Psoriasis-In-Depth

An in-depth report on the causes, diagnosis, treatment, and prevention of psoriasis.

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Highlights

Overview

• Psoriasis is an inflammatory skin condition that affects about 2% of all Americans. It is the most prevalent autoimmune condition.
• There are several types of psoriasis. The most common type is plaque psoriasis, accounting for about 90% of cases. Other types are guttate, inverse, erythrodermic, and pustular psoriasis.

Causes

• Doctors believe that psoriasis is caused by abnormalities in the immune system, enzymes, and other factors that regulate skin cell division. In basic terms, an abnormal immune response triggers inflammation and rapid production of immature skin cells.
• Genes play a role in the development of psoriasis. Researchers have discovered that a variation in a group of genes known as LCE can protect against the condition. One of these genes codes for proteins that help maintain the skin's barrier.
• However, studies of monozygotic twins suggest there are also environmental factors.
• Eight key psoriasis susceptibility genes (designated PSORS 1 to 9) seem to be involved with psoriasis. Several different mutations of these genes are associated with psoriasis.
• Certain histocompatibility antigens (HLA) are strongly associated with psoriasis.

Risk Factors

• 35% of people with psoriasis have one or more family members with the disorder.
• There may be a link between being overweight and psoriasis.
• People with celiac disease have a higher risk for psoriasis. Gluten-free diets may help people with celiac disease reduce psoriasis symptoms along with symptoms related to celiac.
• People with psoriasis may be at higher risk for dyslipidemia, or high cholesterol/triglyceride levels, and heart disease.

Treatment

• Treatment options for moderate to severe psoriasis include topical and systemic medications, phototherapy, and excimer laser. Combination therapies are often more effective than one treatment alone.
• Phototherapy, which involves exposure of the skin to ultraviolet light, can help improve the symptoms of psoriasis, but may increase the risk of developing skin cancer.
• Biologic drugs that target the root of the disease, the immune system, are used in the treatment of psoriasis that does not respond to topical treatments or covers a large body surface area. Several drugs are approved and more are under study.
• Biologic drugs approved for the treatment of psoriasis include ustekinumab (Stelara), secukinumab (Cosentyx), etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab (Cimzia), ixekizumab (Taltz), tildrakizumab (Ilumya), guselkumab (Tremfya), brodalumab (Siliq), and risankizumab (Skyrizi).
• Apremilast (Otezla) is an oral medicine that is not a biologic.
• Researchers continue to investigate the effects of other dietary factors, such as omega-3 fatty acids (found in fish oil) and Vitamin D supplements, as well as lifestyle factors in treating psoriasis.

Outlook

Psoriasis has been linked to an increased risk for:

• Heart attack and cardiovascular disease
• Crohn disease
• Ulcerative colitis
• Lymphoma
• Depression

People with psoriasis should work with their doctors to prevent or manage these conditions.

Introduction

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

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

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

The prevalence of psoriasis in men and women is about the same.

Types of Psoriasis

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

Plaque Psoriasis

Plaque psoriasis leads to skin patches that start off in small areas, about 1/8 of an inch wide. They usually appear in the same areas on opposite sides of the body.

The patches slowly grow larger and develop thick, dry plaque. If the plaque is scratched or scraped, bleeding spots the sizes of pinheads may appear underneath as a result of the inadequately protected capillaries. This is known as the Auspitz sign, which can also appear in other skin conditions.

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

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

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

Patches most often occur on the:

• Elbows
• Knees
• Lower back near the sacrum

They may also be seen on the:

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

Psoriasis of the scalp affects about 50% of people with psoriasis and appears as severe seborrheic dermatitis or dandruff. In some cases, the psoriasis may cover the scalp with thick plaques that extend down from the hairline to the forehead.

