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In This Report

•	Highlights
•	Introduction
•	Causes
•	Risk Factors
•	Prognosis
•	Diagnosis
•	Treatment
•	Topical Medications
•	Other Medications
•	Phototherapy
•	Managing Psoriasis
•	Resources
•	References

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Psoriasis

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Psoriasis

Highlights

Research

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

Drug Research

Results from a Phase III (late-stage) study show that adalimumab (Humira) is more effective than methotrexate in the treatment of moderate-to-severe psoriasis. In the study, 80% of patients treated for 16 weeks with adalimumab reported a 75% or better improvement, compared with 36% of patients treated with methotrexate.

Drug Approvals

An ointment containing a combination of the drugs calcipotriol and betamethasone was approved by the Food and Drug Administration (FDA) in January 2006 for the treatment of adults with psoriasis. The product, marketed in the U.S. as Taclonex, was more effective in clinical studies than either drug alone.

Drug Warnings

As of December 31, 2005, everyone who takes, prescribes, or dispenses the drug isotretinoin (Accutane) must enroll in a national registry called iPLEDGE, which is designed to prevent pregnancies in women taking this drug. Accutane has also been linked to suicide and suicidal attempts.

Introduction

Psoriasis is a chronic skin disorder marked by periodic flare-ups of sharply defined red patches, covered by a silvery, flaky surface. The primary 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 manufactured.
• Keratinocytes are immature skin cells that produce keratin, a tough protein that helps form hair and nails as well as skin. In normal cell growth, keratinocytes mature and migrate from the bottom (basal) layer to the surface and are shed unobtrusively. This process takes about a month.
• In psoriasis, however, the keratinocytes multiply very rapidly and travel from the basal layer to the surface in only about 4 days. The skin cannot shed these cells quickly enough, so they accumulate in thick, dry patches, or plaques.
• Silvery, flaky areas of dead skin build up on the surface of the plaques and are shed. The underlying skin layer, the dermis, is red and inflamed (swollen).
• The dermis contains nerves, blood vessels, and lymphatic vessels. They supply the abnormally multiplying keratinocytes with their blood, and also transport strong immune factors that cause the underlying inflammation and redness.

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

Plaque Psoriasis

Plaque psoriasis is the most common form of psoriasis, and causes skin patches with the following characteristics:

• The patches start off in small areas, about one-eighth of an inch in diameter. They usually appear symmetrically (in the same areas on opposite sides of the body).
• The patches gradually enlarge 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 be wavy and snake-like.
• Eventually separate patches may join together to form larger areas as the disorder develops. In some cases, the patches can become very large and cover wide areas of the back or chest (known as geographic plaques because they resemble maps).

Location of Plaque Psoriasis:

• Patches most often occur on the elbows, knees, and the lower back.
• About half of patients develop psoriasis on the scalp. Many patients have only a few patches in this location. In some cases, however, psoriasis can cover the scalp with thick plaques that may even extend down from the hairline to the forehead. It rarely affects the face in adulthood, however.
• Patches also can appear on the palms and soles, in the genital areas of both men and women, above the pelvic bone, and on the thighs and calves.
• 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.

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

Psoriatic Arthritis

Psoriatic arthritis (PsA) is an inflammatory condition characterized by stiff, tender, and inflamed joints. About 80% of PsA patients have psoriasis in the nails. Arthritic and skin flare-ups tend to occur at the same time. It is not clear whether psoriatic arthritis is a unique disease or a genuine variation of psoriasis, though evidence suggests they are both caused by the same immune system problem.

Location of Joint Pain Psoriatic Arthritis. Some experts define five forms of PsA. They differ in the location and severity of the affected joint:

• Symmetric PsA: Symmetric arthritis occurs in the same location on both sides of the body. It usually affects multiple pairs of joints, and, in about half of the cases, the condition will progress. The condition is very similar to, but less disabling than, rheumatoid arthritis. The psoriasis itself is often severe.
• Asymmetric PsA: Asymmetric PsA 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 symmetric locations.
• Distal Interphalangeal Predominant (DIP): DIP involves the joints of the fingers and toes closest to the nail, and 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 experience stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. The spine can be involved in up to three-quarters of all 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 arthritis that affects less than 5% of PsA cases. It principally 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.

Course of Psoriatic Arthritis. Although patients with psoriatic arthritis tend to have mild skin symptoms, the disease is systemic, affecting the whole 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, whose letters form the symptoms:

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

Prevalence of Psoriatic Arthritis. Estimates on its prevalence among those with psoriasis range from 2% to as high as 42%. AIDS patients and those with severe psoriasis are at higher risk for developing PsA.

Causes

The precise causes of psoriasis are unknown. It is generally believed that psoriasis is a disorder in which factors in the immune system, enzymes, and other materials that regulate skin cell division become damaged. This abnormal immune response causes rapid production of keratinocytes (immature skin cells) and inflammation. Such events are likely to be triggered by environmental factors, such as weather or stress, in people with genetic factors that make them susceptible (vulnerable).

