorders. They remove fluid and sodium from the body. Low doses of a class of diuretics known as thiazides are sometimes used to reduce the amount of calcium released by the kidneys into the urine. Thiazides include:

Hydrochlorothiazide (Esidrix, HydroDiuril)
Chlorothiazide (Diuril)
Trichlormethiazide (Metahydrin, Naqua)
Chlorthalidone (Hygroton)

However, thiazides also cause potassium loss, which reduces citrate levels and can increase the risk for stones. Patients taking thiazide pills should also take potassium citrate, to prevent citrate loss. Amiloride (Midamor) is a potassium-sparing diuretic, which may be used if a thiazide does not work.

Citrates. Citrate salts are often given to people with calcium oxalate or uric acid stones:

Potassium magnesium citrate is available over the counter. It is proving to be very beneficial in preventing kidney stones. In one study, potassium magnesium citrate reduced the risk for kidney stone recurrence by 85%.
Potassium citrate (K-Lyte, Polycitra-K, Urocit-K) is given as the only treatment to people with normal urine calcium levels. Between 70 - 75% of patients with recurrent stones have ongoing remission (no stone recurrence) with potassium citrate treatment. However, some people cannot tolerate potassium citrate because of side effects (stomach problems).
Magnesium citrate (Citroma, Citro-Nesia) may help people who develop calcium stones from impaired intestinal absorption due to short bowel disease.

None of these products should be used by people with struvite stones, urinary tract infections, bleeding disorders, or kidney damage. Patients who take citrate supplements containing potassium should not take any other medications that either contain this mineral or prevent its loss (such as so-called potassium-sparing diuretics). People with peptic ulcers should avoid citrate supplements, or discuss using non-tablet forms with their doctor.

Phosphates. Phosphates help reduce the breakdown of bone that releases calcium into the bloodstream. They are also involved in the kidney's reabsorption of calcium from the urine.

Phosphate compounds:

Neutral (nonacidic) sodium or potassium phosphate (K-Phos, Neutral, Neutra-Phos) is usually taken four times a day after meals to prevent kidney stones unless otherwise directed by the doctor. Diarrhea is a possible side effect.
Cellulose phosphate (Calcibind) is recommended only for severe hypercalciuria that is associated with recurrent calcium stones and is caused by excessive absorption of calcium from the intestines. However, this drug may increase oxalate levels and decrease magnesium levels, which can lead to different stones. Taking magnesium supplements and reducing dietary oxalates, calcium, and ascorbic acid may help offset these risks. Cellulose phosphate may also cause bloating.

Avoid acidic forms of phosphate, since they increase the risks for both hypocitraturia and hypercalciuria.

Cholestyramine (Questran, Questran Light) is a drug used to reduce cholesterol levels. However, it also binds with oxalate in the intestine, so it is also used to reduce high oxalate levels in urine (hyperoxaluria). The drug usually comes in a powder that is dissolved in liquid.

Bloating and constipation are common side effects of this drug. Cholestyramine also interferes with other medications, including digoxin (Lanoxin) and warfarin, and may contribute to calcium loss and osteoporosis. In order to prevent such interactions, take other drugs 1 hour before, or 4 - 6 hours after, taking cholestyramine.

Long-term use of cholestyramine may cause deficiencies of vitamins A, D, E, and K. Vitamin supplements may be necessary.

Sodium Bicarbonate. Patients whose persistently acidic urine causes uric acid stones may take sodium bicarbonate to reduce urine acidity. Patients taking sodium bicarbonate must test their urine regularly with pH paper, which turns different colors depending on whether the urine is acidic or alkaline. Too much sodium bicarbonate can cause the urine to become too alkaline. This increases the risk for calcium phosphate stones. Patients who need to reduce the amount of sodium they take in (as a result of other medical conditions) should not use sodium bicarbonate.

Potassium Citrate. Potassium citrate, which restores citrate to the urine, is useful for patients with high levels of uric acid in the urine.

Allopurinol. Allopurinol (Lupurin, Zyloprim) is very effective in reducing high levels of uric acid, and may be helpful for patients with uric acid stones. Allopurinol will not prevent calcium stones from forming. There is also a slight risk for the formation of xanthine stones with this drug. Side effects include diarrhea, headache, and fever. More severe complications include blood disorders that may produce fatigue, bleeding, or bruising. The drug may also increase the risk for cataracts.

About 2% of patients experience an allergic reaction to allopurinol that causes a rash. In rare cases, the rash can become severe and widespread enough to be life threatening. Allergic individuals who have experienced only a mild rash to sodium bicarbonate may be able to build up their tolerance for allopurinol by undergoing a desensitization process. In this process, patients start with small doses of allopurinol and gradually increase them, if no reaction develops.

Allopurinol reduces uric acid levels rapidly, so it may trigger an attack of gout in vulnerable people. To prevent this problem, patients taking allopurinol should also take a nonsteroidal anti-inflammatory drug (NSAID) for 2 or 3 months. Aspirin should not be taken, since it increases uric acid levels. Patients should discuss the appropriate NSAID choice with their doctor.

Before patients can receive any medical treatment for struvite stones, they must have surgery to completely remove the stones.

Antibiotics for Eliminating Infection. Persons with struvite stones receive ongoing treatment with antibiotics to keep the urine free of the bacteria that cause urinary tract infections. Careful follow-up and urine testing is extremely important. A high-pH urine indicates low acidity and an increased risk of infection.

Acetohydroxamic Acid (AHA). Acetohydroxamic acid (AHA or Lithostat) is beneficial when used with long-term antibiotics. AHA blocks enzymes that bacteria release, and has been effective in preventing stones even when bacteria are present. Side effects, however, can be severe. The drug reduces iron levels in the body, so anemia is a common problem. Patients may need to take iron supplements. Other side effects include nausea, vomiting, depression, anxiety, rash, persistent headache, and, rarely, small blood clots in the legs.

Experts recommend this drug only for patients with healthy kidneys who have chronic diseases caused by specific struvite-causing organisms.

Patients taking this medicine should avoid alcohol. Pregnant women should not take acetohydroxamic acid.

Organic Acids. Medical treatments to dissolve stones may be useful in patients who do not respond to other medications, or in combination with surgeries. Acidic urine dissolves struvite stones, so the doctor may wash the urinary tract with a solution of organic acids (such as Renacidin). Candidates for such washes must have sterile urine (no bacteria or other organisms in the urine) and healthy kidney function. In surgical patients, the wash is performed 4 or 5 days after the operation. The wash starts with saline (salt solution) for 1 - 2 days and, if there are no problems, the organic acid solution follows for another 1 or 2 days, until all stones dissolve. Regular urine tests are necessary to ensure that the bacteria do not return.

Aluminum Hydroxide Gel. An aluminum hydroxide anti-acid gel may reduce phosphate levels that are important in struvite stone formation, but it has a long-term risk of causing aluminum toxicity. Long-term reduction of phosphorus can also increase the risk for calcium oxalate stones. Experts recommend limiting phosphorus through a low-protein diet, rather than through the use of this gel.

The first-line treatment for cystine stones is increasing the alkalization of urine so the stones can dissolve. If alkalization fails, drug treatments may include d-penicillamine, alpha-mercaptopropionylglycine (tiopronine), or captopril. These medications lower cystine concentration.

Patients with cystine stones must drink plenty of fluids, much more than patients with other stones. The patients should drink at least four quarts of water over a 24-hour period.

Other Treatments

Surgery is usually needed if the stone is too large to pass on its own, if there are signs that the stone is growing, or if the stone is blocking the urine flow and causing a urinary tract infection or kidney damage.

Until recently, the procedure to remove a stone was a very painful, major surgery, requiring 4-6 weeks of recovery. Today, treatments for stones are much less invasive. Major surgery is performed in less than 2% of patients.

Stone removal procedures:

Extracorporeal shock wave lithotripsy (ESWL) is used for small stones (less than one centimeter, or slightly less than half an inch) that occur in the upper part of the ureter and do not pass on their own. One study indicated lithotripsy might even be safe and effective for patients whose stones are associated with malformed kidneys, although such patients are at higher risk for stone recurrence and should be carefully monitored.
Percutaneous nephrolithotomy (PNL). PNL can be used for very large stones in the upper urinary tract, when ESWL fails, for kidney transplant patients, or when the kidneys or surrounding areas are malformed. PNL is the preferred procedure for drug-resistant cystine stones, which are usually also resistant to shock wave therapy.
Ureteroscopy. For stones in the lower tract, ureteroscopy is generally the best procedure, although lithotripsy is also usually feasible and patients ordinarily prefer it.
Standard open surgery (nephrolithotomy) may be required if any of these procedures fail or are not appropriate, or in special cases, such as when the patient is very obese.

Most procedures are more effective for calcium and uric acid stones and less effective for struvite and cystine stones, although new techniques may be improving their effects on all stones.

Extracorporeal shock wave lithotripsy (ESWL) is a technique that uses sound waves (ultrasound) to break up simple stones in the kidney or upper urinary tract. ("Extracorporeal" means "outside the body," and "lithotripsy" means stone-breaking.) ESWL is not used for cystine stones. The procedure generally does not work for stones larger than three centimeters in diameter (which is slightly over an inch). There are several variations of ESWL. The following is a typical procedure:

Most ESWL procedures use some anesthesia, although they are often done on an outpatient basis.
The patient is positioned in a water bath. (In some procedures the patient lies on a soft cushion.)
The procedure uses ultrasound to generate shock waves that travel through the skin and body tissues until they hit the dense stones. (The doctor pinpoints the stone during treatment by using x-rays or ultrasound.)
The shock waves crush the stones into tiny sand-like pieces that usually pass easily through the urinary tract.
The shattered stone fragments may cause discomfort as they pass through the urinary tract. In such cases, the doctor may insert a small tube called a stent through the bladder into the ureter to help the fragments pass. This practice, however, has not proved to speed up passage of the stones in most cases and is not used routinely.

Extracorporeal shock wave lithotripsy (ESWL) is a procedure used to shatter simple stones in the kidney or upper urinary tract. Ultrasonic waves are passed through the body until they strike the dense stones. Pulses of sonic waves pulverize the stones, which are then more easily passed through the ureter and out of the body in the urine.

Success rates of ESWL range from 50 - 90%, depending on the location of the stone and the surgeon's technique and level of experience. Recovery time is short, and most people can resume normal activities in a few days.

Complications. Complications may include the following:

The most common complication is blood in the urine, which lasts for a few days after treatment. To reduce the chances of bleeding, doctors usually tell patients to avoid taking aspirin and other NSAIDs, which can promote bleeding, for 7 - 10 days before the treatment.
Bruising and minor discomfort due to the shock waves are common in the back or abdomen.
Sometimes the stone does not completely break up with one treatment, and additional treatments may be required. Inability to pass stone fragments may also be a particular problem in patients who have cysts or other kidney problems.
Higher risk for diabetes later. A 2006 study published in the journal Urology found that 17% of patients who received shock-wave lithotripsy developed diabetes later in life. The diabetes risk was related to the number and intensity of shocks.
Higher risk for hypertension (high blood pressure). The same study that linked ESWL to diabetes also showed that people who received shock-wave lithotripsy treatment were 47% more likely to develop high blood pressure than those who had their stones treated without surgery.

ESWL appears to be safe for children, although a 2001 study reported temporary damage in the kidney tubules after treatment. It is unclear if this complication has any long-term consequences. Experts recommend using the least amount of shocks and impact possible in young people. If more than one treatment is needed, there should be a waiting period of at least 15 days between treatments.

Percutaneous nephrolithotomy may be used when ESWL is not available or effective (such as if the stone is very large, in an inaccessible location, or is a cystine stone). It is also preferred over ESWL for stones that have remained in the ureter for more than 4 weeks.

It is more effective than ESWL for patients with severe obesity, and appears to be safe for the very elderly and the very young. Success rates are nearly 98% for kidney stones and 88% for ureteral stones. They may vary by the technique used and the specific patients. For example, success rates are slightly lower in children, although the procedure can be done safely in young patients. Long-term effects are unknown.

A typical procedure is as follows:

The surgeon makes a tiny incision in the back and creates a tunnel directly into the kidney.
The surgeon then inserts an instrument called a nephroscope through the tunnel.
The stone is located and removed. If it is large, it is destroyed using ultrasound, lasers, or other devices. The surgeon then removes the fragments. An advantage of percutaneous nephrolithotomy over ESWL is that the surgeon is able to remove the stone fragments directly, instead of relying on their natural passage from the kidney.
Generally, patients stay in the hospital for 5 or 6 days and may need a small device called a nephrostomy tube left in the kidney during the healing process.

Devices Used to Destroy Stones. For large stones, some type of energy-delivering device may be needed to break the stone into small pieces. They are referred to as intracorporeal lithotripsy devices (meaning stone breakers within the body). The device may be one of the following:

Ultrasound is currently the preferred method. It results in a stone-free rate of 94%. A rigid nephroscope delivers the ultrasound waves.
Pneumatic (compressed air) lithotripsy uses a probe that comes in direct contract with a stone. Compressed air causes a piston to collide rapidly with the probe, and the result is a "jackhammer" action against the stone, causing the stone to break up. This method, however, can send stone fragments into other parts of the urinary tract.
A more recent device uses a combination pneumatic probe and ultrasound, with stone-free rates of 80 - 89%. It may prove to be superior to ultrasound alone and be effective against stones of all types.
The holmium laser literally melts the stones and destroys up to 100% of stones of any composition. It uses a flexible nephroscope and has an excellent safety record. It should be used sparingly, however, with particular caution against large uric acid stones until more is understood about its effect. Another device, the erbium: YAG laser, although showing promise in lithotripsy, is not currently practical.

Complications. Complication rates are about 3%. Major complications occur in about 1% of cases. These complications may include scarring of the tissue, but studies indicate that it does not impair kidney function, even if the patient requires repeat surgery. There is also a risk for blood loss during and after the procedure, which, in some cases, can be significant.

Because the procedure requires large volumes of fluid, fluid overload is a potential problem, particularly in children or patients with heart disease.

In some cases, infection may result. Other complications may include a collapsed lung and injuries to areas outside the kidney (but within the operative area), such as the abdomen or chest.

Ureteroscopy may be used for stones in the middle and lower ureter. With the arrival of smaller instruments, this procedure can be done successfully in children as well. The procedure involves the following:

The patient receives a general anesthetic, though no incision is required for the procedure.
The surgeon passes a small fiberoptic instrument called a ureteroscope through the urethra and bladder into the ureter.
The surgeon locates the stone or stones.
The surgeon can remove smaller stones by grasping them with small forceps. A laser or pneumatic device breaks up large stones.
The surgeon may decide to leave a small tube, or stent, in the ureter for a few days after treatment, to help the lining of the ureter heal.

Complication rates range from 10 - 20%, with major problems occurring in up to 6% of patients. In some cases, large stones are not broken up into small enough pieces. This can result in blockage of the urinary tract and possible kidney damage.

Imaging tests, such as ultrasound or spiral CT, are useful within 3 months to check for residual stones, and a second procedure may be required. The risk of complications is highest when the procedure is performed by less experienced surgeons, or if stones are found in the kidney. The risk for perforation of the ureter increases the longer the procedure takes.

Open surgery involves incisions through the patient's flank and into the kidney. The surgeon will cool the kidneys using ice. X-rays during the procedure help locate the stone. At the beginning of the surgery, the surgeon will isolate the arteries supplying the kidneys, ensuring they are not harmed during the surgery. The surgeon will then locate and remove the stone. The surgeon will also correct any blockage in the affected area. The surgery, called nephrolithotomy, is very invasive and is restricted to the following:

Patients with very large or complex stones that cannot be removed using less invasive measures
Very obese patients

Some centers report success with extracorporeal shock wave lithotripsy, however, in patients who would normally be nephrolithotomy candidates. Therefore, even these patients should discuss other options with their surgeon.

The procedure is not appropriate for patients with:

Bleeding or clotting disorders
Untreated widespread infection
Severe and chronic kidney insufficiency (unless removing the stone will improve kidney function)

Complications

Between 70 - 90% of crystals remain tiny enough so that they can travel through the urinary tract and leave the body in the urine without being noticed. When they do cause symptoms, however, kidney stones have been described as one of the most painful disorders to afflict humans. The pain they cause is sometimes called renal colic. ("Renal" means "kidney.")

Obstruction and Infection. Although kidney stones often lead to obstruction (blockage) of the urinary tract, the blockage is usually temporary and causes no lasting damage. In some cases, however, particularly if the obstruction progresses with no symptoms, infection may occur, which can be serious and need immediate attention.

Kidney Failure. It is very rare for kidney stones to cause kidney failure, although some people have risk factors that make them more vulnerable to this serious complication. Risk factors include the following:

Very frequent recurrences (such as in people with cystine stones or other inherited forms of kidney stone disorders)
Accompanying episodes of urinary tract infections with obstruction, a particular risk with struvite stones
A history of multiple urologic procedures for kidney stones
Greater size of the kidney stone gravel

Without preventive treatment, calcium stones recur in 10% of patients within a year of the first attack, and in half of patients within 5 - 7 years. Individual risk for recurrence, however, varies depending on the stone and the underlying condition. For example, a 15-year-old with inherited cystine stones has a very high risk for recurrence, while a middle-aged man with a first calcium oxalate stone has a good chance of never passing another.

Prevention

All individuals who have experienced kidney stones should take some specific preventive measures to prevent recurrence. The following are some general observations:

The most important dietary recommendations for reducing the risk for calcium stones are increasing fluid intake, restricting sodium, and reducing protein intake.
A lower risk for calcium stones is also associated with higher potassium intake.
A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. (Increasing calcium alone may pose a modest risk for stones.)
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine, which promote stone formation.

Because different kidney stone types may require specific dietary changes, patients should work with their doctors to develop an individualized plan. It is important to note that nutritional considerations are very important in preventing recurrence, and patients should be vigilant in complying with the proper diet.

Good voiding habits, particularly frequent urination, are important. Therefore, of all the preventive recommendations, drinking enough fluids is the most important guideline for people with any type of kidney stones.

In general, patients with calcium or uric acid stones should drink at least 10 full glasses of fluid each day (at least half should be water). This includes one with each meal and drinking fluids at night, even if it means getting up from sleep. Fluid intake should produce at least two and a half quarts of urine each day.
To prevent cystine stones, patients should drink even more water -- over a gallon, or 16 8-ounce cups, every day. Patients should drink this amount at regular intervals throughout the night and day.

In all cases, patients need more fluid after exertion and during times of stress. If they drink enough, the urine should be pale and almost watery, not dark and yellow.

Water. Although water is best, it may vary depending on its source. Variations in water itself may have different impacts. One study reported that drinking hard tap water increased urinary calcium concentration by 50% compared to soft bottled water. On the other hand, mineral water containing both calcium and magnesium may reduce several risk factors for both calcium and uric acid stone formation.

Juices and Specific Effects. Other beverages have various positive or negative effects, depending on the type of stone:

Lemon Juice: Drinking one-half cup of pure lemon juice (enough to make eight glasses of lemonade) every day raises citrate levels in the urine, which might protect against calcium stones. (While orange juice also increases citrate levels, it does not lower calcium and it raises oxalate levels. Therefore, it is not recommended.)
Cranberry and Apple Juice: Apple and cranberry juice contain oxalates, and both have been associated with a higher risk for calcium oxalate stones. Cranberry juice has properties that may increase the risk for both calcium oxalate and uric acid stones. On the other hand, cranberry juice helps prevent urinary tract infections and so may be helpful for reducing the risk for struvite and brushite stones. (These stones are far less common, however.)
Black Currant Juice: In one study, black currant juice reduced urine acidity and was associated with protection against uric acid stones.
Grapefruit Juice: A number of studies have found a risk for stones from drinking grapefruit juice. In one study, just one 8-ounce cup of grapefruit juice per day increased the risk for forming stones by 44%.

Other Beverages and Their Effects on Stone Formation.

Soft Drinks. Patients with stones should avoid cola drinks, since they can severely reduce citrate levels in the urine. Many soft drinks contain phosphoric acid, which increases the risk for stones. Some research shows that drinking one quart (less than three 12-ounce cans) of soda per week may increase a person's risk of developing stones by 15%.
Alcohol. Wine may be protective against kidney stones. A study conducted in Finland, suggests that the risk of developing stones also decreases with beer consumption. However, it is important to remember that beer is high in oxalates. Beer and other alcoholic beverages also contain purines, which may increase the specific risk for the less common uric acid stones in susceptible people. Binge drinking, in any case, increases uric acid and the risk for stones.
Coffee and Tea. Some research reported a lower risk for stones in people who drink tea and both regular and decaffeinated coffee.

A long-term 2002 study followed men with calcium oxalate stones and high levels of urinary calcium. The study found that a low-sodium, low-protein diet, containing normal levels of calcium, dramatically reduced the recurrence of stones compared to a diet that was simply low in calcium.

Salt Restriction. Because salt intake increases the amount of calcium in urine, patients with calcium stones should limit their sodium intake. Sodium may also increase levels of urate, the crystalline substance that can trigger formation of recurrent calcium oxalate stones. Although the relative contribution of limiting sodium intake has not been confirmed, some researchers believe that restricting sodium along with increasing fluid intake is the most important dietary measure for preventing stones.

Protein Restriction. Protein increases uric acid, calcium, and oxalate levels in the urine, and reduces citrate levels. Diets high in protein, particularly meat protein, have been consistently connected with kidney stones. (Meat protein has a higher sulfur content and produces more acid than vegetable protein.) A 2002 study of those following a high-protein, low-carbohydrate diet (such as the Atkins diet, for example), found dramatically increased levels of urinary uric acid and calcium after just several weeks. These effects put patients at higher risk for not just kidney stones, but possibly osteoporosis as well. According to Swiss studies, about a third of people at risk for calcium stones may have a sensitivity to meat proteins that causes mild hyperoxaluria.

Whether restricting meat protein alone has any protective value without restricting sodium as well is unknown. Most studies to date have found no difference in stone development between people with low and normal meat protein diets over four years. A 2000 study reported that only dramatic reductions in meat protein had any preventive effect against stone recurrence.

Although the precise role of dietary protein in kidney stones needs further clarification, it is reasonable for everyone to consume meat protein in moderation. People with struvite stones, who need to reduce phosphates in their diets, should also cut down on proteins.

Calcium from Foods. Dietary calcium recommendations for kidney stone prevention need to be determined on an individual basis. A doctor will suggest calcium guidelines based on a patient's age, gender, body size, and type of stone. Most studies indicate that dietary calcium (found in milk, yogurt, and cheese) protects against many types of calcium oxalate stones. Large studies of both men and women found that those with the highest intake of calcium from foods had a much lower risk for stones than those who had little calcium in their diets. A diet containing a normal amount of calcium, but reduced amounts of animal protein and salt, may protect against stones better than a low-calcium regimen. However, calcium metabolism changes as people age. Some studies suggest that a high calcium intake protects against kidney stones in men younger than age 60, but not in older men.

Dietary calcium may actually bind the oxalate in foods, preventing it from being absorbed into the blood and excreted into the urine. In a normal healthy diet, dairy products supply almost 80% of the daily calcium requirement. For people who have calcium stones associated with resorption (the breakdown of bone that releases calcium into the bloodstream), limiting calcium intake could cause further bone loss.

Calcium Supplements. Evidence on calcium supplements is mixed, although in general many studies suggest that they reduce oxalate levels and so help prevent calcium oxalate stones. One study suggested that taking 500 mg of calcium supplements a day regularly may "reprogram" the intestines to absorb less calcium and may therefore be protective. Experts generally agree that calcium supplementation within dosage recommendations (about 1,200 mg per day) remains safe. In one study, however, women who took calcium supplements had a 20% higher risk for stones. Research indicates that dosages of calcium above 2,000 mg per day are clearly associated with the formation of stones. Some experts speculate that this higher risk may occur because supplements are often taken in the morning, either without food or with breakfast, which is typically low in oxalates. Taking supplements with later meals may not produce the same risk.

Calcium Restriction in Certain Cases. Some patients, such as those whose stones are caused by genetic defects in which the intestine absorbs too much calcium, may need to limit calcium intake. More studies are needed to define this group precisely.

Fiber may be beneficial for people with kidney stones. In addition, some fiber-rich foods may contain compounds that help protect against kidney stones. A wide variety of high-fiber plant foods contain a compound called phytate (also called inositol hexaphosphate, InsP6, or IP6), which appears to help prevent crystallization of calcium salts, both oxalate and phosphate. Phytate is found in legumes and wheat and rice bran. (Soybeans are also rich in phytate but they are also very high in oxalates, so the overall effects of soy on kidney stones are not clear.)

A high intake of purines can increase the amount of uric acid in the urine. Those at risk for uric acid stones should reduce their intake of foods and beverages that contain purines. These include beer and other alcoholic beverages, anchovies, sardines, yeast, organ meats (such as liver and kidneys), legumes (including dried beans, peas, and soybeans), mushrooms, spinach, asparagus, cauliflower, and poultry.

Most people with calcium oxalate stones should not avoid oxalate-rich foods unless the doctor specifically recommends a restrictive diet. Oxalate binds with calcium in the intestine, which may actually reduce calcium absorption. Some studies, in fact, indicate that eating foods containing oxalates and calcium together may reduce the risk of stones. Most of the foods that contain oxalates are very important for good health. Limiting oxalates may be particularly harmful in people with bowel disorders marked by malabsorption.

Foods high in oxalic acid include beets, soy, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard.
Foods containing moderate amounts of oxalates include beans (green and wax), blackberries, blueberries, carrots, celery, coffee (roasted), concord grapes, currants, dandelion greens, endive, gooseberries, lemon peel, okra, green onions, oranges, green peppers, black raspberries, strawberries, and sweet potatoes.

Certain fats may play a beneficial or harmful role in specific cases of kidney stones.

Restricted Fats in Patients with Stones Associated with Bowel Disease. Patients who have stones associated with short-bowel syndrome should eat foods with lower amounts of fats and oxalates. If patients with short-bowel syndrome eat too much fat, calcium may bind to unabsorbed fat instead of to oxalates. This increased oxalate levels, resulting in increased risk of stone formation.

Fish Oil. Omega-3 fatty acids, found in oily fish like mackerel, salmon, and albacore tuna, have many health benefits, but the most current evidence suggests they do not help prevent kidney stones. A 2005 study of over 200,000 adults found that increased omega-3 fatty acid intake did not reduce kidney stone risk.

Vitamin B6. Vitamin B6, or pyridoxine, is used to treat people with primary hyperoxaluria, a severe inherited disorder. Patients should not try to treat themselves with vitamin B6. Very high doses (500 to 2,000 mg daily over long periods) can cause nerve damage, with loss of balance and numbness in the feet and hands. Food sources of vitamin B6 include meats, oily fish, poultry, whole grains, dried fortified cereals, soybeans, avocados, baked potatoes with skins, watermelon, plantains, bananas, peanuts, and brewer's yeast.

