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•	In-Depth Reports Home

In This Report

•	Highlights
•	Introduction
•	Types of Psoriasis
•	Causes
•	Risk Factors
•	Diagnosis
•	Treatment
•	Topical Medications
•	Systemic Medications
•	Phototherapy
•	Managing Psoriasis
•	Outlook
•	Resources
•	References

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Psoriasis

Highlights

• An estimated 5 million people have been diagnosed with psoriasis, and as many as 3.2 million adults have the disease without knowing it. Men are more likely to be undiagnosed than women.

Causes

• Researchers have discovered seven new DNA variations that increase the risk of psoriasis. The same DNA variations linked to psoriasis and psoriatic arthritis are also associated with four autoimmune diseases: type 1 diabetes, Grave's disease, celiac disease, and rheumatoid arthritis, suggesting that all of these diseases have the same genetic basis.

Treatment

• The drug, efalizumab (Raptiva), was withdrawn from the U.S. market because of the risk of causing multifocal leukoencephalopathy.
• The drug etanercept (Enbrel), which is currently approved to treat psoriasis in adults, is also effective in children and adolescents with moderate-to-severe plaque psoriasis. There is currently no FDA-approved systemic (body-wide) drug available to treat psoriasis in young patients.
• The FDA has approved adalimumab (Humira) for moderate-to-severe chronic plaque psoriasis. Studies have shown that the drug significantly improves symptoms in most patients.
• The investigational biologic drug, ustekinumab, appears to reduce psoriasis symptoms after 12 weeks of treatment, compared to placebo (inactive drug). The drug's manufacturer has applied for FDA approval.
• An investigational drug that is similar to cyclosporine but with fewer side effects has shown promise in clinical trials. In studies, ISA247 significantly reduced symptoms of plaque psoriasis compared to placebo. Most of the side effects with the drug were mild, and included headache and upper respiratory tract infections.

Introduction

An estimated 5 million Americans have been diagnosed with psoriasis, and as many as 3.2 million people have the disease without knowing it. Psoriasis is a chronic skin disorder in which there are 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 people 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 skin layer underneath (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

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 of time. 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

They may also be seen on the:

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

Psoriatic arthritis (PsA) is an inflammatory condition that leads to 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 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. The condition usually affects multiple joints. In about half of the cases, symmetric PsA 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. However, research has also linked smoking to an increased risk of psoriasis, and because smoking causes serious health problems and should not be considered as a way to delay this type of psoriasis.

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.

Inflammatory Response and Autoimmunity

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 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 are a type of white blood cell designed to recognize foreign substances (antigens) and launch an offensive or defensive action against them. Lymphocytes include two subtypes known as T cells and B cells:

• 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.

A type of T cell called a helper T cell stimulates B cells and other white blood cells to attack a foreign substance. In psoriasis, however, the helper T cell appears 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.

In psoriasis, helper T cells also release or stimulate the production of powerful immune factors called cytokines. In small amounts, cytokines are very important for healing. However, the high level of these cytokines that occurs in psoriasis can cause serious damage, including inflammation and injury during the psoriasis disease process.

Genetic Factors

A combination of genes is involved with increasing a person's susceptibility to the conditions leading to psoriasis. However, researchers are still unsure as to exactly how the disease is inherited.

HLA Molecules. The processes leading to all autoimmune diseases involve the human leukocyte antigen (HLA) system. Most immune disorders are associated with problems with this system. However, other genetic and environmental factors are required to actually trigger the disease.

Four key genes (named PSOR 1 - 4) seem to be involved with psoriasis. Seven recently identified DNA variations also may increase the risk of psoriasis. The variations are located in an area that helps the body distinguish its own cells from foreign invaders. These same DNA variations linked to psoriasis and psoriatic arthritis were also associated with four autoimmune diseases: type 1 diabetes, Grave's disease, celiac disease, and rheumatoid arthritis, suggesting that all of these diseases have the same genetic basis.

Triggers

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. 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 Koebner Response. The Koebner 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 (NSAID) -- Note: Other NSAIDs, such as meclofenamate, may actually improve the condition.
• Progesterone, used in female hormone therapies

Severe flare-ups may occur in people with psoriasis who stop taking their steroid pills 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 Koebner response.

Risk Factors

Risk factors for psoriasis include:

• Age under 20. About 40% of people 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 often 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.

Disease Severity

The severity of psoriasis 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.

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

Although 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 are pills or injections that affect the whole body, not just the skin
• Phototherapy, which uses light to treat psoriasis lesions

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

Treatment Sequences

Giving treatment in a particular order can help provide 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.

Rotational Therapy

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.

Oral and Injected Therapy

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.

Combination Therapies

Doctors increasingly use combinations of pills, creams, ointments, and phototherapy instead of single medications. Combinations of oral treatments are particularly useful, because the doses of each drug can be reduced. This lowers the risk of severe side effects. Thousands of combinations are possible, and patients should discuss with their doctors the best treatment for their 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 clear up symptoms completely, however.

