Psoriasis

Charles Camisa

CHAPTER SECTION LINKS

Definition and etiology
Prevalence and risk factors
Pathophysiology
Signs and symptoms
Diagnosis

Therapy
Summary

Definition and etiology

Psoriasis is a common papulosquamous skin disease that may be associated with a seronegative spondyloarthropathy. The etiology of psoriasis is unknown.

Prevalence and risk factors

Psoriasis affects 2% of the U.S. population, and about 11% of these patients have psoriatic arthritis (PSA). Psoriasis may begin at any age, but the mean age at onset is 30 years. Men and women are affected equally.

U.S. primary care physicians initially see 58% of the estimated 150,000 new cases of psoriasis per year, but dermatologists handle 80% of the 3 million office and hospital visits for psoriasis each year.

The form that psoriasis takes in a patient depends on a combination of genetic influences, environmental factors (e.g., trauma and climate), associated diseases (especially infections), and concomitant medications. Certain drugs, notably lithium, antimalarials, β-adrenergic blockers, interferons, and ethanol (if abused) have been reported to induce psoriasis or aggravate preexisting disease in some patients. Emotional stress may also lead to a flare of psoriasis.

Pathophysiology

The psoriatic skin lesions are the result of inflammation in the dermis and hyperproliferation with abnormal differentiation of the epidermis. The primary pathologic process is most likely dysregulation of activated T cell interactions with antigen-presenting cells and overproduction of proinflammatory cytokines such as interferon-α and tumor necrosis factor-α (TNF). Evidence for this theory derives from the dramatic improvement of severe psoriasis in patients treated with broadly immunosuppressive drugs used in organ transplantation, such as cyclosporine and tacrolimus.

Signs and symptoms

Figure 1: Click to Enlarge

Although considered a single disease, psoriasis has several morphologic expressions and a full range of severity. Plaque-type psoriasis, or psoriasis vulgaris, is the most common form, occurring in about 80% of all psoriasis patients. A typical lesion is a well-demarcated, red-violet plaque surmounted by white silvery scales (Fig. 1).

Symmetry of lesions is the rule, and the face is usually spared. The most commonly involved areas are the elbows, knees, scalp, sacrum, umbilicus, intergluteal cleft, and genitalia. About 70% of patients complain of pruritus, skin pain, or burning, especially when the scalp is involved.

Guttate psoriasis (Fig. 2), named for its small droplet-shaped lesions, accounts for about 18% of all cases. This type is more common among children and young adults and is more likely to involve the face. Patients frequently have a history of upper respiratory tract infection or pharyngitis. Some cases of acute guttate flares following streptococcal throat infection are precipitated by the superantigen exotoxin.

Figure 2: Click to Enlarge

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Figure 4: Click to Enlarge

C. Pustular psoriasis (Fig. 3) accounts for about 1.7% of cases. It is characterized by sterile pustules, which may be generalized or localized to the palms and soles. There is a female predominance in localized pustular psoriasis, but the incidence is equal in men and women in the generalized type. The average age at onset for pustular psoriasis is 50 years.

The least common form of psoriasis is exfoliative dermatitis or psoriatic erythroderma (Fig. 4) accounting for 1% to 2% of all cases. Erythroderma is defined as a scaling pruritic, inflammatory skin eruption that involves almost 100% of the body surface. Erythrodermic psoriasis usually develops gradually or acutely during the course of chronic plaque-type psoriasis, but it may be the first manifestation of psoriasis, even in children. The mean age at onset is about 50 years. Men with the condition outnumber women, and concomitant psoriatic arthropathy is common. The most common precipitating factor is the inappropriate or excessive use of potent topical, oral, and intramuscular corticosteroids. Patients are at risk for Staphylococcus aureus septicemia as a result of their compromised skin barrier.

The nails are involved in up to 50% of psoriasis patients; in patients with PSA, the prevalence exceeds 80%. Pitting of the nail plate is the most common manifestation. The pits tend to be large, deep, and randomly dispersed on the nail plate. Small red spots in the lunula or yellow-brown spots (oil droplet sign) in the nail bed correspond to lesions of psoriasis there.

PSA affects up to one third of patients with psoriasis. PSA is a destructive arthropathy and enthesopathy with some clinical features in common with rheumatoid arthritis. Arthritis occurs after the onset of the skin eruption in two thirds of cases. The severity of skin and nail involvement does not correlate with the severity of joint disease in patients with PSA. Although the systemic agents used to treat psoriasis are often effective for PSA, the specific management of PSA is beyond the scope of this chapter.

Diagnosis

A clinical diagnosis is usually sufficient for classic skin and nail lesions. The differential diagnosis includes eczema, pityriasis rubra pilaris, drug reactions, tinea corporis, secondary syphilis, and cutaneous T cell lymphoma. Therefore, it may be necessary to perform skin biopsy, potassium hydroxide (KOH) examination of scales, and serologic tests.

