Eruptive papules during efalizumab (anti-CD11a) therapy of psoriasis vulgaris: a case series

We present a group of 15 patients who developed inflammatory papules while on efalizumab therapy (Raptiva, Genentech Inc, anti-CD11a). Immunohistochemistry showed that there were increased CD11b+, CD11c+ and iNOS+ cells (myeloid leukocytes) in the papules, with relatively few CD3+ T cells. While efalizumab caused a decreased expression of CD11a on T cells, other circulating leukocytes from patients receiving this therapy often showed increased CD11b and CD11c. In the setting of an additional stimulus such as skin trauma, this may predispose to increased trafficking into the skin using these alternative β2 integrins. In addition, there may be impaired immune synapse formation, limiting the development of these lesions to small papules. There is little evidence for these papular lesions being "allergic" in nature as there are few eosinophils on biopsy, and they respond to minimal or no therapy even if efalizumab is continued.We hypothesize that these papules may represent a unique type of "mechanistic" inflammatory reaction, seen only in the context of drug-induced CD11a blockade, and not during the natural disease process.Newer biological agents have dramatically improved therapeutic options for patients with psoriasis vulgaris requiring systemic therapy. Curiously, despite our knowledge of the target antigen of these biologic therapies, there may be unknown or unexpected biological effects. Efalizumab (Raptiva, Genentech Inc) is an FDA-approved treatment for moderate-to-severe psoriasis vulgaris. Recent phase III randomized, double-blind, placebo controlled trials have shown that an excellent clinical result (Psoriasis Activity and Severity Index, PASI 75) is obtained by week 12 in approximately 30% of patients [1-3]. Efalizumab is a humanized monoclonal antibody to CD11a, one of the chains of the β2 integrin lymphocyte function-associated antigen (LFA)-1. LFA-1 binds to intercellular adhesion molecules (ICAMs), allowing leukocyte migration across endothelial membra