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

Less Common Forms of Psoriasis
Psoriasis Form	Description of Skin Patches	Comments
Guttate Psoriasis	The patches are teardrop-shaped and appear suddenly, usually over the trunk and often on the arms, legs, or scalp. They often disappear without treatment over the course of several months.	Guttate psoriasis can occur as the initial outbreak of psoriasis, often in children and young adults 1 to 3 weeks after a viral or bacterial (usually streptococcal) respiratory or throat infection. A family history of psoriasis and stressful life events are also highly linked with the start of guttate psoriasis. Guttate psoriasis can also develop in people who have already had other forms of psoriasis, most often in people treated with widely-applied topical (rub-on) products containing corticosteroids.
Inverse Psoriasis	Patches usually appear as smooth inflamed areas without a scaly surface. They occur in the folds of the skin, such as under the armpits or breast, or in the groin.	Inverse psoriasis may be especially difficult to treat. It is easily misdiagnosed as fungus as it is not in the usual areas psoriasis appears and may be present along with a fungal or yeast infection.
Seborrheic Psoriasis	Patches appear as red scaly areas on the scalp, behind the ears, above the shoulder blades, in the armpits or groin, or in the center of the face.	Seborrheic psoriasis may be especially difficult to treat. It may be called sebopsoriasis.
Nail Psoriasis	Tiny white pits are scattered in groups across the nail. Toenails and sometimes fingernails may have yellowish spots. Long ridges may also develop across and down the nail. The nail bed often separates from the skin of the finger and collections of dead skin can build up underneath the nail.	Over one half of the people with psoriasis have abnormal changes in their nails, which may appear before other skin symptoms. In some cases, nail psoriasis is the only symptom. Nail psoriasis is linked to psoriatic arthritis. Fingernails are affected more often than toenails. This is often misdiagnosed as nail fungus.
Generalized Erythrodermic Psoriasis (also called psoriatic exfoliative erythroderma)	This is a rare and severe form of psoriasis, in which the skin surface becomes scaly and red. The disease covers all or nearly all of the body.	About 20% of such cases evolve from psoriasis itself. The condition may also be triggered by certain psoriasis treatments and other medications, such as corticosteroids or synthetic antimalarial drugs. This can be life threatening and often requires hospitalization.
Pustular Psoriasis	Patches become pus-filled and blister-like. The blisters eventually turn brown and form a scaly crust or peel off. The pustules are sterile, and do not contain bacteria. Pustules usually appear on the hands and feet. When they form on the palms and soles, the condition is called palmar-plantar pustulosis.	Pustular psoriasis may erupt as the first occurrence of psoriasis, or it may evolve from plaque psoriasis. A number of conditions may trigger pustular psoriasis, including infection, pregnancy, certain drugs, and metal allergies. Pustular psoriasis can also accompany other forms of psoriasis and can be very severe. Evidence to guide treatment is extremely limited.

Psoriatic Arthritis

Psoriatic arthritis (PsA) is an inflammatory condition that leads to stiff, tender, and inflamed joints. About 10% to 20% of people with psoriasis develop psoriatic arthritis. People with psoriasis who also have AIDS and people with severe psoriasis are at a higher risk of developing PsA.

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

PsA is often divided into 5 forms. The forms differ according to the location and severity of the affected joint:

• Symmetric PsA. Accounts for about half of all PsA. Symptoms occur in the same location on both sides of the body. The condition usually affects multiple joints. In about one half of the cases, symmetric PsA will get worse. The condition is very similar to, but less disabling than, rheumatoid arthritis. The psoriasis itself is often severe. The fingers can take on the classic sausage digit appearance if both the proximal and distal interphalangeal joints are involved.
• Asymmetric PsA. This form involves periodic joint pain and redness, usually in only one to three joints, which can be the knee, hip, ankle, wrist, or one or more fingers. The pain does not occur in the same location on both sides of the body. This accounts for about 30% of PsA.
• Distal interphalangeal predominant (DIP). DIP involves the joints of the fingers and toes closest to the nail. It occurs in about 5% of PsA cases and is often associated with psoriatic nail involvement.
• PsA in the spine. Inflammation in the spinal column (spondylitis) is the primary symptom in about 5% of PsA cases. Such people may have stiffness and burning sensations in the neck, lower back, sacroiliac, or spinal vertebrae. The spine can be involved in many people 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. This may be associated with inflammatory bowel disease.
• Arthritis mutilans. This is a severe, deforming, and progressive form of arthritis. It affects less than 5% of PsA cases. It mainly affects the small joints of the hands and feet, but it can also be found in the neck and lower back. Arthritic and skin flares and remissions tend to coincide.

People who start to smoke after developing psoriasis may delay the onset of psoriatic arthritis, according to some studies, while other studies suggest smoking makes psoriasis and psoriatic arthritis worse. Smoking may also affect the medications used to treat the diseases.

Causes

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

Inflammatory Response and Autoimmunity

The Normal Immune System Response

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

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

The Infection Fighters

The primary infection-fighting units are different types of white blood cells (leukocytes).

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

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

A type of T cell called a helper T cell stimulates B cells and other white blood cells to attack a foreign substance. In psoriasis, however, the helper T cell appears to direct the B cells to produce autoantibodies ("self" antibodies), which attack the body's own skin cells. In psoriatic arthritis, cells in the joints also come under attack.

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

Genetic Factors

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

HLA Molecules

The processes leading to all autoimmune diseases involve the human leukocyte antigens (HLA), a group of protein markers found on cells. Most immune disorders are associated with problems in how the body reacts to these different protein markers or antigens. However, other genetic and environmental factors are required to actually trigger the disease. Certain HLA types are associated with different types of psoriasis.

Nine key psoriasis susceptibility genes (designated PSORS 1 to 9) seem to be involved with psoriasis. Certain variations or changes in these genes may increase the risk for psoriasis. These same variations linked to psoriasis and psoriatic arthritis is also associated with four known autoimmune diseases:

• Type 1 diabetes
• Graves disease
• Celiac disease
• Rheumatoid arthritis

This suggests that all of these diseases have the same genetic basis.

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

Triggers

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

Weather

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

Stress and Strong Emotions

Stress, unexpressed anger, and emotional disorders, including depression and anxiety, are strongly associated with psoriasis flare-ups. Research has suggested that stress can trigger specific immune factors associated with psoriasis flares.