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

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

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

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

T cells are further categorized as killer T cells or helper T cells (TH cells).

• Killer T cells directly attack antigens found on bacteria or other cells.
• Helper T cells also recognize antigens, but their role is two fold. They stimulate B cells and other white cells to attack the antigen. They also produce cytokines, powerful immune factors that have an important role in the inflammatory process.

Helper T cells and the Inflammatory Response. The actions of the TH cells are of special interest. Researchers have observed high numbers of TH cells in psoriatic plaques:

• The activated TH cells enter the skin cells in psoriasis and, in the case of psoriatic arthritis, the joints.
• TH cells normally stimulate B cells to produce antibodies. In psoriasis, however, they appear to direct the B cells to produce autoantibodies ("self" antibodies), which are directed against the body's own cells. In psoriasis, TH cells target self skin cells. In psoriatic arthritis, cells in the joints also come under attack.
• Autoantibodies remain in circulation in the resulting autoimmune process, continuing to mount an immune attack against these cells.

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

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

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

Genetic Factors

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

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

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

Environmental and Other Triggers

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

Weather. Weather is a strong factor in psoriasis:

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

Stress and Strong Emotions. Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. In one study, nearly 40% of patients remembered a specific stressful event that occurred within a month of a psoriasis flare. A 2001 study suggested that stress can trigger specific immune factors associated with psoriasis flares. Some evidence indicated that people with psoriasis may respond to stress differently from those without the skin disease. In one study, psoriasis patients had fewer aggressive verbal responses than others did when confronted with hostile situations.

Infection. Infections caused by viruses or bacteria can trigger some cases of psoriasis. Some examples include the following:

• Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and so-called "strep" throat, are known to trigger guttate psoriasis in children and young adults. The infections may also worsen ordinary plaque psoriasis.
• The 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 an indirect role in the continuation of psoriasis. This HPV form is not the virus associated with cervical cancer and genital warts.
• Helicobacter pylori (H. pylori) infection, a major cause of peptic ulcers, has been proposed as a possible cause of psoriasis. Research in 2001 indicated that this is highly unlikely, at least in children.

It seems reasonable to assume that pustular psoriasis, which resembles an infection, is caused by some organism, but none to date have been identified.

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

Drugs. Numerous drugs can worsen or cause an eruption of pre-existing, inactive psoriasis, including the following:

• The anti-malarial drug chloroquine
• Certain drugs used for hypertension and heart problems, including angiotensin-converting enzyme (ACE) inhibitors. Beta-blockers may actually trigger the onset of psoriasis and produce flare-ups in people who already have it.
• Progesterone used in female hormone therapies
• Lithium, which is used in bipolar disorder, may trigger the onset of the disease and cause severe flare-ups in people who already have psoriasis.
• Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), can cause or worsen psoriasis. Other NSAIDs, such as meclofenamate, may actually improve the condition.
• Withdrawing from oral steroids (steroids taken by mouth), or from very strong steroid ointments that cover wide skin areas, can cause flare-ups of severe psoriasis. The flare-ups may be of various psoriatic forms, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.
• Medications that cause rashes, a side effect of many drugs, can trigger psoriasis as part of the Köbner response.

Risk Factors

Between 5.8 and 7.5 million Americans have psoriasis, and it affects between 2 - 3% of the world's population.

Gender. Some studies have indicated that more men than women have psoriasis.

Age. About 40% of patients report developing psoriasis before age 20, and 10% had the disease before age 10. Psoriasis (most often plaque psoriasis) can even occur in infants, although mild or non-typical symptoms in young patients can make it difficult to diagnose the problem properly.

Family History

About 35% of those with psoriasis have one or more family members with the disorder. One study reported that the lifetime risk for psoriasis is 4% in someone with no family history of psoriasis, 28% with one affected parent, and 68% with both parents affected by psoriasis.

Geography and Ethnicity

Climate plays a role in risk. Some studies have found that the disorder develops earlier and more frequently in colder climates. For example, psoriasis occurs more frequently in African-Americans and in Caucasians who live in colder climates than in people of any ethnicity who live in Africa. Psoriasis is also common in Japanese individuals. It is uncommon in Native Americans of either North or South American descent.

Prognosis

Although psoriasis is not fatal, it can increase the risk for drug and alcohol abuse that, in some studies, has increased mortality rates in psoriasis patients. Even in its mildest form, psoriasis can still cause itching, burning, stinging, and bleeding. These symptoms can be very debilitating in more severe cases.

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

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

The palm of the hand equals 1% of the body. It is important to remember, however, that the severity of the disease is also measured by its effect on a person’s quality of life.

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
• Inverse psoriasis (which occurs in the folds of the skin)
• Scalp psoriasis
• Psoriatic arthritis

Course of Psoriasis

Psoriasis is lifelong and not curable. Although it is also marked by rapid cell growth, psoriasis is neither cancerous nor contagious. In general, studies report the following features of its course:

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

Emotional and Social Consequences

Effect on Quality of Life. The emotional and social consequences of psoriasis should not be underestimated.

