FitSugar

Blisters Hurt, Treatment Shouldn't

FitSugar — Wed, 15 Aug 2007 09:30:00 -0700

Yesterday, while running on the treadmill, I did not notice that my sock had a rather unfortunate fold in it which left me an even more unfortunate blister on my heel. So I went on the search for what I should do to help heal it rapidly.

Here are some good suggestions I came across on caring for a blister, from the University of Michigan Health System:

Steps should be taken to avoid further irritating the problem area.
Large blisters can be carefully drained with a sterilized needle, then covered with antibiotic ointment and a bandage.
For extra protection, purchase a moleskin at a drugstore. Cut a hole that's larger than the blister in the moleskin, creating a moleskin "donut." Then apply the moleskin so that the hole is over the blister.
See your doctor about any blisters that don't heal in a reasonable amount of time, or look like they may be infected.

Source

Psoriasis

FitSugar — Wed, 08 Oct 2008 17:35:27 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment

Psoriasis that develops on the hands or feet is often very difficult to treat. However, an advanced clinical trial showed that a medication called efalizumab (Raptiva) effectively cleared or nearly cleared moderate-to-severe symptoms in adults after 12 weeks.

Several studies have shown that most people with severe psoriasis who are treated with infliximab (Remicade) have significant improvement in symptoms by week 10. The findings were presented at the 2007 annual meeting of the American Academy of Dermatology.

Continuing etanercept (Enbrel) after 12 weeks improves disease severity without an increase in infections or side effects, according to a study published in the Archives of Dermatology.

Disease classification

The National Psoriasis Foundation has proposed a new way to classify psoriasis. Instead of being grouped as mild, moderate, or severe, the group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

Coexisting conditions

Studies from Newfoundland and Germany have revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Previous research has found an increased risk of heart disease in psoriasis patients. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Such patients should receive comprehensive health examinations to reduce the risk, the authors recommended. Study participants were considered to have severe psoriasis if they required systemic treatment.

Smoking and psoriasis

Introduction

Psoriasis is a chronic skin disorder marked by periodic flare-ups of sharply defined red patches, covered by a silvery, flaky surface. The main disease activity leading to psoriasis occurs in the epidermis, the top five layers of the skin.

The process starts in the basal (bottom) layer of the epidermis, where keratinocytes are made. Keratinocytes are immature skin cells that produce keratin, a tough protein that helps form hair, nails, and skin. In normal cell growth, keratinocytes grow and move from the bottom layer to the skin's surface and shed unnoticed. This process takes about a month.

In persons with psoriasis, the keratinocytes multiply very rapidly and travel from the basal layer to the surface in about 4 days. The skin cannot shed these cells quickly enough, so they build up, leading to thick, dry patches, or plaques. Silvery, flaky areas of dead skin build up on the surface of the plaques before being shed. The underlying skin layer (dermis), which contains the nerves and blood and lymphatic vessels, becomes red and swollen.

Types of Psoriasis

Various forms of psoriasis exist. Some can occur alone or at the same time as other types, or one may follow another. The most common type is called plaque psoriasis, also known as psoriasis vulgaris.

Plaque psoriasis leads to skin patches that start off in small areas, about one-eighth of an inch wide. They usually appear in the same areas on opposite sides of the body.

The patches slowly grow larger and develop thick, dry plaque. If the plaque is scratched or scraped, bleeding spots the sizes of pinheads appear underneath. This is known as the Auspitz sign.

Some patches may become ring shaped (annular), with a clear center and scaly raised borders that may appear wavy and snake-like.

As the disease progresses, eventually separate patches may join together to form larger areas. In some cases, the patches can become very large and cover wide areas of the back or chest. This is known as geographic plaques because the skin lesions resemble maps.

Plaque psoriasis may persist for long periods. More often it flares up periodically, triggered by certain factors such as cold weather, infection, or stress.

Patches most often occur on the:

Elbows
Knees
Lower back

The may also be seen on the:

Upper pelvic bone area
Bottom of the feet
Calves and thighs
Genital areas
Palms of hands

Psoriasis of the scalp affects about 50% of patients. In some cases, the psoriasis may cover the scalp with thick plaques that extend down from the hairline to the forehead.

Psoriasis patches rarely affects the face in adulthood. In children, psoriasis is most likely to start in the scalp and spread to other parts of the body. Unlike in adults, it also may occur on the face and ears.

Psoriatic arthritis (PsA) is an inflammatory condition characterized by stiff, tender, and inflamed joints. Estimates on its prevalence among those with psoriasis range from 2 - 42%. AIDS patients and those with severe psoriasis are at higher risk for developing PsA.

About 80% of PsA patients have psoriasis in the nails. Arthritic and skin flare-ups tend to occur at the same time. It is not clear whether psoriatic arthritis is a unique disease or a genuine variation of psoriasis, although evidence suggests they are both caused by the same immune system problem.

Although patients with psoriatic arthritis tend to have mild skin symptoms, the disease affects the entire body. PsA, therefore, is more serious than the more common plaque psoriasis. Infrequently, the course of PsA has been associated with a syndrome known by the acronym SAPHO, which stands for:

Synovitis (inflammation in the joints)
Acne
Pustule eruptions
Hyperostosis (abnormal bony growths)
Osteolysis (bone destruction)

Some experts group PsA into five forms. The forms differ according to the location and severity of the affected joint:

Symmetric PsA: Symptoms occur in the same location on both sides of the body. It usually affects multiple joints. In about half of the cases, the condition will get worse. The condition is very similar to, but less disabling than, rheumatoid arthritis. The psoriasis itself is often severe.
Asymmetric PsA: This form involves periodic joint pain and redness, usually in only one to three joints, which can be the knee, hip, ankle, wrist, or one or more fingers. The pain does not occur in the same location on both sides of the body.
Distal interphalangeal predominant (DIP): DIP involves the joints of the fingers and toes closest to the nail. It occurs in about 5% of PsA cases.
PsA in the spine: Inflammation in the spinal column (spondylitis) is the primary symptom in about 5% of PsA cases. Such patients may have stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. The spine can be involved in many patients with PsA, even though stiffness and burning sensations in these areas are not the primary symptoms. When it affects the spine, psoriatic arthritis most frequently targets the sacrum (the lowest part of the spine). Movement is difficult.
Arthritis mutilans: This is a severe, deforming, and progressive form of arthritis. It affects less than 5% of PsA cases. It mainly affects the small joints of the hands and feet, but it can also be found in the neck and lower back. Arthritic and skin flares and remissions tend to coincide.

People who start to smoke after developing psoriasis may delay the onset of psoriatic arthritis, according to research presented at the 2007 annual meeting of the Society for Investigational Dermatology. Researchers found that in nonsmokers, the time between psoriasis diagnosis and psoriatic arthritis development was 13 years, compared to 23 among those who started smoking after the onset of psoriasis. Study participants who smoked before developing psoriasis had psoriatic arthritis occur in about 8 years. However, smoking causes serious health problems and should not be considered as a way to delay this type of psoriasis.


Psoriasis Form	Description of Skin Patches	Comments
Guttate Psoriasis	The patches are teardrop-shaped and appear suddenly, usually over the trunk and often on the arms, legs, or scalp. They often disappear without treatment.	Guttate psoriasis can occur as the initial outbreak of psoriasis, often in children and young adults 1 - 3 weeks after a viral or bacterial (usually streptococcal) respiratory or throat infection. A family history of psoriasis and stressful life events are also highly linked with the start of guttate psoriasis. Guttate psoriasis can also develop in patients who have already had other forms of psoriasis, most often in people treated with widely-applied topical (rub-on) products containing corticosteroids.
Inverse Psoriasis	Patches usually appear as smooth inflamed patches without a scaly surface. They occur in the folds of the skin, such as under the armpits or breast, or in the groin.	Inverse psoriasis may be especially difficult to treat.
Seborrheic Psoriasis	Patches appear as red scaly areas on the scalp, behind the ears, above the shoulder blades, in the armpits or groin, or in the center of the face.	Seborrheic psoriasis may be especially difficult to treat.
Nail Psoriasis	Tiny white pits are scattered in groups across the nail. Toenails and sometimes fingernails may have yellowish spots. Long ridges may also develop across and down the nail. The nail bed often separates from the skin of the finger and collections of dead skin can build up underneath the nail.	Over half of patients with psoriasis have abnormal changes in their nails, which may appear before other skin symptoms. In some cases, nail psoriasis is the only symptom.
Generalized Erythrodermic Psoriasis (also called psoriatic exfoliative erythroderma)	This is a rare and severe form of psoriasis, in which the skin surface becomes scaly and red. The disease covers all or nearly all of the body.	About 20% of such cases evolve from psoriasis itself. The condition may also be triggered by certain psoriasis treatments, and other medications such as corticosteroids or synthetic antimalarial drugs.
Pustular Psoriasis	Patches become pus-filled and blister-like. The blisters eventually turn brown and form a scaly crust or peel off. Pustules usually appear on the hands and feet. When they form on the palms and soles, the condition is called palmar-plantar pustulosis.	Pustular psoriasis may erupt as the first occurrence of psoriasis, or it may evolve from plaque psoriasis. A number of conditions may trigger pustular psoriasis, including infection, pregnancy, certain drugs, and metal allergies. It can also accompany other forms of psoriasis and be very severe.

Causes

The precise causes of psoriasis are unknown. It is generally believed to be due to damage in factors in the immune system, enzymes, and other materials that control skin cell division. This prompts an abnormal immune response, which causes rapid production of immature skin cells and inflammation.

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

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign invaders, such as bacteria or viruses.
The masses of blood cells that gather at the injured or infected site produce factors to repair wounds, clot the blood, and fight infections.
In the process, the surrounding area becomes inflamed (red and swollen), and some healthy tissue is injured.

The 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 substances (antigens) and launch an offensive or defensive action against them:

B cells produce antibodies, which are designed to attack the antigens. Antibodies can either ride along with a B cell or travel on their own.
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 (TH cells).

Killer T cells directly attack antigens found on bacteria or other cells.
Helper T stimulate B cells and other white cells to attack the antigen.

The actions of the helper T cells are of special interest. Researchers have found high numbers of helper T cells in psoriatic plaques. Helper T cells normally stimulate B cells to produce antibodies. In psoriasis, however, they appear to direct the B cells to produce autoantibodies ("self" antibodies), which attack skin cells. In psoriatic arthritis, cells in the joints also come under attack.

Helper T cells also release or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are very important for healing. If overproduced, however, they can cause serious damage, including inflammation and injury during the psoriasis disease process. In psoriasis, researchers are particularly interested in cytokines known as GRO-alpha, tumor necrosis factor, and certain interleukins.

Cytokines attract large numbers of other large white blood cells known as neutrophils. Neutrophils stimulate the production of arachidonic acid, producing two key players in the inflammatory process:

Leukotrienes: These chemicals attract even more white blood cells to the inflamed area.
Prostaglandins: These chemicals widen blood vessels and increase blood flow.

A combination of genes is involved with increasing a person's susceptibility to the conditions leading to psoriasis.

HLA Molecules. The processes leading to all autoimmune diseases involve the human leukocyte antigen (HLA) system. HLA molecules pick off parts of antigens and present them on the surface of a cell so that the various infection-fighting factors in the immune system can recognize and destroy them. Most immune disorders, including psoriatic arthritis, are due to problems with this system. For example, psoriasis patients with an HLA genetic factor called HLA-CW6 tend to develop psoriasis at an earlier than average age. However, only 10% of people who have this gene develop psoriasis. Other genetic and environmental factors are required to actually trigger the disease.

PSORs. Researchers have now identified four key genes (named PSOR 1 - 4) that are involved with psoriasis. Of particular interest are the genes located in regions on specific chromosomes that are linked to HLA and tumor necrosis factor, another immune factor strongly associated with psoriasis.

Weather, stress, injury, infection, and medications, while not direct causes, are often important in triggering the disease process leading to the start and worsening of psoriasis.

Weather. Cold, dry weather is a common trigger of psoriasis flare-ups. Hot, damp, sunny weather helps relieve the problem in most patients. However, some people have photosensitive psoriasis, which actually improves in winter and worsens in summer when skin is exposed to sunlight.

Stress and Strong Emotions. Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. In one study, nearly 40% of patients remembered a specific stressful event that occurred within a month of a psoriasis flare. Other research has suggested that stress can trigger specific immune factors associated with psoriasis flares.

Infection. Infections caused by viruses or bacteria can trigger some cases of psoriasis. For example:

Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and strep throat, are known to trigger guttate psoriasis in children and young adults. The infections may make ordinary plaque psoriasis worse.
Human immunodeficiency virus (HIV) is also associated with psoriasis.
An uncommon form of human papillomaviruses (HPV) called EV-HPV has been associated with psoriasis. Although EV-HPV is probably not a direct cause, it may play a role in the continuation of psoriasis. This HPV form is not the virus associated with cervical cancer and genital warts.

Skin Injuries and the Köbner Response. The Köbner response is a delayed response to skin injuries, in which psoriasis develops later on at the site of the injury. In some cases, even mild abrasions can cause an eruption, which may be a factor in the frequency of psoriasis on the elbows or knees. It should be noted that psoriasis can develop in areas with no history of skin injury.

Medications. Drugs that can trigger the onset of the disease, worsen symptoms, or cause a flare-up include:

Angiotensin-converting enzyme (ACE) inhibitors, drugs used to treat high blood pressure and heart problems
Beta-blockers, drugs used to treat high blood pressure and heart problems
Chloroquine, a medicine used to treat malaria
Lithium for bipolar disorder treatment
Indomethacin, a nonsteroidal anti-inflammatory drug (NSAIDs) -- Note: Other NSAIDs, such as meclofenamate, may actually improve the condition.
Progesterone, used in female hormone therapies

Flare-ups of severe psoriasis may occur in persons who stop taking steroids taken by mouth, or who discontinue use of very strong steroid ointments that cover wide skin areas. The flare-ups may be of various psoriatic forms, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.

Medications that cause rashes, a side effect of many drugs, can trigger psoriasis as part of the Köbner response.

Risk Factors

Between 5.8 and 7.5 million Americans have psoriasis. Risk factors for psoriasis include:

Age under 20. About 40% develop the condition before age 20. Psoriasis (most often plaque psoriasis) can even occur in infants.
Climate. Some studies have found that the disorder develops earlier and more frequently in colder climates. For example, psoriasis occurs more frequently in African-Americans and in Caucasians who live in colder climates than in people of any ethnicity who live in Africa.
Ethnicity. Psoriasis is uncommon in Native Americans of either North or South American descent.
Family history of the disease. About 35% of those with psoriasis have one or more family members with the disorder.
Male gender. Some studies have indicated that more men than women have psoriasis.

Diagnosis

A microscopic examination of tissue taken from the affected skin patch is needed to make a definitive diagnosis of psoriasis and to distinguish it from other skin disorders. Usually in psoriasis, the examination will show a large number of dry skin cells, but without many signs of inflammation or infection. Specific changes in the nails are often strong signs of psoriasis.

Several conditions produce symptoms that resemble those of psoriasis. For example:

Seborrheic psoriasis is hard to distinguish from seborrheic dermatitis (dandruff is one form of this condition). Seborrheic dermatitis patches are usually greasy, yellowish, and crusty. Nail involvement may also help differentiate psoriasis.
Generalized erythrodermic psoriasis may be confused with drug allergic reactions, atopic eczema, and symptoms of lymphomas.
Fungal infections, other skin conditions, or circulation problems may also cause nail changes typical of psoriasis.

Symptoms of psoriatic arthritis may also resemble the following:

Rheumatoid arthritis (RA). As in rheumatoid arthritis, psoriatic arthritis can cause pain or tenderness in one or more joints, and morning stiffness is common. People with psoriatic arthritis, however, lack a particular antibody, called rheumatoid factor, which is found in the blood of many people with rheumatoid arthritis.
Systemic lupus erythematosus (SLE). Symptoms of SLE may include both a psoriasis-like rash and arthritis, which could make the diagnosis difficult.
Reiter's disease. Reiter's disease is a syndrome that includes arthritis and inflammation in the eyes and urinary tract. It also causes skin lesions that are very similar to psoriasis, which are usually raised patches on the lips, penis, palms, and soles.
Gout. Gout causes pain, often in the fingers and toes.

Some evidence now indicates that inflammation in psoriatic arthritis may be distinguished from other arthritic conditions by its occurrence in sites where muscle tissue inserts into the bone (called enthesitis) rather than in the joint, which is a common site in other inflammatory arthritic conditions.

Severity of psoriasis itself ranges from one or two flaky inflamed patches to widespread pustular psoriasis that, in rare cases, can be life threatening. To help determine the best treatment for a patient, doctors usually classify the disease as mild to severe. The classification depends on how much of the skin is affected:

Mild psoriasis affects less than 3% of the body surface. Most cases of psoriasis are limited to less than 2% of the skin.
Moderate psoriasis covers 3 - 10% of the skin.
If more than 10% of the body is affected, the disease is considered severe.

The palm of the hand equals 1% of the body. The severity of the disease is also measured by its effect on a person’s quality of life.

However, the National Psoriasis Foundation has proposed a new classification method. The group suggests a new two-tiered system that classifies patients as needing either local or body-wide (systemic) treatment.

While disease severity impacts treatment success, some forms of psoriasis can be very resistant to treatment even though they are not categorized as severe. They include:

Any psoriasis on the palms and soles (hand and foot psoriasis)
Inverse psoriasis (which occurs in the folds of the skin)
Scalp psoriasis
Psoriatic arthritis

Treatment

Many creams, ointments, lotions, and pills are available for the treatment of psoriasis. Many patients require only over-the-counter treatment, or even none at all during relapses.

About a third of patients with psoriasis, however, do not respond to over-the-counter remedies and lifestyle changes, and require aggressive treatments. In some cases, such treatments need to be lifelong.

In general, there are three treatment options for patients with psoriasis.

Topical medications such as lotions, ointments, creams, and shampoos
Body-wide (systemic) medications, which involve pills or injections that affect the whole body, not just the skin
Phototherapy, which uses light to treat psoriasis lesions

Individual requirements vary widely, and treatment selection must be carefully discussed with the doctor.

Giving treatment in a particular order is a strategy for providing both quick relief of symptoms and long-term maintenance. It involves three main steps:

The quick fix, to clear the psoriatic lesions during an acute outbreak (for example, a high-strength topical steroid in mild-to-moderate psoriasis, or an oral immunosuppressant in more severe cases)
The transitional phase, intended to gradually introduce the maintenance drug
Ongoing maintenance therapy

Choices for transitional or maintenance treatments depend on the severity of the condition. Some examples are described in the following sections.

In severe chronic cases, a doctor may recommend rotational therapy. This approach alternates treatments. The goal is to prevent severe side effects or build-up of resistance from long-term use of a single medicine. An example of a rotational schedule may be the following:

The patient gets phototherapy for about 2 years.
The patient then takes one or two powerful body-wide drugs for 1 - 2 years and stops.
Phototherapy starts again, and the cycle repeats.

Some doctors use the Koo-Menter Psoriasis Instrument (KMPI) to decide which patients should receive a pill or an injection. The KMPI’s questions include:

Does psoriasis cover at least 5% of the patient’s body?
Is the patient disabled by psoriasis?
Does psoriasis affect the patient’s quality of life?

If the answer to these questions is "yes," three additional questions are considered:

Is light therapy inappropriate for the patient?
Is the patient’s psoriasis resistant to light therapy?
Does the patient have psoriatic arthritis?

If the answer to these questions is “yes,” a doctor may decide to prescribe a pill or injected drugs.

Doctors increasingly use combinations of pills, creams, ointments, and phototherapy instead of single medications. Combinations of oral treatments are particularly useful, since the doses of each drug can be reduced. This lowers the risk of severe side effects. Thousands of combinations are possible, and the patient and doctor should discuss the best treatment for individual needs.

Topical Medications

Topical medications are those applied only to the surface of the body. They come in the following forms:

Creams
Foams
Gels
Lotions
Occlusive tapes
Ointments
Shampoos
Solutions
Sprays

In general, topical treatments are the first line for mild-to-moderate psoriasis, but they may also be used, alone or in combination, with more powerful treatments for moderate-to-severe cases. Topical medicines rarely produce complete clearance, however.

Corticosteroid topical treatments are the mainstay of psoriasis treatments in the United States. They work for most patients. Such treatments:

Decrease inflammation
Block cell production
Relieve itching

Corticosteroids are available in a wide range of strengths, and are generally given as follows:

Less potent drugs are used for mild-to-moderate psoriasis.
Stronger drugs are reserved for more severe disease.

In the past, topical steroids have been used twice a day. Studies are reporting, however, that certain drugs may work just as well if taken once a day. Most studies have evaluated high-potency steroids, but one study suggested that those of medium strength, such as triamcinolone (Aureocort, Tri-Adcortyl), may be equally beneficial as a once-daily treatment. However, corticosteroids used alone clear psoriasis in only 4 - 36% of patients.

Combination therapy. Combinations with other drugs are often needed. For example, an effective, topical regimen uses the following combination for maintenance therapy:

A high-potency steroid (such as halobetasol) on the weekend
A vitamin D3 topical medication called calcipotriene, twice daily on weekdays

In one study, more than 75% of patients with mild-to-moderate psoriasis remained in remission for at least 6 months with this regimen.

Side Effects. The more powerful the corticosteroid, the more effective it is. But it also has a higher risk for severe side effects. Side effects may include:

Burning
Irritation
Dryness
Acne
Thinning of the skin; skin may become shiny, fragile, and easily cut
Dilated (widened) blood vessels
Loss of skin color

Loss of Effectiveness. In most cases, the patients become tolerant to the effects of the drugs, and the drugs no longer work as they should. Some experts recommend using intermittent therapy (also called weekend or pulse therapy). This type of treatment involves applying a high-potency topical medication for 3 full days each week.

Note: This list is not all inclusive.
Low potency (some are available over the counter)	Desonide (Tridesilon, DesOwen) Flumethasone pivalate (Locorten) Fluocinolone acetonide (Synalar, Derma-Smoothe) Hydrocortisone (Hytone, Penecort, Synacort, Cort-Dome, Nutracort, Westcort) Triamcinolone acetonide (Aristocort)
Low to medium potency	Alclometasone dipropionate (Aclovate) Hydrocortisone (Locoid, Pandel) Hydrocortisone valerate (Westcort) Prednicarbate (Dermatop)
Medium to upper-mid potency	Clocortolone pivalate (Cloderm) Fluticasone propionate (Cutivate) Mometasone furoate (Elocon) Triamcinolone acetonide (Aureocort, Tri-Adcortyl, Kenalog)
High potency	Betamethasone (Diprosone) Amcinonide (Cyclocort) Desoximetasone (Topicort) Diflorasone diacetate (Florone, Maxiflor) Fluocinonide (Lidex) Halcinonide (Halog)
Very high potency	Halobetasol propionate (Ultravate) Betamethasone (Diprolene, Luxiq) Clobetasol propionate (Temovate, Olux) Diflorasone diacetate (Florone, Maxiflor, Psorcon)

Coal tar preparations have been used to treat psoriasis for about 100 years, although their use has declined with the introduction of topical vitamin D3-related medicines. Crude coal tar stops the action of enzymes that contribute to psoriasis, and helps prevent new cell production. Tar is often used in combination with other drugs and with ultraviolet B (UVB) phototherapy.

Side Effects. Preparations have the following drawbacks:

Stains on clothing
Skin irritation
Sun sensitivity and increased risk of sunburn for up to 24 hours after use

Anthralin (Dritho-Scalp, Drithocreme, Micanol) is related to a medication called chrysarobin, in use since the early 1900s. Anthralin slows skin cell reproduction and can produce remissions that last for months. It is recommended only for chronic or inactive psoriasis, not for acute or inflamed eruptions. Persons with kidney problems should use anthralin with caution.

As with tar, its use has also declined with introduction of the topical vitamin D-related medicines, but newer formulations, such as Micanol, have made its use more tolerable. Micanol (Psoriatec) is an anthralin formulated in microcapsules, which dissolve and allow the drug to be delivered directly to the target skin areas. It is particularly useful for scalp psoriasis, and it is less likely to stain.

Side Effects. Anthralin may cause the following side effects:

Skin irritation and burning
Staining of clothes, hair, fabrics, plastics, and other household products

Patients should not use anthralin on their faces. Fair skinned people should generally avoid it. Triethanolamine (CuraStain) is a chemical that can neutralize anthralin and help reduce irritation from short-contact anthralin treatment. It should be applied 1 or 2 minutes before washing off the anthralin. It is then reapplied after drying the skin.

Washing stained items with hypochlorite (Clorox) detergents can help remove stains. Many people use disposable gloves while applying the treatment to avoid staining hands.

Application. Apply anthralin only to the psoriasis plaques. Rub the cream in well, and wipe off any excess. Wash off only with lukewarm water, not soap. Using hot water will trigger the staining action. A technique called short-contact anthralin therapy (SCAT), also called minute therapy, is useful for local areas of psoriasis. In such cases, anthralin is applied for only 10 minutes to an hour.

A topical form of vitamin D3, calcipotriene (Dovonex) is proving to be both safe and effective. It is now available in a foam preparation, which makes compliance even easier. Several other topical vitamin D3 related drugs showing promise include maxacalcitol (Oxarol), tacalcitol, and calcitriol (Silkis).

Calcipotriene appears to:

Block skin cell reproduction
Enhance the maturity of keratinocytes (the impaired skin cells in psoriasis)
Acts as an anti-inflammatory

It works just as well as moderate topical corticosteroids, short-term anthralin, and coal tar in improving mild-to-moderate plaque psoriasis. Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug.

Using the drug in combination with other topical and systemic treatments may improve effectiveness. Calcipotriene doesn't work as well as the highest potency corticosteroids, but products or regimens that combine both medications are proving to be more effective than either one alone. Taclonex, an ointment containing both calcipotriol and betamethasone, was approved by the U.S. Food and Drug Administration (FDA) in January 2006 for the treatment of adults with psoriasis. Studies show the combination works better than either drug alone.

Combining vitamin D ointments with systemic medicines, notably methotrexate, acitretin, or cyclosporine, increases effectiveness and allows lower doses or either medication, thereby reducing side effects.

Studies also report success in some patients who use vitamin D ointments in combination with phototherapy treatment.

Side Effects. Calcipotriene may cause the following side effects:

A possible lowering of vitamin D levels, which may affect bone growth in some children
A possible increase in blood calcium levels (seen in some people who apply calcipotriene to large areas)
Skin irritation in about 20% of patients, particularly on the face and in skin folds

Calcipotriene appears to cause greater skin irritation than potent corticosteroids. Diluting the drug with petrolatum or applying topical corticosteroids to sensitive areas may prevent this problem.

Retinoids are related to vitamin A. They are used for various skin disorders. Tazarotene (Tazorac) is the first topical retinoid found to be effective for mild-to-moderate psoriasis. It is available in cream or gel form.

Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. It can be used on the scalp and nails, but it is not recommended for the genital areas or around the eyes. The gel should be used on only 20% of the body at anytime; the cream on up to 35%. (Note: The palm of the hand is about 1% of the body surface.)

Combining topical retinoids with other psoriasis treatments, such as with topical steroids, works better than using the drug by itself.

Side Effects. Tazarotene may cause dryness and irritation of healthy skin. Applying zinc oxide and moisturizer around the treated area can protect the healthy skin.

At levels high enough to be effective for psoriasis, tazarotene can cause severe skin irritation on treated areas. This medicine, then, is usually used in combination with other treatments, therefore allowing a lower dose. Mixing the drug in equal amounts with petroleum jelly (Vaseline) initially and then gradually increasing the amount of tazarotene may help the skin areas become less sensitive. It should be noted that the skin can become very red while it is actually improving.

Vitamin A derivatives (drugs related to vitamin A) have been associated with birth defects and should not be used by women who are pregnant, who wish to conceive, or who are nursing.

Salicylic acid applied to the skin helps remove scaly plaque and enhance the actions of other medications. It should not be used to cover wide areas of the body, since it can cause nausea and ringing in the ears. Combinations with high potency steroids, such as mometasone furoate (Combisor), clobetasol propionate, and betamethasone, are proving to be very helpful. Only Combisor is available in the United States.

Watertight (occlusive) tapes or wrappings may help heal psoriasis. Occlusive tapes are particularly useful for psoriatic cuts on the palms and soles. In such cases, the tape should be applied across the cuts until they heal.

Occlusive tapes retain sweat, which helps restore moisture to the outer skin layer and prevent scaling. They also protect against abrasion and irritation.

High-Potency Corticosteroid Tapes. Applying a corticosteroid beneath an occlusive tape, or using a tape that already has a potent corticosteroid (Cordran Tape) such as flurandrenolide may be especially beneficial. Studies are showing that high-potency corticosteroid-containing tapes are more effective than using high-potency corticosteroid ointments alone.

However, the tapes are expensive and are associated with a high rate of skin irritation, increased secondary infections, and a greater chance of symptoms relapse after treatment is stopped. Infection risk may be reduced by changing tapes every 12 hours.

The use of corticosteroids under occlusive tapes on large areas of psoriasis also increases the risk for adrenal insufficiency, a sometimes dangerous condition that occurs because the body loses its ability to produce natural steroids. Children are especially vulnerable to this effect.

Other Medications with Occlusive Tapes or Wrappings. The tapes may be used in combination with other medications, such as fluorouracil. Occlusive wrappings are not usually used with tazarotene (Tazorac) and should never be used without a doctor's recommendation.

Numerous topical medications are under investigation. One such medication, tacrolimus (Protopic), is an immunosuppressant that is proving to be useful in allergic skin disorders and is being studied for psoriasis. Studies have been mixed on its benefits, although new delivery methods may make it more effective. It may prove to be safe for sensitive areas, such as the face. Pimecrolimus (Elidel), a similar medication, is also being studied.

Systemic Medications

Systemic treatment uses various medications that affect the whole body, not just the skin. Many systemic drugs used for psoriasis are also used for other severe diseases, including autoimmune diseases (especially rheumatoid arthritis) and cancer.

Systemic treatments for psoriasis may be taken by mouth or injection. The medicines can have significant side effects and are generally reserved for severe psoriasis.

At this time, the only systemic medications specifically approved for psoriasis are:

Cyclosporine
Methotrexate
Retinoids

As with all medications for psoriasis, the patient should use the lowest strength medication first. The primary treatment is called a first-line treatment, the next is known as a second-line treatment, and so on. Combinations of medications are often used.

Methotrexate (Rheumatrex) is a biologic drug that interferes with cell reproduction and has anti-inflammatory properties. It is a first line, or primary, systemic drug used to treat adults with severe psoriasis. The medicine is one of the few systemic drugs proven to help patients with psoriatic arthritis.

The drug is taken weekly, not daily. (Deadly reactions have been reported in people who mistakenly took it once a day.)

Side Effects. Common side effects of methotrexate include:

Anemia
Headache
Mild hair loss
Mouth sores
Nausea
Possible muscle aches
Rash
Vomiting

Many of these side effects are due to folic acid deficiency. Patients should ask their doctor if folic acid supplements (generally recommended at 1 - 5 mg daily) are necessary.

More serious side effects include:

Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. Patients with active infections should avoid this drug.
Infertility, miscarriage, and birth defects. If used during pregnancy, the drug can cause miscarriages or birth defects in the baby. It may harm fertility in men.
Kidney complications.
Liver damage. In one study, 25% of patients taking methotrexate for 5 years developed scarring of the liver. Those with existing liver problems should not take this medicine, if possible. Regular monitoring for liver toxicity, including blood tests and liver biopsies, is important in patients who take the drug.
Lung disease. This side effect can be sudden and severe, and occurs in up to 5% of people who take methotrexate. Risk factors include diabetes, existing lung inflammation, protein in urine, and use of rheumatoid arthritis drugs called DMARDs.
Lymphomas. A few cases have been reported, which are most likely related to the drug's immune-suppressing (lowering) effects. In most instances, the disease has gone into remission when the drug was stopped. Most studies have found no significant risk for cancers in patients taking methotrexate.
Osteoporosis. Low doses of methotrexate do not appear to have any significant effect on bone loss, but long-term studies are needed to confirm this.
Radiation recall: An uncommon side effect in patients who have previously been burned by radiation cancer treatments or sunburns. In such cases, a flare-up of symptoms occurs in the previously affected skin areas.
Severe anemia. Folic acid supplements can offset this effect.
Toxic effects on bone marrow. This can cause reduced blood cell production.

Despite its side effects, some experts view methotrexate as the best therapy for widespread plaque psoriasis. It may also be effective for some patients with other severe forms of the disease, including psoriatic arthritis, generalized erythrodermic, and pustular psoriasis.

Methotrexate appears to be effective in children, but more safety research is needed.

Drug Interactions. Many drugs interact with methotrexate, occasionally with harmful results. For example, the antibiotic trimethoprim-sulfamethoxazole increases the toxicity of methotrexate.

A serious, harmful reaction can occur if methotrexate is taken with common, nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen. Other NSAIDs, namely ketoprofen, flurbiprofen, and piroxicam, appear to be safe when given with methotrexate and may be used in patients with psoriatic arthritis. Rheumatoid arthritis (RA) patients who take methotrexate often take NSAIDs as well, but methotrexate doses in psoriasis patients are usually much higher than those in RA.

People Who Should Avoid Methotrexate. Pregnant and nursing mothers should never take methotrexate because it increases the risk for severe, even fatal, birth defects and miscarriage. The drug should be discontinued several months before planning a pregnancy. It may also cause temporary impairment of fertility in men.

Persons with the following conditions should also avoid taking methotrexate:

Alcoholism
Anemia or other blood abnormalities
Immunosuppression
Kidney problems
Liver problems (including hepatitis)
Rheumatoid arthritis
Peptic ulcers

Patients at risk for liver complications include those with diabetes and obesity. Anyone with a history of hepatitis should have a liver biopsy before taking methotrexate.

Oral retinoids are vitamin A-related medications taken by mouth. This group of medicines is also a first-line treatment for adults with severe psoriasis. Oral retinoids used for psoriasis include acitretin (Soriatane) and isotretinoin (Accutane).

Acitretin is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic variants. When used alone, it is much less effective against more common forms, such as plaque or guttate psoriasis. However, combinations with PUVA phototherapy can markedly improve the response even in these patients.

Accutane, more commonly used to treat acne, is far less potent than acitretin, but may still be effective against pustular psoriasis and also be effective with phototherapy.

Oral retinoids help control cell reproduction and have anti-inflammatory properties. They may even improve arthritis that accompanies psoriasis.

Combination therapy. Acitretin may work the best when combined with other treatments, usually topical drugs and especially phototherapy. Combination therapy allows lower doses of oral retinoids to be used, which diminishes many skin and mucous membrane side effects. Acitretin combined with phototherapy has some of the highest clearance rates of any treatment.

Side Effects. All retinoids have the same potentially serious toxicities as do high doses of vitamin A. Side effects include:

Bone and joint pain
Bruising
Depression and possible suicide risk (with isotretinoin)
Eye problems, including blurred vision, cataracts, conjunctivitis, and a sudden deterioration in night vision
Fatigue
Headache
Increased bone growth, particularly in the ankles, pelvic area, and knees
Increased triglyceride levels
Liver damage
Nail problems
Skin and mucous membrane problems, including dry nose, nosebleeds, dry eyes, chapped lips, thinning hair, dry or "sticky" feeling skin, and peeling of the palms and soles

In rare cases, retinoids, particularly isotretinoin, may cause a condition called benign intracranial hypertension (pseudotumor cerebri), which occurs in the brain. Symptoms include headache, nausea, vomiting, and blurred vision. Patients experiencing these symptoms should call a doctor immediately and stop taking the drug.

Oral retinoids should not be taken during pregnancy.

Despite these side effects, oral retinoids remain among the safest systemic therapies for psoriasis. A low-fat diet, aerobic exercise, and fish oil supplements may help reduce the side effects. Certain cholesterol-lowering drugs, including gemfibrozil (Lopid) or certain statins, such as atorvastatin (Lipitor), may help control triglyceride levels.

Maintenance doses should be as low as possible and should be taken every second or third day.

Taking retinoids during pregnancy significantly increases the risk for severe birth defects in the unborn child. Pregnant or nursing women or those planning to become pregnant should not use these drugs. Women of childbearing age who take retinoids should have regular pregnancy tests.

Doctors recommend that acitretin should not be given to any woman who may become pregnant within 3 years of taking it. Drinking alcohol changes acitretin to a retinoid that is stored in fat cells for 3 years. It may have the potential for causing birth defects during that time. It's important to note that cooking products and over-the-counter preparations, such as cough syrup, may contain alcohol and be inadvertently consumed.
Women who are pregnant or plan to become pregnant should not use isotretinoin. As of December 31, 2005, everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE.

Cyclosporine (Neoral, Sandimmune, SangCya) blocks certain immune factors and may be effective for all forms of psoriasis. It is also a first line, or primary, systemic drug used to treat adults with severe psoriasis. Neoral is the preparation used most often for psoriasis and clears psoriasis in many patients within 8 - 12 weeks.

Side Effects. Cyclosporine has significant side effects if used for a long time, notably kidney problems and non-melanoma skin cancers. It should be reserved for patients who do not respond to phototherapy or less potent systemic medications (for example, methotrexate or acitretin).

Common and temporary side effects include:

Fatigue
Gingivitis
Gout
Hair growth
Headaches
Joint pain
Tremor

More serious complications may include:

Kidney damage
High blood pressure (Some doctors advise treating high blood pressure with calcium channel blockers, since other standard blood pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.)
High cholesterol and lipid levels
High levels of calcium and low levels of magnesium
Increased risk for infections
Liver problems
Lymphomas
Skin cancers (Patients who have taken cyclosporine after PUVA therapy have a higher incidence of squamous cell skin cancer. According to a 2003 study, the risk is six times that of the general population. The risks are highest with long use and previous use of PUVA, methotrexate, or other immunosuppressants.)

