Excellent psoriasis treatment article

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Excellent psoriasis treatment article

Postby Nick Balgowan » Thu Jun 15, 2006 10:32 am

Although this appears to be an excellent article, I do not necessarily agree with everything that it says or claims.


WHAT IS PSORIASIS?

General Definition of Psoriasis
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. Here, 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 proliferate very rapidly and travel from the basal layer to the surface in only about four 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.


The dermis contains nerves and blood and lymphatic vessels, which supply the abnormally multiplying keratinocytes with their blood supply and also transport potent 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. [For other variants of psoriasis See Table Less Common Forms of Psoriasis.]

Plaque Psoriasis
Description of Plaque Psoriasis Patches. Plaque psoriasis is the most common form 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, that is, 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 size of pinheads appear underneath (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).
Plaque psoriasis develops in the following locations:

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 of the legs.


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
Description of 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 dysfunction.

Location of Joint Pain Psoriatic Arthritis. Some experts define five forms of PsA as determined by the location and severity of the joint involvement:

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 only in one to three joints, which can be in 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 symptoms in about 5% of PsA cases. Such patients may experience stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. It should be noted that the spine can be involved in up to three-quarters of all patients with PsA, even though it is not the primary symptom. 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 also frequently affects 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 manifestations, the disease is systemic; that is, it affects the body as a whole. 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.




Less Common Forms of Psoriasis
Psoriasis Form

Description of Skin Patches

Comments


Guttate Psoriasis

The patches are teardrop-shaped and erupt suddenly, usually over the trunk and often on the arms, legs, or scalp.


The teardrop patches often resolve on their own without treatment.
Guttate psoriasis can occur as the initial outbreak of psoriasis, often in children and young adults one to three 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 onset of guttate psoriasis.

Guttate psoriasis can also develop in patients who have already had other forms of psoriasis most likely in people treated with widely-applied topical corticosteroid dressings.


Inverse Psoriasis

Patches usually appear as smooth inflamed patches without a scaly surface.

They occur in the folds of the skin, such as under the armpits or breast or in the groin.

Inverse psoriasis may be especially resistant to treatment.


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.

Psoriasis of the scalp may be especially resistant to treatment.


Nail Psoriasis

The characteristic signs are tiny white pits 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 accumulate 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 manifestation of psoriasis.


Generalized Erythrodermic Psoriasis (also called psoriatic exfoliative erythroderma)

This is a rare severe and form, 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. It can also be caused by certain treatments of psoriasis.

This condition can also erupt after withdrawal from other agents, including 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, metal allergies.

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




WHAT IS THE CAUSE OF PSORIASIS?

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 biochemical substances that regulate skin cell division become impaired. This abnormal immune response causes rapid proliferation 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.

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

When an injury or an infection occurs, white blood cells are mobilized to rid the body of any foreign 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 any infective agents.


In the process, the surrounding area becomes inflamed and some healthy tissue is injured.


Under normal conditions, the immune system has other factors that control and limit this inflammatory process.
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-cell s and B-cells. Both types of cells are designed to recognize foreign substances (antigens) and to 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, Cytokines, and the Inflammatory Response. The actions of the helper T-cells (TH cells) are of special interest. Researchers have observed high numbers of TH cells in psoriatic plaques:

The activated TH cells infiltrate the skin cells in psoriasis and, in the case of psoriatic arthritis, also the joints. (There has been some debate over whether psoriatic arthritis is a unique disorder, but evidence now suggests that both psoriatic arthritis and psoriasis are caused by the same faulty immune process.)


TH cells normally stimulate B-cells to produce antibodies. In the case of psoriasis, however, they appear to direct the B-cells to produce autoantibodies ("self" antibodies), which are directed against the body's own cells. In the case of psoriasis, they target self antigens in skin cells; in psoriatic arthritis, cells in the joints also come under attack.


In the resulting autoimmune process, autoantibodies remain in circulation and continue 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 indispensable 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 interleukins 8 (IL-8), 11 (IL-11), and 12 (IL-12), which appear to play strong roles in the destructive psoriatic process, and in IL-10, which may be protective and block cell growth leading to psoriasis.