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

Researchers have reported the following:

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

Higher Risk for 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.

Physical and Medical Complications of Psoriasis

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

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

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. Studies report this happens in about 5 - 16% of patients. Psoriasis patients with other arthritic conditions (osteoarthritis or rheumatoid arthritis) in the joints of the fingers tend to have a higher risk.
• People with PsA may have a higher risk for respiratory illnesses.

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

Diagnosis

A microscopic examination of tissue taken from the affected skin patch is required 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. Changes in the nails typical of psoriasis are often strong indicators of psoriasis.

Ruling Out Other Conditions

Distinguishing Psoriasis Patches from Other Disorders. Several conditions produce symptoms that resemble those of psoriasis. Examples include:

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

Distinguishing Psoriatic Arthritis from Other Conditions. Psoriatic arthritis may resemble the following:

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

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

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.

Treatment Options

In general, the following three treatment options are used for psoriasis, from least to greatest strength:

• Topical (rub on) Medications. Options include lotions, ointments, creams, and shampoos. These may be useful for mild-to-moderate psoriasis. Topical medicines rarely produce complete clearance, however.
• Phototherapy. Options include light-wave radiation treatments using broad- or narrow- band ultraviolet B (UVB) light, or psoralen with ultraviolet A light (PUVA). This treatment is effective for moderate-to-severe psoriasis. Phototherapies are more effective than drugs and have fewer side effects than most systemic (body-wide) medications. Even more promising, in a 2000 analysis comparing several psoriasis treatments, an advanced phototherapy called narrow band UVB achieved the highest complete clearance rate (86% of patients).
• Body-Wide (Systemic) medications. This treatment employs various pills that affect the whole body, not just the skin. These medicines have significant side effects and are generally reserved for severe psoriasis.

Determining the most effective treatments requires controlled comparison studies. In any case, individual requirements vary widely, and treatment selection must be carefully discussed with the doctor.

Treatment Sequences

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

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

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

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 (oral) 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, since the doses of each drug can be reduced. This lowers the risk of severe side effects. Thousands of combinations are possible, and the patient and doctor should discuss the best treatment for individual needs.

Topical Medications

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

• Ointments
• Gels
• Solutions
• Creams
• Sprays
• Foams
• Lotions
• Shampoos
• Occlusive tapes

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 Corticosteroids

Benefits. Corticosteroid topical treatments are the mainstays of psoriasis treatments in the US, and are effective for most patients. They have many benefits, including the following:

• They reduce inflammation
• They inhibit cell proliferation
• They relieve itching (sometimes itching can also be a side effect of the drug itself, however)

Brands differ in potency (strength), and many are available in numerous forms, including lotions, solutions, creams, emollient creams, ointments, gels, sprays, and on tape. Foam preparations are in particular making compliance (following treatment recommendations) much easier. Injections of certain steroids, such as triamcinolone, may help treat nail psoriasis.

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

• Less potent drugs should be used for mild-to-moderate psoriasis.
• Higher-potency agents are suitable for more severe disease.

Topical Treatment. An example of a topical treatment that uses a single agent is as follows:

• Patients use a high-potency topical corticosteroid, such as halobetasol (Ultravate) daily, until the psoriasis plaque flattens out. This is the transitional phase.
• After the transitional phase, the patient uses the medicine only on the weekends for maintenance.

In the past, topical steroids have been used twice a day. Studies are reporting, however, that certain agents can be used effectively only once daily. Most studies have used high-potency steroids, but a 2001 study suggested that medium-potency agents, such as triamcinolone (Aureocort, Tri-Adcortyl), may be equally beneficial as a once-daily treatment. In any case, however, corticosteroids used alone are effective in clearing psoriasis in only 4 - 36% of patients.

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

• A high-potency steroid (e.g., halobetasol) on the weekend
• The vitamin D3 topical agent, calcipotriene, twice daily on weekdays

In one study, over three-quarters of patients with mild-to-moderate psoriasis remained in remission for at least 6 months with this regimen.

Side Effects. The more powerful a drug, the more effective it is. But it also has a higher risk for severe side effects. They can include the following:

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

Do not use corticosteroids during pregnancy or nursing. The high-potency drugs carry a small risk for adrenal insufficiency, which is usually mild. If this occurs, the body loses its ability to produce natural steroid hormones for a period of time after the drug has been withdrawn, which can cause serious complications. With topical steroids, however, this event is uncommon and usually mild.

Loss of Effectiveness. In most cases, the patients become tolerant to the effects of the drugs, and the drugs become ineffective. Some experts recommend using intermittent therapy (also called weekend or pulse therapy). This type of treatment involves applying a high-potency topical agent for 3 full days each week. In one study, intermittent treatment maintained improvement for 6 months in 60% of patients.

Coal Tar

Coal tar preparations have been used for 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:

• The drug can cause sun sensitivity, and increase the risk of sunburn for up to 24 hours after use.
• It has a strong smell.
• It can stain clothing.
• It irritates the skin.
• Ingesting the medication is life threatening. In such cases, call poison control immediately.