To reduce complications of cyclosporine, the dosage is decreased after improvement occurs. Maintenance therapy is usually limited to a year, although some experts believe that a microemulsion form of Neoral (Neoral-Neo) may be safe for up to 2 years. Patients should be monitored regularly for high blood pressure and signs of kidney or liver problems and skin cancers.

Patients Who Should not Use Cyclosporine. Because the drug suppresses the immune system, people with active infections or cancer should avoid it. Patients with uncontrolled high blood pressure and impaired kidney function should also not use this medication. Cyclosporine therapy for children with psoriasis has not been well studied.

Drug and Food Interactions. Cyclosporine interacts with numerous drugs -- both prescription and over-the-counter preparations -- and also grapefruit and grapefruit juice.

Biological response modifiers, sometimes called "biologics," belong to a new class of drugs that are considered the most exciting development in psoriasis treatment. Biologics are genetically engineered drugs that interfere with specific components of the autoimmune response. Because of their precise targets, these drugs do not damage the entire immune system the way that general immunosuppressants do.

Biologics are considered second- or third-line treatments, and may be used alone or sometimes in combination with first-line systemic drugs.

There are different types of biologics used to treat psoriasis:

T cell blockers block immune cells linked to inflammation.
Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.

Types of T-cell blockers:

Alefacept (Amevive). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Studies suggest that the drug produces 50 - 75% improvement in symptoms. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. Patients need weekly blood tests to make sure T cell levels do not drop too low. Side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infection and cancer.
Efalizumab (Raptiva). This drug is approved for the treatment of moderate-to-severe plaque psoriasis. Many patients experience 50 - 75% improvement in symptoms within 4 - 6 weeks of starting the drug. Patients give themselves shots of this drug for 12 weeks. Some clinical trials suggest that a longer course of treatment (24 weeks) may also be safe and effective for patients with chronic plaque psoriasis. Some patients have flare-ups of psoriatic lesions after stopping efalizumab. Very serious, but rare, side effects include hemolytic anemia and antibiotic-resistant infections.

Types of TNF blockers:

Etanercept (Enbrel) is approved for the treatment of psoriatic arthritis and moderate-to-severe plaque psoriasis. The drug is given either alone or in combination with methotrexate. Side effects include infections and lymphoma, a type of cancer. Patients inject themselves under the skin, once or twice a week for 12 weeks. However, a 2007 study published in the Archives of Dermatology found that continuing etanercept after 12 weeks lowers the severity of disease without increasing infections or side effects. Study participants randomly received 50 milligrams of the drug or a placebo biweekly up to 84 weeks. Strongest improvements were noted at 48 weeks among those who received the drug.
Infliximab (Remicade) is approved for the treatment of psoriatic arthritis. Patients receive three intravenous infusions during the first 6 weeks of treatment. After the initial treatment period, patients receive an infusion every 8 weeks. Therapy takes 2 hours and is given in a doctor’s office or clinic. Patients with a history of infection or heart failure should not take this drug. Several studies have shown that symptoms improve significiantly by week 10 in the majority of patients with severe psoriasis who are treated with infliximab.
Adalimumab (Humira) is being tested in clinical trials for treatment of psoriasis and psoriatic arthritis. Results from a Phase III (late-stage) study show that the drug works better than methotrexate in the treatment of moderate-to-severe psoriasis.
Efalizumab (Raptiva) appears to effectively clear or nearly clear moderate-to-severe hand and foot psoriasis after 12 weeks. This type of psoriasis is often very difficult to control and treat.

Interleukins (IL) being investigated as sources or targets of therapy include IL-4, IL-2, IL-8, IL-11, and IL-12. For example, in a 2003 study, 75% of patients with severe psoriasis who were treated with interleukin-4 (rhuIL-4) experienced improvement rates of more than 68%.

A study of 180 patients with moderate-to-severe plaque psoriasis has shown that an investigational medicine called ABT-874 greatly reduced symptoms in most patients. ABT-874 targets proteins that are responsible for psoriasis-related inflammation.

Leflunomide. Leflunomide (Arava) is a disease-modifying antirheumatic drug (DMARD), which blocks autoimmune antibodies and is a powerful anti-inflammatory medication. It is proving to be active against psoriatic arthritis. Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury.

Sulfasalazine. Sulfasalazine (Azulfidine) is sometimes used for psoriasis. In one major analysis, sulfasalazine and methotrexate were the only medications proven to help patients with psoriatic arthritis. Many people, however, stop taking the drug because of common side effects that include headaches, gastrointestinal complaints, and rash. Benefits, if any, should be apparent in 4 - 6 weeks.

Immunosuppressants. Some immunosuppressants being studied for psoriasis include tacrolimus (Prograf), pimecrolium, and sirolimus. In one study, for example, tacrolimus showed an 83% reduction in symptoms in patients with psoriasis who used the drug. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and so have fewer side effects. (Some are also being studied as topical treatments.)

Phototherapy

Phototherapy means to treat with light.

When sunlight penetrates the top layers of the skin, this ultraviolet radiation bombards the DNA inside skin cells and injures it. This can cause wrinkles, aging skin, and skin cancers. However, these same damaging effects can destroy the skin cells that form psoriasis patches.

Phototherapy for psoriasis can be given as ultraviolet A (UVA) light in combination with medications, or as variations of ultraviolet B (UVB) light with or without medications. Not everyone is a candidate. For example, it may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

Ultraviolet A (UVA) is a main part of sunlight. UVA phototherapy uses a photosensitizing medication (usually psoralen) in combination with UVA radiation to be effective. A photosensitizing medication makes a person more sensitive to light. Treatment with psoralen and UVA is referred to as PUVA. This approach is very powerful and effective in more than 85% of patients who use it. However, it poses a higher risk for skin cancers than UVB.

PUVA treatments cause inflammation and redness in the skin to develop within 2 - 3 days after treatment. Such damage inhibits skin cell proliferation and reduces psoriasis plaque formation.

Forms of psoralen include methoxsalen, 8-methoxypsoralen (8-MOP), or bergapten (5-MOP). The effectiveness of the treatment is based on a chemical reaction in the skin between the psoralen and light, which creates redness and inflammation that prevents the psoriasis disease process.

People should avoid this treatment if they are taking drugs or have conditions that cause them to be light sensitive. They should also take protective measures before, during, and after each treatment.

Initial PUVA Treatment Phase. The initial phase typically follows these steps:

Psoralen is typically taken by mouth in the form of 8-methoxypsoralen (for example, Oxsoralen) 75 minutes to 2 hours before the treatment starts. Psoralen reaches the skin through the bloodstream, where it increases the skin's sensitivity to UVA radiation.
Topical preparations of psoralen are alternatives to pills. They can be "painted on" or applied to the affected areas by soaking or bathing in a psoralen solution. PUVA-bath therapy may be especially useful for persistent psoriasis on the palms and soles or for patients with liver disease or who get severe nausea from taking the pill form. UVA should be given within 15 minutes of using topical psoralen.
The patient enters and stands in a light box, a unit lined with ultraviolet lamps. The initial UVA exposure time is very short (seconds to several minutes), and then increases to 20 minutes or longer. The amount of time a person is exposed to UVA rays depends on the skin type, with the shortest times recommended for fair-skinned patients.
Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, since the full effects of the treatments are not evident for 48 hours.

It takes an average of about 25 PUVA treatments for full effect, but during that period, treatment intensity may vary.

If there is no response after 10 treatments, the doctor may increase the UVA energy.
If there is still no response after 15 treatments, the psoralen dosage may be increased.
If a patient's skin does not improve at all or worsens after these changes, the treatment is temporarily stopped. PUVA may be causing a toxic response in such cases, and, often, the condition gradually improves over the following 2 weeks.
If the skin does not improve over the following 2 weeks, PUVA treatment has failed. If skin improves during this resting period, treatment resumes.

Maintenance Phase. Once the psoriasis has improved by about 95%, the patient may be put on a maintenance schedule. Often only one or two treatments a month are needed, but some people may need more frequent treatments. As maintenance continues and the interval between treatments lengthens, the patients may become more susceptible to tanning and sunburn. They should reduce exposure to natural sunlight during this time.

Success Rates. Nearly 90% of patients achieve marked improvement or clearing within 20 - 30 treatment sessions.

Combinations. Combining acitretin, calcipotriene, methotrexate, or tazarotene gel with PUVA may enhance effectiveness or increase response. In addition, combinations may allow for lower doses of radiation or medications to be used, minimizing side effects. Retinoids may also help protect against skin cancers, while methotrexate may increase the risk. In some cases, patients resistant to PUVA or UVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA.

The psoralen methoxsalen causes a general ill-feeling and nausea in 20% of patients. Dividing up the dose and taking it in 15-minute intervals with food, or taking ginger 20 minutes before taking the drug, may be helpful.
Skin reactions, including itching, sunburn, and blistering, are common. These can generally be avoided with careful administration of PUVA therapy and protective measures. Antihistamines, baths with special oatmeal preparations (Aveeno), and capsaicin ointment (Zostrix) may be helpful.
After treatment, white spots commonly develop where psoriasis plaques had been, particularly in people with naturally darker skin. If they are troublesome, tanning products may help darken them. Small, dark raised spots called PUVA lentigines may also develop in affected areas with long-term treatment
Prolonged standing may trigger fainting in people with certain heart or blood pressure problems.
People with liver disease should discuss using topical psoralens, since oral forms may have adverse effects on the liver.
UVA penetrates the skin more deeply than UVB, so there is a greater danger of deep skin damage, accelerated skin aging, and skin cancers. Anyone who needs to avoid sunlight should not get this treatment.
The procedure increases the risk for cataracts if eyes are not protected for up to 24 hours after treatment.

Special Warning on PUVA and Skin Cancers. It has been known for some time that PUVA can change DNA and cause genetic mutations. PUVA is known to increase the risk for squamous cell skin cancer and slightly increase the risk for basal cell skin cancer, both of which are nearly always curable. One study reported an increased risk of melanoma. The risk for skin cancers is higher in persons who have:

A family or personal history of skin cancer
Light skin and fair or red hair
Received radiation or x-ray treatments or taken immunosuppressant drugs
Received over 200 PUVA treatments

Discussions are under way about discontinuing PUVA for psoriasis. The arguments generally are as follows:

Opponents of PUVA argue that studies suggest a long-term risk for melanoma, starting about 15 years after treatment, particularly in people who receive more than 250 treatments. In one long-term study, only 9 out of 1,380 patients developed melanoma. However, 7 of these cases occurred in the last 5 years of the study, indicating that the danger persists and more patients in this study are likely to develop this serious skin cancer as time goes on.
Supporters of PUVA argue that it is not yet known if the people who developed melanoma experienced sunburn during the procedures or if they already had risk factors for skin cancers. If so, then properly given treatments could still be considered safe for patients without risk factors. They also argue that PUVA is still the most effective treatment for severe psoriasis, and the alternatives are usually very powerful and relatively new drugs that may have even more serious side effects. Furthermore, the addition of retinoids may protect against skin cancers while proving to be a very effective combination.

Side effects of UVA radiation can be severe. Protective measures are needed during, before, and after treatment. Patients should avoid prolonged exposure to the sun for 24 hours before the oral treatment starts.

Protective Measures During Treatment:

Patients should wear specially designed goggles to protect the eyes from UVA radiation.
Sensitive areas, such as genitals, abdominal skin, and breasts, should be covered until tanning occurs in the exposed areas, after about a third of the treatment period. Note that PUVA is associated with a high risk for genital skin cancers, so male genitals must be covered throughout the process.

The following safety features should be available in the PUVA chamber:

Lamps with protective shields
A viewing window for a health professional to check the patient periodically
A door that can be opened by the patient easily and with little pressure
A timer that terminates the session automatically
An accessible alarm device

Protective Measures After Treatment. The drugs used in PUVA increase susceptibility for a natural sunburn for hours after treatment. The patient should take the following precautions:

Patients should wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. They should begin wearing them as soon as they take the drug, and for at least 12 hours after the treatment. This is important to prevent a PUVA reaction around the eyes that can cause cataracts. There is no need to wear these glasses after sundown.
For about 8 hours after taking the drug, patients must also avoid exposure to daylight, even if the day is cloudy or exposure occurs through windows.
Patients who must go out should wear heavy opaque clothing (clothes that do not let light through), including hats and gloves.
Patients should apply sunblock over all exposed areas, including the lips. The sunblock should have an SPF (sun protection factor) of more than 15 and include ingredients that block both UVB and UVA radiation.
No patient should spend a long time in sunlight for at least 2 days after the combined treatment.

Ultraviolet B is another main part of sunlight, and is the main cause of sunburn. It generally affects the outer skin layers. UVB radiation reduces the abnormally rapid skin cell growth that occurs with psoriasis.

Types of UVB therapy:

Broadband UVB
Narrowband UVB (NB-UVB)
Laser treatments

Broad spectrum or broad band UVB is radiation in the wavelength of 290 - 350 nanometers, and is the standard UVB phototherapy treatment in the United States. It is not as potent as the treatments that use narrow-band UVB or PUVA, and is not useful for chronic psoriasis.

Broadband UVB may be given with or without medications. When used without medication (known as selective ultraviolet phototherapy), UVB treatment generally is given as follows:

Treatment starts in the doctor's office or another medical setting. Once the disease has stabilized, the patient can obtain a prescription for equipment that can be used at home. Even at home, treatment must always be supervised.
In preparation, the patient fully undresses, although unaffected areas may be covered to avoid overexposure.
The initial session may last as little as a few seconds, depending on whether the patient has a lighter or darker skin, with the lightest skin exposed to the briefest session. The duration increases with each treatment until the skin clears or the patient experiences itching or irritation. It should be noted that the condition may worsen initially.
UVB therapy usually requires about 20 - 40 treatments (about three per week). Full results take about 3 weeks.

Use of Medication. UVB was commonly used with coal tar (the Goeckerman regimen) in past decades, and then with anthralin (the Ingram regimen). Other medications are being studied with some success, and may prove to be tolerated better.

The Goeckerman regimen requires daily treatments for up to 4 weeks. The coal tar or anthralin are applied once or twice each day and then washed off before the procedure. Studies indicate that a low-dose (1%) coal tar preparation is as effective as high dose (6%). Such regimens are unpleasant, but still useful for some patients with severe psoriasis, since they can achieve long-term remission (up to 6 - 12 months).

Some evidence suggests that using a simple emollient (such as Vaseline or mineral oil) that enhances UVB light penetration can be effective. This addition to the treatment increases the risk for sunburns, however, and patients must be careful to avoid sun exposure. Researchers are tring combinations of other topical and oral medications. For example, combining UVB with methotrexate, or retinoids such as a tazarotene gel or oral acitretin, is producing positive results. Combinations with any of these drugs, however, must be supervised carefully to avoid serious reactions.

Side Effects of UVB. The treatment can cause itching and redness. UVB radiation from sunlight is known to increase the risk for skin cancers. There is no strong evidence, however, that UVB treatments pose any risk for skin cancers except on male genitalia. This risk, however, can be significant (4.5%) at high doses.

Narrow band radiation may be safer than other approaches, and some experts now believe it should be the first option for patients with chronic plaque psoriasis.

NB-UVB is used without medications and is very strong. Whether it has any affect, however, on the disease process itself is unclear. The light wavelength is between 310 - 312 nanometers, which, theoretically, is the most beneficial part of sunlight.

Exposure times are shorter but of higher intensity than with broadband UVB. This therapy is probably less likely than PUVA to cause skin cancers.

Clearance of 75% typically occurs after 10 - 12 treatments. NB-UVB treatments performed three times a week achieve results that are equal to twice-weekly PUVA treatments. Weekly NB-UVB treatments are not effective. Studies so far are mixed on whether NB-UVB remission rates are equal to those of PUVA.

Patients prefer NB-UVB over other PUVA treatments because they do not have to wear protective eyewear, take medications, or experience unpleasant side effects, notably nausea. It is also safe for pregnant women and children.

Combinations with topical medications, such as tazarotene or psoralens, may help NB-UVB therapy work better.

Laser UVB Treatment. A recent variation of a device called an excimer laser (Xtrac) delivers a precise UVB wavelength of 308 nanometers. The laser is more effective than narrow-band UVB for localized psoriasis, since it allows very specific areas of skin to be targeted. (Note: The therapy is not suitable for the scalp.) Generally, 8 - 10 treatments given twice a week will clear psoriasis. Remission rates are similar to NB-UVB, but the excimer laser can clear the psoriasis faster and at lower doses. It also spares the healthy skin around it. Blistering is a common side effect. More comparison studies are needed to determine risk and benefits compared to NB-UVB, particularly any long-term risk for skin cancer.

Pulsed-Dye Lasers. Pulsed-dye lasers give off high-intensity yellow light, which destroys the tiny blood vessels that make up psoriatic plaques. This treatment has been used for years to remove birthmarks, such as port wine stains and unsightly blood vessels on the skin. Some studies have reported significant (but not complete) improvement, and remissions that have lasted up to 13 months. Treatment sessions last up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to six sessions to clear the target areas. Bruising is common, and there is a small risk for scarring.

Home tanning devices and tanning salons are not usually recommended, but they may be helpful for patients without access to a medical unit. In a 2003 study, many patients achieved a significant reduction in symptoms when taking acitretin and exposed to a UVB commercial tanning unit (specifically, a Wolff tanning bed).

However, UV outputs can vary widely among tanning beds and salons. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including a risk for skin cancer.

Managing Psoriasis

Although sunburn carries a risk for skin cancer and can make psoriasis worse, regular exposure to the sun helps clear psoriasis in people with mild-to-moderate conditions. People should cover non-affected areas with clothing or sunscreen and sun bath only until the skin starts to tan.

Vacations in sunny areas, such as Hawaii or the Caribbean, can offer relief. For those who can afford it, a prolonged stay of several weeks at the Dead Sea in Israel has proven to significantly improve or clear 88% of those with psoriasis who go there. The region offers a unique combination of intense but naturally filtered UVA radiation combined with minerals and salts from the sea.

Because of the association between negative emotions and psoriatic flare-ups, relaxation and anti-stress techniques may be helpful. A small 1999 study found that hypnosis aimed at reducing stress may relieve symptoms.

Another study found that some patients with psoriasis had a traumatic or stressful event coincide with the appearance of psoriasis. Talking to a psychiatrist about the issue resulted in significant symptom improvement in 62% of study patients who recalled such an event.

If skin becomes dry and itchy, the patient may try the following:

Soak in a warm bath for about 15 minutes.
Afterward, apply salicylic acid first, which removes scaly skin and may promote the penetration of both moisturizers and topical prescription medications.
Then, apply a thick moisturizer or emollient, such as Vaseline, Cetaphil cream, or Eucerin cream. Lotions are not good enough moisturizers.
Special gloves made of Gore-Tex (DermaPore) may be worn at night over a thick moisturizer cream. These gloves are protective but also allow moisture to escape.

Some experts suggest that many common moisturizers may actually increase water loss in psoriasis, but studies still have to confirm this. In the meantime, if moisturizers help relieve the condition, patients should use them.

Capsaicin (Zostrix) is an ointment prepared from the active ingredient in hot chili peppers. It is used to relieve arthritic pain and may help relieve psoriatic itching. Capsaicin should be handled using a glove and applied to affected areas three or four times daily. The patient will usually have a burning sensation when the drug is first applied, but this sensation lessens with use.

Folic Acid. Patients should be sure they get enough of the B vitamin folate (folic acid). Folate-rich foods include liver, asparagus, fruits, green leafy vegetables, dried beans and peas, orange juice, and yeast. Many types of bread and other commercial grain products now have added folic acid.

Omega-3 Fatty Acids. Omega-3 fatty acids, particularly those found in some fish oil, have anti-inflammatory properties that may benefit some patients with psoriasis and other autoimmune conditions.

Patients with persistent psoriasis may be tempted to try alternative or untested treatments, including herbs and other nontraditional therapies. Researchers at the Medical College of Georgia say green tea slowed the growth of skin cells in animal studies and may one day prove to be useful in treating psoriasis. More research is needed.

Several traditional remedies for psoriasis include various other herbal supplements, but to date no clinical studies have been reported on these substances. No one should use any unproven therapy without consulting a doctor to be sure such treatment is not harmful, and does not interfere with any standard medications they take.

Herbal remedies and dietary supplements are not regulated by the FDA. This means that manufacturers and distributors do not need FDA approval to sell their products. In addition, any substance that affects the body's chemistry can, like any drug, produce side effects that may be harmful. There have been many reported cases of serious and even deadly side effects from herbal products.

The following are special concerns for people taking natural remedies for psoriasis:

Zinc pyrithione is sometimes used, but its effectiveness is doubtful. A number of so-called natural psoriasis products (Skin-Cap, Blue Cap, Miralex) that contain this compound also contain prescription-strength corticosteroids. Such steroids have the same side effects as those in standard psoriasis agents. These products have been banned in the U.S. and Canada, but similar untested medications are available over the Internet.
Gotu Kola (Centella asiatica) is sometimes applied in a cream for psoriasis. The oral form of the herb has serious side effects, however, including increasing the risk for miscarriage in pregnant women.

Outlook

Psoriasis is lifelong and not curable. Although it is also marked by rapid cell growth, psoriasis is neither cancerous nor contagious.

In general, studies report the following features of its course:

The condition almost always relapses. In a few cases, large areas of plaque can persist for years.
Psoriasis nearly always goes into remission, however, often clearing on its own. In one study, 30% of patients reported untreated psoriasis going into remissions that lasted 1 - 54 years.
Psoriasis can improve during pregnancy, especially during the second and third months. Increased levels of estrogen may be responsible for this improvement. Relapse may occur after giving birth.

The emotional and social consequences of psoriasis should not be underestimated.

Many patients suffer severe humiliation and depression if plaques are visible. Some even withdraw from society and become isolated.
Some patients are forced to leave their jobs and go on disability if the condition becomes incapacitating.

Researchers have reported the following:

Surveys of patients with psoriasis report a negative mental and physical impact that is nearly equivalent to that of other major chronic conditions, including cancer, high blood pressure, diabetes, heart disease, and depression.
In one study, 75% of patients reported that psoriasis hurt their confidence.
Another study reported that 8% of people with psoriasis felt their life was not worth living.

Some patients, particularly men, use alcohol and smoking as self-medication to reduce the emotional consequences of psoriasis. In fact, studies have found that people with psoriasis have higher mortality rates, mostly from heavy drinking. Smoking has also been cited as a major risk, particularly for pustular psoriasis. Some experts believe that drinking and smoking may actually cause biological damage that contributes to psoriasis itself.

However, smoking may delay the onset of psoriatic arthritis in some patients, depending on when they started the habit. Psoriatic arthritis tends to occur about a decade after psoriasis develops. The review of 281 psoriasis patients showed that the condition appeared after about 13 years in nonsmokers, compared to 23 years in those who began smoking after the first onset of psoriasis. Psoriatic arthritis appeared after 8 years in people who smoked before developing psoriasis.

Folate Deficiency in Severe Psoriasis. Severe psoriasis can also cause folate deficiency. Folate is a B vitamin that is important for nerve function, preventing birth defects. It also prevents elevations of homocysteine, a factor that may play a critical role in heart disease.

Skin Cancers. In one study, patients with severe psoriasis (who receive medications that affect the whole body) were at higher than normal risk for developing cancers, primarily skin cancers and lymphomas. The risk was not any higher for patients with milder psoriasis. There is some indication, however, that patients with psoriasis have a higher risk for non-melanoma skin cancers regardless of treatments.

Heart Attacks. A study released in October 2006 shows an increased risk of heart attacks in people with psoriasis. The risk was highest in young patients with severe psoriasis.

Other Coexisting Conditions: Studies done in Newfoundland and Germany have also revealed increased cases of diabetes, obesity, arthritis, and cancer in patients with psoriasis. Research is underway to determine if there are genetic links between psoriasis and these conditions.

Increased Risk of Death. Severe psoriasis has been linked to a significant increase in a patient's risk of death. A study of more than 713,000 patients showed that severe psoriasis increased mortality by 50%. Study authors encourage patients to receive comprehensive health examinations to reduce the risk. Study participants were considered to have severe psoriasis if they required systemic treatment.

Impaired Temperature Regulation. Erythrodermic psoriasis, in which psoriasis covers the entire skin, can cause abnormalities in the body's ability to regulate temperature.

Zumbusch Psoriasis. A combination of erythrodermic and pustular psoriasis causes a serious condition called Zumbusch psoriasis:

The condition can develop abruptly.
Symptoms may include fever, chills, weight loss, and muscle weakness.
Patients may develop excessive fluid build-up, protein loss, and electrolyte imbalances. In such cases, hospitalization is required. Fluid and chemical balances must be restored and temperature stabilized as soon as possible.

Zumbusch psoriasis can be life threatening, particularly in the elderly. The condition is very rare in children and, if it occurs, tends to improve more quickly than in adults, possibly even without medication.

Most cases of psoriatic arthritis (PsA) are mild, but complications can occur:

Severe joint deformity and destruction (called arthritis mutilans) may develop, generally in the small joints of the hands and feet. Studies report this happens in about 5 - 16% of patients. Psoriasis patients with other arthritic conditions (osteoarthritis or rheumatoid arthritis) in the joints of the fingers tend to have a higher risk.
People with PsA may have a higher risk for respiratory illnesses.

Some earlier studies indicated that patients with psoriatic arthritis had a shorter lifespan than the general population, but more recent studies found no significant difference.

Resources

www.psoriasis.org -- National Psoriasis Foundation
www.aad.org -- American Academy of Dermatology
www.niams.nih.gov -- National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.clinicaltrials.gov -- Find clinical trials

References

Gelfand JM, Neimann AL, Shin DB, et al. Risk of myocardial infarction in patients with psoriasis. JAMA. 2006 Oct 11;296(14):1735-41.

U.S. Food and Drug Administration. CDER Drug and Biologic Approvals for Calendar Year 2006 -- Updated through August 31, 2006. Last accessed on 15 October, 2006.

FDA Announces Strengthened Risk Management Program to Enhance Safe Use of Isotretinoin (Accutane) for Treating Severe Acne. US Food and Drug Administration. Rockville, MD: National Press Office; August 12, 2005.

Anstey AV and Kragballe K. Retrospective assessment of PASI 50 and PASI 75 attainment with a calcipotriol/betamethasone dipropionate ointment. Int J Dermatol. 2006 Aug;45(:970-5.

National Psoriasis Foundation. About Psoriasis: Statistics. Last Accessed 9 October, 2006.

Antoni CE, Kavanaugh A, Kirkham B, Tutuncu Z, Burmester GR, Schneider U. Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum. 2005;52(4):1227-1236.

Bowcock AM, Cookson WO. The genetics of psoriasis, psoriatic arthritis and atopic dermatitis. Human Mol Genet. 2004;13 Spec No 1:R43-55.

Feldman SR, Koo JY, Menter A, Bagel J. Decision points for the initiation of systemic treatment for psoriasis. J Am Acad Dermatol. 2005;53(1):101-107.

Murase JE, Chan KK, Garite TJ, Cooper DM, Weinstein GD. Hormonal effect on psoriasis in pregnancy and post partum. Arch Dermatol. 2005;141(5):601-6.

Review Date:
9/19/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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

A.D.A.M. Copyright

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

adam.com

Herpes simplex

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Symptoms
Transmission
Risk Factors
Complications
Diagnosis
Similar Conditions
Home Remedies and Preventio...
Treatment for Genital Herpe...
Treatment for Oral Herpes...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Herpes Diagnosis

In 2006, the U.S. Centers for Disease Control (CDC) released updated guidelines for diagnosis and management of sexually transmitted diseases.

For diagnosis of genital herpes, the CDC recommends the use of both skin and blood tests.
Blood (or type-specific serologic) tests must be able to detect antibodies to glycoprotein G (gG). According to the CDC, gG serologic tests are much more accurate than other types of blood tests and are the only ones that should be used. These blood tests can help determine whether genital herpes is caused by herpes simplex virus-1 (HSV-1) or herpes simplex virus-2 (HSV-2).
Although HSV-1 has traditionally been the main cause of oral herpes, and HSV-2 the main cause of genital herpes, HSV-1 is now causing up to 50% of all cases of genital herpes. Prognosis may vary depending on the type of virus involved.

Herpes Treatment

Acyclovir (Zovirax), famiciclovir (Famvir), and valacyclovir (Valtrex) are used for episodic treatment (when herpes outbreaks occur) or suppressive treatment (preventing outbreaks). Valacyclovir may be a particularly good choice for reducing the risk of herpes transmission among heterosexual couples when only one partner is infected with HSV-2.
According to a 2007 review of studies involving over 6,000 patients, these drugs are very effective in reducing herpes recurrences.

Herpes and HIV

Treatment of HSV-2 can help reduce HIV levels in women who are infected with both viruses, indicates a study published in 2007 in the New England Journal of Medicine. In the trial, women who received twice-daily valacyclovir therapy for 12 weeks had reduced genital-track shedding of HIV and blood HIV levels compared to women who received placebo. Researchers are now focusing on the major question: Whether treatment of genital herpes can help prevent HIV transmission.

Introduction

Herpes simplex virus (HSV) commonly causes infections of the skin and mucous membranes. Sometimes it can cause more serious infections in other parts of the body. HSV is one of the most difficult viruses to control and has plagued mankind for thousands of years.

Herpes simplex is part of a group of other herpes viruses that include human herpesvirus 8 (the cause of Kaposi's sarcoma) and herpes zoster (the virus responsible for shingles and chicken pox). They differ in many ways, but the viruses share certain characteristics, notably the word "herpes," which is derived from a Greek word meaning "to creep." This refers to the unique characteristic pattern of all herpes viruses to "creep along" local nerve pathways to the nerve clusters at the end, where they remain in an inactive state for some indeterminate time.

There are two forms of the herpes simplex virus:

Herpes simplex virus 1 (HSV-1)
Herpes simplex virus 2 (HSV-2)

These viruses are distinguished by different proteins on their surfaces. They can occur separately, or they can both infect the same individual. Until recently, the general rule has been to assume that HSV-1 infections occur in the oral cavity (mouth) and are not sexually transmitted, while HSV-2 attacks the genital area and is sexually transmitted. It is now widely accepted, however, that either type can be found in either area and at other sites. In fact, HSV-1 is now responsible for up to half of all new cases of genital herpes.

For infection to occur, the following conditions must apply:

The herpes simplex virus passes moves through bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores.
The virus must have direct access to the noninfected person through injuries in their skin or mucus surfaces (such as in the mouth or genital area).

When herpes simplex virus enters the body, the infection process typically takes place as follows:

The virus enters vulnerable cells in the lower layers of skin tissue and tries to reproduce in the cell nuclei. Scientists are close to decoding the genetic structure of herpes simples virus and to discovering how the virus works its way into specific cells. The virus may have specially shaped proteins called cell adhesion molecules that can allow the virus to enter healthy cells. For example, protein receptors on cells called nectin 1 and 2 may bind to some subtypes of the virus and help the infection move from cell to cell.
Even after it has entered the cells, the virus never causes symptoms in most cases.
However, if the virus destroys the host cells when it multiplies, inflammation and fluid-filled blisters or ulcers appear. Once the fluid is absorbed, scabs form, and the blisters disappear without scarring.
After the first time they multiply, the viral particles are carried from the skin through branches of nerve cells to clusters at the nerve-cell ends (the dorsal root ganglia).
Here, the virus lives in an inactive (latent) form. The virus does not multiply, but both the host cells and the virus survive.
At unpredictable times, the virus begins multiplying again. It then goes through a period called shedding. During those times, the virus can be passed into bodily fluids and infect other people. Unfortunately, a third to half of the times shedding occurs without any symptoms at all.
Eventually, the symptoms return in most cases, causing a new outbreak of blisters and sores.

This close-up view of early herpes outbreak shows small, grouped blisters (vesicles) and lots of inflammation (erythema).

Symptoms

Symptoms vary depending on the stage of the virus, the initial or primary outbreak, and recurrence. Both herpes simplex viruses 1 and 2 produce similar symptoms, but they can differ in severity depending on the site of infection. More than 60% of new herpes simplex virus 2 (HSV-2) infections and about a third of new herpes simplex virus 1 (HSV-1) infections do not produce symptoms.

Skin Eruptions and Pain. Skin eruptions will appear 2 - 12 days after the initial exposure to the virus.

The first sign of infection is fluid accumulation (edema) at the infection site, which is quickly followed by small, grouped blisters -- the characteristic herpes virus lesions.
These form on an inflamed skin base, which is more visible in dry skin areas.
The blisters then dry out and heal rapidly without scarring within 7 - 10 days. Blisters in moist areas heal more slowly than others. The lesions may sometimes itch, but itching decreases as they heal.
When the crust falls off, the lesions are no longer contagious. (Rarely, the virus may still be active in nearby tissue.)
Once the virus gains entry to a site in the body, it can also spread to nearby mucosal areas through nerve cells. This characteristic spreading can cause fairly large infected areas to erupt at some distance from the initial crop of sores.

The primary skin infection with either herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2) lasts up to 2 - 3 weeks, but skin pain can last 1 - 6 weeks in the first (primary) virus attack.

Other Symptoms. Some patients experience other symptoms as well, which may occur before the actual outbreak (called a prodrome).

Fever rising to about 102°F, muscle aches, headache, and flu-like malaise. These general symptoms usually go away within a week.
Lymph glands near the site may be swollen as well.

It may be especially important to identify a first (primary) infection -- if possible -- and to treat it as soon as possible. Some preliminary research suggests that early treatment may limit the number of viruses that remain latent in the body and reduce the frequency of recurrent outbreaks.

Latency. After an outbreak, the herpes simplex virus goes into a stage known as latency. During that time, the virus does not produce symptoms and cannot be transmitted to other people.

Asymptomatic Shedding. At certain times, the virus undergoes shedding. During this phase the virus multiples and can be transmitted through fluids and infect other people. This occurs during an outbreak. However, in a third to half of cases shedding occurs without any symptoms at all (asymptomatic). One study reported that about 40% of all people infected with herpes simplex virus (HSV) had sheeding of the virus without symptoms more than 5% of the time. (Other evidence suggests shedding occurs much more often -- 9 - 28% of the time.) About half of shedding episodes without symptoms happen within a few days before or after an outbreak and can last about 1.5 days. Asymptomatic shedding is much more common with herpes simplex virus 2 (HSV-2) than with herpes simplex virus 1 (HSV-1).

Symptoms of Recurrence. Herpes simplex nearly always recurs. The site on the body and the type of virus influence how often it comes back. The virus usually takes the following course:

Prodrome. The outbreak of infection is often preceded by a prodrome, an early group of symptoms that may include itching skin, pain, or an abnormal tingling sensation at the site of infection. The patient may also have a headache, enlarged lymph glands, and flu-like symptoms. The prodrome, which may be as few as 2 hours or as many as 2 days, steps when the blisters develop. About 25% of the time, recurrence does not go beyond the prodrome stage.
Outbreak. Recurrent outbreaks of herpes simplex virus (HSV) feature most of the same symptoms at the same sites as the primary attack, but they tend to be milder and briefer. After blisters erupt, they typically heal in 6 - 10 days. Occasionally, the symptoms may not resemble those of the primary episode but appear as fissures and scrapes in the skin or as general inflammation around the affected area.

Triggers of Recurrence. It is not completely known what triggers renewed infection, but several different factors may be involved. These include sunlight, wind, fever, local physical injury, menstruation, suppression of the immune system, and emotional stress. Some studies link recurrence in genital herpes to persistent stress (lasting longer than a week) and high levels of anxiety. Oral herpes can be provoked within about 3 days of intense dental work, particularly root canal or tooth extraction, as well as after laser skin resurfacing, a popular form of cosmetic surgery.

Timing of Recurrences. Recurrent outbreaks may occur at intervals of days, weeks, or years. For most people, outbreaks recur with more frequency during the first year after an initial attack. During that period, the body mounts an immune response to HSV, and in most healthy people recurring infections tend to become progressively less severe and less frequent. The immune system, however, cannot kill the virus completely.

Oral herpes (herpes labialis) is most often caused by herpes simplex virus 1 (HSV-1) but can also be caused by herpes simplex virus 1 (HSV-2). It usually affects the lips and, in some primary attacks, the mucous membranes in the mouth. A herpes infection may occur on the cheeks or in the nose, but facial herpes is very uncommon.

Primary Oral Herpes Infection. If the primary (or initial) oral infection causes symptoms, they can be very painful, particularly in small children.

Blisters form on the lips but may also erupt on the tongue.
The blisters eventually rupture as painful open sores, develop a yellowish membrane before healing, and disappear within 3 - 14 days.
Increased salivation and foul breath may be present.
Rarely, the infection may be accompanied by difficulty in swallowing, chills, muscle pain, or hearing loss.

In children, the infection usually occurs in the mouth. In adolescents, the primary infection is more apt to appear in the upper part of the throat and cause soreness.

Recurrent Oral Herpes Infection. Most patients have only a couple of outbreaks a year, although up to 10% of patients experience more frequent recurrences. (HSV-2 oral infections recur less frequently than HSV-1.) Recurrences are usually much milder than primary infections and are known commonly as cold sores or fever blisters (because they may arise during a bout of cold or flu). They usually show up on the outer edge of the lips and rarely affect the gums or throat. (Cold sores are commonly mistaken for the crater-like mouth lesions known as canker sores, which are not associated with herpes simplex virus.)

Genital herpes, which typically affects the penis, vulva, or rectum, is usually caused by herpes simplex virus 2 (HSV-2), although the rate of simplex virus 1 (HSV-1) genital infection is increasing. Studies now report, in fact, that the cases of new symptomatic genital infections are equally split between HSV-1 and HSV-2. Some studies even report a higher incidence of genital HSV-1 cases. While there is no difference in treatment, there can be a difference in disease course. Initial genital infections due to HSV-1 may be more severe than those caused by HSV-2. Recurrences tend to be milder and less frequent than with HSV-2, however.

