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Alefacept in the Treatment of Recalcitrant Palmoplantar and Erythrodermic Psoriasis

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Alefacept in the Treatment of Recalcitrant Palmoplantar and Erythrodermic Psoriasis Alefacept in the Treatment of Recalcitrant Palmoplantar and Erythrodermic Psoriasis Trisha A. Prossick, MD; Donald V. Belsito, MD Alefacept is the first biologic agent approved by in the treatment of psoriasis.1 Prior clinical studies the US Food and Drug Administration for moder- demonstrated efficacy in chronic plaque psoriasis ate to severe chronic plaque psoriasis. Prior clini- but excluded patients with palmoplantar psoriasis cal studies excluded patients with palmoplantar or erythroderma.2-4 We report 2 patients with recal- psoriasis or erythroderma. We report 2 patients citrant psoriasis who responded completely to a full with recalcitrant psoriasis who responded com- course of alefacept: one patient with severe palmo- pletely to a full course of alefacept. One patient plantar psoriasis recalcitrant to acitretin and metho- presented with severe palmoplantar psoriasis trexate, and another patient with erythroderma who recalcitrant to acitretin and methotrexate; another was transitioned successfully from cyclosporine A. patient presented with erythroderma and was transitioned successfully from cyclosporine A. Case Reports Alefacept provides another treatment option for Patient 1—A 35-year-old healthy Guatemalan man palmoplantar and erythrodermic psoriasis and presented with a 6-month history of pruritic hand should be considered in the management of and foot dermatitis. His medical and family histo- patients with these conditions. ries were unremarkable, and a review of systems Cutis. 2006;78:178-180. revealed negative findings, except for the skin. Results of a physical examination demonstrated erythematous scaly plaques on his palms and soles lefacept, the first biologic agent approved by with extension onto the dorsal hands and feet. the US Food and Drug Administration for Results of a potassium hydroxide examination and A moderate to severe chronic plaque psoriasis, fungal culture were negative. The patient initially is a fusion protein that binds to CD2 on T cells, was given diflorasone diacetate ointment 0.05% thus blocking the co-stimulatory interaction with and urea cream 40%, with minimal improvement. leukocyte function–associated antigen-3 (LFA-3) Because of his lack of response, 2 biopsies of the on antigen-presenting cells. Alefacept also inter- skin were performed, the results of which con- acts with FcRIII immunoglobulin G receptors on firmed the diagnosis of psoriasis vulgaris. natural killer cells and macrophages, resulting in Because of the patient’s poor response to vari- apoptosis of activated memory T cells. The resultant ous potent topical steroids and keratolytics, he was reduction in the number of activated memory T cells given systemic treatment. Initially, he was treated in the skin correlates with the efficacy of alefacept with sulfasalazine 1500 mg/d in divided doses, but this therapy was discontinued after 4 months because of lack of improvement. Acitretin 50 mg/d Accepted for publication May 1, 2006. then was started, which provided some relief but was From private practice, Shawnee Mission, Kansas, and the University discontinued after 5 months because of moderate of Missouri-Kansas City. hair loss. The patient subsequently failed a 6-month Dr. Prossick reports no conflict of interest. Dr. Belsito is a course of methotrexate 15 mg/wk. Alefacept 15 mg consultant, member of the speakers bureau, and principal was initiated and administered intramuscularly once investigator for Biogen Idec and Genentech, Inc, and a consultant and member of the speakers bureau for Abbott Laboratories and weekly along with the use of potent topical ste- Amgen Inc. roids. Within 8 weeks, the patient demonstrated a Reprints: Donald V. Belsito, MD, 6516 Aberdeen Rd, Mission Hills, response, with complete clearance by the end of the KS 66208 (e-mail: [email protected]). course. Weekly monitoring of his CD4 cell count 178 CUTIS® Alefacept for Psoriasis demonstrated a decline to less than 250 cells/L high-dose cyclosporine A 4 mg/kg daily in divided (reference range, 500–1500 cells/L) on 2 separate doses. While the patient was being given cyclo- occasions, which subsequently necessitated holding sporine A, amlodipine 5 mg/d was added to his off the medication twice and thus extended the total therapeutic regimen for renal protection, which course duration to 14 weeks. Otherwise, the medi- stabilized the small increase in his blood urea nitro- cation was well-tolerated and the patient had no gen and creatinine levels. In addition, the patient subjective complaints. On cessation of treatment, developed hypertrichosis, a known side effect of the patient flared back to baseline within 2 weeks