Anthralin

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

Side Effects. As with tar, its use has also declined with introduction of the topical vitamin D-related medicines, but newer formulations, such as Micanol, have made its use more tolerable. Micanol (Psoriatec) is an anthralin formulated in micro-capsules, 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, unlike anthralin.

• Skin irritation and burning: 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 a minute or two before washing off the anthralin. It is then reapplied after drying the skin.
• Brown staining: Older forms of anthralin, such as Drithocreme, can stain hair, fabrics, plastics, and other household products. Micanol does not stain household products if used with cool water. Washing stained items with hypochlorite (Clorox) detergents can help remove stains.
• Although topical preparations do not appear to affect areas other than the skin, people with kidney problems should use anthralin with caution.

Application. Apply anthralin only to the psoriasis plaques. Many people use disposable gloves to avoid staining hands. The areas can usually be protected with dressings. 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 (rub-on) form of vitamin D3, calcipotriene (Dovonex), called calcipotriol in Europe, is proving to be both safe and effective. It is now available in a foam preparation, which makes compliance even easier. Several other topical vitamin D3 analogs (related drugs) showing promise include maxacalcitol (Oxarol), tacalcitol, and calcitriol (Silkis), the active form of vitamin D.

Benefits. Calcipotriene has the following benefits:

• It appears to help block skin cell multiplication.
• It enhances the maturity of keratinocytes (the impaired skin cells in psoriasis).
• It has anti-inflammatory properties.

It is at least as effective as moderate topical corticosteroids, short contact anthralin, and coal tar in improving mild to moderate plaque psoriasis. Unlike steroids, patients do not develop thinning of the skin or tolerance to the drug.

Combinations. Combinations with other topical and oral treatments may improve effectiveness.

• Calcipotriene is not as effective as the highest potency corticosteroids, but products or regimens that combine both agents are proving to be more effective than either agent alone. An ointment containing a combination of the drugs calcipotriol and betamethasone was approved by the Food and Drug Administration (FDA) in January 2006 for the treatment of adults with psoriasis. The product, marketed in the U.S. as Taclonex, was more effective in clinical studies than either drug alone.
• Studies also report success in some patients who use vitamin D ointments in combination with phototherapy treatment.
• Combining vitamin D ointments with oral agents, notably methotrexate, acitretin, or cyclosporine, increases effectiveness and allows lower doses or either medication, thereby reducing side effects.

Side Effects of calcipotriene include the following:

• Calcipotriene causes skin irritation in about 20% of patients, particularly on the face and in skin folds. In fact, it causes greater skin irritation than potent corticosteroids. Diluting the drug with petrolatum or applying topical corticosteroids to sensitive areas may prevent this problem.
• Although the drug appears to be safe and effective in children, there is some concern that it may lower levels of vitamin D to the extent that it could affect bone growth. More studies are needed to assess this effect.
• There have been some reports of hypercalcemia (too much calcium in the blood) in some people who apply calcipotriene to large areas.

Topical Retinoids

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

Benefits. Tazarotene benefits the targeted skin tissue without causing the bad body-wide effects of oral retinoids. Also unlike steroids, patients do not develop thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. It can be used on the scalp and nails, but it is not recommended for the genital areas or around the eyes. The gel should be used on only 20% of the body at anytime, the cream on up to 35%. As mentioned above, the palm of the hand is about 1% of the body surface.

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

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

Combinations. Combinations, such as with topical steroids or phototherapy, are more effective than the use of the drug alone. Unlike vitamin D3, phototherapy with either UVA or UVB inactivates this medicine, although there is a higher risk for sunburn with this combination.

Salicylic Acid

Topical salicylic acid is useful for removing scaly plaque and enhancing other agents. It should not be used to cover wide areas of the body, since it can cause nausea and ringing in the ears. Combinations with high potency steroids, such as mometasone furoate (Combisor), clobetasol propionate, and betamethasone, are proving to be very helpful. Only Combisor is available in the US.

Investigative Topical Agents

Numerous topical agents are under investigation. One such agent, 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 agent, is also being studied.

Other Medications

Other treatments for psoriasis may be taken by mouth (oral) or given by an injection (injected). These drugs are called "systemic" because they affect the entire body. Many of the systemic drugs used for psoriasis are also used for other severe diseases, including autoimmune diseases (especially rheumatoid arthritis) and cancer. Nearly all are powerful medications with potentially serious side effects. These drugs should be used only for severely incapacitating cases of psoriasis, which do not respond to lifestyle changes or topical treatments. They should be used only in very extreme circumstances in children.

As with all medications for psoriasis, the least potent agents should be used first:

• Methotrexate and oral retinoids are the first-line, or primary, systemic drugs for adults with severe psoriasis. Cyclosporine is also an option.
• Second-line drugs include hydroxyurea, sulfasalazine, and thioguanine.
• Third-line agents include tacrolimus.