Primary Genital Herpes Infection. The first outbreak usually occurs in or around the genital area 3 - 14 days after exposure to the virus. If there is a long time between the initial infection and the first outbreak of symptoms, the episode may be quite mild because the immune system has already produced antibodies to the virus. These kinds of first infections are less transmissible, heal faster, and produce fewer symptoms.

In about 80% of initial outbreaks of genital herpes, patients develop symptoms such as flu-like discomfort and fever. The virus sheds for about 3 weeks. Symptoms in men and women are very different from each other.

In women, the pattern of a first infection is often more complicated and severe than in men:

In addition to general flu-like discomfort, women may experience nerve pain, itching, lower abdominal pain, urinary difficulties, and yeast infections before or during the eruption of the skin blisters.
When the outbreak occurs, blisters form raw sores (ulcers) almost immediately. Later they become crusted and fill with a grayish-white fluid. A new crop often occurs during the second week and is accompanied by swollen lymph glands in the groin. The symptoms may last as many as 6 weeks.
Lesions commonly appear around the vaginal opening, on the buttocks, in the vagina, or on the cervix. If lesions occur inside the vagina, they are not visible and pain may be minimal. Such women, then, may be unaware that they have genital herpes. In such cases, the blisters produce a discharge that is still highly infectious.
Lesions develop in places other than the genital region in 10 - 18% of primary HSV-2 infections. In most of these cases, outbreaks occur in the urethra (the channel that carries urine) where they can cause painful burning during urination. Inflammation of the internal reproductive organs, including the uterus lining (endometrium) and the fallopian tubes, is rare.

In men, about 6 - 10 blisters typically develop on the head or shaft of the penis. They rarely occur at the base. In some cases, they can occur on the buttocks, around the anus, or on the thighs.

Recurrent Genital Herpes Infection. In general, recurrences are much milder than the initial outbreak. The virus sheds for a much shorter period of time (about 3 days) compared to in an initial outbreak of 3 weeks. Women may have only minor itching, and the symptoms may be even milder in men.

On average, people have four recurrences a year, although this varies widely depending on the severity of the initial outbreak. Men, for example, have 20% more recurrences of genital herpes than women even though their symptoms are milder. There are also some differences in frequency of recurrence depending on whether HSV-2 or HSV-1 causes genital herpes:

HSV-2 Genital Herpes Recurrences. HSV-2 genital infections recur more often than HSV-1, and they tend to be more severe. Up to 90% of HSV-2 genital infections recur within the first year after primary infection. Many patients report 5 - 8 recurrences in the first year, but some have them as often as every 2 weeks. Some, though, have only one initial outbreak without any subsequent recurrences, a rate more typical of those with HSV-1.
HSV-1 Genital Herpes Recurrences. In one study, 38% of patients with HSV-1 genital infections had no recurrences in the first year after primary infection, 35% had one recurrence, and 27% had 2 or more recurrences. The average time to recurrence was about 7.5 months. Only 7% of those with genital HSV-1 had two or more recurrences annually for at least 2 years.

Patients with genital herpes usually notice a significant reduction in recurrence by the seventh year after infection. Some patients, however, particularly those with genital HSV-2, may actually face an increase in recurrence during the first 5 years.


Location and type	Symptoms	Treatments
*Eye (ocular herpetic infection).* Affects only one eye at a time. Usually caused by HSV-1, but acute cases in the retina are more likely to be due to HSV-2. The incidence has been highest in children, although it is increasing in older individuals.	Primary: Inflammation of the cornea (keratitis), causing sudden and severe pain, blurred vision, or corneal lesions. A cloudy layer can form over the cornea. Swelling may occur around the eyes. Heals within 2 - 3 weeks. Recurrence: About 40% of people have more than one recurrence, usually keratitis in a single eye, but symptoms may be present in the other eye as well. In the experience of some doctors, short, intense exposure to sunlight may trigger a recurrence, but there is no clear evidence concerning sunlight or any other potential triggers. Branching, ulcerous lesions of the cornea may occur later in the disease. Stromal keratitis, inflammation of inner layers of the cornea, occurs in about 25% of patients. It is a late immune response to the infection and can, in some cases, be very serious. In the U.S., it is the major cause of blindness in the cornea (which is still very uncommon).	Medications of Ocular HSV. Ocular HSV should be treated carefully since certain treatments may aggravate the condition. Artificial tears may be appropriate for mild cases. Treatments include trifluridine (Viroptic) eye drops or acyclovir or vidarabine (Vira A) ointments. Adding interferon, an immune system booster, to trifluridine may speed healing. Interferon in combination with debridement is also helpful. With treatment, most HSV ocular infections resolve within 5 - 9 days. Taking long-term oral acyclovir after an initial episode of ocular HSV reduces recurrences by about 45%. Medications for Stromal Keratitis. Oral acyclovir also protects against stromal keratitis in patients with a history of it. Trifluridine or cidofovir may also be protective against it. Neither drug, however, has any effect once stromal keratitis develops. Treatment includes artificial tears for mild cases and topical steroids for moderate-to-severe inflammation. Procedures. Patients with ocular HSV may also need debridement, in which the surgeon scrapes away the injured tissue with a cotton swab. The patient may wear a patch or soft contact lens afterward. Patients with HSV who show scarring in the cornea may need surgery. In rare cases, a corneal transplant may be necessary.
*Brain (HSV encephalitis).* Usually HSV-1, although HSV-2 is typically the cause in newborns. In about 25% of HSV-1 encephalitis cases, the infection may be caused by a new strain of the virus. About a third of cases occur in people under 20 years old, half over age 50, and the balance between ages 20 -50.	Fever, headache, stiff neck, seizures, partial paralysis, stupor, or coma. Other symptoms: smell and taste disturbances, double vision, odd mental states, bizarre or psychotic behavior, loss of the ability to speak or understand, memory loss, confusion, emotional volatility.	Intravenous acyclovir is the treatment of choice for encephalitis and should be started immediately if this complication is suspected. It must be administered for at least 10 days. In rare cases, surgical measures may be needed to relieve the buildup of pressure in the brain.
*Finger (herpetic whitlow)*. One finger, usually thumb or index finger in adults. Any finger in children. HSV-1 the cause in 60% of cases, and HSV-2 in 40% of cases. HSV-1 is usually caused by finger-sucking in children or as an occupational condition in adults (usually health care workers not using gloves). HSV-2 is usually acquired by touching infected genital areas.	Primary: Itching or pain, swelling, flushing of the skin, localized tenderness of the infected finger. Clear-yellowish or pus-filled blisters may appear on fingertip lasting 2 - 3 weeks. Soft tissue around fingernail may become painfully infected. Finger blisters may become secondarily infected with common bacteria, causing fever and swollen glands in the armpit. Recurrence: Sometimes intense burning, nerve pain, or excessive sensitivity.	Topical acyclovir for acute attack and oral acyclovir for prevention of recurrences.
Lower back. Usually caused by HSV-2 and typically occurs in bedridden patients or those with AIDS.	Numbness, tingling of the buttocks or the area around the anus, urinary retention, constipation, and impotence. Weakness or extreme skin sensitivity in the lower extremities, possibly persisting for months. Headaches, stiff neck, and, very rarely, paralysis in lower extremities caused by inflammation of the spinal cord.	Acyclovir, or foscarnet in patients resistant to acyclovir.
Peripheral nervous system. Affecting nerves other than in the brain and spine. Usually caused by HSV-1.	Portion of the face temporarily paralyzed (Bell's palsy). Other areas of the body may exhibit numbness or loss of feeling to the touch.	Acyclovir or similar drugs in combination with oral prednisone.
*Other skin areas (herpetic erythema multiforme).* May follow any form of recurrent HSV. Is relatively rare.	Circular or irregular eruptions on backs of arms and hands. Recurrence of erythema multiforme is common in the same areas. This is actually an allergic reaction that lasts 2 - 3 weeks.	Usually minor and resolves without complications. Acyclovir and symptom relievers (common pain relievers, cold compresses, topical steroids, saline gargles).
Esophagus. Usually caused by HSV-1. Typically occurs in immunocompromised patients or in those taking long-term steroids or other immunosuppressant drugs, but can occur in infected people with normal immune systems.	Difficulty swallowing or burning, squeezing throat pain while swallowing, weight loss, pain in or behind the upper chest while swallowing. Herpes lesions difficult to differentiate from other throat sores.	Intravenous acyclovir may be recommended. Recurrences are rare in patients with healthy immune systems, so preventive therapy is usually unnecessary in these patients.

Click the icon to see an image of herpetic esophagitis.

Transmission

To infect people, the herpes simplex viruses (both HSV-1 and HSV-2) must get into the body through broken skin or a mucous membrane, such as inside the mouth or on the genital area. Each virus can be carried in bodily fluids (saliva, semen, fluid in the female genital tract) or in fluid from herpes sores. The risk for infection is highest with direct contact of blisters or sores during an outbreak.

Once the virus has contact with the mucous membranes or skin wounds, it begins to replicate. The virus is then transported within nerve cells to their roots where it remains inactive (latent) for some period of time. During inactive periods, the virus cannot be transmitted to another person. However, at some point, it often begins to multiply again without causing symptoms (called shedding ). During shedding, the virus can infect other people through exchange of bodily fluids.

Sometimes, infected people can transmit the virus and infect other parts of their own bodies (most often the hands, thighs, or buttocks). This process, known as autoinoculation, is uncommon, since people generally develop antibodies that protect against this problem.

Oral herpes (usually HSV-1) has been detected in both the saliva and blood of patients with active oral infections. It is the most prevalent form of herpes simplex virus, and infection is most likely to occur during preschool years. Oral herpes is easily spread by direct exposure to saliva or even from droplets in breath. Skin contact with infected areas is enough to spread it. Transmission most often occurs through close personal contact, such as kissing. In addition, because herpes simplex virus 1 can be passed in saliva, people should also avoid sharing toothbrushes or eating utensils with an infected person.

Genital herpes is most often transmitted through sexual activity, and people with multiple sexual partners are at high risk. The virus, however, can also enter through the anus, skin, and other areas.

People with active symptoms of genital herpes are at very high risk for transmitting the infection. Unfortunately, evidence suggests about one-third of all herpes simplex virus 2 (HSV-2) infections occur when the virus is shedding but producing no symptoms. Most people either have no symptoms or don't recognize them when they appear.

In the past, genital herpes was mostly caused by HSV-2, but herpes simplex virus 1 (HSV-1) genital infection is increasing, most likely to due to oral sex. Shedding of genital HSV-1 is less common than with HSV-2, but transmission obviously still occurs, as evidenced by the rising prevalence of genital HSV-1. In fact, a person who carries both HSV-1 and HSV-2 poses a greater risk for sexually transmitting HSV-2 than a person who carries only HSV-2. A person who is infected with only HSV-1 has some protection against being infected by HSV-2.

Risk Factors

Everyone is at risk for herpes simplex virus. According to the latest U.S. data from 1999 - 2004, 57.7% of Americans ages 14 – 49 are infected with herpes simplex virus 1 (HSV-1). About 17% of Americans in the same age range test positive for herpes simplex virus 2 (HSV-2). Infection rates for both viruses have declined since the late 1980s. However, infection is lifelong.

Oral herpes is usually caused by HSV-1. The highest incidence of first infection occurs between 6 months and 3 years of age. The incidence in children varies among regions and countries, with the highest rates occurring in crowded and unsanitary regions. Studies suggest that by age 5 more than a third of children in low-income areas are infected compared to 20% of children in middle-income areas. However, by the time children in middle-income areas reach their 30s, about 60% have become infected with HSV-1. After age 40, socioeconomic differences in infection rates become even less pronounced.

The number of Americans with genital herpes increased by 30% from the late 1970s through the early 1990s. However, recent surveys indicate that prevalence is decreasing. A 2006 study in the Journal of the American Medical Association found that among Americans age 14 - 49, the prevalence of herpes simplex virus 2 (HSV-2) decreased by 19% from 1988 - 2004. The decrease was greatest among teenagers age 14 - 19.

The prevalence of herpes virus simplex 1 (HSV-1) also declined, but the percentage of genital herpes infections caused by HSV-1 more than tripled. Among people infected with HSV-1, but not HSV-2, 1.8% were diagnosed with genital herpes from 1999 to 2004 compared with 0.4% from 1988 to 1994. (HSV-2 still causes the majority of genital herpes infections.)

Although the prevalence of genital herpes is declining in the United States, it still remains in epidemic proportions. According to the U.S. Centers for Disease Control and Prevention, at least 45 million Americans age 12 and over have had genital herpes. About 1 in 5 teenagers and adults are infected with genital herpes.

Gender. Anyone who is sexually active is at risk for genital herpes. Studies indicate that around 22% of Americans are infected with HSV-2, with the risk higher in women (26%) than in men (18%). Men, however, have twice as many recurrent infections as women.

Women have an 80 - 90% chance of contracting HSV-2 after unprotected sexual activity with an infected partner and are 4 times more likely to be infected than men. In one study of sexually active American teenagers, 15% of the females had evidence of being infected with HSV-2, compared to none of the males. Having a drinking problem greatly increased the likelihood of infection in these young women.

Ethnicity. Although African-Americans are more likely to test positive for HSV-2, Caucasians have a higher risk for active genital symptoms. Over the past few years, the greatest increase in HSV-2 has occurred in Caucasian teenagers.

Compromised Immune Systems. People with compromised immune systems, notably patients with HIV, are at very high risk for HSV-2. Between 68 - 81% of patients with HIV are infected with HSV-2. These patients are also at risk for more severe complications from herpes. Other immunocompromised patients include those taking drugs that suppress the immune system and transplant patients.

The following are examples of people who are at particularly risk for specific forms of herpes.

Health care providers, including doctors, nurses, and dentists. This group is at higher than average risk for herpetic whitlow, herpes that occurs in the fingers.
Wrestlers, rugby players, and other athletes who participate in direct contact sports without protective clothing. These individuals are at risk for herpes gladiatorum, an unusual form of HSV-1 that is spread by skin contact with exposed herpes sores and usually affects the head or eyes.

Complications

The severity of symptoms depends on where and how the virus enters the body. Except in very rare instances and in special circumstances, the disease is not life threatening, although it can be very debilitating and cause great emotional distress.

Pregnant women who are infected with either herpes simplex virus 2 (HSV-2) or herpes simplex virus 1 (HSV-1) genital herpes have a higher risk for miscarriage, premature labor, retarded fetal growth, or transmission of the herpes infection to the infant while in the uterus or at the time of delivery. Recurrence in women previously infected with herpes is also common during pregnancy.

However, although about 1 million pregnancies occur each year in women who have been infected with HSV-2, complications occur in fewer than 4 in 1,000 infected pregnant women.

Approach to the Pregnant Herpes Patient. The approach to a pregnant woman who has been infected by either HSV-1 or HSV-2 in the genital area is usually determined by when the infection was acquired and the mother's condition around the time of delivery:

If lesions are present at the time of birth, Cesarean section is usually recommended. An important 13-year study confirmed that this approach helps prevent transmission. In the study, the baby became infected in only 1.1% of Cesarean sections compared to 7.7% of vaginal deliveries. (Even a Cesarean section is no guarantee that the child will be virus-free, and the newborn must still be tested.)
If lesions erupt shortly before the baby is due then samples must be taken and sent to the laboratory. Samples are cultured to detect the virus at 3 - 5-day intervals prior to delivery to determine whether viral shedding is occurring. If no lesions are present and cultures indicate no viral shedding, a vaginal delivery can be performed and the newborn is examined and cultured after delivery.

Some doctors now recommend anti-viral medication for pregnant women who are infected with HSV-2. Recent studies indicate that acyclovir (Zovirax) or valacyclovir (Valtrex) can help reduce the recurrence of genital herpes and the need for Cesarean sections. Women begin to take the drug on a daily basis beginning in the 36th week of pregnancy (last trimester).

Although 25 - 30% of pregnant women in the U.S. and Europe have a history of herpes simplex virus (HSV-2) infection, the risk of transmission to the newborn is low, occurring in between one in 3,500 - 20,000 births, depending on the population group.

The greatest danger to the baby is from an asymptomatic infection during a vaginal delivery in women who acquired the virus for the first time late in the pregnancy. In such cases, 30 - 50% of newborns become infected. Recurring herpes and a first infection that is acquired early in the pregnancy pose a much lower risk (less than 1%) to the infant.

The reasons for the higher risk with a late primary infection are:

During a first infection, the virus is shed for longer periods, and more viral particles are excreted.
An infection that first occurs in the late term does not allow the mother to develop antibodies that would help her baby fight off the infection at the time of delivery.

The risk for transmission also increases if infants with infected mothers are born prematurely, if there is invasive monitoring, or if instruments are required during vaginal delivery. Transmission can occur if the amniotic membrane of an infected woman ruptures prematurely, or as the infant passes through an infected birth canal. Very rarely, the virus is transmitted across the placenta, a form of the infection known as congenital herpes.

Infants may acquire congenital herpes from a mother with an active herpes infection at the time of birth. Aggressive treatment with antiviral medication is required, but may not help systemic herpes.

Unfortunately, only 5% of infected pregnant women have a history of symptoms, so in many cases herpes infection is not suspected, or symptoms are missed, at the time of delivery. Occasionally, lesions on the mother's buttocks may help indicate the presence of the virus.

Herpes infection in a newborn is a very serious and even-life threatening condition if it goes undiagnosed and untreated. Fortunately, since the introduction of acyclovir the outlook for these children has significantly improved. In general, there are three categories of herpes in the newborn.

Localized infection affects the skin, eyes, and mucous membranes. Herpes simplex virus 1 (HSV-1) usually causes this temporary. However, in some cases, most often herpes simplex virus 2 (HSV-2) infections, later complications develop in 5 - 10% of infants. If untreated, the virus may lead to very severe complications, notably disseminated or central nervous system infection.
Disseminated disease can affect internal organs, such as the liver, lungs, and adrenal glands. It is fatal in up to 80% of newborns if left untreated, and those who survive are at high risk for complications, particularly in the eyes. If infants are treated, however, survival rates are close to 90%.
Central nervous system infection can cause meningitis or encephalitis. This form is also highly fatal, and complications that affect learning and mental functions are common in surviving children.

Factors that Indicate a Higher Risk for Severe Complications. These may include:

Acute infection in the mother at delivery
Prematurity
Seizures in the infant
Disseminated intravascular coagulopathy, a blood-clotting disorder that can occur in response to infection

Factors that Indicate a Lower Risk for Severe Complications. These may include:

Newborn infection caused by a recurring HSV-2 infection in the mother. (Mothers with such infections appear to pass along protective antibodies to the newborn. However, antibodies to HSV-1 do not appear to offer similar protection to the newborn.)
Newborn infections that are confined to the skin and do not cause frequent outbreaks within the first 6 months.

Tests for the Newborn at Risk for Herpes. Any newborn with an infected or high-risk mother should be tested and checked carefully for symptoms. (Experts are divided, however, over whether the high cost of testing mothers specifically for HSV before delivery, even in high-risk groups, is worth the benefit for such a small group of mothers and infants.)

In the asymptomatic newborn delivered from an infected mother, cultures should be taken between 24 - 48 hours after birth. A culture taken right at the time of delivery may give a false indication of infection in the baby, simply because it can carry some of the mother's virus from the birth canal.
Testing specimens for viral DNA using a test called polymerase chain reaction is proving to be very important in newborns, particularly when central nervous system infection is suspected, since it eliminates the need for brain biopsies.
While results are pending, the baby should be checked regularly for rashes and blisters, particularly in areas where the skin is broken, along with any signs of illness including fever, lethargy, respiratory distress, and poor feeding.

Symptoms of Herpes in the Newborn. Although treatments have improved the outlook of infected newborns, there has been little change over the past 20 years in the time between the onset of symptoms and the initiation of treatments. Doctors and parents should be suspicious of any signs if there is any risk of infection to the newborn.

When symptoms occur in newborns, they usually become apparent within 5 - 17 days of life, but they may develop as early as 24 hours or as late as 34 days.

An unstable temperature can be the first indication of the infection.
About half of infected infants develop a rash. Lesions may range from raised spots to large isolated blisters. They can be anywhere on the skin or eyes or in the mouth.
The other half of infected infants develop no lesions until later in the course of the infection. The absence of lesions, therefore, in high-risk infants should not be considered a guarantee that HSV has not been transmitted.
Other symptoms to watch for include irritability, blotchy skin, discharge in the eyes, sensitivity to light, tearing, lethargy, jaundice, pallor, coughing, rapid breathing, a swollen abdomen (enlarged spleen), seizures, or tremors. Doctors should suspect infection in any infant with fever, irritability, lethargy, or poor feeding at 1 week of age.

Treatment of Herpes in the Newborn. If doctors suspect herpes virus infection in a newborn, intravenous acyclovir treatment should begin immediately, since the potential dangers of the condition far outweigh any risks associated with the drug.

The following are recommendations for treating infants who have been infected or are at risk for infection:

If disseminated or central nervous system infection has developed or is suspected, intravenous acyclovir treatment should continue for 21 days.
If the infection is limited to the skin, eyes, or mouth and the infant is at low risk for more serious complications, treatment may be given for 10 - 14 days.

The American Academy of Pediatrics Committee on Infectious Diseases now recommends higher-than-standard doses to improve outcome in infants who have any of these infections. Investigators are studying whether giving long-term acyclovir by mouth to newborns following the initial infection will improve the outcome.

Herpes Encephalitis. Each year in the U.S., herpes accounts for 2,100 cases of encephalitis, a rare but extremely serious brain disease. Herpes simplex virus 1 (HSV-1) is usually the cause, except in newborns. In about 70% of cases of infant herpes encephalitis, the disease occurs when a latent herpes simplex virus 2 (HSV-2) is activated. Untreated, herpes encephalitis is fatal over 70% of the time. Respiratory arrest can occur within the first 24 - 72 hours. Fortunately, rapid diagnostic tests and treatment with acyclovir have both significantly improved survival rates (up to about 80%) and reduced complication rates (to nearly 40%). For those who recover, nearly all suffer some impairment, ranging from very mild neurological changes to paralysis. Recovery from herpes encephalitis depends on the patient's age, the level of consciousness, duration of the disease, and the promptness of treatment. The best chances for a favorable outcome occur in patients who are treated with acyclovir within 2 days of becoming ill.

Herpes Meningitis. Herpes meningitis, an inflammation of the membranes that line the brain and spinal cord, occurs in up to 10% of cases of primary genital HSV-2. Women are at higher risk than men for herpes meningitis. Symptoms include headache, fever, stiff neck, vomiting, and sensitivity to light. Fortunately, herpes meningitis usually resolves without complications, lasting for up to a week, although recurrences have been reported.

Click the icon to see an image of the meninges of the brain.

Alzheimer's Disease. Some studies indicate a higher risk for Alzheimer's in people who have both HSV-1 and a gene called ApoE4, a known risk factor for Alzheimer's. Furthermore, a protein found in HSV-1 has been shown to mimic beta amyloid, a protein that is critical in the development of Alzheimer's disease.

Other Neurologic Diseases. Other neurologic syndromes that have been linked to HSV infection include epilepsy, multiple sclerosis, atypical pain syndromes, ascending or transverse myelitis (inflammation of the spinal column), and neuralgia (severe stabbing pain along a nerve or group of nerves).

A form of herpes infection called eczema herpeticum, also known as Kaposi's varicellum eruption, can affect patients with skin disorders and immunocompromised patients. The disease tends to develop into widespread skin infection that resembles impetigo. Symptoms appear abruptly and can include fever, chills, and malaise. Clusters of dimpled blisters emerge over 7 - 10 days and spread widely. They can become secondarily infected with staphylococcal or streptococcal organisms. When treated, lesions heal in 2 - 6 weeks. Untreated, this condition can be extremely serious and possibly fatal.

Herpetic infections of the eye (ocular herpes) occur in about 50,000 Americans each year. In most cases it causes inflammation and sores on the lids or outside of the cornea that go away in a few days.

Click the icon to see an image of the eye.

Stromal Keratitis. Stromal keratitis occurs in up to 25% of cases of ocular herpes. In this condition, deeper layers of the cornea are involved, possibly as an abnormal immune response to the original infection. In these rare cases, scarring and corneal thinning develop, which may cause the eye's globe to rupture, resulting in blindness. Although rare, it is the major cause of corneal blindness in the US.

Iridocyclitis. Iridocyclitis is another serious complication of ocular herpes, in which the iris and the area around it become inflamed.

Herpes can cause multiple painful ulcers on the gums and mucous membranes of the mouth, a condition called gingivostomatitis. This condition usually affects children 1 - 5 years of age. It nearly always subsides within 2 weeks.Rarely, it can lead to a viral infection. Children with gingivostomatitis commonly develop herpetic whitlow (herpes of the fingers).

A herpetic whitlow is an infection of the herpes virus around the fingernail. In children, this is often caused by thumbsucking or finger sucking while they have a cold sore. It is seen in adult health care workers, such as dentists, because of increased exposure to the herpes virus. The use of rubber gloves prevents herpes whitlow in health care workers.

Not least among the damaging effects of genital herpes is its impact on the social and emotional life of patients. In one survey of patients with herpes, 82% felt depressed, and 75% were worried about rejection. Over 25% had suicidal thoughts. In nearly 80% of the respondents, the disease had a profound effect on their sexual lives. The patient must notify sexual partners, past and present, about their condition, a deeply humiliating experience. Guilt and anger are common emotions, and relationships may be shattered. It is important to note that the condition is often dormant for many years and may not have been transmitted by a current sexual partner. Support groups or couple therapy can be very helpful.

Herpes simplex is particularly devastating when it occurs in immunocompromised patients and, unfortunately, coinfection is common. People infected with herpes have a three-fold increased risk for contracting HIV. Furthermore, studies have reported that 68 - 81% of patients with HIV are also infected with herpes simplex virus 2 (HSV-2).

Patients with HIV are particularly vulnerable to complications. When a person has both viruses, there appears to be a synergy between them, with each virus increasing the severity of the other. HSV-2 infection increases HIV levels in the genital tract, which makes it easier for the HIV virus to be transmitted to sexual partners. In addition, episodes of herpes recurrence increase, at least temporarily, HIV viral load. An important 2007 study in the New England Journal of Medicine indicated that treatment of HSV-2 with valacyclovir can help reduce plasma and genital levels of HIV in women who are infected with both viruses. Researchers are continuing to investigate whether treatment of HSV-2 may help reduce the risk of HIV transmission.

Herpes simplex in any patient with a seriously compromised immune system can cause serious and even life-threatening complications, including:

Pneumonia
Inflammation of the esophagus
Encephalitis (inflammation of the brain)
Destruction of the adrenal glands
Disseminated herpes (spread of infection throughout the body)
Liver damage, including hepatitis

Hepatitis caused by primary or recurrent herpes can sometimes develop into a life-threatening condition called fulminant liver failure. This condition is treatable with medications, or even a liver transplant, when diagnosed promptly. Early symptoms may include nausea, vomiting, and abdominal pain. (This is an uncommon complication in HSV-infected people with healthy immune systems, but cases have been reported, such as after surgical procedures.)

Less serious conditions include stomach and anal ulcers, inflammation in the colon, and eczema herpeticum.

Several conditions have been linked to herpes infections, although the association has not been substantiated in most cases.

Arthritis, usually in a single joint, has been sporadically reported as a result of herpes infection.
People with herpes simplex virus 2 (HSV-2) may be more likely to get sexually transmitted hepatitis C.
Some evidence suggests that herpes simplex virus 1 (HSV-1) may slightly increase the risk for certain cancers of the mouth or throat in people who are already at higher risk because of cigarette smoking or infection with another microorganism called human papillomavirus.
Some studies have reported associations between herpes simplex and heart disease, including lower survival rates. Such infections may produce persistent inflammation in the arteries leading to heart trouble. Research is ongoing.
Other rare complications of herpes simplex include erosion or ulcers in the lining of the esophagus and stomach. Certain kidney and blood diseases have also been reported in conjunction with HSV infection. These are very uncommon, however, particularly in people with healthy immune systems.

Diagnosis

The herpes simplex virus is usually identifiable by its characteristic lesion: A thin-walled blister on an inflamed base of skin. However, other conditions can resemble herpes, and doctors cannot base a herpes diagnosis on visual inspection alone. In addition, some patients who carry the virus may not have visible genital lesions. Laboratory tests are essential for confirming herpes diagnosis. These tests include virologic tests (which examine samples of skin taken from the lesion) and serologic tests (blood tests that detect antibodies).

In its 2006 guidelines for sexually transmitted diseases, the U.S. Centers for Disease Control (CDC) recommends that both virologic and serologic tests be used for diagnosing genital herpes. Patients diagnosed with genital herpes should also be tested for other sexually transmitted diseases.

According to the CDC, up to 50% of first-episode cases of genital herpes are now caused by herpes simplex virus 1 (HSV-1). However, recurrences of genital herpes, and viral shedding without overt symptoms, are much less frequent with HSV-1 infection than herpes simplex virus 2 (HSV-2). It is important for doctors to determine whether the genital herpes infection is caused by HSV-1 or HSV-2, as the type of herpes infection influences prognosis and treatment recommendations.

Viral culture tests are made by taking a fluid sample, or culture, from the lesions as early as possible, ideally within the first 3 days of appearance. The viruses, if present, will reproduce in this fluid sample but may take 1 - 10 days to do so. If infection is severe, testing technology can shorten this period to 24 hours, but speeding up the timeframe during this test may make the results even less accurate. Viral cultures are very accurate if lesions are still in the clear blister stage, but they do not work as well for older ulcerated sores, recurrent lesions, or latency. At these stages the virus may not be active enough to reproduce sufficiently to produce a visible culture.

Polymerase chain reaction (PCR) tests are much more accurate than viral cultures, and the CDC recommends this test for detecting herpes in spinal fluid when diagnosing herpes encephalitis (see below). PCR can make many copies of the virus’ DNA so that even small amounts of DNA in the sample can be detected. PCR is much more expensive than viral cultures and is not FDA-approved for testing genital specimens. However, because PCR is highly accurate, many labs have used it for herpes testing.

An older type of virologic testing, the Tzanck smear test, uses scrapings from herpes lesions. The scrapings are stained and microscopically examined for the virus. Findings of specific giant cells with many nuclei or distinctive particles that carry the virus (called inclusion bodies) indicate herpes infection. The test is quick but accurate 50 - 70% of the time. It cannot distinguish between virus types or between herpes simplex and herpes zoster. The Tzanck test is not reliable for providing a conclusive diagnosis of herpes infection and is not recommended by the CDC.

Serologic (blood) tests can identify antibodies that are specific to the virus and its type, herpes virus simplex 1 (HSV-1) or herpes virus simplex 2 (HSV-2). When the herpes virus infects someone, their body’s immune system produces specific antibodies to fight off the infection. If a blood test detects antibodies to herpes, it’s evidence that you have been infected with the virus, even if the virus is in a non-active (dormant) state. The presence of antibodies to herpes also indicates that you are a carrier of the virus and might transmit it to others.

Newer “type-specific” assays test for antibodies to two different proteins that are associated with the herpes virus:

Glycoprotein gG-1 is associated with HSV-1
Glycoprotein gG-2 is associated with HSV-2

Although glycoprotein (gG) type-specific tests have been available since 1999, many of the older nontype-specific tests are still on the market. The CDC recommends only type-specific glycoprotein (gG) tests for herpes diagnosis.

Serologic tests are most accurate when administered 12 - 16 weeks after exposure to the virus. Recommended tests include:

HerpeSelect. This includes two tests: ELISA (enzyme-linked immunosorbent assay) or Immunoblot. They are both highly accurate in detecting both types of herpes simplex virus. Samples need to be sent to a lab, so results take longer than the in-office Biokit test.
Biokit HSV-2 (also marketed as SureVue HSV-2). This test detects HSV-2 only. Its major advantages are that it requires only a finger prick and results are provided in less than 10 minutes. It is very accurate, although slightly less so than the other tests. It is also less expensive.
Western Blot Test. This is the gold standard for researchers with accuracy rates of 99%. It is costly and time consuming, however, and is not as widely available as the other tests.

False-negative (testing negative when herpes infection is actually present) results can occur if tests are done in the early stages of infection. False-positive results (testing positive when herpes infection is not actually present) can also occur, although more rarely than false-negative. Your doctor may recommend that you have the test repeated.

Experts recommend serologic herpes tests especially for:

People who have had recurrent genital symptoms but no negative herpes viral cultures
Confirming infection in people who have visible symptoms of genital herpes
Determining if the partner of someone diagnosed with genital herpes has acquired herpes
People who have multiple sex partners and who need to be tested for different types of STDs

At this time, doctors do not recommend screening for HSV-1 or HSV-2 in the general population.

It make take a number of test to diagnose herpes encephalitis.

Imaging Tests. Electroencephalography traces brain waves and can identify about 80% of cases. Computed tomography or magnetic resonance imaging scans may be used to differentiate encephalitis from other conditions.

Brain Biopsy. Brain biopsy is the most reliable method of diagnosing herpes encephalitis, but it is also the most invasive and is generally performed only if the diagnosis is uncertain.

Polymerase Chain Reaction (PCR). The polymerase chain reaction (PCR) assay looks for tiny pieces of the DNA of the virus, and then replicates them millions of times until the virus is detectable. This test can identify specific strains of the virus and asymptomatic viral shedding. PCR identifies HSV in cerebrospinal fluid and gives a rapid diagnosis of herpes encephalitis in most cases, eliminating the need for biopsies. The CDC recommends PCR for diagnosing herpes central nervous system infections.

Similar Conditions

Canker Sores (Aphthous Ulcers). Common canker sores (known medically as aphthous ulcers) are often confused with the cold sores of herpes simplex virus 1 (HSV-1). Canker sores frequently crop up singly or in groups on the inside of the mouth or on or under the tongue. They are usually white or grayish crater-like ulcers with a sharp edge and a red rim. They usually heal in 2 weeks without treatment.

Canker sores (Aphthous ulcers) are very common. Typically, they are a shallow ulcer with a white or whitish/yellow base surrounded by a reddish border. This ulcer is seen in an individual with AIDS and is located in front and just below the bottom teeth.

Thrush (Candidiasis). Candidiasis is a yeast infection that causes a whitish overgrowth in the mouth. It is most common in infants but can appear in people of all ages, particularly those with impaired immune systems.

Click the icon to see an image of thrush.

Other conditions that may be confused with oral herpes include herpangina (a form of the Coxsackie A virus), sore throat caused by strep or other bacteria, and infectious mononucleosis.

Conditions that may be confused with herpes simplex virus 2 (HSV-2) include bacterial and yeast infections, genital warts, herpes zoster (shingles), molluscum (a virus disease which produces small rounded swellings), scabies, syphilis, and certain cancers.

In a few cases, HSV-2 may occur without lesions and resemble cystitis and urinary tract infections.

Simple corneal scratches can cause the same pain as herpetic infection, but these usually resolve within 24 hours and don't exhibit the corneal lesions characteristic of herpes simplex.

Skin disorders that may mimic herpes simplex include shingles and chicken pox (both caused by varicella-zoster, another herpes virus), impetigo, and Stevens-Johnson syndrome, a serious inflammatory disease usually caused by a drug allergy.

Click the icon to see an image of the shingles.

Click the icon to see an image of chickenpox.

Home Remedies and Prevention

Patients can manage most herpes simplex infections that develop on the skin at home with over-the-counter painkillers and measures to relieve symptoms.

Several simple steps can produce some relief:

Hygiene is important. Avoid touching the sores. Wash hands frequently during the day. Fingernails should be scrubbed daily. Keep the body clean.
Drink plenty of water.
Keep blisters or sores clean and dry with cornstarch or similar product. (Women should not use talcum powder because it may increase their risk for ovarian cancer.)
Some people report that drying the genital area with a blow dryer on the cool setting offers relief.
Avoid tight-fitting clothing, which restricts air circulation and slows healing of the sores.
Choose cotton underwear, rather than synthetic materials.
Local application of ice packs may alleviate the pain and help reduce recurrences by suppressing the virus.
Lukewarm baths may be helpful. (For people who have pain on urination, some experts recommend urinating in the bath water at the end of the bathing time. This dilutes the urine and prevents burning the sores. Urinating in a cool shower is also helpful and is less offensive to many people. )
Wearing sun block helps prevent sun-triggered recurrence of herpes simplex virus 1 (HSV-1).
Avoid sex during both outbreaks and prodromes (the early symptoms of herpes), which include tingling, itching, or tenderness in the infected areas.
Over-the-counter medications such as aspirin, acetaminophen (Datril, Panadol, Tylenol), or ibuprofen (Advil, Medipren, Motrin, Nuprin), can be used to reduce fever and local tenderness. Children should take acetaminophen. Never give children aspirin.

In one study, stress management techniques developed using cognitive-behavioral methods not only were effective in reducing depression in those with hepres simplex virus 2 (HSV-2) but blood test results also revealed lower levels of HSV-2 antibodies, a possible sign of decreased viral activity. In any case, reducing stress using relaxation techniques does no harm.

Many herbal and dietary supplement products claim to help fight herpes infection by boosting the immune system. There has been little research on these products, and little evidence to show that they really work. Some are capsules taken by mouth. Others come in the form of ointment that is applied to the skin. Popular herbal and supplement remedies for herpes simplex include:

Echinacea (Echinacea purpurea )
Siberian ginseng (Eleutherococcus senticosus )
Aloe (Aloe vera )
Bee products that contain propolis, a tree resin collected by bees
Lysine
Zinc

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

The following are special concerns for people taking natural remedies for herpes simplex:

Echinacea can lower white blood cell levels when taken for long periods of time. This herb can also interfere with drugs that are used to treat immune system disorders.
Siberian ginseng can raise blood pressure levels.
Bee products (like propolis) can cause allergic reactions in people who are allergic to bee stings.
Do not take Lysine with certain types of antibiotics.
'Taking zinc in large amounts (more than 200 mg/day) can cause stomach upset.

