Generalized pustular drug eruptions: Confirmation by in vitro tests

Background. Generalized pustular eruptions are characterized by acute onset of aseptic pustules in febrile patients with leukocytosis after exposure to the offending drug. They have been regarded as uncommon manifestations of adverse drug reactions. Until now few confirmation studies have been carded out. Objective. Our purpose was to describe a series of patients with generalized pustular drug eruption. The diagnosis and etiological role of drugs in these cases was confirmed by two in vitro tests, namely the macrophage migration inhibitory factor (MIF) and the mast cell degranulation (MCD) tests. Methods. The clinical, pathological and laboratory findings in six patients with generalized pustular eruption were studied prospectively. The MIF and MCD tests were performed with the drugs taken by the patients. Results. The dermatological manifestations included numerous pustules on large erythematous areas, papules and erythema multiforme-like lesions. The pustular eruption developed between 12 h and 5 days after the administration of the provoking drug. The histopathological changes were characterized by subcorneal pustules, papillary edema and mixed cell inflammatory infiltrate. In two biopsies the infiltrate displayed numerous eosinophils. Laboratory investigations revealed leukocytosis with neutrophilia (4 of 6 patients) and eosinophilia and hyperimmunoglobulinemia E (2 of 6 patients). MCD tests with the suspected drugs (Ampicillin, Cefazolin, Tetracycline, Griseofulvin, Enalapril Maleate) were positive in all patients. Positive MIF results were seen in five of the six patients. Withdrawal of the drug led to fast recovery. Conclusion. The diagnosis of pustular drug eruptions depends on circumstantial evidence, some characteristic clinicopathological findings and exclusion of alternative diagnoses of other disseminated pustular eruptions. In vitro tests, namely MIF and MCD tests, are a useful diagnostic aid in the identification of the offending drugs.