Vitamin C. Ascorbic acid (vitamin C) may change in the body to tiny crystals, called oxalates. These crystals do not dissolve. People with hyperoxaluria (too much oxalate in the urine) should avoid vitamin C supplements. Even for men with normal oxalate levels, higher consumption of vitamin C (more than 1,000 mg a day) may increase kidney stone risk.

Magnesium and potassium may help reduce the risk for kidney stones in men.

Because of an association between stress and kidney stones, relaxation and stress management techniques may also be beneficial.

Dietary Considerations. People with kidney stones appear to be more sensitive to certain foods than people who do not form kidney stones. Therefore, vulnerable people should make specific changes in their diet. They should work with their doctors to develop a dietary plan that fits their individual situation. Drinking plenty of fluids is important for preventing recurrence of any kidney stone.

Indications for Drug Treatments. If dietary treatments fail, drug therapy may be helpful. A number of drugs are available to prevent recurrences of calcium oxalate and other stones. Medications that inhibit the formation of stones include allopurinol, thiazide, potassium citrate, and potassium-magnesium citrate. In addition, drug treatments can sometimes also help prevent other complications related to stones, such as osteoporosis.

Correcting Underlying Conditions Known to Cause Kidney Stones. It is also important to treat and correct, if possible, any underlying disorder that may be causing stones to form. Such disorders include distal renal tubular acidosis, hyperthyroidism, sarcoidosis, and certain cancers. To prevent calcium stones that form in hyperparathyroid patients, a surgeon may remove the affected parathyroid gland (located in the neck). In most cases, only one of the glands is enlarged. Removing it ends the patient's problem with kidney stones.

Resources

www.kidney.niddk.nih.gov -- National Kidney and Urologic Diseases Information Clearinghouse
www.urologyhealth.org -- American Urological Association
www.kidney.org -- National Kidney Foundation
www.ohf.org -- Oxalosis and Hyperoxaluria Foundation

References

Cameron MA, Maalouf NM, Adams-Huet B, Moe OW, Sakhaee K. Urine composition in type 2 diabetes: predisposition to uric Acid nephrolithiasis. J Am Soc Nephrol. 2006 May;17(5):1422-8. Epub 2006 Apr 5.

Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164(:885-891.

Finkielstein VA. Strategies for preventing calcium oxalate stones. CMAJ. 2006;174(10); 1407-1409.

Krambeck AE, Gettman MT, Rohlinger AL, Lohse CM, Patterson DE, Segura JW. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of followup. J Urol. 2006;175(5):1742-7.

Sinha MK, Collazo-Clavell ML, Rule A, et al. Hyperoxaluric nephrolithiasis is a complication of Roux-en-Y gastric bypass surgery. Kidney International. 2007;72:100-107.

Straub M, Hautmann RE. Developments in stone prevention. Curr Opin Urol. 2005;15(2):119-126.

Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol. 2004;15(12):3225-3232.

Taylor EN, Stampfer MJ, Curhan GC. Fatty acid intake and incident nephrolithiasis. Am J Kidney Dis. 2005;45(2):267-274.

Taylor EN, Stampfer MJ, Curhan GC. Obesity, weight gain, and the risk of kidney stones. JAMA. 2005;293(4):455-462.

Taylor EN, Stampfer MJ, Curhan GC. Diabetes mellitus and the risk of nephrolithiasis. Kidney Int. 2005 Sep;68(3):1230-5.

Wasserstein AG. Nephrolithiasis. American Journal of Kidney Diseases. 45(2);2005:422-28.

Review Date:
7/24/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Ulcerative colitis

FitSugar — Wed, 08 Oct 2008 17:35:30 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approval

In 2007, the FDA approved LIALDA, the first once-daily mesalamine pill for treating mild-to-moderate ulcerative colitis. Other types of mesalamine need to be taken several times a day.

Genetic Research

Scientists have made an important discovery by identifying a gene associated with inflammatory bowel disease. In a 2006 paper published in Science, researchers announced that variations in the interleukin-23 receptor (IL23R) gene can either increase or decrease the risk for developing ulcerative colitis and Crohn’s disease.

Clostridium Difficile

Patients with ulcerative colitis are particularly susceptible to Clostridium difficile, a nasty bacterial infection that causes severe diarrhea. According to several 2007 studies, C. difficile is becoming increasingly common among these patients. Experts recommend that doctors monitor patients with ulcerative colitis for signs of this difficult-to-treat infection.

Pregnancy

Women with inflammatory bowel disease have twice the risk of pregnancy complications as healthy women, according to a 2006 review in Gut. Premature birth, low birth weight, and birth defects are among the complications. Active flares of disease during pregnancy especially increase the risks for problems.

Infliximab (Remicade)

Infliximab (Remicade) is helpful for promoting remission and healing in patients with moderate-to-severe ulcerative colitis who have not responded to other drugs, according to a 2006 review in the Cochrane Database.
Infliximab works by blocking the effects of tumor necrosis factor (TNF), a substance that plays a role in inflammatory diseases. Infliximab is the only biologic drug approved for treatment of ulcerative colitis. Researchers are studying other types of biologic drugs as well.
According to a 2007 consensus statement from the American Gastroenterological Association, infliximab should be used only for patients who have not been helped by other drugs, such as immunosuppressants and corticosteroids. It is not recommended as a first-line treatment for ulcerative colitis.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis
Crohn's disease

Some evidence suggests that they are part of a biologic continuum, but at this time they are considered distinct disorders with somewhat different treatment options. The basic distinctions are location and severity. As many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines that is usually confined to the ileum, the terminal portion of the small intestine. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other inflammatory bowel diseases have been linked with an increased risk of colorectal cancer.

Ulcerative Colitis. Ulcerative colitis occurs only in the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and usually diminishes higher in the colon. It is sometimes divided into one of four categories depending on the location of the disease:

Click the icon to see an image of the structure of the colon.

Proctitis. Disease only in the rectum (the lowest part of the large intestine that connects with the anus). Constitutes about 30% of cases.
Proctosigmoiditis. Disease in the rectum and sigmoid (the next portion of the intestine leading up from the rectum). Constitutes about 30% of cases.
Left-Sided Colitis. Disease in the left side of the large intestine. Constitutes about 40% of cases.
Pancolitis. Disease in entire colon. Very uncommon.

Click the icon to see an image of the types of ulcerative colitis.

In most patients the location of the disease does not change, but as many as 30% of patients with proctitis or proctosigmoiditis will experience some progression.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, which is sometimes referred to as the ileocecal region. Crohn's disease less frequently occurs in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon, form a string of contiguous ulcers in one part of the colon, or develop as multiple scattered clusters of ulcers skipping healthy tissue in between. [See In-Depth Report #103: Crohn's disease.]

The gastrointestinal (GI) tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

Small Intestine. The small intestine, despite its name, is the longest part of the gastrointestinal tract and is about 20 feet long. Food that passes from the stomach into the small intestine first passes through three parts:

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Large Intestine. Undigested material, such as plant fiber, is passed to the large intestine, mostly in liquid form. The large intestine is approximately 6 feet long and is the final portion of the digestive tract. It follows the small intestine and includes the cecum, the appendix, the colon, and the rectum, which extends to the anus.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections:

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they pass through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the small intestine.

Click the icon to see an image of the large intestine.

Causes

Inflammatory bowel disease (IBD) can have many causes. Often, genetic problems in the intestine allow viruses or bacteria to trigger an immune response that causes inflammation and injury in the intestines. In IBD, the defense systems appear to be impaired, either from defects in the mucosal lining that provides a barrier in the intestine or an inability to make repairs after injury.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

Lymphocytes include two subtypes known as T cells and B cells. Both types of cells are designed to recognize foreign invaders (antigens) and to launch an offensive or defensive action against them:

B cells produce antibodies, substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two-fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T Cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appears to occur in inflammatory bowel disease (IBD), although each disorder has a different balance:

Patients with ulcerative colitis favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These proteins affect mostly mucosal areas in the intestine.
Research indicates that Crohn's disease patients have increased activity in TH1 cells, which activates interleukin-2 (IL-2) and interferon-gamma. These substances affect intestinal cells. Tumor necrosis factor may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs. Interleukin 6 inhibits a natural process called apoptosis,in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Adhesion Molecules. Increased levels of certain molecules called E-selectin and intercellular adhesion molecule-1 (ICAM-1) also appear to play a major role in the inflammatory process by causing damaging immune factors to accumulate on intestinal cells.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. Such increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Although the causes of inflammatory bowel disease are not yet known, genetic factors certainly play some role. Between 10 - 20% of people with ulcerative colitis have family members with the disease. Several identified genes and chromosome locations play a role in the development of ulcerative colitis, Crohn's disease, or both. Genetic factors appear to be more important in Crohn's disease, although there is evidence that both conditions have some genetic defects in common.

In 2006, scientists identified variations in the interleukin-23 receptor (IL23R) as an important genetic link to both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the injurious processes that lead to inflammatory bowel disease.

Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. However, according to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD. In addition, studies conclusively report that the measles, mumps, and rubella (MMR) vaccine does not cause Crohn’s disease, ulcerative colitis, or autism.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles. It is important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis (UC)	Crohn's Disease (CD)
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal bleeding	Blood is almost always present in stools. It may be readily visible or visible using only a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Hallmark symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 -20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms of CD.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

Complications

Surgical removal of the colon is the only cure for ulcerative colitis, but the disease varies greatly in severity. In one 10-year study, 87% of patients went into complete remission after a single attack, and only 8% developed a chronic persistent condition. Mortality rates were about the same as in the general population, although they were higher in patients with UC with severe initial attacks or extensive disease. Surgical and medical treatments have complications of their own that can be very severe.

Ulcerative colitis is considered mild if a patient has the following symptoms:

Four or fewer bowel movements a day
Only occasional blood in the stool
A normal temperature and pulse rate
Normal hemoglobin or red blood cell count
No abnormalities observed on x-rays of the colon.

Ulcerative colitis is considered serious if the following symptoms are present:

More than six movements a day
Frequent-to-persistent blood and mucus in the stool (in serious cases, stool is liquid and looks like anchovy sauce)
Fever
A rapid pulse
Anemia
Abnormal x-rays of the colon
Tenderness in the abdomen when pressed, with possible distention

Malabsorption and Malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition typically develops rapidly after the condition has been present for some time.

Toxic Megacolon. Toxic megacolon is a serious complication that can occur if inflammation spreads into the deeper layers of the colon. In such cases, the colon enlarges and becomes paralyzed. In severe cases, it may rupture, which is a life-threatening event needing emergency surgery. Symptoms include weakness and abdominal pain and bloating. You may be disoriented or groggy. X-rays are needed to confirm the diagnosis, but barium enemas and colonoscopies should not be performed. Medications used for pain and diarrhea, such as opiates and drugs that reduce spasms of the colon, may increase the risk of toxic megacolon. People with ulcerative colitis have a higher than normal risk, although this is still not common. Its incidence is decreasing with treatment advances.

Toxic megacolon is characterized by extreme inflammation and distention of the colon. Common symptoms are pain, distention of the abdomen, fever, rapid heart rate, and dehydration. This is a life-threatening complication that requires immediate medical treatment.

Bleeding. Bleeding due to ulcers in the colon is a common complication of UC. It can increase the risk for anemia. In some cases, bleeding can be massive and dangerous, requiring surgery.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

Colorectal Cancers. Patients with ulcerative colitis have a higher than normal risk for cancers of the colon and rectum. About 5 - 8% of patients with ulcerative colitis will develop colorectal cancer within 20 years of their ulcerative colitis diagnosis. The risk of colorectal cancer increases with the duration and severity of the ulcerative colitis condition. The presence of inflammatory polyps (pseudopolyps) more than doubles the risk. Some research suggests that anti-inflammatory drugs, such as 5-ASA, may help reduce the risk of cancer. Doctors also advise that patients with ulcerative colitis receive regular (every 1 - 3 years) colonoscopy exams to help screen for cancer. According to a 2006 study, patients with ulcerative colitis who are diagnosed with colorectal cancer have a worse prognosis, and poorer survival, than those without ulcerative colitis. [See In-Depth Report #55: Colon and rectal cancers.]

Click the icon to see an image of the colonoscopy procedure.

People with inflammatory bowel disease (IBD) have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Asthma. According to a 2005 study, people with IBD are 1.5 times more likely to have asthma than people without IBD. Of all the conditions that can accompany IBD, asthma is the most common. People with IBD are also at increased risk for bronchitis and other lung inflammations.

Eyes. Inflammation in parts of the eye is a common complication. Retinal disease, including detachment can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints.

Bones. Low body weight and calcium loss from corticosteroids contribute to osteoporosis (bone loss). However, ulcerative colitis itself causes less bone loss than Crohn’s disease.

Click the icon to see an image of osteoporosis.

Heart. People with IBD have more than three times the risk of developing pericarditis (inflammation of the sac enclosing the heart) than healthy people

Anemia. People with ulcerative colitis have a higher than normal risk for anemia.

Liver and Gallbladder Disorders. People have a higher than average risk for mild but not severe liver abnormalities. There is a higher risk (although rare) for primary sclerosing cholangitis, which is persistent inflammation of the bile duct that can later cause serious obstruction.

Skin Disorders. Patients with ulcerative colitis have a higher risk for skin disorders and may experience ulcer eruptions called pyoderma gangrenosum that heal in the center and spread.

Thromboembolism (Blood Clots). People with ulcerative colitis are at higher risk for blood clots, especially in the legs and pelvic area.

Click the icon to see an image depicting a thrombus.

Kidney Disorders. People with ulcerative colitis have a higher than normal risk for kidney stones.

Click the icon to see an image of kidney stones.

Lung Involvement. Lung involvement may develop but it can progress for years without symptoms.

Mouth Sores. There is a slightly higher than average risk for mouth sores and infections in people with ulcerative colitis , but they are uncommon and lower than those with Crohn's disease.

Delayed Growth and Development in Children. Children with ulcerative colitis are at slightly higher than average risk for delayed growth, but their risk is lower than the risk is for people with Crohn's disease.

Fertility. Fertility rates in women are close to normal, but ulcerative colitis surgery can increase the risk for infertility. Prematurity rates are high with both types of IBD.

Hodgkin's Disease. Patients with ulcerative colitis may be at higher risk for Hodgkin's disease, according to a 2000 study. The risk of other cancers was not increased, however.

Menstrual Problems in Women. Menstrual problems are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment of side effects and complications of the diseases, such as fistulas.

Pregnancy. Inflammatory bowel disease doubles the risk of pregnancy complications. According to a 2007 review, women with inflammatory bowel disease are nearly twice as likely to give birth prematurely. Children born to mothers with this disease are more than twice as likely to be below normal weight and to have birth defects. If a woman experiences active bouts of disease during the course of her pregnancy, her risk for complications increases.

Neurologic Factors. Inflammatory bowel disease has been associated with neurologic complications, including a higher risk for dementia, movement disorder, and stroke. People with IBD have a higher risk for developing multiple sclerosis and inflammation of the optic nerve (optic neuritis).

Emotional Factors. The emotional consequences of ulcerative colitis cannot be overestimated. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. ulcerative colitis takes a serious toll on work, family, and social activities. According to a 2005 survey, 40% of patients report incapacitating symptoms at least 180 days per year. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD). Crohn's disease was once thought to be far less common than ulcerative colitis, but the two conditions are now estimated to occur about equally. The incidence may vary depending on gender, age, and geography:

Men and women have equal risk for ulcerative colitis.
IBD is diagnosed most often in young people ages 10 - 19, but it can occur at any age. A smaller peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10.
Ulcerative colitis is most common among people of European descent. People of African descent have a lower incidence than Caucasians. Low incidence regions include Asia and South America. Ethnically, Ashkenazi Jewish people have a particularly high risk.
Ulcerative colitis may disproportionately affect people of higher socioeconomic classes, but evidence for this is inconclusive.

Smoking. Smokers have lower than average rates of ulcerative colitis (but higher than average rates of Crohn's disease). Some patients with ulcerative colitis, in fact, have reported that their disorder began after they quit smoking, and many studies have reinforced the association between smoking and protection against ulcerative colitis. (This information is certainly no encouragement to smoke. Rather, patients should ask their doctor about trials using nicotine replacement aids.)

Breast-feeding. Breast-feeding appears linked to lower risk for ulcerative colitis.

Left-Handedness. People who are left-handed have a significantly higher risk for both inflammatory bowel diseases as well as for certain other diseases associated with immune system abnormalities.

Depression. One study reported that patients with ulcerative colitis were more likely to have a history of depression or anxiety than those without inflammatory bowel disease. Some researchers suggest that depression may alter the immune system and make people more susceptible to ulcerative colitis.

Diagnosis

The doctor will take your medical history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children, in whom inflammatory bowel disease (IBD) may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be taken, such as the following:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis cases.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are endoscopic procedures. They are important in the diagnosis of both ulcerative colitis and Crohn's disease. Both procedures involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor may also insert instruments through the endoscope to remove a tissue sample for a biopsy.

Sigmoidoscopy, which is used to examine the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful. Ulcerative colitis almost always involves the lower left colon and rectum and is diagnosed using sigmoidoscopy. The doctor usually observes an evenly distributed inflamed surface lining the intestine, and the bowel wall bleeds easily when touched with a swab.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is helpful for distinguishing between Crohn's disease and ulcerative colitis and in screening for colon cancer.

Patients diagnosed with ulcerative colitis may also need periodic endoscopies to evaluate their condition when symptoms flare up. However, a 2005 study suggested that these routine endoscopies may not be necessary. The study found that doctors can get as much information about a person's disease when patients self-report their symptoms as they can from endoscopies.

X-rays and Barium Enema. The double-contrast barium enema, which uses an x-ray image, is less expensive than a colonoscopy for viewing the entire colon. Although not as accurate as colonoscopy, it is very valuable in diagnosing both Crohn's disease and ulcerative colitis in early stages. In patients with active ulcerative colitis, this procedure may increase the risk for toxic megacolon.

A barium enema is a valuable diagnostic tool that helps detect abnormalities in the large intestine (colon). A barium enema, along with colonoscopy, remains standard in the diagnosis of colon cancer, ulcerative colitis, and other diseases of the colon.

X-rays of the abdomen are also useful when a patient has a severe attack of ulcerative colitis. In such cases, the edges of the colon are swollen and irregular. X-rays may also reveal thickened walls and other signs of severity.

Ultrasound. Intestinal wall ultrasound may be useful for identifying the extent and severity of Crohn's disease. Although it is unclear if ultrasound is useful for an initial diagnosis, one study indicated that, when used by experienced professionals, it is effective for identifying Crohn's disease or ulcerative colitis.

Other Imaging Procedures. Magnetic resonance spectroscopy (MRS) is a variant of magnetic resonance imaging (MRI) that may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.

Positron emission tomography (PET) and computed tomography (CT) scans may be useful for determining the extent of the disease on the intestine and for detecting abscesses and other complications of advanced IBD.

A promising experimental technique called virtual colonoscopy allows three-dimensional imaging of the colon without using invasive instruments. The procedure involves pumping air into the colon and scanning the intestine using computed tomography (CT) or magnetic resonance imaging (MRI). It is very safe, requires no sedation, and takes only about 10 minutes.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of tests for antibodies in people with UC will show perinuclear-staining antineutrophil cytoplasmic antibodies. Over 50% of Crohn's people have anti-Saccharomyces cerevisiae antibodies. Such tests are expensive and infrequently performed, but they may be useful in cases of uncertainty.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis, cause many of the same symptoms as inflammatory bowel disease. Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Microscopic Colitis. Microscopic colitis causes chronic watery diarrhea, but the colon lining shows little or no signs of inflammation. It may be genetically linked to celiac sprue. Most patients can expect to improve.

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a lot of people with inflammatory bowel disease (IBD) and is usually first noticed in children.

Click the icon to see foods to avoid when you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of a patient with IC is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before a diagnosis of inflammatory bowel disease can be confirmed.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to irritabel bowel syndrome can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

Malnutrition is very common in ulcerative colitis, although it tends to be more severe in Crohn's disease. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (Non-Caffeinated). Drinking plenty of water is extremely important. It not only benefits the intestine but also helps prevent kidney stones, which are common in inflammatory bowel disease (IBD). Vegetable juice and sports drinks may be helpful for restoring important minerals.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency and so patients may need more protein than the general population.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of your calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) might be specifically protective for IBD and may also reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so you should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber. Fiber may help reduce damage in the intestinal tract caused by UC, and may even help protect against cancer. Oat bran is of particular interest. In the intestinal tract, this whole grain increases levels of a fatty acid called butyrate, which may help reduce GI symptoms due to ulcerative colitis. However, high-fiber foods can cause gas, bloating, and pain, particularly in people with IBD. Available commercial products (Beano) can reduce gas. Eating small, frequent meals can also help.

Potassium-rich Foods. Potassium rich foods help protect the intestine. They may also reduce the risk for kidney stones. Such foods include bananas, oranges, pears, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, have been associated with protection against inflammation, including in the intestinal tract. Some studies have even reported lowered use of anti-inflammatory medications in people who consume fish oil. Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids. Standards for optimal amounts and forms of omega-3 fatty acids have not yet been established, however.

Omega-3 fatty acids, found plentifully in oily fish, flaxseed, and canola oils, may help people with inflammatory bowel disease.

Exclusion diets are those that eliminate certain allergenic foods or those that might irritate the intestine. To determine these foods, patients use a so-called elimination-and-challenge approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. Elimination diets, however, are very difficult to maintain, and it is not clear if they prevent relapse.

Typical foods to avoid are:

Saturated fats, found in animal and dairy products. People with inflammatory bowel disease should limit fats. Some studies have found an association between high-fat intake and later development of ulcerative colitis. Animal (saturated) fats are often suspected in IBD.
Milk products. Some people with inflammatory bowel disease are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant people are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine). Fruits may be protective, but you should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in people with inflammatory bowel disease (IBD), particularly in people who have had intestinal surgery. People with IBD are at risk for the most common types of stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendations for reducing the risk for kidney stones are increasing fluid and restricting sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Sufficient protein, particularly in children with IBD, is very important and should be weighed against any risk for stones.
You should increase intake of potassium-rich foods.
You should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. You should avoid or limit intake oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids and dietary potassium and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
People who have stones associated with short-bowel syndrome should eat less fat and foods containing oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones must be tailored to the dietary requirements of IBD. You should work with your doctor to develop an individualized plan.

Researchers are currently investigating a mix of bacteria (called probiotics), specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are helpful bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms, such as by excreting certain acids (lactate, acetate) that inhibit harmful bacteria or competing with them for nutrients. Evidence is now suggesting that probiotics may help maintain remission in patients with IBD. They are also proving to be effective in people with pouchitis -- a common surgical complication. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which is found in yogurt and other fermented milk products. Others, such as bifidobacteria and GG lactobacilli, however, may prove to be more important in inflammatory bowel disease (IBD). Other probiotics include lactobacilli rhamnosus, casel, plantarium, bulgaricus, salivarius, Enterococcus faecium, and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods themselves can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and overseas. To date, however, no studies have determined any clear benefits from any specific organism or formulation.

Vitamins. Deficiencies of vitamins A, C, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with IBD, particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which protect the body against damaging particles. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer in patients with ulcerative colitis. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic in high doses, patients should discuss specific dosages with their doctors.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD. Zinc is specifically important for gastrointestinal health. Calcium and magnesium are critical for health and strong bones. Selenium is a potent antioxidant. Iron supplements may be required for anemia. A doctor should advise patients carefully on the correct dosages since minerals can be toxic in high levels.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

To reduce mild-to-moderate diarrhea, take one teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Anti-diarrhea drugs, such as loperamide (Imodium) and atropine/diphenoxylate (Lomotil), may help. In very ill patients, large doses of some drugs, such as Lomotil, can trigger the onset of toxic megacolon.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous (IV) iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in inflammatory bowel disease that does not respond to iron alone. Crohn's disease patients benefit from the combination. Patients with ulcerative colitis usually improve on IV iron alone.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and such drugs will not affect the basic illness.

Acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs) are used for relieving mild pain. NSAIDs include aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), and celecoxib (Celebrex), the only COX-2 inhibitor left on the market. NSAIDs have been thought to cause symptom flare-ups in patients with inflammatory bowel disease (IBD). However, a comprehensive 2006 study concluded that these drugs are as safe for patients with IBD as for other people, and that they can help prevent relapse as well as provide short-term pain relief. Still, long-term use of NSAIDs can cause stomach bleeding and, with the exception of aspirin, may increase the risks for heart attack and stroke. Acetaminophen can cause liver damage if taken in high doses or combined with alcoholic drinks. Discuss with your doctor whether acetaminophen, NSAIDs, or other pain relievers are appropriate for you.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Patients with inflammatory bowel disease (IBD), in fact, may have a more exaggerated physical response to stressful events than people without IBD. Although no evidence exists to confirm that stress reduction techniques, such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

Castor Oil Pack. Some people report relief from the use of a castor oil pack for 3 consecutive days. The oil is applied directly to the skin and then covered with a clean soft cloth and plastic wrap. A hot water bottle or heating pad is then placed over the pack for 30 - 60 minutes.

Acupuncture. Acupuncture may help relieve symptoms in some patients.

Medications

Drugs cannot cure inflammatory bowel disease, but they can help reduce the inflammation and accompanying symptoms in up to 80% of patients. The primary goal of drug therapy is to reduce inflammation in the intestine.

Drugs Used. Drug therapies for ulcerative colitis aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission).

Aminosalicylates. Mild-to-moderate ulcerative colitis is usually treated with aspirin-like medications called aminosalicylates, or 5-ASAs. These drugs are also used to treat relapses. They may be administered rectally in patients who have mild-to-moderate disease that occurs only in the lower intestine. They may also be taken by mouth.
Corticosteroids. Corticosteroids (steroids) may be added or used alone to reduce acute inflammation. (Because of their significant side effects, they are not recommended for long-term use and maintenance therapy). Steroids may be administered rectally as an alternative to an aminosalicylate if the disease is limited to the lowest parts of the intestine. Forms taken by mouth may treat moderate-to-severe cases. People who do not respond to less aggressive treatments may need intravenous steroids.
Immunosuppressants. Drugs that suppress the immune system (immunosuppressants) are useful, either alone or in combinations, for disease that does not respond to other treatments or for maintenance of remissions.
Biologic Drugs. Unlike drugs that are made from chemicals, biologic drugs are produced from living organisms. Biologics are designed to stimulate the immune system and interfere with specific proteins (cytokines) involved with the inflammatory response. Infliximab (Remicade) is the first biologic drug approved for ulcerative colitis. It blocks a cytokine called tumor necrosis factor (TNF).

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed and symptoms such as diarrhea, abdominal cramps, and tenesmus (straining painfully or ineffectively to defecate or urinate) are normal or close to normal.

Aminosalicylates contain the compound 5-aminosalicylic acid, or 5-ASA, which helps reduce inflammation. These drugs are used to prevent relapses and maintain remission in mild-to-moderate Crohn’s disease.