Neutrophils. Cytokines attract to the scene large numbers of other large white blood cells known as neutrophils. Neutrophils stimulate the production of arachidonic acid, which triggers about 30 different chemicals, including two key players in the inflammatory process:

Leukotrienes, which attract even more white blood cells to the area, and


Prostaglandins, which open 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 disease 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. It should be noted, however, that 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 PSORs 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, an 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 onset and worsening of psoriasis.

Weather. Weather is a strong factor in psoriasis:

Cold, dry weather is a common precipitant 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 perpetuation 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. 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 disruption.)

Drugs. A number of drugs can worsen or induce pre-existing latent 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. (It 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. (It should be noted that other NSAIDs, such as meclofenamate, may actually improve the condition.)


Withdrawing from oral steroids or high-potency steroid ointments that cover wide skin areas can cause flare-ups of severe psoriasis, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.


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

WHO GETS PSORIASIS?

General Risk Factors
An estimated 6.4 million Americans (about 2.5% of the population) have psoriasis, and it affects between 0.5% to 3% of the world's population.

Gender. Some studies have indicated a higher prevalence in men than in women.

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 atypical symptoms in young patients can make it difficult to diagnose 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 afflicted family members, 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.

HOW SERIOUS IS PSORIASIS?

Severity of Psoriasis
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. The skin is usually categorized as mild to severe depending on the extent of the psoriasis to help determine treatment:

Mild psoriasis affects less than 5% of the body surface. Most cases of psoriasis are limited to less than 2% of the skin.


Moderate psoriasis covers 5% to 20% of the skin. (Some experts believe the cut-off should be lowered to 10%, particularly when psoriasis involves hands or feet.)


About 5% of cases fall into the moderate to severe category, which extends beyond 20% of the skin's surface. In general severe psoriasis affects over 30% of the body. Widespread psoriasis (erythrodermic psoriasis and generalized pustular psoriasis) can be life threatening. Fortunately these occurrences are rare.
Some forms of psoriasis can be very resistant to treatment even though they are not categorized as severe. They include the following:

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 spontaneously. In one study, 30% of patients reported untreated psoriasis going into remissions that lasted from one to 54 years.
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 undermined their confidence.


Another reported that 8% of people with psoriasis felt their life was not worth living.
Higher Risk for Substance Abuse. A number of 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 the onset of psoriasis itself.

Physical and Medical Complications of Psoriasis
Folate Deficiency in Severe Psoriasis. Severe psoriasis can also cause folate deficiency, a B vitamin that is important for neurologic function, preventing birth defects, and preventing 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 effect the whole body) are 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, in fact, that patients with psoriasis have a higher risk for nonmelanoma 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, possibly even without medication, than in adults.

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

Severe joint deformity and destruction (called arthritis mutilans), generally in the small joints of the hands and feet, may develop. Studies report an incidence of about 5% to 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 ones have found no significant difference.

HOW IS PSORIASIS DIAGNOSED?

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 proliferation 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. A number of conditions produce symptoms that resemble those of psoriasis. Examples include the following:

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.


Reiters 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 psoriatic arthritis may be distinguished from other arthritic conditions by inflammation 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.

WHAT ARE THE GENERAL TREATMENT GUIDELINES FOR PSORIASIS?

Many medications used topically (on the skin) or orally 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 potency:

Topical 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) or psoralen with ultraviolet A (PUVA). This therapy is effective for moderate-to-severe psoriasis. Phototherapies are more effective than drugs and have fewer side effects than most systemic agents. Even more promising, in a 2000 analysis comparing a number of psoriasis treatments, an advanced phototherapy called narrow band UVB achieved the highest complete clearance rate (86% of patients).


Systemic Agents. This treatment employs various oral drugs that affect the whole body system, not just the skin. These agents have significant side effects and are generally reserved for severe psoriasis.


Controlled comparison studies are needed to determine the safest and most effective treatments. In any case, individual requirements vary widely and treatment selection must be carefully discussed with the physician.
Treatment Sequences
Administering therapies in a specific sequence 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 (e.g., a high-potency 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 regimens depend on the severity of the condition. Some examples are described in the following sections.

