CASE 7: Moderately severe Psoriasis Vulgaris

A 35-year-old man presents with extensiveplaques over much of thetrunk and extremities. This severeflare of psoriasis developed after astressful emotional experience.(Case and photograph courtesy of Drs Marti Jill Rotheand Jane M. Grant-Kels.)
How would you proceed?A REVIEW OF THE OPTIONSPhototherapy. UV light therapyor systemic therapy generally is neededfor adequate control of moderatelysevere psoriasis vulgaris. UV-B is thefirst-line treatment; psoralen-UV-A(PUVA) is also an option. The concurrentuse of the systemic retinoid acitretincan heighten the effect of phototherapy.Methotrexate, acitretinalone, cyclosporine, and mycophenolate mofetil are also used to treat severepsoriasis.Until the early 1990s, the "goldstandard" therapy required a 1-monthhospital stay for daily or twice-dailyUV-B, crude coal tar, and anthralintreatments. An average 6- to 9-monthremission was achieved. Often, outpatientUV-B treatments were administeredas maintenance therapy afterhospital discharge.Changes in health care policy regardingutilization of inpatient hospitalservices spurred the opening of psoriasisoutpatient day treatment centersthat provide similar care. Althoughhighly safe and effective, the UV-B,coal tar, and anthralin regimen can beinconvenient for patients, and the costmay not be reimbursed by insurers.An important advance in phototherapyis narrowband UV-B (NB-UV-B), in which UV lamps emit a narrowrange of wavelengths in the UVB spectrum; these are thought to beprimarily responsible for the efficacyof UV-B therapy. NB-UV-B appears tobe more effective than broadbandUV-B (BB-UV-B) and nearly as effectiveas PUVA.³PUVA still plays an importantrole in the treatment of psoriasis vulgaris;however, since the advent ofNB-UV-B, the number of patients receivingPUVA has declined. SystemicPUVA requires the ingestion of psoralen90 minutes before UV-A treatment.Psoralen induces cutaneousand ocular photosensitivity that persistsfor 24 hours; therefore, protectivemeasures, such as UV-A protectiveglasses; sunscreen; protectiveclothing; and sun avoidance whileoutdoors, in a car, or near a picturewindow, are required. Other potentialadverse effects of PUVA include nauseafrom ingestion of psoralen, photoaging,and freckling. The risk of skin cancer increases after 200 ormore treatments.⁴ The skin cancerrisk with UV-B is unclear.An average of 20 to 30 treatmentsof NB-UV-B, BB-UV-B, orPUVA usually are needed to obtainmarked improvement. Typically, phototherapyis given initially 3 times aweek. Once significant clearing isachieved, UV therapy sessions aredecreased to twice weekly and thenonce weekly. PUVA, but not UV-B,can be administered as infrequentlyas once every 3 to 4 weeks for maintenancetherapy.Concomitant treatment withlow-dose acitretin or isotretinoin enhancesthe efficacy of UV and reducesthe thickness and scaling ofplaques. In addition, the retinoid mayconfer chemoprotection against skincancer. Acitretin can be prescribed inhigher dosages as monotherapy;however, the drug is more effectivefor psoriasis vulgaris and is better toleratedwhen given in low dosages incombination with UV therapy.Dose-related side effects of acitretininclude desquamation of palmsand soles, sticky palms and soles, dryskin and mucous membranes, fragileskin, brittle nails, and alopecia. Systemiceffects, such as elevated triglycerideand transaminase levels, mayoccur. The teratogenicity of acitretinis also a concern. Because isotretinoinhas a significantly shorter halflife,prescribe this retinoid instead ofacitretin in combination with UV therapyfor women of childbearing potential.However, as monotherapy forpsoriasis vulgaris, isotretinoin is notas effective as acitretin.Immunosuppressive therapy.Cyclosporine and methotrexate areextremely effective for psoriasis vulgarisbut are generally reserved forpatients who do not respond to UVtherapy, have concomitant psoriaticarthritis, or are unable to visit a phototherapycenter for treatments. Becauseof cyclosporine's rapid onset of action, it is ideal for the acute treatmentof a severe flare.The most significant side effectsof cyclosporine are hypertension andreduced renal function. Monitor electrolyte,blood urea nitrogen, creatinine,lipid, and magnesium levels;liver function; and blood pressureevery 2 weeks for the first 3 monthsof therapy and then monthly. Reducethe dosage if the creatinine level exceeds25% to 30% of baseline. If hypertensiondevelops, lower the dosage ofcyclosporine and/or initiate antihypertensivetherapy with a calciumchannel blocker.Keep in mind that cyclosporinecan interact with numerous medications.Ideally, the immunosuppressantis prescribed for no longer than1 to 2 years, after which the patient isgradually weaned to an alternativetherapy, such as acitretin. Patientswho were previously treated withPUVA are at increased risk for cutaneousmalignancy. Treatment withcyclosporine may increase this risk;therefore, monitor these patientsclosely for suspicious skin lesions.Methotrexate is highly effectivefor the treatment of psoriasis vulgaris;however, it is contraindicated in patientswith liver disease, and thedosage must be reduced in patientswith renal insufficiency.Methotrexate-induced hepatotoxicityis more likely to develop in patientswith psoriasis than in those whohave rheumatoid arthritis. Therefore,a liver biopsy needs to be performedwhen a cumulative dose of 1.5 g isreached. If grade I or grade IIchanges are found in the specimen,liver biopsies need to be performedafter each additional 1 to 1.5 g ofmethotrexate. Repeat the test every 6months in patients with grade IIIAbiopsy changes (mild fibrosis). Discontinuemethotrexate in those patientswith grade IIIB (moderate tosevere fibrosis) or grade IV (cirrhosis)biopsy findings.Monitor liver function and completeblood cell (CBC) count monthlyin patients who take methotrexate.Draw blood for testing the day beforethe usual weekly dose of the drug isgiven. Prescribe folic acid, 1 to 5 mgdaily, to offset nausea and bone marrowsuppression. Caution men andwomen who take or have takenmethotrexate within the previous 3months to avoid conceiving a child.Mycophenolate mofetil is a moderatelyeffective systemic treatmentthat is usually considered when othertreatments fail or are contraindicated.Because of the risk of bone marrowsuppression, monitor the CBC count.GI intolerance-including nausea,vomiting, and diarrhea-may alsooccur.Biologic agents. These newmedications, which are discussed inthe Quick Take on page 890, likelyhave a role in the treatment of thisform of psoriasis.CASE 7:APPROACH AND OUTCOMEA trial of 35 BB-UV-B treatmentsfailed to significantly improvethe patient's condition. After 25 PUVAsessions, the disease was nearlycleared; PUVA treatments were graduallydecreased from 3 times perweek to a maintenance regimen ofonce every other week.