Infected people should take several steps to avoid transmitting the virus to others. It is almost impossible to defend against the transmission of oral herpes simplex virus 1 (HSV-1) since it can be transmitted by very casual contact.

Preventing Transmission During an Outbreak. When an outbreak of herpes occurs, the following precautions are useful:

Persons carrying any herpes virus should carefully wash their hands and nails after contact with the infected area so as not to transmit the virus to other sites on the body.
Although transmission from objects such as toilet seats and towels is unlikely, keeping personal items separate during an active infection may help to reduce transmission to other household members. The virus can live for up to 2 hours on cloth and for 4 hours on plastic.
If genital lesions are present, infected persons should abstain from sexual intercourse.

Preventing Sexually Transmitted Disease. Any infected man or a partner of an infected woman should wear a condom during any sexual activity, even when symptoms are not present. Condoms are also important during oral sex, as an increasing number of new genital herpes cases are due to HSV-1, particularly among younger people.

The use of condoms for preventing the transmission of herpes simplex virus 2 (HSV-2) is not foolproof. Even a small tear can permit passage of the virus. However, studies show that regular condom use can significantly reduce the risk of HSV-2 infection.

Condoms made of latex are less likely to slip or break than those made of polyurethane. “Natural” condoms made from animal skin do not protect against HSV infection because herpes viruses can pass through them.

Women appear to be better protected than men are by male condoms. The reason may be that men shed HSV-2 from the skin of the penis, which is covered by the condom. However, in women the virus is often shed from skin areas around the genital area, which can have contact to skin areas in the male outside the condom.

The female condom is another option for infected women or partners of infected men. The female condom covers a large area and is an effective barrier to sexually transmitted viruses.

Note on Lubricants and Spermicides. Only water-based lubricants (K-Y Jelly, Astroglide, AquaLube, glycerin) should be used. Oil-based lubricants (petroleum jelly, body lotions, cooking oil) can weaken latex.

Some condoms come prelubricated with sperm-killing substances called spermicides, which are no longer recommended. The standard active ingredient in spermicides is nonoxynol-9, which attacks the surface of the sperm cell. Nonoxynol-9 does not provide any additional protection against sexually transmitted diseases (STDs). It can cause yeast and urinary tract infections in women. In addition, it can cause irritation around the genital areas, which makes it easier for herpes and other STDs to be transmitted. In fact, research indicates that it actually increases the risk for HIV in women.

Treatment for Genital Herpes

No drug can cure herpes simplex virus. The infection may recur after treatment has been stopped, and, even during therapy, a patient can still transmit the virus to another person. Drugs can, however, reduce symptoms and improve healing times.

Antiviral drugs called nucleosides or nucleotide analogues are the main drugs used to treat genital herpes. They are taken by mouth. (Acyclovir is also available as an ointment, but the oral form is much more effective.) These drugs limit herpes viral replication and its spread to other cells. They are not cures, however.

Three drugs are approved to treat genital herpes:

Acyclovir (Zovirax or generic)
Valacyclovir (Valtrex)
Famiciclovir (Famvir)

When a patient has herpes for the first time, the drug is taken several times a day for 7 -10 days. Then the drugs are used either to suppress the virus or to treat outbreaks.

To treat outbreaks, regimens depend on the medication and dosage prescribed:

Acyclovir: 400 mg three times a day for 2 days or 800 mg twice a day for 5 days
Valacyclovir: 500 mg twice a day for 3 days or 1 g once a day for 5 days
Famiciclovir: 125 mg twice a day for 5 days or 1000 mg twice a day for 1 day. (In 2006, famiclovir was approved as the first one-day treatment for recurrent genital herpes.)

To suppress outbreaks, treatment requires taking pills daily on a long-term basis. (Acyclovir and famiciclovir are taken twice a day, valacyclovir once a day.) Suppressive treatment can reduce outbreaks by 70 – 80%. It is generally recommended for patients who have frequent recurrences (6 or more outbreaks per year). Valacyclovir may work especially well for preventing herpes transmission among heterosexual patients when one partner has herpes simplex virus 2 (HSV-2) and the other partner does not. However, valacyclovir may not be as effective as acyclovir or famiciclovir for patients who have very frequent recurrences of herpes (more than 10 outbreaks per year).

Because the frequency of herpes recurrences often diminishes over time, patients should discuss annually with their doctors whether they should stay with drug therapy or discontinue it. Studies suggest that daily drug therapy is safe and effective for up to 6 years with acyclovir, and up to 1 year with valacyclovir or famciclovir.

Side Effects. Nausea and headache are the most common side effects, but in general these drugs are safe. Although there is some evidence these drugs may reduce shedding, they probably do not prevent it entirely. The use of condoms during asymptomatic periods is still essential, even when patients are taking these medications.

Risk for Resistant Viruses. As with antibiotics, doctors are concerned about signs of increasing viral resistance to acyclovir and similar drugs, particularly in immunocompromised patients (such as those with AIDS). Some experts believe, however, that the prevalence of drug-resistant viruses will be low for many years. They feel that widespread use of antiviral drugs will prevent many cases of herpes from developing and will slow the spread of the disease. Even patients on long-term suppressive drug therapy show few signs of drug resistance. However, patients who do not respond to standard regimens should be monitored for emergence of drug resistance.

Some doctors believe that developing an effective herpes vaccine is the only practical way to control the disease and the spread of infection. Furthermore, if such a vaccine becomes available, then universal immunization may be the best approach. Vaccines also hold the potential for eliminating latent, lifelong infections.

In 2002, the National Institute of Allergy and Infectious Diseases (NIAID) launched the Herpevac Trial for Women. The NIAID seeks to enroll 7,500 women between the ages of 18 and 30 who test negative for both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infection. The trial is being conducted at more than 40 sites in the United States and Canada. Participants are randomly assigned to receive either three doses of the experimental herpes vaccine or an investigational hepatitis A vaccine. The women will be observed for 20 months following the initial vaccination to determine if they contract genital herpes (or, for the control group, hepatitis A) during this time. The vaccine used in the trial does not contain live virus and will not itself cause infection.

The premise for the Herpevac trial is based on results from two studies published in the New England Journal of Medicine in 2002. In these studies, a glycoprotein D vaccine was effective in preventing genital herpes in women who were not infected with HSV-1 or HSV-2. For uninfected women, the risk of contracting genital herpes was reduced by nearly 75 percent. The vaccine was not useful, however, for women already infected with HSV-1 and was ineffective in men regardless of their virus status.

Treatment for Oral Herpes

Acyclovir (Zovirax), valacyclovir (Valtrex), and famciclovir (Famvir) -- the anti-viral pills used to treat genital herpes -- can also treat the cold sores associated with oral herpes. In addition, acyclovir is available in topical form, as is penciclovir (a related drug).

These ointments or creams help shorten healing time and duration of symptoms. However, none are truly effective in eliminating outbreaks.

Penciclovir (Denavir) heals herpes simplex virus 1 (HSV-1) sores on average about half a day faster than without treatment, stops viral shedding, and reduces the duration of pain. Ideally, the patient should apply the cream within the first hour of symptoms, although benefits have also been noted with later application. It is continued for 4 consecutive days, and should be reapplied every 2 hours while awake.
Acyclovir cream (Zovirax) works best when applied early on (at the first sign of pain or tingling).
Docosanol cream (Abreva) is the only FDA-approved non-prescription ointment for oral herpes. The patient applies the cream five times a day, beginning at the first sign of tingling or pain. Studies have been mixed on the cream’s benefits.
Over-the-counter topical anesthetics may provide modest relief. They include Anbesol gel, Blistex lip ointment, Campho-phenique, Herpecin-L, Viractin, and Zilactin.

Resources

www.ashastd.org -- American Social Health Association
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.cdc.gov/std/herpes -- Centers for Disease Control and Prevention
www.herpesdiagnosis.com -- Herpes Diagnosis
www.herpesalliance.org -- International Herpes Alliance
www.gotherpes.com -- Herpes support site
www.niaid.nih.gov/dmid/stds/herpevac -- Herpevac (herpes vaccine) clinical trial information

References

Centers for Disease Control and Prevention, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006 Aug 4;55(RR-11):1-94.

Lebrun-Vignes B, Bouzamondo A, Dupuy A, Guillaume JC, Lechat P, Chosidow O. A meta-analysis to assess the efficacy of oral antiviral treatment to preventgenital herpes outbreaks. J Am Acad Dermatol. 2007 Aug;57(2):238-46. Epub 2007 Apr 9.

Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L, et al. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. 2007 Feb 22;356(:790-9.

Review Date:
9/9/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Shingles and chickenpox (Varicella-zoster virus)

FitSugar — Wed, 08 Oct 2008 17:35:12 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Vaccination
Diagnosis
Treatment for Chickenpox...
Treatment for an Acute Shin...
Treatment for Postherpetic ...
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Chickenpox Immunization Schedule

In 2007, the U.S. Centers for Disease Control (CDC) updated the immunization schedule for the chickenpox vaccine. The CDC now recommends that children receive two doses of the vaccine. Children should receive:

The first dose when they are 12 – 15 months old
The second dose when they are 4 – 6 years old

If your child has been previously vaccinated, make sure that the pediatrician administers a second “catch-up” dose. It is clear that one dose of chickenpox vaccine does not provide complete protection against chickenpox. Adults who are at high risk of contracting chickenpox should also receive two doses of the chickenpox vaccine.

Shingles Vaccine

In 2006, the FDA approved the first shingles vaccine (Zostavax). The CDC now recommends that all adults with intact immune systems who are age 60 years and older receive this vaccine to help prevent herpes zoster (shingles). This includes adults who have previously had a shingles attack. Evidence indicates that Zostavax can help prevent the occurrence of shingles by about 50%. The vaccine can also help prevent the development of post-herpetic neuralgia (the nerve pain that can follow shingles) by 67%.

Scientists Identify Varicella-Mediating Protein

The varicella-zoster virus causes both chickenpox and shingles. After a chickenpox attack, the virus can lie dormant in the body for many years. Once reactivated, the virus quickly travels through nerve cells, causing rash and nerve pain. In 2006, scientists at the U.S. National Institutes of Health identified a specific protein that causes the virus to spread throughout cells in the body. Researchers hope that this important discovery may lead to new drug treatments for shingles.

Investigational Treatments for Postherpetic Neuralgia

Intravenous antiviral drug treatment, followed by oral antiviral drugs, may help reduce postherpetic neuralgia pain, according to a small study published in the Archives of Neurology.

Introduction

Shingles and chickenpox were once considered separate disorders. Researchers now know that they are both caused by a single virus of the herpes family known as varicella-zoster virus (VZV). The word herpes is derived from the Greek word "herpein," which means "to creep," a reference to a characteristic pattern of skin eruptions. VZV is still referred to by separate terms:

Varicella: The primary infection that causes chickenpox
Herpes zoster: The reactivation of the virus that causes shingles

Varicella (Chickenpox). When patients with chickenpox cough or sneeze, they expel tiny droplets that carry the virus. If a person who has never had chickenpox or been vaccinated inhales these particles, the virus enters the lungs. From here it passes into the bloodstream. When it is carried to the skin it produces the typical rash of chickenpox.

Chickenpox is caused by the varicella-zoster virus, a member of the herpes virus family. The same virus also causes herpes zoster, shingles, in adults. Chickenpox is extremely contagious, and can be spread by direct contact, droplet transmission, and airborne transmission. Symptoms range from fever, headache, stomach ache, or loss of appetite before breaking out in the classic pox rash. The rash can consist of several hundred small, itchy, fluid-filled blisters over red spots on the skin. The blisters often appear first on the face, trunk, or scalp and then spread to other parts of the body

Herpes Zoster (Shingles). The varicella virus also travels to nerve cells called dorsal root ganglia. These are bundles of nerves that transmit sensory information from the skin to the brain. Here, the virus can hide from the immune system for years, often for a lifetime. This inactivity is called latency.

Click the icon to see an image of shingles.

If the virus becomes active after being latent, it causes the disorder known as shingles. The virus in this later form is referred to as herpes zoster. The virus spreads in the ganglion and to the nerves connecting to it. Nerves most often affected are those in the face or the trunk. The virus can also spread to the spinal cord and into the bloodstream. In 2006, scientists at the U.S. Institutes of National Health identified a specific protein, called insulin-degrading enzyme, which causes the varicella-zoster virus to spread throughout cells in the body. The scientists hope that this discovery may eventually help in developing new drug therapies for treating shingles.

It is not clear why the varicella virus reactivates in some people but not in others. In many cases, the immune system has become impaired or suppressed from certain conditions such as AIDS, other immunodeficient diseases, or certain cancers or drugs that suppress the immune system. Aging itself increases the risk for shingles.

The varicella-zoster virus belongs to a group of herpes viruses that includes eight human viruses (it also includes animal viruses as well). Herpes viruses are similar in shape and size and reproduce within the structure of a cell. The particular cell depends upon the specific virus. The human herpes viruses are:

Herpes Simplex Virus 1 (HSV-1; causes cold sores and sometimes genital herpes)
Herpes Simplex Virus 2 (HSV-2; causes genital herpes and sometimes cold sores)
Varicella-zoster Virus (VZV; causes chickenpox and shingles)
Cytomegalovirus (CMV; causes mononucleosis and retinitis)
Epstein-Barre Virus (EBV; causes mononucleosis
Human Herpesvirus 6 (HHV6; causes roseola)
Human Herpesvirus 7 (HHV7; causes roseola)
Human Herpesvirus 7 (HHV8; causes Kaposi's sarcoma)

All herpes viruses share some common properties, including a pattern of active symptoms followed by latent inactive periods that can last for months, years, or even for a lifetime. [See In-Depth Report #52: Herpes simplex.]

Symptoms

The time between exposure to the virus and eruption of symptoms is called the incubation period. For chicken pox, this period is 10 - 20 days. The patient often develops fever, headache, swollen glands, and other flu-like symptoms before the typical rash appears. While fevers are low grade in most children, some can reach up to 105° F.

These symptoms subside once the rash breaks out. One or more tiny raised red bumps appear first, most often on the face, chest, or abdomen. They become larger within a few hours and spread quickly, eventually forming small blisters on a red base. The numbers of blisters vary widely. Some patients have only a few spots, others can develop hundreds. Each blister is filled with clear fluid that becomes cloudy in several days. It takes about 4 days for each blister to dry out and form a scab. During its course, the rash itches, sometimes severely. Usually separate crops of blisters occur over 4 - 7 days, and the entire disease process lasts 7 - 10 days.

Chickenpox itself usually occurs only once, although mild second infections, marked by the telltale rash, have been reported in older children years after their first infection.

Shingles nearly always occurs in adults. It develops on one side of the body. Usually two, and sometimes three, identifiable symptom stages occur:

The first is known as the prodrome, a cluster of warning symptoms that appear before the outbreak of the infection.
The second stage comprises the symptoms of the active infection itself.
In many patients, a third syndrome known as postherpetic neuralgia develops.

One form of shingles is known as zoster sine herpes, in which pain occurs first without a rash. Pain is so common to all stages of herpes zoster that doctors often refer to all syndromes with a single term: Zoster-Associated Pain (ZAP).

Prodrome (Pain).

Pain is the primary early symptom for shingles, and it occurs in all patients. The pain most often occurs in the skin at the site of the re-activated virus. The pain may be experienced as sharp, aching, piercing, tearing, or similar to an electric shock.
The affected skin may itch, feel numb, and be unbearably sensitive to touch. Often the patient experiences a combination of these sensations along with pain.
In addition, some patients may have flu-like symptoms such as muscle aches. (Some people have fever, but it is uncommon.)

The prodrome stage lasts 1 - 5 days before the infection becomes active and the skin rash erupts. Occasionally, the pain can last weeks or even months before the rash erupts.

Active Shingles. The rash that marks the active infection follows the same track of inflamed nerves as the prodrome pain. Between 50 - 60% of cases occur on the trunk. The second most common site is the head, particularly on one side of the face. It may also erupt on the neck or lower back. If the face is affected, there is a danger that the infection can spread to the eye or mouth. A rash that follows the side of the nose is a warning that the cornea of the eye is in danger.

This is a picture of herpes zoster (shingles) on the neck and cheek. The same virus that causes chickenpox is responsible for outbreaks of shingles. Outbreaks of shingles often follow the distribution of nerves in the skin. This distribution pattern is called a dermatome (see the "dermatomes" picture).

The active infection is typically marked by the following sequence:

A rash appears, starting as well-defined, small, red, clear spots.
Within 12 - 24 hours, these pimples develop into small fluid-filled blisters.
The blisters grow, merge, and become pus-filled.
Pain is common during the active infection.
Within about 7 - 10 days (as with chickenpox), the blisters form crusts and heal. In some cases it may take as long as a month before the skin clears completely. Healing takes even longer in patients who have impaired immune systems, and, in such cases, the blisters may persist for months.

Zoster Sine Herpete. Sometimes pain develops without a rash, a condition known as zoster sine herpete. This usually occurs in elderly patients. Symptoms include burning or shooting pain, numbness, tingling, itching, headache, fever, chills, and nausea. An accurate early diagnosis of shingles in such cases is often difficult. Some evidence suggests that some cases of Bell's palsy (in which part of the face becomes paralyzed) might actually be an indication of zoster sine herpete.

Postherpetic Neuralgia. Postherpetic neuralgia (PHN) is pain that persists for longer than a month after the onset of herpes zoster. (Some experts define persistent pain as subacute herpetic neuralgia if it lasts between 1 - 3 months, and as PHN if it lasts beyond 3 months.) PHN occurs in approximately 10 - 20% of patients who have shingles.

Risk for Recurrence of Shingles. Shingles can recur, but the risk is low (1 - 5%). Some evidence suggests that a first zoster episode boosts the immune system to ward off another attack. To support this theory, some elderly people with zoster who are exposed to children with chickenpox appear to have extra protection against a second zoster attack. In people with impaired immune systems, such as those with AIDS, a booster effect does not occur. These patients are at particular risk for multiple recurrences of shingles.

Risk Factors

The varicella-zoster virus is responsible for both chickenpox and herpes zoster, but its method of infection is different in both diseases.

Both the active varicella and zoster form of the virus can cause chickenpox.
The shingles virus in its latent (inactive) form is never infectious.

Catching Chickenpox. Most people get chickenpox from exposure to other people with chickenpox. It is most often spread through sneezing, coughing, and breathing. It is so contagious that few nonimmunized people escape this common disease when they are exposed to someone else with the disease.

People can also catch chickenpox from direct exposure to a shingles rash if they have not been immunized by vaccination or a previous bout of chickenpox. In such cases, transmission happens during the active phase when blisters have erupted but have not formed dry crusts. Herpes zoster spreads only from the rash. A person with shingles cannot transmit the virus by breathing or coughing.

Developing Shingles. Shingles itself can develop only from a reactivation of the varicella-zoster virus in a person who has previously had chickenpox. In other words, shingles itself is never transmitted from one person to another either in the air or through direct exposure to the blisters.

Between 75 - 90% of chickenpox cases occur in children under 10 years of age. Before the introduction of the vaccine, about 4 million cases of chickenpox were reported in the U.S. each year. Since a varicella vaccine became available in the U.S. in 1995, however, the incidence of disease and hospitalizations due to chickenpox has declined by nearly 90%.

The disease usually occurs in late winter and early spring months. It can also be transmitted from direct contact with the open sores. (Clothing, bedding, and such objects do not usually spread the disease.)

A patient with chickenpox can transmit the disease from about 2 days before the appearance of the spots until the end of the blister stage. This period lasts about 5 - 7 days. Once dry scabs form, the disease is unlikely to spread.

Most schools allow children with chickenpox back 10 days after onset. Some require children to stay home until the skin has completely cleared, although this is not necessary to prevent transmission.

About 500,000 cases of shingles occur each year in the U.S. Anyone who has had chickenpox has risk for shingles later in life, which means that 90% of adults in the U.S. are at risk for shingles. Shingles occurs, however, in 10 - 20% of these adult over the course of their lives, so certain factors must exist to increase the risk for such outbreaks.

The Aging Process. The risk for herpes zoster increases as people age, and the overall number of cases will undoubtedly increase as the baby boomer generation gets older. One study estimated that a person who reaches age 85 has a 50% chance of having herpes zoster. The risk for postherpetic neuralgia (PHN) is also highest in older people with the infection and increases dramatically after age 50. PHN is persistent pain and is the most feared complication of shingles.

Immunosuppression. People whose immune systems are impaired from diseases such as AIDS or childhood cancer have a risk for herpes zoster that is much higher than those with healthy immune systems. Herpes zoster in people who are HIV-positive may be a sign of full-blown AIDS. Certain drugs used for HIV, called protease inhibitors, may also increase the risk for herpes zoster.

Cancer. Cancer places people at risk for herpes zoster. At highest risk are those with Hodgkin's disease (13 - 15% of these patients develop shingles). About 7 - 9% of patients with lymphomas, and between 1 - 3% of patients with other cancers, have herpes zoster. Chemotherapy itself increases the risk for herpes zoster.

Immunosuppressant Drugs. Patients who take certain drugs that suppress the immune system are at risk for shingles (as well as other infections). They include:

Azathioprine (Imuran)
Chlorambucil (Leukeran)
Cyclophosphamide (Cytoxan)
Cyclosporine (Sandimmune, Neoral)
Cladribine (Leustatin)

These drugs are used for patients who have undergone organ transplantation and are also used for severe autoimmune diseases caused by the inflammatory process. Such disorders include rheumatoid arthritis, systemic lupus erythematosus, diabetes, multiple sclerosis, Crohn's disease, and ulcerative colitis.

Lack of Exposure to Children Infected with Chickenpox. Interestingly, one study suggested that previously infected adults who are exposed to children with chickenpox may receive an extra boost in antibody production, which can actually help them fight off herpes zoster. This means that as more children are vaccinated against chickenpox, more adults may be at risk for herpes zoster.

Risk Factors for Shingles in Children. Although most common in adults, shingles occasionally develops in children. One study reported that only 5% of cases occur in those under age 15. Children with immune deficiencies are at highest risk. Children with no immune problems but who had chickenpox before they were 1 year old also have a higher risk for shingles.

Complications

Chickenpox (varicella) rarely causes complications, but it is not always harmless. It can cause hospitalization and, in rare cases, death. Fortunately, since the introduction of the vaccine in 1995, hospitalizations have declined by nearly 90%, and there have been few fatal cases of chickenpox.

Adults have the greatest risk for dying from chickenpox, with infants having the next highest risk. Males (both boys and men) have a higher risk for a severe case of chickenpox than females. Children who catch chickenpox from family members are likely to have a more severe case than if they caught it outside the home. The older the child the higher the risk for a more severe case. But even in such circumstances, chickenpox is rarely serious in children. Other factors put individuals at specifically higher risk for complications of chickenpox.

Recurrence of Chickenpox. Recurrence of chickenpox is possible, but uncommon. One episode of chickenpox usually means lifelong immunity against a second attack. However, people who have had mild infections may be at greater risk for a breakthrough infection later on.

Reactivation of the Virus as Shingles (Herpes Zoster). The major long-term complication of varicella is the later reactivation of the herpes zoster virus and the development of shingles. Shingles occurs in about 20% of people who have had chickenpox.

Aside from itching, the complications described below are very rare.

Itching. Itching, the most common complication of the varicella infection, can be very distressing, particularly for small children. Certain home remedies are available that can alleviate the discomfort (see Treatment for Chickenpox section).

Secondary Infection and Scarring. Small scars may remain after the scabs have fallen off, but they usually clear up within a few months. In some cases, a secondary infection may develop at sites which the patient has scratched. The infection is usually caused by the bacteria Staphylococcus aureus or Streptococcus pyogenes. Permanent scarring may occur as a result. Children with chickenpox are at much higher risk for this complication than adults are, possibly because they are more likely to scratch.

Ear Infections. Some children are at higher risk for ear infections from chickenpox. Hearing loss is a very rare result of this complication.

A middle ear infection is also known as otitis media. It is one of the most common of childhood infections. With this illness, the middle ear becomes red, swollen, and inflamed because of bacteria trapped in the eustachian tube.

Bacterial Superinfection. Bacterial superinfection of the skin caused by group A streptococcus is the most common serious complication of chickenpox (but it is still rare). The infection is usually mild, but if it spreads in deep muscle, fat, or in the blood, it can be life-threatening. Infection can cause serious conditions such as necrotizing fasciitis (the so-called flesh-eating bacteria) and toxic shock syndrome (TSS).

Symptoms include:

A persistent or recurrent high fever
Redness, pain, and swelling in the skin and the tissue beneath

Pneumonia. Pneumonia is suspected if coughing and abnormally rapid breathing develop in patients who have chickenpox. Adults and adolescents with chickenpox are at some risk for serious pneumonia. Pregnant women, smokers, and those with serious medical conditions are at higher risk for pneumonia if they have chickenpox. Oxygen and intravenous acyclovir are key treatments for this condition. Pneumonia that is caused by varicella can result in lung scarring, which may impair oxygen exchange over the following weeks, or even months.

Click the icon to see an image of pneumonia.

Effects on the Brain and Central Nervous System.

Inflammation in the Brain. Encephalitis and meningitis, infections or inflammation in the central nervous systems, have occurred in a few varicella patients, both children and adults. This condition can be very dangerous, causing coma and even death. Fortunately, it is extremely rare. Symptoms vary. The patient may become over-agitated or may exhibit loss of coordination and poor balance.
Stroke. Although stroke in children is extremely rare, a condition called cerebral vasculitis, in which blood vessels in the brain become inflamed, has been associated with varicella-zoster. Varicella may be a factor in some cases of stroke in young adults.

Effects During Pregnancy. The risk for chickenpox in a pregnant woman is very low (1 - 7 cases in 10,000). However, chickenpox places the woman at risk for life-threatening pneumonia. Infection in the pregnant woman in the first trimester also poses a 1 - 2% chance for infecting the developing fetus, which is an extremely serious condition. (Herpes zoster is even rarer in pregnant women, and there is almost no risk for the unborn child in such cases.)

Disseminated Varicella. Disseminated varicella, chickenpox that spreads to organs in the body, is extremely serious and is a major problem for patients with compromised immune systems. An immune system may become compromised as a result of diseases such as AIDS, inherited conditions, or certain drugs. For example, disseminated varicella occurs in up to 35% of children with chickenpox who are taking cancer chemotherapy. In such cases, mortality rates are between 7 - 30%.

Reye Syndrome. Reye syndrome, a disorder that causes sudden and dangerous liver and brain damage, is a complication of chickenpox and other viruses in children who take aspirin. The disease can lead to coma and is life-threatening. Symptoms include rash, vomiting, and confusion beginning about a week after the onset of the disease. Because of the strong warnings against children taking aspirin, this condition is, fortunately, nearly nonexistent.

Other Rare Complications of Chickenpox. Other extremely rare complications of varicella include problems in blood clotting, and inflammation of the nerves in the hands and feet. Inflammation can also occur in other areas of the body, such as the heart, testicles, liver, joints, or kidney. Children should never be given aspirin when they have a viral infection.

Pain. The pain and discomfort of the active herpes zoster infection is the primary symptom and complication of herpes zoster. The pain usually takes one of these forms:

Continuous burning or aching pain
Periodic piercing pain
Spasm similar to electric shock

Such experiences may also be more intense than even normal responses, defined in the following ways:

Allodynia is pain caused by factors, such as a light touch of clothing or a cold wind, which occurs from very little stimulation.
Hyperalgesia is a more intense painful response to a normally painful experience.

The pain tends to be more severe at night. Temperature changes can also affect pain. The pain may extend beyond the areas of the initial zoster attack. In most cases, it does not affect daily life. Rarely, however, the pain of herpes zoster affects sleep, mood, work, and overall quality of life. This can lead to fatigue, loss of appetite, depression, social withdrawal, and impaired daily functioning.

Itching. Many patients report itching (postherpetic itch) as the primary symptom, rather than pain. In rare cases, it can be disabling.

Postherpetic Neuralgia (PHN). Postherpetic neuralgia (PHN) is pain that persists for longer than a month after the onset of herpes. It is the most common severe complication of shingles. It is not clear why PHN occurs. Some theories for its development are:

The herpes zoster virus appears to produce persistent inflammation in the spinal cord that causes long-term damage, including nerve scarring.
Nerves that are injured in the initial attack may regrow abnormally and provoke an exaggerated response in the brain that signals intense sensitivity or pain.

In people with herpes zoster, the risk of developing PHN ranges from 10 - 70%. In general, however, the risk is likely to be in the lower range. People with impaired immune systems do not seem to be at any higher risk for persistent PHN than those with normal immune systems.

The following are risk factors for PHN:

Age. PHN affects about 25% of herpes zoster patients over 60 years old. The older a person is, the longer PHN is likely to last. It rarely occurs in people under age 50.
Gender. Some studies suggest that women may be at slightly higher risk for PHN than men.
Severe or Complicated Shingles. People who had prodromal symptoms or a severe attack (numerous blisters and severe pain) during the initial shingles episode are also at high risk for PHN. The rate is also higher in people whose eyes have been affected by zoster.

In most cases, PHN resolves within 3 months. Some experts define persistent pain after a herpes zoster attack as subacute herpetic neuralgia if it lasts between 1 - 3 months and as PHN only if it lasts beyond 3 months. Studies report that only about 10% of patients experience pain after a year. Unfortunately, when PHN is severe and treatments have not been very effective, the persistent pain and abnormal sensations can be profoundly frustrating and depressing for patients.

Secondary Infection in the Blisters. If the blistered area is not kept clean and free from irritation, it may become infected with Streptococcus A or Staphylococcus bacteria. If the infection is severe, scarring can occur.

Guillain-Barre Syndrome. Guillain-Barre syndrome is caused by inflammation of the nerves and has been associated with a number of viruses, including herpes zoster. The arms and legs become weak, painful, and, sometimes, even paralyzed. The trunk and face may be affected. Symptoms vary from mild to severe enough to require hospitalization. The disorder resolves in a few weeks to months. Other viruses ( C. jejuni, cytomegalovirus, and Epstein-Barr) may have a stronger association to this syndrome than herpes zoster. One study, in fact, found no higher incidence of herpes zoster virus in patients with Guillain-Barre than in the general population.

Effects on Face and Ears.

Ramsay Hunt Syndrome. Ramsay Hunt syndrome occurs when herpes zoster causes facial paralysis and rash on the ear (herpes zoster oticus) or in the mouth. Symptoms include severe ear pain and hearing loss, ringing in the ear, loss of taste, nausea, vomiting, and dizziness. Ramsay Hunt syndrome may also cause a mild inflammation in the brain. The dizziness may last for a few days or even for weeks, but usually resolves. Severity of hearing loss varies from partial to total; however, this too usually always goes away. Facial paralysis, on the other hand, may be permanent.
Bell's Palsy. Bell's palsy is partial paralysis of the face. There is some indication that this syndrome may suggest a reactivation of herpes zoster, even if no rash appears.

In some cases, it is difficult to distinguish between Bell's palsy and Ramsay Hunt syndrome, particularly in the early stages. Ramsay Hunt syndrome tends to be more severe than Bell's palsy. Although evidence is weak on treating facial involvement of herpes zoster, some experts recommend oral prednisone (a corticosteroid) and an antiviral drug within 7 days of symptom onset. Even though nearly all cases of Bell's palsy and the majority of Ramsay Hunt syndrome resolve without problems, the possibility of residual symptoms with Ramsay Hunt and the early resemblance between the two syndromes warrants this treatment.

Effects on the Brain. Inflammation of the membrane around the brain (meningitis) or in the brain itself (encephalitis) is a rare complication in people with herpes zoster. The encephalitis is generally mild and resolves in a short period. In rare cases, particularly in patients with impaired immune systems, it can be severe and even life-threatening.

Click the icon to see an image of the meninges of the brain.

Effects in the Urinary Tract. In rare situations, herpes zoster can infect the urinary tract and cause difficulty in urination. The condition is temporary but may require a catheter for patients who have trouble urinating.

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

Infections in the Eye. If shingles occurs in the face, the eyes are at risk, particularly if the path of the infection follows the side of the nose. If the eyes become involved (called herpes zoster ophthalmicus), a severe infection can occur that is difficult to treat and can threaten vision. AIDS patients may be at particular risk for a chronic infection in the cornea of the eye.

Click the icon to see an image of the eye.

Herpes zoster can also cause a devastating infection in the retina called imminent acute retinal necrosis syndrome. In such cases, visual changes develop within weeks or months after the herpes zoster outbreak has resolved. Although this complication usually follows a herpes outbreak in the face, it can occur after an outbreak in any part of the body. Prompt treatment with acyclovir can often halt its progress, at least in people with healthy immune systems. Either acyclovir or valacyclovir, a similar drug, may prevent other eye complications, such as conjunctivitis (pink eye), inflammation of the cornea, and pain.

Disseminated Herpes Zoster. As with disseminated chickenpox, disseminated herpes zoster, which spreads to other organs, can be serious to life-threatening, particularly if it affects the lungs. People with compromised immune systems are at greatest danger, with risk of 5 - 25%. It is very rare in people with healthy immune systems.

In very rare cases, herpes zoster has been associated with Stevens-Johnson syndrome, an extensive and serious condition in which widespread blisters cover mucous membranes and large areas of the body.

Elderly people. The older the patient, the higher the risk for complications from either chickenpox or shingles. Adults who smoke are at particularly higher risk for pneumonia from chickenpox.

Patients with Compromised Immune Systems. People with suppressed immune systems from diseases such as AIDS, leukemia, or those who take immunosuppressive drugs, are at the highest risk for severe and even unusual forms of VZV. Examples include chronic chickenpox with persistent sores, or disseminated varicella-zoster (in which the infection spreads to internal organs).

Patients with Serious Illnesses. People with serious illnesses may be at risk for complications of the varicella-zoster virus. Patients with diseases, such as Hodgkin's disease, who receive bone marrow or stem cell transplants are at higher risk for herpes zoster and its complications. An inactivated vaccine given before the procedure may be helpful.

Pregnant Women. Pregnant women who become infected with the varicella-zoster virus, whether in the form of chickenpox or shingles, are at increased risk for serious pneumonia.

The risk for the infant is lower or higher depending on when the mother became infected.
Chickenpox in the mother during early pregnancy poses a slightly increased risk for birth defects in the infant, but it is not usually viewed as grounds for terminating a pregnancy.
The highest risk for birth defects is about 2%, which usually occurs if the mother has chickenpox between the 13th and 20th week. Even in such cases, birth defects may only result in minor skin abnormalities. More serious defects include a smaller than normal head, eye problems, low birth weight, and mental retardation.
If women develop chickenpox (not shingles) within 5 days before and 2 days after delivery, their newborns are at risk for life-threatening varicella.

Newborns and Infants. Chickenpox in newborns is a life-threatening condition. Although chickenpox can still be very dangerous in older infants, most are protected by antibodies in breast milk from mothers who have had chickenpox. Children under age 1 who develop chickenpox are at higher risk for childhood shingles. All infants should have as little exposure as possible to people with chickenpox.

Vaccination

There are two types of varicella vaccines:

A chickenpox vaccine for vaccinating children, adolescents, and some adults
A shingles vaccine for vaccinating adults age 60 years and older

A live-virus vaccine (Varivax) produces persistent immunity against chickenpox. [A vaccine (Proquad) for children ages 1 - 12 years now combines measles, mumps, rubella, and varicella in one product.] The vaccine can prevent chickenpox or reduce the severity of the illness if it is used within 3 days, and possibly up to 5 days, after exposure to the infection.

In 2007, the U.S. Centers for Disease Control’s Advisory Committee on Immunization Practices (ACIP) revised the immunization schedule for the chickenpox vaccine. The new schedule recommends that children receive TWO doses of the chickenpox vaccine with:

The first dose administered when the child is 12 – 15 months years of age, and
The second dose administered when the child is 4 – 6 years of age

As of 2007, all children should routinely receive these vaccinations. For children who have previously received one dose of the chickenpox vaccine, the ACIP recommends that they receive a “catch-up” second dose during their regular doctor’s visit. This second dose can be given at any time as long as it is at least 3 months after the first dose. Experts pushed for the new second-dose policy due to a number of recent chickenpox outbreaks among previously vaccinated schoolchildren.

A 2007 study in the New England Journal of Medicine also found that one dose of the vaccine may not be enough to provide complete immunity. Among 350,000 patients researchers studied over 10 years, 11,356 were reported to have chickenpox. A total of 1,080 of the patients had breakthrough disease, a modified form of chickenpox with a mild rash that can occur in some vaccinated people. According to the study, those most at risk were children ages 8 - 12 years who had been vaccinated at least 5 years before their current chickenpox infection.

The U.S. Centers for Disease Control and Prevention (CDC) recommends that every healthy adult without a known history of chickenpox be vaccinated. Adults in the following groups should strongly consider vaccination:

Those with high risk of exposure or transmission (hospital or day care workers, parents of young children)
People in contact with those who have compromised immune systems
Nonpregnant women of childbearing age
International travelers

As with other live-virus vaccines, the chickenpox vaccine is not recommended for:

Women who are pregnant or who may become pregnant within 30 days of vaccination.
People whose immune systems are compromised by disease or drugs (such as after organ transplantation). Experts report that the vaccine is safe in children with acute lymphoblastic leukemia (ALL). Certain children who are HIV-positive may be candidates for the vaccine. An inactivated chickenpox vaccine may be safe for patients undergoing bone marrow transplants when given before and after the operation.

Patients who cannot be vaccinated but who are exposed to chickenpox receive immune globulin antibodies against varicella virus. This helps prevent complications of the disease if they become infected.

