Do the physical and histologic features and time course in acute generalized exanthematous pustulosis reflect a pattern of cytokine dysregulation?

Abstract

Acute generalized exanthematous pustulosis (AGEP) is characterized by fever and an indurated erythematous eruption early, with the development of nonfollicular pinhead sterile pustules on an erythematous background. The eruption progresses and resolves relatively rapidly. Although drugs are believed to be the major etiologic agents, other immune modulators, including infections, heavy metals, and radiation, have been implicated. The purpose of this study was to document underlying diseases in patients with AGEP and to determine if this data and the histologic features suggested an underlying pattern of immune dysregulation. Twenty-one patients with new or recurrent episodes of AGEP were questioned concerning underlying diseases. The histopathologic features seen in the biopsy sections and the approximate time of biopsy during the course of their eruptions were recorded. Two patients had a history of psoriasis and one patient had a family history of psoriasis, two patients had diagnoses of sarcoid, two patients had inflammatory bowel disease, one had autoimmune thyroiditis, and one patient had multiple sclerosis. Biopsies done at the onset of the eruption showed marked to moderate papillary dermal edema and a mixed dermal inflammatory infiltrate. Shortly thereafter, biopsies showed spongiform pustules within the epidermis and occasional dyskeratotic cells with residual perivascular dermal edema. Although no definitive vasculitis was seen, there was leukocytoclasis within the dermal infiltrate in the majority of biopsy specimens performed more than 48 hours after the onset of the eruption. The histologic features seen in AGEP and the disease associations suggest that patients who develop this eruption may have an underlying tendency for development of a pattern of immune dysregulation characterized by a T helper-1 cytokine pattern.