The standard aminosalicylate drug is sulfazine (Azulfidine). This drug combines the 5-ASA drug mesalamine with sulfapyridine, a sulfa antibiotic. While sulfazine is cheap and effective, the sulfa component of the drug can cause unpleasant side effects, including headache, nausea, and rash.

Patients who cannot tolerate sulfazine or who are allergic to sulfa drugs have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are taken as pills several times a day. In 2007, the Food and Drug Administration approved LIALDA, the first once-daily mesalamine pill for patients with ulcerative colitis. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)
Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children and women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs. They are used only for active ulcerative colitis. Steroids are frequently combined with other drugs to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time. Because they have serious long-term effects, steroids are not useful for maintenance therapy. Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

Immunosuppressant drugs are now being used for long-term therapy, especially for very active inflammatory bowel disease that does not respond to standard treatments. Such drugs suppress or restrain actions of the immune system and therefore its inflammatory response, which causes ulcerative colitis. Immunosuppressants can prevent relapse, even when used alone, and in some studies have proved to help maintain remissions in ulcerative colitis for up to 2 years.

Azathioprine (Imuran, Azasan) and 6-mercaptopurine (6-MP, Purinethol) are the standard oral immunosuppressant drugs. However, it can take 3 - 6 months for these drugs to have an effect. To speed up the response, they are sometimes prescribed along with a corticosteroid drug. Lower steroid doses are then needed, resulting in fewer side effects. Corticosteroids may also be withdrawn more quickly. For this reason, immunosuppressants are sometimes referred to as steroid-sparing drugs.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). Cyclosporine A is also given intravenously to patients with severe ulcerative colitis. These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. Methotrexate (MTX, Rheumatrex) is another fast-acting type of injectable immunosuppressant that is effective for Crohn’s disease. However, methotrexate does not appear to be helpful for ulcerative colitis. (Antibiotics, which are used to treat Crohn's disease, are also not helpful for ulcerative colitis.)

General side effects of immunosuppressants may include nausea, vomiting, and liver or pancreatic inflammation. Patients should receive frequent blood tests to monitor bone marrow, liver, and kidneys. Patients who take cyclosporine A or tacrolimus need to have their blood pressure and kidney function checked regularly. Immunosuppressants are usually not recommended for women who are pregnant or breast-feeding.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. One such drug, infliximab (Remicade), was approved in 2005 for treatment of moderate-to-severe ulcerative colitis in patients who have not responded to other drugs, such as corticosteroids. In 2006, infliximab was approved to help maintain as well as induce remission. Doctors do not recommend infliximab as a first-line drug for ulcerative colitis.

Infliximab targets an inflammatory immune factor known as tumor necrosis factor (TNF). Studies indicate that infliximab may reduce ulcerative colitis symptoms and help patients achieve remission. Infliximab may also help heal ulcers and inflammation of the colon’s inner lining (mucosa). Some patients who take infliximab may be able to avoid surgical removal of the colon.

Infliximab is given as a 2-hour intravenous infusion in a doctor’s office. After the first dose, the patient receives a second dose 2 weeks later, and a third dose 6 weeks after that. After these three doses, the drug is given every 8 weeks.

Common side effects may include a skin reaction at the injection site, stomach pain, and coughing. Potential serious side effects include tuberculosis, pneumonia, and other respiratory infections; lymphoma (a type of cancer); liver failure; and aplastic anemia. Infliximab is not appropriate for most patients with heart failure.

Researchers are currently studying other biologic drugs for treatment of ulcerative colitis. These investigational drugs include adalimumab (Humira), which is approved for Crohn’s disease, and visilizumab (Nuvion), rituximab (Rituxan), basiliximab (Simulect), and golimumab (CNTO 148). To date, however, infliximab is the only biologic drug approved for treatment of ulcerative colitis.

Interferon. Interferons suppress important inflammatory factors in the immune system. They are used in treating multiple sclerosis. Research suggests that the drug interferon (IFN) beta-1a (Avonex, Rebif) may help patients with ulcerative colitis. Side effects include flu-like symptoms and reactions at the site of injection. More research is needed.

Rosiglitazone. The diabetes drug rosiglitazone (Avandia) is being studied as a short-term treatment for mild-to-moderate ulcerative colitis in patients who are not helped by 5-aminosalicylic acid (5-ASA) drugs. Research presented at the 2007 Digestive Disease Week conference indicated that rosiglitazone may have some benefit for select patients. However, this drug has been associated with increased risk for heart failure, and possibly heart attack, in patients with diabetes. More research is needed.

Alicaforsen. Antisense drugs bind to target RNA and block the production of key proteins. Alicaforsen is an antisense drug that inhibits an intercellular adhesion molecule (ICAM-1) thought to play a pivotal role in the inflammatory process. Several clinical trials of alicaforsen enemas have reported encouraging results for improvement of ulcerative colitis symptoms. More research is needed.

Adsorptive Granulocyte and Monocyte Apheresis (GMA). Adsorptive apheresis is a process in which the fluid part of the blood, called plasma, is removed from blood cells. The procedure involves withdrawing blood from the patient, filtering it through a device, and then infusing the filtered blood back into the patient. The process removes inflammatory antibodies and other immunologically active substances. It is used for patients with rheumatoid arthritis and may be helpful for patients with ulcerative colitis. Some clinical trials have reported promising results for treatment of refractory ulcerative colitis. More research is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies are reporting significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger inflammatory bowel disease. More research, however, is needed.

Surgery

In 20% of people with ulcerative colitis, drug therapy is not effective, and surgery to remove diseased sections is necessary. In these people, part, or all ,of the colon is removed, depending on the extent of the disease. Surgeries may also be required because of hemorrhage, chronic illness, perforation of the colon, or to prevent colon cancer. Studies report that surgery improves the quality of life in most patients. Some experts are urging, in fact, that many patients should consider intestinal surgery in the early stages of the disease.

Proctocolectomy is removal of the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements. It can achieve a complete cure, but it is a last resort. There are different variations that may be performed depending on various factors. The procedure must be performed only on patients in whom it is absolutely clear that ulcerative colitis, and not Crohn’s disease, is causing the inflammatory bowel disease (IBD). Discovering underlying Crohn's disease or other problems during the procedure can increase the risk for complications.

Ileostomy. In some proctocolectomies, the surgeon creates an opening in the abdominal wall (called a stoma) to allow passage of waste material. This part of the procedure is referred to as an ileostomy, and the stoma is created in the lower right corner of the abdomen. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Ileoanal Anastomosis. Ileal pouch anal anastomosis (IPAA), also simply called ileoanal anastomosis, has now largely replaced ileostomy because it preserves part of the anus and allows for more normal bowel movements. The procedure creates a natural pouch to collect waste, rather than using an ileostomy bag. The standard procedure involves:

The colon is removed as in proctocolectomy, but the surgeon only strips the superficial diseased inner layer of the rectum, leaving the sphincter muscles intact.
The anus is then attached to the ileum (the final portion of the small intestine leading to the colon).
A pouch is constructed out of the small bowel above the anus. The pouch is able to collect waste material, and the patient can pass bowel movements normally through the anus, although they are watery and more frequent than normal (five or six times a day). Closing the pouch with a staple, rather than hand-sewn stitches, achieves better continence rates.
A temporary abdominal opening (ileostomy) is usually required, but it is typically closed up in a second operation a few months later.

Flatulence is the most socially distressing problem. Unfortunately many of the fiber rich vegetables and whole grains that can benefit patients with ulcerative colitis can also cause gas. (Surgical patients should avoid or chew thoroughly insoluble fiber foods, such as popcorn, olives, and vegetable skins, which can obstruct the stoma.) Some pouching systems have filters that can help limit flatulence. Typically, flatulence occurs 2 - 4 hours after eating, which may help patients time their meals to ensure privacy afterward.

Patients must increase fluid intake, and include not only water but also broth, sports drinks, and vegetable juice to maintain appropriate levels of sodium and potassium.

Patients should avoid time-released, coated, or large pills, which often are not completely absorbed and may block the stoma.

The ileostomy does not interfere with bathing or showering or most physical activity. (Patients should avoid contact sports.) As a rule, the surgeries do not impair sexual function. If it does, according to one study, taking sildenafil (Viagra) restores sexual function to near or complete improvement in 80% of men.

Complications are common with any intestinal operation. In about 5 - 10% of IPAA procedures, complications occur that require conversion to an ileostomy. In general, patient satisfaction is very high with this procedure. Over 80% of patients report better or much better quality of life 5 years after the procedure. According to one study, 90% of patients can expect to have a functioning pouch for at least 20 years. Most patients can postpone their bowel movements until they are convenient. Bowel movements still average about seven a day.

Pouchitis. Inflammation of the pouch (pouchitis) is the most common complication of the pouch procedures, and one study reported its occurrence in up to 60% of patients. Symptoms include rectal bleeding, cramps, and fever. It can usually be easily treated. According to one study, however, in about 10% of these patients the condition becomes chronic, and the pouch may need to be removed. Metronidazole (Flagyl) is effective in treating active flare-ups of pouchitis. Evidence also suggests that the use of a probiotic (VSL-3) helps maintain remission in chronic pouchitis.

Irritable Pouch Syndrome. Irritable pouch syndrome is a problem that includes frequent movements, an urgent need to defecate, and abdominal pain. There are no signs of inflammation, however, as there are with pouchitis. Stress and diet play a role in this condition, and it is usually relieved after a bowel movement.

Fecal Incontinence. About 70% of patients are fully continent indefinitely after the procedure. (In other words, they experience no leakage.) The other patients typically experience occasional spotting and minor leakage, which is manageable.

Infertility. IPAA triples the risk of infertility in women with ulcerative colitis. The surgery may cause scarring or blocking of fallopian tubes, which increases the risk of infertility. About 48% of women who undergo this procedure become infertile

Severe scarring at the incision occurs in more than half of patients. One study found that placing an experimental absorbable membrane made from hyaluronate (a natural lubricating substance) along the incision reduced the rate of scarring up to 15%. When the rectum is removed, there is a small danger of injury to the nerves that control erection and bladder function.

Small bowel obstruction may occur with some of the procedures. If this occurs in pouch procedures, the pouch may need to be removed.

Pelvic infection occurs in less than 10% of pouch procedures (more often after hand-sewn than stapled anastomoses), and it occurs almost four times more often in men than in women. It is also more common in patients with ulcerative colitis who also have toxic megacolon.

Valve leakage may occur or the catheter may become blocked in continent ileostomies. In at least 10% of these procedures, the valve needs to be repaired later on.

Some studies have also reported that appendectomy (removal of the appendix) protects against ulcerative colitis. It may be that removing the appendix alters the T cell balance in the immune system that then works in favor of people with UC. One study suggested, however, that specific inflammatory conditions leading to appendicitis were the protective factors -- and only in people under age 20. (An appendectomy may actually increase the risk for Crohn's disease.)

Click the icon to see an illustrated series detailing an appendectomy surgery.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Clark M, Colombel JF, Feagan BC, Fedorak RN, Hanauer SB, Kamm MA, et al. American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006. Gastroenterology. 2007 Jul;133(1):312-39.

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.

Lawson MM, Thomas AG, Akobeng AK. Tumour necrosis factor alpha blocking agents for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2006 Jul 19;3:CD005112.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Review Date:
8/30/2007
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 17:35:29 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Complications
Risk Factors
Diagnosis
Dietary Factors
Symptom Management
Medications
Surgery
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Biologic Drugs

In February 2007, the FDA approved adalimumab (Humira) for treatment of adult patients with moderate-to-severe Crohn’s disease. Adalimumab and infliximab (Remicade) are now the two biologic drugs approved for Crohn’s disease. Infliximab is approved for treating both adults and children.
As of August 2007, the FDA was considering approving natalizumab (Tysabri) for moderate-to-severe Crohn’s disease in patients who have not responded to, or cannot tolerate, other therapies. However, natalizumab has serious risks -- in 2007, the European medicine agency rejected natalizumab for Crohn’s disease treatment.
Certolizumab (Cimzia) is another biologic drug that is showing promise for Crohn’s disease, according to several 2007 studies in the New England Journal of Medicine.
The risks of biologic drugs need to be weighed against their potential benefits, according to a 2007 consensus statement from the American Gastroenterological Association. These drugs may be appropriate as initial treatments for select patients who have fistulas or for patients who have not been helped by corticosteroid drugs.

Genetic Research

In 2006 and 2007, scientists achieved major breakthroughs in identifying specific genes associated with Crohn’s disease. Among these recent discoveries:

The interleukin-23 receptor (IL23R) gene is associated with variations that can either increase or decrease the risk for Crohn’s disease and ulcerative colitis.
The ATG16L1 gene regulates a process called autophagy, which involves how a cell digests itself. Scientists think that waste build-up from improperly regulated autophagy may play a role in the inflammatory response associated with Crohn’s disease.
Other recently identified genes that may be linked with Crohn’s disease include PHOX2B and NCF4.

Pregnancy Complications

According to a 2007 review in Gut, inflammatory bowel disease significantly increases the risk for pregnancy complications, such as premature birth, low birth weight, and birth defects. Women who experience disease flares during pregnancy are especially at risk.

Introduction

Inflammatory bowel disease (IBD) is a general term that covers two disorders:

Ulcerative colitis (UC)
Crohn's disease (CD)

Some evidence suggests that these two diseases are part of a biologic continuum. At this time, however, they are considered distinct disorders with somewhat different treatment options. The basic distinctions between UC and CD are location and severity. However, as many as 10% of patients with IBD have features and symptoms that match the criteria for both disorders, at least in the early stages. (This is called indeterminate colitis.)

Crohn's disease, also called regional enteritis, is a chronic inflammation of the intestines which is usually confined to the terminal portion of the small intestine, the ileum. Ulcerative colitis is a similar inflammation of the colon, or large intestine. These and other IBDs (inflammatory bowel disease) have been linked with an increased risk of colorectal cancer.

Crohn's Disease. Crohn's disease is an inflammation that extends into the deeper layers of the intestinal wall. It is found most often in the area bridging the small and large intestines, specifically in the ileum and the cecum, sometimes referred to as the ileocecal region. Crohn's disease occurs less frequently in other parts of the gastrointestinal tract, including the anus, stomach, esophagus, and even the mouth. It may affect the entire colon or form a string of contiguous ulcers in one part of the colon. It may also develop as multiple scattered clusters of ulcers throughout the gastrointestinal tract, skipping healthy tissue in between.

Click the icon to see an image of Crohn's disease.

Ulcerative Colitis. Ulcerative colitis is an inflammatory disease of the large intestine. Ulcers form in the inner lining, or mucosa, of the colon or rectum, often resulting in diarrhea, blood, and pus. The inflammation is usually most severe in the sigmoid and rectum and typically diminishes higher in the colon. The disease develops uniformly and consistently until, in some people, the colon becomes rigid and foreshortened. [See In-Depth Report #69: Ulcerative colitis.]

Click the icon to see an image of the structure of the colon.

The gastrointestinal tract (the digestive system) is a tube that extends from the mouth to the anus. It is a complex organ system that first carries food from the mouth down the esophagus to the stomach and then through the small and large intestine to be excreted out through the rectum and anus.

Esophagus. The esophagus, commonly called the food pipe, is a narrow muscular tube, about 9 1/2 inches long, that begins below the tongue and ends at the stomach.

Stomach. In the stomach, acids and stomach motion break food down into particles small enough so that nutrients can be absorbed by the small intestine.

First it enters the duodenum
Then the jejunum, and
Finally the ileum

Most of the digestive process occurs in the small intestine.

Cecum and Appendix. The cecum and the appendix are located in the lower-right quadrant of the abdomen.

Colon. The colon absorbs excess water and salts into the blood. The remaining waste matter is converted to feces through bacterial action. The colon is divided into four major sections.

The first section, the ascending colon, extends upward from the cecum on the right side of the abdomen.
The second section, the transverse colon, crosses the upper abdomen to the left side.
The third section extends downward on the left side of the abdomen toward the pelvis and is called the descending colon.
The final section is the sigmoid colon.

Rectum and Anus. Feces are stored in the descending and sigmoid colon until they are passed through the rectum and anus. The rectum extends through the pelvis from the end of the sigmoid colon to the anus.

Click the icon to see an image of the digestive system.

Click the icon to see an image of the stomach.

Click the icon to see an image of the structure of the small intestine.

Click the icon to see an image of the structure of the colon.

Causes

Inflammatory bowel disease has many different causes. It is due in many cases to a genetic susceptibility that enables an organism such as a virus or bacteria to trigger an abnormal immune reaction, which in turn, causes an inflammatory response in the intestines. Although Crohn's disease has features that resemble an autoimmune disease (in which the body's immune system attacks its own cells), some researchers think that it may be due to initial immune deficiencies.

The Immune System's Infection Fighters. The primary infection-fighting units are two types of white blood cells: lymphocytes and leukocytes.

B cells produce antibodies, which are separate substances that can either ride along with a B cell or travel on their own to attack the antigen.
T cells have special receptors attached to their surface that recognize the specific antigen.

T cells are further categorized as killer T cells or helper T cells.

Killer T cells directly attack antigens that occur in any cells that contain a nucleus.
Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and Inflammatory Bowel Disease. The actions of the helper T cells (TH cells) are of special interest in inflammatory bowel disease:

TH cells stimulate other white blood cells called B cells to produce antibodies. In this case, however, they appear to direct the B cells to produce autoantibodies, which are directed against the body's own cells.
TH cells also secrete or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are indispensable for healing. If overproduced, however, they can cause serious damage, including inflammation and cellular injury. Cytokines, particularly specific ones known as tumor necrosis factor, interferon-gamma, and interleukins, cause intestinal inflammation and damage, which, in a vicious cycle, attract even more helper T cells.

Helper T cells are further categorized as TH1 and TH2. An imbalance in these two types appear to occur in IBD, although each disorder has a different balance:

Ulcerative colitis patients favor a TH2 response, which activates the interleukins IL-5, IL-6, and IL-10. These mostly affect mucosal areas in the intestine.
Research indicates that patients with Crohn's disease have increased activity in TH1 cells, activating interleukin-2 (IL-2) and interferon-gamma, which affect intestinal cells. Tumor necrosis factor (TNF) may be a particularly potent immune factor in Crohn's disease. It is important in properties that regulate inflammation and cell proliferation. If genetic or other factors increase production of this immune compound, it can lead to great harm.

Interleukin 6 appears to play a part in both IBDs, by inhibiting a natural process called apoptosis, in which cells self-destruct. As a result, cells proliferate faster than they die, causing an excessively strong immune response.

Matrix Metalloproteinase. Greater activity of enzymes called matrix metalloproteinase has been detected in the colons of patients with IBD. These increased levels tend to break down the extracellular matrix, a barrier composed of structural proteins and elastic fibers that surrounds and supports cells, in this case in the colon. Researchers suggest that this activity may cause persistent damage once the inflammatory process has triggered IBD.

Specific Genes Involved. The first important genetic discovery for Crohn’s disease was the identification of the genetic variant CARD15 (also called NOD2), which alters the immune system so that it launches an over-reaction in response to bacteria, causing inflammation. However, this genetic factor only affects a small percentage of Crohn’s disease cases and is not involved with ulcerative colitis.

In 2006, scientists made a significant genetic research breakthrough by identifying the interleukin-23 receptor (IL23R) as a major link to the development of both Crohn’s disease and ulcerative colitis. Interleukin 23 is a cytokine that plays an important part in the inflammatory response and inflammatory diseases. Interestingly, scientists found that certain variations in the IL23 receptor gene can either increase or decrease the risk for inflammatory bowel disease. Further research in 2007 indicated that IL23R gene variants may also increase or decrease the risk for Crohn’s disease in children.

Also in 2007, scientists identified several other genetic risk factors for Crohn’s disease, including the genes PHOX2B, NCF4, and ATG16L1. Scientists are particularly interested in the ATG16L1 gene. This gene regulates autophagy, the process in which a cell digests its own cytoplasm, including cellular waste products such as bacteria. Problems with autophagy may lead to a build-up of unprocessed waste products within the cell. This build-up may then provoke the inflammatory response associated with Crohn’s disease. Mutations of the ATG16L1 gene have been linked to increased susceptibility to Crohn’s disease in both adults and children.

Future genetic research may help develop targeted drug therapy for treatment of inflammatory bowel disease.

One theory suggests that viruses or bacteria within the intestine may alter properties in the lining and intestinal tract. Over time, these changes may trigger the processes that lead to inflammatory bowel disease.

Measles. Some studies report that children with IBD may have had more and earlier childhood infections. The measles virus has been of particular interest. According to the U.S. Centers for Disease Control, and many studies, the measles virus does not cause Crohn’s or IBD.

Much publicity has centered on whether the vaccine for measles, mumps, and rubella (the MMR vaccine) causes conditions such as autism and Crohn’s disease. This theory has been rigorously reviewed and refuted in many well-conducted studies, including several published in 2006. The evidence clearly indicates that the MMR vaccine does not increase the risk of Crohn’s disease, other inflammatory bowel disease, or autism.

Mycobacteria. A type of bacterium associated with tuberculosis is another possible candidate for an infectious cause of Crohn’s disease.

Escherichia coli. The intestine normally harbors E. coli bacteria. In most cases, the bacteria are harmless and even protective. Some E. coli strains, however, can bind to the intestinal walls and penetrate the lining. These damaging strains may be associated with Crohn’s disease.

Cytomegalovirus. Cytomegalovirus (CMV) is a common virus that is also under suspicion as a contributor to severe cases of IBD.

Inflammatory bowel disease is much more prevalent in industrialized nations and in higher-income groups. Diet may play some role, although studies have been conflicting over its importance.

Symptoms

The two major inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, share certain characteristics:

Symptoms usually appear in young adults.
Symptoms can develop gradually or have a sudden onset.
Both are chronic. In either disease, symptoms may flare up (relapse) after symptom-free periods (remission) or symptoms may be continuous without treatment.
Symptoms can be mild or very severe and disabling.
The severity of symptoms and relapse rates of both IBDs vary with seasons, with the highest risk in the winter and autumn and lowest in summer.

The two disorders, however, have different symptom profiles and is it important to differentiate between them, since they require different treatments.


Symptoms	Ulcerative Colitis	Crohn's Disease
Diarrhea	Recurrent diarrhea is very common, but onset may be very gradual and mild or it may not be present. Feces may also contain mucus.	Recurrent diarrhea is fairly common.
Rectal Bleeding	Blood is almost always present in stools. It may be readily visible or visible only using a microscope (called occult blood).	Bleeding not as common as in UC, but can occur.
Constipation	Constipation can be a symptom of UC, but not as common as diarrhea. Can occur during flare-ups. May occur when the inflamed rectum triggers a reflex response in the colon that causes it to retain the stool.	Constipation in Crohn's disease is usually a symptom of obstruction in the small intestine.
Abdominal Symptoms	Pain is not prominent symptom, but can vary. May cause vague discomfort in the lower abdomen, an ache around the top of the hipbone, or cramps in the middle of the abdomen. Severe pain can occur during flare-ups. Vomiting and nausea.	Main symptom is recurrent episodes of pain in the lower right part of the abdomen or above the pubic bone. Often preceded by and relieved by defecation. Bloating, nausea, and vomiting may also occur. Intestinal pain may also be an indication of a serious condition, such as an abscess, or a perforation of the intestinal wall.
Fever	May occur with severe attacks.	Usually low-grade. Spiking fever and chills indicates complications.
Loss of appetite, weight loss, and impaired growth in children	Often not evident in mild or even moderately severe UC. Occasionally impairs growth in children and teenagers.	Common. Typical weight loss is 10 - 20% of normal. Commonly impairs growth in children and teenagers.
Abnormal defecation: Increased frequency, a feeling of incomplete evacuation, and tenesmus (a painful urge for a bowel movement even if the rectum is empty). Fecal incontinence.	Symptoms may be mild or severe.	Can occur in active stages.
Anal ulcers and fistulas: (channels that can burrow between organs, loops of the intestine, or between the intestines and skin).	Almost never a symptom.	Fistulas and ulcers around the anus may be early symptoms.
Neurologic or psychiatric symptoms	No.	May be early signs of Crohn's disease when accompanied by gastrointestinal problems.

There are three body views (front, back and side) that may be helpful if you are uncertain of a body area. Many areas are referred to by both descriptive and technical names. For example, the back of the knee is called the popliteal fossa. However, areas like the "flank" may not have both names, so the location may be unclear.

Click the icon to see a depiction of an anorectal fistula.

Complications

The outlook for Crohn's disease varies widely. Crohn's disease can range from being benign (such as when limited Crohn's disease occurs only around the anus in older people) or it can be very severe. At the extreme end, some patients may experience only one episode and others suffer continuously. Although recurrences tend to be the norm, disease-free periods can last for years or decades in some patients. Although Crohn's disease cannot be cured even with surgery, treatments are now available that can offer significant help to most patients. Crohn's disease is rarely a direct cause of death, and most people can live a normal lifespan with this condition.

Mild Crohn's Disease. The fewer bowel movements, the milder the disease. In mild disease, abdominal pain is absent or minimal. The patient has a sense of well-being that is normal or close to normal. There are few, if any, complications outside the intestinal tract. The doctor does not detect any mass when pressing the abdomen. The red blood cell count is normal or close to normal, and the patient is not underweight.

Severe Crohn's Disease. In severe Crohn's disease, the patient has bowel movements frequent enough to require opiates or other potent anti-diarrhea medication. Abdominal pain is severe and usually located in the lower right quadrant of the abdomen. (The location of the pain might not indicate the site of the actual problem, a phenomenon known as referred pain.) The red blood cell count is low. The patient has a poor sense of well-being and experiences complications that may include weight loss, joint pain, inflammation in the eyes, reddened or ulcerated skin, fistulas, abscesses, and fever. The surgical and medical treatments of Crohn's disease, as with ulcerative colitis, have complications of their own that can be severe.

Malabsorption and malnutrition. Malabsorption is the inability of the intestines to absorb nutrients. In IBD, this occurs as a result of bleeding and diarrhea, as a side effect from some of the medications, and as a result of surgery. Malnutrition usually develops slowly and tends to become severe, with multiple nutritional deficiencies. It is very common, ranging from 25 - 80% of patients with Crohn's disease.

Ulcer, Fistulas, and Abscesses. Between 30 - 40% of patients with Crohn's disease experience complications around the anal area from inflammation. Fistulas (channels beneath the skin) frequently develop from the deep ulcers that can form with Crohn's. If fistulas develop between the loops of the small and large intestines, they can interfere with absorption of nutrients. They often form pockets of infection or abscesses, which may become life threatening without treatment.

Bleeding. Massive bleeding can occur in 1 - 2% of cases and may be recurrent. Bleeding is usually from a localized area in the intestine. Surgery may be performed to remove the bleeding sites.

Colorectal Cancers. Patients with inflammatory bowel disease have a slightly higher risk for colorectal cancer. The risk is greater for patients with severe ulcerative colitis than for those with Crohn’s disease. Patients with Crohn’s disease do have a 40-fold increased risk for small bowel cancer. (However, small bowel cancer is a very rare type of cancer.) The risk increases with the severity of the condition and the length of time the patient has had Crohn’s. [See In-Depth Report #55: Colon and rectal cancers.]

