Case 4 -

Acute Generalized Exanthematous Pustulosis Secondary to Vancomycin Therapy James W. Patterson, M.D.

Acute generalized exanthematous pustulosis is a febrile illness associated with neutrophilic leukocytosis and a characteristic eruption. The latter consists of patchy erythema studded with small pustules. The eruption begins on the face or in intertriginous areas and then disseminates. Other cutaneous findings include edema of the face and hands, erythema multiforme-like vesicular lesions, and mucous membrane changes. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer The vast majority of cases are drug-induced, although examples have also been triggered by enterovirus or associated with pregnancy. The list of inciting drugs has become quite extensive. Vancomycin is a well-known cause, but other agents include terbinafine, simvastatin, ranitidine, ibuprofen, celecoxib and valdecoxib, hydroxychloroquine, bleomycin, ciprofloxacin, and lincomycin. The signs and symptoms begin within two days of exposure to a drug (probably indicating immunologic recall of a previously administered agent), and lesions last from 1-2 weeks. Microscopic findings include subcorneal and spongiform pustules with papillary dermal edema and a mixed perivascular infiltrate composed of neutrophils and eosinophils. Occasionally, interface dermatitis with apoptotic keratinocytes can be observed, and leukocytoclastic vasculitis has been described. The clinical and histopathologic differential diagnosis can include the von Zumbusch form of pustular psoriasis, erythema multiforme, other types of drug eruptions, or the "drug rash with eosinophilia and systemic symptoms" (DRESS) syndrome. Treatment is largely symptomatic. The majority of patients display positive patch test reactions to the causative medication, and in vitro lymphocyte proliferative responses to specific agents have been demonstrated. These results suggest that drug-specific T-cells are at work, capable of releasing neutrophil-activating cytokines. Interestingly, biopsies of the patch test sites have shown spongiotic dermatitis with perivascular lymphocytes, findings typical for delayed hypersensitivity reactions. References: Beltraminelli HS, Lerch M et al: Acute generalized exanthematous pustulosis induced by the antifungal terbinafine: case report and review of the literature. Br J Dermatol 2004; 140: 1172-1173. Ersoy S, Paller AS et al: Acute generalized exanthematous pustulosis in children. Arch Dermatol 2004; 140: 1172-1173. Girardi M, Duncan KO et al: Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis. Am J Dermatopathol 2005; 27: 343-346.