At this time, the only agents specifically approved for psoriasis are methotrexate, the retinoids, and cyclosporine.

Systemic Regimens. As with all psoriasis treatments, combinations are often used. The following is an example of a systemic regimen with combination treatments:

• The patient starts with an immunosuppressant, such as cyclosporine.
• Acitretin, a vitamin A derivative, is then added (the transitional phase).
• If the drugs are effective, the cyclosporine is withdrawn gradually after a few months and acitretin continues at as low a dose as possible for maintenance.
• Phototherapy using PUVA is added if acitretin cannot control psoriasis.

Methotrexate

Methotrexate (Rheumatrex) is very effective for severe psoriasis. Despite its adverse effects, some experts view methotrexate as the best therapy for widespread plaque psoriasis. It may also be effective for some patients with other severe forms of the disease, including psoriatic arthritis, generalized erythrodermic and pustular psoriasis. One center reported that 80% of patients reported prolonged improvement. Methotrexate appears to be effective in children, but more safety research is needed.

Methotrexate has the following beneficial properties:

• It interferes with cell reproduction.
• It has anti-inflammatory properties.
• It is one of the few systemic agents proven to help patients with psoriatic arthritis.

It is important to note that the recommended dose 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 are nausea and vomiting, rash, mild hair loss, headache, and mouth sores. It may also cause muscle aches. Many of these side effects, as well as anemia, a more serious complication, are due to folic acid deficiency. Anemia is a condition where there is a low level of red blood cells in the body. As a result, less oxygen reaches the organs in the body. Patients should ask their doctor about folic acid supplements (generally recommended at 1 - 5 mg daily). Patients who experience severe nausea may choose injections, which are as effective and less expensive than oral drugs.

More serious complications of methotrexate include the following:

• Liver damage: In one study, 25% of patients taking methotrexate for 5 years developed cirrhosis, liver scarring. People 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. Timing of biopsies depends on any risk factors for liver damage.
• Toxic effects on bone marrow, which can cause reduced blood cell production
• Osteoporosis: Low doses of methotrexate do not appear to have any significant affect on bone loss, but long-term studies are needed to confirm this.
• Kidney complications
• Increased risk for infections, particularly herpes zoster (shingles) and pneumonia. Methotrexate suppresses the immune system. Patients with active infections should avoid this drug.
• Lung disease: This side effect can be sudden and severe, and occurs in up to 5% of people who take methotrexate. It deserves special mention. There are five key risk factors for methotrexate-induced lung diseases: age, diabetes, existing rheumatoid involvement in the lung, protein in the urine, and previous use of rheumatoid arthritis drugs called DMARDs (particularly sulfasalazine, oral gold, and d-penicillamine). Patients should report any symptoms, such as coughing or shortness of breath, which might indicate lung injury.
• Severe anemia from folic acid deficiencies. Folic acid supplements can offset this effect.
• Negative effects on reproduction: In pregnant women, the drug can cause miscarriages, or birth defects in the baby. It may harm fertility in men.
• Lymphomas: A few cases have been reported, which are most likely related to the drug's immune-suppressing (lowering) effects. In most instances, the disease has gone into remission when the drug was stopped. Most studies have found no significant risk for cancers in patients taking methotrexate.
• Radiation recall: An uncommon side effect in patients who have previously been burned by radiation cancer treatments or sunburns. In such cases, a flare-up of symptoms occurs in the previously affected skin areas.

Drug and Alcohol Interactions.Alcohol and many drugs interact with methotrexate, occasionally with toxic results. Patients should tell their doctor about any other medications they are taking. The following are just a few examples:

• Many of the common nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Advil), or naproxen (Aleve), cause serious toxic interactions. Some NSAIDs, namely ketoprofen, fluorobiprofen, and piroxicam, appear to be safe when given with methotrexate and may be used in patients with psoriatic arthritis. Rheumatoid arthritis patients who take methotrexate often take NSAIDs as well, but methotrexate doses in psoriasis patients are usually much higher than those in RA.
• Specific antibiotics interact with methotrexate. Of note, the antibiotic trimethoprim-sulfamethoxazole increases the toxicity of methotrexate.

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. Other people who should avoid methotrexate are alcoholics, those who also have kidney or liver abnormalities (such as hepatitis), people who have active infections, and patients with impaired immune systems. Patients at risk for liver complications include diabetes and people who are obese. Anyone with a previous history of hepatitis should have a biopsy before treatment. Others who might avoid methotrexate are people with peptic ulcers, rheumatoid arthritis, anemia, or other blood abnormalities.

Oral Retinoids

Oral retinoids are related to vitamin A. Those used for psoriasis include acitretin (Soriatane) and isotretinoin (Accutane). Acitretin is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic variants. When used alone, it is much less effective against more common forms, such as plaque or guttate psoriasis. However, combinations with PUVA phototherapy can markedly improve the response even in these patients.

Accutane, more commonly used to treat acne, is generally far less potent than acitretin, but may still be effective against pustular psoriasis and also be effective with phototherapy. An older agent, etretinate (Tegison) was very effective but produced severe side effects and has been withdrawn from the market.