Rotational Therapy
In severe chronic cases, a physician may recommend rotational therapy. This approach alternates treatments. The goal is to prevent severe side or tolerance effects from prolonged use of a single agent. An example of a rotational schedule may be the following:

Phototherapy is administered for about two years and stopped.


One or two powerful systemic drugs are then administered for one or two years and withdrawn.


Phototherapy is started again, and the cycle is repeated.
Combination Therapies
Combinations of oral agents, topical therapies, and phototherapy are increasingly used rather than single agents. Combinations of oral agents are particularly useful since the doses of each one can be reduced, thereby lowering the risk for severe side effects. Thousands of combinations are possible, and the patient and physician should discuss the most beneficial for individual needs. [See Table Possible Psoriasis Treatment Combinations.]




Possible Psoriasis Treatment Combinations
Treatments

Topical steroids

Topical Tar or anthralin

Topical vitamin D3 (calcipotriene)

Topical Retinoid (tazarotene)

Photo-therapy

Oral Methotrexate

Oral Retinoid

(Acitretin may be the agent most used in combos)

Oral Cyclosporine


Topical steroids

NA

No

Yes. Very effective with high-potency steroids.

Yes

Question-able benefit.

No

Yes

No


Topical Tar or anthralin

No

No

No

No

Yes (UVB)

No

Yes

No


Topical vitamin D3, (calcipotriene)

Yes. Very effective with high-potency steroids.

No

NA



May be useful with PUVA.

No

Yes

Yes


Topical Retinoid (tazarotene)

Yes

No

NA

NA

Yes for UVA and UVB (NB-UVB very effective).

No

No

No


Phototherapy

Questionable benefit.

Yes (UVB)

May be useful with PUVA.

Yes for UVA and UVB (NB-UVB very effective).

UVB and PUVA may be combined.

May be effective, but requires careful monitoring for skin cancer.

Low dose acitretin with either UVB or PUVA among the most effective treatments.

Use with UVB or PUVA may increase skin cancer risk.


Oral Methotrexate

Yes

No

No

No

May be effective, but requires careful monitoring for skin cancer.

NA

No (some experts believe may be able to overlap while switching).

Low dose combination effective. Requires careful monitoring.


Oral Retinoids

(Acitretin may be the agent most used in combinations.)

Yes

Yes

Yes

No

Low dose acitretin with either UVB or PUVA among the most effective treatments.

No (some experts believe may be able to overlap while switching).

NA

Requires careful monitoring.


Oral Cyclosporine

Yes

No

Yes

No

Use with UVB or PUVA may increase skin cancer risk.

Low dose combination very effective. Requires careful monitoring.

Requires careful monitoring.

NA





WHAT ARE THE TOPICAL THERAPIES FOR PSORIASIS?

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 [See Box 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. [See Table Possible Psoriasis Treatment Combinations.]

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

They reduce inflammation.


They inhibit cell proliferation.


They alleviate itching. (Sometimes itching can also be a side effect of the drug itself, however.)
Brands differ in potency and many are available in a number of formulations, including lotions, solutions, creams, emollient creams, ointments, gels, sprays, and on tape. Foam preparations are particularly making compliance much easier. Injections of certain steroids, such as triamcinolone, may help treat nail psoriasis.

They are also 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 indicated for more severe disease. [For specific brands and potencies, see Box Some Topical Corticosteroids Used for Psoriasis.]
Topical Regimen. An example of a topical regimen that uses a single agent is as follows:

A high-potency topical corticosteroid, such as halobetasol (Ultravate) used daily until the psoriasis plaque flattens out. (The transitional phase)


After that the steroid is applied only on the weekends for maintenance.
Topical steroids generally have been administered twice a day. Studies are reporting, however, that certain agents can be applied 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-Adcortl), may be equally beneficial as a once-daily treatment. In any case, however, corticosteroids used alone are effective in clearing psoriasis in only 4% to 36% of patients.

Combinations with other agents 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 six months with this regimen.

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

Burning.


Irritation.


Dryness.


Acne.


Thinning of the skin that may become shiny, fragile, and easily cut.


Dilated blood vessels.


