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Saturday, April 21, 2012

Psoriasis

Author: Dr Jack Resneck Jr University of California San Francisco 2009-10-16

Psoriasis: A Common, Chronic Skin Disease with Many Distinctive Clinical Forms
Introduction

Psoriasis is a common, chronic skin disorder present in about 2-3% of the world’s population.  The most typical form is characterized by round, red skin lesions covered by silvery white scales, most commonly occurring on the knees, elbows, and scalp.  There are many distinctive clinical forms of psoriasis, and the severity of the disease varies greatly from patient to patient.  The course is usually chronic, with intermittent remissions.  Descriptions of patients with psoriasis date back over 2,400 years, at which time the disease was confused with leprosy.   Psoriasis is rarely life-threatening, but can profoundly impair the quality of life of affected patients.

 

Who Gets Psoriasis?

The prevalence of psoriasis appears to be highest among populations with Western European or Scandinavian heritage, but the disease has been reported in all ethnic groups.  Accurate figures are difficult to obtain, but psoriasis appears to be significantly less common in Africans, African Americans, Asians, and Native Americans.  Psoriasis can appear at any age, but most commonly begins in young adulthood. (The average age at onset is 27, and 75% of cases occur before age 46.) The disease is equally common in males and females.  There is a strong genetic component – about 30% of patients with psoriasis have an affected first degree relative – but it’s not yet clear how this works as multiple and complex genes appear to be involved.

 

What Causes Psoriasis?

Psoriasis was previously thought to be a disorder primarily of skin cells (keratinocytes), but is now recognized to be mediated by the immune system.  Changes in skin cell differentiation and proliferation are probably initiated and perpetuated by T –lymphocyte cells (a type of white blood cell) and their signals to many other components of the immune system.  These T-cells from an affected patient can induce psoriatic lesions when experimentally injected into normal human skin. 
As discussed above, genetic factors play some role, but environmental factors – such as infection, alcohol intake, smoking, and certain medications – also contribute to disease susceptibility.  Psoriasis is not contagious.

 

Types of Psoriasis

Psoriasis occurs in several clinical forms, which are often distinct, though individual patients may have features of more than one form.
-Plaque psoriasis (also known as psoriasis vulgaris) accounts for 80-90% of cases. Individual lesions (or “plaques”) are usually red, sharply defined, and covered by white or silvery scale. They can be small or large, thick or thin. The degree of body surface affected can vary from just a few small areas to nearly total-body involvement, but the rash is usually relatively symmetric. The scalp, elbows, and knees are most commonly affected, but the lower back, umbilical area, hands, feet, and genitals are also frequently involved. Lesions sometimes appear at sites of injury or trauma to the skin (Koebner reaction). Individual lesions may last for months, or even years at the same location. The rash is often without symptoms other than appearance, but it may itch or burn.
 
-Inverse (flexural) psoriasis typically occurs in the armpits, groin, under the breasts, or in the gluteal crease (the horizontal crease between the buttocks). It usually consists of shiny red patches with minimal or no scale.
-Guttate psoriasis occurs abruptly with the development of small (2-5mm), dew-drop-shaped lesions on the trunk and extremities. It often follows a streptococcal or viral upper respiratory infection and resolves within a few months of onset. Some patients with guttate psoriasis, however, may go on to develop classic plaque disease.
-Sebopsoriasis is a form in which lesions resemble seborrheic dermatitis, with yellow, greasy soft scales on lesions appearing on the face, scalp, armpits, or under the breasts.
-Pustular psoriasis of the palms and soles (palmoplantar psoriasis) consists of discrete red scaly areas on the palms or soles, sometimes with small non-infectious pustules. It may resemble or be confused with a form of eczema affecting the hands and feet.

-Generalized pustular psoriasis is a widespread form of psoriasis characterized by the sudden
development of tiny, non-infectious pustules that coalesce into larger pus-filled “lakes” over broad areas of red skin. Patients often have fever, and may require hospitalization for their widespread skin involvement or other complications. This form can be triggered by the use of or withdrawal from systemic steroids (such as prednisone), and by certain infections.
-Erythrodermic psoriasis is another form of widespread disease in which the entire body (often except for the face) becomes red and possibly scaly. This form may also require hospitalization, and can resemble a number of other diseases that may generate widespread redness (atopic dermatitis, pityriasis rubra pilaris, drug eruptions, and cutaneous T-cell lymphoma).

 

What are Some Other Manifestations of Psoriasis?

As many as 1 in 4 psoriasis patients may also have arthritis as a manifestation of their disease, with joint pain, stiffness, or damage.  About half of patients with psoriasis have distinctive changes to their fingernails or toenails.  These may include pitting, onycholysis (nail plate separation), oil spots (orange-yellow discolored spots), and damaged nails resembling a fungal infection.  Some recent research suggests that cardiovascular disease is increased in patients with severe psoriasis, and that patients with severe psoriasis may die three to four years earlier than patients without psoriasis.
Psoriasis substantially alters the quality-of-life of many affected patients.  One landmark study found that the impact of psoriasis on patients’ physical and mental functioning was comparable to that seen in cancer, arthritis, hypertension, heart disease, diabetes, and depression.  These results shed some light on the profound degree of stigmatization that many psoriasis patients experience.