Benefits. Oral retinoids have the following beneficial properties for patients with psoriasis:

• They have anti-inflammatory actions.
• They help regulate cell reproduction.
• They may even improve arthritis that accompanies psoriasis.

Combinations.Acitretin may be most effective in combination with other treatments, usually topical drugs and especially phototherapy. The drug results in faster and more complete responses to PUVA and UBV treatments. Acitretin and phototherapy, in fact, have some of the highest clearance rates of any treatment. Furthermore, lower radiation doses can be used, which may decrease the risk of skin cancers, and some research suggests that retinoids may temporarily suppress the development of these malignancies. Combination therapy also allows lower doses of oral retinoids to be used, which diminishes many skin and mucous membrane side effects. In addition to combination treatments, some experts recommend the following to reduce the toxic effects of acitretin:

• Maintenance doses should be as low as possible and should be taken every second or third day.
• Patients should eat a low-fat diet and get daily aerobic exercise to maintain healthy triglyceride levels. Triglycerides are a type of fat molecules in the blood. They may cause heart disease.

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

• Of special note, retinoids pose a significant risk for birth defects when taken by pregnant women. Children and women who wish to bear children should not take these agents.
• Skin and mucous membrane problems are common. These include dry nose, nosebleeds, dry eyes, chapped lips, thinning hair, dry or "sticky" feeling skin, and peeling of the palms and soles. Nail problems may also develop. Studies on isotretinoin indicate that many of these side effects may be relieved with vitamin E supplements (800 IU daily), but studies on acitretin have not been done.
• Bone and joint pain, fatigue, bruising, and headaches may also occur.
• The drugs may cause eye problems, including blurred vision, cataracts, conjunctivitis, and a sudden deterioration in night vision.
• Retinoids carry a high risk for increased bone growth, particularly in the ankles, pelvic area, and knees.
• They increase levels of triglycerides. Certain cholesterol-lowering agents, including gemfibrozil (Lopid) or statins, such as atorvastatin (Lipitor), may prevent this problem.
• 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.
• The drugs also can cause damage to the liver, so patients should be monitored regularly.
• Isotretinoin has been associated with depression and possible risk for suicide in some people.

Despite these side effects, oral retinoids remain among the safest systemic therapies for psoriasis. A low-fat diet, aerobic exercise, and fish oil supplements may help reduce the side effects.

Cyclosporine

Cyclosporine (Neoral, Sandimmune, SangCya) blocks certain immune factors and may be effective for all forms of psoriasis. Neoral is the preparation used most often for psoriasis and clears psoriasis in between 60 - 91% of patients within 8 - 12 weeks. 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 agents (for example, methotrexate or acitretin).

Side Effects. Common and temporary side effects include headaches, gingivitis, joint pain, gout, body hair growth, tremor, and fatigue.

More serious complications may include the following.

• Kidney damage: This is a significant complication, and prolonged use always causes some kidney injury.
• High blood pressure (occurring in up to 30% of patients): Some experts advise treating high blood pressure with calcium-channel blockers, since other standard blood-pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.
• Unhealthy cholesterol and lipid levels: Patients may need to take cholesterol-lowering agents.
• Abnormalities in the liver
• Increased risk for infections
• Skin cancers: Patients who have taken cyclosporine after PUVA therapy have a higher incidence of squamous cell carcinoma. According to a 2003 study, the risk is six times that of the general population. The risks are highest with long duration and previous use of PUVA, methotrexate, or other immunosuppressants.
• Lymphomas: The use of cyclosporine after transplantation has been associated with a higher risk for lymphomas, although whether cyclosporine used for skin diseases poses any higher risk is unknown.
• High levels of calcium and low levels of magnesium: These effects can usually be offset by magnesium supplements and eating potassium-rich foods.

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

Second- and Third-Line Systemic Agents

Second- or third-line agents are used alone or sometimes in combination with first-line systemic drugs if those medications fail. Most are investigational and are generally less safe than first-line agents.

Sulfasalazine. Sulfasalazine (Azulfidine) is sometimes used for psoriasis. In one major analysis, sulfasalazine and methotrexate were the only agents 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.

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

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. Four such drugs have been approved since 2003. 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.

T-Cell Blockers. In psoriasis, and other inflammatory diseases, T cells (a type of immune cells) become overactive. Drugs that block T cell activation can help prevent psoriasis flare-ups and reduce symptoms.