Infection

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

• Streptococcal infections in the upper respiratory tract, such as tonsillitis, sinusitis, and strep throat, are known to trigger guttate psoriasis in children and young adults. These infections may also worsen ordinary plaque psoriasis.
• Human immunodeficiency virus (HIV) is also associated with psoriasis. This was an unexpected finding, as HIV infection depletes the T cells thought to mediate psoriasis.
• An uncommon strain of human papillomaviruses (HPV), called EV-HPV, has been associated with psoriasis. Although EV-HPV is probably not a direct cause, it may play a role in the continuation of psoriasis. This HPV strain is not one of the viruses that cause cervical cancer and genital warts.

Skin Injuries and the Koebner Response

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

Medications

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

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

Severe flare-ups may occur in people with psoriasis who stop taking their steroid pills, or who discontinue the use of very strong steroid ointments that cover wide skin areas. The flare-ups may be of various psoriatic forms, including guttate, pustular, and erythrodermic psoriasis. Because these drugs are also used to treat psoriasis, this rebound effect is of particular concern.

Medications that cause rashes (a side effect of many drugs) can trigger psoriasis as part of the Koebner response.

Risk Factors

Risk factors for psoriasis include:

• Age under 20. About 40% of people develop the condition before age 20. Psoriasis (most often plaque psoriasis) can even occur in infants.
• Climate. Some studies have found that the disorder develops earlier and more frequently in colder climates. For example, psoriasis occurs more often in African Americans and in White people who live in colder climates than in people of any ethnicity who live in Africa.
• Ethnicity. Psoriasis is uncommon in Native Americans of either North or South American descent.
• Family history of the disease. About 35% of those with psoriasis have one or more family members with the disorder.
• Lifestyle factors. Smoking, obesity, and alcohol use and abuse increase the risk of getting psoriasis and boost its severity.
• Co-morbidities. Having other conditions, such as celiac disease, increases the risk for psoriasis.
• Infections, such as streptococcal infections, can trigger guttate psoriasis or exacerbate psoriasis.
• Stress can also trigger psoriasis along with certain medications.

Diagnosis

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

Disease Severity

The severity of psoriasis ranges from one or two flaky inflamed patches to widespread pustular psoriasis that, in rare cases, can be life threatening. To help determine the best treatment for a patient, doctors usually classify the disease as mild, moderate, and 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% to 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 surface.

The severity of the disease is also measured by its effect on a person's quality of life.

The National Psoriasis Foundation has proposed a new classification method. The group suggests a two-tiered system that classifies people with psoriasis as needing either local or body-wide (systemic) treatment. Physicians may also use several assessment tools to evaluate severity.

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

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

Risk factors, triggers, and comorbidities will also be assessed at the time of diagnosis.

Treatment

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

Many people with psoriasis, however, do not respond to over-the-counter remedies and lifestyle changes, and require aggressive treatments. In some cases, such treatments need to be lifelong.

In general, there are three treatment options for people with psoriasis:

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

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

Treatment Sequences

Giving treatment in a stepwise order can help provide quick symptom relief and long-term maintenance. It involves 3 main steps:

• The quick fix, to clear the psoriatic lesions during an acute outbreak (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.

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

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

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

Topical Medications

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

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

In general, topical treatments containing steroids are the first line for mild-to-moderate psoriasis, but they may also be used, alone or in combination, with more powerful treatments for moderate-to-severe cases. Topical medicines rarely clear up symptoms completely, however.

Topical Corticosteroids

Topical corticosteroids are the mainstay of psoriasis treatment in the United States. These drugs work for most people because they:

• Decrease inflammation
• Block cell production
• Relieve itching

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

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

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

• Low potency (some are available over-the-counter)
• Low-to-medium potency
• Medium- to upper-mid potency
• High potency
• Very high potency

The potency is determined by the molecule and the vehicle in which it is compounded.

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

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

Side Effects

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

• Acne
• Burning
• Dilated (widened) blood vessels
• Skin dryness
• Skin irritation
• Loss of skin color
• Thinning of the skin; skin may become shiny, fragile, and easily broken
• Absorption into the bloodstream with systemic side effects such as increased blood sugar

Loss of Effectiveness

In most cases, people become tolerant to the effects of the drugs, and the drugs no longer work as well as they should. Some experts recommend using intermittent therapy (also called weekend or pulse therapy). This type of treatment involves applying a high-potency topical medication for 3 full days each week. Topical steroids are usually not used for more than 2 consecutive weeks to prevent tolerance and thinning of the skin.

Topical Vitamin D3-Related Treatments

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

Calcipotriene appears to:

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

It works just as well as moderate topical corticosteroids, short-term anthralin, and coal tar in improving mild-to-moderate plaque psoriasis. These work well but may have a smell or not be cosmetically elegant. But unlike with steroids, people do not develop thinning of the skin or tolerance to the drug, which makes it attractive as a long-term agent.