Therapy

Treatments for psoriasis are divided into six levels ( Table 1 ). The choice of treatment depends on the severity of disease and response in the individual patient.

Table 1: Treatments for Psoriasis

Level 1	Level 2	Level 3	Level 4 *	Level 5 *	Level 6
Emollients	Natural sunlight	Acitretin (may be combined with UVB light or with PUVA)	Sulfasalazine	Azathioprine	Alefacept
Keratolytics Salicylic acid Lactic acid Urea	Ultraviolet B (UVB) light	Methotrexate	Hydroxyurea	6-Thioguanine	Efalizumab
Calcipotriene	UVB light and coal tar (Goeckerman regimen)	Cyclosporine	Calcitriol	Mycophenolate mofetil	Etanercept
Anthralin (usually short contact)	UVB light and anthralin (Ingram regimen)		Antibiotics	Tacrolimus	Infliximab
Corticosteroids Topical Hydrocolloid occlusive dressing Intralesional injections	UVB narrowband light (311 nm to 313 nm)				Adalimumab
Coal tar	Psoralen and ultraviolet A (UVA) light (PUVA)
Tazarotene	Psoralen, UVA light and UVB light

* Not approved for psoriasis treatment by the U.S. Food and Drug Administration.

Level 1: Topical Treatments

Emollients (bland lubricants) should be tried first, followed by keratolytic lotions containing salicylic acid or urea. Most patients are treated with both topical corticosteroids and calcipotriene. A new combination ointment containing calcipotriene and betamethasone for once daily application was approved in 2006.

Level 2: Phototherapy

Phototherapy is highly effective, clearing 80% to 100% of the skin. However, some maintenance therapy is usually necessary. The disadvantages to this treatment method are that it requires special equipment, two or three office visits a week, and is expensive. Additionally, it carries a short-term risk of sunburn and a theoretical long-term risk of skin cancer. As alternatives, natural sunlight and ultraviolet light (UVA) tanning beds are only mildly therapeutic.

Level 3: Systemic Treatments

Systemic treatments are more effective than level 2 treatments, but they are usually more expensive and have greater potential for toxicity. Systemic treatments for psoriasis are generally prescribed after consultation with the dermatologist.

Methotrexate is the antimetabolite most often prescribed by dermatologists for moderate-to-severe psoriasis. Hepatotoxicity is the primary clinical concern when planning long-term methotrexate therapy. Mild transaminase elevations (less than twice the upper limit of normal) are to be expected during therapy, but these levels do not correlate with hepatic fibrosis. The guidelines for monitoring for liver damage differ for rheumatologists and dermatologists. The American College of Rheumatology does not recommend liver biopsy during treatment unless 5 of 9 or 6 of 12 liver enzyme levels in a 12-month period are elevated or unless the serum albumin concentration decreases below normal. A 1998 consensus conference of the American Academy of Dermatology recommends liver biopsy at baseline only if the patient has significant risk factors. The initial liver biopsy is done after a 1 g to 1.5 g cumulative dose and is repeated after 3 g and 4 g cumulative doses. Folic acid supplementation 1 mg/day is recommended because it mitigates the gastrointestinal effects of methotrexate without reducing efficacy. It also prevents megaloblastic anemia.

Nephrotoxicity and hypertension are the two most serious side effects of cyclosporine therapy. Although it is very effective for severe psoriasis, cyclosporine has been relegated to brief intermittent courses or crisis intervention after the approval of safer biologic immunomodulators (level 6).

Levels 4 and 5: Experimental Treatments

Treatments in levels 4 and 5 are not approved by the U.S. Food and Drug Administration (FDA) for psoriasis. Level 4 treatments are slightly to moderately effective but are less toxic than level 5 treatments. Level 5 treatments are reserved for the most severe and recalcitrant cases, including PSA.

Level 6: Biologic Immunomodulators

Level 6 treatments are the biologic immunomodulators—some of which are currently FDA-approved for psoriasis, PSA, and other indications. The biologics are monoclonal antibodies and fusion proteins that represent a new paradigm for treatment of moderate-to-severe psoriasis. These compounds are designed to antagonize cell-cell interactions, memory-effector T cells, or proinflammatory cytokines.

Alefacept is a fusion protein composed of leukocyte function antigen-3 and human IgG1 domains that is administered as a once weekly intramuscular dose of 15 mg for 12 weeks. In double-blind placebo-controlled phase III studies, 21% of patients achieved >75% improvement at 14 weeks compared with 5% receiving placebo. Alefacept was the first biologic to receive FDA approval for psoriasis in 2003. Although no serious side effects have been encountered, alefacept is now the least often prescribed biologic because of insufficient therapeutic response rates.