Intestinal Blockage. Inflammation from Crohn's disease produces scar tissue known as strictures that can constrict the intestines, causing bowel obstruction with severe cramps and vomiting. Strictures usually occur in the small intestine but can also occur in the large intestine.

Intestinal Infections. Inflammatory bowel disease can increase patients’ susceptibility to Clostridium difficile, a species of intestinal bacteria that causes severe diarrhea. As its name implies, C. difficile is difficult to treat and is resistant to many types of antibiotics. It is usually acquired in a hospital. However, several 2007 studies indicated that C. difficile is increasing among patients with inflammatory bowel disease and that many patients acquire this infection outside of the hospital setting. Patients with ulcerative colitis are at particularly high risk.

People with inflammatory bowel disease have a higher risk of developing other inflammatory diseases that affect the lungs and central nervous system.

Eyes. Inflammation in the eyes may sometimes be an early sign of Crohn’s disease. Retinal disease, including detachment, can occur but is rare. People with accompanying arthritic complications may be at higher risk for eye problems.

Joints. Inflammation causes arthritis and stiffness in the joints. The back is commonly affected. Patients with Crohn’s disease are also at risk for clubbing (abnormal thickening and widening at the ends of fingers and toes).

Click the icon to see an image of nail clubbing.

Bones. Crohn’s disease, and the corticosteroid drugs used to treat it, can cause osteopenia (low bone density) and osteoporosis (bone loss).

Anemia. Internal blood loss from ulcers in the intestine is a particular problem in Crohn's disease because of the impaired ability to absorb vitamins and minerals necessary for blood production.

Liver and Gallbladder Disorders. Patients have a higher than average risk for mild but not severe liver problems. They have double the normal risk for gallstones.

Click the icon to see an image of gallstones.

Mouth Sores. Canker sores are common, and when they occur they persist. Those at higher risk are males and younger people. Mouth yeast infections also common in people with Crohn's disease.

Skin Disorders. Patients with Crohn’s disease are likely to develop red knot-like swellings. Such swellings or other skin lesions, such as ulcers, may spread to sites far removed from the colon, (including the arms and legs). People with Crohn's disease have an increased risk for psoriasis.

Thromboembolism (Blood Clots). Clots may occur, most likely in the legs and pelvic area.

Click the icon to see an image of a thrombus.

Urinary Tract and Kidney Disorders. Urinary tract infections are common. Patients have an increased risk for kidney stones. Amyloidosis (deposits of a protein called amyloid in the kidney or other organs) is a rare but very serious kidney condition.

Click the icon to see an image of kidney stones.

Delayed Growth and Development in Children. Up to half of children with Crohn’s disease have impaired physical growth, and nearly all are underweight. About 30% reach puberty late, but once it occurs, hormonal cycles tend to be normal.

Infertility. Infertility rates are only slightly lower than average. Active disease at conception increases risk for miscarriage or prematurity. Men may have lower sperm count during active disease or because of impaired nutrition, but in general fertility is normal.

Menstrual Problems. Menstrual problems in women are common, including premenstrual disorder, abnormal bleeding, and pain. Pain with intercourse occurs in about half of patients. Sexual function may be impaired, not only because of the emotional impact, but also by treatment side effects and complications of the disease, such as fistulas.

Emotional Factors. The emotional consequences of UC cannot be overestimated, particularly in children. Eating becomes associated with fear of abdominal pain before the end of the meal. Frequent attacks of diarrhea can cause such a strong sense of humiliation that social isolation and low self-esteem may result. Adolescents with IBD may have added problems that increase emotional distress, including weight gain from steroid treatments and delayed puberty.

Risk Factors

About 1 - 2 million Americans suffer from inflammatory bowel disease (IBD), and about 400,000 of these patients have Crohn's disease. (This wide variation is due to the difficulty in diagnosing these disorders and because people in remission may not be identified.) The number of people with Crohn's disease may be increasing, and Crohn's disease is now considered to be the second most common chronic inflammatory disorder (after rheumatoid arthritis).

IBD often runs in families. The incidence may vary depending on gender, age, and geography:

Women may be slightly more at risk for Crohn's disease than men. Both genders are equally at risk for ulcerative colitis.
IBDs in general are diagnosed most often in young people age 10 - 19, but they can occur at any age. Another lesser peak onset occurs in people ages 50 - 80. About 2% of IBD cases appear in children below age 10. Between 10 - 15% of patients with Crohn's are children, and the childhood prevalence appears to be increasing.
IBD occurs four times more often in Americans of Northern European descent than in African-Americans. Scandinavia has the highest rate of Crohn's disease in the world. Studies in Britain suggest, however, that Asians may have a higher rate of IBD than people of European descent. Ashkenazi Jewish people have an even higher risk, five times that of the general population.
IBD seems to be more common among city than country dwellers and occurs more frequently in developed than in less developed nations, indicating that both genetic factors and environmental conditions, such as diet, may be involved in its development.
People who are left-handed have a significantly higher risk for both IBDs as well as certain other diseases associated with problems in the immune system.

Diagnosis

The doctor will take a history and perform a thorough physical examination. The disease is particularly difficult to diagnose in children. In children, IBD may be mistaken for an infection or even depression if other characteristic symptoms, such as bloody diarrhea and weight loss, are not present. Slow growth may be a key feature in making a diagnosis, particularly of Crohn's disease, in children.

Several laboratory tests may be performed:

Blood tests are used for various purposes. An increased number of white blood cells may indicate the presence of inflammation. Blood tests are used to determine the presence of anemia and to measure liver enzymes. (They are abnormal in about 3% of ulcerative colitis patients.) New blood tests that measure certain antibodies may make it easier to differentiate Crohn's disease from ulcerative colitis in children.
A stool sample is taken and examined for blood, infectious organisms, or both.

Standard Endoscopic Procedures. Flexible sigmoidoscopy and colonoscopy are procedures that involve snaking a fiberoptic tube called an endoscope through the rectum to view the lining of the colon. The doctor can also insert instruments through it to remove tissue samples.

Sigmoidoscopy, which is used to examine only the rectum and left (sigmoid) colon, lasts about 10 minutes and is done without sedation. It may be mildly uncomfortable, but it is not painful.
Colonoscopy allows a view of the entire colon and requires a sedative, but it is still performed on an outpatient basis. It is important in differentiating between Crohn's disease and ulcerative colitis and in screening for colon cancer.

There are three basic tests for colon cancer: a stool test (to check for blood); sigmoidoscopy (inspection of the lower colon); and colonoscopy (inspection of the entire colon). All three are effective in catching cancers in the early stages, when treatment is most beneficial.

The procedures may help the doctor to distinguish between ulcerative colitis and Crohn's disease, as well as other diseases. A variation called chromoendoscopy uses a blue stain during the process to reveal fine details on the intestinal lining. It might prove to be useful for identifying areas that may be precancerous and need to be biopsied.

Wireless Capsule Endoscopy. Wireless capsule endoscopy (WCE) is a newer imaging approach that is very useful for diagnosing Crohn's disease. With WCE, the patient swallows a capsule containing a tiny camera that records and transmits images as it passes through the gastrointestinal tract. Some studies have found it to be much more accurate for evaluating small bowel disease than barium x-rays or CT scans. Patients also find it easier to tolerate than standard endoscopy.

Ultrasound. Intestinal wall ultrasound is proving to be useful for identifying the extent and severity of Crohn's disease. It is uncertain if ultrasound is useful for an initial diagnosis.

Upper and Lower Gastrointestinal Barium X-Rays. An upper gastrointestinal barium x-ray may be used if Crohn's disease is suspected in the small intestine. Swallowed barium passes into the small intestine and shows up on an x-ray image, which may reveal inflammation, ulcers, and other abnormalities.

Click the icon to see an image of the barium enema procedure.

Positron Emission Tomography (PET) and Computed Tomography (CT) Scans. PET/CT scans are proving to be extremely useful in evaluating active IBD. With Crohn's disease, CT scans may show thickened walls and complications, such as fistulas, which occur outside the intestine.

Magnetic Resonance Imaging (MRI). Magnetic resonance imaging is another advanced imaging technique that may be useful for detecting abscesses and other injuries related to Crohn's disease in the pelvis. A variant called magnetic resonance spectroscopy (MRS) may prove to be useful for differentiating between Crohn's disease and ulcerative colitis.


Endoscopy	Ulcerative colitis almost always involves the lower left colon and rectum and can be diagnosed using sigmoidoscopy. Crohn's disease may require colonoscopy as well. Endoscopy often reveals ulcers, diseased regions that have a cobblestone-like appearance in Crohn's disease, but not in ulcerative colitis.
X-Rays (Barium Enema) or Computed Tomography Scans	In ulcerative colitis, inflammation is usually evenly distributed on the surface lining of the intestine, and the bowel wall bleeds easily when touched with a swab. The pattern observed in Crohn's disease is usually one of scattered patches of ulcers that are deep, thick, and large. Crohn's disease produces pockets (fissures) or channels (fistulas). They do not occur with UC. In ulcerative colitis the ileum (the lower part of the small intestine) is often dilated while it is narrowed in Crohn's disease.
Laboratory Tests	Tissue samples obtained from a patient with Crohn's disease may reveal granulomas, small collections of inflammatory cells. Granulomas may also be present in other conditions, however. Tissue samples should also be examined for the presence of cancerous cells. About 70% of antibody tests for patients with UC will show immune factors called perinuclear-staining antineutrophil cytoplasmic antibodies, and over 50% of Crohn's patients have anti-Saccharomyces cerevisiae antibodies. Each antibody group shows up only occasionally in the other disorder. Researchers are also investigating other antibodies, such as antilaminaribioside and antichitobioside, which may serve as new markers for Crohn’s disease.

Irritable Bowel Syndrome. Irritable bowel syndrome (IBS), also known as spastic colon, functional bowel disease, and spastic colitis cause many of the same symptoms as inflammatory bowel disease (IBD). (However, it is NOT the same as inflammatory bowel disease.) Bloating, diarrhea, constipation, and abdominal cramps are all symptoms of IBS. Irritable bowel syndrome is not caused by inflammation, however, and no fever or bleeding occurs. Behavioral therapy may be helpful in treating IBS. (Psychological therapy does not improve inflammatory bowel disease.)

Celiac Sprue. Celiac sprue, or celiac disease, is an intolerance to gluten (found in wheat) that triggers inflammation in the small intestine and causes diarrhea, vitamin deficiencies, and stool abnormalities. It occurs in a significant number of people with inflammatory bowel disease and is usually first noticed in children.

Click the icon to see foods to avoid if you have celiac sprue.

Interstitial Cystitis. Interstitial cystitis (IC) is an inflammation of the bladder wall that occurs almost exclusively in women. Some evidence suggests that the risk for IBD in these patients is 100 times above that in the general population and that there may be some common factor to both conditions. The average age of patients with interstitial cystitis is 40, but 25% of cases occur in women under age 30. Symptoms are very similar to urinary tract infections, but no bacteria are present. Pain during sex is a very common complaint in these patients, and stress may intensify symptoms.

Infections. If endoscopy reveals inflammation, a doctor must always rule out possible infections before confirming a diagnosis of inflammatory bowel disease.

Acute Appendicitis. Crohn's disease may cause tenderness in the right lower part of the abdomen, where the appendix is located, that resembles an appendicitis.

Click the icon to see an image of the appendix.

Cancer. Colon or rectal cancers must always be ruled out when symptoms of IBD occur.

Intestinal Ischemia. Symptoms similar to IBD can be caused by blockage of blood flow in the intestine. This is more likely to occur in elderly people.

Dietary Factors

The role of diet and nutrition is very important in Crohn's disease and should be considered for four separate situations:

As important add-on treatment to medical therapies for maintaining nutrition and correcting any nutritional deficiencies
As primary treatment for reducing disease activity
As maintenance therapy on a long-term basis in the case of severe intestinal failure or short-bowel syndrome
For reversing growth-failure in children

Malnutrition is very common in Crohn's disease. In fact, patients with Crohn's appear to burn fat calories at a higher rate than the general population and most patients are underweight. Some experts recommend that children with inflammatory bowel disease increase their calorie and protein intake by 150% of the daily recommended allowance for their specific ages and heights. Studies indicate that nutritional support in children is as important as medications for achieving remission. People whose weights are normal or no less than 90% of normal do not need to add extra calories.

Fluids (non-caffeinated). Drinking plenty of water is extremely important. Vegetable juice and sports drinks may be helpful for restoring important minerals. People with inflammatory bowel disease (IBD) should avoid caffeinated beverages in general, although green tea may have some benefits for Crohn's disease.

Protein. Proteins are very important for growth in children and for repair of cells. Diarrhea can cause protein deficiency, and patients with inflammatory bowel disease may need more protein than the general population. Oily fish, such as salmon and tuna, may be particularly beneficial in Crohn's disease. Other options are poultry and lean meats. Dried beans and legumes also provide protein.

Complex Carbohydrates. Complex carbohydrates, found in whole grains, fruits, and vegetables, should make up half of a patient's calories. Fresh fruit (such as apples, grapefruit, oranges, plums, blueberries, raspberries, and strawberries) may actually be specifically protective for IBD and may possibly reduce the risk for colon cancer. (Simple sugars can increase inflammation, however, so patients should avoid dried fruits and high-sugar fruits, such as grapes, pineapple, and watermelon.)

Foods made up of complex carbohydrates are also often a good source of fiber, which may help reduce damage in the intestinal tract caused by inflammation. However, high-fiber foods can cause gas, bloating, and pain, particularly in IBD patients. Commercial products (such as Beano) are available that can reduce gas. Eating small, frequent meals can also help.

Liquid Supplements. Over-the-counter liquid diets that meet full nutritional needs and are absorbed in the upper intestine, such as Ensure, Sustacal, and other products, may be helpful for some patients with Crohn's. However, it is important to note that no studies have determined this.

Potassium-rich Foods. Examples are potatoes, avocados, and bananas.

Exclusion Diets. Exclusion diets are those that eliminate certain foods that may cause allergies or irritate the intestine. To determine these foods, patients use an "elimination/challenge" approach. First, they remove all suspect foods from their diet for 2 weeks and then reintroduce one food every 3 days. Patients then watch for any symptoms that might indicate an allergic or irritant response, including gastrointestinal problems, headaches, and flushing. This approach, however, may be very difficult, and studies are weak in confirming its value for maintaining remission.

Typical foods people with inflammatory bowel disease (IBD) may avoid include:

Fats. Fats appear to worsen intestinal inflammation in Crohn's disease. Patients should limit fats, particularly saturated fats, found in meat and dairy products. However, certain fatty acids, such as those found in fish oil, may be helpful. The optimal balance between a low-fat diet with addition of these fatty acids is under investigation.
Milk products. Some people with IBD are lactose intolerant (unable to digest the sugar lactose, found in milk products). However, milk, along with the calcium it contains, has been associated with a lower risk for colon cancer. Taking lactase tablets or specially prepared dairy products may help. (Many lactose-intolerant patients are still able to eat yogurt with active cultures, which could be helpful for IBD.)
Foods associated with inflammation (alcohol, simple sugars, and caffeine).
Fruits may be protective, but patients should avoid dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Foods that may irritate the intestine, particularly so-called Brassica vegetables (cabbage, Brussels sprouts, broccoli, cauliflower, kale).

Kidney stones are painful and common complications in inflammatory bowel disease (IBD), particularly in patients who have had intestinal surgery. IBD patients are at risk for the most common types of kidney stones -- those composed of either calcium oxalate or uric acid crystals. The following are some considerations in reducing the risk for stones:

The most important dietary recommendation is to increase fluid and restrict sodium intake.
Limiting protein is recommended for reducing kidney stones. However, people with IBD who have frequent diarrhea are protein deficient. Having enough protein in the diet, particularly in children with IBD, is very important. Patients should weigh the importance of protien against any risk for kidney stones.
Patients should eat more potassium-rich foods (bananas, watermelon, cantaloupe, oranges, tomatoes, beans).
Patients should try to correct any dietary habits that cause acidic or alkaline imbalances in the urine that promote stone formation.
Many kidney stones are formed from calcium-oxalate stones. Patients should avoid or limit intake of oxalate-rich foods, such as beets, beet tops, black tea, chenopodium, chocolate, cocoa, dried figs, ground pepper, lamb quarters, lime peel, nuts, parsley, poppy seeds, purslane, rhubarb, sorrel, spinach, and Swiss chard. A high calcium diet does not appear to increase the risk for kidney stones as long as it also contains plenty of fluids, dietary potassium, and phosphate. Importantly, calcium is associated with protection against colon cancer and osteoporosis -- two conditions that are associated with IBD.
Patients who have stones associated with short-bowel syndrome should eat less fat and foods that contain oxalates. In these people, calcium may bind to unabsorbed fat instead of to oxalates, which increase oxalate levels.

The general recommendations for avoiding kidney stones need to be tailored to the dietary requirements of IBD. Patients should work with their doctors to develop a plan.

Researchers are currently investigating bacteria (called probiotics) and specific foods (called prebiotics) that are metabolized by these bacteria, and the compounds they produce (called synbiotics). Some evidence suggests that alone or in combination, they may have significant benefits in the intestine.

Probiotics are bacterial strains that by themselves may provide a barrier against harmful bacteria, possibly through various mechanisms such as excreting certain acids (lactate, acetate) that inhibit harmful bacteria or compete with them for nutrients. It has been suggested that probiotics may help maintain remission in patients with inflammatory bowel disease (IBD). The specific bacterial strains that might be beneficial, however, are not fully known. The most well-known probiotics are the lactobacilli strains, such as acidophilus, which are found in yogurt and other fermented milk products. Others, however, may prove to be more important, such as bifidobacteria and GG lactobacilli. Other probiotics that may be beneficial for patients with IBD include lactobacilli rhamnosus, casel, plantarium, bulgaricus, and salivarius, and also Enterococcus faecium and Streptococcus thermophilus.
Prebiotics are specific non-digestible molecules called fructo-oligosaccharides, which stimulate the growth of probiotics. These molecules are found in many foods, including Jerusalem artichokes, onions, salsify, bananas, honey, garlic, and leeks. (However, some of these foods can irritate the intestine in patients with IBD.)

Researchers are investigating probiotics, prebiotics, or both for intestinal protection, including benefits for patients with IBD. Foods and supplements containing these substances are available in the U.S. and are heavily marketed in Europe, Japan, and Australia. To date, however, no studies have determined any clear benefits of any specific organism or formulation.

Crohn's disease and surgical procedures that remove parts of the small intestine can inhibit absorption of vitamins, fats, and other important supplements. Taking certain supplements -- such as fish oil, antioxidants, and mineral supplements -- may be beneficial for patients with Crohn's disease.

Vitamins. Deficiencies of vitamins A, C, D, E, B12, and folate (a B vitamin) may result from malabsorption. In general, vitamin supplements may be recommended for everyone with inflammatory bowel disease (IBD), particularly for children to avoid growth retardation. Vitamins A, C, and E are antioxidants, which are scavengers of damaging particles in the body. Folic acid supplements are particularly important for patients who must restrict fresh fruits and vegetables and for those taking sulfasalazine. Folate deficiencies may contribute to the increased risk for colon cancer. Monthly injections of vitamin B-12 may be necessary. Vitamin D is necessary for bone protection. Because some vitamins, such as A and D, can be toxic at high doses, patients should discuss specific dosages with their doctors.

Omega-3 Fatty Acids. The role of fats in inflammatory bowel disease is complex and not fully known. Some evidence suggests that patients with Crohn's burn fat calories at a higher rate than the general population. Patients with IBD may be deficient in essential fatty acids, particularly omega-3 fatty acids (polyunsaturated fats found in oily fish and certain vegetable products such as flaxseed and canola oils). Such fatty acids are also available in supplements as docosahexaenoic (DHA) and eicosapentaneoic (EPA) acids, which are specific compounds found in fish oil.

Omega-3 fatty acids, found plentifully in oily fish and flaxseed and canola oils, are beneficial to people afflicted with inflammatory bowel disease.

Mineral Supplements. Supplements of calcium, magnesium, zinc, selenium, and iron may be needed to offset deficiencies in patients with severe IBD.

Calcium and magnesium are critical for health and strong bones. Many patients with IBD suffer from calcium and vitamin D deficiencies, which cause low bone density. Studies indicate that calcium and vitamin D supplements may be adequate to increase bone density without drugs.
Selenium is a potent antioxidant.
Zinc is important for wound healing, and deficiencies may promote fistulas in Crohn's disease.
Iron supplements may be required for anemia. However, iron overdose is very dangerous. As few as three adult iron tablets can poison children, even fatally. No one, even adults, should take a double dose of iron if one is missed. A doctor should advise patients on correct dosage.

Enteral Nutrition. Enteral nutrition uses a feeding tube that is inserted either through the nose and down through the throat or directly through the abdominal wall into the gastrointestinal tract. It is the preferred method for feeding patients with malnutrition who cannot tolerate eating by mouth. The nutritional formulas used in enteral administration include:

Polymeric diets (containing a balance of standard nutrients).
Elemental diets (predigested nutrients that are absorbed in the first meter of the small intestine). These diets are used less commonly than polymeric diets.

In children, enteral nutrition is given for 6 - 8 weeks. Simple foods are then introduced (chicken, potato, rice), and more complex foods (milk, fiber, wheat-based foods) are then added gradually. However, relapse is still common.

Total Parenteral Nutrition. Total parenteral nutrition (TPN), or hyperalimentation, is the intravenous administration of nutrients through an indwelling catheter (tube). It is used for very severe IBD when patients cannot tolerate any nutrition by mouth or with a feeding tube, and may even be useful as a primary therapy for patients with Crohn's (although not for those with fistulas). It is usually given in the hospital, although increasingly people are giving it to themselves at home. The procedure carries a risk for complications, some serious, including infection, blood clots, and liver failure.

Symptom Management

The following are some ways of managing diarrhea, constipation, or both:

Mild-to-moderate diarrhea may be reduced by taking 1 teaspoon of psyllium hydrophilic colloid (Metamucil) twice a day in a glass of water.
Antidiarrheal drugs include loperamide (Imodium) and a combination of atropine and diphenoxylate (Lomotil). In very ill patients, large doses of some antidiarrheal drugs, such as Lomotil, can trigger the onset of toxic megacolon. Toxic megacolon is a life-threatening complication of other intestinal conditions. It is characterized by a very inflated colon, abdominal distention, and sometimes fever, abdominal pain, or shock.
Opiates or drugs used to relax muscle spasms may help relieve mild-to-moderate diarrhea and abdominal cramps, but they should be used for very short periods and not for severe cases.
Cholestyramine (Questran) has been found to be useful for reducing diarrhea in patients who have had ileal resections.
Bulk-type laxatives can help constipation.

Iron supplements may be required for anemia. Intravenous iron with or without erythropoietin (a hormone that acts in the bone marrow to increase the production of red blood cells) is effective for severe anemia in IBD that does not respond to iron alone. Patients with Crohn's disease benefit most from the combination.

Antidepressants may help relieve emotional problems. However, inflammatory bowel disease is not a psychological disorder, and these drugs will not affect the basic illness.

Although stress is not a cause of inflammatory bowel disease, there are reports of an association between stress and symptom flare-ups. Although no evidence exists to confirm that stress reduction techniques such as relaxation methods, meditation, or cognitive therapy, manage the disease, they might be helpful.

The effects of exercise in Crohn's disease are uncertain. Some research indicates that moderate exercise may trigger excess production of chemicals that could cause flare-up. One small study, however, reported significant improvement in patients who had been sedentary but then embarked on a 12-week exercise program. They walked a little over 2 miles three times a week. During that period there were no flare-ups, and they felt physically and emotionally better than before.

Medications

The primary goal of drug therapy is to reduce inflammation in the intestine. Drugs are effective in reducing the inflammation and accompanying symptoms in up to 80% of patients. Unfortunately, relapses are still frequent, and researchers continue to look for the optimal treatments that will both control symptoms and prevent relapse.

Drugs Used for Crohn's Disease. Drug therapies for Crohn’s disease aim to resolve symptoms (induce remission) and prevent flare-ups (maintain remission). The drugs used depend on the severity of the condition:

Mild-to-moderate Crohn's disease is generally treated with antibiotics and an oral aminosalicylate, such as mesalamine or sulfasalazine. (Some researchers suggest, however, that corticosteroids may be more effective than these drugs in patients with disease in the small intestine and ascending colon. Furthermore, new forms of oral corticosteroids, such as budesonide, may have a lower risk for adverse effects.)

Moderate-to-severe Crohn's disease is treated with corticosteroids, immunosuppressants, or biologic drugs such as infliximab or adalimumab. These drugs may be used alone or in combinations. Some patients with severe Crohn's may be candidates for surgery.

Determining Success. Therapy is considered successful if it can push the disease into remission (and keep it there) without causing significant side effects. The patient's condition is generally considered in remission when the intestinal lining has healed, and symptoms, such as diarrhea, abdominal cramps, and tenesmus (painful defecation), are normal or close to normal. It is sometimes difficult to define remission in Crohn's disease because diagnostic test results do not always correlate with a patient's symptoms or complications outside the intestine.

Patients who cannot tolerate sulfazine, or who are allergic to sulfa drugs, have other options for aminosalicylate drugs, including mesalamine (Asacol, Pentasa), olsalazine (Dipentum), and balsalazide (Colazal). These drugs, like sulfazine, are available as pills. Mesalamine is also available in enema (Rowasa) and suppository (Canasa) forms.

Mesalamine can cause kidney problems and should be used with caution by patients with kidney disease. Common side effects of aminosalicylate drugs include:

Abdominal pain and cramps (mesalamine, balsalazide)
Diarrhea (mesalamine, olsalazine)· Gas (mesalamine)
Nausea (mesalamine)
Hair loss (mesalamine)
Headache (mesalamine, balsalazide)
Dizziness (mesalamine)

All mesalamine preparations, including sulfasalazine, appear to be safe for children, and for women who are pregnant or nursing.

General Guidelines. Corticosteroids (commonly called steroids) are powerful anti-inflammatory drugs used for treating Crohn's disease in adults. Because of their severe side effects, steroids should be reserved for those with moderate-to-severe disease or those who relapse after other therapies. Steroids appear to be safe for pregnant women and can be used if necessary during pregnancy.

Corticosteroids are frequently combined with other drugs, such as 5-aminosalicylic acid (or 5-ASA) drugs, to produce more rapid symptom relief and to allow quicker withdrawal, although such combinations do not improve remission time.

In general, corticosteroids are recommended only for short-term use for achieving remission in active Crohn's disease. The lowest possible dose should be used for the shortest amount of time. Long-term treatments cause significant side effects, and alternative drugs exist. Corticosteroids do not prevent flare-ups and are rarely used for maintenance treatment.

Patients who are malnourished are less likely to respond to steroids, and those who had an initial inadequate response to steroids are also less likely to do well with repeat therapy. Some patients who have had Crohn's disease for a long time may have partial or complete resistance to corticosteroids.