• Alefacept (Amevive) received FDA approval in January 2003 for treatment of moderate-to-severe plaque psoriasis. It was the first biologic drug approved for psoriasis. Studies suggest that the drug produces 50 - 75% improvement in symptoms. Alefacept is given in a doctor's office or clinic. Patients receive weekly injections for 12 weeks. Blood tests are also done weekly to make sure that T cell levels do not drop too low. Alefacept's side effects are generally mild and include sore throat, dizziness, and cough. There have been a few reports of serious infection and cancer.
• Efalizumab (Raptiva) was FDA-approved in December 2003 for treatment of moderate-to-severe plaque psoriasis. Many patients experience 50 - 75% improvement in symptoms within 4 - 6 weeks of starting the drug. Unlike alefacept, patients can inject efalizumab by themselves at home. Weekly subcutaneous (under the skin) injections are given for 12 weeks. Recent clinical trials suggest that a longer course of treatment (24 weeks) may also be safe and effective for patients with chronic plaque psoriasis. Some patients experience flare-ups of psoriatic lesions after stopping efalizumab. Very serious, but rare, side effects include hemolytic anemia (due to red blood cell destruction), and antibiotic-resistant infections.

Tumor Necrosis Factor (TNF) Blockers. Activated T cells release chemical messengers that cause an inflammatory response. This inflammatory response can increase skin cells in psoriasis and cause joint pain in psoriatic arthritis. The TNF blockers used to treat psoriasis target the chemical messenger TNF-alpha.

• Etanercept (Enbrel) was approved in 2002 for treatment of psoriatic arthritis, and in 2004 for treatment of moderate-to-severe plaque psoriasis. In 2005, etanercept was also approved to improve physical function in patients with psoriatic arthritis. The drug is given either alone or in combination with methotrexate. Patients inject themselves under the skin, once or twice a week for 12 weeks. Etanercept can cause infections and should not be used by patients with weakened immune systems or heart failure. TNF-blockers have also been associated with increased risk of developing lymphomas (a type of cancer).
• Infliximab (Remicade) was approved in 2005 for treatment of psoriatic arthritis. Patients receive three intravenous infusions during the first 6 weeks of treatment. After this initial treatment period, patients receive an infusion every 8 weeks. The infusions take 2 hours and are given in a doctor’s office or clinic. Patients with a history of infection or heart failure should not take this drug.
• Adalimumab (Humira) is another TNF-blocker. It is being tested in clinical trials for treatment of psoriasis and psoriatic arthritis. Results from a Phase III (late-stage) study show that adalimumab (Humira) is more effective than methotrexate in the treatment of moderate-to-severe psoriasis. In the study, 80% of patients treated for 16 weeks with adalimumab reported a 75% or better improvement, compared with 36% of patients treated with methotrexate.

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

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

Phototherapy

Phototherapy means to treat with light.

When sunlight penetrates the top layers of the skin, this ultraviolet radiation bombards the genetic material, 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 administered as ultraviolet A (UVA) light in combination with medications, or as variations of ultraviolet B (UVB) light with or without medications. Not everyone is a candidate. For example, it may not be appropriate for patients who should avoid sunlight or those with very severe psoriasis.

Psoralens and Ultraviolet A Radiation (PUVA)

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

PUVA treatments cause inflammation and redness in the skin to develop within 2 - 3 days after treatment. Such damage inhibits skin cell proliferation and reduces psoriasis plaque formation. PUVA employs a combination of a psoralen drug and UVA radiation. 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 (e.g., 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 administered within 15 minutes of using topical psoralen.
• The patient enters and stands in the "light box," a unit lined with ultraviolet lamps. The initial UVA exposure time is very short (seconds to several minutes), and then increases to 20 minutes or longer. The amount of time a person is exposed to UVA rays depends on the skin type, with the shortest times recommended for fair-skinned patients.
• Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, since the full effects of the treatments are not evident for 48 hours.

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

• If there is no response after 10 treatments, the doctor may increase the UVA energy.
• If there is still no response after 15 treatments, the psoralen dosage may be increased.
• If a patient's skin does not improve at all or worsens after these changes, the treatment is temporarily stopped. PUVA may be causing a toxic response in such cases, and, often, the condition gradually improves over the following two 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. Effectiveness may be enhanced, or response may come faster, by combining PUVA with oral retinoids such as acitretin, or drugs such as calcipotriene, methotrexate, or tazarotene gel. In addition, combinations may allow for lower doses of radiation or medications to be used, minimizing side effects. Retinoids may also help protect against skin cancers, while methotrexate may increase the risk. In some cases, patients resistant to PUVA or UVB may respond when the phototherapies are combined.

Side Effects and Complications of PUVA. Adverse side effects include the following:

• The psoralen methoxsalen causes malaise and nausea in 20% of patients. Dividing up the dose and taking it in 15-minute intervals with food, or taking the herb 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 (Zostrix) -- an ointment prepared from the active ingredient in hot chili peppers -- may be helpful.
• After treatment, white spots commonly develop where psoriasis plaques had been, particularly in people with naturally darker skin. If they are troublesome, tanning products may help darken them. Small, dark raised spots called PUVA lentigines may also develop in affected areas with long-term treatment
• Prolonged standing may trigger fainting in people with certain heart or blood pressure problems.
• People with liver disease should discuss using topical psoralens, since oral forms may have adverse effects on the liver.
• UVA penetrates the skin more deeply than UVB, so there is a greater danger of deep skin damage, accelerated skin aging, and skin cancers. Anyone who needs to avoid sunlight should not get this treatment.
• The procedure increases the risk for cataracts if eyes are not protected for up to 24 hours after treatment.

