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Abstract
Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging.
Highlights
Acute generalized exanthematous pustulosis (AGEP) is a rare and severe skin reaction.While AGEP occurs most frequently as an adverse effect of pharmacological treatment or drugs, it may result from contact with chemicals or dyes [1,2], or as a response to certain organisms [3]
Pharmacological treatments reported as suspect agents triggering AGEP include, among others, antibiotics and other anti-infectives, cardiovascular drugs, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and hydroxychloroquine [7–13]
From the >800 identified articles in PubMed and Embase, 250 published case reports or case series were included in the analysis [5,16–264], resulting in 297 patients included in the extracted database
Summary
Acute generalized exanthematous pustulosis (AGEP) is a rare and severe skin reaction. While AGEP occurs most frequently as an adverse effect of pharmacological treatment or drugs, it may result from contact with chemicals (e.g., mercury) or dyes [1,2], or as a response to certain organisms (e.g., cytomegalovirus, Chlamydia pneumonia, and Escherichia coli) [3]. It has been suggested that AGEP affects one to five patients per million per year, and it has been associated with up to a 5% mortality rate, often due to multi-organ failure or secondary infections [3,4]. The key clinical feature of AGEP is the sudden presence of several miniscule, non-follicular intradermal pustules on an erythematous edematous background [5,6]. Pharmacological treatments reported as suspect agents triggering AGEP include, among others, antibiotics and other anti-infectives, cardiovascular drugs, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and hydroxychloroquine [7–13]
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