Discomfort at the Injection Site. About 20% of vaccine recipients have pain, swelling, or redness at the injection site.
Severe Side Effects. Only about 5% of adverse reactions are serious. Such events include seizures, pneumonia, anaphylactic reaction, encephalitis, Stevens-Johnsons syndrome, neuropathy, herpes zoster, and blood abnormalities.
Risk of Transmission. The vaccine may produce a mild rash within about a month of the vaccination, which can transmit chickenpox to others. Individuals who have recently been vaccinated should avoid close contact with anyone who might be susceptible to severe complications from chickenpox until the risk for a rash passes.
Later Infection. Months or even years after the vaccination, some people develop a mild infection termed modified varicella-like syndrome (MVLS). The condition appears to be less contagious and has fewer complications than naturally acquired chickenpox.

In 2006, a shingles vaccine was approved for use in the United States. The zoster vaccine (Zostavax) is a stronger version of the chickenpox vaccine. Study results published in 2005 suggested that the zoster vaccine can prevent about half of all shingles cases and two-thirds of postherpetic neuralgia cases. The CDC recommends that all adults age 60 years and older who have intact immune systems should receive this vaccine

Varicella-zoster immune globulin (VariZIG) is a substance that triggers an immune response against the varicella-zoster virus. It is used to protect high-risk patients who are exposed to chickenpox, or those who cannot receive a vaccination of the live virus. Such groups include:

Pregnant women with no history of chickenpox
Newborn infants whose mothers had signs or symptoms of chickenpox around the time of delivery (5 days before to 2 days after)
Premature infants
Immunocompromised children and adults with no antibodies to VZV
Recipients of bone-marrow transplants (even if they have had chickenpox)
Patients with a debilitating disease (even if they have had chickenpox)

For these patients, VariZIG should be given within 96 hours of exposure to someone with chickenpox. (Note: VariZIG is a new formulation of an older drug called VZIG, which is no longer being produced.)

Diagnosis

Both chickenpox (varicella) and shingles (zoster) can usually be diagnosed by symptoms alone. If a diagnosis is still unclear after a physical examination, diagnostic tests may be required.

Either variation of the virus may be confused with other disorders.

Ruling out Disorders that Resemble Chickenpox. Chickenpox, particularly in early stages, may be confused with herpes simplex (the disorder more commonly referred to as "herpes"), or impetigo, insect bites, and scabies.

Ruling out Disorders that Resemble Shingles. The early prodrome stage of shingles can cause severe pain on one side of the lower back, chest, or abdomen before the rash appears. It therefore may be mistaken for disorders, such as gallstones, that cause acute pain in internal organs.

In the active rash stage, shingles may be confused with herpes simplex, particularly in young adults if the blisters occur on the buttocks or around the mouth. Herpes simplex, however, does not usually generate chronic pain.

A diagnosis may be difficult if herpes zoster takes a non-typical course, such as with Bell's palsy or Ramsay Hunt syndrome in the face, or if it affects the eye, or causes fever and delirium.

In most cases of chickenpox and shingles, the symptoms alone are sufficient to make a diagnosis. In some patients, such as those who are immunosuppressed, if the symptoms are not straightforward the doctor performs one or more additional tests to detect the virus itself. The tests usually aim to distinguish between varicella-zoster and herpes simplex viruses.

Virus Culture. A viral culture uses specimens taken from the blister, fluid in the blister, or sometimes spinal fluid. They are sent to a laboratory, where it takes 1 - 14 days to detect the virus in the preparation made from the specimen. It is also sometimes used in vaccinated patients to determine if a varicella-like infection is caused by a natural virus or by the vaccine. This test is useful, but it is sometimes difficult to recover the virus from the samples.

Immunofluorescence Assay. Immunofluorescence is a diagnostic technique used to identify antibodies to a specific virus. In the case of herpes zoster, the technique uses ultraviolet rays applied to a preparation composed of cells taken from the zoster blisters. The specific characteristics of the light as seen through a microscope will identify the presence of the antibodies. This test is less expensive than a culture, more accurate, and results are faster.

Polymerase Chain Reaction (PCR). Polymerase chain reaction (PCR) techniques use a piece of the DNA of the virus, which is then replicated millions of times until the virus is detectable. This technique is expensive but is useful for unusual cases, such as identifying infection in the central nervous system.

Treatment for Chickenpox

Acetaminophen. Patients with chickenpox do not have to stay in bed unless fever and flu symptoms are severe. To relieve discomfort, a child can take acetaminophen (Tylenol), with doses determined by the doctor. A child should never be given aspirin, or medications containing aspirin, as aspirin increases the risk for a dangerous condition called Reye syndrome.

Soothing Baths. Frequent baths are particularly helpful in relieving itching, when used with preparations of finely ground (colloidal) oatmeal. Commercial preparations (Aveeno) are available in drugstores, or one can be made at home by grinding or blending dry oatmeal into a fine powder. Use about 2 cups per bath. The oatmeal will not dissolve, and the water will have a scum. A 1/2 - 1 cup of baking soda in a bath may also be helpful.

Lotions. Calamine lotion and similar over-the-counter preparations can be applied to the blisters to help dry them out and soothe the skin.

Antihistamines. For severe itching diphenhydramine (Benadryl) is useful and may help children sleep.

Preventing Scratching. Small children may have to wear mittens so that they don't scratch the blisters and cause a secondary infection. All patients with varicella, including adults, should have their nails trimmed short.

Acyclovir is an antiviral drug that may be used in adult varicella patients or those of any age with a high risk for complications and severe forms of chickenpox. The drug may also benefit smokers with chickenpox, who are at higher than normal risk for pneumonia. Some experts recommend its use for children who catch chickenpox from other family members because such patients are at risk for more serious cases. To be effective, oral acyclovir must be taken within 24 hours of the onset of the rash. Early intravenous administration of acyclovir is essential treatment for chickenpox pneumonia.

Treatment for an Acute Shingles Attack

The treatment goals for an acute attack of herpes zoster include:

Reduce pain
Reduce discomfort
Hasten healing of blisters
Prevent the disease from spreading

Over-the-counter (OTC) remedies are often effective in reducing the pain of an attack. Antiviral drugs (acyclovir and others), oral corticosteroids, or both are sometimes given to patients with severe symptoms, particularly if they are older and at risk for postherpetic neuralgia (PHN). In addition, psychological therapies aimed at coping and reducing the effects of pain may be useful.

Applied Cold. Cold compresses soaked in Burrow's solution (an OTC remedy) and cool baths may help relieve the blisters. It is important not to break blisters as this can cause infection. Experts advise against warm treatments, which can intensify itching. Patients should wear loose clothing and use clean loose gauze coverings over the affected areas.

Itch Relief. In general, to prevent or reduce itching, home treatments are similar to those used for chickenpox. Patients can try antihistamines, (particularly Benadryl), oatmeal baths, and calamine lotion.

Over-the-Counter Pain Relievers. For an acute shingles attack, patients may take over-the-counter pain relievers:

Children should take acetaminophen. (Shingles is very rare in children.)
Adults may take aspirin or other nonsteroidal anti-inflammatory drugs, such as ibuprofen (Advil). Such remedies, however, are not very effective for postherpetic neuralgia.

Nucleoside Analogues. The best class of drugs developed against varicella-zoster are those known as nucleoside, or guanosine, analogues, which are able to block viral reproduction. None of these drugs can actually destroy the virus and cure the disease, but they can significantly reduce the severity of the attack, hasten healing, and reduce the duration. There is some evidence that early treatment with these drugs can reduce the risk for postherpetic herpes.

These anti-viral drugs are usually taken for 7 days. Ideally they should be started within 72 hours of the onset of infection. The earlier they are given the more effective these drugs are, but they can be helpful even if treatment is started after 3 days. Combinations of antiviral therapy with other drugs, such as tricyclic antidepressants or anticonvulsant drugs, are under investigation

Acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are approved for shingles. Acyclovir is the oldest, most studied of these drugs, but either famciclovir (Famvir) or valacyclovir (Valtrex), which are both metabolized into acyclovir, are now preferred to treat herpes zoster in most patients. They relieve symptoms better than acyclovir and require fewer daily doses (typically three) than the five doses needed with acyclovir.

Because herpes zoster tends to resolve fairly quickly in young adults, these drugs are generally reserved for patients at greatest risk for complications or persistent pain. They include:

Elderly people
Those with infections that threaten the eye
Patients who are HIV positive or immunocompromised in other ways
Patients whose infection covers a larger-than-average surface area of the skin
Those with very severe pain

These drugs appear to have little or no harmful effect on healthy cells and can penetrate most body tissues, including cerebrospinal fluid. Evidence to date suggests that they are safe during pregnancy.

Possible side effects of nucleoside analogues include rash, headache, fatigue, tremor, nausea and vomiting. Seizures are a very rare side effect. Patients with AIDS or other diseases that compromise the immune system are at increased risk for kidney damage and blood clots. Patients with suppressed immune systems are also more likely to have viral resistance to these drugs. These drugs are safe to take during pregnancy.

Foscarnet. Foscarnet (Foscavir) is a powerful antiviral drug known as a pyrophosphate analogue. It is used in cases of VZV strains that have become resistant to acyclovir and similar drugs. Administered intravenously, the drug can have toxic effects. It can impair kidney function (which is reversible) and cause seizures. Fever, nausea, and vomiting are common side effects. It can also cause ulcers on genital organs. As with other drugs, it does not cure shingles.

Brivudin. Brivudin (Helpin, Zostex) is another anti-viral drug, but it is not available in the U.S. It needs to be taken only once a day.

Oral corticosteroids, including prednisolone or prednisone, are powerful anti-inflammatory medications. They have some benefit for reducing pain and accelerating healing in acute attacks when used with acyclovir. (They are not recommended without acyclovir.) They also may be helpful for improving symptoms of Bell's palsy and Ramsay Hunt syndrome. Corticosteroids do not appear to prevent a further shingles attack or reduce the risk for PHN. Side effects of corticosteroids can be severe, and patients should take oral steroids at as low a dose and for as short a time as possible. (Injected or intravenous steroids, however, may offer specific relief for PHN without significant side effects.)

Epidural blocks are injections of local anesthetics and steroids outside the tough membrane surrounding the spinal cord (the dura matter). The injected drugs block the nerves and may offer relief from acute herpes zoster pain for some people. A 2006 study found that a single epidural injection helps slightly to relieve shingles pain for a month, but the effect does not last any longer. The injection does not help prevent postherpetic neuralgia.

Treatment for Postherpetic Neuralgia

Postherpetic neuralgia (PHN) is difficult to treat. Once PHN develops, a patient may need a multidisciplinary approach that involves a pain specialist, psychiatrist, primary care physician, and other health care providers.

In 2004, the American Academy of Neurology (AAN) issued treatment guidelines for postherpetic neuralgia based on an extensive review of published studies. The AAN recommends:

Tricyclic antidepressants (amitriptyline, nortriptyline, desipramine, maprotiline)
Anticonvulsants (gabapentin and pregabalin)
Lidocaine skin patches
Opioids (oxycodone, methadone, morphine)

Topical Pain Relievers. Creams, patches, or gels containing various substances can provide some pain relief.

Lidocaine and Other Anesthetic Patches. A patch that contains the anesthetic lidocaine (Lidoderm) is approved specifically for postherpetic neuralgia (PHN). One to four patches can be applied over the course of 24 hours. Another patch (EMLA) contains both lidocaine and prilocaine, a second anesthetic. The most common side effects are skin redness or rash.
Capsaicin (Zostrix) is prepared from the active ingredient in hot chili peppers. An ointment form has been approved for postherpetic neuralgia. Its benefits are limited, however. A patch form that uses a higher than standard dose may work better. In one study, it reduced pain by 33% in nearly half of patients. Capsaicin should not be used until the blisters have completely dried out and are falling off the skin. Capsaicin ointment should be handled using a glove, and applied to affected areas three or four times daily. The patient will usually experience a burning sensation when the drug is first applied, but this sensation diminishes with use. It may take up to 6 weeks for the patient to experience its full effect, and about a third of patients cannot tolerate the burning sensation.
Topical Aspirin. Topical aspirin, known chemically as triethanolamine salicylate (Aspercreme), may bring relief.
Menthol-Containing Preparations. Topical drugs containing menthol, such as high-strength Flexall 454, may be helpful.

Skin Coolants. Ethyl chloride (Chloroethane) and fluori-methane are chemicals that cool the blood vessels in the skin. Sprays that contain these chemicals are not anesthetics, but are used to inactivate the sensitive areas. To use the spray, the patient must be in a comfortable position. The spray bottle is held upside-down, about 12 - 18 inches from the targeted area, and the face must be covered if the spray is being used near the head.

Tricyclic antidepressants relieve pain in up to two-thirds of patients. These drugs not only relieve depression, which can be common in PHN sufferers, but certain tricyclics specifically block sodium channels, which play a role in causing pain in PHN. Nortriptyline (Pamelor, Aventyl), amitriptyline (Elavil, Endep), and desipramine (Norpramin) are standard drugs.

According to one study, two-thirds of patients obtain pain relief if they take tricyclics within 3 months to a year after a herpes zoster attack. The drugs are less successful when taken after that. It may take several weeks for the drugs to become fully effective. They do not work as well in patients who experience burning pain or allodynia (pain that occurs with normally non-painful stimulus, such as a light touch or wind).

Unfortunately, tricyclics have side effects that are particularly severe in the elderly, who are also more likely to have PHN. Desipramine and nortriptyline have fewer side effects than amitriptyline and are preferred for older patients. Side effects include dry mouth, blurred vision, constipation, dizziness, difficulty urinating, disturbances in heart rhythms, and an abrupt drop in blood pressure when standing up.

Certain anticonvulsant drugs have effects that block over-excitation of nerve cells and may be helpful for PHN patient. (Anticonvulsant drugs are also known as anti-seizure drugs.)

Gabapentin. Gabapentin (Neurontin) was the first anticonvulsant drug approved for PHN. Studies suggest significant pain relief in patients with PHN and reduction in the use of opioids. Many patients also report improved quality of life, including better sleep. Gabapentin is also showing promise in combination with valacyclovir for reducing pain from an acute herpes zoster attack.

Side effects include skin rashes, increased risk for infection, headache, dizziness, sleepiness, swelling, and upset stomach. Some people experience visual disturbances, ringing in the ears, agitation, or odd movements when drug levels are at their peak. These side effects may limit their value in older people who are at risk of falling. In general, however gabapentin is safer than tricyclic antidepressants for elderly patients.

Pregabalin. Pregabalin (Lyrica) is similar to gabapentin. Like gabapentin, side effects can include sleepiness and dizziness

Other Anticonvulsant Drugs. The AAN guidelines found insufficient evidence to recommend carbamazepine (Tegretol).

Opioids. Patients with severe pain that does not respond to tricyclic antidepressants may need powerful painkilling opioid drugs. They may be taken by mouth or delivered through a skin patch. Oxycodone is the standard opioid for PHN. Morphine is also used. Methadone (Dolophine) may also be helpful. A 2005 study found that morphine worked best when combined with the anticonvulsant gabapentin. Constipation, drowsiness, and dry mouth are common side effects of opioids.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. It has opioid-like properties but is not as addictive. (Dependence and abuse have been reported, however.) It can cause nausea but not severe gastrointestinal problems, as NSAIDs can. Studies suggest it might be very helpful for PHN patients, particularly those with heart problems or other conditions that restrict tricyclic antidepressants.

Intrathecal Corticosteroid Injections. Epidural (also called intrathecal) injections of corticosteroids are administered within the the tough membrane surrounding the spinal cord. The corticosteroids are sometimes combined with anesthetics. Some older studies indicated that these injections may relieve PHN pain, but this treatment is still under investigation and is not common medical practice. A 2006 study reported that epidural injections may provide slight temporary relief for acute shingles attacks, but they do not prevent PHN.

Antiviral Drugs. Researchers are investigating whether treatment with antiviral drugs may help reduce the pain associated with postherpetic neuralgia. A small 2006 study suggested that a 2-week course of therapy with intravenous acyclovir, followed by 1-month treatment with oral valacyclovir, may help relieve pain.

Surgery. Certain surgical techniques in the brain or spinal cord attempt to block nerve centers associated with postherpetic neuralgia. These methods carry risk for permanent damage, however, and should be used only as a last resort when all other methods have failed and the pain is intolerable. Most studies indicate that surgery does not relieve PHN pain.

Stress Reduction Techniques. A number of relaxation and stress-reduction techniques may be helpful for managing chronic pain. They include meditation, deep breathing exercises, biofeedback, and muscle relaxation. Such techniques may apply to those with severe pain from acute infection and from persistent long-term postherpetic neuralgia. [See In-Depth Report #31: Stress.]

Behavioral Cognitive Therapy. Behavioral cognitive therapy is showing benefit in enhancing patients' beliefs in their own abilities for dealing with pain. Using specific tasks and self-observation, patients gradually shift their fixed ideas that they are helpless against the pain that dominates their lives to the perception that it is a manageable experience. The skill of the therapist is very important to its success.

Many people with chronic pain such as PHN turn to alternative treatments for relief. Aside from hypnosis, little evidence indicates that these treatments work for PHN. Remedies include:

Hypnosis
Topical use of diluted apple cider vinegar
Acupuncture
Colostrum (a pre-milk fluid produced by mammals)
Pantothenic acid (Vitamin B5)

Resources

www.cdc.gov -- Centers for Disease Control and Prevention
www.niaid.nih.gov -- National Institute of Allergy and Infectious Diseases
www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.neuropathy.org -- Neuropathy Association

References

American Academy of Pediatrics Committee on Infectious Diseases. Recommended immunization schedules for children and adolescents--United States, 2007. Pediatrics. 2007 Jan;119(1):207-8.

Centers for Disease Control and Prevention (CDC). A new product (VariZIG) for postexposure prophylaxis of varicella available under an investigational new drug application expanded access protocol. MMWR Morb Mortal Wkly Rep. 2006 Mar 3;55(:209-10.

Centers for Disease Control and Prevention (CDC). Varicella outbreak among vaccinated children--Nebraska, 2004. MMWR Morb Mortal Wkly Rep. 2006 Jul 14;55(27):749-52.

Chaves SS, Gargiullo P, Zhang JX, Civen R, Guris D, Mascola L, et al. Loss of Vaccine-Induced Immunity to Varicella over Time. N Engl J Med. 2007 Mar 15;356(11):1121-9.

Davis MM, Marin M, Cowan AE, Guris D, Clark SJ. Physician attitudes regarding breakthrough varicella disease and a potential second dose of varicella vaccine. Pediatrics. 2007 Feb;119(2):258-64.

Li Q, Ali MA, Cohen JI. Insulin degrading enzyme is a cellular receptor mediating varicella-zoster virus infection and cell-to-cell spread. Cell. 2006 Oct 20;127(2):305-16.

Lopez AS, Guris D, Zimmerman L, Gladden L, Moore T, Haselow DT, et al. One dose of varicella vaccine does not prevent school outbreaks: is it time for a second dose? Pediatrics. 2006 Jun;117(6):e1070-7.

Quan D, Hammack BN, Kittelson J, Gilden DH. Improvement of postherpetic neuralgia after treatment with intravenous acyclovir followed by oral valacyclovir. Arch Neurol. 2006 Jul;63(7):940-2.

Review Date:
3/15/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Foot pain

FitSugar — Wed, 08 Oct 2008 17:35:02 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Treatment: Corns and Callus...
Treatment: Bunions
Treatment: Hammertoes
Treatment: Ingrown Toenails...
Treatment: Forefoot Pain...
Treatment: Heel Pain
Treatment: Flat Feet
Treatment: Abnormally High ...
Treatment: Tarsal Tunnel Sy...
Treatment: Foot Injury
Prevention
Shoes
Insoles and Orthotics
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Treatment for Ingrown Toenail:

Orthonyxia, a surgical technique that implants a small metal brace into the top of the nail, was as effective as traditional surgical techniques for preventing ingrown toenail from recurring, according to one study.
A nonsurgical method for treating ingrown toenail with chemicals uses either sodium hydroxide or phenol, but one study shows that sodium hydroxide procedures have a better outcome and faster recovery than phenol procedures.

Treatment for Forefoot Pain:

Ultrasound-guided injection of alcohol might provide relief from Morton's neuroma, according to one study. Symptoms improved in 94% of patients who had the treatment, a success rate comparable to that of surgery.

Treatment for Heel Pain:

NSAIDs reduce pain and disability in people with plantar fasciitis when used with other techniques, such as night splints and stretching.
Studies show that extracorporeal shockwave therapy provides a very small reduction in heel pain without side effects. It may be a good option for patients who haven't responded well to conservative treatment.

Work-related Foot Problems:

An estimated 120,000 job-related foot injuries occur every year, about a third of them involving the toes. A number of foot problems -- including arthritis of the foot and ankle, toe deformities, pinched nerves between the toes, plantar fasciitis, adult-acquired flat foot, and tarsal tunnel syndrome -- have been attributed to repetitive use at work.

Introduction

Foot pain is very common. About 75% of people in the United States have foot pain at some time in their lives. Most foot pain is caused by shoes that do not fit properly or that force the feet into unnatural shapes (such as pointed-toe, high-heeled shoes).

The foot is a complex structure of 26 bones and 33 joints, layered with an intertwining web of more than 120 muscles, ligaments, and nerves. It serves the following functions:

Supports weight
Acts as a shock absorber
Serves as a lever to propel the leg forward
Helps maintain balance by adjusting the body to uneven surfaces

Because the feet are very small compared with the rest of the body, the impact of each step exerts tremendous force upon them. This force is about 50% greater than the person's body weight. During a typical day, people spend about 4 hours on their feet and take 8,000 - 10,000 steps. This means that the feet support a combined force equivalent to several hundred tons every day.

Foot pain generally starts in one of three places: the toes, the forefoot, and the hindfoot.

The Toes. Toe problems most often occur because of the pressure imposed by ill-fitting shoes.

The Forefoot. The forefoot is the front of the foot. Pain originating here usually involves one of the following bone groups:

The metatarsal bones (five long bones that extend from the front of the arch to the bones in the toe)
The sesamoid bones (two small bones embedded at the top of the first metatarsal bone, which connects to the big toe)

The Hindfoot. The hindfoot is the back of the foot. Pain originating here can extend from the heel, across the sole (known as the plantar surface), to the ball of the foot (the metatarsophalangeal joint).

Condition	Location	Symptoms	Recommended Footwear
Toe Pain
Corns and calluses	Around toes, usually little toe, bottom of feet or areas exposed to friction.	Hard, dead, yellowish skin.	Wide (box-toed) shoes; soft cushions under heel or ball of foot, or customized or gel insoles for calluses. Doughnut-shaped pads for corns.
Ingrown toenails	Toenails.	Nail curling into skin causes pain, swelling, and, in extreme cases, infection.	Sandals, open-toed shoes.
Bunions and bunionettes (tailor's bunion)	Big toe (bunions) or little toe (bunionettes).	The following can occur alone or in combination: Metatarsus primus varus. The first (big toe) metatarsal bone shifts away from the second, and the big toe points inward. Medial exostosis. This is a bony bump at the base of the big toe, which protrudes outward. Area next to bony bump is red, tender, and occasionally filled with fluid. Toe joint may be inflamed. Hallux valgus. This is a deformity in which the bone and joint of the big toe shift and grow inward, so that the second toe crosses over the big toe.	Soft, wide-toed shoes or sandals. Bunion shields or splints. Thick doughnut-shaped moleskin pads, custom-made orthotics or foot slings, if necessary. Avoid shoes with stitching along the side of the "bump."
Morton's neuroma (also called interdigital neuroma)	Inflammation of the nerve, usually between the third and fourth toes and bottom of the foot near these toes.	Cramping and burning pain, or electric-shock sensation. The condition may produce a thick protective sheath around the nerve that feels like a ball. This may be detected by pressing top to bottom on the top of the foot using one hand and moving the other hand from side to side. Morton's neuroma is aggravated by prolonged standing and relieved by removal of the shoes and forefoot massage.	Wide (box-toed) shoes. Orthotic or insole with pad that reduces stress on the painful area.
Hammertoe or claw toe	Usually second toe, but may develop in any or all of the three middle toes.	Toes form hammer or claw shape. In hammertoe, the first knuckle of the toe is mainly affected. In claw toe the entire toe is deformed. No pain at first, but pain increases as tendon becomes tighter and toes stiffen.	Wide (box-toed) shoes. Toe pads or specially designed shields, splints, caps, or slings. (Splints or slings are not for people with diabetes.)
Front-of-the-Foot Pain
Metatarsalgia	Ball of the foot.	Acute, recurrent, or chronic pain without a known cause.	Wide (box-toed) shoes. Orthotic with pad that reduces metatarsal pressure. Gel cushions. Metatarsal bandage.
Stress fracture	Most often in the area beneath the second or third toe.	Sudden pain (which persists) when injury occurs.	Low-heeled shoes with stiff soles.
Sesamoiditis	Ball of foot beneath big toe.	Pain and swelling.	Low-heeled shoe with stiff sole and soft padding inside.
Heel and Back-of-the-Foot Pain
Plantar fasciitis or heel spurs	Back of the arch right in front of heel.	At onset, some people report a tearing or popping sound. Pain is most severe with first steps after getting out of bed. Pain decreases after stretching, returns after inactivity.	Over-the-counter foot insole (cut quarter-size hole surrounding painful area). Possible night splints. Orthotics if necessary.
Bursitis of the heel	Center of the heel.	Pain, with warmth and swelling. Increases during the day.	Heel cup.
Haglund's deformity (pump bump)	Fleshy area on the back of the heel.	Tender swelling aggravated by shoes with stiff backs.	Soft shoes. Heel pads. Possible orthotic to support heel.
Achilles tendinitis	Achilles tendon: area along the back between calf muscles and heel.	Pain worsens during physical activities (particularly running), after which the tendon usually swells and stiffens. If it ruptures, popping sound may occur followed by acute pain similar to a blow at the back of the leg.	Insoles, tendon strap, heel cups.
Arch and Bottom-of-the Foot Pain
Tarsal tunnel syndrome	Anywhere along the bottom of the foot.	Numbness, tingling, or burning sensations, pain, most commonly felt at night.	Specially designed orthotics to relieve pressure.
Flat feet or posterior tibial tendon dysfunction (PTTD)	The arch.	No arch. Often no pain or discomfort. Three stages in PTTD: Pain and weakness in the tendon. The arch flattens but is still flexible. The foot becomes rigid and possibly painful at the ankle. Sometimes people report fatigue, pain, or stiffness in the feet, legs, and lower back.	For children, possible custom-made insoles.
High arches (hollow feet)	The arch.	High arches. Lower back pain, possible tendency to lower limb injuries.

Causes

Nearly all causes of foot pain can be grouped under one of the following:

Ill-fitting shoes. Poorly fitting shoes are a frequent cause of foot pain. High-heeled shoes concentrate pressure on the toes and can aggravate, if not cause, problems with the toes.
Certain medical conditions. Any medical condition that causes a disturbance in the way a person walks can contribute to foot pain. This may include diseases or conditions that lead to pain or numbness in the feet (such as diabetes), leg and foot deformities, spinal problems, and neurological disorders such as Parkinson's disease or cerebral palsy.
High-impact exercise. High-impact exercising, such as jogging or strenuous aerobics, can injure the feet. Common injuries include corns, calluses, blisters, muscle cramps, acute knee and ankle injuries, plantar fasciitis, and metatarsalgia.

Arthritic Conditions. Arthritic conditions, particularly osteoarthritis and gout, can cause foot pain. Although rheumatoid arthritis almost always develops in the hand, the ball of the foot can also be affected.

Diabetes. Diabetes is an important cause of serious foot disorders. [For more information, see In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Obesity. Obesity can cause foot and ankle pain.

Pregnancy. Pregnancy can cause fluid buildup and swollen feet. The increased weight and imbalance of pregnancy contributes to foot stress.

Medications. Some medications, such as calcitonin and drugs used for high blood pressure, can cause foot swelling.

Click the icon to see an image of foot inspection.

Risk Factors

A risk factor is anything that increases your chances of getting a disease or condition. The following are factors that increase your risk for foot pain:

Elderly people are at very high risk for foot problems. As you age, your feet widen and flatten, and the fat padding on the sole of the foot wears down. The skin on the feet also becomes dryer. Foot pain in older adults may be the first sign of age-related conditions, such as arthritis, diabetes, and circulatory disease. Foot problems can also impair balance and function in this age group.

Taking fashion to extreme limits, some people have turned to cosmetic surgery as a drastic way to fit into high-heeled shoes. Procedures include surgical shortening of the toes, narrowing of feet, or injecting silicone into the pads of the feet. Such methods may increase your risk for future foot pain. The American Orthopaedic Foot and Ankle Society (AOFAS) and other foot-related medical associations have expressed concern over this trend. The AOFAS strongly advises against cosmetic foot surgery and urges consumers to carefully consider the relative risks and benefits of undergoing unnecessary surgical procedures.

Women are at higher risk than men for severe foot pain, probably because of high-heeled shoes. Severe foot pain appears to be a major cause of general disability in older women.

An estimated 120,000 job-related foot injuries occur every year, about a third of them involving the toes. A number of foot problems -- including arthritis of the foot and ankle, toe deformities, pinched nerves between the toes, plantar fasciitis, adult-acquired flat foot, and tarsal tunnel syndrome -- have been attributed to repetitive use at work.

For example, in a study of New York police officers who walked an average of 3 miles a day, 20% experienced foot pain at the end of their workday. (Insoles can relieve much of this pain.) No studies, however, have scientifically distinguished between injuries due to work versus those due to regular use. This is an important issue because of its potential impact on disability claims.

Pregnant women have an increased risk of foot problems due to weight gain, swelling in their feet and ankles, and the release of certain hormones that cause ligaments to relax. These hormones help when bearing the child, but they can weaken the feet.

People who engage in regular high-impact aerobic exercise are at risk for plantar fasciitis, heel spurs, sesamoiditis, shin splints, Achilles tendon, and stress fractures. Women are at higher risk for stress fractures than are men.

Gaining weight puts added stress on the feet and can lead to foot or ankle injuries. The added pressure on the soft tissues and joints of the foot in overweight people increases the likelihood of developing tendinitis and plantar fasciitis.

Treatment: Corns and Calluses

A corn is a protective layer of dead skin cells that forms due to repeated friction. It is cone-shaped and has a knobby core that points inward. This core can put pressure on a nerve and cause sharp pain. Corns can develop on the top of, or between, toes. If a corn develops between the toes, it may be kept pliable by the moisture from perspiration and is therefore called a soft corn.

Corns develop as a result of friction from the toes rubbing together or against the shoe. They often occur from the following:

Shoes, socks, or stockings that fit too tightly around the toes
Pressure on the toes from high-heeled shoes
Shoes that are too loose, due to the friction of the foot sliding within the shoe
Deformed and crooked toes

Calluses are composed of the same material as corns. Calluses, however, develop on the ball or heel of the foot. The skin on the sole of the foot is ordinarily about 40 times thicker than the skin anywhere else on the body, but a callus can even be twice as thick. A protective callus layer naturally develops to guard against excessive pressure and chafing as people get older and the padding of fat on the bottom of the foot thins out. If calluses get too big or too hard, they may pull and tear the underlying skin.

Risk factors for calluses include the following:

Poorly fitting shoes
Walking regularly on hard surfaces
Flat feet

Of note, in people with diabetes, the presence of calluses is a strong predictor of ulceration, particularly in those who have a history of foot ulcers.

Preventing Corns and Calluses and Relieving Discomfort. To prevent corns and calluses and relieve discomfort if they develop:

Do not wear shoes that are too tight or too loose. Wear well-padded shoes with open toes or a deep toe box (the part of the shoe that surrounds the toes). If necessary, have a cobbler stretch the shoes in the area where the corn or callus is located.
Wear thick socks to absorb pressure, but do not wear tight socks or stockings.
Apply petroleum jelly or lanolin hand cream to corns or calluses to soften them.
Use doughnut-shaped pads that fit over a corn and decrease pressure and friction. They are available at most drug stores.
Place cotton, lamb's wool, or mole skin between the toes to cushion any corns in these areas.

Removing Corns and Calluses. To remove a corn or callus, soak it in very warm water for 5 minutes or more to soften the hardened tissue, then gently sand it with a pumice stone. Several treatments may be necessary. Do not trim corns or calluses with a razor blade or other sharp tool. Unsterile cutting tools can cause infection, and it is easy to slip and cut too deep, causing excessive bleeding or injury to the toe or foot.

Medicated Solutions and Pads. There are numerous over-the-counter pads, plasters, and medications for removing corns and calluses. These treatments commonly contain salicylic acid, which may cause irritation, burns, or infections that are more serious than the corn or callus. Use caution with these medications. The following people should not use them:

Patients with diabetes
Patients with reduced feeling in the feet due to circulation problems or neurological damage
Patients who do not have the flexibility or eyesight to use them properly

Treatment: Bunions

A bunion is a deformity that usually occurs at the head of one of the five long bones (the metatarsal bones) that extend from the arch of the foot and connect to the toes. A bunion typically develops in the following way:

Most often it occurs in the first metatarsal bone (the one that attaches to the big toe). A bunion may also develop in the bone that joins the little toe to the foot (the fifth metatarsal bone), in which case it is known as either a bunionette or a tailor's bunion.
A bunion begins to form when the big or little toe is forced in toward the rest of the toes, causing the head of the 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 toward the rest of the toes. One important bunion deformity, hallux valgus, causes the bone and joint of the big toe to shift and grow inward, so that the second toe crosses over it.

Several conditions can cause bunions:

Narrow high-heeled shoes with pointed toes can put enormous pressure on the front of the foot.
Injury in the joint may cause a bunion to develop over time.
Genetics play a role in 10 - 15% of all bunions.

Flat feet, gout, arthritis, and occupations (such as ballet) that place undue stress on the feet can also increase the risk for bunions.

Shoes and Protective Pads. Pressure and pain from bunions and bunionettes can be relieved by wearing appropriate shoes, such as the following:

Soft, wide, low-heeled leather shoes that lace up
Athletic shoes with soft toe boxes
Open shoes or sandals with straps that don't touch the irritated area

A thick doughnut-shaped, moleskin pad can protect the protrusion. In some cases, an orthotic can help redistribute weight and take pressure off the bunion. Nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroid injections may offer some pain relief.

Surgery. If discomfort persists, surgery may be necessary, particularly for more serious conditions, such as hallux valgus. There are more than 100 surgical variations, ranging from removing the bump to realigning the toes.

The most common surgery, an office procedure known as bunionectomy, involves shaving down the bone of the big toe joint. In one procedure the surgeon uses a very small incision, through which the bone-shaving drill is inserted. The physician shaves off the bone, guided by feel or x-ray. This technique is not a cure, but patient satisfaction is high and results are long-lasting.

Click the icon to see an illustrated series detailing bunion removal.

More extensive surgeries may be required to realign the toe joint. Although there are variations of each, they generally involve one or more of the following:

Osteotomy (cutting and realigning the joint). Long-term studies on osteotomies report that 90% of patients are satisfied with the procedure.
Exostetectomy (removal of the large bony growth). This technique is only useful when there is no shift in the toe bone itself.
Arthrodesis (removal of damaged portion of the joint, followed by implantation of screws, wires, or plates to hold the bones together until they heal). This is the gold standard procedure for very severe cases or when previous procedures have failed. Most patients report good results.
Arthroplasty (removal of damaged portion of the joint with the goal of achieving a flexible scar). This technique offers symptom relief and faster rehabilitation than arthrodesis, but it can cause deformity and some foot weakness. Arthroplasty tends to be used in older patients. Biologic or synthetic implants for supporting the toes are showing promise as part of this procedure.
Tendon and Ligament Repair. If tendons and ligaments have become too loose, the surgeon may tighten them.

In severe cases, surgeons are testing bone grafts to restore bone length in patients who have had previous bunion surgeries or damage from osteoarthritis.

Complications, though uncommon in even the most complex procedures, can include:

Continued pain
Infection
Possible numbness
Irritation from implants used to support the bone
An excessively shortened metatarsal bone

Recovery from more invasive procedures, such as arthrodesis or osteotomy, may take 6 - 8 weeks, and it can be that long before a patient can put full weight on the foot. In such cases, the patient will need to wear a cast or use crutches. Elderly patients may need wheelchairs.

Treatment: Hammertoes

A hammertoe is a permanent deformity of the toe joint, in which the toe bends up slightly and then curls downward, resting on its tip. When forced into this position long enough, the tendons of the toe shrink, and the toe stiffens into a hammer- or claw-like shape.

Hammertoe is most common in the second toe, but it can develop in any or all of the three middle toes if they are pushed forward and do not have enough room to lie flat in the shoe. The risk is increased when the toes are already crowded by the pressure of a bunion. Risks include:

Lying down for long periods
Diabetes
Diseases that affect the nerves and muscles

Click the icon to see an image of a hammertoe.

Treatment for Hammertoe. At first, a hammertoe is flexible, and any pain it causes can usually be relieved by putting a toe pad, sold in drug stores, into the shoe. To help prevent and ease existing discomfort from hammertoes, shoes should have a deep, wide toe area. As the tendon becomes tighter and the toe stiffens, other treatments, including exercises, splints, and custom-made shoe inserts (orthotics) may help redistribute weight and ease the position of the toe.

Surgery. Patients with severe cases of hammertome may need surgery. If the toe is still flexible, only a simple procedure that releases the tendon may be involved. Such procedures sometimes require only a single stitch and a Band-Aid. If the toe has become rigid, surgery on the bone is necessary, but it can still be performed in the doctor's office. A procedure called PIP arthroplasty involves releasing the ligaments at the joint and removing a small piece of toe bone, which restores the toe to its normal position. The toe is held in this position with a pin for about 3 weeks, and then the pin is removed. One study reported that 92% of patients who had arthroscopy were still pain free after 5 years.