Efalizumab is a humanized monoclonal antibody directed against the CD-11a subunit of leukocyte function antigen-1 (LFA-1) expressed on T cells. By blocking the interaction of LFA-1 and its ligand intercellular adhesion molecule-1, T cell activation and migration into psoriatic plaques are decreased. In phase III trials, efalizumab injected once weekly at 1 mg/kg achieved >75% improvement after 12 weeks in 27% of patients compared with 4% receiving placebo. About 50% of patients maintained >75% improvement after 3 years of open-label treatment. Efalizumab was also approved by the FDA for psoriasis in 2003. It is recommended to monitor platelet counts for the first few months of therapy and to continue therapy to maintain the response. About 10% of patients experience a flare of their disease either during or after abruptly stopping efalizumab.

Tumor Necrosis Factor Inhibitors

Etanercept is a cloned and engineered fusion protein made of two p75 TNF receptors and the Fc portion of human IgG. It binds and inactivates TNF and prevents its significant proinflammatory effects in the target tissue of skin and joints. Etanercept is a disease modifying antirheumatic drug that is FDA approved for rheumatoid and psoriatic arthritis with and without methotrexate. In the pivotal phase III studies of etanercept in psoriasis, 25 mg administered twice weekly by subcutaneous injection and 50 mg twice weekly gave >75% improvement in 34% and 49% of patients, respectively, after 12 weeks compared with 4% receiving placebo. Etanercept was approved for psoriasis by the FDA in 2004 at a starting dose of 50 mg twice weekly for 12 weeks followed by 25 mg twice weekly for maintenance. Slight recrudescence of disease occurred in some patients after the step down in dosage, but the mean percent improvement was stable after 48 weeks. In studies, only wheal-like injection site reactions occurred at higher frequency with etanercept than placebo. Infrequent associations of new onset or aggravation of demyelinating diseases, congestive heart failure, and aplastic anemia have been observed without assigning cause and effect. No baseline or monitoring laboratory tests are required.

Infliximab is a chimeric (human-mouse) monoclonal antibody that binds TNF. It is FDA approved for rheumatoid and psoriatic arthritis and Crohn's disease with and without methotrexate. It is delivered by an intravenous infusion over a 2-hour period. Phase II trials of infliximab as monotherapy indicated high efficacy in psoriasis. In phase III trials, 1462 patients were treated with placebo, 3 mg/kg, or 5 mg/kg infliximab infusions given at weeks 0, 2, and 6. The proportion of patients achieving >75% improvement in the severity score at 10 weeks was 3%, 71%, and 79%, respectively. Maintenance therapy was continued at 5 mg/kg every 8 weeks, and the response was sustained for 26 weeks. The serious immediate infusion reaction rate is 1%, and about 1% of patients experience delayed hypersensitivity reactions consisting of myalgia, arthralgia, fever, or rash. Neutralizing antibodies are formed in about 20% of patients treated for 1 year, which may result in “dose creep,” whereby dose escalation or more frequent dosing of infliximab becomes necessary to keep symptoms under control. Concomitant methotrexate administration reduces the development of antichimeric antibodies. Current practice is to repeat infusions of 5 mg/kg every 6 to 8 weeks to maintain response.

Adalimumab is a human anti-TNF monoclonal antibody that blocks the interaction of TNF with the p55 and p75 cell-surface receptors. It is currently approved for rheumatoid and psoriatic arthritis. Phase III studies of patients with both psoriasis and PSA showed that 59% achieved >75% improvement in skin disease after 24 weeks at a dosage of 40 mg every other week by subcutaneous injection.

The greatest theoretical risks associated with the biologic immunomodulators discussed here are serious infections, particularly granulomatous, and increased rates of malignancy, particularly the lymphoproliferative diseases. To date, controlled trials and post-marketing surveillance studies have not conclusively demonstrated a higher-than-expected frequency of lymphomas in patients who have been treated the longest with anti-TNF agents; however, the risk for reactivating tuberculosis is considered greater for infliximab and adalimumab than with etanercept. Therefore, screening for tuberculosis is required before administering the monoclonal antibodies.

Summary

Psoriasis affects 2% of the U.S. population; about 11% of these patients have psoriatic arthritis.
There are four clinical variants of psoriasis, but plaque type is the most common (80% of cases).
Consultation with a dermatologist is recommended if the patient fails to respond to topical therapy (level 1) and natural sunlight or tanning bed exposure.
Psoriasis is considered moderate to severe if it involves more than 5% of body surface area.
Phototherapy, systemic, or biologic therapies (levels 2 through 6) are recommended for moderate-to-severe psoriasis.