Topical Corticosteroids

Topical corticosteroids are the mainstay of psoriasis treatment 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 drug 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

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:

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

Loss of Effectiveness. In most cases, 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.

Coal Tar

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

Anthralin (Dritho-Scalp, Drithocreme, Micanol) 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. People with kidney problems should use anthralin with caution.

As with tar, anthralin's use has also declined since the 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 their 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.

Topical Vitamin D3-Related Treatments

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 using it 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)
• Act 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 with 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 its 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 its effectiveness. Because combining medications allows patients to use lower doses of both medications, it reduces 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.

Topical Retinoids

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

Unlike with 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 any time; the cream on up to 35% of the body.

Combining topical retinoids with other psoriasis treatments, such as 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 is usually used in combination with other treatments, allowing a lower dose. Mixing the drug in equal amounts with petroleum jelly (Vaseline) at first, and then gradually increasing the amount of tazarotene may help the skin areas become less sensitive. 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

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, because 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.

Occlusive Tapes

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 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 returning 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.

Investigational Medications

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. In patients with psoriasis of the face, a 1% pimecrolimus cream applied twice a day may significantly improve symptoms.

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, patients 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

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 that has been 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 they should take folic acid supplements (generally recommended at 1 mg daily).

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. This drug should not be used during pregnancy, because it can cause miscarriages or birth defects in the baby. It may harm fertility in men.
• Kidney complications.
• Liver damage. This drug may cause 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 the urine, and use of rheumatoid arthritis drugs called DMARDs.
• Lymphomas. A few cases of lymphoma have been reported, which are most likely related to the drug's immune-suppressing (lowering) effects. In most instances, the disease went 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. This is an uncommon side effect in patients who have 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 methotrexate's side effects, some experts view it as the best therapy for widespread plaque psoriasis. It may also be effective for some patients with generalized erythrodermic and pustular psoriasis, as well as psoriatic arthritis.

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.

People with the following conditions should also avoid taking methotrexate:

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

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

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 types. When used alone, it is much less effective against more common forms of psoriasis, such as plaque or guttate psoriasis. However, when combined with PUVA phototherapy it can markedly improve the response, even in patients with these forms of psoriasis.

Accutane, more commonly used to treat acne, is far less potent than acitretin, but it may still be effective against pustular psoriasis. The drug may 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 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 mucus 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 mucus 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 whole-body 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.

Oral Retinoids and Pregnancy

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.

• 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 to cause birth defects during that time. Be cautious about cooking products and over-the-counter preparations, such as cough syrup, which may contain alcohol.
• Women who are pregnant or who plan to become pregnant should not use isotretinoin. Everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE, which ensures that no woman starts retinoid therapy while pregnant or trying to get pregnant.

Cyclosporine

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 it 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, because 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 take cyclosporine after PUVA therapy have a higher incidence of squamous cell skin cancer. The risks are greatest 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 to use 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.

Newer forms of cyclosporine that have fewer side effects are being investigated.

Biological Response Modifiers

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 traditionally second- or third-line treatments, and may be used alone or in combination with first-line systemic drugs. Depending on the severity of psoriasis, some of these drugs may be used earlier in the course of treatment. Studies of these medications have primarily been done on patients who are over 18 years old.

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. It is very effective for psoriasis of the scalp. However, it doesn't work for all patients. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. They 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.

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. Continuing etanercept after 12 weeks may lower the severity of disease without increasing infections or side effects. Although etanercept has not been studied in children who have psoriasis, it has been shown to be safe and effective for treating children with rheumatoid arthritis.
• 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 most patients with severe psoriasis who are treated with infliximab.
• Adalimumab (Humira) has been approved for moderate-to-severe chronic plaque psoriasis. It is given by injection weekly at first, and then bi-weekly.

Investigational Biologics

Interleukins (IL) being investigated as sources or targets of therapy include IL-4, IL-2, IL-8, IL-11, and IL-12. The investigational biologic drug, ustekinumab, which targets IL-12 and IL-23, has been shown to reduce or clear symptoms in some patients with psoriasis. The drug's manufacturer has applied for FDA approval.

Another investigational medicine called ABT-874 has greatly reduced symptoms in most patients studied. ABT-874 targets proteins that are responsible for psoriasis-related inflammation.

Other Second- and Third-Line Treatments

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. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and have fewer side effects. (Some immunosuppressants 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, phototherapy may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

Psoralens and Ultraviolet A Radiation (PUVA)

Ultraviolet A (UVA) is a main part of sunlight. UVA phototherapy uses a photosensitizing medication (usually psoralen) in combination with UVA radiation. 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 to develop in the skin 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, because the full effects of the treatments are not evident for 48 hours.

It takes an average of about 25 PUVA treatments for the full effect to be seen, 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, 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 its effectiveness or increase the 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 (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, because 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 the 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 people 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 treatment of psoriasis, for the following reasons:

• 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.
• Supporters of PUVA argue that it is not yet known whether 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, adding retinoids may protect against skin cancers while increasing the treatment's effectiveness.

