Psoriasis

Highlights

Overview:

Causes

Treatment

Outlook

Introduction

An estimated 7.5 million Americans (2.2% of the population) have psoriasis. Psoriasis is a chronic skin disorder in which there are sharply defined red patches on the skin, covered by a silvery, flaky surface. The disease activity may wax and wane over time.

The main disease activity leading to psoriasis occurs in the epidermis, the top five layers of the skin. The process starts in the basal (deepest) 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 they are 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 1/8 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. These are 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:

They may also be seen on the:

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.

Less Common Forms 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 areas 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. Nail psoriasis is linked to psoriatic arthritis.

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.

Pustular psoriasis can also accompany other forms of psoriasis and can be very severe.

Psoriatic Arthritis

Psoriatic arthritis (PsA) is an inflammatory condition that leads to stiff, tender, and inflamed joints. Estimates on its prevalence among people with psoriasis range from 2 - 42%. Psoriasis patients who also have AIDS and people 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.

PsA is often divided into five forms. The forms differ according to the location and severity of the affected joint:

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, it 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 caused by damage to factors in the immune system, enzymes, and other substances that control skin cell division. This combination of factors prompts an abnormal immune response, which causes inflammation and rapid production of immature skin cells.

Inflammatory Response and Autoimmunity

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

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:

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 the body's own 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. 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 antigens (HLA), a group of protein markers found on cells. Most immune disorders are associated with problems in how the body reacts to these different protein markers or antigens. However, other genetic and environmental factors are required to actually trigger the disease.

Eight key psoriasis susceptibility genes (designated PSORS 1 - 8) seem to be involved with psoriasis. Certain variations or changes in these genes may increase the risk of psoriasis. These same variations linked to psoriasis and psoriatic arthritis are also associated with four known autoimmune diseases: type 1 diabetes, Grave's disease, celiac disease, and rheumatoid arthritis, suggesting that all of these diseases have the same genetic basis.

The presence of a recently identified variation in a group of genes known as LCE can protect against the development of psoriasis.

Triggers

Weather, stress, injury, infection, and medications, while not direct causes, are often important in triggering, and worsening, the 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:

Skin Injuries and the Koebner Response. The Koebner response is a delayed response to skin injuries, in which psoriasis develops later at the site of the injury. In some cases, even mild abrasions can cause an eruption, which may be why psoriasis tends to frequently occur on the elbows or knees. However, psoriasis can develop in areas that have not been injured.

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

Severe flare-ups may occur in people with psoriasis who stop taking their steroid pills, or who discontinue the 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:

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:

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.

In general, severe or widespread psoriasis is harder to treat. However, some forms of psoriasis can be very resistant to treatment, even though they are not categorized as severe. They include:

Treatment

Many creams, ointments, lotions, and pills are available to treat psoriasis. Some patients require only over-the-counter treatment, or even no treatment.

Many 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:

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

Treatment Sequences

Giving treatment in a stepwise order can help provide quick symptom relief and long-term maintenance. It involves three main steps:

Choices for transitional or maintenance treatments depend on the severity of the condition.

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

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:

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. These drugs work for most patients because they:

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

Topical steroids are often rated by how strong or potent they are:

In the past, topical steroids were used twice a day. For some patients, certain drugs may work just as well if applied once a day. Both high-potency steroids, and possibly medium-strength steroids, such as triamcinolone (Aureocort, Tri-Adcortyl), may be beneficial as a once-daily treatment.

However, corticosteroids used alone are not enough for most patients. Combining topical steroids with other topical drugs (see below) is often needed. Many patients also need oral medicines.

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

Loss of Effectiveness. In most cases, patients become tolerant to the effects of the drugs, and the drugs no longer work as well 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.

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 that are showing promise include maxacalcitol, tacalcitol, and calcitriol (Vectical).

Calcipotriene appears to:

It works just as well as moderate topical corticosteroids, short-term anthralin, and coal tar in improving mild-to-moderate plaque psoriasis. But 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 body-wide treatments may improve its effectiveness. Calcipotriene doesn't work as well as the highest potency corticosteroids, but combining both medications is proving to be more effective than taking either one alone. Taclonex, an ointment containing both calcipotriol and betamethasone, is available 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, combination treatments reduce 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:

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.