Loss of skin color.
Corticosteroids should not be used during pregnancy or when 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 they become ineffective. Some experts recommend using intermittent therapy (called weekend or pulse therapy), which involves applying a high-potency topical agent for three full days each week. In one study, intermittent treatment maintained improvement for six months in 60% of patients.




Some Topical Corticosteroids Used for Psoriasis
Low potency (Some are available over the counter)

Hydrocortisone low potency (Hytone, Penecort, Synacort, Cort-Dome, Nutracort, Westcort).

Desonide (Tridesilon, DesOwen).

Flumethasone pivalate (Locorten).

Fluocinolone acetonide (Synalar, Derma-Smoothe).

Triamcinolone acetonide (Aristocort)


Low to medium potency

Alclometasone dipropionate (Aclovate).

Hydrocortisone low to medium potency (Locoid, Pandel).

Hydrocortisone valerate (Westcort).

Prednicarbate (Dermatop).


Medium to upper-mid potency

Clocortolone pivalate (Cloderm).

Fluticasone propionate (Cutivate). A low-dose ointment (0.005%) is proving to be effective for psoriasis on the face and in folds of the skin, but not in other areas.

Mometasone furoate (Elocon). (Only needs to be administered once a day. May be as or more effective than corticosteroids at the same strength while having a lower risk for severe side effects.)

Triamcinolone acetonide (Aureocort, Tri-Adcortyl, Kenalog). Available as a topical cream or as an injectable agent to treat nail psoriasis.


High potency

Betamethasone (Diprosone) (Also available in lower potencies)

Amcinonide (Cyclocort)

Desoximetasone (Topicort)

Diflorason (Florone, Maxiflor)

Fluocinonide (Lidex)

Halcinonide (Halog)


Very high potency

Halobetasol propionate (Ultravate).

Betamethasone (Diprolene). Available as a foam (Luxiq), which was developed for the scalp but patients are finding it preferable for trunk and extremities as well. In one study, 72% of patients were clear or almost clear of disease after 28 days of treatment, compared with 47% who were clear after using the lotion. The foam turns to liquid on the trunk or extremities and is a cosmetically preferred option for many patients.

Clobetasol propionate (Temovate). Also available as a foam.

Diflorasone diacetate (Florone, Maxiflor, Psorcon). Psorcon is a gel form that may be particularly helpful.



Tar
Tar preparations have been used for psoriasis for about 100 years although its use has declined with the introduction of topical vitamin D3 analogs. Crude coal tar inhibits enzymes that contribute to psoriasis and helps prevent cell proliferation. Tar is often used in combinations with other drugs and with ultraviolet B (UVB) phototherapy. [See What Are Phototherapy Treatments for Psoriasis? below.]

Side Effects. Preparations have the following drawbacks:

The drug can cause sun sensitivity and increase the risk for 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 poison control should be called immediately.
Anthralin
Benefits. Like coal tar, anthralin (Dritho-Scalp, Drithocreme, Micanol), called dithranol in Europe, is a traditional medication, in use since the early 1900s. Anthralin benefits patients with psoriasis by slowing skin cell reproduction. Remissions can last for months. Anthralin 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 vitamin D topical analogs, but newer formulations, such as Micanol, have made its use more tolerable.

Skin irritation and burning. It should not be used on the face. Fair skinned people should generally avoid it. (Small studies have indicated that topical vitamin E (the tocopherol form) may help reduce this side effect.)


Brown staining. Older forms of anthralin, such as Drithocreme, irritate the skin and can stain hair, fabrics, plastics, and other household products. Micanol is less irritating and stains the skin but 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 are advised to use anthralin with caution.
Application.

The following are some suggestions for application of the anthralin Micanol:

Use a small amount of cream and rub only into areas affected by psoriasis.


Apply once a day and do not leave on longer than 30 minutes or as advised by the physician.


Wash off only with lukewarm water, not soap. (Using hot water will trigger the staining action.)


Wash with soap after the cream is completely cleared.
To apply the Micanol to the scalp, the following is recommended:

Wash hair first with shampoo and rinse.


Apply Micanol to the areas affected by psoriasis while the hair is damp. Try to avoid healthy areas of the scalp.


Wash hands immediately with cool water and no soap. Then wash with soap and warm water. (Or use disposable gloves to apply Micanol.)


