Abstract
Introduction: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous drug reaction characterized by the sudden appearance of non-follicular sterile pustules on an erythematous background which is accompanied by fever and peripheral blood neutrophilia. While the clinical differentiation between AGEP and common delayed-type drug hypersensitivity reactions, such as maculopapular rash (MPR), is well-defined, the pathomechanism, causative drugs, and other possible contributing factors remain poorly studied to date. Methods: In this retrospective case-control study we compared clinical data on suggested causative drugs, drug testing, and comorbidities between a group of 52 patients with a confirmed diagnosis of AGEP (both clinically and histologically) and a group of 63 patients with confirmed MPR. Results: Evaluation of the causative drugs revealed that beta-lactam antibiotics represent the most common culprit drug in both AGEP and MPR, while antimycotics (p = 0.002), glucocorticoids (p = 0.0106) and NSAIDs (p = 0.0064) were significantly more frequent in AGEP. Skin patch tests and in vitro lymphocyte transformation tests (LTT) showed higher positivity rates in MPR compared to AGEP, with all non-beta-lactam antibiotics tested with LTT leading to negative results in AGEP. A detailed analysis of comorbidities suggested a possible association between diseases of the upper gastrointestinal tract and AGEP. Conclusions: This study highlights the differences in causative drugs and comorbidities between AGEP and MPR, emphasizing the need for further research to enhance the understanding and management of AGEP.