cyclosporine, and pedal edema that likely was despite the use of topical steroids. Because he was secondary to the calcium channel blocker.5 As the within the recommended 12-week treatment-free cyclosporine gradually was decreased, the patient follow-up period, alefacept could not be reiniti- flared once again. UVB treatment 3 times weekly ated. He was started on dexamethasone 6 mg and was restarted but was ineffective in controlling tapered over 18 days, and subsequently went into a the exacerbation during the attempt to taper the prolonged (4 months) remission. cyclosporine. The patient then was given alefacept Patient 2—A 32-year-old white man presented 15 mg intramuscularly every week, which allowed with a 3-year history of diffuse erythematous patches the cyclosporine to be tapered every 2 weeks with and scaly plaques treated intermittently by his pri- only minor flaring that was controlled with topi- mary care medical doctor with prednisone. He had cal tacrolimus ointment 0.1%. By the 13th week a history of adult-onset asthma, and his medica- of treatment, the patient was completely clear and tions included fluticasone proprionate/salmeterol the cyclosporine was discontinued. Other than a (250 g/50 g) inhalation powder and fexofenadine one-time decrease in his CD4 cell count to less hydrochloride. A review of systems was positive only than 250 cells/L, the patient tolerated the medi- for asthma symptoms. Prior evaluation by an aller- cation without complaints. The patient continued gist demonstrated immunoglobulin E radioallergo- to do well during the observation period but began sorbent test results that were positive for cat dander, flaring approximately 5 months following his last dust mites, and tree pollens. Despite these results, injection. A second course of alefacept was insti- the patient continued to reside with 7 cats. On phys- tuted, which controlled his flare. ical examination, the patient was erythrodermic, Because of the patient’s repeat skin biopsy that with generalized scale. There was no lymphadenopa- demonstrated features of an allergic component, thy or hepatosplenomegaly present. At his initial patch testing to the North American Contact visit, the differential diagnoses for his erythroderma Dermatitis Group standard allergen tray, as well included psoriasis vulgaris, atopic dermatitis, allergic as the Kansas University Medical Center supple- contact dermatitis, seborrheic dermatitis, drug erup- mental and textile allergen trays, were evaluated tion, and pityriasis rubra pilaris. Routine laboratory after the patient was clear and no longer receiving tests demonstrated results within reference range for cyclosporine. The only positive test reaction was to complete blood count, chemistry panel, and liver sodium gold thiosulfate; however, the patient did function tests. Screening results for human immu- not possess any gold dental amalgams, wear gold nodeficiency virus were negative. Histopathologic jewelry, or drink any gold-containing liquor. We evaluation of results from 2 separate biopsies of the believe his erythroderma was caused by underlying skin was consistent with psoriasis vulgaris. psoriasis vulgaris treated intermittently with oral Initially, the patient underwent UVB treatment prednisone and possibly exacerbated by an allergic 3 times weekly and was restarted on a prednisone reaction to cat dander. taper. Toward the end of this taper, sulfasalazine 1500 mg/d in divided doses was added to his thera- Comment peutic regimen but was unsuccessful in preventing Psoriasis is recognized as a T-cell–mediated immune a flare. Acitretin 50 mg/d then was given, but disease, and the new biologic agents have shown once the patient discontinued the prednisone, the promising efficacy. In a double-blinded, random- erythroderma recurred. Biopsies of the skin were ized, placebo-controlled phase 3 trial of 507 patients performed again, with histopathologic findings with chronic plaque psoriasis, 33% of patients in now demonstrating a spongiotic dermatitis with the intramuscular alefacept group achieved a 75% prominent eosinophils. Cyclosporine A 2.3 mg/kg or more reduction in the Psoriasis Area and Severity daily was started in addition to another prednisone Index (PASI) at any time during the study period taper. Again, the patient continued to flare when- compared with 13% of patients in the placebo ever the prednisone was decreased. Good control group.2 In a follow-up extension study to the finally was achieved after a gradual increase to phase 3 trial, the median duration of a 50% or more VOLUME 78, SEPTEMBER 2006 179 Alefacept for Psoriasis reduction in PASI was 209 days in those patients of the adverse effects of hypertension and renal who achieved a score of 75, and longer in patients toxicity, the use of cyclosporine generally is limited who received 2 courses of alefacept.3 Alefacept was to no more than
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