Protective Measures with PUVA Therapy

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 the genitals, abdominal skin, and breasts, should be covered until the exposed areas tan, which usually occurs 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 care professional to check the patient periodically
• A door that can be opened by the patient easily and with little pressure
• A timer that ends the session automatically
• An accessible alarm device

Protective Measures After Treatment. The drugs used in PUVA make patients more likely to get a natural sunburn for a few hours after treatment. Patients should take the following precautions:

• Wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. Patients 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, avoid exposure to daylight, even if the day is cloudy or exposure is only through windows.
• Wear heavy opaque clothing (clothes that do not let light through) outside, including hats and gloves.
• 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.
• Do not spend a long time in sunlight for at least 2 days after the combined treatment.

UVB Therapy

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
• Narrow-band UVB (NB-UVB)
• Laser treatments

Broadband Ultraviolet B (UVB) Radiation

Broad spectrum or broadband 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 is generally given as follows:

• Treatment starts in the doctor's office or another medical setting. Once the disease has stabilized, the patient can get 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 lighter or darker skin. The lightest skin is exposed to the briefest session. The duration increases with each treatment until the skin clears or the patient experiences itching or irritation. 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 better tolerated.

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 a high-dose (6%) preparation. Such regimens are unpleasant, but are still useful for some patients with severe psoriasis, because 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 trying 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 that UVB treatments pose any risk for skin cancers except on male genitals. This risk, however, can be significant (4.5%) at high doses.

Narrow-Band Ultraviolet B (NB-UVB) Radiation

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 effect on the disease process itself is unclear. The light wavelength is between 310 - 312 nanometers, which 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 such as nausea. NB-UVB is also safe for pregnant women and children.

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

Laser Treatments

Laser UVB Treatment. A 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, because 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 those of 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 for 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.

Commercial Tanning Units

Home tanning devices and tanning salons are not usually recommended, but they may be helpful for patients who do not have access to a medical unit. Many patients have 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 up psoriasis in people with mild-to-moderate conditions. People should cover non-affected areas with clothing or sunscreen and sunbathe 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 stay of several weeks at the Dead Sea in Israel has been proven to significantly improve or clear psoriasis in 88% of the patients who travel there. The region offers a unique combination of intense but naturally filtered UVA radiation combined with minerals and salts from the sea.

Reducing Stress and Anxiety

Because of the association between negative emotions and psoriatic flare-ups, relaxation and anti-stress techniques may be helpful. Hypnosis aimed at reducing stress may relieve symptoms.

Some patients have had a traumatic or stressful event coincide with the appearance of psoriasis. Talking to a psychiatrist about the issue may significantly improve symptoms.

Treating Dry Skin

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, which removes scaly skin and may help moisturizers and topical prescription medications penetrate the skin.
• Then, apply a thick moisturizer or emollient, such as Vaseline, Cetaphil cream, or Eucerin cream. Lotions are not good enough moisturizers.
• Wear special gloves made of Gore-Tex (DermaPore) at night over a thick moisturizer cream. These gloves are protective but also allow moisture to escape.

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

Remedies for Itching and Irritation

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.

Dietary Factors

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 oils, have anti-inflammatory properties that may benefit some patients with psoriasis and other autoimmune conditions.

Alternative Remedies

Patients with persistent psoriasis may be tempted to try alternative or untested treatments, including herbs and other nontraditional therapies. Green tea slowed the growth of skin cells in animal studies, and may one day prove to be useful in treating psoriasis, but more research is needed.

Various other herbal supplements have been used for psoriasis, but to date no clinical studies have been reported on these substances. Do not use any unproven therapy without first consulting a doctor to be sure such treatment is not harmful, and does not interfere with any medications you take.

Herbs and Supplements

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 drugs. 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 is 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.
• Increased levels of estrogen may be responsible for this improvement. Relapse may occur after giving birth.

Emotional and Social Consequences

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

• Many patients have 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.

Substance Abuse

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. One review of 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.

Physical and Medical Complications of Psoriasis

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

Skin Cancers. Patients with severe psoriasis (who receive medications that affect the whole body) may be at higher-than-normal risk for developing cancers, primarily skin cancers and lymphomas. The risk is not any higher in 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.

Obesity, diabetes, and heart risks: There are also increased risks of diabetes, heart disease, heart attacks, and cancer in patients with psoriasis. It is not yet known whether there are genetic links between psoriasis and some of these conditions. The connection may also have to do with shared risk factors, such as smoking and obesity. Patients with moderate-to-severe psoriasis should be screened, and possibly treated, for cardiovascular risks.

Complications of Erythrodermic and Pustular Psoriasis

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.

Complications of Psoriatic Arthritis

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. 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

Chen YJ, Wu CY, Shen JL, Chu SY, Chen CK, Chang YT, Chen CM. Psoriasis independently associated with hyperleptinemia contributing to metabolic syndrome. Arch Derm. 2008;144:1571-1575.

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

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