 

How is Psoriasis Diagnosed?

Most cases of psoriasis are straightforwardly diagnosed by dermatologists or other physicians without further testing. In some more difficult cases, a small skin biopsy may aid in establishing the diagnosis or excluding other skin diseases.

 

How is Psoriasis Treated?

Psoriasis is a chronic condition without a known cure, so therapies are targeted at controlling disease symptoms to improve patients’ quality of life. Management is generally individualized, taking into account the severity of the disease, the impact of the disease on the patient, and the risks of each treatment. Because of the chronic nature of psoriasis and the limitations of current therapies, as many as 40% of psoriasis patients report being frustrated by the ineffectiveness of their current treatment.

Topical Treatments:

-Corticosteroids. Topical steroids are a mainstay of psoriasis treatment. They come in a variety of vehicles (creams, ointments, lotions, foams) and a wide array of potencies (from over-the-counter hydrocortisone to high-strength prescription forms). The potency should be chosen based both on the severity of disease and the body location being treated. Covering the area with dressings, polyethylene films, or special suits can increase the penetration of topical steroids. The primary side-effects of topical steroid treatment are local acne and skin thinning, but when used appropriately, topical corticosteroids are safe and effective.
-Calcipotriol. This vitamin D-3 analog can be used alone or in combination with corticosteroids. The primary side effect is local irritation, but, very rarely, this medication can also cause abnormalities in calcium levels.
 
-Dithranol (anthralin) is sometimes used in hospitals or other psoriasis treatment centers, but it can stain clothing and irritate skin.
 
-Tazarotene (a topical retinoid) is sometimes combined with a corticosteroid.
 
-Coal tar and tar extracts can be compounded into agents for topical use.
 
-Calcineurin inhibitors (tacrolimus or pimecrolimus) may be helpful for thin psoriasis lesions in areas prone to corticosteroid side-effects.

 

Phototherapy:

-Treatment with ultraviolet light dates back thousands of years, when patients noted that their psoriatic disease improved with sunlight. Options for medical phototherapy include ultraviolet B (UVB), topical or oral psoralen followed by exposure to ultraviolet A (PUVA), and narrowband UVB. The Goeckerman technique involves the combination of tar preparations applied to the skin and UVB phototherapy; it is highly effective in producing disease-free remissions.
 
-The Excimer laser delivers light at a frequency close to that of narrowband UVB phototherapy to individual lesions.

 

Oral Medications:

-Methotrexate is a chemotherapy agent which is highly effective for severe disease. It is most often given orally or as an injection in weekly doses. The primary risks include liver damage, bone marrow suppression, and kidney damage.
 
-Cyclosporine is an immune system suppressant that is also highly effective for severe disease. Its long-term use is primarily limited by the risk of kidney damage.
 
-Acitretin is a systemic retinoid with partial efficacy against plaque psoriasis and higher efficacy in erythrodermic and pustular psoriasis. It is sometimes combined with phototherapy. Common side-effects include dry skin and increased triglycerides. Less common side-effects include liver damage and bone changes. It can cause birth defects during or up to two years after treatment.
 
-Oral or intramuscular corticosteroids are rarely used for psoriasis, as there are significant risks associated with their use. Many psoriasis patients experience severe “rebound” of their disease with severe flares after discontinuation of systemic corticosteroids. Another risk is the possible occurrence of pustular psoriasis eruptions after use of these medications.
 
-Oral antibiotics are imperative for those patients with guttate psoriasis brought on by Streptococcal pharyngitis.

 

Biologic Injectable Therapies:

A series of newer agents (Etarnercept, Infliximab, Adalimimab, Alefacept, Golimumab, and Ustekinumab) are now used to treat selected cases of psoriasis or psoriatic arthritis. These drugs target specific steps in the immune pathway in order to block the disease process. Most of these agents are delivered by patient-administered injections, but Infliximab (which acts more rapidly and achieves a response in the highest percentage of patients) requires IV infusion.
 
All of the biologic agents suppress some part of the normal immune response. The risks with each drug vary, but may include (for certain drugs) reactivation of tuberculosis, formation of antibody responses, serious infections, exacerbation of multiple sclerosis, or an increase in the risk of lymphomas. Recommendations for pre-treatment screening and laboratory monitoring during therapy are different for each of these medications.
 
These drugs are all expensive, and predicting which patients will respond to a given drug is difficult or impossible. For some patients, these biologic agents have produced dramatic responses with spectacular improvements in quality of life.
 
While few psoriasis drugs have been evaluated head to head in studies designed to compare their efficacy, one published article did look at reported efficacy from different psoriasis agents. This study suggested that some older forms of treatment (Goeckerman, PUVA with retinoids, and Cyclosporine) actually outperformed many of the newer biologic agents.
 
A number of additional biologic agents are currently in various stages of development and/or clinical trials.
 
(Nothing in this Knol should be construed as individual medical advice. Patients should consult with their own physician regarding the diagnosis and treatment of psoriasis. Not all of the medications discussed are FDA-approved for the treatment of psoriasis, and some side-effects and contraindications have not been listed.)
 

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Selected References (click to link to Pubmed citations)