Do not leave Micanol on the scalp for longer than 30 minutes.


Rinse off with cool water. (Do not use soap or shampoo.)


After Micanol cream is completely rinsed out, wash hair with regular shampoo again, if desired.
Topical Vitamin D3 Analogs
A topical 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 vitamin D3 analogs, such as maxacalcitol and tacalcitol, are also showing promise.

Benefits. Calcipotriene has the following benefits:

It appears to help block skin cell proliferation.


It enhances the maturity of keratinocytes (the impaired skin cell 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. Calcipotriene is not as effective as the highest potency corticosteroids, such as halobetasol, but regimens that combine both agents have been shown to be more effective than either drug alone. Improvement occurs between two and six weeks after starting treatment, and most cases of psoriasis clear by 14 to 36 weeks after treatment. Compliance is very good.

Studies also reports dramatic success in some patients who use it in combination with PUVA. Ultraviolet A (UVA) radiation inactivates the drug, so it must be used after this form of phototherapy.

Side Effects. They 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 (excessive levels of calcium in the blood) in some people who apply it to large areas, but this does not appear to be significant in people who apply less than 100 grams a week.
Topical Retinoids
Retinoids are vitamin A derivatives and are being used for various skin disorders. Tazarotene (Tazorac, Zorac) is the first topical retinoid found to be effective for mild to moderate psoriasis.

Benefits. Tazarotene gel benefits the targeted skin tissue without causing the adverse systemic effects of oral retinoids. Also unlike steroids, patients do not develop thinning of the skin or tolerance to the drug.

Side Effects. When used alone, tazarotene can cause severe skin irritation at levels high enough to be effective for psoriasis. This agent, then, is usually used in combinations with other treatments, therefore allowing a lower dose.

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

Salicylic Acid
Topical salicylic acid (the active ingredient in aspirin) 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.





Occlusive Tapes
Watertight (occlusive) tapes may help heal psoriasis and are particularly useful for psoriatic cuts on the palms and soles. (In such cases, the tape should be applied across the cuts until they heal.) Occlusive tapes retain sweat, which helps restore moisture to the outer skin layer and prevent scaling. They also protect against abrasion and irritation.

High-Potency Corticosteroid Tapes. Applying a corticosteroid beneath an occlusive tape or using one already impregnated with a potent corticosteroid (Cordran Tape), such as flurandrenolide, may be especially beneficial. Studies are showing that high-potency corticosteroid-impregnated tapes are more effective than using high-potency corticosteroid ointments alone. The downsides are the following:
The corticosteroid-impregnated tape is expensive.


It produces a higher incidence of skin irritation than the ointment alone.


It produces more pronounced rebound effects than the ointment (a relapse of symptoms after stopping treatment).


Steroid-impregnated tapes increase the risk for secondary infections, which may be prevented by changing the tapes every 12 hours.


The use of corticosteroids under occlusive materials on large areas of psoriasis 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 susceptible.
Fluorouracilwith Occlusive Tapes. One study applied a cream containing fluorouracil underneath an occlusive tape. The dressing was applied two or three times a week for an average of about 16 weeks and resulted in 90% clearing in 11 out of 15 patients. Improvement persisted beyond three months in five patients.



WHAT ARE THE SYSTEMIC TREATMENTS FOR PSORIASIS?

Systemic treatments involve oral or injected drugs, which 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 severe incapacitating cases of psoriasis that do not respond to lifestyle changes or topical (or other less potent) therapies. And 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.
It should be noted that 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 as 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. For example, one center reported that 80% of patients reported prolonged improvement. Methotrexate appears to be effective in children, but more safety research is needed.

It 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. Fatal toxicities 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. Patients should ask their physician about supplements (generally recommended at 1 to 5 mg of folic acid daily). Patients who experience severe nausea may opt for injections, which are effective and less expensive than oral agents.

More serious complications include the following:

Liver damage. (In one study, 25% of patients taking methotrexate for five years developed cirrhosis, liver scarring.) People with existing liver problems should not take it 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 suppression of blood cell production.


Osteoporosis. (Low doses 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 and so should be avoided in patients with active infections.