Corticosteroid Types. Prednisone (Deltasone), methylprednisolone (Medrol), and hydrocortisone (Cortef, Cortisol) are the most common corticosteroids. Newer steroids, such as budesonide (Entocort), affect only local areas in the intestine and do not circulate throughout the body. Such drugs may avoid the widespread side effects that are a serious problem with long-term treatment using older conventional steroids. Recent studies suggest that budesonide can help prolong and maintain remission periods in patients with Crohn’s disease.

Administering Corticosteroids. Most corticosteroids can be taken as a pill. For patients who cannot take oral forms, methylprednisolone and hydrocortisone may also be given intravenously or rectally as a suppository, enema, or foam. The severity or location of the condition often determines the form.

Side Effects of Corticosteroids. Standard steroids can have distressing and sometimes serious long-term side effects, including:

Susceptibility to infection
Weight gain (particularly increased fatty tissue on the face and upper trunk and back)
Acne
Excess hair growth
High blood pressure (hypertension)
Weakened bones (osteoporosis)
Cataracts and glaucoma
Diabetes
Muscle wasting
Menstrual irregularities
Upper gastrointestinal ulcers
Personality change, including irritability, insomnia, psychosis, and depression; such emotional changes are sometimes severe enough to produce suicidal thoughts

Withdrawing from Corticosteroids. Once the intestinal inflammation has subsided, steroids must be withdrawn very gradually in order to give the body time to recover its own ability to produce natural steroids. Withdrawal symptoms, including fever, malaise, and joint pain, may occur if the dosage is lowered too rapidly. If this happens, the dosage is increased slightly and maintained until symptoms are gone. More gradual withdrawal is then resumed.

For very active inflammatory bowel disease that does not respond to standard treatments, immunosuppressant drugs are used for long-term therapy. Such drugs suppress or limit actions of the immune system and therefore its inflammatory response, which causes Crohn's disease. Immunosuppressants may help maintain remission in Crohn's disease and heal fistulas and intestinal ulcers caused by this disease. These drugs are sometimes combined with a corticosteroid drug for treating active disease flares.

Other pill forms of immunosuppressants include cyclosporine A (Sandimmune, Neoral) and tracrolimus (Prograf). These drugs are quicker-acting than azathiopine and 6-mercaptopurine. Cyclosporine A generally takes 1 - 2 weeks to take effect. For patients who have Crohn’s disease accompanied by fistulas, Cyclosporine A may be given intravenously. For patients whose condition affects the mouth or area around the anus, tracrolimus is available as a topical ointment.

Methotrexate (MTX, Rheumatrex, Mexate) is another fast-acting type of immunosuppressant. It is given by weekly injections and may be an option for patients with severe Crohn’s disease who have not been helped by other immunosuppressant drugs. However, methotrexate can cause miscarriages and birth defects. Because of these pregnancy complications, both men and women who take methotrexate should use birth control.

Antibiotics are often used to induce remission in mild-to-moderate Crohn's disease. They are also important for treating fistulas, bacterial overgrowth, abdominal abscesses, and any infections around the anus and genital areas. Stopping antibiotics brings on relapse, so long-term therapy is required, carrying a risk for side effects.

The standard antibiotics used for inducing remission in Crohn's disease are ciprofloxacin (Cipro) and metronidazole (Flagyl). Ciprofloxacin is the antibiotic of choice. Over time, metronidazole can cause peripheral neuropathy, a nerve disorder that can cause numbness and tingling in the hands and feet. Other side effects associated with netronidazole include nausea, vomiting, diarrhea, loss of appetite, dizziness, and headaches.

Although ciprofloxacin causes fewer side effects than metrondizaole, it can interact with antacids (Rolaids, Tums) and vitamin and mineral supplements that contain calcium, iron, or zinc. Do not take antacids or vitamin supplements at the same time as the ciprofloxacin dose.

Biologic response modifiers are genetically engineered drugs that target specific proteins involved with the body’s inflammatory response. Of special interest for patients with Crohn's disease are drugs such as infliximab and adalimumab, which target the inflammatory immune factor known as tumor necrosis factor (TNF).

According to a 2007 consensus statement from the American Gastroenterological Association, biologic drugs are generally not used as first-line treatment for most patients with Crohn’s disease. However, some patients -- especially those who have not responded to corticosteroids or who suffer from fistulas -- may benefit from initial treatment with infliximab or other biologic drugs. In all cases, the benefits of biologic drugs need to be weighed against their potential risks, which can include increased risk for infections, lymphoma, and drug-related side effects.

Infliximab (Remicade) acts against TNF and was the first biologic drug approved for treating adults with Crohn's disease. It is made from a genetically designed antibody called a monoclonal antibody (MAb) that blocks the activity of tumor necrosis factor-alpha (TNF-a). In 2006, the FDA approved infliximab for children with active Crohn’s disease.

Infliximab cannot cure Crohn’s disease, but it can help control symptoms and, possibly, keep the disease in remission. Studies suggest that up to 80% of patients respond initially, and about a third of all patients remain in remission after a single infusion. Remissions last a few weeks to several months. A 6-week course of infliximab helps close and heal fistulas in half of patients and reduces drainage in 70%. The drug is also being studied for maintenance therapy, although given some significant side effects, it will most likely be reserved for active disease that does not respond to other treatments.

Infliximab’s severe side effects may include tuberculosis, pneumonia, and other infections; lymphoma (a type of cancer); liver failure; and aplastic anemia.

Adalimumab (Humira) was approved early in 2007 for treating adult patients with moderate-to-severe Crohn's disease. Like infliximab, adalimumab blocks TNF. Also approved for treating symptoms of rheumatoid arthritis, adalimumab requires injections to initiate treatment, followed by a maintenance shot every other week.

Adalimumab's label includes a boxed warning. The medicine has been associated with serious, sometimes fatal, infections, including tuberculosis and sepsis. Other severe side effects may include lymphoma, upper respiratory infections, sinusitis, and nausea.

Several other TNF modifiers are being investigated. Among the most promising, according to several 2007 studies in the New England Journal of Medicine, is certolizumab (Cimzia).

Selective adhesion molecule inhibitors block the genetic expression of cell adhesion molecules (CAMs). CAMs play an important role in the accumulation of immune factors that cause the inflammatory response. Natalizumab (Tysabri) is a monoclonal antibody that blocks alpha4 integrin, a protein that binds to CAMs. This drug is approved to treat multiple sclerosis and is also being studied for Crohn’s disease. Studies have suggested that natalizumab can help patients with Crohn’s disease achieve and maintain remission.

However, natalizumab is associated with severe side effects, including a rare neurological condition called progressive multifocal leukoencephalopathy (PML). A 2006 study found that patients who take natalizumab have a very low risk for PML. Still, the potential benefits of natalizumab need to be weighed against its risks for serious side effects. As of summer 2007, the FDA was considering approving natalizumab for treatment of moderate-to-severe Crohn’s disease in patients who have failed or cannot tolerate other therapies

Other Biologic Therapies. Investigators are researching other biologic therapies that target other types of immune factors that play a role in the inflammatory response. These factors include interferons, anti-interferon antibodies, anti-interleukin antibodies, p65 anti-sense oligonucleotides, growth factors, and others. Several 2006 studies indicated that fontolizumab (HuZaf), an anti-interferon gamma monoclonal antibody, shows promise as a treatment for Crohn’s disease. Sargramostim (Leukine), a granulocyte-macrophage colony stimulating factor, is another biologic drug that may help improve symptoms and quality of life for patients with active Crohn’s disease. Visilizumab (Nuvion), which targets the CD3 receptor on T cells, is another biologic drug being investigated. More research in each of these areas is needed.

Parasites. Inflammatory bowel disease is rare in countries where intestinal infection with parasites called helminthes is common. Small studies have reported significant remission rates in patients with Crohn's disease or ulcerative colitis who have swallowed the eggs of a specific parasitic worm. The parasite does not invade tissue or spread other diseases. The parasite induces production of specific T cells, called TH-2, which are immune factors that may be protective against overactivity of cytokines that trigger Crohn's. More research is needed.

Growth Factors. Growth factor hormones increase immune factors, so one would think they might be harmful for patients with Crohn's disease. However, some research suggests that growth factors may be helpful for speeding healing in certain patients, including children. More research, however, is needed.

Surgery

Between two-thirds to three-quarters of patients with Crohn's eventually need surgery when medication cannot control symptoms. Among children with Crohn's, half require surgery within 5 years of diagnosis.

In general, surgery is used to remove damaged areas of the colon:

The entire colon (proctocolectomy) or a section of it (subtotal colectomy) may need to be removed in cases of extensive disease in the large intestine.
Resection or strictureplasty, which removes limited sections of the colon, may be appropriate for many patients.

Surgery is useful only for reducing symptoms. It cannot cure Crohn's disease because new disease can appear in other areas of the intestine. Surgery may be helpful for relieving symptoms and to correct blockage, perforation, fistulas, or bleeding.

Surgery has reportedly improved the quality of life in most patients, except for those who continued to have active disease. Many children with Crohn's who have suffered growth problems catch up to near-normal growth levels after surgery. Some experts urge, in fact, that many patients should consider surgery in the early stages of the disease.

Some patients may be candidates for a procedure called strictureplasty, which involves cutting and stitching only the areas obstructing the intestine, so that it widens the intestine without removing sections of it. It involves the following:

A balloon attached to a catheter (a thin tube) is passed along the intestine.
If it becomes blocked, then a stricture (an obstruction) is indicated.
The surgeon widens the intestine at the point, but does not remove sections of it.
The procedure is by no means foolproof. Nearly half of patients require re-operation, but strictureplasty in the jejunum and ileum of the small intestine is safe and generally effective over the long term. It may not be useful for Crohn's disease in duodenum (the first section of the small intestine).

The invasiveness of the surgical procedure to remove damaged portions of the colon depends on the severity of the disease.

Resection of the Colon. In most cases of Crohn's disease, only a part of the colon needs to be removed, a procedure called resection.

Click the icon to see an illustrated series depicting large bowel resection surgery.

Subtotal Colectomy. Subtotal colectomy is more extensive than resection and removes more of the colon. Disease in the upper parts of the small intestine tends to require more extensive surgery than in the lower small intestine.

In general, either procedure requires a general anesthetic and involves the following:

An incision is made in the abdomen.
The diseased portion of the colon is identified and removed. (Strictureplasty is sometimes used alone with resection.)
Once a diseased segment of the colon is removed, the two ends are reconnected, and this connection is called an anastomosis.

Open Surgery or Laparoscopy. Resection or subtotal colectomy may be performed using one of two surgical approaches:

Open surgery, which requires a wide abdominal incision.
Laparoscopy, which uses a few small incisions through which a tube is inserted containing a tiny camera for viewing the area. To date, however, this procedure is best suited for patients with short-segment disease in the ileum who also have no other complications, such as fistulas and abscesses.

Click the icon to see an image of a laparoscopy procedure.

Short-bowel syndrome. If large segments of the small intestine are removed, the patient is at higher risk for short-bowel syndrome, a complication in which there is a problem absorbing nutrients. The risk is far lower with strictureplasty. The condition used to be fatal, but patients now can live normal and productive lives using total parenteral nutrition (the intravenous administration of nutrients), which can be self-administered at home in many cases.
Leakage or obstruction in the areas where the colon has been reconnected (the anastomosis).
Infections. In a 2003 study, the use of drugs that modify the immune system (azathioprine, 6-MP, methotrexate, and infliximab) was effective in reducing the risk for serious infection in the abdomen.

Proctocolectomy with ileostomy is removal of the entire colon and creation of an ileostomy. It involves the following:

To perform proctocolectomy, the surgeon removes the entire colon, including the lower part of the rectum and the sphincter muscles that control bowel movements.
To perform ileostomy, the surgeon makes a small opening in the lower right corner of the abdomen called a stoma. The surgeon then connects cut ends of the small intestine to this opening. A bag is placed over the opening and accumulates waste matter. It requires emptying several times a day.

Recurrence of Crohn's disease is very common after any procedure. The risk may be 7 - 25% for each year after resection, with an average risk of 50% at 5 years after resection. (Even if the entire colon is removed, there is still a high chance of recurrence in the rectum and a somewhat lower risk for recurrence in the small intestine.)

Patients at highest risk for recurrence include:

Smokers
Those whose disease occurred in the ileum (the lowest part of the small intestine) and colon
Those with abscesses or fistulas
Those have had previous surgeries

Various drugs are used to prevent recurrence. They include the antibiotic metronidazole (Flagyl), mesalamine, infliximab, and mercaptopurine. These drugs can have severe side effects. And, it is not clear if these or any other drugs are effective in preventing recurrence. Even if medications can help prevent recurrence in some patients, it is not yet known how to identify this subset of patients. (In any case, steroids do not appear to help prevent recurrence.)

In some cases, surgery is needed for emergency conditions that can occur with Crohn's disease. Emergency surgery is used to:

Stop severe intestinal bleeding
Clear small bowel obstruction
Drain and heal abscesses or fistulas
Repair perforation

Procedures for transplanting the small intestine in patients with intestinal failure are under investigation. These are still experimental and are being tested in patients who have lost so much of their small intestine that they must rely on total parenteral nutrition (intravenous administration of nutrition). Small-bowel transplantation is a more difficult procedure than some other transplants, because of the high rate of potential complications, including infection and organ rejection. Patients who have transplants must take immunosuppressant drugs for the rest of their lives. Furthermore, there is some evidence that Crohn's disease recurs in the transplanted bowel.

Resources

www.ccfa.org -- Crohn's & Colitis Foundation of America
www.gastro.org -- American Gastroenterological Association
www.acg.gi.org -- American College of Gastroenterology
www2.niddk.nih.gov -- National Digestive Diseases Information Clearinghouse

References

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of the T300A non-synonymous variant of the ATG16L1 gene with susceptibility to paediatric Crohn's disease. Gut. 2007 Aug;56(:1171-1173.

Baldassano RN, Bradfield JP, Monos DS, Kim CE, Glessner JT, Casalunovo T, et al. Association of variants of the interleukin-23 receptor gene with susceptibility to pediatric Crohn's disease. Clin Gastroenterol Hepatol. 2007 Jul 5; [Epub ahead of print]

Cornish J, Tan E, Teare J, Teoh TG, Rai R, Clark SK, et al. A meta-analysis on the influence of inflammatory bowel disease on pregnancy. Gut. 2007 Jun;56(6):830-7. Epub 2006 Dec 21.

Cummings JR, Cooney R, Pathan S, Anderson CA, Barrett JC, Beckly J, et al. Confirmation of the role of ATG16l1 as a Crohn's disease susceptibility gene. Inflamm Bowel Dis. 2007 Aug;13(:941-6.

Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, et al. Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology. 2006 Aug;131(2):366-78.

Dubinsky MC, Wang D, Picornell Y, Wrobel I, Katzir L, Quiros A, et al. IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease. Inflamm Bowel Dis. 2007 May;13(5):511-5.

Issa M, Vijayapal A, Graham MB, Beaulieu DB, Otterson MF, Lundeen S, et al. Impact of Clostridium difficile on inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):345-51.

Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.

Rodemann JF, Dubberke ER, Reske KA, Seo da H, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007 Mar;5(3):339-44.

Sandborn WJ, Feagan BG, Stoinov S, Honiball PJ, Rutgeerts P, Mason D, et al. Certolizumab pegol for the treatment of Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):228-238.

Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N Engl J Med. 2007 Jul 19;357(3):239-250.

Tremaine WJ. Inflammatory bowel disease and Clostridium difficile-associated diarrhea: a growing problem. Clin Gastroenterol Hepatol. 2007 Mar;5(3):310-1.

Tremelling M, Cummings F, Fisher SA, Mansfield J, Gwilliam R, Keniry A, et al. IL23R variation determines susceptibility but not disease phenotype in inflammatory bowel disease. Gastroenterology. 2007 May;132(5):1657-64. Epub 2007 Feb 24.

Review Date:
8/30/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Zinc

FitSugar — Wed, 08 Oct 2008 17:35:25 -0700

Overview

Overview
Dietary Sources
Available Forms
How to Take It
Precautions
Possible Interactions
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Zinc is an essential trace mineral, so you get it through the foods you eat. Next to iron, zinc is the most common trace mineral in the body and is found in every cell. It has been used since ancient times to help heal wounds and plays an important role in the immune system, reproduction, growth, taste, vision, and smell, blood clotting, and proper insulin and thyroid function.

Zinc also has some antioxidant properties. Therefore it helps protect cells in the body from damage caused by free radicals. Free radicals may contribute to the aging process as well as the development of a number of health problems, including heart disease and cancer. Antioxidants such as zinc can neutralize free radicals and may reduce or even help prevent some of the damage they cause.

Your body doesn't need a large amount of zinc; the recommended daily allowance for adults is 8 - 11 mg. A mild zinc deficiency isn't uncommon but taking a multivitamin plus eating a healthy diet should give you all the zinc you need. It's rare for people in industrialized countries to be seriously deficient in zinc. Low zinc levels are sometimes seen in the elderly, alcoholics, people with anorexia, and people on very restricted diets. People who have malabsorption syndromes, such as Crohn's disease or celiac disease, may also be deficient in zinc.

Symptoms of zinc deficiency include loss of appetite, poor growth, weight loss, lack of taste or smell, poor wound healing, skin problems (such as acne, atopic dermatitis and psoriasis), hair loss, lack of menstrual period, night blindness, white spots on the fingernails, and depression.

Zinc lessens the amount of copper your body absorbs, and high doses of zinc can cause a copper deficiency. For that reason, it is usually recommended that you take 2 mg of copper along with a zinc supplement.

Acne

Some studies suggest that taking oral zinc supplements may help improve acne. However, most studies used a high dose of zinc that could have toxic effects, and not all studies found any benefit. There is some evidence that a topical form of zinc, used in conjunction with the topical antibiotic erythromycin, might be helpful.

Age-Related Macular Degeneration

Zinc is often recommended to slow the progress of age-related macular degeneration, an eye disease that occurs when the macula, the part of the retina that is responsible for central vision, starts to deteriorate. A major clinical trial, the Age Related Eye Disease Study (AREDS1), found that people who had macular degeneration could slow its progression by taking zinc (80 mg), vitamin C (500 mg), vitamin E (400 mg), beta-carotene (15 mg), and copper (2 mg). But not all studies have found zinc to be helpful. One 2007 study found that people with macular degeneration had deposits with high levels of zinc, leading some researchers to wonder if zinc actually contributes to macular degeneration. A new study, AREDS2, is examining exactly what role zinc plays in macular degeneration.

Colds

Many people believe that taking zinc lozenges or using zinc nasal spray when they first show signs of a cold can reduce the duration and severity of symptoms, but the evidence is decidedly mixed. More and better studies are needed that examine which kinds of zinc may be effective and against which kinds of cold viruses.

Immune Response

Zinc is necessary for a healthy immune system, and people who are deficient in zinc tend to be more susceptible to a variety of infections. For that reason, zinc supplements are sometimes suggested to improve your overall immunity and ward off infections, but that may only work if you are deficient in zinc to start with.

Sickle Cell Disease

People who have sickle cell disease are often deficient in zinc. Studies suggest that taking zinc supplements may help reduce symptoms of the disease. Children who took zinc showed improvements in height and weight, and had fewer sickle-cell crises.

Stomach Ulcers

Some studies suggest that zinc may help speed the healing of gastric ulcers.

Attention Deficit Hyperactivity Disorder (ADHD)

Some evidence suggests that taking zinc may cause a slight improvement in symptoms, reducing hyperactivity, impulsivity, and impaired socialization in children. However, there was no change in attention deficit symptoms, and zinc may only benefit children who are deficient to start with. Zinc may be most helpful to children with a high body mass index, low levels of free fatty acids in their blood, and low levels of zinc.

Herpes simplex

Topical preparations of zinc have shown benefit in relieving symptoms and preventing recurrences of oral herpes lesions (canker sores).

HIV/AIDS

Zinc deficiency is common in people with HIV (even before symptoms appear) or AIDS. In people with AIDS, low levels of zinc may be a result of poor absorption, medications, and loss of this important nutrient through vomiting or diarrhea. Zinc deficiency leads to increased susceptibility to infection in people with AIDS (called an opportunistic infection). Some studies show that HIV positive people who take zinc have fewer infections, gain more weight, and have a better immune system response. But not all studies agree, and one even suggests that taking zinc may be associated with higher death rates. If you have HIV or AIDS, talk to your doctor before taking zinc or any supplement.

Wilson's Disease

Some early research suggests that zinc may be beneficial in treating Wilson's disease, a condition which causes copper to build up in the body. Because zinc lessens the body's absorption of copper, it may help reduce levels of copper in people with Wilson's disease.

Other

Other conditions may increase the need for zinc or affect how your body absorbs or uses this mineral. It is not known, however, whether taking zinc will help treat any of these conditions:

Acrodermatitis enteropathica (a skin disorder due to an inherited inability to absorb zinc properly)
Alcoholism
Cirrhosis (liver disease)
Kidney disease
Celiac disease
Inflammatory bowel disease (ulcerative colitis and Crohn's disease)
High blood pressure
Pancreatic conditions
Pregnancy

Dietary Sources

Your body absorbs 20 - 40% of the zinc present in food. Zinc from animal foods like red meat, fish, and poultry is more readily absorbed by the body than zinc from plant foods. Zinc is best absorbed when taken with a meal that contains protein.

The best sources of zinc are oysters (richest source), red meats, poultry, cheese (ricotta, Swiss, gouda), shrimp, crab, and other shellfish. Other good, though less easily absorbed, sources of zinc include legumes (especially lima beans, black-eyed peas, pinto beans, soybeans, peanuts), whole grains, miso, tofu, brewer's yeast, cooked greens, mushrooms, green beans, tahini, and pumpkin, and sunflower seeds.

Available Forms

Zinc is available in several forms. Zinc sulfate is the least expensive form, but it is the least easily absorbed and may cause stomach upset.

More easily absorbed forms of zinc are zinc picolinate, zinc citrate, zinc acetate, zinc glycerate, and zinc monomethionine. If zinc sulfate causes stomach irritation, you can try another form, such as zinc citrate.

The amount of elemental zinc is listed on the product label (usually 30 - 50 mg). To determine the amount to take in supplement form, remember that you get about 10 - 15 mg from food.

Zinc lozenges, used for treating colds, are available in most drug stores. There are also nasal sprays developed to reduce nasal and sinus congestion. Nasal gels seem to work better than the spray.

How to Take It

You should take zinc with water or juice. However, if zinc causes stomach upset, it can be taken with meals. Don't take zinc at the same time as iron or calcium supplements.

A strong relationship exists between zinc and copper. Too much of one can cause a deficiency in the other. Long-term use of zinc (including zinc in a multivitamin) should be accompanied by copper.

Do not give zinc supplements to a child without talking to your doctor.

Daily intake of dietary zinc (according to the U.S. recommended dietary allowances) are listed below:

Pediatric

Infants birth to 6 months: 2 mg (AI)
Infants 7 - 12 months: 3 mg (RDA)
Children 1 - 3 years: 3 mg (RDA)
Children 4 - 8 years: 5 mg (RDA)
Children 9 - 13 years: 8 mg (RDA)
Males 14 - 18 years: 11 mg (RDA)
Females 14 - 18 years: 9 mg (RDA)

Adult

Males 19 years and older: 11 mg (RDA)
Females 19 years and older: 8 mg (RDA)
Pregnant females 14 - 18 years: 12 mg (RDA)
Pregnant females 19 years and older: 11 mg (RDA)
Breastfeeding females 14 - 18 years: 13 mg (RDA)
Breastfeeding females 19 years and older: 12 mg (RDA)

Therapeutic ranges (elemental zinc):

Men: 30 - 60 mg daily
Women: 30 - 45 mg daily

You should not take high doses of zinc for more than a few days unless your doctor tells you to. Talk to your doctor before taking more than 40 mg of zinc per day.

Precautions

Because of the potential for side effects and interactions with medications, you should take dietary supplements only under the supervision of a knowledgeable health care provider.

Research has shown that less than 40 mg a day is a safe amount to take over time, but researchers are not sure what happens if more is taken over a long period.

Common side effects of zinc include stomach upset, nausea, vomiting, and a metallic taste in the mouth. High doses of zinc can cause dizziness, headache, drowsiness, increased sweating, loss of muscle coordination, alcohol intolerance, hallucinations, and anemia.

Very high doses of zinc may actually weaken immune function. High doses of zinc may also lower HDL ("good") cholesterol and raise LDL ("bad") cholesterol.

Possible Interactions

If you are being treated with any of the following medications, you should not use zinc without first talking to your health care provider.

Amiloride (Midamor) -- Amiloride is a potassium-sparing diuretic (water pill) that may increase the levels of zinc in your blood. Do not take zinc supplements if you take amiloride.

Blood pressure medications, ACE Inhibitors -- A class of medications called ACE inhibitors, used to treat high blood pressure, may decrease the levels of zinc in your blood. ACE inhibitors include:

Captopril (Capoten)
Benazepril (Lotensin)
Enalapril (Vasotec)
Lisinopril (Zestril)
Fosinopril (Monopril)
Ramipril (Altace)
Perindopril (Aceon)
Quinapril (Accupril)
Moexipril (Univasc)
Trandolapril (Mavik)

Antibiotics -- Zinc may decrease your body's absorption of two kinds of antibiotics, quinolones and tetracyclines. These include:

Ciprofloxacin (Cipro)
Levofloxacin (Levaquin)
Ofloxacin (Floxin)
Moxifloxacin (Avelox)
Norfloxacin (Noroxin)
Gatifloxacin (Tequin)
Tetracycline
Minocycline (Minocin)
Demeclocycline (Declomycin)

However, doxycycline (Vibramycin) does not seem to interact with zinc.

Cisplatin (Platinol-AQ) -- This drug, used for chemotherapy to treat some types of cancers, may cause more zinc to be excreted in your urine. If you are undergoing chemotherapy, do not take zinc or any other supplement without talking to your oncologist.

Deferoxamine (Desferal) -- This medication, used to remove excess iron from the blood, also increases the amount of zinc that is lost in urine.

Immunosuppressant medications -- Since zinc may make the immune system stronger, it should not be taken with corticosteroids (such a prednisone), cyclosporine, or other medications intended to suppress the immune system.

Nonsteroidal anti-inflammatory drugs (NSAIDs) -- Zinc interacts with NSAIDs and could reduce the absorption and effectiveness of these medications. Examples of NSAIDs, which help to reduce pain and inflammation, include ibuprofen (Advil, Motrin), naprosyn (Aleve), piroxicam (Feldene), and indomethacin (Indocin).

Penicillamine -- This medication, used to treat Wilson's disease (where excess copper builds up in the brain, liver, kidney, and eyes) and rheumatoid arthritis, decreases the levels of zinc in your blood.