Using the drug in combination with other topical and body-wide treatments may improve its effectiveness. Calcipotriene does not work as well as the highest potency corticosteroids, but combining both medications is proving to be more effective than taking either one alone. Taclonex, an ointment containing both calcipotriol and betamethasone, is available for the treatment of adults with psoriasis. Studies show the combination works better than either drug alone. Enstilar is a foam version of this combination.

Combining vitamin D ointments with systemic medicines, notably methotrexate, acitretin, or cyclosporine, increases their effectiveness. Because combining medications allows people to use lower doses of both medications, combination treatments reduce side effects.

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

Side Effects

Calcipotriene may cause the following side effects:

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

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

Coal Tar

Coal tar preparations have been used to treat psoriasis for about 100 years, although their use is now rare since the introduction of biologic therapies. Crude coal tar stops the action of enzymes that contribute to psoriasis and helps prevent new cell production. Tar was often used in combination with other drugs and with ultraviolet B (UVB) phototherapy. Tar can also help with itchy lesions and can be used on the scalp. Its safety in pregnant or lactating women is unclear as tar has mutagenic potential.

Coal tar preparations have the following drawbacks:

• They stain clothing
• They cause skin irritation
• They are not cosmetically elegant and may smell
• People using coal tar have increased sun sensitivity and increased risk of sunburn for up to 24 hours after use

Anthralin

Anthralin (Dritho-Scalp, Drithocreme, and Micanol) slows skin cell reproduction and can produce remissions that last for months. It is recommended only for chronic or inactive psoriasis, not for acute or inflamed eruptions. People with kidney problems should use anthralin with caution.

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

Side Effects and Drawbacks

Anthralin may cause the following problems:

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

People should not use anthralin on the face. Fair-skinned people should generally avoid it.

Triethanolamine is a chemical that can neutralize anthralin and help reduce irritation from short-contact anthralin treatment. It should be applied 1 or 2 minutes before washing off the anthralin. It is then reapplied after drying the skin.

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

Application

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

Topical Retinoids

Retinoids are related to vitamin A. They are used for various skin disorders, and most commonly used in acne preparations. Tazarotene (Tazorac) is the most potent of the retinoids and was the first topical retinoid found to be effective for mild-to-moderate psoriasis. It is available in cream, foam, or gel form. Other retinoids have not proven effective in psoriasis.

Unlike steroids, retinoids do not cause thinning of the skin or tolerance to the drug. Only a very small amount is needed on each lesion. Retinoid gel can be used on the scalp and nails, but it is not recommended for the genital areas or on the eyelids. The gel should be used on only 20% of the body at any time; the cream can be used on up to 35% of the body.

Combining topical retinoids with other psoriasis treatments, such as topical steroids, works better than using the drug by itself. In 2019, a combination of tazarotene and the topical steroid halobetasol (Duobrii) has been approved for psoriasis.

Side Effects

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

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

Vitamin A derivatives (drugs related to vitamin A) have been associated with birth defects and should not be used by women who:

• Are pregnant
• Wish to conceive
• Are nursing

Salicylic Acid

Salicylic acid applied to the skin helps remove scaly plaque and enhance the penetration and actions of other medications. It should not be used to cover wide areas of the body, because it can cause nausea and ringing in the ears. Combinations with high-potency steroids, such as mometasone furoate, clobetasol propionate, and betamethasone, are proving to be very helpful. Salicylic acid is helpful in shampoo form for those with thick scales of scalp psoriasis.

Occlusive Tapes

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

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

High-Potency Corticosteroid Tapes

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

However, the tapes are expensive and are associated with:

• A high rate of skin irritation
• Increased infections
• A greater chance of symptoms returning after treatment is stopped

Infection risk may be reduced by changing tapes every 12 hours.

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

Other Medications with Occlusive Tapes or Wrappings

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

Topical Immunosuppressants

Tacrolimus (Protopic) and pimecrolimus (Elidel) are approved for the treatment of psoriasis. These topical agents block the immune response which leads to skin inflammation and plaque build-up. They are especially useful for sensitive areas, such as the face, armpit, and groin areas, and are considered first-line treatment for flexural psoriasis. They are approved for use in children ages 2 and older. Adverse effects are rare, but there is a label warning of the increased risk for skin malignancy and lymphoma with long term use. They do not induce thinning of the skin like steroids, so they are a good option for the face and genital area or for a person with thin skin.

Systemic Medications

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

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

Systemic medications approved for treating psoriasis include:

• Cyclosporine
• Methotrexate
• Retinoids
• Biologic response modifiers
• Psoralen
• Apremilast

Off-label Systemics

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

• Hydroxyurea (Hydrea)
• Isotretinoin
• Mycophenolate mofetil
• Sulfasalazine
• 6-thioguanine
• Tacrolimus

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

Several biologic agents to treat psoriasis are available or under study, including oral medications, monoclonal antibodies, anti-interleukin antibodies.

Methotrexate

Methotrexate is a biologic drug that interferes with cell reproduction and has anti-inflammatory properties. It is a first-line, or primary, systemic drug used to treat adults with severe psoriasis. It has been used for psoriasis since the 1950s.

