Cross-comparison of patch test and lymphocyte proliferation responses in patients with a history of acute generalized exanthematous pustulosis

An adverse cutaneous reaction to a systemically administered drug may rarely manifest as acute generalized exanthematous pustulosis (AGEP). Several recent reports have documented positive patch test results in patients with a history of AGEP, while two have demonstrated drug-specific in vitro lymphocyte proliferative responses. These findings suggest that drug-specific T cells mediate AGEP. We describe two patients with a history of AGEP who each demonstrated positive patch test results specific for the inciting drug: Patient #1 to the antibiotic metronidazole, and Patient #2 to the calcium channel-blocker diltiazem. Histologic examination of biopsy specimens taken from the patch test sites of these patients revealed spongiotic dermatitis and perivascular lymphocytes consistent with a delayed-type hypersensitivity reaction, rather than demonstrating subcorneal neutrophilic pustules more typical of AGEP. In vitro testing by measuring peripheral T cell proliferative responses to chemically purified drug correlated with the clinical response. In a direct cross-comparison, patch test results were shown to correlate with in vitro lymphocyte proliferative responses in two patients with a history of AGEP to different drugs. These findings provide additional evidence that the pathogenesis of AGEP involves a T cell-mediated immune response.