Large retrospective study offers insight into the course of AGEP disease and its complications

Among the most notable findings was that acute generalized exanthematous pustulosis is usually triggered by antimicrobial agents and may be associated with liver or kidney complications in some patients.

A great retrospective To analyse of patients with acute generalized exanthematous pustulosis (AGEP) – a rare and serious cutaneous adverse reaction – helps paint a clearer picture of clinical features, disease course and outcome.

The study of 340 patients from 10 different sites across the United States is the largest cohort of its kind to date and adds valuable insights into AGEP, the researchers said. Previous studies have mostly consisted of small retrospective case series of fewer than 50 patients, they added.

Among the most notable findings is that the onset of AGEP is acute, is usually triggered by antimicrobial agents and, for some patients, may be associated with hepatic or renal complications.

Almost half of the 310 patients for whom data are available developed a fever while in the healthcare setting, which occurred on average 1 day after the first indications of erythema or pustules ( IQR, 0-3) and lasted for a median of 2 days (IQR, 1-4).

When examining the causes of AGEP, drugs were suspected in the majority (85.6%) of cases, and 151 cases were related to a single drug suspected or known to have been started before or on the day erythema or pustules were observed for the first time. β-lactam antimicrobials were suspected to cause approximately 40% of these cases. Of these, 17.9% of cases were suspected to be caused by cephalosporin and 11.3% were suspected to be caused by piperacillin combined with tazobactam. The time from when the patient started treatment to when they developed AGEP occurred within a median of 3 days (IQR, 1-9).

“Whether infections themselves can be a cause of AGEP has long been debated. In our series of 340 patients, only 3 patients (0.9%) had an infection listed as a suspected cause by the dermatology team (2 with negative or incomplete negative serological results, and 1 with positive results at both blood and wound culture). results for Staphylococcus aureus),” the researchers explain.

“While it is theoretically possible for a foreign pathogen to elicit an immune response similar to that of a foreign substance, such as a drug or intravenous contrast agent (a suspected cause in 2.1% of our cases), it appears to be rare, and future studies should better elucidate this association, if it exists,” they said.

There were 298 patients whose aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were checked at least once during the period they had AGEP, of whom 8.4% had elevations acute AST and ALT levels. The researchers noted that this is consistent with previous findings from smaller studies. The median time to peak AST and ALT levels in these patients was 6 days (IQR, 3-9) after onset of AGEP.

Among 319 of the patients, 7.8% presented with acute renal failure, with creatinine levels increasing to at least 1.5 times their baseline level before having AGEP. The time to peak of creatinine levels occurred on average 4 days (IQR, 2-5) after the development of AGEP.

“Our methods cannot determine a causal association between AGEP and target organ damage, as these abnormalities could be secondary to other comorbidities or iatrogenic causes, such as initial infection and subsequent antimicrobial therapy,” wrote the researchers.

“These frequencies of acute renal failure and acute transaminitis are likely lower than true frequencies given our strict exclusion of patients without baseline data for comparison, but even these conservative values ​​demonstrate the need to monitor these patients for systemic complications” , the authors concluded.


Creadore A, Desai S, Alloo A, et al. Clinical characteristics, disease course, and outcomes of patients with acute generalized exanthematous pustulosis in the United States. JAMA Dermatol. Published online January 5, 2022. doi:10.1001/jamadermatol.2021.5390

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