The drug is taken once weekly by mouth or subcutaneous injection.

Side Effects

Many people are able to tolerate methotrexate with few side effects. Possible side effects include:

• Anemia, usually causing no noticeable symptoms
• Headache
• Mild and slow hair loss that is reversible when the medication is stopped
• Increased likelihood of becoming sunburned
• Mouth sores
• Nausea, usually mild and improves over time
• Possible muscle aches
• Rash
• Vomiting (rare)

Many of these side effects are due to folic acid deficiency. People should ask their doctor if they should take folic acid supplements (generally recommended at 1 mg daily on the days not taking the methotrexate).

More serious, but relatively uncommon side effects include:

• Increased risk for infections, particularly shingles and pneumonia. Methotrexate suppresses the immune system. People with active infections should avoid this drug.
• Infertility, miscarriage, and birth defects. This drug should not be used during pregnancy, because it can cause miscarriages or birth defects. It may harm fertility in men.
• Kidney damage.
• Liver damage, most commonly in people with existing liver problems. Regular monitoring for liver toxicity includes blood tests and sometimes liver biopsies. People who are properly monitored rarely have any permanent liver damage.
• Cough and shortness of breath. Risk factors for these side effects include diabetes, existing lung problems, protein in the urine, and the use of rheumatoid arthritis drugs of a type called DMARD.
• Severe anemia. Folic acid supplements can offset this effect.
• Toxic effects on bone marrow. This can cause reduced blood cell production.

Despite methotrexate's side effects, some experts view it as the best therapy for widespread plaque psoriasis. It may also be effective for some people with generalized erythrodermic and pustular psoriasis.

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

Drug Interactions

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

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

People Who Should Avoid Methotrexate

Pregnant and nursing mothers should never take methotrexate because it increases the risk for severe, even fatal, birth defects and miscarriage. The drug should be discontinued several months before the actual pregnancy. Methotrexate may also cause temporary impairment of fertility in men. People with Hepatitis B should not take methotrexate.

People with the following conditions are unlikely to be given methotrexate:

• Alcoholism
• Anemia or other blood abnormalities
• Kidney problems
• Liver problems (including hepatitis)
• Peptic ulcers
• Suppressed immune system

Oral Retinoids

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

Acitretin (Soriatane) is the retinoid of choice and may be dramatically effective for severe psoriasis, particularly pustular or erythrodermic types. It is also effective in a low-dose formulation for symptoms of nail psoriasis. When used alone, it is much less effective against more common forms of psoriasis, such as plaque or guttate psoriasis. However, when combined with UVB phototherapy it can markedly improve the response, even in people with these forms of psoriasis. It is not effective for psoriatic arthritis.

Isotretinoin (Accutane), more commonly used to treat acne and not FDA-approved for psoriasis, is far less potent than acitretin, but it may still be effective against pustular psoriasis. The drug may also be effective with phototherapy.

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

Combination therapy

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

Side Effects

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

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

In rare cases, retinoids, particularly isotretinoin, may cause a condition called benign intracranial hypertension (pseudotumor cerebri), which occurs in the brain. Symptoms include headache, nausea, vomiting, and blurred vision. People experiencing these symptoms should call a doctor immediately and stop taking the drug. There is increased risk for this with concomitant use of tetracycline antibiotics.

Oral retinoids should not be taken by women of child-bearing age, as acitretin can stay in the body for up to 3 years and lead to severe birth defects.

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

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

Oral Retinoids and Pregnancy

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

• Acitretin is an oral retinoid used typically for first line-therapy of chronic palmoplantar or pustular psoriasis. It may be used in combination with other therapies to treat plaque psoriasis. Acitretin should not be given to any woman who may become pregnant within 3 years of taking it. Drinking alcohol changes acitretin to a retinoid that is stored in fat cells for 3 years. It may have the potential to cause birth defects during that time. Be cautious about cooking products and over-the-counter preparations, such as cough syrup, which may contain alcohol.
• Women who are pregnant or who plan to become pregnant should not use isotretinoin. Everyone who takes, prescribes, or dispenses the drug must enroll in a national registry called iPLEDGE, which helps to ensure that no woman starts retinoid therapy while pregnant or trying to get pregnant.

Cyclosporine

Cyclosporine blocks certain immune factors and may be effective for all forms of psoriasis. It is also a first-line, or primary, systemic drug used to treat adults with severe psoriasis, von Zumbusch pustular psoriasis, or erythrodermic psoriasis. Cyclosporine often clears psoriasis in many patients within 8 to 12 weeks.