Treatment: Ingrown Toenails

Ingrown toenails can occur on any toe but are most common on the big toes. They usually develop when tight-fitting or narrow shoes put too much pressure on the toenail and force the nail to grow into the flesh of the toe. Incorrect toenail trimming can also contribute to the risk of developing an ingrown toenail. Other causes are:

Fungal infections
Injuries
Abnormalities in the structure of the foot
Repeated impact on the toenail from high-impact aerobic exercise

An ingrown toenail is a condition in which the edge of the toenail grows into the skin of the toe. The big toe is most commonly affected. Symptoms include pain, redness, and swelling around the toenail.

Caring for Toenails. Trim toenails straight across and keep them long enough so that the nail corner is not visible. If the nail is cut too short, it may grow inward. If the nail does grow inward, do not cut the nail corner at an angle. This only trains the nail to continue growing inward. When filing the nails, file straight across the nail in a single movement, lifting the file before the next stroke. Do not saw back and forth. A cuticle stick can be used to clean under the nail.

Treatments. To relieve pain from ingrown toenails, try wearing sandals or open-toed shoes. Soaking the toe for 5 minutes twice a day in a warm water solution of Domeboro or Betadine can help. People who are at increased risk for infections, such as those with diabetes, should have professional treatment.

Antibiotic ointments can treat ingrown toenails that are infected. Apply the ointment by working a wisp of cotton under the nail, especially the corners, to lift the nail up and drain the infection. The cotton will also help force the toenail to grow out correctly. Change the cotton daily, and use the antibiotic consistently.

In severe cases, more intensive treatments are needed. Surgery involves simply cutting away the sharp portion of ingrown nail, removing the nail bed, or removing a wedge of the affected tissue. One study found that orthonyxia, a newer surgical technique that implants a small metal brace into the top of the nail, is as effective as traditional surgical techniques for preventing ingrown toenails from recurring.

Nonsurgical methods can also treat ingrown toenails. One technique uses chemicals to remove the skin. Both sodium hydroxide and phenol may be used, but research shows that sodium hydroxide produces a better outcome and faster recovery than phenol. Other nonsurgical methods include using cauterization (heating), or lasers, to remove the skin.

Treatment: Forefoot Pain

Forefoot pain refers to pain and discomfort felt toward the top of the foot. The rate of forefoot pain and deformity increases with age. When a cause cannot be determined, any pain on the ball of the foot is generally referred to as metatarsalgia.

Forefoot pain may be due to:

Morton's neuroma
Sesamoiditis
Stress fractures

A neuroma usually means a benign tumor of a nerve. However, Morton’s neuroma, also called interdigital neuroma, is not actually a tumor. It is a thickening of the tissue surrounding the nerves leading to the toes. Morton’s neuroma usually develops when the bones in the third and fourth toes pinch together, compressing a nerve. It can also occur in other locations. The nerve becomes enlarged and inflamed. The inflammation causes a burning or tingling sensation and cramping in the front of the foot. Other causes of this condition include:

Tight, poorly-fitting shoes
Injury
Arthritis
Abnormal bone structure

Treatment for Neuromas. Pain from Morton's neuroma can be reduced by massaging the affected area. Roomier shoes (box-toed shoes), pads of various sorts, and cortisone injections in the painful area are also helpful. A combination of cortisone injections and shoe modifications provides better immediate relief than changes in footwear alone. Ultrasound-guided injection of alcohol might also provide relief from Morton's neuroma, research finds.

If these treatments are not effective, the enlarged area may need to be surgically removed. In one long-term study of one surgeon's experience, 85% of patients reported good to excellent satisfaction nearly 6 years after surgery. About 65% were pain free. Some numbness is common afterward, but it rarely bothers patients. Occasionally, the nerve tissue may re-grow and form another neuroma.

Sesamoiditis is an inflammation of the tendons around the small, round bones that are embedded in the head of the first metatarsal bone, which leads to the big toe. Sesamoid bones bear much stress under ordinary circumstances; excessive stress can strain the surrounding tendons. Often there is no clear-cut cause, but sesamoid injuries are common among people who participate in jarring, high-impact activities, such as ballet, jogging, and aerobic exercise.

Treatment for Sesamoiditis. Rest and reducing stress on the ball of the foot are the first lines of treatment for sesamoiditis. A low-heeled shoe with a stiff sole and soft padding inside is all that is usually required. In severe cases, surgery may be necessary.

A stress fracture in the foot, also called fatigue or march fracture, usually results from a break or rupture in any of the five metatarsal bones (mostly the second or third). These fractures are caused by overuse during strenuous exercise, particularly jogging and high-impact aerobics. Women are at higher risk for stress fracture than men.

A fracture in the first metatarsal bone, which leads to the big toe, is uncommon because of the thickness of this bone. If it occurs, however, it is more serious than a fracture in any of the other metatarsal bones because it dramatically changes the pattern of normal walking and weight bearing.

Treatment for Stress Fractures. Patients should seek treatment if pain persists for 3 weeks. In a study of young athletes, treatment after that time reduced the chance that they could return to their sport. Surgery may be needed if conservative measures fail. In most cases, however, stress fractures heal by themselves if you avoid rigorous activities. Some health care providers recommend moderate exercise, particularly swimming and walking. It is best to wear low-heeled shoes with stiff soles. Occasionally, a health care provider may recommend wearing a special wooden shoe and a compressive wrap to make walking more comfortable.

Treatment: Heel Pain

The heel is the largest bone in the foot. Heel pain is the most common foot problem and affects 2 million Americans every year. It can occur in the front, back, or bottom of the heel. Types of heel pain include:

Achilles tendinitis
Bursitis of the heel
Excess pronation
Haglund's deformity
Heel spur syndrome
Plantar fasciitis

Each type of heal pain is described in more detail below. General treatment guidelines are as follows:

The American Orthopaedic Foot and Ankle Society (AOFAS) suggests shoe inserts, medications, and stretching as a first line of therapy for heel pain. One study found that 95% of women who used an insert and did simple stretching exercises for the Achilles tendon and plantar fascia experienced improvement after 8 weeks.
If these treatments fail, the patient may need prescription heel orthotics and extended physical therapy. Surgery may be an option if other methods have failed.

Achilles tendinitis is an inflammation of the tendon that connects the calf muscles to the heel bone. It is caused by small tears in the tendon from overuse or injury. This condition is most common in people who engage in high-impact exercise, particularly jogging, racquetball, and tennis.

People at highest risk for this disorder from these activities are those with a shortened Achilles tendon. Such people tend to roll their feet too far inward when walking, and may bounce when they walk. A shortened tendon can be due to an inborn structural abnormality, or it can develop from regularly wearing high heels.

An inflamed or torn Achilles tendon causes intense pain and affects mobility.

Evidence is uncertain about the best way to treat either acute or chronic Achilles tendinitis. Some approaches include:

Treatments to Relieve Pain and Reduce Inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), may help ease pain and reduce inflammation. It is also helpful to apply ice for 20 - 30 minutes, four or five times a day. (Note: Corticosteroid injections are sometimes used, although evidence suggests they don't help very much, and they can pose a risk for rupture of the tendon.)

Gentle Stretching. Gentle calf muscle stretches may also help reduce pain and spasms. If the calf is swollen, elevate the leg. Exercise is safe when the heel is no longer swollen or tender, even if pain is still present. If pain increases with exercise, stop immediately.

Laser Therapy. Low-level laser therapy that emits energy directed at pain trigger points has helped some patients. No strong evidence supports its use to date, however.

Surgery vs. Nonsurgical Treatment. Chronic inflammation may lead to rupture of the Achilles tendon. If pain continues, the ruptured tendon will require a cast and perhaps surgery, called tendon transfer. Although some experts believe a cast without surgery is a sufficient treatment for such rupture, there is a chance the tendon may rupture again in the future, even after it heals. Some experts suggest surgery for active people and nonsurgical treatment for older people.

Surgery requires a long incision with a postoperative period of immobilization that can average 6 weeks. Complications can include a significant surgical scar, infection, and muscle atrophy, although surgery reduces pain and preserves foot function in the long term. Less invasive techniques are being tested. In one study, selected patients with ruptured tendons were hospitalized for about 5 days and fitted with special footgear (Variostabil, which continuously raised the back of the foot). The footgear was effective for most patients, and the tendon ruptured again in only 5% of cases.

Bursitis of the heel is an inflammation of the bursa, a small sack of fluid beneath the heel bone. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), and steroid injections will help relieve pain from bursitis. Applying ice and massaging the heel are also beneficial. A heel cup or soft padding in the heel of the shoe reduces direct impact when walking.

Pronation is the normal motion that allows the foot to adapt to uneven walking surfaces and to absorb shock. Excessive pronation occurs when the foot has a tendency to turn inward and stretch and pull the fascia. It can cause not only heel pain, but also hip, knee, and lower back problems.

Haglund's deformity, known medically as posterior calcaneal exostosis, is a bony growth surrounded by tender tissue on the back of the heel bone. It develops when the back of the shoe repeatedly rubs against the back of the heel, aggravating the tissue and the underlying bone. It is commonly called pump bump because it frequently occurs with high heels. (It can also develop in runners, however.)

Treatment for Haglund's Deformity. Applying ice followed by moist heat will help ease discomfort from a pump bump. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen (Advil), will also reduce pain. Your doctor may recommend an orthotic device to control heel motion. Corticosteroid injections are not recommended because they can weaken the Achilles tendon.

In severe cases, surgery may be necessary to remove or reduce the bony growth. According to one study, however, surgery was not effective for more than 30% of patients and, in fact, the condition worsened in 14% of patients who had surgery. A more recent study reported that surgery cured 90% of cases, but patients took 6 months to 2 years to fully recover. Experts advise patients to try all conservative measures before choosing surgery.

Plantar fasciitis is a common foot problem that accounts for 1 million office visits per year. Plantar fasciitis occurs from small tears and inflammation in the wide band of tendons and ligaments that stretches from the heel to the ball of the foot. This band, much like the tensed string in a bow, forms the arch of the foot and helps serve as a shock absorber for the body.

The term plantar means the sole of the foot, and fascia refers to any fibrous connective tissue in the body. Most people with plantar fasciitis experience pain in the heel with their first steps in the morning. The pain also often spreads to the arch of the foot. The condition can be temporary, or it may become chronic if ignored. Resting can provide relief, but only temporarily.

Heel spurs are calcium deposits that can develop under the heel bone as a result of the inflammation that occurs with plantar fasciitis. Heel spurs and plantar fasciitis are sometimes blamed interchangeably for pain, but plantar fasciitis can occur without heel spurs, and spurs commonly develop without causing any symptoms at all.

Causes of Plantar Fasciitis. The cause of plantar fasciitis is often unknown. It is usually associated with overuse during high-impact exercise and sports. Plantar fasciitis accounts for up to 9% of all running injuries. Because the condition often occurs in only one foot, however, factors other than overuse are likely to be responsible in many cases. Other causes of this injury include poorly-fitting shoes, lack of calf flexibility, or an uneven stride that causes an abnormal and stressful impact on the foot.

Treatment Goals. The three major treatment goals for plantar fasciitis are:

Reducing inflammation and pain
Reducing pressure on the heel
Restoring strength and flexibility

Embarking on an exercise program as soon as possible and using NSAIDs, splints, or heel pads as needed can help relieve the problem. Pain that does not subside with NSAIDs may require more intensive treatments, including leg supports and even surgery.

Exercises to Restore Strength and Flexibility. Stretching the plantar fascia is the mainstay therapy for restoring strength and flexibility. One exercise involves the following:

Put the hands on a wall and lean against them.
Place the uninjured foot on the floor in front of the injured foot.
Raise the heel of the injured foot.
Gently stretch the injured leg and foot.

With stretching treatments, the plantar fascia nearly always heals by itself but it may take as long as a year, with pain occurring intermittently. A moderate amount of low-impact exercise (such as walking, swimming, or cycling) also seems to be beneficial.

Treatment. Inflammation and pain is most commonly treated with ice and over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin or ibuprofen. NSAIDs reduce pain and disability in people with plantar fasciitis when used with other techniques, such as night splints and stretching.

Corticosteroids are powerful anti-inflammatory agents. An injection of a steroid plus a local anesthetic (such as xylocaine) may provide relief in severe cases of plantar fasciitis. (Steroid injections are not used for pain that is only due to heel spurs). For athletes or performers who need immediate relief, an effective method is to administer the steroid dexamethasone using a procedure called iontophoresis, which introduces the drug into the foot's tissue using an electrical current.

Several non-drug approaches can relieve pressure on the heel, including:

Sturdy Shoes and Insoles. It is important to wear comfortable but sturdy shoes that have thick soles, rubber heels, and a sole insole to relieve pressure. (An insole with an arch support might also be helpful.) Cutting a round hole about the size of a quarter in the sole cushion under the painful area may help support the rest of the heel while relieving pressure on the painful spot. Heel cups are not very useful. When combined with exercises that stretch the arch and heel cord, over-the-counter insoles may offer the same relief as prescribed orthotics.
Night Splints. Some evidence suggests that splints worn at night may be helpful for some people. One device, for example, uses an Ace bandage and an L-shaped fiberglass splint to keep the foot stretched while the patient is sleeping. This allows the muscle to heal. One study reported that nearly any splint, regardless of cost, is equally effective in about three-quarters of patients. Although patient compliance may be better with custom-made prescribed orthotics than with tension night splints, one study found they are equally effective in improving pain.
Elevated Heels. Some people report relief from mild symptoms with the use of shoes or cowboy boots that have elevated heels. This approach, however, may not work in some people and is not recommended for anyone with a moderate-to-severe condition. (Heel cups have not been proven to be very useful.)
Orthotics. For severe conditions, such as fallen arches or structural problems that cause imbalance, insoles, called orthotics, molded from a plaster cast of the patient's foot may be needed. (See "Insoles and Orthotics" section).
Extracorporeal Shock Wave Therapy (ESWT). ESWT may be used as an alternative to surgery for patients who have not responded to other treatments. The therapy uses low-dose sound waves to injure the surrounding tissues in the heel, which is believed to trigger healing of the tissues that are causing the pain. Studies show that the treatment provides a very small reduction in heel pain without side effects. It can be considered as an option for patients who haven't responded well to extensive conservative treatment.
Surgery. Surgery may be needed for some patients, typically those who have disabling heel pain that does not respond to other treatments for at least a year. A typical surgery is called instep plantar fasciotomy. It relieves pressure on the nerves that are causing pain by removing and therefore releasing part of the plantar fascia. A less invasive method uses a procedure called endoscopy, which requires smaller incisions. Wearing a below-the-knee walking cast after surgery for 2 weeks may reduce the need for pain relief and speed recovery time compared to the use of crutches.
Botox. Small studies show that injections of botulinum toxin (Botox), a protein used to temporarily paralyze certain muscles, reduces pain and improves patients' future ability to walk. More research is needed on this treatment.

Treatment: Flat Feet

Flat foot, or pes planus, is a defect of the foot that eliminates the arch. The condition is most often inherited. Arches, however, can also fall in adulthood, in which case the condition is sometimes referred to as posterior tibial tendon dysfunction (PTTD). This occurs most often in women over age 50, but it can occur in anyone. The following are risk factors for PTTD:

Wearing high heels for long periods of time is a particular risk for flat feet. Over the years, the Achilles tendon in the back of the calf shortens and tightens, so the ankle does not bend properly. The tendons and ligaments running through the arch then try to compensate. Sometimes they break down, and the arch falls.
Some studies have indicated that the earlier a person starts wearing shoes, particularly for long periods of the day, the higher the risk for flat feet later on.
Other conditions that can lead to PTTD include obesity, diabetes, surgery, injury, rheumatoid arthritis, or the use of corticosteroids.

Some research suggests that flat feet in adults can, over time, actually exert abnormal pressure on the ankle joint that can cause damage. One indirect complication of flat arches may be urinary incontinence or leakage during exercise. The less flexible the arch, the more force reaches the pelvic floor, jarring the muscles that affect urinary continence. Nevertheless, whether flat feet pose any significant problems in adults is unknown. For example, one study on athletes with flat feet indicated that they had no higher risk for leg or foot injuries than did athletes with normal arches.

Treatment for Flat Feet in Children. Doctors usually can't diagnose flat feet until a child is 6 years old. Children with flat feet typically don't have symptoms, and often outgrow the condition. Children who are experiencing symptoms might need to change shoes or wear arch supports. In rare cases, minimally invasive joint insert surgery may be an option.

Treatment for Flat Feet in Adults. In general, conservative treatment for flat feet acquired in adulthood (posterior tibial tendon dysfunction) involves pain relief and insoles or custom-made orthotics to support the foot and prevent progression.

In severe cases, surgery may be required to correct the foot posture, usually with procedures called osteotomies or arthrodesis that typically lengthen the Achilles tendon and adjust tendons in the foot. One procedure uses an implant to support the arch. These procedures have potential complications. Conservative methods should be tried first.

Treatment: Abnormally High Arches

An overly-high arch (hollow foot) can cause problems. Army studies have found that recruits with the highest arches have the most lower-limb injuries and that flat-footed recruits have the least. Contrary to the general impression, the hollow foot is much more common than the flat foot.

Clawfoot, or pes cavus, is a deformity of the foot marked by very high arches and very long toes. Clawfoot is a hereditary condition, but can also occur when muscles in the foot contract or become unbalanced due to nerve or muscle disorders.

Claw toe is a deformity of the foot in which the toes are pointed down and the arch is high, making the foot appear claw-like. Claw toe can be a condition from birth or develop as a consequence of other disorders.

Treatment: Tarsal Tunnel Syndrome

Tarsal tunnel syndrome results from compression of a nerve that runs through a narrow passage behind the inner ankle bone down to the heel. It can cause pain anywhere along the bottom of the foot. It can occur with:

Diabetes
Back pain
Arthritis
Injury to the ankle
Abnormal blood vessels
Scar tissue that press against the nerve

Magnetic resonance imaging (MRI) and the dorsiflexion-eversion test can diagnose this syndrome.

Treatment for Tarsal Tunnel Syndrome. Specially designed shoe inserts called orthotics can relieve pain from tarsal tunnel syndrome, because they help redistribute weight and take pressure off the nerve. Corticosteroid injections may also help. Surgery is sometimes performed, particularly if symptoms persist for more than a year, although its benefits are a matter of debate. Tarsal tunnel syndrome caused by known conditions, such as tumors or cysts, may respond better to surgery than tarsal tunnel syndrome of unknown cause. It can take months after this surgery for a person to recover and resume normal activities. Only experienced surgeons should perform tarsal tunnel syndrome surgery.

Treatment: Foot Injury

If you suspect that you have broken or fractured bones in a toe or foot, call a doctor, who will probably order x-rays. Even if you can walk, you still might have a fracture. People are often able to walk even if a foot bone has been fractured, particularly if it is a chipped bone or a toe fracture.

Over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat mild pain caused by muscle inflammation. Aspirin is the most common NSAID. Others include ibuprofen (Motrin, Advil, Nuprin, Rufen), ketoprofen (Actron, Orudis KT), naproxen (Aleve, Naprelan), and tolmetin (Tolectin). A gel containing ibuprofen can be applied to sore joints. Acetaminophen (Tylenol) is not an NSAID, and although it is a mild pain reliever, it will not reduce inflammation. It is important to note that high doses or long-term use of any NSAID can cause gastrointestinal disturbances with sometimes serious consequences, including dangerous bleeding. No one should take NSAIDs for prolonged periods of time without consulting a doctor.

The acronym RICE stands for rest, ice, compression, and elevation -- the four basic elements of immediate treatment for an injured foot.

Rest. Patients should get off injured foot as soon as possible.
Ice. This is particularly important to reduce swelling and promote recovery during the first 48 hours. Wrap a bag or towel containing ice around the injured area on a repetitive cycle of 20 minutes on, 40 minutes off.
Compression. Lightly wrap an Ace bandage around the area.
Elevation. Elevate the foot on several pillows.

Minor injuries like sprains may be treated at home if broken bones are not suspected. The acronym RICE is helpful for remembering how to treat minor injuries: "R" stands for rest, "I" is for ice, "C" is for compression, and "E" is for elevation. Pain and swelling should decrease within 48 hours, and gentle movement may be beneficial, but don't put pressure on a sprained joint until the pain is completely gone (one to several weeks).

Prevention

The American Podiatric Medical Association offers the following tips for preventing foot pain:

Don't ignore foot pain -- it's not normal. If the pain persists, see a doctor who specializes in podiatry.
Inspect feet regularly. Pay attention to changes in color and temperature. Look for thick or discolored nails (a sign of developing fungus), and check for cracks or cuts in the skin. Peeling or scaling on the soles of feet could indicate athlete's foot. Any growth on the foot is not considered normal.
Wash feet regularly, especially between the toes, and dry them completely.
Trim toenails straight across, but not too short. (Cutting nails in corners or on the sides increases the risk for ingrown toenails.)
Make sure shoes fit properly. Purchase new shoes later in the day when feet tend to be at their largest, and replace worn out shoes as soon as possible.
Select and wear the right shoe for specific activities (such as running shoes for running).
Alternate shoes. Don't wear the same pair of shoes every day.
Avoid walking barefoot, which increases the risk for injury and infection. At the beach or when wearing sandals, always use sunblock on your feet, as you would on the rest of your body.
Be cautious when using home remedies for foot ailments. Self-treatment can often turn a minor problem into a major one.
It is critical that people with diabetes see a podiatric physician at least once a year for a checkup. People with diabetes, poor circulation, or heart problems should not treat their own feet, including toenails, because they are more prone to infection.

Skin creams can help maintain skin softness and pliability. A pumice stone or loofah sponge can help get rid of dead skin.

Taking a warm footbath for 10 minutes two or three times a week will keep the feet relaxed and help prevent mild foot pain caused by fatigue. Adding 1/2 cup of Epsom salts increases circulation and adds other benefits. Taking footbaths only when the feet are painful is not as helpful.

In addition to wearing proper shoes and socks, walking often -- and properly -- can prevent foot injury and pain. The head should be erect, the back straight, and the arms relaxed and swinging freely at the side. Step out on the heel, move forward with the weight on the outside of the foot, and complete the step by pushing off the big toe.

Exercises specifically for the toe and feet are easy to perform and help strengthen them and keep them flexible. Helpful exercises include the following:

Raise and curl the toes 10 times, holding each position for a count of five.
Put a rubber band around both big toes and pull the feet away from each other. Count to five. Repeat 10 times.
Pick up a towel with the toes. Repeat five times.
Pump the foot up and down to stretch the calf and shin muscles. Perform for 2 or 3 minutes.

Early Development. The first year of life is important for foot development. Parents should cover their babies' feet loosely, allowing plenty of opportunity for kicking and exercise. Change the child's position frequently. Children generally start to walk at 10 - 18 months. They should not be forced to start walking early. Wearing just socks or going barefoot indoors helps the foot develop normally and strongly and allows the toes to grasp. Going barefoot outside, however, increases the risk for injury and other conditions, such as plantar warts.

Shoes. Children should wear shoes that are light and flexible, and since their feet tend to perspire, their shoes should be made of materials that breathe. Replace footwear every few months as the child's feet grow. Footwear should never be handed down. Protect children's feet if they participate in high-impact sports.

Shoes

In general, the best shoes are well cushioned and have a leather upper, stiff heel counter, and flexible area at the ball of the foot. The heel area should be strong and supportive, but not too stiff, and the front of the shoe should be flexible. New shoes should feel comfortable right away, without a breaking-in period.

Well-fitted shoes with a firm sole and soft upper are the best way to prevent many problems with the feet. They should be purchased in the afternoon or after a long walk, when the feet have swelled. There should be 1/2 inch of space between the longest toe and the tip of the shoe (remember, the longest toe is not always the big toe), and the toes should be able to wiggle upward.

Stand when being measured, and have both feet sized, buying shoes that fit whichever foot is largest. Wear the same socks as you would regularly wear with the new shoes. Women who are accustomed to wearing pointed-toe shoes may prefer the feel of tight-fitting shoes, but with wear their tastes may adjust to shoes that are less confining and properly fitted.

Ideally, the shoe should have a removable insole. Thin, hard soles may be the best choice for older people. Elderly people wearing shoes with thick inflexible soles may be unable to sense the position of their feet relative to the ground, significantly increasing the risk for falling.

High heels are the major cause of foot problems in women. Although people believe that foot binding is a problem limited to Chinese women of the past, many fashionable high heels are designed to constrict the foot by up to an inch. Women who insist on wearing high-heeled shoes should at least look for shoes with wide toe room, reinforced heels that are relatively wide, and cushioned insoles. They should also keep the amount of time they spend wearing high heels to a minimum.

The way shoes are laced can be important for preventing specific problems. Laces should always be loosened before putting shoes on. People with narrow feet should buy shoes with eyelets farther away from the tongue than people with wider feet. This makes for a tighter fit for narrower feet and a looser fit for wider feet. If, after tying the shoe, less than an inch of tongue shows, the shoes are probably too wide. Adjust tightness both at the top and bottom of the shoe. When shoes with high arches cause pain, skip eyelets when lacing them to relieve pressure.

If shoes need breaking in, place moleskin pads next to areas on the skin where friction is likely to occur. Once a blister occurs, moleskin is not effective. Change shoes during the day, and rotate between different pairs of shoes. As soon as the heels show noticeable wear, replace the shoes or their heels.

Avoid extreme variations between exercise, street, and dress shoes.

Exercise and Sports. Shoes purchased for exercise should be specifically designed for a person's preferred sport. For instance, a running shoe should especially cushion the forefoot, while tennis shoes should emphasize ankle support. Athletic socks are almost as important as shoes. Experts often recommend padded acrylic socks.

Occupational Footwear. Because a number of occupations put the feet in danger, workers in high-risk jobs should be sure their footwear is protective. For example, non-electric workers at risk for falling or rolling objects or punctures should wear shoes with steel toes and possibly other metal foot guards. Electric workers should wear footgear with no metal parts (or insulated steel toes) and rubber soles and heels. Chemical workers should wear shoes made of synthetics or rubber, not leather.


Aerobic Dancing	Sufficient cushioning to absorb shock and pressure, which should be many times greater than shock from walking. Arches that maintain side-to-side stability. Thick upper leather support. Box toe. Orthotics may be required for people with ankles that over-turn inward or outward. Soles should allow for twisting and turning.
Cycling	Rigid support across the arch to prevent collapse during pedaling. Heel lift. Cross-training or combo hiking/cycling shoes may be sufficient for the casual biker. Toe clips or specially designed shoe cleats for serious cyclers. In some cases, orthotics may be needed to control arch and heel and balance the forefoot.
Running	Sufficient cushioning to absorb shock and pressure. Fully bendable at the ball of the foot. Enough traction on the sole to prevent slipping. Consider insole or orthotic with arch support for problem feet.
Tennis	Allows side-to-side sliding. Low-traction sole. Snug fitting heel with cushioning. Padded toe box with adequate depth. Soft-support arch.
Walking	Lightweight. Breathable upper material (leather or mesh). Wide enough to accommodate ball of the foot. Firm padded heel counter that does not bite into heel or touch anklebone. Low heel close to ground for stability. Good arch support. Front provides support and flexibility.

Insoles and Orthotics

Insoles are flat cushioned inserts that are placed inside the shoe. They are designed to reduce shock, provide support for heels and arches, and absorb moisture and odor. In general, they can be very helpful for many people.

People respond very differently to specific insoles. What may work for one person may not for another. Consider the thickness of socks when purchasing insoles to be sure they do not squeeze the toes up against the shoes. Insoles can be purchased in athletic and drug stores. Shoe stores that specialize in foot problems often sell customized, but more expensive, insoles. In general, over-the-counter insoles offer enough support for most people's foot problems. Most well-known brands of athletic shoes have built-in insoles.

Brands and Materials. There are many types of insoles available. They are composed of various materials, such as cork, leather, plastic foam, and rubber. Very effective insoles are now made from viscoelastic polymers (such as Sorbothane, Airplus, Spenco, Dr. Scholl's Massaging Gel, and others), which are gel-like materials that act both as liquids and solids.

Heel Cushions for Shortened Achilles Tendons. People who have developed short, tightened Achilles tendons (usually women who have worn high-heeled shoes for prolonged periods) should consider using heel cushions. Like insoles, heel cushions are inserted inside the shoes. They should be at least 1/8 inch thick, but not more than 1/4 inch thick.

For severe conditions, such as fallen arches or structural problems that cause imbalance, podiatrists or physicians may need to fit and prescribe orthotics, or orthoses, which are insoles molded from a plaster cast of the patient's foot. Orthotics are usually categorized as rigid, soft, or semi-rigid.

Before seeking prescription orthotics, people with less severe problems should consider testing the lower-priced, over-the-counter insoles.

Types of orthotics include:

Rigid Orthotics. Rigid orthotics are used to control motion in two major foot joints that lie directly below the ankle. They are often used to prevent excessive pronation (the turning in of the foot) and are useful for people who are very overweight or have uneven leg lengths. Some experts warn that rigid orthotics may cause sesamoiditis or benign tumors from pinched nerves.
Soft Orthotics. Soft orthotics are designed to absorb shock, improve balance, and remove pressure from painful areas. They are made from a lightweight material and are often beneficial for people with diabetes or arthritis. Soft orthotics need to be replaced periodically, and because they are bulkier than rigid orthotics, they may require larger shoes.
Semi-Rigid Orthotics. Semi-rigid orthotics are designed to provide balance, often for a specific sport. They are typically made of layers of leather and cork reinforced by silastic.

Resources

www.apma.org -- American Podiatric Medical Association
www.aofas.org -- American Orthopaedic Foot and Ankle Society
www.acfas.org -- American College of Foot and Ankle Surgeons
www.aapsm.org -- American Academy of Podiatric Sports Medicine
www.apta.org -- American Physical Therapy Association
www.diabetes.org -- American Diabetes Association
http://ndep.nih.gov/campaigns/Feet/Feet_overview.htm -- National Diabetes Education Program
www.arthritis.org -- Arthritis Foundation
www.podiatrynetwork.com -- Podiatry Network

References

Bostanci S, Kocyigit P, Gurgey E. Comparison of phenol and sodium hydroxide chemical matricectomies for the treatment of ingrowing toenails. Dermatol Surg. 2007;33:680-685.

Donley BG, Moore T, Sferra J, Gozdanovic J, Smith R. The efficacy of oral nonsteroidal anti-inflammatory medication (NSAID) in the treatment of plantar fasciitis: a randomized, prospective, placebo-controlled study. Foot Ankle Int. 2007;28:20-23.

Frey C, Zamora J. The effects of obesity on orthopaedic foot and ankle pathology. Foot Ankle Int. 2007;28:996-999.

Gollwitzer H, Diehl P, von Korff A, Rahlfs VW, Gerdesmeyer L. Extracorporeal shock wave therapy for chronic painful heel syndrome: a prospective, double blind, randomized trial assessing the efficacy of a new electromagnetic shock wave device. J Foot Ankle Surg. 2007;46:348-357.

Hughes RJ, Ali K, Jones H, Kendall S, Connell DA. Treatment of Morton's neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.

Kruijff S, van Det RJ, van der Meer GT, van den Berg IC, van der Palen J, Geelkerken RH. Partial matrix excision or orthonyxia for ingrowing toenails. J Am Coll Surg. 2008;206:148-153.

Malay DS, Pressman MM, Assili A, Kline JT, York S, Buren B, Heyman ER, Borowsky P, LeMay C. Extracorporeal shockwave therapy versus placebo for the treatment of chronic proximal plantar fasciitis: results of a randomized, placebo-controlled, double-blinded, multicenter intervention trial. J Foot Ankle Surg. 2006;45:196-210.

Review Date:
12/14/2007
Reviewed By:
Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M., Inc.

A.D.A.M. Copyright

adam.com

Systemic lupus erythematosus

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Systematic Lupus Erythematosus (SLE)

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

Symptoms and Diagnosis

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

Treatment

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

Living with SLE

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

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

Introduction

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

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

Lupus has many different symptoms. Common ones include:

Fatigue
Joint pain or swelling
Skin rashes

Causes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of mononucleosis.

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

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

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

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

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

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

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

Risk Factors

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

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

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

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

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

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

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

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

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

Symptoms

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of vasculitis.

Other symptoms include:

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

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

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

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

A number of conditions may resemble SLE:

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

Complications

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

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

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

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

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

The degree of severity depends on different factors:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of pericarditis.

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

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

SLE affects the lungs in about 60% of patients:

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

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

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

Click the icon to see an image of the kidney.

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

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

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

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

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

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

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

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

Click the icon to see an image of osteoporosis.

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

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

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

Research suggests that the following factors predict a successful pregnancy:

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

Pregnancy Risks

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

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

Birth Complications

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

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

Diagnosis

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

1. Characteristic rash across the cheek

2. Discoid lesion rash

3. Photosensitivity

4. Oral ulcers

5. Arthritis

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

7. Evidence of kidney disease

8. Evidence of severe neurologic disease

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

10. Immunologic abnormalities

11. Positive antinuclear antibody (ANA)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Click the icon to see an image of an electrocardiogram.

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

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

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

Treatment

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

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

Prednisone
Aspirin
Hydroxychloroquine

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

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

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

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

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

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

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

Treatment for Cutaneous and Mild SLE

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

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

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

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

For people with lupus, NSAIDs may help relieve:

Joint pain and swelling
Muscle pain

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

Other NSAID side effects may include:

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

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

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

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

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

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

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

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

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

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

Side Effects. Side effects of antimalarials may include:

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

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

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

Treatment for Severe SLE

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

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

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

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

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

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

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

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

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

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

Specific Immunosuppressants. The most common immunosuppressants are:

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

The most frequent side effects of immunosuppressants include:

Stomach and intestinal problems
Skin rash
Mouth sores
Hair loss

Serious side effects of immunosuppressants include:

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

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

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

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

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

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

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

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

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

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


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

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

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

Lifestyle Changes

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

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

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

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

Resources

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

References

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

A.D.A.M. Copyright

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Epidermolysis bullosa

admin — Thu, 04 Sep 2008 18:46:15 -0700

Overview

Definition
Alternative Names
Causes, incidence, and risk factors
Symptoms
Signs and tests
Treatment
Expectations (prognosis)
Complications
Calling your health care provider
Prevention

Illustrations

Epidermolysis bullosa, dominant dystrophic

Epidermolysis bullosa, dystrophic

HEALTH GUIDE REFERENCE FROM A.D.A.M

Definition

Epidermolysis bullosa is a group of inherited disorders in which skin blisters develop in response to minor injury.

Alternative Names

Junctional epidermolysis bullosa; Dystrophic epidermolysis bullosa; Hemidesmosomal epidermolysis bullosa; Weber-Cockayne syndrome

Causes, incidence, and risk factors

There are four main types of epidermolysis bullosa:

Epidermolysis bullosa simplex
Junctional epidermolysis bullosa
Dystrophic epidermolysis bullosa
Hemidesmosomal epidermolysis bullosa

Another rare type of epidermolysis bullosa, called epidermolysis bullosa acquisita, is an autoimmune disorder. This may be indistinguishable from another autoimmune skin disorder called mucous membrane pemphigoid.

Depending on the type present, epidermolysis bullosa varies in severity from minor blistering of the skin to a lethal form involving other organs. The condition generally starts at birth or soon after that. Epidermolysis bullosa acquisita, however, usually appears in adults over age 50, although it has been reported in children. Also, mild cases of epidermolysis bullosa simplex may remain undiagnosed until adulthood.

The classification of epidermolysis bullosa is complicated. Even within the main types mentioned, there are many different subtypes of this condition. For example, Weber-Cockayne is the most common form of epidermolysis bullosa simplex. This type involves blistering of the palms and soles and may include excessive sweating.

All of the different types of epidermolysis bullosa are generally inherited. Therefore, having a family history of the disease, especially an affected parent, is a risk factor. The inheritance pattern may be dominant or recessive. A dominant form means that an offspring can inherit the gene or trait from one affected parent. The recessive form means that both parents must carry a gene and transmit that gene to the offspring in order for the infant or child to be affected. The recessive forms of epidermolysis bullosa tend to be more severe.

The hallmark of these conditions is the formation of large, fluid-filled blisters that develop in response to minor trauma. Some infants may have large blisters at birth. Others start shortly after birth. Chafing (wearing away) of the skin, rubbing, or even increased room temperature may cause blisters to form.

In the severe forms, scarring after blister formation may cause deformities, fusion of the fingers and toes, and contracture deformities (for example, at the fingers, elbows and knees). If the mouth and esophagus are involved, blistering and scarring lead to feeding and swallowing difficulties.

Secondary infection is common.

Symptoms

Symptoms depend on the type of epidermolysis bullosa, but can include:

Blistering of the skin as a result of minor trauma or temperature change
Blistering present at birth
Nail loss or deformed nails
Blistering in or around the mouth and throat, causing feeding difficulty or swallowing difficulty
Blistering around the eyes and nose
A hoarse cry, cough, or other respiratory difficulties
Dental abnormalities such as tooth decay
Alopecia (hair loss)
Milia (tiny white bumps or pimples)

For epidermolysis bullosa acquisita, there is an association with Crohn's disease (an inflammatory bowel disease) and, possibly, lupus. Symptoms of these conditions may be present, therefore, in adults who present with this type of epidermolysis bullosa.

Signs and tests

Your physician may suspect epidermolysis bullosa based upon the appearance of the skin. A skin biopsy, genetic testing, and special microscopic tests applied to the skin samples are needed to confirm the diagnosis. Special skin tests also distinguish epidermolysis bullosa acquisita presenting in a child (which does happen on rare occasion) from other forms of epidermolysis bullosa.

Your doctor may also do a blood test to see if there is anemia. If there are wounds that are healing poorly, a culture may be done to check for bacterial infection.

If swallowing or feeding difficulties are present, upper endoscopy or an upper GI series may be performed.

In an infant with epidermolysis bullosa or suspected epidermolysis bullosa, growth curves will be followed very closely.

If contractures are present, the range of motion of limbs will be tested.