Thiazide diuretics (water pills) -- This class of medications lowers the amount of zinc in your blood by increasing the amount of zinc that is passed in your urine. If you take thiazide diuretics, your doctor will monitor levels of zinc and other important minerals in your blood:

Chlorothiazide (Diuril)
Hydrochlorothiazide
Chlorthalidone (Hygroton)
Indapamide (Lozol)
Metolozone (Zaroxolyn)
Polythiazide (Renese)
Quinethazone (Hydromox)
Trichlormethiazide (Metahydrin, Naqua, Diurese)

Supporting Research

Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. ArchOphthalmol. 2001;119(10):1417-1436.

Al-Maroof RA, Al-Sharbatti SS. Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. Saudi Med J. 2006 Mar;27(3):344-50

Altaf W, Perveen S, Rehman KU, et al. Zinc supplementation in oral rehydration solutions: experimental assessment and mechanisms of action. J Am Coll Nutr. 2002;21(1):26-32.

Anderson RA, Roussel AM, Zouari N, Mahjoub S, Matheau JM, Kerkeni A. Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. J Am Coll Nutr. 2001;20(3):212-218.

Arnold LE, Pinkham SM, Votolato N. Does zinc moderate essential fatty acid and amphetamine treatment of attention deficit/hyperactivity disorder? J Child Adolesc Psychopharmacol. 2000;10:111-117.

Baumgaertel A. Alternative and controversial treatments for attention-deficit/hyperactivity disorder. Pediatr Clin of North Am. 1999;46(5):977-992.

Bekaroglu M, Aslan Y, Gedik Y. Relationships between serum free fatty acids and zinc, and attention deficit hyperactivity disorder: a research note. J Child Psychol Psychiatry. 1996;37(2):225-227.

Belongia EA, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med. 2001;111(2):103-108.

Berger MM, Spertini F, Shenkin A, et al. Trace element supplementation modulates pulmonary infection rates after major burns: a doublt-blind, placebo-controlled trial. Am J Clin Nutr. 1998;68(2):365-371.

Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28:181-90.

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.

Brion M, Lambs L, Berthon G. Metal ion-tetracycline interactions in biological fluids. Part 5. Formation of zinc complexes with tetracycline and some of its derivatives and assessment of their biological significance. Agents Actions. 1985;17:230-242.

Brouwers JR. Drug interactions with quinolone antibacterials. Drug Saf. 1992;7(4):268-281.

Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Prog Retin Eye Res. 2000;19(2):205-221.

Chausmer AB. Zinc, insulin and diabetes. J Am Coll Nutr. 1998;17(2):109-115.

Cho E, Stampfer MJ, Seddon JM, et al. Prospective study of zinc intake and the risk of age-related macular degeneration. Ann Epidemiol. 2001;11(5):328-336.

Congdon NG and West KP. Nutrition and the eye. Curr Opin Opthalmol. 1999;10:464-473.

Das UN. Nutritional factors in the pathobiology of human essential hypertension. Nutrition. 2001;17(4):337-346.

Dendrinou-Samara C, Tsotsou G, Ekateriniadou E, et al. Anti-inflammatory drugs interacting with Zn(II), Cd(II) and Pt(II) metal ions. J Inorg Biochem. 1998; 71: 171-179.

Dreno B, Amblard P, Agache P, Sirot S, Litoux P. Low doses of zinc gluconate for inflammatory acne. Acta Derm Venereol. 1989;69:541-543.

Dreno B, Trossaert M, Boiteau HL, Litoux P. Zinc salts effects on granulocyte zinc concentration and chemotaxis in acne patients. Acta Dermatol Venereol. 1992;72:250-252.

Eby GA, Halcomb WW. Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common-cold treatment: a double-blind, placebo-controlled clinical trial. Altern Ther Health Med. 2006 Jan-Feb;12(1):34-8.

Fortes C, Forastiere F, Agabiti N, et al. The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc. 1998;46:19-26.

Garland ML, Hagmeyer KO. The role of zinc lozenges in treatment of the common cold. Ann Pharmacother. 1998;32:63-69.

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.

Girodon F, Lombard M, Galan P, et al. Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab. 1997;41(2):98-107.

Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med. 2001;7(3):49-56.

Golik A, Zaidenstein R, Dishi V, et al. Effects of captopril and enalapril on zinc metabolism in hypertensive patients. J Am Coll Nutr. 1998;17:75-78.

Grahn BH, Paterson PG, Gottschall-Pass KT, Zhang Z. Zinc and the eye. J Am Coll Nutr. 2001;20(2 Suppl):106-118.

Hambridge M. Human zinc deficiency. J Nutr. 2000;130(5S suppl):1344S-1349S.

Herzberg M, Lusky A, Blonder J, Frenkel Y. The effect of estrogen replacement therapy on zinc in serum and urine. Obstet Gynecol. 1996;87(6):1035-1040.

Hines Burnham, et al, eds. Drug Facts and Comparisons. St. Louis, MO: Facts and Comparisons; 2000:1295.

Hirt M, Nobel Sion, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. ENT J. 2000;79(10):778-780, 782.

Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001.

Intorre F, Polito A, Andriollo-Sanchez M, Azzini E, Raguzzini A, Toti E, et al. Effect of zinc supplementation on vitamin status of middle-aged and older European adults: the ZENITH study. Eur J Clin Nutr. 2007 Jul 11; Epub ahead of print

Karyadi E, West CE, Schultnick W, et al. A double blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status. Am J Clin Nutr. 2002;75:720-727.

Kristal AR, Stanford JL, Cohen JH, Wicklund K, Patterson RE. Vitamin and mineral supplement use is associated with reduced risk of prostate cancer. Can Epidemiol. 1999;8(10):887-892.

Krowchuk DP. Treating acne. A practical guide. Med Clin North Am. 2000;84(4):811-828.

Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst. 2007;99:754-64.

Lengyel I, Flinn J, Peto T, Linkous D, Cano K, Bird A, et al. High concentration of zinc in sub-retinal pigment epithelial deposits. Exp Eye Res. 2007 Apr;84(4):772-780.

Li RC, Lo KN, Lam JS, et al. Effects of order of magnesium exposure on the postantibiotic effect and bactericidal activity of ciprofloxacin. J Chemother. 1999;11(4):243-247.

Lih-Brody L, Powell Sr, Collier KP, et al. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig Dis Sci. 1996;41(10):2078-2086.

Meyer F, Galan P, Douville P, et al. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int J Cancer. 2005;116:182-6.

Meynadier J. Efficacy and safety study of two zinc gluconate regimens in the treatment of inflammatory acne. Eur J Dermatol. 2000;10:269-273.

Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions [see comments]. Arch Intern Med. 1998;158(20):2200-2211.

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.

Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11(1):45-54.

Osendarp SJ, van Raaij JM, Darmstadt GL, Baqui AH, Hautvast JG, Fuchs GJ. Zinc supplementation during pregnancy and effects on growth and morbidity in low birthweight infants: a randomised placebo controlled trial. Lancet. 2001;357(9262):1080-1085.

Otomo S, Sasajima M, Ohzeki M, Tanaka I. Effects of D-penicillamine on vitamin B6 and metal ions in rats [in Japanese]. Nippon Yagurigaku Zasshi. 1980;76(1):1-13.

Papageorgiou PP, Chu AC. Chloroxylenol and zinc oxide containing cream (Nels cream) vs. 5% benzoyl peroxide cream in the treatment of acne vulgaris. A double-blind, randomized, controlled trial. Clin Exp Dermatol. 2000;25:16-20.

Patrick L. Nutrients and HIV: part 2 -- vitamins A and E, zinc, B-vitamins, and magnesium. Alt Med Rev. 2000;5(1):39-51.

Penny ME, Peerson JM, Marin RM, et al. Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru. J Pediatr. 1999;135(2 Pt 1):208-217.

Physicians' Desk Reference. 54th ed. Montvale, NJ: Medical Economics Co., Inc.: 2000:678-683.

Pizzorno JE, Murray MT. Textbook of Natural Medicine. New York, NY: Churchilll Livingstone. 1999:1210; 1274;1383-1384.

Prasad AS. Clinical and biochemical manifestations of zinc deficiency in human subjects. J Am Coll Nutr. 1985;4(1):65-72.

Prasad AS, Beck FW, Kaplan J, et al. Effect of zinc supplementation on incidence of infections and hospital admissions in sickle cell disease (SCD). Am J Hematol. 1999;61(3):194-202.

Prasad AS, Fitzgerald JT, Bao B, Beck FW, Chandrasekar PH. Duration of symptoms and plasma cytokine levels in patients with the common cold treated with zinc acetate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2000;133(4):245-252.

Pronsky Z. Food-Medication Interactions. 9th ed. Pottstown, Pa: Food-Medicine Interactions; 1995.

Sazawal S, Black RE, Jalla S, et al. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatr. 1998;102(part 1):1-5.

Seitz HK, Poschl G, Simanowski UA. Alcohol Cancer. Recent Dev Alcohol. 1998;14:67-95.

Shah D, Sachdev HP. Effect of gestational zinc deficiency on pregnancy outcomes: summary of observation studies and zinc supplementation trials. Br J Nutr. 2001;85 Suppl 2:S101-S108.

Shanker AH, Prasad AS. Zinc and immune function: the biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68(2 Suppl):447S-463S.

Shay NF, Manigan HF. Neurobiology of zinc-influenced eating behavior. J Nutr. 2000;130:1493S-1499S.

Sinclair S. Male infertility: nutritional and environmental considerations. Altern Med Rev. 2000;5(1):28-38.

Toren P, Eldar S, Sela BA, et al. Zinc deficiency in attention-deficit hyperactivity disorder. Biol Psychiatry. 1996; 40:1308-1310.

Toyoda M, Morohashi M. An overview of topical antibiotics for acne treatment. Dermatology. 1998;196(1):130-134.

VandenLangenberg GM, Mares-Perlman JA, Klein R, Klein BE, Brady WE, Palta M. Associations between antioxidant and zinc intake and the 5-year incidence of early age-related maculopathy in the Beaver Dam Eye Study. Am J Epidemiol. 1998;148(2):204-214.

van Leeuwen R, Boekhoorn S, Vingerling JR, et al. Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA. 2005;294:3101-7.

Walter RM Jr, Uriu-Hare JY, Olin KL, et al. Copper, zinc, manganese, and magnesium status and complications of diabetes mellitus. Diabetes Care. 1991;14(11):1050-1056.

Wong Wy, Thomas CM, Merkus JM, Zielhuis GA, Steegers-Theunissen RP. Male factor subfertility: possible causes and the impact of nutritional factors. Fertil Steril. 2000;73(3):435-442.

Zaichick VYe, Sviridova TV, Zaichick SV. Zinc in the human prostate gland: normal, hyperplastic and cancerous. Int Urol Nephrol. 1997;29(5):565-574.

Zozaya JL. Nutritional factors in high blood pressure. J Hum Hypertens. 2000;14 Suppl 1:S100-S104.

Review Date:
9/26/2007
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

Magnesium

FitSugar — Wed, 08 Oct 2008 17:35:25 -0700

Overview

Overview
Uses
Dietary Sources
Available Forms
How to Take It
Precautions
Possible Interactions
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Overview

Magnesium is a mineral that is involved in over 300 reactions in the body. It is important for every organ in the body, particularly the heart, muscles, and kidneys. It also contributes to the composition of teeth and bones. Most importantly, it activates enzymes, contributes to energy production, and helps regulate calcium levels as well as copper, zinc, potassium, vitamin D, and other important nutrients in the body.

Magnesium is available in many foods. However, most people in the United States probably do not get as much magnesium as they should from their diet. Magnesium is found in whole unprocessed foods in the diet. However, different methods for calculating amounts of magnesium in foods often lead to conflicting results. In addition, not all foods have been thoroughly analyzed.

Despite the fact that dietary levels of magnesium are often low, actual deficiency of this nutrient is rare. Certain medical conditions, however, can upset the body's magnesium balance. For example, intestinal flu with vomiting or diarrhea can cause temporary magnesium deficiencies. Certain stomach and bowel diseases (such as irritable bowel syndrome or IBS and ulcerative colitis), diabetes, pancreatitis, hyperthyroidism (high thyroid hormone levels), kidney malfunction, and use of diuretics can lead to deficiencies. Too much coffee, soda, salt, or alcohol intake as well as heavy menstrual periods, excessive sweating, and prolonged stress can also lower magnesium levels.

Symptoms of magnesium deficiency may include agitation and anxiety, restless leg syndrome (RLS), sleep disorders, irritability, nausea and vomiting, abnormal heart rhythms, low blood pressure, confusion, muscle spasm and weakness, hyperventilation, insomnia, poor nail growth, and even seizures.

Foods rich in magnesium include unrefined grains, nuts and green vegetables. Green leafy vegetables are particularly good sources of magnesium because of their chlorophyll content.

Uses

Getting enough magnesium may help facilitate the results of conventional treatment for the following conditions:

Asthma and emphysema

A population-based clinical study of over 2,500 children aged 11 - 19 years found that low dietary magnesium intake may be associated with a risk of developing asthma. The same was found in a group of over 2,600 adults aged 18 - 70. In addition, some clinical studies suggest that intravenous and inhaled magnesium can help treat acute attacks of asthma in children aged 6 - 18 as well as adults. However, evidence from other clinical studies report that long-term oral magnesium supplementation does not lead to improved control in adult asthma.

Attention deficit/hyperactivity disorder (ADHD)

Some experts believe that children with attention deficit/hyperactivity disorder (ADHD) may be exhibiting the effects of mild magnesium deficiency (such as irritability, decreased attention span, and mental confusion). In one clinical study of 116 children with ADHD, 95% were magnesium deficient. In a separate clinical study, 75 magnesium-deficient children with ADHD were randomly assigned to receive magnesium supplements in addition to standard treatment or standard treatment alone for 6 months. Those who received magnesium demonstrated a significant improvement in behavior, whereas those who received only standard therapy without magnesium exhibited worsening behavior.

These results suggest that magnesium supplementation, or at least high amounts of magnesium in the diet, may prove to be beneficial for children with ADHD.

Depression

Major depression is a mood disorder characterized by a sense of inadequacy, despondency, decreased activity, pessimism, and sadness where these symptoms severely disrupt and negatively affect the person's life. Clinical studies have found that dietary deficiencies of magnesium, coupled with excess calcium and stress may cause many cases of other related symptoms, including agitation, anxiety, irritability, confusion, sleeplessness, headache, confusion, and hyperexcitability.

Diabetes

Type 2 diabetes is associated with low levels of magnesium in the blood. A large clinical study of over 2000 people found that higher dietary intake of magnesium may protect against development of type 2 diabetes. Magnesium was found to improve insulin sensitivity in these people, reducing the risk of developing type 2 diabetes. Other clinical studies have found similar results, especially in the elderly. Magnesium deficiency in diabetic patients may decrease their immunity, making them more susceptible to infections and illnesses.

Fibromyalgia

Results of a preliminary clinical study including 24 people with fibromyalgia suggest that a proprietary tablet containing both malic acid and magnesium may improve pain and tenderness associated with this health condition when taken for at least 2 months. Others suggest that the combination of calcium and magnesium may be helpful for some people with fibromyalgia.

However, a review article evaluating many studies concluded that magnesium with malic acid offered no relief for those with this condition. Whether these supplements ease the discomfort of fibromyalgia may vary from one individual to the next. More studies are needed.

Heart disease

Magnesium is essential to heart health. This mineral is particularly important for maintaining a normal heart rhythm and is often used by physicians to treat irregular heartbeat (arrhythmia). People with congestive heart failure (CHF) are often at particular risk for developing an arrhythmia. For this reason, your doctor may determine that magnesium should be a part of the treatment of CHF.

Results of studies using magnesium to treat heart attack survivors, however, have been inconsistent. Some studies have reported reduced death rates as well as fewer arrhythmias and improved blood pressure when magnesium is used as part of the treatment following a heart attack. In a hospital setting, if you have had a heart attack, the doctor will determine if magnesium supplementation, either intravenously or orally, is necessary.

High blood pressure

Eating low-fat dairy products along with lots of fruits and vegetables on a regular basis is associated with lower blood pressure. All of these foods are rich in magnesium as well as calcium and potassium. Singling out which of these nutrients is responsible for lowering blood pressure is difficult. A large clinical study of over 8,500 women found that a higher intake of dietary magnesium may decrease the development of high blood pressure in women.

Human immunodeficiency virus (HIV)

Several clinical studies suggest that between 30 - 65% of people with human immunodeficiency virus (HIV) have low levels of magnesium. Those with low levels may be more likely to complain of fatigue (excessive tiredness), diminished energy, and confusion. Whether magnesium supplements would improve these symptoms in people with HIV, however, has not been evaluated.

Intravenous magnesium is sometimes used by doctors to lower high blood pressure in a hypertensive crisis. Using magnesium supplements (even oral ones) for high blood pressure should only be done under the supervision of a competent health care provider.

Inflammatory bowel disease (IBD)

People with inflammatory bowel disease (IBD, particularly ulcerative colitis) may have low magnesium levels. In addition, there is some early clinical evidence that dietary magnesium supplements may be of some value for preventing IBD flare-ups.

Infertility and miscarriage

A small clinical study of infertile women as well as women with a history of miscarriage found that low levels of magnesium may impair reproductive function and increase the risk for miscarriage. The authors of the study suggest that one aspect of the treatment of infertility (particularly in women with a history of miscarriage) should include magnesium along with selenium. More research in this area is needed.

Menopause

Because magnesium improves the absorption of calcium from the gastrointestinal tract, some practitioners suggest that women take calcium and magnesium together at a ratio of 2:1, particularly around the time of menopause. This helps prevent osteoporosis (loss of bone mass).

In addition, as estrogen levels drop during menopause, magnesium levels seem to diminish as well. For this reason, magnesium may also help to relieve some menopausal symptoms such as hot flashes, depression, and insomnia. More research is needed.

Migraine headache

Magnesium levels tend to be lower in those with migraine headaches, including children and teenagers, when compared to those with tension headaches or no headaches at all. In addition, a few clinical studies suggest that magnesium supplements may decrease the length of time that one suffers from a migraine and reduces the amount of medication needed.

Some experts suggest that oral magnesium may be an appropriate alternative to prescription medication for people who suffer from migraine headaches. Other experts suggest that combining magnesium with the herb feverfew along with vitamin B2 (riboflavin) may be particularly helpful when you have a headache.

On the other hand, magnesium sulfate seems to be less effective than prescription medications for preventing migraines in those who have 3 or more headaches per month. The only exception to this may be women who get migraine headaches around the time of their menstrual period. In addition, magnesium supplements may prove to be a welcome option for migraine sufferers who cannot tolerate medications due to side effects or who can't take migraine medications due to pregnancy or heart disease. These issues are under scientific investigation.

Osteoporosis

Calcium, vitamin D, magnesium, and other micronutrient deficiencies are believed to play a role in the development of osteoporosis. Adequate intake of calcium, magnesium, and vitamin D coupled with overall proper nutrition and weight-bearing exercise throughout childhood and adulthood are the primary preventive measures for this condition, in both men and women.

Preeclampsia and eclampsia

Intravenous magnesium sulfate is commonly used to prevent complications from preeclampsia and eclampsia. Preeclampsia is a condition characterized by a sharp rise in blood pressure during the third trimester of pregnancy. Women with preeclampsia may develop seizures, which is then called eclampsia. Magnesium, administered in the hospital intravenously (IV or into the veins), is the treatment of choice to prevent or treat seizures associated with eclampsia.

Premenstrual Syndrome (PMS)

Scientific evidence and clinical experience suggest that magnesium supplements may help relieve symptoms associated with PMS, particularly bloating, insomnia, leg swelling, weight gain, and breast tenderness. Preliminary information suggests that magnesium may be helpful for alleviating mood swings as well.

Stroke

Population-based information suggests that people with low magnesium in their diet may be at greater risk for stroke. Some preliminary clinical evidence suggests that magnesium sulfate may be helpful in the treatment of a stroke or transient ischemic attack (TIA, or a temporary disturbance of blood supply to an area of the brain). More research is needed to know for certain if use of this mineral following a stroke or TIA is helpful.

Other

A small clinical study including only 10 patients found that magnesium improved insomnia related to restless legs syndrome (a disorder characterized by uncomfortable sensations in the legs, which are worse during periods of inactivity or rest or while sitting or lying down). In another study including 42 patients undergoing abdominal hysterectomy, those who received intravenous magnesium sulfate before and after surgery required fewer pain-killers, experienced less discomfort, and slept better after surgery compared to those who received placebo.

Magnesium levels were also reported lower in alcoholics and those addicted to heroin. More studies are needed in using magnesium for addictive disorders.

Dietary Sources

Rich sources of magnesium include tofu, legumes, whole grains, green leafy vegetables, wheat bran, Brazil nuts, soybean flour, almonds, cashews, blackstrap molasses, pumpkin and squash seeds, pine nuts, and black walnuts. Other good dietary sources of this mineral include peanuts, whole wheat flour, oat flour, beet greens, spinach, pistachio nuts, shredded wheat, bran cereals, oatmeal, bananas, and baked potatoes (with skin), chocolate, and cocoa powder. Many herbs, spices, and seaweeds supply magnesium, such as agar seaweed, coriander, dill weed, celery seed, sage, dried mustard, basil, cocoa powder, fennel seed, savory, cumin seed, tarragon, marjoram, poppy seed.

Available Forms

Magnesium is available in many forms. Recommended types include magnesium citrate, magnesium gluconate, and magnesium lactate, all of which are more easily absorbed into the body than other forms such as magnesium oxide. Time-release preparations may improve magnesium absorption. Ask your health care provider.

Other familiar sources of magnesium are magnesium hydroxide (often used as a laxative or antacid) and magnesium sulfate (generally used orally as a laxative or in multivitamins, or added to a bath). Some magnesium can be absorbed through the skin.

How to Take It

Be sure to check with your health care provider before taking magnesium supplements and before considering them for a child. Under certain circumstances, such as certain heart arrhythmias and preeclampsia, a doctor will have magnesium administered intravenously (into the veins) in the hospital.

It is a good idea to take a B vitamin complex, or a multivitamin containing B vitamins, because the level of vitamin B6 in the body determines how much magnesium will be absorbed into the cells.

Dosages are based on the dietary reference intakes (DRIs) issued from the Food and Nutrition Board of the United States Government's Office of Dietary Supplements, part of the National Institutes of Health.

Pediatric

For infants and children up to 3 years of age: The recommended dietary intake is 40 - 80 mg daily.

For children 4 - 6 years of age: The recommended dietary intake is 120 mg daily.

For children 7 - 10 years of age: The recommended dietary intake is 170 mg daily.

For adolescent and adult males: The recommended dietary intake is 270 - 400 mg daily.

For adolescent and adult females: The recommended dietary intake is 280 - 300 mg daily.

For pregnant females: The recommended dietary intake is 320 mg daily.

For breast-feeding females: The recommended dietary intake is 340 - 335 mg daily.

Magnesium needs increase during times of protein synthesis, such as pregnancy, recovering from surgery and illnesses, and athletic training.

Precautions

Because of the potential for side effects and interactions with medications, dietary supplements should be taken only under the supervision of a knowledgeable health care provider. Individuals with heart or kidney disease should not take magnesium supplements except under the guidance of a qualified health care provider.

It is extremely rare to overdose on magnesium from food alone. However, people who consume excessive amounts of milk of magnesia (as a laxative or antacid) or epsom salts (as a laxative or tonic) may overdose on this magnesium, especially if they have kidney problems. Too much magnesium can cause serious health problems, including nausea, vomiting, severely lowered blood pressure, slowed heart rate, deficiencies of other minerals, confusion, coma, and even death. More common side effects from magnesium include upset stomach and diarrhea.

Magnesium competes with calcium for absorption and can cause a calcium deficiency if calcium intake levels are already low. Magnesium may be depleted from the body due to certain medications. Medications that may decrease magnesium levels in the body include chemotherapy drugs, diuretics, digoxin (Lanoxin), hormonal supplementation, steroids, and certain antibiotics.

Possible Interactions

If you are currently being treated with any of the following medications, you should not use magnesium without first talking to your health care provider.

Antibiotics --The absorption of quinolone antibiotics, such as ciprofloxacin (Cipro) and moxifloxacin (Avelox), tetracycline antibiotics, including tetracycline (Sumycin), doxycycline (Vibramycin), and minocycline (Minocin), and nitrofurantoin (Macrodandin), may be diminished when taking magnesium supplements. Therefore, magnesium should be taken 1 hour before or 2 hours after taking these medications to avoid interference with absorption.

Blood Pressure Medications, Calcium Channel Blockers --Magnesium may increase the likelihood of negative side effects (such as dizziness, nausea, and fluid retention) from calcium channel blockers (particularly nifedipine or Procardia) in pregnant women. Other calcium channel blockers include amlodipine (Norvasc), diltiazem (Cardizem), felodipine (Plendil), and verapamil (Calan).

Diabetic Medications -- Magnesium hydroxide, commonly found in antacids such as Alternagel, may increase the absorption of glipizide and glyburide, medications used to control blood sugar levels. Ultimately, this may prove to allow for reduction in the dosage of those medications.

Digoxin -- It is important that normal levels of magnesium be maintained while taking digoxin (Lanoxin) because low blood levels of magnesium can increase adverse effects from this drug, including heart palpitations and nausea. In addition, digoxin can lead to increased loss of magnesium in the urine. A health care provider will follow magnesium levels closely to determine whether magnesium supplementation is necessary in individuals taking digoxin.

Diuretics -- Two types of diuretics known as loop (such as furosemide or Lasix) and thiazide (including hydrochlorothiazide) can deplete magnesium levels. For this reason, doctors who prescribe diuretics may consider recommending magnesium supplements as well.

Hormone Replacement Therapy for menopause -- Magnesium levels tend to decrease during menopause. Clinical studies suggest, however, that hormone replacement therapy may help prevent the loss of this mineral. Postmenopausal women or those taking hormone replacement therapy should talk with a health care provider about the risks and benefits of magnesium supplementation.

Levothyroxine -- There have been case reports of magnesium containing antacids reducing the effectiveness of levothyroxine, which is taken for an under active thyroid. This is important because many people take laxatives containing magnesium without letting their doctor know.

Penicillamine -- Penicillamine, a medication used for the treatment of Wilson's disease (a condition characterized by high levels of copper in the body) and rheumatoid arthritis, can inactivate magnesium, particularly when high doses of the drug are used over a long period of time. Even with this relative inactivation, however, supplementation with magnesium and other nutrients by those taking penicillamine may reduce side effects associated with this medication. A health care provider can determine whether magnesium supplements are safe and appropriate if you are taking penicillamine.

Tiludronate and Alendronate -- Magnesium may interfere with absorption of medications used in osteoporosis, including alendronate (Fosamax). Magnesium supplements or magnesium-containing antacids should be taken at least 1 hour before or 2 hours after taking these medications to minimize potential interference with absorption.

Others -- Aminoglycoside antibiotics (such as gentamicin and tobramycin), thiazide diuretics (such as hydrochlorothiazide), loop diuretics (such as furosemide and bumetanide), amphotericin B, corticosteroids (prednisone or Deltasone), antacids, and insulin may lower magnesium levels. Please refer to the depletions monographs on some of these medications for more information.