Special Warning on PUVA and Skin Cancers. It has been known for some time that PUVA can change DNA and cause genetic mutations. PUVA is known to increase the risk for squamous cell skin cancer and slightly increases the risk for basal cell skin cancer, both of which are nearly always curable. The risk for skin cancers is higher in the following patients:

• Patients who have had over 200 treatments
• Patients with a family or personal history of skin cancer
• Patients with light skin and fair or red hair
• Patients who have had radiation or x-ray treatments or taken immunosuppressant drugs

Even more worrisome was a study reporting an increased risk of melanoma, a very serious skin cancer. Discussions are under way, in fact, about discontinuing PUVA for psoriasis. The arguments generally are as follows:

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

UVB Therapy

Ultraviolet B is one of the primary components 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.

The current standard treatments using this radiation involve exposure to a light source for a set length of time at regular schedules. Either treatment can be administered at home. Another recent option is the excimer laser that emits a precise wavelength for local areas. The treatments are:

• Broadband UVB. This has been the standard UVB phototherapy treatment in the US. The wavelength of the UVB light doctors use is 290 - 350 nm. It can be used with or without the aid of medications. It is not as potent as the treatments that use narrow-band UVB or PUVA, and is not useful for chronic psoriasis.
• Narrowband UVB (NB-UVB) may be safer than other approaches, and some experts now believe it should be the first option for patients with chronic plaque psoriasis. NB-UVB is used without medications and is very strong. Whether it has any affect, however, on the disease process itself is unclear. The light wavelength is between 310 - 312 nm, which, theoretically, is the most beneficial part of sunlight.
• The excimer laser is proving to be more effective for treating local areas of psoriasis than many standard treatments. It gives off a precise UVB wavelength of 308 nm.

Broadband Ultraviolet B (UVB) Radiation

Broad spectrum or broad band UVB is radiation in the wavelength of 290 - 350 nm, and is the standard UVB phototherapy treatment in the US. It may be administered with or without medications. When used without medication (known as selective ultraviolet phototherapy), UVB treatment generally is administered as follows:

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

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

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

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

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

Narrow Band Ultraviolet B (NB-UVB) Radiation

Narrow band radiation uses fluorescent lighting that emits radiation in a specific range, 310 - 312 nm. This, theoretically, is the most beneficial component of sunlight. Exposure times are shorter but of higher intensity than with broadband UVB.

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. It is also probably less likely than PUVA to cause skin cancers. Studies are mixed on whether NB-UVB remission rates are equal to those of PUVA, but so far it would seem that they are.

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

Some experts believe that NB-UVB should be the first choice for patients with chronic plaque, with PUVA reserved for patients who fail this treatment.

According to one 2002 study, however, NB-UVB does not have any affect on the disease process itself. In the study, NB-UVB radiation affected only the specific areas of skin that it targeted. Given these results, it is not clear if this approach has any significant long-lasting value for treating chronic psoriasis. Combinations with topical agents, such as tazarotene or psoralens, may improve its effectiveness.

Laser Treatments

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

Pulsed-Dye Lasers. Pulsed-dye lasers emit high-intensity yellow light, which destroy 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. Treatments last up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to six sessions to clear the target areas. Bruising is common, and there is a small risk for scarring.

Commercial Tanning Units

Home tanning devices and tanning salons are not ordinarily recommended, but they may be helpful for patients without access to a medical unit. In a 2003 study, many patients achieved a significant reduction in symptoms with a combination of acitretin and exposure to a UVB commercial tanning unit (A Wolff tanning bed). However, UV outputs can vary widely among tanning beds and salons. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including a risk for skin cancer.

Managing Psoriasis

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

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

Emotional Support

Because of the association between negative emotions and psoriatic flare-ups, relaxation and anti-stress techniques may be helpful. Many are available. The following are some studies suggesting that emotional support may have an impact on psoriasis:

• One study looked at patients with psoriasis who discussed with a psychiatrist any traumatic or other stressful event that occurred when the skin condition appeared. In the study, 68% of patients recalled such an event, and 62% experienced significant improvement after the talk session.
• Another study reported that patients treated with antidepressants along with topical corticosteroids for psoriasis experienced greater skin improvement than those who took the steroid alone.
• Hypnosis aimed at reducing stress may relieve symptoms, according to a small 1999 study.

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

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

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

Resources

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

References

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

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

FDA Announces Strengthened Risk Management Program to Enhance Safe Use of Isotretinoin (Accutane) for Treating Severe Acne. US Food and Drug Administration. Rockville, MD: National Press Office; August 12, 2005. Press Release P05-52.

Anstey AV and Kragballe K. Retrospective assessment of PASI 50 and PASI 75 attainment with a calcipotriol/betamethasone dipropionate ointment. Int J Dermatol. 2006 Aug;45(8):970-5.

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

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

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

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

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

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