Treatment

The goal of treatment is to prevent the formation of blisters and subsequent complications. The intensity of care depends upon the severity of the disease. Recommendations often include measures to avoid skin trauma and to avoid high environmental temperatures.

To prevent infection, excellent skin care is required, especially if any blistered areas become crusted or denuded (exposed or raw). Follow the instructions of your health care provider closely. Recommendations might include regular whirlpool therapy and application of topical antibiotics to these wound-like areas. Your health care provider will let you know if a bandage or dressing is required, and what type.

If there are swallowing difficulties, use of oral steroids for short periods of time may be prescribed. Long term use of steroids for epidermolysis bullosa is generally not recommended, however. If candida is present in the mouth or esophagus, medication for that secondary infection would be prescribed as well.

Good dental hygiene is very important, including regular dental visits. It is best to be followed by a dentist with experience treating those with epidermolysis bullosa.

Proper nutrition is also important. When skin injury is extensive, increased calorie and protein intake may be necessary to help recovery. Work closely with a nutritionist. When blisters or complications are present in the mouth or esophagus, hard or brittle foods (such as pretzels, nuts, and chips) should be avoided. Eating soft foods can help prevent worsening of these lesions.

Working with a physical therapist can help maintain the range of motion of involved joint areas and minimize contractures.

Skin grafting for denuded or ulcerated areas of the skin may be necessary. Other surgical procedures for complications of epidermolysis bullosa might be recommended as well. Such surgeries include dilation of the esophagus if a stricture (narrowing) is present, repair of hand deformities, and removal of squamous cell carcinoma lesions if they develop.

Other treatments under investigation for epidermolysis bullosa include protein and gene therapy.

Epidermolysis bullosa acquisita may be treated with oral steroids and medication that suppresses the immune system. These may, however, increase the risk of secondary infection, particularly the latter drug category. Studies using interferon are also underway.

Expectations (prognosis)

The outcome depends on the severity of the illness. Mild forms of epidermolysis bullosa improve with age. Scarring from several types of epidermolysis bullosa can restrict mobility significantly and, therefore, impair daily activities. Lethal forms of the epidermolysis bullosa have a very high mortality rate. (See Complications section.)

Complications

Infection, including sepsis
Esophageal stricture
Periodontal disease
Loss of function of hands and feet
Eye disorders, even blindness
Muscular dystrophy
Severe malnutrition secondary to feeding difficulty, leading to failure to thrive
Anemia
Squamous cell skin cancer -- if someone with epidermolysis bullosa survives childhood, metastatic squamous cell cancer of the skin is the most common cause of death. This skin cancer occurs in those with recessively inherited dystrophic epidermolysis bullosa. Those with epidermolysis bullosa often develop this skin cancer between the ages of 15 and 35. In addition, the skin cancer can occur anywhere on the skin. In other words, unlike the general public, it is not more likely to happen in sun-exposed areas.
Death -- death rate is as high as 87% in the first year of life for infants with the lethal form of junctional epidermolysis bullosa. On the other hand, dominantly inherited simplex and dystrophic epidermolysis bullosa, and mild forms of junctional epidermolysis bullosa may not lessen life expectancy at all.

Calling your health care provider

If your infant exhibits any blistering shortly after birth call your health care provider. If you have a family history of epidermolysis bullosa, further interaction with your health care provider or a genetic counselor may be appropriate.

Prevention

Genetic counseling is recommended for prospective parents with a family history of any form of epidermolysis bullosa.

During pregnancy, chorionic villus sampling to test the fetus is available. For couples at high risk of having an offspring with epidermolysis bullosa, the test can be done as early as week 8-10 of the pregnancy. Speak with your obstetrician and genetic counselor.

To prevent skin trauma and blistering, it may help to wear padding around trauma-prone areas like elbows, knees, ankles, and buttocks. Contact sports should be avoided.

Patients with epidermolysis bullosa acquisita who are on steroids for longer than one month may require calcium and vitamin D supplements to prevent osteoporosis.

Review Date: 10/17/2006

Reviewed By: Michael S. Lehrer, M.D., Department of Dermatology, University of Pennsylvania Medical Center, Philadelphia, PA. Review provided by VeriMed Healthcare Network.

A.D.A.M. Copyright

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Source Doc: 1_001457

Varicella-zoster virus

FitSugar — Wed, 08 Oct 2008 17:35:11 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

The varicella–zoster virus (VZV) can cause two diseases: chickenpox (varicella) and shingles (herpes zoster). Before a vaccine was developed in 1994, chickenpox was a common contagious childhood disease that produced itchy blisters but rarely caused serious problems. However, if adults who had not had the disease as children contracted it, it could cause more serious complications.

Shingles is caused by a reactivation of the virus that causes chickenpox. Once you have had chickenpox, the varicella-zoster virus lies dormant in your nerves and can re-emerge as shingles. Shingles, which is characterized by a rash of blisters, can be very painful but is not life-threatening. Some people who develop shingles also develop a condition caused postherpetic neuralgia, which causes the skin to remain painful even after the rash is gone. Shingles is most common in people over 60 or in those with a weak immune system. A vaccine is available that reduces your risk of getting shingles.

Signs and Symptoms

Chickenpox

The typical rash of chickenpox is made up of groups of small, itchy blisters surrounded by inflamed skin. The rash usually begins on the face, scalp, or chest, quickly spreading throughout the body. It usually appears a few days after you have been exposed. Over four days, each blister tends to dry out and form a scab, which then falls off between 9 to 13 days later.

The rash is usually preceded or accompanied by:

Fever, usually low-grade
Fatigue
Headache
Flu-like symptoms

Shingles

The typical rash of shingles begins as redness followed by blisters that usually cover only one side of your body. The rash follows the path of the nerve where the virus has lain dormant. About 50 to 60% of people with shingles have the rash on their trunk. The next most common site is one side of the face, which may even involve the tongue, eye, or ear.

Before the rash appears, you will have warning symptoms of pain (usually a sharp, aching, piercing, tearing, or burning sensation) on the part of your body where the rash appears 1 to 5 days later. That area may also feel itchy, numb, and unbearably sensitive to touch, even just from your clothes touching your skin.

Other symptoms that you may experience include:

Fever
Malaise (feeling unwell) and other flu-like symptoms including muscle aches
Headache
Swollen lymph nodes
Upset stomach

Causes

Chickenpox

Both chickenpox and shingles are caused by the varicella-zoster virus, a tyupe of herpes virus. The virus is spread through direct contact with the rash or by sneezing, coughing, and breathing – in other words, when someone with chickenpox sneezes or coughs, there are droplets with the VZV virus in the air. The virus is contagious from two days before the rash appears until all of the blisters have crusted over.

Shingles

While shingles is caused by the same virus that leads to chickenpox, the way you develop this painful skin condition is different. After you have had chickenpox, the virus lives in a dormant state (as if it is hibernating) in nerve cells along your spine. Later in life, when it "wakes up" (usually from a weakened immune system, aging, or other risk factor), the virus travels down the path of the particular nerve where it was "hibernating," causing pain \followed by the rash. Anyone who has had chickenpox can get shingles, although a vaccine can reduce your risk.

Risk Factors

Chicken Pox

Exposure to the virus if you have not had chickenpox nor received the vaccine
Age under 10
Time of year: late winter and early spring is the most common time that the virus is spread

Shingles

Age (most common in people over 60)
Stress
Weakened immune system (for example, people with HIV/AIDS, or those taking immune-suppressing drugs due to autoimmune diseases or organ transplants)
Having had chickenpox before age 1

Diagnosis

Your doctor can usually diagnose chickenpox easily because because of its characteristic rash. If there is any doubt, however, the doctor may take a scraping from one of the blisters to look at under the microscope.

Similarly, if you have shingles, your doctor can usually make a diagnosis from the history of pain and other symptoms and the rash itself. He or she may take a scraping from one of the blisters for a laboratory test.

Preventive Care

Chickenpox

The chickenpox vaccine (Varivax) is given to every child over 1 year old. If a peson receives the vaccine before age 13, then he or she only needs one dose. If a person receives the vaccine when he or she is older than 13, a second dose is needed1 to 2 months later.
If you have never had chickenpox or the vaccine, avoid contact with anyone who has chickenpox.
To avoid spreading to others, children with chickenpox should be kept out of school or daycare until all of the blisters have scabbed over.

Shingles

If you have never had chickenpox, the chickenpox vaccine can reduce your risk of getting chickenpox and shingles. Even if you do get the disease, having had the vaccine reduces the risk of complications.
The shingles vaccine (Zostavax) can reduce the risk of getting shingles among people who are over 60 and have had chickenpox. It doesn't completely ensure you won't get shingles, but if you do, having had the vaccine reduces the severity and the risk of postherpetic neuralgia.
The shingles vaccine is not recommended for people who
- Have ever had a reaction to gelatin or neomycin
- Have a weakend immune system
- Take drugs to suppress the immune system (such as corticosteroids)
- Have tuberculosis
- Have a history of lymphatic or bone marrow cancer
One study found that older adults who practice tai chi regularly had a better immune response to the varicella virus, and their immunity increased even more when they had the shingles vaccine.

Treatment Approach

Both chickenpox and shingles generally get better by themselves, unless you are at high risk for complications. The goal of treatment is to reduce pain and itching.

Lifestyle

You can reduce symptoms of chickenpox and shingles with some simple steps:

Apply cool water compresses to your skin or soak in a bathtub filled with cool water
Add finely ground oatmeal (there are special brands sold in drugstores) to the bathtub
Apply calamine or an over-the-counter hydrocortisone lotion to the affected areas
Trim your fingernails to avoid infection
For small children with chickenpox, cover hands with loose fitting, soft cotton or flannel mittens to prevent scratching

Medications

Chickenpox

Antihistamine - If itching is severe, your doctor may suggest an antihistamine (such as Benadryl)
Acyclovir (Zovirax) - an antiviral drug prescribed for children who are at high risk of complications form chickenpox, or for adults who have chickenpox.
Pain relievers - Acetaminophen (Tylenol) and ibuprofen (Advil, Motrin) can help reduce pain. Do not give aspirin to children under 18 because of the risk of a rare but serious illness called Reye's syndrome.

Shingles

Antiviral drugs - Most effective when started within 72 hours of the first sign of a rash, these drugs are often given to people who are at risk of postherpetic neuralgia. They include

Acyclovir (Zovirax)
Famciclovir (Famvir)
Valacyclovir (Valtrex)

Corticosteroids - used with Zovirax to reduce inflammation

Pain relievers - For pain associated with shingles, an over-the-counter pain reliever such as acetaminophen (Tylenol) or ibuprofen (Advil, Motrin) may be effective. For severe pain or pain associated with postherpetic neuralgia, your doctor may prescribe a narcotic (opioid) pain reliever.

For postherpetic neuralgia

Capsaicin - contains a pain reliever derived from chili peppers that produces a burning sensation when applied to the skin. It is available as an ointment (Zostrix) or a patch. A 2003 study reported that the patch reduced pain by 33% in about half of people with postherpetic neuralgia.

Lidocaine patch (Lidoderm) - applied to the skin to reduce pain.

Tricyclic antidepressants - Low doses of tricyclics, especially nortiptyline (Pamelor), may help reduce pain.

Gabapentin (Neurontin) - an anticonvulsant (antiseizure) medication may also help reduce pain

Nutrition and Dietary Supplements

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider.

Adenosine monophosphate (AMP) - Injections of AMP, a compound that is made by the body, has been examined in an early study for treating the initial symptoms of shingles as well as preventing postherpetic neuralgia. People with shingles were given injections of either 100 mg of AMP or placebo; at the end of 4 weeks, 88% of those who got AMP were pain-free compared to 43% who got placebo. Note that the study used injections of AMP; it is not known whether oral AMP would have any effect.
Vitamins B-12 and E - A few studies suggest that vitamin E (1,200 to 1,600 mg per day) and injections of B-12 (but not oral B-12) might help reduce symptoms of postherpetic neuralgia, but the studies were not of good quality. More research is needed.

Herbs

The use of herbs is a time-honored approach to strengthening the body and treating disease. Herbs, however, can trigger side effects and can interact with other herbs, supplements, or medications. For these reasons, herbs should be taken with care, under the supervision of a healthcare practitioner.

Cayenne (Capsicum frutescens/Capsicum spp.) - Capsaicin cream made from cayenne pepper can relieve pain when applied to the skin. Capsaicin may help relieve the pain of post-herpetic neuralgia, and an over-the-counter ointment is approved for this treatment (see Medications). Capsaicin causes burning when applied to the skin, so use sparingly and do not use around eyes, nose, or mouth.

German Chamomile (Matricaria recutita) - Traditionally, this herb has been used to treat skin conditions and childhood illness like chickenpox. However, no scientific studies have examined whether chamomile is helpful in treating chickenpox.

Licorice (Glycyrrhiza glabra) - Traditionally, licorice gel has been used topically (applied to the skin) to treat shingles and postherpetic neuralgia. In test tubes, one of the constituents of licorice, glycyrrhizin, stops the varicella zoster virus from reproducing. However, no scientific studies have examined whether licorice gel is helpful in treating either condition.

Acupuncture

Although the results of scientific studies have been somewhat mixed, acupuncture may help relieve the nerve pain associated with shingles, especially when combined with traditional medications. Acupuncturists treat people based on an individualized assessment of the excesses and deficiencies of qi located in various meridians. In the case of shingles, a qi deficiency is usually detected in the liver meridian and an excess in the gallbladder meridian. Acupuncturists will often provide needle or moxibustion treatment (a technique in which the herb mugwort is burned over specific acupuncture points) around painful areas.

Homeopathy

Although very few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the following remedies for the treatment of chickenpox and shingles based on their knowledge and experience. Before prescribing a remedy, homeopaths take into account a person's constitutional type. A constitutional type is defined as a person's physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate treatment for each individual.

Chickenpox:

Antimonium crudum - for irritable children who are extremely sensitive to touch and may have a thick white coating on the tongue
Antimonium tartaricum - for large, slowly appearing pox lesions accompanied by cough.
Mercurius - for large, pus-filled pox which may ooze; this remedy is most appropriate for individuals who sweat profusely and may have enlarged lymph nodes
Pulsatilla - for fever associated with chicken pox; children who tend to be whiny, clingy, and weepy but have very little thirst despite the fever
Rhus toxicodendron - for severe itching that worsens at night and improves with warm compresses or a bath; this remedy is the most commonly prescribed
Sulphur - for extremely itchy lesions that worsen with heat or bathing and which children will often scratch to the point of bleeding

Shingles:

Arsenicum - for intense burning sensation that improves with warmth and worsens with cold
Lachesis - for particularly dark, sometimes purple, lesions on the left side of the body
Mezereum - for burning, sharp pains that worsen with touch; this remedy is most appropriate for individuals who are naturally chilly and sensitive to cold
Ranunculus bolbosus - for lesions located on the chest or back; pain worsens with touch and movement
Rhus toxicodendron - for intense itching and pain that may be relieved by touch

Mind/Body Medicine

The following relaxation techniques may help reduce the pain and stress associated with shingles and postherpetic neuralgia:

Meditation
Breathing exercises
Progressive muscle relaxation
Biofeedback

People with post-herpetic neuralgia have reported some relief from using hypnosis.

Other Considerations

Pregnancy

If you get chickenpox when you are pregnant, the infection may spread to the fetus.

Special Populations

If your immune system is weakened, shingles blisters may spread to other parts of your body and it will likely take longer for the symptoms to heal, maybe lasting for months. Conditions that weaken your immune function include:

HIV or AIDS
Organ transplant recipient
Cancer, especially leukemia, Hodgkin's disease and other lymphomas, or receiving chemotherapy
Having an autoimmune disease (like rheumatoid arthritis, lupus, multiple sclerosis, and Crohn's disease) and are taking drugs that suppress your immune system

Warnings and Precautions

Do not give aspirin to children under 18, due to the risk of a rare but serious illness called Reye’s syndrome.
Call your doctor if you experience confusion, vomiting, or weakness, even paralysis, of the arms, legs, trunk, or face during or soon after a chickenpox or shingles infection.

Prognosis and Complications

While chickenpox usually goes away on its own, severe and sometimes fatal infections may occur, particularly in newborn infants, adults, and people whose immune systems are weakened (see Special Populations). Such potential infections include:

Encephalitis (a brain infection)
Myocarditis (an infection of the heart muscle)
Pneumonia
Secondary bacterial skin infection

Shingles usually clears up in 2 to 3 weeks. Your chance of getting another bout of shingles is only 1% to 5% if you have a healthy immune system. If you have a weakened immune system (see Special Populations), your risk for recurrence is higher.

Potential complications from shingles include:

Shingles lesions involving the mouth or eye; the latter may lead to blindness if not treated
Postherpetic neuralgia (persistent pain for months to years even after the skin lesions have cleared up)
Secondary bacterial skin infections
Encephalitis (a brain infection) or sepsis (an infection in your blood stream, affecting many organs in the body).

Supporting Research

Aikawa Y, Yoshiike T, Ogawa H. Effect of glycyrrhizin on pain and HLA-DR antigen expression on CD8-positive cells in peripheral blood of herpes zoster patients in comparison with other antiviral agents. Skin Pharmacol. 1990;3:268-271.

Betts RF. Vaccination strategies for the prevention of herpes zoster and postherpetic neuralgia. J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S143-7.

Boaler J. Acupuncture in the management of herpes zoster. Acupunct Med. 1996;14(2);80-83.

Cummings S, Ullman D. Everybody's Guide to Homeopathic Medicines. 3rd ed. New York, NY: Penguin Putnam; 1997: 119-120, 263-264.

Davies SJ, Harding LM, Baranowski AP. A novel treatment of postherpetic neuralgia using peppermint oil. Clin J Pain. 2002;18(3):200-202.

Gillingham G. Herpes zoster and post herpetic neuralgia. J Tradit Chin Med. 1995;47:5-7.

Homsy J, Katabira E, Kabatesi D, et al. Evaluating herbal medicine for the management of Herpes zoster in human immunodeficiency virus-infected patients in Kampala, Uganda. J Altern Complement Med. 1999;5(6):553-565.

Hu J. Acupuncture treatment of herpes zoster. J Tradit Chin Med. 2001;21(1):78-80.

Hui F, Cheng A, Chiu M, Vayda E. Integrative approach to the treatment of postherpetic neuralgia: a case series. Altern Med Review. 1999;4(6):429-435.

Irwin MR, Olmstead R, Oxman MN. Augmenting immune responses to varicella zoster virus in older adults: a randomized, controlled trial of Tai Chi. J Am Geriatr Soc. 2007 Apr;55(4):511-7.

Johnson RW, Whitton TL. Management of herpes zoster (shingles) and postherpetic neuralgia. Expert Opin Pharmacother. 2004 Mar;5(3):551-9. Review.

Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996: 174-175.

Kenney JK, Jamjian C, Wheeler MM. Prevention and management of pain associated with herpes zoster. J Pharm Care Pain Symptom Control. 1999;7(3):7-26.

Leffowitz M, Marini RA. Management of postherpetic neuralgia. Ann Acad Med Singapore. 1994;23(Suppl):139S-144S.

Niv D, Maltsman-Tseikhin A. Postherpetic neuralgia: the never-ending challenge. Pain Pract. 2005 Dec;5(4):327-40.

Pieroni A. Medicinal plants and food medicines in the folk traditions of the upper Lucca Province, Italy. J Etnopharmacol. 2000;70(3):235-273.

Rains C, Bryson HM. Topical capsaicin: A review of its pharmacological properties and therapeutic potential in post-herpetic neuralgia, diabetic neuropathy, and osteoarthritis. Drugs Aging. 1995;7(4):317-328.

Reilly MP. Clinical applications of acupuncture in anesthesia practice. CRNA. 2000;11(4):173-179.

Roxas M. Herpes zoster and postherpetic neuralgia: diagnosis and therapeutic considerations. Altern Med Rev. 2006 Jun;11(2):102-13. Review.

Stankus SJ, Dlugopolski M, Packer D. Management of herpes zoster (shingles) and postherpetic neuralgia. Am Fam Physician. 2000;61(:2437-2438.

Tyring SK. Management of herpes zoster and postherpetic neuralgia. J Am Acad Dermatol. 2007 Dec;57(6 Suppl):S136-42. Review.

Ullman D. Homeopathic Medicine for Children and Infants. New York, NY: Penguin Putnam; 1992: 58-59.

Ullman D. The Consumer's Guide to Homeopathy. New York, NY: Penguin Putnam; 1995: 174-176.

Wu J, Guo Z. Twenty-three cases of postherpetic neuralgia treated by acupuncture. J Tradit Chin Med. 2000;20(1):36-37.

Review Date:
12/23/2007
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

Herpes simplex virus

FitSugar — Wed, 08 Oct 2008 17:34:55 -0700

Overview

Signs and Symptoms
Causes
Risk Factors
Diagnosis
Preventive Care
Treatment Approach
Other Considerations
Supporting Research

HEALTH GUIDE REFERENCE FROM A.D.A.M

Herpes simplex virus (HSV) infections are very common worldwide. HSV-1 (usually known as a cold sore) is transmitted through kissing or sharing drinking utensils, and HSV-2 (usually known as genital herpes) through sexual contact. You may be infected and not show symptoms for a long time. Often symptoms are triggered by exposure to the sun, fever, menstruation, emotional stress, a weakened immune system, or an illness.

There is not cure for herpes, and once you have it, it is likely to recur; however, some people may have one outbreak and then never have another one. In between herpes outbreaks, the virus lies dormant (as if it is hibernating or sleeping) in nerve cells.

While exposure to HSV-1 is extremely common – as many as 90% of American adults have been exposed to the virus – and there is no stigma to having a cold sore, HSV-2 or genital herpes can cause embarrassment. Although there is no cure for genital herpes, an infected person can take steps to preventing spreading the disease and can continue to have a sex life.

While most herpes infections do not cause serious complications, infections in infants and in people with weakened immune systems or herpes infections that affect the eyes can be life-threatening.

Signs and Symptoms

HSV-1

Small, painful blisters filled with fluid around the lips or edge of the mouth
Tingling or burning around the mouth or nose (often a few days before blisters appear)
Fever
Sore throat
Swollen lymph nodes in neck

HSV-2

Small red blisters or open sores on genitals or inner thighs; in women, often occur inside the vagina
May be painful or not
In women, vaginal discharge
Fever, muscle aches
Headache Painful urination
Swollen lymph glands in the groin

Causes

HSV-1 is transmitted through saliva. Kissing, using the same eating utensils, sharing personal items (such as a razor), and receiving oral sex from someone who has HSV-1 can cause you to contract the virus.

HSV-2 is a sexually transmitted disease.

Both herpes viruses can be contagious even if the infected person does not have active symptoms or visible blisters.

Also, a mother can pass the infection to her baby during vaginal birth, especially if there are active blisters around the vagina at the time of delivery.

Risk Factors

Oral herpes (cold sores)

Everyone is at risk for oral herpes from HSV-1. In fact, studies suggest that by adolescence 62% of Americans are infected with HSV-1 and by the time people are in their 40s, 90% have been infected.

Genital herpes

All sexually active people are at risk for genital herpes. Having multiple sexual partners puts you at even greater risk. Women have a greater risk of being infected after sex with an unprotected partner than men do. Estimates of how many Americans are infected range from 20% to 30%.

Other factors

People with weakened immune systems, such as people with HIV/AIDS or those who take immunosuppressant drugs to treat an autoimmune disease or because of organ transplant, are at increased risk for severe cases of herpes.

Diagnosis

In many instances, your doctor is able to make the diagnosis of herpes from examining you and no tests are required. If your doctor is not 100% certain, however, then he or she make take a sample from the blisters to test for the virus. Finally, there is a blood test that may be helpful for making a diagnosis, especially if your doctor suspects herpes but you don't have an active infection.

Preventive Care

HSV-1

Avoiding kissing people with visible core sores
Don't share personal items
Wash your hands frequently
If you have HSV-1, be careful touching your eyes and genitals; don't perform oral sex on your partner
Use sunscreen
Reduce stress

HSV-2

Avoid having sex if you or your partner has an outbreak (active infection) of herpes. Herpes outbreaks are not always obvious and your partner may be contagious without you knowing it. Anyone involved in an ongoing sexual relationship with a partner infected with HSV-2 should get counseling from a healthcare practitioner on how to best keep yourself safe.
Avoid touching the sores
Use or have your partner use a latex condom (even when sores are not visible)
Limit the number of sex partners

Treatment Approach

Herpes cannot be cured, so the goals of treatment are to reduce the number of outbreaks and to lessen symptoms when you do have an outbreak.

Cold sores usually go away by themselves in no more than 1 to 2 weeks. Using medications may shorten the outbreak and decrease discomfort.

Antiviral medications for genital herpes can reduce outbreaks and help speed recovery when an outbreak does occur. They can also lessen the chances of spreading the virus.

Coping with the emotional and social aspects of having genital herpes is part of treatment. Relaxation techniques and support groups can help.

Lifestyle

For cold sores, applying either heat or cold to blisters may help relieve pain. Try ice or warm compresses.

For genital herpes, wear cotton underwear and avoid tight fitting clothes as they can restrict air circulation and slow the healing of lesions.

Be sure to tell your partner or potential partner that you have herpes.

Medications

Antiviral medicines - may help shorten the duration of a herpes outbreak and suppress recurring outbreaks. For genital herpes, there are two types of therapy: episodic and suppressive. With episodic therapy, you take medication at the first sign of an outbreak and for several days to shorten the duration or prevent a full outbreak. With suppressive therapy, you may take medication daily to keep outbreaks from occurring. Antiviral medications include:

Acyclovir (Zovirax)
Famciclovir (Famvir)
Valacyclovir (Valtrex)

Topical medications (for oral herpes) - include the antiviral cream Penciclovir (Denavir) and an over-the-counter cream, docosanol (Abreva).

Nutrition and Dietary Supplements

Because supplements may have side effects or interact with medications, they should be taken only under the supervision of a knowledgeable healthcare provider.

Lysine (1 to 3 g per day) - Although not all studies agree, several studies suggest that lysine may help reduce the number of recurring outbreaks of cold sores and possibly genital herpes. Most of the studies have involved people with cold sores or with both cold sores and genital herpes. A few studies also suggest that lysine may help shorten the duration of an outbreak. The evidence is somewhat stronger for cold sores: the research to date is not entirely conclusive, lysine supplements have been used to help treat or prevent mouth and genital lesions caused by herpes. Taking lysine supplements or increasing lysine in your diet (from foods like fish, chicken, eggs, and potatoes) may speed recovery time and reduce the chance of recurrent breakouts of the herpes infection. If you have high cholesterol, heart disease, or high triglycerides (type of fatty material in the blood, generally measured when you have your cholesterol checked), it is best, at this point, not to use lysine because animal studies suggest that this supplement may raise cholesterol and triglyceride levels.
Propolis - A resin made by bees, propolis is loaded with flavonoids (antioxidants that help fight infection and boost immune function). Test tube studies show it can stop HSV-1 and HSV-2 from reproducing. One small study of people with genital herpes compared an ointment made from propolis to Zovirax ointment. People using propolis saw the lesions heal faster than those using topical Zovirax. More studies are needed to say for sure whether propolis works.
Zinc - In test tubes, zinc is effective against HSV-1 and HSV-2. In one small study in people, those who applied zinc oxide cream to cold sores saw them heal faster than those who applied a placebo cream.

Herbs

Lemon balm (Melissa officinalis) - Several studies suggest that topical ointments containing lemon balm may help heal cold sores. In one study, for example, those who applied lemon balm cream to their lip sores saw a reduction in redness and swelling after two days.
Aloe (Aloe vera) - Preliminary evidence suggests that aloe gel used topically may improve the symptoms of genital herpes in men. In two studies, men who used the aloe vera cream (0.5% aloe) saw lesions heal faster than those who used a placebo cream. It isn't know whether aloe vera would also help heal cold sores.
Rhubarb cream (Rheum palmatum) - In one Swiss study, a cream made from sage (Salvia officinalis) and rhubarb was as effective as Zovirax in healing cold sores. Sage by itself was not beneficial. More research is needed.
Eleutherococcus or Siberian ginseng (Eleutherococcus senticosus/Acanthopanax senticosus) -Although not all studies agree, one 6-month study of 93 people with genital herpes found that Siberian ginseng reduced the frequency, severity, and duration of outbreaks. This herb should not be taken if you have high blood pressure, obstructive sleep apnea (repeated, prolonged periods when breathing stops while sleeping), narcolepsy (frequent day time sleeping), are pregnant or breastfeeding.
Peppermint oil (Mentha x piperita ) - In test tubes, peppermint oil has stopped a number of viruses from reproducing, including herpes. However, it isn't known whether peppermint oil would have any effect on the herpes virus in humans.

Homeopathy

Although few studies have examined the effectiveness of specific homeopathic therapies, professional homeopaths may consider the remedies described below for the treatment of herpes based on their knowledge and experience. One study of 53 people with genital herpes did show that the majority had improvement in their symptoms and were less likely to have recurrent outbreaks when treated with homeopathy. Participants in this study were followed for up to 4 years.

Before prescribing a remedy, homeopaths take into account a person's constitutional type. A constitutional type is defined as a person's physical, emotional, and psychological makeup. An experienced homeopath assesses all of these factors when determining the most appropriate remedy for each individual.

For cold sores:

Natrum muriaticum - for eruptions at the corners of the mouth that occur during periods of emotional stress and tend to worsen in the daytime
Rhus toxicodendron - for eruptions consisting of many small blisters that itch intensely at night
Mercurius - for children who drool and may have a fever
Sepia - for outbreaks that do not improve with other homeopathic remedies; this remedy is most appropriate for individuals who tend to have a lack of energy and don't tolerate cold weather

For genital lesions:

Graphites - for large, itchy lesions in individuals who are overweight
Natrum muriaticum - for eruptions that occur during periods of emotional stress and symptoms that tend to worsen in the daytime
Petroleum - for lesions that spread to anus and thighs; symptoms tend to worsen in winter and improve in summer
Sepia - for outbreaks that do not improve with other homeopathic remedies; this remedy is most appropriate for individuals who tend to have a lack of energy and don't tolerate cold weather

Mind/Body Medicine

Support groups - Having genital herpes can impact your social and emotional life. In fact, if you have herpes, it is quite common to feel depressed, angry, and even guilty. Worrying about possible rejection by someone with whom you are hoping to become intimate is also typical. Joining a support group where members share experiences and problems can help relieve the stresses associated with having genital herpes. If you are in a committed relationship, seeing a couples' therapist with your partner may also be helpful.
Relaxation techniques - Using relaxation techniques, such as yoga, guided imagery, and meditation, on a daily basis may help you feel better overall and cope with stresses related to having herpes.
Self-hypnosis - Self-hypnosis using guided imagery may also help relieve stress. In one 6-week training program, participants with frequently recurring genital herpes were able to reduce outbreaks by nearly 50% and improve their mood, including reducing feelings of depression and anxiety.
Other - Individual therapy with a psychiatrist, psychologist, or social worker; and techniques such as biofeedback can help reduce emotional symptoms associated with herpes.

Other Considerations

Pregnancy

Herpes viruses can be transmitted to a newborn during vaginal delivery, especially if the mother has active lesions in the vagina at the time of delivery. Herpes infections in newborns can be life-threatening or cause disability. Delivery by cesarean section (C-section) will be recommended to avoid infecting the baby.

Special Populations

Newborns – herpes infections contracted during delivery from the mother can lead to meningitis, herpes infection in the blood, chronic skin infection, and may even be fatal.

You are more likely to have severe, frequent outbreaks and to experience complications from herpes if your immune system is suppressed from:

HIV or AIDS
Chemotherapy for cancer
Long-term use of high doses of corticosteroids
Medications that intentionally suppress the immune system

Warnings and Precautions

If you are diagnosed with genital herpes, you should be tested for other sexually transmitted diseases such as chlamydia and gonorrhea.

Prognosis and Complications

Herpes is a chronic, recurrent infection. The initial symptoms usually appear within 1 to 3 weeks of exposure to the virus and last 7 to 10 days (for cold sores) or 7 to 14 days (for genital lesions). Usually the number of outbreaks is greatest in the first year and higher for HSV-2 genital lesions than HSV-1 cold sores. Each year after that, the number of outbreaks usually goes down and they become less severe. But you can never completely get rid of the virus.

Complications of herpes include:

Herpetic keratitis – herpes infection of the eye leading to scaring within the cornea and possible blindness
Persistent herpes infection, without lesion-free periods
Herpes infection in the esophagus
Herpes infection of the liver which can lead to cirrhosis (liver failure)
Encephalitis and/or meningitis (serious brain infections)
Lung infection
Eczema herpetiform – widespread herpes across the skin

Supporting Research

Allen P. Tea tree oil: the science behind the antimicrobial hype. Lancet. 2001;358(9289):1245.

Ames M. Herpes: Comprehensive treatment strategy. Int J Integra Med. 2000;2(5):6-9.

Beauman JG. Genital herpes: a review. Am Fam Physician. 2005 Oct 15;72(:1527-34. Review.

Binns SE, Hudson J, Merali S, Arnason JT. Antiviral activity of chacterized extracts from Echinacea spp. (Heliantheae: Asteraceae) against herpes simplex virus (HSV-I). Planta Med. 2002;68(9):780-783.

Brennan P. Homeopathic remedies in prenatal care. J Nurse Midwifery. 1999;44(3):291-299.

Carson CF, Ashton L, Dry L, Smith DW, Riley TV. Melaleuca alternifolia (tea tree) oil gel (6%) for the treatment of recurrent herpes labialis. J Antimicrob Chemother. 2001;48(3):450-451.

Cummings S, Ullman D. Everybody's Guide to Homeopathic Medicines. 3rd ed. New York, NY: Penguin Putnam; 1997: 259-260.

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison's Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill; 1998:1080-1086.

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Fried RG. Nonpharmacologic treatments in psychodermatology. Dermatol Clinics. 2002;20910;177-185.

Gaby AR. Natural remedies for Herpes simplex. Altern Med Rev. 2006 Jun;11(2):93-101. Review.

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.

Griffith RS, Walsh DE, Myrmel KH, Thmpson RW, Behforooz A. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175(4):183-190.

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Hijikata Y, Tsukamoto Y. Effect of herbal therapy on herpes labialis and herpes genitalis. Biotherapy. 1998;11(4):235-240.

Huleihel M, Isanu V. Anti-herpes simplex virus effect of an aqueous extract of propolis. Isr Med Assoc J. 2002;4(11 Suppl):923-927.

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Jonas WB, Jacobs J. Healing with Homeopathy: The Doctors' Guide. New York, NY: Warner Books; 1996: 234.

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Koytchev R, Alken RG, Dundarov S. Balm mint extract (Lo-701) for topical treatment of recurring herpes labialis. Phytomedicine. 1999;6(4):225-230.

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Review Date:
12/23/2007
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

Rheumatoid arthritis

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

In This Report

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

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Treatment Approaches

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

Fish Oil for Joint Pain

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

Introduction

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

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

The process probably develops in the following way:

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

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

Click the icon to see an image of rheumatoid arthritis.

Causes

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Risk Factors

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

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

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

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

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

Heavy long-term smoking is a very strong risk factor for RA, particularly in patients without a family history of the disease.
Women who have a shorter fertility time (and so lower levels of reproductive hormones) may be at higher risk.
History of blood transfusions.

Most studies have not found any association between silicone breast implants and rheumatoid arthritis or other autoimmune disease (except possibly Sjögren syndrome).

Reports from a Dutch study suggest that hay fever sufferers have a reduced risk of developing rheumatoid arthritis, and, conversely, arthritis patients are less likely to have hay fever.

Symptoms

The hallmark symptom of rheumatoid arthritis is morning stiffness that lasts for at least an hour. (Stiffness from osteoarthritis, for instance, usually clears up within half an hour.) Even after remaining motionless for a few moments, the body can stiffen. Movement becomes easier again after loosening up.

Swelling and pain in the joints must occur for at least 6 weeks before a diagnosis of rheumatoid arthritis is considered. The inflamed joints are usually swollen and often feel warm and "boggy" when touched. The pain often occurs symmetrically but may be more severe on one side of the body, depending on which hand the person uses more often.

Although rheumatoid arthritis almost always develops in the wrists and knuckles, the knees and joints of the ball of the foot are often affected as well. Indeed, many joints may be involved, including those in the cervical spine, shoulders, elbows, tips, temporomandibular joint (jaw), and even joints between very small bones in the inner ear. Rheumatoid arthritis does not usually show up in the fingertips, where osteoarthritis is common, but joints at the base of the fingers are often painful.

In about 20% of people with RA, inflammation of small blood vessels can cause nodules, or lumps, under the skin. They are about the size of a pea or slightly larger, and are often located near the elbow, although they can show up anywhere. Nodules can occur throughout the course of the disease. Rarely, nodules may become sore and infected, particularly if they are in locations where stress occurs, such as the ankles. On rare occasions, nodules can reflect the presence of rheumatoid vasculitis, a condition that can affect blood vessels in the lungs, kidneys, or other organs.

Fluid may accumulate, particularly in the ankles. In rare cases, the joint sac behind the knee accumulates fluid and forms what is known as a Baker cyst. This cyst feels like a tumor and sometimes extends down the back of the calf causing pain.

Symptoms such as fatigue, weight loss, and fever may accompany early rheumatoid arthritis. Some people describe them as being similar to those of a cold or flu except, of course, RA symptoms can last for years.

In children, juvenile rheumatoid arthritis, also known as Still's disease, is usually preceded by high fever and shaking chills along with pain and swelling in many joints. A pink skin rash may be present.

Complications

Rheumatoid arthritis is not fatal, but complications of the disease may shorten survival by a few years in some individuals. Although type 2 rheumatoid arthritis is progressive and there is no cure, over time the disease becomes less aggressive, and symptoms may even improve.

