Generalized pustular psoriasis following with-drawal of efalizumab

Journal of Drugs in Dermatology, Jan-Feb, 2004 by Minh-Ly N. Gaylor, Madeleine Duvic

Abstract

Efalizumab is one of the new biologic therapies targeting T-lymphocyte activity for the treatment of chronic plaque psoriasis. Common adverse effects include headaches, nonspecific infection, nausea, chills, and fever. Rebound of psoriasis following discontinuation of the drug has been reported. Relapse events can manifest as recurrent plaque psoriasis, guttate psoriasis, psoriatic erythroderma, and pustular psoriasis. We report a second case of withdrawal flare resulting in generalized pustular psoriasis.

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Introduction

Enhanced understanding of the role of T-lymphocytes in the pathogenesis of psoriasis has led to the development of a number of biologic therapies in the treatment of psoriasis (1). Leukocyte function-associated antigen-1 (LFA-1), composed of CD11a and CD18 subunits, is a T-lymphocyte surface receptor that upon binding to its ligand, intercellular adhesion molecule-1 (I-CAM-1), promotes T-cell activation, migration, and cytotoxic function (2). Efalizumab is an anti-CD11a antibody that inhibits the binding of LFA-1 to I-CAM-1 and thus, inhibits T-cell activity believed to induce inflammation in psoriasis (3).

Recently, the FDA's Dermatologic and Ophthalmic Drugs and Advisory Committee (DODAC) supported the use of efalizumab for moderate to severe chronic plaque psoriasis based on evidence from four randomized. Phase III clinical trials (4).

Thus far, adverse events associated with efalizumab have been described as mild to moderate in severity. Relapse or "rebound" of psoriasis following the discontinuation of the drug has been reported in ~5% of patients (5,6). Relapse events mainly involved the recurrence of plaque psoriasis as well as psoriasis variants including guttate psoriasis, psoriatic erythroderma, and pustular psoriasis (7). We present a case of a man who developed zoster, stopped efalizumab, and then developed generalized pustulosis followed by severe exfoliative erythroderma.

Case Report

A 33-year-old Asian male with a 10-year history of plaque psoriasis and 7-year history of psoriatic arthritis presented in April of 2001. He had failed multiple therapies including PUVA, systemic corticosteroids, methotrexate, and cyclosporine and had severe psoriasis with plaques covering 82% of his body surface area. Deformities of his distal extremities were present. By May 2001, he was enrolled on an experimental trial of efalizumab and received doses of 1-2 mg/kg subcutaneously every week for 28 months until his acute event. During the first 23 months of therapy, the patient experienced significant improvements in arthritic pain and the appearance of his psoriasis, with an affected body surface area as low as 9%. When the dose was decreased at 8 months to 1 mg/kg, he had one notable psoriatic flare which resolved with increasing the dose to 2 mg/kg.

In September of 2003, nearly 2 1/2 years after the drug therapy was started, the patient presented with an acute herpes zoster outbreak on his left flank. The efalizumab doses were withheld until further evaluation and the patient was given a 7-day prescription for oral valacyclovir 500 mg three times a day and dicloxacillin 250 mg four times a day, which he did not take. Two weeks later, he returned with fever and pustulosis overlying exfoliative erythroderma. A hemorrhagic plaque at the site of the zoster was present on his left flank. Mucosal surfaces were intact (Figures 1A, 1B).

[FIGURE 1A OMITTED]

[FIGURE 1B OMITTED]

Complete blood count had a WBC of 11.8 X 103 and differential of 80% neutrophils, 16% lymphocytes, and <1% eosinophils. Electrolytes and urinalysis were normal. Patient was advised to complete his course of valacyclovir and start the dicloxacillin. When seen one week later, the pustules had resolved but now he had severe, generalized erythroderma with diffuse coarse scaling and fissures. Skin cultures grew Staphylococcus aureus and Pseudomonas species.

Discussion

We report the second case of generalized pustular psoriasis upon withdrawal of efalizumab, which eventually progressed to severe exfoliative erythroderma. Other agents used in the treatment of psoriasis also known to cause generalized pustular psoriasis upon discontinuation include systemic and high-potency corticosteroids, cyclosporine, and methotrexate (8,9). The mechanism by which this occurs is still unclear.

Efalizumab has been known for its early onset of action and ease of use with home dosing for the treatment of plaque psoriasis (5). Commonly reported adverse effects include headaches, nonspecific infection, nausea, chills, pain, and fever, with headaches being the most common dose-limiting toxicity (10). Adverse events were normally observed within hours of the first or second doses of efalizumab and often decreased with subsequent injections (8).

Relapse of the psoriasis upon discontinuation of the drug has been reported in a number of patients. Table 1 lists the types of flares reported within a 12-week period following the withdrawal of efalizumab (7). Although 7 patients were reported as developing pustules, only one other was generalized. The remaining patients had pustular lesions localized to the groin, palms, or soles. In addition, 8 patients experienced exfoliative erythroderma and 5 required hospitalization (7).