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, that 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 and birth defects in the offspring. It may impair fertility in men.


Lymphomas. A few cases have been reported, which are most likely related to the drug's immune-suppressing 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 by sunburns. In such cases, a flare-up of symptoms occur in the previously affected skin areas.


Drug and Alcohol Interactions. Alcohol and many drugs interact with methotrexate, and in some cases the combinations can be toxic. Patients should discuss with their physicians 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, 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. (It should be noted that 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), 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 peptic ulcers, rheumatoid arthritis, and anemia or other blood abnormalities.

Oral Retinoids
Oral retinoids are derivatives of 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 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. It still may be useful for HIV patients.

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 agents, usually topical agents and especially with 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.
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. [See Box Oral Retinoids and Pregnancy.]


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, which are lipids (fatty molecules in the blood) that are proving to be danger for the heart. Certain cholesterol-lowering agents, including gemfibrozil (Lopid) or statins, such as atorvastatin (Lipitor), may prevent this.


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 the physician 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.





Oral Retinoids and Pregnancy
Retinoids taken by pregnant women pose a significant 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. There are some differences in retinoid effects, however.
Acitretin is cleared from the body in about three or four weeks, so the agent does not to appear to pose a for birth defects beyond that time. There is one important exception: Drinking alcohol converts acitretin to etretinate, which is a retinoid that is stored in fat cells for three years. Therefore, it may have the potential for causing birth defects during that time. Therefore, if a woman drinks alcohol while taking acitretin or any time during the two months after she stops, she must wait three years to conceive. Because some cooking products and over-the-counter preparations, such as cough syrup, may contain alcohol and be inadvertently ingested, some experts advise that acitretin not be given to any woman-regardless of alcohol use, who may become pregnant within three years of taking it.


Isotretinoin is safer for women who wish to become pregnant since it is safely gone from the body within a month. The interaction with alcohol is not totally known, but the wisest route is to avoid alcohol and all alcohol-containing products when taking it.


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% and 91% of patients within eight to 12 weeks.

Many physicians are reluctant to prescribe cyclosporine because of its many side effects, particularly toxic effects on the kidney when taken long term. A newer microemulsion formulation (Neoral-Neo), provided in short, intermittent doses, may be as effective and safer than the standard continuous administration therapy for moderate to severe psoriasis. And, cyclosporine may actually be safer for short-term use than methotrexate. Cyclosporine may be also be safer during pregnancy than methotrexate or retinoids. Data to date suggests that it does not increase the risk for birth defects (although it may pose a higher chance for premature deliveries). More research is needed.

Side Effects. Cyclosporine has significant side effects and should be reserved for patients who do not respond to phototherapy or less potent systemic agents (e.g., methotrexate or acitretin). Cyclosporine can have considerable side effects, particularly on the kidney. 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 the microemulsion form of Neoral is safe for up to two years. Patients should be monitored regularly for hypertension and signs of kidney or liver abnormalities.

Side effects include the following:

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. Being careful not to exceed the standard dose and reducing it if tests indicate kidney abnormalities can reduce the risk.


High blood pressure (occurring in up to 30% of patients). Some experts advise treating high blood pressure with calcium-channel blockers, since other standard anti-hypertensive 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. Short-term use of the drug in psoriasis patients does not appear to pose such a risk, but the effects of long-term use are unknown. The use of cyclosporin 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 with magnesium supplements and eating potassium rich foods.

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 investigative and are generally less safe than first-line agents.

Sulfasalazine. Sulfasalazine (Azulfidine) 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 four to six weeks.

Tacrolimus. Tacrolimus (Prograf) is an immunosuppressant and similar in its actions to cyclosporine. One study showed an 83% reduction in symptoms in patients with psoriasis who used the drug, although it is a relatively new drug and studies have been limited. Side effects include diarrhea, numbness or tingling, and insomnia. As with cyclosporine, high blood pressure, kidney damage, and infections can occur. Patients should be monitored regularly.

Hydroxyurea. Hydroxyurea (Hydrea), a cancer drug, appears to inhibit cell reproduction and also increases water content in red blood cells and may be effective against psoriasis. Almost half of people who respond we
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