Side Effects

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

Common and temporary side effects include:

• Fatigue
• Gingivitis
• Gout
• Excessive growth of body hair
• Headaches
• Joint pain
• Tremor

More serious complications may include:

• Kidney damage.
• High blood pressure (Some doctors advise treating high blood pressure with calcium channel blockers, because other standard blood pressure drugs may worsen psoriasis. Calcium channel blockers also help prevent kidney problems.)
• High cholesterol and lipid levels.
• High levels of calcium and low levels of magnesium.
• Increased risk for infections.
• Liver problems.
• Lymphomas (cancers of the lymphatic system).
• Skin cancers (People who take cyclosporine after PUVA therapy have a higher incidence of squamous cell skin cancer. The risks are greatest with long-term and previous use of PUVA, methotrexate, or other immunosuppressants.)

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

People Who Should not Use Cyclosporine

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

Drug and Food Interactions

Cyclosporine interacts with numerous drugs, including prescriptions, over-the-counter preparations and grapefruit and grapefruit juice.

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

Biological Response Modifiers

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

Biologics are traditionally second- or third-line treatments, but are quickly becoming the standard of care as first line treatments for moderate to severe psoriasis. Although studies of these medications have primarily been done on people who are over 18 years old, several are approved for patients under the age of 18.

The biologics traditionally used to treat plaque psoriasis (described below) are now also considered in the treatment of pustular psoriasis. Many studies testing new biologics are underway.

There are different types of biologics used to treat psoriasis:

• Tumor necrosis factor (TNF) blockers target the chemical messenger TNF-alpha, which is released during the inflammatory response.
• Interleukin blocking monoclonal antibodies injections for 12 weeks. They need blood tests every 2 weeks.

Types of TNF blockers:

• Etanercept was the first approved biologic for the treatment of moderate-to-severe plaque psoriasis, and for people with psoriatic arthritis. The drug is given either alone or in combination with methotrexate. People inject themselves under the skin once or twice a week for 12 weeks at a higher dose and then drop down to a lower weekly dose. The drug may be effective in people with psoriasis who have not responded to other biologic drugs or other therapies, and it is also effective in people who have not yet received biologic treatments. It has been shown to be safe and effective for treating children with rheumatoid arthritis and in 2016 got the FDA indication for pediatric psoriasis.
• Adalimumab has been approved for moderate-to-severe chronic plaque psoriasis. It is given by injection weekly at first, and then bi-weekly long term. It appears better tolerated than methotrexate. This drug is also approved for psoriatic arthritis.
• Infliximab is a TNF inhibitor given by IV infusion. It is often considered for, second- or third-line therapy for chronic plaque psoriasis.
• Certolizumab is a monoclonal antibody targeting TNF-alpha approved for moderate to severe plaque psoriasis and psoriatic arthritis. It is administered by injection every other week.

Side effects and risks of TNF blockers:

• All of the TNF inhibitors carry the potential for an increased risk for serious infections. Upper respiratory infections are the most common infections that occur.
• Uncommon infections caused by fungi and tuberculosis bacteria also occur in people using anti-TNF medications. People using anti-TNF medications who display symptoms of body-wide (systemic) illness should be tested. Because these infections are uncommon, previous delays in diagnosis have resulted in death in some people.
• People receiving these drugs are at risk of reactivating old tuberculosis (TB) infections. People are also at a higher risk of developing TB. The FDA recommends TB screening with a purified protein derivation (PPD) skin test or a blood test called QuantiFERON-gold.
• Whether TNF inhibitors increase the risk for lymphoma and skin cancers is a debated issue.

A number of other side effects are also possible.

Monoclonal Antibodies

Anti-interleukin monoclonal antibodies bind to proteins or cells and stimulate the immune system to destroy those cells. New monoclonal antibodies targeting various interleukins are continuously being developed. Currently FDA-approved anti-interleukin antibodies for psoriasis include:

• Ustekinumab is an anti-interleukin antibody approved for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. It is given by injection about every 3 months and may be used as first-line treatment with approval down to the age of 12.
• Secukinumab, ixekizumab, brodalumab, tildrakizumab, risankizumab, and guselkumab are other anti-interleukin antibody drugs approved for the treatment of moderate-to-severe plaque psoriasis. These medicines are very effective in achieving clearance of most of a person's psoriatic lesions.

Apremilast

Apremilast, a PDE4 inhibitor, is an oral anti-inflammatory. It was approved for the treatment of moderate to severe plaque psoriasis and psoriatic arthritis. People may see an improvement in about 4 months when taken twice daily. Side effects may include:

• Diarrhea
• Nausea
• Upper respiratory tract infection
• Headache
• Depression

It has not yet been studied for safety in pregnant women. Unlike biologics, it is not associated with the reactivation of TB.

Other Second- and Third-Line Treatments

Immunosuppressants

Some oral immunosuppressants being studied for psoriasis include tacrolimus, pimecrolimus, and sirolimus. Studies have been limited, however. Side effects of these medications are similar to those of cyclosporine. Pimecrolimus may specifically target the skin and have fewer side effects. (Some immunosuppressants are also being studied as topical treatments.)

Phototherapy

Phototherapy means to treat with ultraviolet light.