Supporting Research

Altura BM, Altura BT. New perspectives on the role of magnesium in the pathophysiology of the cardiovascular system. Magnesium. 1985;4(5-6):226-244.

American Diabetes Association. Magnesium supplementation in the treatment of diabetes. Diabetes Care. 1992;15:1065-1067.

Appel LJ. Nonpharmacologic therapies that reduce blood pressure: a fresh perspective. Clin Cardiol. 1999;22(Suppl. III):III1-III5.

Balfour JA, Wiseman LR. Moxifloxacin. Drugs. 1999;57(3):363-374.

Baumgaertel A. Alternative and controversial treatments for attention-deficit/hyperactivity disorder. Pediatr Clin of North Am. 1999;46(5):977-992.

Bendich A. The potential for dietary supplements to reduce premenstrual syndrome (PMS) symptoms. J Am Coll Nutr. 2000;19(1):3-12.

Britton J, Pavord I, Richards K, Wisniewski A, Knox A, Lewis S. Dietary magnesium, lung function, wheezing, and airway hyperactivity in a random adult population sample. Lancet. 1994; 344:357-362.

Brouwers JR. Drug interactions with quinolone antibacterials. Drug Saf. 1992;7:268-281.

Bureau I, Anderson RA, Arnaud J, Raysiguier Y, Favier AE, Roussel AM. Trace mineral status in post menopausal women: impact of hormonal replacement therapy. J Trace Elem Med Biol. 2002;16(1):9-13.

Burgess E, Lewanczuk R, Bolli P, et al. Recommendations on potassium, magnesium and calcium. CMAJ. 1999;160:S35-S45.

Cashman KD, Flynn A. Optimal nutrition: calcium, magnesium and phosphorous. Proc Nutr Soc. 1999;58:477-487.

Chiladakis JA, Stathopoulos C, Davlouros P, Manolis AS. Intravenous magnesium sulfate versus diltiazem in paroxysmal atrial fibrillation. Int J Cardiol. 2001;79(2-3):287-291.

Ciarallo L, Brousseau D, Reinert S. Higher-dose intravenous magnesium therapy for children with moderate to severe acute asthma. Arch Ped Adol Med. 2000;154(10):979-983.

Ciarallo L, Sauer AH, Shannon MW. Intravenous magnesium therapy for moderate to severe pediatric asthma: results of a randomized, placebo-controlled trial. > J Pediatr. 1996;129(6):809-814.

Crippa G, Sverzellati E, Girogi Pierfranceschi M, Carrara GC. Magnesium and cardiovascular drugs: interactions and therapeutic role. Ann Ital Med Int. 1999;14(1):40-45.

Dacey MJ. Hypomagnesemic disorders. Crit Care Clin. 2001;17(1):155-173.

Davis WB, Wells SR, Kuller JA, Thorp JM Jr. Analysis of the risks associated with calcium channel blockade: implications for the obstetrician-gynecologist. Obstet Gynecol Surv. 1997; 52(3):198-201.

Demirkaya S, Vural O, Dora B, Topcuoglu MA. Efficacy of intravenous magnesium sulfate in the treatment of acute migraine attacks. Headache. 2001;41(2):171-177.

De Valk HW. Magnesium in diabetes mellitus. Neth J Med. 1999;54(4):139-146.

Diener HC, Kaube H, Limmroth V. A practical guide to the management and prevention of migraine. Drugs. 1998;56(5):811-824.

Dietary Guidelines for Americans 2005. Rockville, MD: US Dept of Health and Human Services and US Dept of Agriculture; 2005.

Dorup I, Skajaa K, Thybo NK. Oral magnesium supplementation restores the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle of patients receiving diuretic treatment. J Internal Med. 1993;233(2):117-123.

Duley L, Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. Cochrane Database Syst Rev. 2001;(1):CD002960.

Duley L, Henderson-Smart D. Magnesium sulphate versus phenytoin for eclampsia. Cochrane Database Syst Rev. 2000;(2):CD000128.

Dyckner T. Relation of cardiovascular disease to potassium and magnesium deficiencies. Am J Cardiol. 1990;65(23):44K-46K.

Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment.Med Hypotheses. 2006;67(2):362-70.

Facchinetti F, Borella P, Sances G, Fioroni L, Nappi RE, Genazzani AR. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 1991;78(2):177-181.

Facchinetti F, Sances G, Borella P, Genazzani AR, Nappi G. Magnesium prophylaxis of menstrual migraine: effects on intracellular magnesium. Headache. 1991;31(5):298-301.

Ford ES, Mokdad AH. Dietary magnesium intake in a national sample of U.S. adults. J Nutr. 2003;133:2879-82. Fox C, Ramsoomair D, Carter C. Magnesium: its proven and potential clinical significance. [Review]. South Med J. 2001;94(12):1195-1201.

Geerling BJ, Stockbrugger RW, Brummer RJ. Nutrition and inflammatory bowel disease: an update. Scand J Gastroenterol. 1999;34(suppl 230):95-105.

Gilliland FD, Berhane KT, Li YF, Kim DH, Margolis HG. Dietary magnesium, potassium, sodium, and children's lung function. Am J Epidemiol. 2002;155(2):125-131.

Hassan TB, Jagger C, Barnett DB. A randomised trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillation. Emerg Med J. 2002;19(1):57-62.

Herzberg M, Lusky A, Blonder J, Frenkel Y. The effect of estrogen replacement therapy on zinc in serum and urine. Obstet Gynecol. 1996;87(6):1035-1040.

Heyka R. Lifestyle management and prevention of hypertension. In: Rippe J, ed. Lifestyle Medicine. 1st ed. Malden, Mass: Blackwell Science; 1999:109-119.

Hijazi N, Abalkhail B, Seaton A. Diet and childhood asthma in a society in transition: a study in urban and rural Saudi Arabia. Thorax. 2000;55:775-779.

Howard JM, Davies S, Hunnisett A. Red cell magnesium and glutathione peroxidase in infertile women: effects of oral supplementation with magnesium and selenium. Magnes Res. 1994;7(1):49-57.

Hornyak M, Voderholzer U, Hohagen F, Berger M, Riemann D. Magnesium therapy for periodic leg movements-related insomnia and restless legs syndrome: an open pilot study. Sleep. 1998:21(5)501-505.

Ince C, Schulman SP, Quigley JF, et al. Usefulness of magnesium sulfate in stabilizing cardiac repolarization in heart failure secondary to ischemic cardiomyopathy. Am J Cardiol. 2001;88(3):224-229.

Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. National Academy Press. Washington, DC, 2004.

ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomized factorial trial assessing early oral captropril, oral mononitrate, and intravenous magnesium sulfate in 58,050 patients with suspected acute myocardial infarction. Lancet. 1995;345(8951):669-685.

Iso H, Stampfer MJ, Manson JE, et al. Prospective study of calcium, potassium, and magnesium intake and risk of stroke in women. Stroke. 1999;30:1772-1779.

Johnson S. The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses. 2001;56(2):163-170.

Kao WH, Folsom AR, Nieto FJ, Mo JP, Watson RL, Brancati FL. Serum and dietary magnesium and the risk for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Arch Intern Med. 1999;159:2151-2159.

Kara M, Hasinoff BB, McKay DW, et al. Clinical and chemical interactions between iron preparations and ciprofloxacin. Br J Clin Pharmacol. 1991;31(3):257-261.

Kass-Annese B. Alternative therapies for menopause. Clin Obstet Gynecol. 2000;43(1):162-183.

Kendler BS. Recent nutritional approaches to the prevention and therapy of cardiovascular disease. Prog Cardiovasc Nurs. 1997;12(3):3-23.

Kinlay S, Buckley NA. Magnesium sulfate in the treatment of ventricular arrhythmias due to digoxin toxicity. J Toxicol Clin Toxicol. 1995;33:55-59.

Kivisto KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther. 1991;49(1):39-43.

Klevay LM, Milne DB. Low dietary magnesium increases supraventricular ectopy. Am J Clin Nutr. 2002;75(3):550-554.

Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder. Magnes Res. 1997;10(2):143-148.

Krauss RM, Eckel RH, Howard B, et al. AHA dietary guidelines. Revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation. 2000;102:2284-2299.

Kushner JM, Peckman HJ, Snyder CR. Seizures associated with fluoroquinolones. Ann Pharmacother. 2001;35(10):1194-1198.

Lambs L, Brion M, Berthon G. Metal ion-tetracycline interactions in biological fluids. Part 3. Formation of mixed-metal ternary complexes of tetracycline, oxytetracycline, doxycycline and minocycline with calcium and magnesium, and their involvement in the bioavailability of these antibiotics in blood plasma. Agents Actions. 1984;14:743-750.

Lehto P, Laine K, Kivisto KT, et al. The effect of pH on the in-vitro dissolution of three second-generation sulphoylurea preparations: mechanism of antacid-sulphonylurea interaction. J Pharm Pharmacol. 1996;48(9):899-901.

Li RC, Lo KN, Lam JS, et al. Effects of order of magnesium exposure on the postantibiotic effect and bactericidal activity of ciprofloxacin. J Chemother. 1999;11(4):24324-24327.

Liu S, Manson JE, Stampfer MJ, et al. A prospective study of whole-grain intake and risk of type 2 diabetes mellitus in US women. Am J Pub Health. 2000;90(9):1409-1415.

Lucas MJ, Leveno KJ, Cunningham FG. A comparison of magnesium sulfate with phenytoin for the prevention of eclampsia. N Engl J Med. 1995;333(4):201-205.

Matsumura M, Nakashima A, Tofuku Y. Electrolyte disorders following massive insulin overdose in a patient with type 2 diabetes. Intern Med. 2000;39(1):55-57.

Mauskop A. Alternative therapies in headache. Is there a role? Med Clin North Am. 2001;85(4):1077-1084.

Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines. Clin Neurosci. 1998;5(1):24-27.

Mazzotta G, Sarchielli P, Alberti A, Gallai V. Intracellular Mg++ concentration and electromyographical ischemic test in juvenile headache. Cephalgia. 1999;19:802-809.

Mersebach H, Rasmussen AK, Kirkegaard L, Feldt-Rasmussen U. Intestinal absorption of levothyroxine by antacids and laxatives: case stories and in vitro experiments. Pharmacol Toxicol. 1999;84(3):107-109.

Mervaala EM, Malmberg L, Teravainen TL, Laakso J, Vapaatalo H, Karppanen H. Influence of dietary salts on the cardiovascular effects of low-dose combination of ramipril and felodipine in spontaneously hypertensive rats. Br J Pharmacol. 1998;123(2):195-204.

Moulin DE. Systemic drug treatment for chronic musculoskeletal pain. Clin J Pain. 2001;17(4 Suppl):S86-S93.

Muir KW. Magnesium for neuroprotection in ischaemic stroke: rationale for use and evidence of effectiveness. CNS Drugs. 2001;15(12):921-930.

Muneyyirci-Delale O, Nacharaju VL, Dalloul M, Altura BM, Altura BT. Serum ionized magnesium and calcium in women after menopause: Inverse relation of estrogen with ionized magnesium. Fertil Steril. 1999;71:869-872.

Naggar VF, Khalil SA. Effect of magnesium trisilicate on nitrofurantoin absorption. Clin Pharmacol Ther. 1979;25(6):857-863.

Neuvonen PJ, Kivisto KT. Enhancement of drug absorption by antacids. An unrecognized drug interaction. Clin Pharmacokinet. 1994;27(2):120-128.

Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs. 1976;11(1):45-54.

Ng SY. Hair calcium and magnesium levels in patients with fibromyalgia: a case center study. J Manipulative Pysiol Ther. 1999;22(9):586-593.

Nielson FH. Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. Magnesium Trace Elem. 1990;9:61-69.

Paolisso G. Daily magnesium supplements improve glucose handling in elderly subjects. Am J Clin Nutr. 1992;55:1161-1167.

Patrick L. Nutrients and HIV: part 2: vitamins A and E, zinc, B-vitamins, and magnesium. Alt Med Rev. 2000;5(1):39-51.

Pearlstein T, Steiner M. Non-antidepressant treatment of premenstrual syndrome. J Clin Psychiatry. 2000;61 Suppl 12:22-27.

Peikart A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalagia. 1996;16(4):257-263.

Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine, a double-blind placebo-controlled study. Cephalagia. 1996;16(6):436-440.

Reif S, Klein I, Lubin F, Farbstein M, Hallak A, Gilat T. Pre-illness dietary factors in inflammatory bowel disease. Gut. 1997;40:754-760.

Rowe BH, Edmonds ML, Spooner CH, Camargo CA. Evidence-based treatments for acute asthma. [Review]. Respir Care. 2001;46(12):1380-1390.

Russell IJ, Michalek JE, Flechas JD, Abraham GE. Treatment of fibromyalgia syndrome with Super Malic: a randomized, double blind, placebo controlled, crossover pilot study. J Rheumatol. 1995;22(5):953-958.

Saunders N, Hammersley B. Magnesium for eclampsia. Lancet. 1995;346(8978):788-789.

Schumacher M, Peraire J, Domingo JL. Trace elements in patients with HIV-1 infection. Trace Elem Electorlytes. 1994;11:130-134.

Seelig MS. Auto-immune complications of D-penicillamine: a possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr. 1982;1(2):207-214.

Seelig MS. ISIS 4: clinical controversy regarding magnesium infusion, thromolytic therapy, and acute myocardial infarction. Nutr Rev. 1995;53(9):261-264.

Skorodin MS, Tenholder MF, Yetter B, et al. Magnesium sulfate in exacertaions of chronic obstructive pulmonary disease. Arch Intern Med. 1995;155(5):496-500.

Skurnik JH, Bogden JD, Baker H. Micronutrient profiles in HIV-1 infected heterosexual adults. J Acquir Immune Defic Syndr. 1996;12:75-83.

Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactive disorder (ADHD): positive response to magnesium oral loading test. Magnesium Research. 1997; 10(2):149-156.

Taylor M. Alternatives to conventional hormone replacement therapy. Compr Ther. 1997;23(:514-532.

Toraman F, Karabulut EH, Alhan HC, Dagdelen S, Tarcan S. Magnesium infusion dramatically decreases the incidence of atrial fibrillation after coronary artery bypass grafting. Ann Thorac Surg. 2001;72(4):1256-1261.

Tramer MR, Schneider J, Marti RA, Rifat K. Role of magnesium sulfate in postoperative analgesia. Anesthesiology. 1996;84(2):340-347.

Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PWF, Kiel DP. Potassium, magnesium and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999;69:727-736.

Walker AF, De Souza MC, Vickers MF, Abeyasekera S, Collins ML, Trinca LA. Magnesium supplementation alleviates premenstrual symptoms of fluid retention. J Womens Health. 1998;7(9):1157-1165.

Walker JJ. Pre-eclampsia. Lancet. 2000;356(9237):1260-1265.

Welch KM. Pathogenesis of migraine. Semin Neurol. 1997;17(4):335-341.

Whang R, Oei TO, Watanabe A. Frequency of hypomagnesia in hospitalized patients receiving digitalis. Arch Intern Med. 1985;145(4):655-656.

Woods KL, Fletcher S. Long-term outcome after intravenous magnesium sulfate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2). Lancet. 1994;343(8901):816-819.

Review Date:
5/14/2007
Reviewed By:
Ernest B. Hawkins, MS, BSPharm, RPh, Health Education Resources; and 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

Gout

FitSugar — Wed, 08 Oct 2008 17:35:16 -0700

In This Report

Highlights
Introduction
Symptoms
Causes and Risk Factors
Triggers
Diagnosis
Treatment: Acute Gout Attac...
Treatment: Preventing Attac...
Other Treatments
Lifestyle Changes
Complications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Types of Gout:

There are two types of gout -- primary and secondary.

Primary gout: The cause is usually unknown. However, primary gout is likely the result of a combination of genetic, hormonal, and dietary factors.
Secondary gout: Secondary gout is caused by medications or medical conditions that cause an increase in the serum (blood) levels of uric acid.

Risk Factors:

Risk factors for gout include:

Advancing age
Male gender
Family history of the condition
Obesity
Use of certain drugs, including diuretics, aspirin, cyclosporine, or levodopa
Drinking a large amount of alcohol, particularly beer
Exposure to lead
Organ transplants
Thyroid problems

Symptoms of a Gout Attack:

Symptoms of a gout attack include:

Severe pain at and around the joint
- May feel like "crushing" or a dislocated bone
- Walking and the weight of bed sheets may be unbearable
- Usually takes 8 - 12 hours to develop
- Occurs late at night or early in the morning and may wake you up
Swelling that may extend beyond the joint
Red, shiny, tense skin over the affected area, which may peel after a few days
Chills and mild fever, loss of appetite, and feelings of ill health

Research News

A large study found that people with gout are at an increased risk of having metabolic syndrome. Metabolic syndrome is a collection of problems, such as abdominal obesity, high blood pressure, and low "good" cholesterol. This syndrome increases a person's risk of heart disease and diabetes.

Introduction

Gout is a painful and common type of arthritis. About 1 in 100 people develop gout. The condition is usually associated with a long-lasting, abnormally high amount of uric acid in the blood, called chronic hyperuricemia.

The rate of gout has increased in recent decades, not only in America but also in other developed countries. The increase is possibly due to dietary and lifestyle changes, greater use of medications that cause hyperuricemia, and aging populations. Gout is very uncommon in developing countries.

Click the icon to see an animation about gout.

Metabolism of Purines. The process leading to hyperuricemia and gout begins with the metabolism of purines, nitrogen-containing compounds that are important for energy. Purines can be divided into two types:

Endogenous purines are manufactured within human cells.
Exogenous purines are obtained from foods.

The process of breaking down purines results in the formation of uric acid in the body. Most mammals have an enzyme called uricase, which breaks down uric acid so it can be easily removed from the body. Because humans lack uricase, uric acid is not as easily removed, and can build up in body tissues.

Uric Acid and Hyperuricemia. Purines in the liver produce uric acid. The uric acid enters the bloodstream, and most of it eventually goes through the kidneys and is excreted in the urine. The remaining uric acid travels through the intestines, where bacteria help break it down.

Normally these actions keep the level of uric acid in the blood plasma (the liquid part of the blood) at a healthy level, which is below 6.8 mg/dL. But under certain circumstances, the body produces too much uric acid or removes too little. In either case, concentrations of uric acid increase in the blood. This condition is known as hyperuricemia.

If concentrations of uric acid reach 7 mg/dL and above, needlelike crystals of a salt called monosodium urate (MSU) form. As MSU crystals build up in the joints, they trigger inflammation and pain, the characteristic symptoms of gout.

Symptoms

The specific symptoms of gout depend on the stage of the disease. Gout is often divided into four stages:

Asymptomatic hyperuricemia
Acute gouty arthritis
Intercritical gout
Chronic tophaceous gout

Asymptomatic means there are no symptoms. Asymptomatic hyperuricemia is considered the first stage of gout. MSU levels slowly increase in the body. This stage lasts for an average of 30 years.

Note: Hyperuricemia does not inevitably lead to gout. In fact, less than 20% of cases develop the full-blown arthritic gout disease.

Acute gouty arthritis occurs when the first symptoms of gout appear. Sometimes the first signs of gout are brief twinges of pain (petit attacks) in an affected joint. These attacks can precede the actual full-blown condition by several years.

MSU crystals form at normal body temperature when the concentration of uric acid in the blood reaches 7 mg/dL. At lower temperatures, MSU crystals form at lower concentrations of uric acid. Since blood temperature falls the further blood gets from the heart, gout strikes the toes and fingers first.

Symptoms of acute gouty arthritis include:

Severe pain at and around the joint
- May feel like "crushing" or a dislocated bone
- Walking and the weight of bed sheets may be unbearable
- Usually takes 8 - 12 hours to develop
- Occurs late at night or early in the morning and may wake you up
Swelling that may extend beyond the joint
Red, shiny, tense skin over the affected area, which may peel after a few days
Chills and mild fever, loss of appetite, and feelings of ill health

Most often symptoms start in one joint.

Monoarticular Gout. Gout that occurs in one joint is called monoarticular gout. About 60% of all first-time monoarticular gout attacks in middle-aged adults occur in the big toe. This occurrence is known as podagra. Symptoms can also occur in other locations, such as the ankle or knee.

Polyarticular Gout. If more than one joint is affected, the condition is known as polyarticular gout. Multiple joints are affected in only 10 - 20% of first attacks. Older people are more likely to have polyarticular gout. The most frequently affected joints are the foot, ankle, knee, wrist, elbow, and hand. The pain usually occurs in joints on one side of the body and it is usually, although not always, in the lower legs and the feet. People with polyarticular gout are more likely to have a slower onset of pain and a longer delay between attacks. People with polyarticular gout are also more likely to experience low-grade fever, loss of appetite, and a general feeling of poor health.

An untreated attack will typically peak 24 - 48 hours after the first appearance of symptoms, and go away after 5 - 7 days. However, some attacks last only hours, while others persist as long as several weeks.

Intercritical gout is the term used to describe the periods between attacks. The first attack is usually followed by a complete remission of symptoms, but, if left untreated, gout nearly always returns. Over two-thirds of patients will have at least one further attack within 2 years of the first attack. By 10 years, over 90% of the patients are likely to have repeat attacks.

Chronic Tophaceous Gout and Tophi. After several years, persistent gout can develop into a condition called chronic tophaceous gout. This long-term condition often produces tophi, which are solid deposits of MSU crystals that form in the joints, cartilage, bones, and elsewhere in the body. In some cases, tophi break through the skin and appear as white or yellowish-white, chalky nodules that have been described as looking like crab eyes.

Click the icon to see an image of tophi gout.

Without treatment, tophi develop about 10 years after the initial onset of gout, although the occurence can range from 3 to 42 years. Tophi are more likely to appear early in the course of the disease in older people. In the elderly population, women appear to be at higher risk for tophi than men. Certain people, such as those who are receiving cyclosporine after a transplant, have a high risk of developing tophi.

Development of Chronic Pain. When gout remains untreated, the intercritical periods typically become shorter and shorter, and the attacks, although sometimes less intense, can last longer. Over the long term (about 10 - 20 years) gout becomes a chronic disorder characterized by constant low-grade pain and mild or acute inflammation. Gout may eventually affect several joints, including those that may have been free of symptoms at the first appearance of the disorder. In rare cases, the shoulders, hips, or spine are affected.

Location of Tophi. Tophi generally form in the following locations:

Curved ridge along the edge of the outer ear
Forearms
Elbow or knee
Hands or feet -- older patients, particularly women, are more likely to have gout in the small joints of the fingers.
Around the heart and spine (rare)

Tophi are generally painless. However, they can cause pain and stiffness in the affected joint. Eventually, they can also erode cartilage and bone, ultimately destroying the joint. Large tophi under the skin of the hands and feet can give rise to extreme deformities.

Uric Acid Nephrolithiasis (Kidney Stones). Persons who have kidney stones that formed from uric acid are more likely to have higher levels of uric acid in their blood than in their urine. This suggests that gout is responsible for this type of kidney stones. Uric acid stones and other forms of kidney stones are present in 10 - 25% of patients with primary gout, a rate of more than 1,000 times that of the general population. In gout caused by other conditions (called secondary gout), the reported rate reaches 42%.

Click the icon to see an image of nephrolithiasis.

Not all of the kidney stones in patients with gout are made of uric acid. Some are made from calcium oxalate, calcium phosphate, or substances combined with uric acid. Uric acid stones can also form when you do not have gout or hyperuricemia.

Chronic Uric Acid Interstitial Nephropathy. Chronic uric acid interstitial nephropathy occurs when crystals slowly form in the structures and tubes that carry fluid from the kidney. It is reversible and not likely to injure the kidneys.

Kidney Failure. Sudden overproduction of uric acid can occasionally block the kidneys and cause them to fail. This occurrence is very uncommon but can develop after any of the following:

Chemotherapy for leukemia or lymphoma
Severe heat stress from vigorous exercise
Epileptic seizures
Corticosteroid therapy for severe allergic reactions

Causes and Risk Factors

Gout is classified as either primary or secondary, depending on what causes the high levels of uric acid in the blood (hyperuricemia).

More than 99% of primary gout cases are referred to as idiopathic, meaning that the cause of the hyperuricemia cannot be determined. Primary gout is most likely the result of a combination of genetic, hormonal, and dietary factors. Secondary gout is caused by drug therapy or by medical conditions other than a metabolic disorder.

The following factors increase your risk for gout:

Advancing age
Male gender
Family history of the condition
Obesity
Use of certain drugs, including diuretics ("water pills"), aspirin, cyclosporine, or levodopa
Drinking a large amount of alcohol, particularly beer
Exposure to lead
Organ transplants
Thyroid problems
Other serious illness

Each risk factor is discussed in more detail below.

Middle-Aged Adults. Gout usually occurs in middle-aged men, peaking in the mid-40s. It is most often associated in this age group with obesity, high blood pressure, unhealthy cholesterol levels, and heavy alcohol use.

Elderly. Gout can also develop in older people, when it occurs equally in men and women. In this group, gout is most often associated with kidney problems and the use of diuretics. It is less often associated with alcohol use.

Children. Except for rare inherited genetic disorders that cause hyperuricemia, gout in children is rare.

Men. Men are significantly at higher risk for gout. In males, uric acid levels rise substantially at puberty. In about 5 - 8% of American men, levels exceed 7 mg/dL (indicating hyperuricemia). However, gout typically strikes after 20 - 40 years of persistent hyperuricemia, so men who develop it usually experience their first attack between the ages of 30 and 50.

Women. Before menopause, women have a significantly lower risk for gout than men, possibly because of the actions of estrogen. This female hormone appears to facilitate uric acid excretion by the kidneys. (Only about 15% of female gout cases occur before menopause.) After menopause the risk increases in women. At age 60 the incidence is equal in men and women, and after 80, gout occurs more often in women.

According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, up to 18% of people with gout have a family history of the condition. Some people with a family history of gout have a defective protein (enzyme) that interferes with the way the body breaks down purines.

Researchers report a clear link between body weight and uric acid levels. In one Japanese study, overweight people had two to more than three times the rate of hyperuricemia as those who maintained a healthy weight. Children who are obese may have a higher risk for gout in adulthood.

Thiazide diuretics are "water pills" used to control hypertension. The drugs are strongly linked to the development of gout. In fact, 75% of patients who develop gout at an older age report the use of diuretics.

Several other medications can increase uric acid levels and raise your risk for gout. These include:

Aspirin -- low doses of aspirin reduce uric acid excretion and increase the chance for hyperuricemia. This may be a problem for older people who take baby aspirin (81 mg) to protect against heart disease.
Niacin (used to treat cholesterol problems)
Pyrazinamide (used to treat tuberculosis)

Drinking excessive amounts of alcohol can raise your risk of gout. Beer is the kind of alcohol most strongly linked with gout, followed by spirits. Moderate wine consumption does not appear to increase the risk of developing gout.

Alcohol use is highly associated with gout in younger adults. Binge drinking particularly increases uric acid levels. Alcohol appears to play less of a role among elderly patients, especially among women with gout.