Treatments for RA are increasingly effective in slowing this debilitating disease, and some may even prevent initial destruction by aggressively reducing inflammation. If bone and ligament destruction and any deformities have occurred, however, the effects are permanent. It is essential, therefore, to seek a doctor's help as soon as symptoms develop. Side effects of the treatments often contribute to the severity of the disease.

Affected joints can become deformed, and the performance of even ordinary tasks may be very difficult or impossible. According to one survey, 70% of patients with rheumatoid arthritis feel the disease prevents them from living a fully productive life. A 2000 study found that about one-third of people with RA stop working within 5 years of onset of the disease.

Rheumatoid arthritis can affect other parts of the body as well as the joints. Some patients with severe disease may then be at higher risk for complications, such as the following:

Peripheral Neuropathy. This condition affects the nerves, most often those in the hands and feet. It can result in tingling, numbness, or burning.
Muscle problems. Many patients have weakness of the muscles.
Anemia. People with RA may develop anemia, which involves a decrease in the production of red blood cells.
Scleritis and Episcleritis. This is an inflammation of the blood vessels in the eye that can result in corneal damage. Symptoms include redness of the eye and a gritty sensation.
Infections. Patients with RA have a higher risk for infections, particularly from some of the immune-suppressing drugs (corticosteroids, anti-tumor necrosis factors, disease modifying drugs) that they take.
Skin Problems. Skin problems are common, particularly on the fingers and under the nails. Some patients develop severe skin complications that include rash, ulcers, blisters (which may bleed in some cases), lumps under the skin, and other problems. Severe skin disease can reflects a more serious case of RA in general.
Osteoporosis. Osteoporosis, a disorder in which bone density decreases, is more common than average in postmenopausal women with RA. The hipbone is particularly affected. The risk for osteoporosis also appears to be higher than average in men with RA who are over 60 years old.
Lung Disease. Patients with RA are susceptible to chronic lung diseases, including interstitial fibrosis, pulmonary hypertension, and other problems. Both rheumatoid arthritis itself and some treatments may cause this damage.
Kidney. Although rheumatoid arthritis only rarely involves the kidney, many of the drugs used to treat it can damage kidneys.
Vasculitis. Vasculitis involves autoimmune inflammatory abnormalities in very small vessels and can affect many organs in the body. Manifestations of vasculitis include mouth ulcers, nerve disorders, rapid worsening of the lungs, inflammation of coronary arteries, and inflammation of the arteries supplying blood to the intestines.
Heart Disease. Inflammation of the heart muscle itself in the sac around the heart can cause many problems. Mounting evidence suggests that RA can increase the risk for heart disease, possibly because of the inflammatory response in RA, which may also injure arteries and heart muscle tissue. Some studies have reported that people with RA are 30 - 50% more likely to suffer heart vessel blockages and 60 - 70% more likely to die as result than people without RA.
Lymphoma and Other Cancers. Research suggests that patients with RA are four times more likely than healthy patients to develop non-Hodgkin’s lymphoma. There has also been concern that some RA treatments may increase the risk for lymphoma. Studies from 2006 indicate that RA’s chronic inflammatory process may play a role in the development of lymphoma. Researchers found that patients with very severe and long-term RA had a substantially increased risk of developing lymphoma. Other 2006 research suggests that RA drugs, such as biologic response modifiers, do not increase lymphoma risk, although they do increase skin cancer risk.
Periodontal Disease. People with RA may be twice as likely as non-arthritic individuals to have periodontal disease. Chronic inflammation and immune dysfunction are central to both diseases.
Pregnancy. Women with RA have an increased risk for premature delivery. They are also three times more likely than healthy women to develop hypertension during the last trimester of pregnancy.

Juvenile rheumatoid arthritis often resolves before adulthood. Patients who experience arthritis in only a few joints do better than those with more widespread (systemic) disease, which is very difficult to treat. Although it can be very serious, very few people die from this condition.

MAS. Macrophage activation syndrome (MAS) is a life-threatening complication of this disorder and requires immediate treatment with high-dose steroids and cyclosporin A. Parents should be aware of symptoms, which include persistent fever, weakness, drowsiness, and lethargy.

Diagnosis

Rheumatoid arthritis can be difficult to diagnose. Many other conditions resemble it and its symptoms can develop insidiously. Blood tests and x-rays may show normal results for months after the onset of joint pain. Even after rheumatoid arthritis has been diagnosed, it is extremely important to determine whether the course of the disease is benign (type 1) or aggressive (type 2) in order to treat the problem appropriately.

Specific findings or presentation more likely to suggest the diagnosis of rheumatoid arthritis include morning stiffness, involvement of three joints at the same time, involvement of both sides of the body, subcutaneous nodules, positive rheumatoid factor, changes in x-rays.

Various blood tests may be used to help diagnose RA, determine its severity, and detect complications of the disease.

Rheumatoid Factor. In RA, antibodies that collect in the synovium of the joint are known as rheumatoid factor. In about 80% of cases of RA, blood tests reveal rheumatoid factor. It can also show up in blood tests of people with other diseases. However, when it appears in patients with arthritic pain on both sides of the body, it is a strong indicator of type 2 RA. The presence of rheumatoid factor plus evidence of bone damage on x-rays also suggests a significant chance for progressive joint damage.

Erythrocyte Sedimentation Rate Test. An erythrocyte sedimentation rate (ESR or sed rate) measures how fast red blood cells (erythrocytes) fall to the bottom of a fine glass tube that is filled with the patient's blood. The higher the sed rate the greater the inflammation. In addition to rheumatoid arthritis, the sed rate can be high in many conditions ranging from infection to inflammation to tumors. The test is used, then, not for diagnosis, but to help determine how serious the condition is.

C-Reactive Protein. High levels of C-reactive protein (CRP) are also indicators of active inflammation. However, because obesity also increases CRP levels, the doctor should consider a patient’s body mass index when evaluating CRP levels during RA diagnosis.

Anti-CCP Antibody Test. The presence of antibodies to cyclic citrullinated peptides (CCP) can identify RA years before symptoms develop. In combination with the test for rheumatoid factor, the CCP antibody test is the best predictor of which patients will go on to develop severe RA. Used in Europe, the test is now beginning to be used somewhat more commonly in the U.S. U.S. laboratories have not yet developed consistent standards for interpreting the test, however.

Tests for Anemia. Anemia is a common complication. Blood tests are needed often to determine the amount of red blood cells (hemoglobin and hematocrit) and iron (soluble transferrin receptor and serum ferritin) in the blood.

Analyzing the synovial fluid might prove to be helpful in detecting markers of joint destruction, but this is not commonly performed. Some investigational examples include the following:

An enzyme called MMP-3 (matrix metalloproteinase 3) is involved with the degradation of cartilage. Its presence in synovial fluid is strongly associated with progressive joint destruction in patients with chronic RA.
High levels urocortin, a member of the peptide family involved in the stress response, may also be a major player in the RA inflammation.

X-Rays. X-rays generally have not been helpful to detect the presence of early rheumatoid arthritis because they cannot show images of soft tissue. The use of a technique known as dual energy x-ray absorptiometry, however, may be useful in detecting early bone loss in rheumatoid arthritis (2 - 27 months after onset). Evidence of damage on x-rays along with elevated rheumatoid factor is a significant predictor for progressive joint destruction.

Ultrasound. Special ultrasound techniques called power Doppler ultrasonography (PDUS) or quantitative ultrasound (QUS) may be helpful in RA. PDUS may be reliable for monitoring inflammatory activity in the joint. QUS, which is used for osteoporosis, can detect bone loss in fingers, which may prove to be a good indicator of early RA.

Magnetic Resonance Imaging. Specially designed magnetic resonance imaging (MRI) equipment called extremity MRI may be able detect bone erosions in the hands of RA patients where x-rays cannot. Further evaluation is necessary.

Symptoms of rheumatoid arthritis can be mimicked by things as benign as a bad mattress or as serious as cancer. A number of rare genetic diseases attack the joints. Physical injuries, infections, and poor circulation are among the many problems that can cause aches and pains. It would be impossible to discuss in this report the dozens of all conditions with symptoms of joint aches and pains.

Osteoarthritis. Osteoarthritis requires some special mention because it is the most common form of arthritis. It differs from RA in several important respects.

Osteoarthritis usually occurs in older people.
It is located in only one or a few joints. (In fact, osteoarthritis is probably most often confused with rheumatoid arthritis if it affects multiple joints in the body.)
The joints are less inflamed.
Progression of pain is almost always gradual.

Gout. Gout also causes swelling and severe pain in a joint, although most commonly starting in one joint. It is particularly difficult to distinguish chronic gout in older people from rheumatoid arthritis, however, since gout in this population can occur in a number of joints. A proper diagnosis can be made with a detailed medical history, laboratory tests, and detection in the affected joint of a salt called monosodium urate (MSU), which identifies gout.


Disease	Specific Subtypes
Osteoarthritis
Infectious Arthritis	Lyme disease, septic arthritis, bacterial endocarditis, mycobacterial and fungal arthritis, viral arthritis
Postinfectious or Reactive Arthritis	Reiter syndrome (a disorder characterized by arthritis and inflammation in the eye and urinary tract), rheumatic fever, inflammatory bowel disease
Crystal Induced Arthritis	Gout and pseudogout
Other Rheumatic Autoimmune Diseases	Systemic vasculitis, systemic lupus erythematosus, scleroderma, Still's Disease (also called juvenile rheumatoid arthritis), Behcet's disease
Other Diseases	Chronic fatigue syndrome, hepatitis C, familial Mediterranean fever, cancers, AIDS, leukemia, bunions, Whipple's disease, dermatomyositis, Henoch-Schonlein purpura, Kawasaki's disease, erythema nodosum, erythema multiforme, pyoderma gangrenosum, pustular psoriasis

Treatment

The treatment of rheumatoid arthritis involves medications and lifestyle changes.

Many drugs are used for managing the pain and slowing the progression of rheumatoid arthritis, but none completely cure the disease. Some experts believe that no single drug will ever cure rheumatoid arthritis because of the many factors that affect the disease at various times. The goals of drug treatment for rheumatoid arthritis include:

Reduce inflammation
Prevent damage to the bones and ligaments of the joint
Preserve movement
To be as inexpensive and as free from side effects as possible over the long-term

The drug categories used for RA include:

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) are the least potent drugs used for RA. These drugs relieve pain by reducing inflammation, but do not affect the course of the disease.
Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are the main drugs used for treating rheumatoid arthritis. They slow the progression of the disease. They are much more effective than NSAIDs but also have more side effects. Methotrexate (Rheumatrex, Trexall) is the most widely used of these drugs.
Biologic Response Modifiers (also known as Biologic DMARDs) are often prescribed to patients who have failed to respond to DMARDs. They may be used alone or in combination with DMARDs such as methotrexate. They modify or block destructive immune factors such as tumor-necrosis factor (TNF). Current anti-TNF drugs include infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira). Other biologic response modifiers include the interleukin-1 antagonist anakinra (Kineret), the T cell co-stimulation modulator abatacept (Orencia), and rituximab (Rituxan), which targets CD20-positive B cells.
Corticosteroids, or steroids, are powerful anti-inflammatory drugs that are used to quickly reduce inflammation. These drugs include prednisone and prednisolone.

The question of how early and how aggressively to treat RA has been the subject of great debate. Among patients with RA, some will go into remission and remain in remission for the length of their lives even in the absence of treatment, while others will go on to develop active, sometimes severe RA.

Current practice has moved towards treating the disease aggressively while it is in its early stages to help prevent it from reaching a more severe and chronic state. Studies have found less joint damage in patients with early, aggressive treatment, particularly with the use of DMARDs and TNF modifiers in combination with methotrexate. Intensive early dosing of methotrexate may help slow progression of rheumatoid arthritis. Early combination therapy with DMARDs and corticosteroids is also showing good results.

During the first year of treatment, combination therapy appears to reduce the progression of joint deterioration more rapidly and effectively than single drug treatment. In addition, patients who have not been helped by one drug often benefit from a combination of drugs. However, over a longer period of time, it is not clear whether a drug combination approach offers many advantages over single drugs. It is also not certain which combination of drugs works best. Depending on your particular health condition, and how you respond to the drugs prescribed, your doctor may try various treatment strategies.

Medications

Two-thirds of people with RA rank pain as their primary reason for seeking professional help. The most common pain relievers for RA are nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs block prostaglandins, the substances that dilate blood vessels and cause inflammation and pain. There are dozens of NSAIDs:

Over-the-counter NSAIDs include aspirin, ibuprofen (Motrin IB, Advil, Nuprin, Rufen), naproxen (Aleve), ketoprofen (Actron, Orudis KT).
Prescription NSAIDs include ibuprofen (Motrin), naproxen (Naprosyn, Anaprox), flurbiprofen (Ansaid), diclofenac (Voltaren), tolmetin (Tolectin), ketoprofen (Orudis, Oruvail), dexibuprofen (Seractil). In 2004, a new NSAID, meloxicam (Mobic) was approved in the U.S. for the management and treatment of rheumatoid arthritis.

Studies suggest that the best times for taking an NSAID may be after the evening meal and then again on awakening. RA symptoms increase gradually during the night, reaching their greatest severity at the time of awakening. Taking NSAIDs with food can reduce stomach discomfort, although it may slow down the pain-relieving effect.

In April 2005, the Food and Drug Administration (FDA) asked drug manufacturers of prescription NSAIDs to include with their products the same warning label used for the COX-2 inhibitor celecoxib (Celebrex). This "black box" warning, the FDA's strongest warning, emphasizes the increased risks for cardiovascular events and gastrointestinal bleeding associated with these drugs’ use. The FDA also requested manufacturers of OTC NSAIDs to revise their labels to include more specific language concerning potential cardiovascular and gastrointestinal risks. Due to its proven heart benefits, aspirin was excluded from these labeling revisions. In December 2006, the FDA proposed even stronger labeling changes to highlight these drugs’ risk for liver damage as well as alcohol and drug interactions.

Long-term, regular use of NSAIDs can increase the risk for heart attack, especially for people who have a heart condition. Long-term use of NSAIDs is also the second most common cause of ulcers and gastrointestinal bleeding. To reduce the risks associated with NSAIDs, take the lowest dose possible for pain relief.

Other possible side effects of NSAIDs may include:

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

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

NSAID-related bleeding and stomach problems may be responsible for 107,000 hospital admissions and 16,500 deaths each year. Those at high risk for bleeding include people over age 60, anyone with a history of ulcers of gastrointestinal bleeding, patients with serious heart conditions, people who abuse alcohol, and those who take medications such as anticoagulants (blood thinners) and corticosteroids.

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

COX-2 Inhibitors (Coxibs). Coxibs inhibit an inflammation-promoting enzyme called COX-2. This drug class was initially thought to provide benefits equal to NSAIDs but cause less gastrointestinal distress. However, following numerous reports of heart problems, skin rashes, and other adverse effects, the FDA re-evaluated the risks and benefits of this drug class. This lead to the removal of rofecoxib (Vioxx) and valdecoxib (Bextra) from the United States market. Celecoxib (Celebrex) is still available, but patients should ask their doctor whether the drug is appropriate and safe for them. In December 2006, the FDA approved celecoxib for the relief of symptoms of juvenile rheumatoid arthritis in patients ages 2 years and older.

Disease-modifying anti-rheumatic drugs (DMARDs) are the standard treatments for RA. They are used either alone or in combination with newer biologic DMARDs.

DMARDs do not have any common properties other than their ability to slow down the progression of rheumatoid arthritis. Many were used for other diseases and were found accidentally to help RA. DMARDs include:

Methotrexate (considered to be the current standard of care)
Leflunomide
Hydroxychloroquine
Sulfasalazine
Gold
Minocycline
Azathioprine
Cyclosporine

Unfortunately, all DMARDs tend to lose effectiveness over time, even methotrexate. Patients rarely use one drug for more than 2 years. Combining DMARDs with each other or with drugs in other categories offers the best approach for many patients. The addition of a corticosteroid to any combination may also be helpful.

All DMARDs may produce stomach and intestinal side effects, and, over the long-term, each poses some risk for rare but serious reactions. (In some cases, however, they may be less harmful than long-term NSAID treatment.)

Methotrexate. Methotrexate (Rheumatrex, Trexall) acts as an anti-inflammatory drug and is now the most frequently used DMARD, particularly for severe disease. It has a faster mode of action than other DMARDs, (it starts working within 3 - 6 weeks), and its effectiveness as a well proven in studies.

Even this drug loses effectiveness, however, when used alone. It may be more effective when used in combination with other DMARDs or other drugs. Recent studies have focused on combining methotrexate with various biological response modifier drugs, especially for treatment of patients with early aggressive arthritis. The combination appears to work better than single drug therapy.

About 20% of patients withdraw from methotrexate because of its side effects. They include nausea and vomiting, rash, mild hair loss, headache, mouth sores, and muscle aches. Methotrexate reduces levels of folic acid (folate) in the body, which can lead to some of these side effects. Doctors may prescribe folic acid supplements to prevent side effects. However, some research suggests that folic acid may interfere with methotrexate’s effectiveness.

Methotrexate is usually given as pills. Patients who need higher doses can take it as an injection. Methotrexate has fewer serious toxic effects than many DMARDs. Although these severe reactions are rare, they may include:

Kidney and liver damage. People at particular risk for liver damage from methotrexate include those with diabetes, obesity, and alcoholism.
Increased risk for infections
Lung disease occurs in up to 5% of people. People who have poor lung function are most at risk.
The drug increases the risk for birth defects and should not be taken by pregnant women. However, methotrexate will not harm a woman’s chance for future healthy pregnancy.

Leflunomide. Leflunomide (Arava) blocks autoimmune antibodies and reduces inflammation. It also may inhibit metalloproteinases (MMP), which are involved in cartilage destruction. It has the following benefits:

It slows disease progression as early as 6 months into treatment.
Comparison studies with methotrexate report a better quality of life with leflunomide, including more energy, greater vitality, and fewer emotional side effects. (Studies comparing their risk for serious adverse effects are mixed. One, for example, showed fewer problems with leflunomide, while another reported identical rates.)

The combination of methotrexate and leflunomide (which has different effects on the immune system) is very effective compared to either drug alone. (This combination poses a risk for liver toxicity and requires monitoring.)

Reports of adverse effects are comparable to those with methotrexate. Common problems include nausea, diarrhea, hair loss, and rash. Potentially serious side effects include infections and liver injury. Everyone taking leflunomide should be monitored regularly, including blood tests for liver function, and anyone with liver problems should not take this drug. Monitoring of serum concentrations of the most active metabolite of leflunomide may help predict treatment response.

Hydroxychloroquine. Hydroxychloroquine (Plaquenil) was originally used for preventing malaria and is now also used for mild, slowly progressive arthritis. It can help relieve pain and improve mobility. It has one of the least toxic profiles of the DMARDs. The downside is that this drug can take up to 6 months to achieve full benefit. It also does not appear to slow disease progression. One study concluded that joint erosion after 2 years was worse than with no DMARD at all.

As with all DMARDs, gastrointestinal complaints are fairly common. This drug used to be associated with eye and vision problems, but with current lower doses this side effect is rare. If vision problems occur, it is usually with people taking very high doses, those with kidney disease, or those over 60 years of age. Still, you should have regular eye exams while taking this drug and notify your doctor if you experience any sudden changes in vision.

Sulfasalazine. Sulfasalazine (Azulfidine) was developed in the 1930s for treating rheumatoid arthritis, but fell into disfavor when gold treatment emerged. It has regained popularity, however, and is now used for both adult and juvenile RA. It works best when the disease is confined to the joints. Symptom relief occurs within 1 - 3 months.

Side effects are common, particularly stomach and intestinal distress, which usually occur early in the course of treatment. (However, serious gastrointestinal side effects, such as stomach ulcers, occur less frequently with sulfasalazine than with NSAIDs.) A coated-tablet form may help reduce side effects. Other side effects include skin rash and headache. Sulfasalazine increases sensitivity to sunlight. Be sure to wear sunscreen (SPF 15 or higher) while taking this drug. People with intestinal or urinary obstructions or who have allergies to sulfa drugs or salicylates should not take sulfasalazine.

Gold. Gold has been a long-standing DMARD for rheumatoid arthritis, although its use has decreased with the development of disease modifying and biologic drugs. Gold is usually administered in an injected form because the oral form, auranofin (Ridaura), is much less effective. There are two injectable forms of gold: Gold sodium thiomalate (Myochrysine) and aurothioglucose (Solganal). It can take 3 - 6 months before injections have an effect on RA symptoms.

Gold injections cause mouth sores in about a third of patients. Skin side effects include itching and rash, which can be severe in some patients. . The most serious side effects of gold injections, while rare, are kidney damage and decreased white blood cell count. Gold injections are not usually given to pregnant women. It is not definite that gold causes birth defects but doctors generally recommend that women use birth control while receiving this drug.

Minocycline. Minocycline (Minocin) is a tetracycline antibiotic that is usually prescribed for patients with mild RA. It can take 2 - 3 months before symptoms begin to improve and up to a year for full benefit. Side effects include upset stomach, dizziness, and skin rash. Long-term use of minocycline can cause changes in skin color, but this side effect usually disappears once the medication is stopped. Minocycline can cause yeast infections in women. Minocycline increases sensitivity to sunlight and patients should be sure to wear sunscreen. In rare cases, minocycline can affect the kidneys and liver.

Azathioprine. Azathioprine (Imuran) suppresses immune system activity. It takes 6 - 8 weeks for early symptom improvement and up to 12 weeks for full benefit. Azathioprine can cause serious problems with the gastrointestinal tract. About 10 - 15% of patients experience nausea and vomiting, often accompanied by stomach pain and diarrhea. (Taking the medication twice daily, instead of once daily, or taking it after eating may help avoid this problem.) Azathioprine can also cause problems with liver function and pancreas gland inflammation, and can reduce white blood cell count.

Cyclosporine. Like azathioprine, cyclosporine (Sandimmune, Neoral) is an immunosuppressant. It is used for people with RA who have not responded to other drugs. It can take a week before symptoms improve and up to 3 months for full benefit. The most serious and common side effects of cyclosporine are high blood pressure and kidney function problems. While kidney function usually improves once the drug is stopped, mild-to-moderate high blood pressure may continue. Cyclosporine can also cause gout or worsen gout in people who have this condition.

Other common side effects include headache, nausea, vomiting, stomach pain and upset, and swelling of hands and feet. About 10% of patients who take cyclosporine develop tremors, increased hair growth, muscle cramps, and numbing or tingling in hands and feet (neuropathy). Swelling of the gums is also common. Patients should practice good dental hygiene, including regular brushing and flossing.

Biologic response modifiers are drugs made from living cells. These drugs target specific components of the immune system that contribute to the joint inflammation and damage that are part of the rheumatoid arthritis disease process.

Currently approved biologic response modifiers include:

Etanercept (Enbrel). Etanercept is an anti-tumor necrosis factor (anti-TNF) drug. Approved in 1998, etanercept was the first biologic response modifier drug for treatment of rheumatoid arthritis. It is also approved for juvenile RA and psoriatic arthritis.
Infliximab (Remicade). Approved in 1999, infliximab is also an anti-TNF drug. It is used in combination with methotrexate.
Adalimumab (Humira). Adalimumab is another anti-TNF drug. First approved in 2002 as a second-line treatment for RA, adalimumab received additional approvals in 2005 as a first-line treatment for RA and psoriatic arthritis. It is used alone or in combination with methotrexate or other DMARDs. It is also showing promising results in clinical trials for juvenile rheumatoid arthritis.
Anakinra (Kineret). Approved in 2001, anakinra targets interleukin-1 (IL-1), another type of immune factor.
Abatacept (Orencia). Approved in 2005 for adults with moderate-to-severe RA who have not responded to DMARD or anti-TNF drugs. Abatacept is known as a T cell co-stimulation modulator. It blocks T cell activation. It is used alone or in combination with other DMARDs aside from anti-TNF drugs.
Rituximab (Rituxan). Approved in 2006, rituximab targets CD20-positive B cells and blocks their activation. It is used in combination with methotrexate for patients with moderate-to-severe RA who have not responded to anti-TNF therapies.

Some of these drugs are used as first-line treatments for RA. Others are used for patients who have not responded to DMARDs or other types of treatment. Depending on the specific drug, they may be used alone or in combination with the DMARD methotrexate. However, biologic response modifiers are not used in combination with each other, as they can lead to serious infections.

As with other rheumatoid arthritis drugs, these drugs do not cure the disease but can help slow progression and joint damage. In recent clinical trials, some patients have achieved remission using methotrexate in combination with infliximab, adalimumab, or rituximab.

Side Effects and Complications. Etanercept, adalimumab, and anakinra are given by injection and may cause pain at the injection site. To prevent injection reactions, patients are sometimes pretreated with betamethasone, a corticosteroid drug, but some research suggests that the steroid does little good. Infliximab, abatacept and rituximab are given by intravenous infusion. Common infusion reactions include headache, nausea, and flu-like symptoms. Because biologic response modifiers affect the immune system, patients who take these drugs have an increased risk for infections.

Other risks associated with these drugs include:

Anti-TNF drugs (etanercept, infliximab, adalimumab) have been associated with sepsis, pneumonia, and tuberculosis; non-melanoma skin cancer, lymphoma, and other malignancies; lupus; heart failure; blood disorders (including aplastic anemia); palmoplantar psoriasis; lung disease; and liver damage.
Anakinra may cause a sudden drop in white blood cells (leukopenia) that increases the risk for infections.
Abatacept should be used cautiously in patients with chronic obstructive pulmonary disorder (COPD) as it may increase the risk for respiratory complications.
Rituximab has been associated with cases of a rare and deadly brain infection called progressive multifocal leukoencephalopathy (PML). It also may cause hepatitis B reactivation, viral infections, and heart rhythm disturbances and other heart problems.

Corticosteroids work rapidly to control inflammation and pain. Long-time use, however, can have severe adverse effects. Still, they are often used under the following conditions:

Oral corticosteroids, such as prednisolone and prednisone (Deltasone, Orasone), are most often used in combination with DMARDs, which significantly enhances the benefits of DMARDs.
Oral corticosteroids are sometimes used in early stage-RA for patients who cannot tolerate NSAIDs. Studies, in fact, suggest that low-dose corticosteroids may significantly slow joint pain when it is the first drug administered and then used for 2 years. (Even low-dose oral steroids have adverse effects on bone density, blood sugar, and weight.)
Higher doses of corticosteroids are used for flareups of vasculitis and severe reactions to medications.
Corticosteroids may also be used during pregnancy to avoid exposure to more toxic drugs.
Daily, low-dose corticosteroids are also needed in some patients to control their rheumatoid arthritis symptoms.
Corticosteroids are sometimes injected directly into joints for relief of flare-ups when only one or a few joints are affected. Experts suggest no more than three or four injections into a specific joint a year. Steroid injections in the joints may be a safe and effective treatment for juvenile rheumatoid arthritis and reduce the need for oral medication.
Corticosteroid pulse therapy (intravenous administration) may work as well as DMARDs.

Side Effects of Oral Corticosteroids. Serious side effects are associated with long-term use of oral steroids. (Low doses may reduce these risks, but they do not eliminate them.) Osteoporosis is a common and particularly severe long-term side effect of prolonged steroid use. Medications that can prevent osteoporosis include calcium supplements, parathyroid hormone, or bisphosphonates (alendronate etidronate, risedronate). Other adverse effects include cataracts, glaucoma, diabetes, fluid retention, susceptibility to infections, weight gain, hypertension, capillary fragility, acne, excess hair growth, wasting of the muscles, menstrual irregularities, irritability, insomnia, and, rarely, psychosis. Recent research suggests that prednisone can increase the risk of developing non-melanoma skin cancer.

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

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

Biologic Drugs. For many years, therapeutic treatment of rheumatoid arthritis focused on T cell mediation. New research is now examining the role of B cells, which become overactive in autoimmune disease, and how B cell depletion may help to reduce disease activity. Other areas of intense research include interleukin receptor antagonists, which target cytokines involved in the inflammatory process.

Many of the current investigational drugs are monoclonal antibodies (MAbs), biologic drugs that are designed to target specific receptors. Promising candidates in late-stage research include tocilizumab (Actemra), golimumab, denosumab, ocrelizumab, ofatumumab, and certolizumab.

Statins. Some research suggests that compounds derived from statins, the highly regarded cholesterol-lowering drugs, may suppress the inflammation responsible for RA damage.

Stem cell transplantation. Stem cells are the early versions of mature, specialized blood cells. Investigators are reporting that transplantation of donated hemopoietic stem cells, which mature into various blood cells, has induced remission in a few children with severe juvenile rheumatoid arthritis. The procedure is promising in select cases, but it can be highly toxic. More studies are needed to determine risks and benefits for RA patients.

Plasmapheresis. A device called the Prosorba column is used to remove inflammatory antibodies from the patient's blood. Small, short-term studies have shown that this therapy may slow or even halt the progression of the disease in a third to a half of patients. Side effects from the Prosorba column may include anemia, fatigue, itching, fever, a drop in blood pressure, and nausea. Nearly all patients experience an immediate flare-up of joint pain that lasts a few days. Some patients develop infection from the catheter used to remove blood. Long-term studies are needed.

Surgery

Certain surgical techniques may be helpful for people with severe deformities or disabilities.

Arthroscopy. Arthroscopy is performed to clean out bone and cartilage fragments that cause pain and inflammation. It is usually performed on the knee, but it also may be done on the hip:

The surgeon makes a small incision and injects a sterile solution to make the joint swell for easier viewing.
A lighted tube, called an arthroscope (which enables the surgeon to view the joint), is then inserted through another small incision.
Through a third incision, the surgeon trims, shaves, or stitches the damaged tissue. (Arthroscopy is most successful when the removal of cartilage only, and not bone, is involved.)

In many cases, the procedure can be done using local anesthetic, and the patient can go home within a day. In the case of knee operations, patients can resume mild activity in a couple of days, but full recovery can take up to 3 months.

Osteotomy. If only a certain section (the medial compartment) of the knee is damaged and deformed, the surgeon may choose to perform osteotomy:

The knee is opened.
A debridement (removal of damaged tissue) is performed in the joint to eliminate the loose or torn fragments that are causing pain and inflammation.
The bone is then reshaped to remove the deformity.

The procedure is best used in heavier adults who are under 60 years old.

Unicompartmental Knee Arthroplasty. Unicompartmental knee arthroplasty (also called unicondylar knee arthroplasty) may be a useful procedure in some cases of limited damage in the knee. It is intended to relieve pain and preserve function as long as possible before a total knee replacement is necessary. The procedure involves a small incision and insertion of small implants. It retains important knee ligaments, which should preserve more movement than a total knee replacement. The procedure is not widely available and is somewhat controversial, since the implants may not be as reliable as those in total knee replacement.

Synovectomy. Synovectomy is a procedure whereby the diseased joint lining is removed. It is used when more conservative measures fail, particularly in the wrist. Studies are suggesting, however, that with the use of lasers for the procedure, eventually synovectomy may prove to be an alternative to DMARD treatments in reducing symptoms and achieving long-term remission.

Joint Replacement Surgery. Eventually, even after these procedures, rheumatoid arthritis may progress to the point that normal functioning is impossible. In such cases, artificial (prosthetic) replacement joint implants may be considered for knees, hips, or other joints. The prosthesis is usually made of a chromium alloy and plastic and may be attached to the adjoining bones using a cement, polymethyl methacrylate, or the prosthesis may be composed of a porous material that allows bone to grow into and eventually adhere to the device.

Although this procedure has usually been performed in people over 60, implants are now lasting 20 years and more and younger patients with severe disability are finding them useful. Uncemented arthroplasty using porous material is showing particularly good results. Studies on hip replacement, for example, now report that after 10 years, 5% of patients require reoperation and 12% of patients report some pain.

Lifestyle Changes

It is important to maintain a balance between rest (which will reduce inflammation) and exercise (which will relieve stiffness and weakness). Studies have suggested that even as little as 3 hours of physical therapy over 6 weeks will help people with RA, and that these benefits are sustained.

The goal of exercise is to:

Maintain a wide range of motion
Increase strength, endurance, and mobility
Improve general health
Promote well-being

In general, doctors recommend the following approaches:

Start with the easiest exercises, stretching and tensing of the joints without movement.
Next attempt mild strength training. (One study found that people with RA who exercised with machines that use compressed air for gentle resistance experienced less pain and increased muscle tone.)
The next step is to try aerobic exercises. These include walking, dancing, or swimming, particularly in heated pools. Avoid heavy impact exercises, such as running, downhill skiing, and jumping.
Tai chi, which uses graceful slow sweeping movements, is an excellent method for combining stretching and range-of-motion exercises with relaxation techniques. It is of particularly value for elderly RA patients who report significantly less pain after practicing this technique.

While traditional guidelines have restricted RA patients to only gentle exercise, recent research suggests that more intense exercise may not only be safe, but may actually produce greater muscle strength and overall functioning. Common sense is the best guide:

If exercise is causing sharp pain, stop immediately.
If lesser aches and pains continue for more than 2 hours afterwards, try a lighter exercise program for a while.
Using large joints instead of small ones for ordinary tasks can help relieve pressure, for instance, closing a door with the hip or pushing buttons with the palm of the hand.

Many patients with RA try dietary approaches, such as fasting, vegan diets, or eliminating specific foods, that seem to worsen RA symptoms. There is little scientific evidence to support these approaches but some patients report anecdotally that they are helpful.

In recent years, a number of studies have suggested that the omega-3 fatty acids contained in fish oil may have anti-inflammatory properties useful for RA joint pain relief. The best source of fish oil is through increased consumption of fatty fish such as salmon, mackerel, and herring. Fish oil supplements are another option, but they may interact with certain medications. If you are thinking of trying fish oil supplements, talk to your doctor first.

Various ointments, including Ben Gay and capsaicin (a cream that use the active ingredient in chilli peppers), may help soothe painful joints.

Orthotic devices are specialized braces and splints that support and help align joints. Many such devices made from a variety of light materials are available and can be very helpful when worn properly.

A number of specially designed appliances and devices are available to ease daily activities.

Although the influence of stress or emotions on the progression of RA is not fully known, having a history of major depression that persists or reoccurs seems to increase the pain, disability, and fatigue. Stress management alone cannot reduce pain, but it may be very helpful in helping people deal with their condition.

One study found that people with RA reported significant clinical improvement after writing about their pain, stress, or other traumatic experiences. Writing for 20 minutes, just a few days a week, resulted in improvement that lasted for months. One study found that spirituality (defined as "a belief in a power outside oneself and one's own existence," as opposed to the practice of any specific religion) is associated with better health, happiness and well-being among RA patients. (Spiritual healing does not appear to offer any advantages.)

People often turn to alternative therapies or nontraditional remedies to relieve the pain of rheumatoid arthritis. Some alternative procedures, such as acupuncture, massage, relaxation techniques, biofeedback, and hypnosis, are not harmful and may be a useful adjunct to standard treatments.

In a small study, acupuncture reduced pain by a third in 73% of patients, and more than half reported at least a 50% improvement in pain. Patients also reduced their use of pain medications. Research presented at the 2006 American College of Rheumatology annual meeting suggested that both electroacupuncture and traditional acupuncture may help reduce joint tenderness.
Balneotherapy, also known as hydrotherapy or spa therapy, is an ancient form of therapy that involves mineral baths to soothe pain, and some patients have reported relief using such baths.
The NIH is conducting clinical trials to examine whether relaxation response, tai chi, stress management, and cognitive-behavioral therapy can help patients with RA feel better.

Herbal remedies used for RA include boswellia, equisetum arvense (horsetail), devil's claw, borage seed oil, and many others. To date, no evidence supports their efficacy.

Researchers are currently conducting studies in animals to determine if supplements extracted from the turmeric spice can help prevent joint inflammation. The U.S. National Institutes of Health is also conducting a clinical trial to compare the clinical effects of the Chinese herb Tripterygium wilfordii Hook F (TwHF) with the pharmaceutical drug sulfasalazine. TwHF is traditionally used in Chinese medicine for its anti-inflammatory properties.

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

Resources

www.niams.nih.gov -- The National Institute of Arthritis and Musculoskeletal and Skin Diseases
www.rheumatology.org -- American College of Rheumatology
www.arthritis.org -- The Arthritis Foundation
www.fda.gov/cder/drug/infopage/cox2 -- FDA information on COX-2 inhibitors and NSAIDs
www.clinicaltrials.gov -- Find a clinical trial

References

Chen YF, Jobanputra P, Barton P, Jowett S, Bryan S, Clark W, et al. A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness. Health Technol Assess. 2006 Nov;10(42):iii-iv, xi-xiii, 1-229.

Donahue KE, Gartlehner G, Jonas DE, Lux LJ, Thieda P, Jonas BL, et al. Systematic Review: Comparative Effectiveness and Harms of Disease-Modifying Medications for Rheumatoid Arthritis. Ann Intern Med. 2007 Nov 19 [Epub ahead of print]

Firestein GS. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005.

Furst DE, Breedveld FC, Kalden JR, Smolen JS, Burmester GR, Sieper J, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii2-22.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM,, et al. Comparison of treatment strategies in early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2007 Mar 20;146(6):406-15.

Goldberg RJ, Katz J. A meta-analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for inflammatory joint pain. Pain. 2007 May;129(1-2):210-23. Epub 2007 Mar 1.

Harris ED Jr. In: Harris ED Jr, ed. Kelley's Textbook of Rheumatology. 7th ed. Saunders; 2005. O’Dell JR. In: Goldman, ed. Cecil Medicine. 23rd ed. Saunders; 2007.

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007 Dec 1;370(9602):1861-74.

Smolen JS, Keystone EC, Emery P, Breedveld FC, Betteridge N, Burmester GR,. et al. Consensus statement on the use of rituximab in patients with rheumatoid arthritis. Ann Rheum Dis. 2007 Feb; 66(2): 143-50.

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