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

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

Certain ointments on the skin can have a negative effect and block the beneficial rays from penetrating the skin. However, some moisturizers with low reflective and absorption qualities applied within 5 minutes of light therapy can enhance phototherapy benefits. These may include:

• Calcipotriene
• Mineral oil
• Glycerol
• Vaseline oil
• Oleic acid

It is unclear which of the phototherapy options below is best. More research is needed.

Psoralen and Ultraviolet A Radiation (PUVA)

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

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

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

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

Initial PUVA Treatment Phase

The initial phase typically follows these steps:

• Psoralen is typically taken by mouth in the form of 8-methoxypsoralen 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 people with liver disease or who get severe nausea from taking the pill form. UVA should be given within 15 minutes of using topical psoralen.
• The person enters and stands in a light box, which is 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 people.

Treatments may be repeated two or three times a week. They should never be performed more frequently than once every other day, because the full effects of the treatments are not evident for 48 hours. It takes an average of about 25 PUVA treatments for the full effect to be seen, but during that period treatment intensity may vary.

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

Maintenance Phase

Once the psoriasis has improved by about 95%, the person 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, people may become more susceptible to tanning and sunburn. They should reduce exposure to natural sunlight during this time.

Success Rates

Nearly 90% of people achieve marked improvement or clearing within 20 to 30 treatment sessions.

Combinations

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

Side Effects and Complications of PUVA

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

Special Warning on PUVA and Skin Cancers

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

• A family or personal history of skin cancer
• Light skin and fair or red hair
• Received radiation or x-ray treatments or taken immune suppressing drugs
• Received more than 200 PUVA treatments

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

• Opponents of PUVA argue that studies suggest a long-term risk for melanoma, starting about 15 years after treatment, particularly in people who receive more than 250 treatments.
• Supporters of PUVA argue that it is not yet known whether the people who developed melanoma experienced sunburn during the procedures, or if they already had risk factors for skin cancers. If so, properly given treatments could still be considered safe for people without risk factors. They also argue that PUVA is still the most effective treatment for severe psoriasis, and the alternatives are usually very powerful and relatively new drugs that may have even more serious side effects. Furthermore, adding retinoids may protect against skin cancers while increasing the treatment's effectiveness.

Protective Measures with PUVA Therapy

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

Protective Measures During Treatment

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

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

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

Protective Measures After Treatment

The drugs used in PUVA make people more likely to get a natural sunburn for a few hours after treatment. People should take the following precautions:

• Wear UVA absorbing wrap-around sunglasses that are designed to completely block out stray radiation. People should begin wearing them as soon as they take the drug, and for at least 12 hours after the treatment. This is important to prevent a PUVA reaction around the eyes, which may lead to cataracts. There is no need to wear these glasses after sunset.
• For about 8 hours after taking the drug, avoid exposure to daylight, even if the day is cloudy or exposure is only through windows.
• Wear heavy opaque clothing (clothes that do not let light through) outside, including hats and gloves.
• Apply sun block over all exposed areas, including the lips. The sun block should have a sun protection factor (SPF) of more than 30 and include ingredients that block both UVB and UVA radiation.
• Do not spend a long time in sunlight for at least 2 days after the combined treatment.

UVB Therapy

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

Types of UVB therapy:

• Broadband UVB
• Narrowband UVB (NB-UVB)
• Laser treatments

Broadband Ultraviolet B (UVB) Radiation

Broad spectrum or broadband UVB is radiation in the wavelength of 290 to 320 nanometers and is the standard UVB phototherapy treatment in the United States. It is not as potent as the treatments that use narrowband UVB or PUVA and is not useful for chronic psoriasis.

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

• Treatment starts in the doctor's office or another medical setting. Once the disease has stabilized, the person can get a prescription for equipment that can be used at home. Research finds that home UVB treatment is just as safe and effective as hospital-based treatment, and people may be more likely to get the treatments they need if they administer them at home. Even at home, treatment must always be supervised to regulate UV exposure.
• In preparation, the person fully undresses, although unaffected areas may be covered to avoid overexposure.
• The initial session may last for just a few seconds, depending on whether the person has lighter or darker skin. The lightest skin is exposed to the briefest session. The duration increases with each treatment until the skin clears or the person experiences itching or irritation. The condition may worsen initially.
• UVB therapy usually requires about 20 to 40 treatments (about 3 per week). Full results take about 3 weeks.

Use of Medication

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

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

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

Side Effects of UVB

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

Narrowband Ultraviolet B (NB-UVB) Radiation

Narrowband radiation may be safer than other approaches, and some scientists now believe it should be the first option for people with chronic plaque psoriasis.

NB-UVB is used without medications and is very strong. Whether it has any effect on the disease process itself is unclear. The light wavelength is between 300 to 320 nanometers, which is the most beneficial part of sunlight for psoriasis.

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

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

People prefer NB-UVB over other PUVA treatments because they do not have to:

• Take medications
• Experience unpleasant side effects, such as nausea

NB-UVB is also safe for pregnant women and children.