Alcohol increases uric acid levels in the following three ways:

Providing an additional dietary source of purines (the compounds from which uric acid is formed)
Intensifying the body's production of uric acid
Interfering with the kidneys' ability to excrete uric acid

Chronic occupational exposure to lead is associated with build-up of uric acid and a high incidence of gout.

Kidney transplantation poses a high risk for renal insufficiency and gout. In addition, other transplantation procedures, such as heart and liver, increase the risk of gout. The procedure itself poses a risk of gout, as does the medication (cyclosporine) used to prevent rejection of the transplanted organ. Cyclosporine also interacts with indomethacin, a common gout treatment.

The kidneys are responsible for removing waste from the body, regulating electrolyte balance and blood pressure, and stimulating red blood cell production.

Treatment of several other conditions can cause significant elevations of uric acid in the blood, and therefore a gout attack. These conditions include:

Leukemia
Lymphoma
Psoriasis

Triggers

Triggers are events or conditions that can set off a gout attack. Certain risk factors, including a purine-rich diet, are also considered a trigger. Triggers include:

Joint injury
Overindulging in alcohol or purine-rich foods
Over-strenuous exercise
Severe illness or infection
Stress
Sudden weight loss
Surgery
Using certain drugs

Hot and humid weather may also be strongly associated with recurrent gout attacks. Such weather can cause sweating and, ultimately, dehydration, which has long been recognized as a potential trigger for gout attacks.

Drinking more water and fluids when it's warm outside could help persons with gout prevent future attacks.

Diagnosis

The first step in diagnosing the disease is to determine which joints are affected. A physical examination and medical history can help confirm or rule out gout. For example, gout is more likely if arthritis first appears in the big toe.

The speed of the onset of pain and swelling is also important. Symptoms that take days or weeks (rather than hours) to develop probably indicate a disorder other than gout.

Abnormal enlargements in joints that had been affected by previous injury or osteoarthritis are possible signs of gout. This is particularly significant in older women who take diuretics ("water pills").

A blood test is usually done to measure uric acid levels and detect hyperuricemia. A low level of uric acid in the blood makes a diagnosis of gout much less probable, and a very high level increases the likelihood of gout, especially if patient has symptoms of gout. Nevertheless, uric acid levels in the blood during an attack of gout can be within or below the normal range, and the presence of hyperuricemia does not necessarily mean someone has gout. However, most doctors feel that closer monitoring of blood uric acid levels in people with gout may help reduce gout flares.

Synovial fluid examination is the most accurate method for diagnosing gout. The synovial fluid is the lubricating liquid that fills the synovium (the membrane that surrounds a joint and creates a protective sac). The fluid cushions joints and supplies nutrients and oxygen to the cartilage surface that coats the bones. This exam also helps detect gout during intercritical periods.

The health care provider uses a needle attached to a syringe to draw out fluid from the affected joint. This is called aspiration. Local anesthesia is not used because it can reduce the effectiveness of the procedure. However, the procedure is usually only mildly uncomfortable. Afterwards, there can be some minor discomfort in the area where the needle was inserted, but it usually goes away quickly.

The fluid sample is sent to a laboratory for analysis. Testing can reveal the presence of monosodium urate (MSU) crystals, which will nearly always confirm a diagnosis of gout. The laboratory can also test the sample for infection.

The procedure itself can cause infection, though this occurs in less than 0.1% of patients. Aspiration sometimes eases the patient's symptoms by reducing swelling and pressure on the tissue surrounding the joint.

Synovial fluid analysis is a method to look at the fluid that cushions a joint. It is done to help diagnose and treat joint-related problems such as gout.

It is sometimes helpful to gauge the amount of uric acid found in a patient's urine, particularly if the patient is young and has pronounced hyperuricemia that might be related to a metabolic disorder. If uric acid in the urine exceeds a particular value, further tests for an enzyme defect or other identifiable cause of gout should be performed. Greater-than-normal amounts of uric acid in the urine also mean that the patient is more likely to develop uric acid kidney stones.

Typically, a 24-hour urine test is performed. The patient discards the first urination sample on the day of the test. Afterward all urine passed over the next 24 hours is collected into a special container, including the first urination on the morning of day two. The container is delivered to the patient's health care provider or sent directly to the laboratory.

The urine is collected during an intercritical period, after the patient has been placed on a purine-reduced diet. The patient is also asked to temporarily stop using alcohol and any medications that can interfere with the test. The patient should not change any of his or her usual eating or drinking patterns when performing this test.

Click the icon to see an image of a uric acid test.

X-Rays. For the most part, x-rays do not reveal any problems during the early stages of gout. Their usefulness lies in assessing the progress of the disorder in its chronic phase and identifying other health problems with symptoms similar to gout. Tophi can be seen on x-rays before they become apparent on physical examination.

Advanced Imaging Techniques. Advanced imaging techniques being investigated for identifying tophi include computed tomography (CT), magnetic resonance imaging (MRI), and Doppler ultrasonography.

As part of the diagnosis, other disorders that produce gout-like symptoms or cause hyperuricemia should be ruled out. In general, it is easy to distinguish acute gout that occurs in one joint from other arthritic conditions. The two disorders that may confuse this diagnosis are pseudogout and septic arthritis. Pseudogout is a condition most likely to be confused with gout.

Chronic gout can often resemble rheumatoid arthritis. Several other conditions may at some point in their course resemble gout.

Pseudogout (also called calcic gout and calcium pyrophosphate dihydrate deposition disease) is a common inflammatory arthritis among older adults. It is very similar to gout, but is caused by deposits of calcium pyrophosphate dihydrate crystals in and around the joints.

Although symptoms of pseudogout resemble gout in some ways, there are differences:

The first attack typically strikes the knee. Other joints commonly affected are the shoulders, wrists, and ankles. At least two-thirds of cases affect more than one joint during a first attack. Pseudogout may involve any joint, although the small joints in the fingers or toes are not commonly affected.
The symptoms of pseudogout also appear more slowly than those of gout, taking days rather than hours to develop.
Pseudogout is more likely to first develop in elderly people, particularly those with osteoarthritis. (It affects 10 - 15% of people over 65.)

Pseudogout is more likely to occur in the autumn while gout attacks are most common in the spring.

Conditions that are associated with a higher risk for pseudogout in elderly patients include underlying acute medical conditions, trauma, or surgery. Medical conditions associated with pseudogout include hypothyroidism, diabetes, gout, and osteoarthritis. Liver transplantation also may increase the risk.

There is no cure for pseudogout. It is a progressive disorder that can eventually destroy joints. Treatments for pseudogout are similar to those for gout and are aimed at relieving the pain and inflammation and reducing the frequency of attacks.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for treating inflammation and pain from pseudogout.
For acute attacks in large joints, fluid aspiration alone or with corticosteroids may help.
Colchicine may be used for acute attacks.
Magnesium carbonate may help dissolve crystals, but existing hard deposits may remain.
Surgery may be required for joint replacement.

Rheumatoid Arthritis. Rheumatoid arthritis can distort the joints of the finger and cause inflammation and pain that may mimic gout. In older people, it is particularly difficult to distinguish chronic gout from rheumatoid arthritis. A proper diagnosis can be made with a detailed medical history, laboratory tests, and identification of MSU crystals.

Osteoarthritis. Gout can coincide and be confused with osteoarthritis in older people, particularly when it occurs in arthritic finger joints in women. In general, gout should be suspected if the joints in the fingertips are unusually enlarged.

Click the icon to see an image of osteoarthritis.

Infections. Joint infections can have features that resemble gout. A correct diagnosis is critical for appropriate treatment. For example, some cases of gout have been confused with infection after joint replacement. On the other hand, joint infection not associated with surgery might indicate sepsis, which is a widespread and potentially life-threatening bacterial infection that can cause inflamed joints, chills, and a spiking fever. The severity of the fever and a high white blood cell count in the joint fluid helps diagnose a septic infection, while urate crystals in the joint are a good indicator of gout.

Charcot Foot. Between 1 - 2.5% of people with diabetes have Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy). This condition is caused by problems in the nerves in the feet. Early changes may resemble gout, with the foot becoming swollen, red, and warm. Recognition and treatment of this condition is very important. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable.

Bunions. A bunion is a foot deformity that usually occurs at the head of the first of five long bones (the metatarsal bones) that extend from the arch and connect to the toes, and may be confused with gout. The first metatarsal bone is the one that attaches to the big toe. A bunion begins to form when the big toe is forced in toward the rest of the toes, causing the head of the first metatarsal bone to jut out and rub against the side of the shoe. The underlying tissue becomes inflamed, and a painful bump forms. As this bony growth develops, the bunion is formed as the big toe is forced to grow at an increasing angle towards the rest of the toes.

Click the icon to see an illustrated series detailing bunion removal.


Disease	Specific Subtypes
Osteoarthritis
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis, osteomyelitis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Pseudogout
Rheumatic Autoimmune Diseases	Rheumatoid arthritis, systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's disease (also called juvenile rheumatoid arthritis)
Fibromyalgia
Other Diseases	Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Behcet's disease, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Treatment: Acute Gout Attack

Acute attacks of gout and long-term treatment of gout and hyperuricemia require different approaches. Treatment usually involves medication. After the first attack, some health care providers advise their patients to keep a supply of medications on hand so that self-medication can begin at the first sign of symptoms of a second acute attack. There are also specific treatments for conditions associated with gout, including uric acid nephropathy and uric acid nephrolithiasis.

Many patients do not require medications. During the period between gout attacks, patients are advised to avoid foods high in purines and to maintain a healthy weight. Patients should also avoid alcohol and reduce any stress.

Drug treatments for acute attacks of gout are aimed at relieving pain and reducing inflammation. They should be started as early as possible.

Medications used in the treatment of gout include:

NSAIDs (nonsteroidal anti-inflammatory drugs)
Colchicine
Corticosteroids

Powerful forms of nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs of choice for an acute attack in younger, healthy patients with no serious health problems, particularly problems that affect the kidneys, liver, or heart. Usually indomethacin is prescribed for 2 - 7 days.

There are dozens of NSAIDs available. Over-the-counter NSAIDs include:

Low-dose Ibuprofen (Motrin IB, Advil, Nuprin)
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)
Indomethacin (Indocin)

Indomethacin (Indocin) is typically the first choice of treatment for patients who have no medical conditions that would interfere with its use. Usually 2 - 7 days of high-dose indomethacin is enough to treat a gout attack. The first dose of indomethacin usually begins to act against the pain and inflammation within 24 hours and often much sooner.

Ibuprofen, naproxen, sulindac, or NSAIDs are good alternatives, particularly for elderly patients who might experience confusion or bizarre sensations with indomethacin. (Aspirin is an NSAID, but is associated with a higher risk for gout and should be avoided.)

Regular use of even over-the-counter NSAIDs can cause certain health problems, such as:

Ulcers and gastrointestinal bleeding
Increased blood pressure -- people with hypertension, severe vascular disease, kidney, or liver problems and those taking diuretics must be closely monitored if they need to take NSAIDs.
Delayed emptying of the stomach, which could interfere with the actions of other drugs. The elderly are at special risk.
Dizziness
Tinnitus (ringing in the ear)
Headache
Skin rash
Depression
Confusion or bizarre sensation (in some higher-potency NSAIDs, notably indomethacin)
Kidney damage

NSAIDs can cause kidney problems, especially in the elderly and those with kidney disease. When caught early enough, these problems generally resolve if the drugs are stopped. Any sudden weight gain or swelling should be reported to a physician. Anyone with kidney disease should avoid these drugs.

Patients with diabetes who take hypoglycemics by mouth may need to adjust their medication dosage if they also take NSAIDs, because of possible harmful interactions between these classes of drugs.

Some studies reported that ibuprofen (but not other NSAIDs) may reduce the heart-protective effects of low-dose aspirin. Additional research is needed to confirm these findings.

Long-term use of NSAIDs is a common cause of ulcers. NSAID-related bleeding and stomach problems may be responsible for over 100,000 hospital admissions and over 15,000 deaths each year. Because there are usually no gastrointestinal symptoms from NSAIDs until bleeding begins, health care providers cannot predict which patients taking these drugs will develop bleeding.

Those at high risk for NSAID-related bleeding include the elderly, anyone with a history of an ulcer or gastrointestinal bleeding, patients with serious heart conditions, those who drink too much alcohol, and persons on certain medications, such anticoagulants (blood thinners), corticosteroids, or bisphosphonates (drugs used for osteoporosis).

Preventing NSAID-Related Ulcers. Switching to alternative pain relievers is the first step in preventing or healing ulcers caused by NSAIDs. If people cannot change drugs, they should use the lowest NSAID dose possible.

In addition, medications are available that may help prevent ulcers in people who need to take NSAIDs. Proton-pump inhibitors (PPIs) are the first drug of choice for preventing ulcers in high-risk individuals. They have been shown to reduce NSAID-ulcer rates by as much as 80% compared with no treatment. Types of these drugs include omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (AcipHex ), and pantoprazole (Protonix). Prevacid is the first proton-pump inhibitor specifically approved for protecting against ulcers in chronic NSAID users.

Arthrotec is a combination of an ulcer-protective drug called misoprostol and the NSAID diclofenac. It too may reduce the risk for gastrointestinal bleeding.

Colchicine is a derivative of the autumn crocus (also called the meadow saffron). It has been used against gout attacks for centuries. It is highly effective, although it is no longer the first drug of choice because of its frequent, unpleasant, and sometimes very serious side effects.

Colchicine may be given to a healthy adult within 48 hours of an attack. It should not be used by elderly patients or those with kidney, liver, or bone marrow disorders. It can also affect fertility and should not be used during pregnancy. The drug can cause gastrointestinal side effects at high dose, including nausea, vomiting, diarrhea, and abdominal cramps. Low doses do not pose as high a risk for gastrointestinal symptoms, and can prevent further attacks, including attacks in patients who are starting anti-hyperuricemic therapies.

Colchicine may be taken by mouth or given by an intravenous line. Those who take it by mouth need doses every hour until either symptoms improve or side effects develop. Improvement should be seen by the tenth dose. It usually eliminates the pain of an acute attack within 48 hours. The intravenous route has some serious side effects, however, and poses an increased risk for injury to the kidney, liver, central nervous system, and bone marrow.

The antibiotic erythromycin, or H2 blockers such as famotidine (Pepcid AC), cimetidine (Tagamet), or ranitidine (Zantac) may intensify the gastrointestinal side effects of colchicine.

Warning Note: Overdose of colchicine can be dangerous, and there have even been reports of death. The drug may also suppress blood cell production and cause nerve and muscular injury in certain people, sometimes even in those not taking high doses.

Corticosteroids may be used in patients who cannot tolerate NSAIDs and they may be particularly beneficial for elderly patients. Injections into an affected joint provide effective relief for many patients, but this is not useful for patients who have multiple affected joints. Steroids taken by mouth may be used for patients who cannot take NSAIDs or colchicine and who have gout in more than one joint. Corticosteroids include triamcinolone and prednisone.

Treatment: Preventing Attacks

After an acute attack some patients remain at high risk for another attack for several weeks during the intercritical period. Such patients include those with kidney insufficiency or those with congestive heart failure who are on diuretics. Low doses of colchicine or NSAIDs may be used to during this period for prevention of another attack. They should be taken in low doses for 1 - 2 months after an attack, or for longer periods in patients who have experienced frequent attacks.

Antihyperuricemic medications reduce levels of uric acid in the body. The decision whether to use an antihyperuricemic medicine and at what point is not entirely clear. Some health care providers do not prescribe them if hyperuricemia is mild, or until a patient has had two gout attacks. Others prescribe them immediately after a single attack. Most of the time, antihyperuricemic therapy means taking a drug routinely throughout life, which many people find difficult.

Experts do not recommend treatment for hyperuricemia that causes no symptoms. Asymptomatic hyperuricemia often does not lead to gout or other health problems. In addition, the drugs used to treat it are expensive and carry certain risks. In unusual circumstances treatment may be justified, for example in patients with very high uric acid levels that threaten the kidney or those with a personal or strong family history of gout, kidney stones, or kidney damage.

Before treatment, some experts recommend a 24-hour urine collection sample in patients with frequent gout attacks to determine whether they are over-producers or under-excreters of uric acid. Also, before starting one of these drugs, any previous acute attack should be completely controlled and the joints should not be inflamed. Some health care providers prefer to wait about a month after an attack.

Low doses of NSAIDs or colchicine are used during several months after introducing anti-hyperuricemic therapies to prevent gout attacks. It should be noted that NSAIDs, particularly aspirin and similar drugs, reduce the effectiveness of uricosurics. These are drugs given to under-excreters of uric acid (see below). Patients taking uricosurics should avoid NSAIDs, if possible.

Long-term treatment of hyperuricemia may be recommended for people who have:

A risk for tophaceous gout
Had more than two or three acute attacks of gout in the past
Unusually severe attacks, or attacks that affect more than one joint
Joint damage from gout, as shown on x-rays
Hyperuricemia caused by an identifiable inborn metabolic deficiency

Uricosurics. These drugs prevent the kidney from reabsorbing uric acid, and therefore increase the amount excreted in the urine. They are appropriate when gout is caused by under-excretion of uric acid, which occurs in about 80% of gout cases. They are not used for patients with reduced kidney function or those with tophaceous gout. Uricosurics are usually the choice for preventing gout in the following patients:

Those under 60 years of age
Those with normal diets
Those who have normal kidney function
Those who have no risk of kidney stones

Uricosuric drug candidates should produce no more than 700 - 800 mg of uric acid in the urine over a 24-hour period.

Probenecid (Benemid, Probalan) and sulfinpyrazone (Anturane) are the standard uricosurics. A more potent uricosuric, benzbromarone, may work for people with severe tophaceous gout and kidney impairment when other drugs do not. In some studies, benzbromarone was equal to or even more effective than allopurinol, another type of antihyperuricemic drug. Because benzbromarone can cause liver failure in some patients, it is available in the U.S. only with special authorization. A uricosuric combined with allopurinol may be beneficial in some cases.

Probenecid is taken two to three times a day, and sulfinpyrazone begins at twice a day and increases to three or four times daily. The initial doses should be low and gradually increased. Probenecid combined with colchicine is more effective than probenecid alone, but everyone responds differently, so the dose should be carefully individualized.

The possible side effects of probenecid and sulfinpyrazone include skin rashes, gastrointestinal problems, anemia, and kidney stone formation. To help reduce acidity and the risk for kidney stones, patients should drink plenty of fluids (ideally water, not caffeinated beverages). Sodium bicarbonate supplemented by acetazolamide can also reduce acidity and the risk for stones.

NSAIDs, particularly aspirin, as well as other salicylate drugs, interfere with uricosuric drugs and reduce effectiveness. Patients who require minor pain relief should instead take acetaminophen (Tylenol). Uricosurics interact with many other drugs, and a patient should be sure to inform their health care provider of all medications they are taking.

People who take these drugs should have normal kidney function. This therapy may not be as beneficial in many elderly patients, who often have some kidney insufficiency.

Allopurinol (Lopurin, Zyloprim). Allopurinol blocks uric acid production. It is the drug most often used in long-term gout treatment for older patients and those who overproduce uric acid.

Allopurinol is taken by mouth once a day in doses of 100 - 600 mg, depending on the patient's response to treatment. When it is first used, allopurinol can trigger further attacks of gout. Therefore, during the first months (or longer) of therapy, the patient also takes an NSAID or colchicine to reduce that possibility.

Allopurinol has positive effects on "bad" cholesterol levels, so it may be better than other drugs for patients with both gout and coronary artery disease.

Side effects, which can be severe, include:

Rash
Diarrhea
Headache
Fever
Leukopenia (a reduction in the number of white blood cells)
Thrombocytopenia (a reduction in the number of platelets)
Cataracts

In rare cases, the rash can become severe and widespread enough to be life threatening (this condition is called toxic epidermal necrolysis, or TEN). Allergic individuals who experience only a mild rash may be able to build up their tolerance for the drug by undergoing a desensitization process.

Allopurinol interacts with certain other drugs, such as azathioprine.

Puricase (PEG-Uricase). This is an experimental drug that has been shown to rapidly reduce excess uric acid. If approved, it may help those who have failed other treatments.

It should be noted that many drugs used for gout can also precipitate acute gout symptoms and so should not be used until symptoms have subsided. The patient should then start treatment with small doses that gradually increase.

Hypertensive Agents. People with gout have a higher risk for high blood pressure. Some of the drugs used to treat hypertension, such as thiazide diuretics, can increase the risk for gout attacks. Newer agents, such as losartan (an angiotensin II receptor antagonist), and amlodipine (a calcium channel blocker), may have beneficial effects on both high blood pressure and gout.

Febuxostat. Febuxostat is the first drug to emerge in many decades as a potential new treatment for chronic gout. It may prove to be an alternative for patients who are allergic to allopurinol. The drug is awaiting approval from the U.S. Food and Drug Administration (FDA).

Other Treatments

Surgery. Large tophi that are draining, infected, or interfering with the movement of joints may need to be surgically removed. When infection is present, the procedure carries a high risk for complications. People most likely to have surgery also tend to have other medical conditions that might worsen their outlook. In one study, experts suggested that better preventive measures, such as the use of allopurinol, could reduce the need for surgery.

Several other surgical procedures are available for relieving pain and improving the function of affected joints. It is sometimes necessary to replace joints.

Hot and Cold Therapy. Rest and protecting the affected joint with a splint can also promote recovery. One study reported that applying ice packs for 30 minutes four times daily significantly reduced pain. However, a different study recommended applying warm water continuously and moving the joint. The theory behind this advice was that the pain in a gout attack is due to grinding from the crystals and that warmth would help dissolve the crystals and relieve pain.

Lifestyle Changes

Any activities that increase energy demands on the body also increase metabolism of purines, which produces uric acid. Avoiding stress and staying healthy are important for the prevention of attacks.

Because uric acid levels are only mildly affected by diet, dietary therapy does not play a large role in the prevention of gout. Still, people who have had an attack of gout may benefit from reducing their intake of purine-rich foods, particularly if they eat unusually large quantities of such foods.

While meat and certain types of seafood and shellfish do produce high levels of purines in the blood, research has suggested that not all purine-rich foods are associated with gout. Eating a moderate amount of purine-rich vegetables (spinach, cauliflower, mushrooms, legumes) does not appear to increase the risk of gout.

Dairy products, especially low-fat products (low-fat yogurt and skim milk), may actually protect against gout. Researchers have also found that taking 500 mg a day of vitamin C significantly reduces uric acid levels. They are investigating whether vitamin C can be used to prevent or treat gout.

Foods to Avoid:

Organ meats (liver, kidneys, sweetbreads)
Red meat (beef, pork, lamb)
Meat extracts (soup, broth, gravies)
Seafood (anchovies, sardines, herring, fish roe, canned tuna fish, shrimp, lobster, scallops, mussels)
Yeast products (beer and baked goods)

A supervised weight-loss program may be a very effective way to reduce uric acid levels in overweight patients. Crash dieting, on the other hand, is counterproductive because it can increase uric acid levels and may cause an acute attack.

Drinking plenty of water and other nonalcoholic beverages helps remove MSU crystals from the body.

Alcohol should be avoided, since it promotes purine metabolism and uric acid production. It also may reduce excretion of uric acid. Heavy drinking, especially binge drinking of beer or distilled spirits, should be avoided.

People with gout should also attempt to avoid activities that cause repetitive joint trauma, such as wearing tight shoes.

Travel is an example of an activity that increases the risk for gout. It not only increases stress, but eating and drinking patterns may change. Before traveling, patients should discuss preventive measures with their health care providers. The doctor may prescribe a prednisone tablet to be taken immediately at the first sign of a gout attack. In most cases, this stops the episode.

Complications

Properly treated gout rarely poses a long-term health threat, though it can be a cause of short-term pain and incapacity for thousands of Americans.

Left untreated, gout can develop into a painful and disabling chronic disorder. Persistent gout can destroy cartilage and bone, causing irreversible joint deformities and loss of motion. Survey results released in 2006 show that two-thirds of persons with gout consider the pain of attacks among the worst they've ever experienced. An estimated 75% of those surveyed said flare-ups made walking very difficult, and about 70% reported trouble putting on shoes or playing sports.

Tophi are firm chalky, gritty clumps of uric acid crystals that build up in tissue surrounding a joint. If gout is not treated, tophi can grow to the size of golf balls and can destroy bone and cartilage in the joints, similar to the process in rheumatoid arthritis. If they lodge in the spine, tophi can cause serious damage including compression, although this is very rare. In extreme cases, joint destruction results in complete disability.

Kidney Stones. Kidney stones occur in 10 - 40% of gout patients, and can occur at any time after the development of hyperuricemia. Although the stones are usually composed of uric acid, they may also be mixed with other materials.

Kidney stones result when urine becomes too concentrated, and substances in the urine crystallize to form stones. Symptoms occur when the stones begin to move down the ureter and cause intense pain. Kidney stones may form in the pelvis or calyces of the kidney or in the ureter.

Kidney Disease. About 25% of patients with chronic hyperuricemia develop progressive kidney disease, which sometimes ends in kidney failure. It should be noted, however, that many experts believe that chronic hyperuricemia is unlikely to be a common cause of kidney disease. In most cases, the kidney disease comes first and causes high concentrations of uric acid.

Gout is found in higher rates in people with high blood pressure, coronary artery disease, and heart failure. Hyperuricemia, in fact, has been associated with a higher risk of death from heart conditions. A large study published in 2007 found an association between gout and having the metabolic syndrome -- a collection of problems, such as abdominal obesity, high blood pressure, high triglycerides levels, and low "good" cholesterol levels. This syndrome increases a person's risk of heart disease and diabetes.

A study published in the August 2006 journal Arthritis & Rheumatism found that gout increases the risk of heart attacks in men with no previous history of heart problems. According to some studies, hyperuricemia may be associated with heart disease, but there is not enough data to confirm such an association.

Click the icon to see an image of coronary artery blockage.

The following are some conditions that are associated with long-term gout:

Cataracts
Dry eye syndrome
Complications in the lungs (in rare cases, uric acid crystals occur in the lungs)

Resources

www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation
www.gouteducation.org -- The Gout & Uric Acid Education Society

References

Choi HK, Ford ES, Li C, Curhan G. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Arthritis Rheum. 2007;57(1):109-15.

Huang HY, Appel LJ, Choi MJ et al. The effects of vitamin C supplementation on serum concentrations of uric acid: results of a randomized controlled trial. Arthritis Rheum. 2005 Jun;52(6):1843-7.

Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum. 2006 Aug;54(:2688-96.

Underwood M. Diagnosis and management of gout. BMJ. 2006;332(7553):1315-9.

Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65(10):1301-11.

Zhang W, Doherty M, Bardin T, et al. EULAR evidence based recommendations for gout. Part II: Management. Report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2006;65(10):1312-24.

Zhang YQ, Chaisson CE, Chen CA, McAlindon TE, Hunter DJ. High Humidity and High Temperature Increase the Risk of Recurrent Gout Attacks: The Online Case-crossover Gout Study. Presentation Number 707. American College of Rheumatology Annual Scientific Meeting, Washington, DC, November 2006.

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