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.

Coal tar preparations have the following drawbacks:

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 than other formulations to stain.

Side Effects and Drawbacks. Anthralin may cause the following problems:

Patients should not use anthralin on the face. 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 in the cream 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 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 steroids, retinoids do not cause thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. Retinoid gel 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 can be used 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 healthy skin.

At levels high enough to be effective for treating psoriasis, tazarotene can cause severe skin irritation on treated areas. This medicine is usually used in combination with other treatments, allowing patients to use 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, clobetasol propionate, and betamethasone, are proving to be very helpful.

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 abrasions 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 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.

Systemic medications approved for treating psoriasis include:


Off-label Systemics. Physicians sometimes prescribe medications off-label. The medications below are not specifically approved for psoriasis, but they are sometimes effective. The following drugs are FDA approved for other conditions, such as acne or cancer, but may sometimes be prescribed for psoriasis:

· Hydrea (hydroxyurea)
· Isotretinoin
· Mycophenolatemofetil
· Sulfasalazine
· 6-thioguanine

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.

Several new agents to treat psoriasis are under study, including oral medications and monoclonal antibodies. The following agents show promising results for plaque psoriasis but none have yet been approved for use:

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 drug is taken weekly, not daily.

Side Effects. Many patients are able to tolerate methotrexate with few side effects. Possible side effects include:

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, but relatively uncommon side effects include:

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.

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.

Taking nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, or naproxen at the same time as methotrexate may change the blood levels of methotrexate. Always talk with your doctor before taking these or any other medications in combinations.

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 the actual pregnancy. Methotrexate may also cause temporary impairment of fertility in men. Patients with Hepatitis B should not take methotrexate.

People with the following conditions are unlikely to be given 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. It is also effective in a low-dose formulation for symptoms of nail psoriasis. 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 greatest success rates of any treatment.

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

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) and 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.

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, von Zumbusch pustular psoriasis, or erythrodermic 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:

More serious complications may include:

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 -- as well as 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 like general immunosuppressants. Biologic drugs are expensive.

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:

Types of T-cell blockers:

Types of TNF blockers:

Side effects and risks of TNF blockers:

A number of other side effects are also possible.



Monoclonal Antibodies

Human monoclonal antibodies bind to proteins or cells and stimulate the immune system to destroy those cells.

Other Second- and Third-Line Treatments

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, the 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.

Psoralen and Ultraviolet A Radiation (PUVA)

Ultraviolet A (UVA) is a main part of sunlight. PUVA therapy 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 treatment with UVB.

PUVA treatments cause inflammation and redness 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 the 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:

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.

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, 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 who are resistant to PUVA or PUVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA.

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 also reported an increased risk of melanoma. The risk for skin cancers is higher in people who have:

Discussions are under way about discontinuing PUVA treatment of psoriasis. The following are pro and con arguments about the procedure:

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:

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

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:

UVB Therapy

Ultraviolet B, another part of sunlight, 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 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 narrowband 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:

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 is 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.

Narrowband Ultraviolet B (NB-UVB) Radiation

Narrowband radiation may be safer than other approaches, and some scientists 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 narrowband 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 risks 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 of psoriasis, and remissions that have lasted up to 13 months. Treatment sessions can take 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 facility. Many patients have achieved a significant reduction in symptoms after taking acitretin and being 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 puts people at 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.

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:

Some scientists 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 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 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 are taking.

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:

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:

Emotional and Social Consequences

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

Researchers have reported the following:

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.

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 blood cell formation and preventing 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 elevated in patients with mild psoriasis. There is some indication, however, that patients with psoriasis have a higher risk for non-melanoma skin cancers, regardless of their treatments.

Obesity, diabetes, and heart risks: Psoriasis has been linked to an increased risk of heart attack and cardiovascular disease. Patients with psoriasis are much more likely to have hardening of the arteries (atherosclerosis) and other blood vessel diseases than people without psoriasis. These conditions are also related to inflammation, which may be why people with psoriasis are more likely to develop diabetes and high blood pressure than people without the condition. 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:

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.

Resources

References

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Review Date: 12/18/2012
Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School. Also reviewed by David Zieve, MD, MHA, Medical Director, A.D.A.M. Health Solutions, Ebix, Inc.
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