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

Laser Treatments

Laser UVB Treatment

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

Pulsed-Dye Lasers

Pulsed-dye lasers give off high-intensity yellow light, which destroys the tiny blood vessels that make up psoriatic plaques. This treatment has been used for years to remove birthmarks, such as port wine stains and unsightly blood vessels on the skin. Some studies have reported significant (but not complete) improvement of psoriasis, and remissions that have lasted up to 13 months. Treatment sessions can take up to 30 minutes and can feel uncomfortable (similar to being repeatedly snapped with a rubber band). It typically takes up to 6 sessions to clear the target areas. Bruising is common, and there is a small risk for scarring.

Hematopoietic Stem Cell Transplantation (HSCT)

Hematopoietic stem cell transplantation is a procedure that injects healthy stem cells into the bone marrow to replace diseased cells. The healthy cells take over and diseases, such as cancer and autoimmune problems, may go into remission. In some cases, the therapy is curative. Reports from a small number of people show that allogeneic transplants, where stem cells come from a healthy donor, have resulted in remission of psoriasis (average follow-up 49 months). Autologous HSCT (where stem cells come from the person) has had less favorable results. More research is needed.

Commercial Tanning Units

Home tanning devices and tanning salons are not usually recommended, but they may be helpful for people who do not have access to a medical facility. Many people have achieved a significant reduction in symptoms after taking acitretin and being exposed to a UVB commercial tanning unit (specifically, a Wolff tanning bed).

However, UV outputs can vary widely among tanning beds and salons. Some units emit UVA radiation, which poses a higher risk for skin cancers. Adverse effects of tanning salons that use UVA or UVB radiation are the same as with any UV phototherapies, including an increased risk for skin cancer. Use of home units should be followed with a physician to regulate UV exposure.

Managing Psoriasis

Although sunburn puts people at risk for skin cancer and can make psoriasis worse, regular exposure to the sun helps clear up psoriasis in people with mild-to-moderate conditions. People should cover non-affected areas with clothing or sunscreen and sunbathe only until the skin starts to tan. While this sun exposure may help clear psoriasis, the sun damage can lead to skin cancer.

Reducing Stress and Anxiety

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

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

Treating Dry Skin

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

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

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

Remedies for Itching and Irritation

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

Dietary Factors

Weight loss and a decrease in alcohol intake may improve symptoms of psoriasis.

The evidence that omega-3 fatty acids, folic acid, vitamin D, and antioxidants improve psoriasis remains unclear. Good quality, controlled trials have yet to be performed.

Alternative Remedies

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

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

Herbs and Supplements

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

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

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

Outlook

Psoriasis is lifelong and is not curable. Although it is also marked by rapid cell growth, psoriasis is neither cancerous nor contagious. Current medications, particularly the biologics, have revolutionized the treatment of psoriasis in that clear skin can be achieved.

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 may go into remission, however, often clearing on its own.
• Increased levels of estrogen may be responsible for this improvement. Relapse may occur after a woman gives birth.

Emotional and Social Consequences

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

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

Researchers have reported the following:

• Surveys of people 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 people reported that psoriasis hurt their confidence.
• Another study reported that 8% of people with psoriasis felt their life was not worth living.

Substance Abuse

Some people, 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 and may block the benefits of the medications used to treat it.

Physical and Medical Complications of Psoriasis

Folate Deficiency in Severe Psoriasis

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

Skin Cancers

People with severe psoriasis who receive medications that affect the whole body may be at higher-than-normal risk for developing cancers, primarily skin cancers and lymphomas. The risk is not elevated in people with mild psoriasis. There is some indication, however, that people with psoriasis have a higher risk for non-melanoma skin cancers, regardless of their treatments. UV treatments may also increase the risk for skin cancers, and medicines that suppress the immune system may increase the risk of developing and spreading of skin cancers.

Obesity, Diabetes, and Heart Risks

Psoriasis, as an inflammatory disease, has been linked to an increased risk for heart attack and cardiovascular disease, although the link has been observed more in hospital-based studies rather than people in the community. People with psoriasis are much more likely to have hardening of the arteries (atherosclerosis) and other blood vessel diseases than people without psoriasis. People with psoriasis may be at higher risk for high cholesterol/triglyceride levels as well. These conditions are also related to inflammation, which may be why people with psoriasis are more likely to develop diabetes and high blood pressure than people without the condition. It is not yet known whether there are genetic links between psoriasis and some of these conditions. The connection may also have to do with shared risk factors, such as smoking and obesity. People with moderate-to-severe psoriasis should be screened, and possibly treated, for cardiovascular risks.

Complications of Erythrodermic and Pustular Psoriasis

Impaired Temperature Regulation

Erythrodermic psoriasis (in which psoriasis covers the entire skin) can cause abnormalities in the body's ability to regulate temperature and requires hospitalization.

von Zumbusch Psoriasis

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

• The condition can develop abruptly.
• Symptoms can include fever, chills, weight loss, and muscle weakness.
• People 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.

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

Resources

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

Related Reports

References

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Review Date: 7/29/2021  

Reviewed By: Ramin Fathi, MD, FAAD, Director, Phoenix Surgical Dermatology Group, Phoenix, AZ. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

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