A 35-year-old man presents with extensive plaques over much of the trunk and extremities. This severe flare of psoriasis developed after a stressful emotional experience. (Case and photograph courtesy of Drs Marti Jill Rothe and Jane M. Grant-Kels.)
How would you proceed? A REVIEW OF THE OPTIONS Phototherapy. UV light therapy or systemic therapy generally is needed for adequate control of moderately severe psoriasis vulgaris. UV-B is the first-line treatment; psoralen-UV-A (PUVA) is also an option. The concurrent use of the systemic retinoid acitretin(Drug information on acitretin) can heighten the effect of phototherapy. Methotrexate(Drug information on methotrexate), acitretin alone, cyclosporine, and mycophenolate mofetil are also used to treat severe psoriasis. Until the early 1990s, the "gold standard" therapy required a 1-month hospital stay for daily or twice-daily UV-B, crude coal tar(Drug information on coal tar), and anthralin treatments. An average 6- to 9-month remission was achieved. Often, outpatient UV-B treatments were administered as maintenance therapy after hospital discharge. Changes in health care policy regarding utilization of inpatient hospital services spurred the opening of psoriasis outpatient day treatment centers that provide similar care. Although highly safe and effective, the UV-B, coal tar, and anthralin regimen can be inconvenient for patients, and the cost may not be reimbursed by insurers. An important advance in phototherapy is narrowband UV-B (NB-UV-B), in which UV lamps emit a narrow range of wavelengths in the UVB spectrum; these are thought to be primarily responsible for the efficacy of UV-B therapy. NB-UV-B appears to be more effective than broadband UV-B (BB-UV-B) and nearly as effective as PUVA.3 PUVA still plays an important role in the treatment of psoriasis vulgaris; however, since the advent of NB-UV-B, the number of patients receiving PUVA has declined. Systemic PUVA requires the ingestion of psoralen 90 minutes before UV-A treatment. Psoralen induces cutaneous and ocular photosensitivity that persists for 24 hours; therefore, protective measures, such as UV-A protective glasses; sunscreen; protective clothing; and sun avoidance while outdoors, in a car, or near a picture window, are required. Other potential adverse effects of PUVA include nausea from ingestion of psoralen, photoaging, and freckling. The risk of skin cancer increases after 200 or more treatments.4 The skin cancer risk with UV-B is unclear. An average of 20 to 30 treatments of NB-UV-B, BB-UV-B, or PUVA usually are needed to obtain marked improvement. Typically, phototherapy is given initially 3 times a week. Once significant clearing is achieved, UV therapy sessions are decreased to twice weekly and then once weekly. PUVA, but not UV-B, can be administered as infrequently as once every 3 to 4 weeks for maintenance therapy. Concomitant treatment with low-dose acitretin or isotretinoin(Drug information on isotretinoin) enhances the efficacy of UV and reduces the thickness and scaling of plaques. In addition, the retinoid may confer chemoprotection against skin cancer. Acitretin can be prescribed in higher dosages as monotherapy; however, the drug is more effective for psoriasis vulgaris and is better tolerated when given in low dosages in combination with UV therapy. Dose-related side effects of acitretin include desquamation of palms and soles, sticky palms and soles, dry skin and mucous membranes, fragile skin, brittle nails, and alopecia. Systemic effects, such as elevated triglyceride and transaminase levels, may occur. The teratogenicity of acitretin is also a concern. Because isotretinoin has a significantly shorter halflife, prescribe this retinoid instead of acitretin in combination with UV therapy for women of childbearing potential. However, as monotherapy for psoriasis vulgaris, isotretinoin is not as effective as acitretin. Immunosuppressive therapy. Cyclosporine and methotrexate are extremely effective for psoriasis vulgaris but are generally reserved for patients who do not respond to UV therapy, have concomitant psoriatic arthritis, or are unable to visit a phototherapy center for treatments. Because of cyclosporine's rapid onset of action, it is ideal for the acute treatment of a severe flare. The most significant side effects of cyclosporine are hypertension and reduced renal function. Monitor electrolyte, blood urea(Drug information on urea) nitrogen, creatinine, lipid, and magnesium levels; liver function; and blood pressure every 2 weeks for the first 3 months of therapy and then monthly. Reduce the dosage if the creatinine level exceeds 25% to 30% of baseline. If hypertension develops, lower the dosage of cyclosporine and/or initiate antihypertensive therapy with a calcium channel blocker. Keep in mind that cyclosporine can interact with numerous medications. Ideally, the immunosuppressant is prescribed for no longer than 1 to 2 years, after which the patient is gradually weaned to an alternative therapy, such as acitretin. Patients who were previously treated with PUVA are at increased risk for cutaneous malignancy. Treatment with cyclosporine may increase this risk; therefore, monitor these patients closely for suspicious skin lesions. Methotrexate is highly effective for the treatment of psoriasis vulgaris; however, it is contraindicated in patients with liver disease, and the dosage must be reduced in patients with renal insufficiency. Methotrexate-induced hepatotoxicity is more likely to develop in patients with psoriasis than in those who have rheumatoid arthritis. Therefore, a liver biopsy needs to be performed when a cumulative dose of 1.5 g is reached. If grade I or grade II changes are found in the specimen, liver biopsies need to be performed after each additional 1 to 1.5 g of methotrexate. Repeat the test every 6 months in patients with grade IIIA biopsy changes (mild fibrosis). Discontinue methotrexate in those patients with grade IIIB (moderate to severe fibrosis) or grade IV (cirrhosis) biopsy findings. Monitor liver function and complete blood cell (CBC) count monthly in patients who take methotrexate. Draw blood for testing the day before the usual weekly dose of the drug is given. Prescribe folic acid(Drug information on folic acid), 1 to 5 mg daily, to offset nausea and bone marrow suppression. Caution men and women who take or have taken methotrexate within the previous 3 months to avoid conceiving a child. Mycophenolate mofetil is a moderately effective systemic treatment that is usually considered when other treatments fail or are contraindicated. Because of the risk of bone marrow suppression, monitor the CBC count. GI intolerance-including nausea, vomiting, and diarrhea-may also occur. Biologic agents. These new medications, which are discussed in the Quick Take on page 890, likely have a role in the treatment of this form of psoriasis. CASE 7:
APPROACH AND OUTCOME A trial of 35 BB-UV-B treatments failed to significantly improve the patient's condition. After 25 PUVA sessions, the disease was nearly cleared; PUVA treatments were gradually decreased from 3 times per week to a maintenance regimen of once every other week.