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Clinical Characteristics, Disease Course, and Outcomes of Patients With Acute Generalized Exanthematous Pustulosis in the US

Educational Objective
To describe the characteristics, course, and outcomes of patients with acute generalized exanthematous pustulosis.
1 Credit CME
Key Points

Question  What are the clinical characteristics, disease course, and outcomes of patients with acute generalized exanthematous pustulosis (AGEP) in the US?

Findings  In this case series evaluation of 340 patients with AGEP, common physical examination and laboratory findings were fever, neutrophilia, eosinophilia, and hypocalcemia. A small percentage of patients experienced acute elevations in creatinine or liver enzyme levels; newly started treatment with antimicrobials was the most common suspected cause, and most patients had experienced resolution or improvement as of the most recent available data.

Meaning  The findings of this case series suggest that AGEP, commonly triggered by antimicrobial agents, may be associated with systemic complications in a minority of patients and typically resolves with symptomatic treatment.

Abstract

Importance  Acute generalized exanthematous pustulosis (AGEP) is a rare, severe cutaneous adverse reaction associated with systemic complications. Currently available data are largely limited to small retrospective case series.

Objective  To describe the clinical characteristics, disease course, and outcomes of a heterogeneous group of patients with AGEP across the US.

Design, Setting, and Participants  A retrospective review of a case series of patients was conducted from January 1, 2000, through July 31, 2020. All 340 included cases throughout 10 academic health systems in the US were scored retrospectively using the EuroSCAR scoring system, and patients with a score corresponding to probable or definite AGEP and aged 18 years or older were included.

Main Outcomes and Measures  Patient demographic characteristics, clinical course, suspected causative agent, treatment, and short- and long-term outcomes.

Results  Most of the 340 included patients were women (214 [62.9%]), White (206 [60.6%]), and non-Hispanic (239 [70.3%]); mean (SD) age was 57.8 (17.4) years. A total of 154 of 310 patients (49.7%) had a temperature greater than or equal to 38.0 °C that lasted for a median of 2 (IQR, 1-4) days. Of 309 patients, 263 (85.1%) developed absolute neutrophilia and 161 patients (52.1%) developed either absolute or relative eosinophilia. Suspected causes of AGEP were medications (291 [85.6%]), intravenous contrast agents (7 [2.1%]), infection (3 [0.9%]), or unknown (39 [11.5%]). In 151 cases in which a single medication was identified, 63 (41.7%) were β-lactam antimicrobials, 51 (33.8%) were non–β-lactam antimicrobials, 9 (6.0%) were anticonvulsants, and 5 (3.3%) were calcium channel blockers. The median time from medication initiation to AGEP start date was 3 (IQR, 1-9) days. Twenty-five of 298 patients (8.4%) had an acute elevation of aspartate aminotransferase and alanine aminotransferase levels, with a peak at 6 (IQR, 3-9) days. Twenty-five of 319 patients (7.8%) experienced acute kidney insufficiency, with the median time to peak creatinine level being 4 (IQR, 2-5) days after the AGEP start date. Treatments included topical corticosteroids (277 [81.5%], either alone or in combination), systemic corticosteroids (109 [32.1%]), cyclosporine (10 [2.9%]), or supportive care only (36 [10.6%]). All-cause mortality within 30 days was 3.5% (n = 12), none of which was suspected to be due to AGEP.

Conclusions and Relevance  This retrospective case series evaluation of 340 patients, the largest known study cohort to date, suggests that AGEP onset is acute, is usually triggered by recent exposure to an antimicrobial, may be associated with liver or kidney complications in a minority of patients, and that discontinuation of the triggering treatment may lead to improvement or resolution.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Accepted for Publication: November 3, 2021.

Published Online: January 5, 2022. doi:10.1001/jamadermatol.2021.5390

Correction: This article was corrected on February 16, 2022, to fix an error in an author degree and affiliation.

Corresponding Author: Arash Mostaghimi, MD, MPA, MPH, Department of Dermatology, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115 (amostaghimi@partners.org).

Author Contributions: Drs Mostaghimi and Creadore had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Creadore, Nelson, Rosenbach, Noe, Mostaghimi.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Creadore, Dewan, Cruz-Diaz, Shaigany, Smith, Wright.

Critical revision of the manuscript for important intellectual content: Creadore, Desai, Alloo, Dewan, Bakhtiar, Femia, Fox, Katz, Micheletti, Nelson, Ortega-Loayza, Patrinely, Plovanich, Rosenbach, Shields, Saleh, Sharif-Sidi, Shinkai, Su, Wanat, Wieser, Noe, Mostaghimi.

Statistical analysis: Creadore, Smith, Noe, Mostaghimi.

Administrative, technical, or material support: Creadore, Desai, Alloo, Dewan, Bakhtiar, Cruz-Diaz, Katz, Nelson, Ortega-Loayza, Plovanich, Rosenbach, Shaigany, Shields, Sharif-Sidi, Su, Wanat, Mostaghimi.

Supervision: Alloo, Fox, Rosenbach, Wanat, Mostaghimi.

Conflict of Interest Disclosures: Dr Ortega-Loayza reported receiving grants from Lilly; fees for serving on the advisory boards of Janssen, BMS, and Boehringer Ingelheim; and consultant fees from Genentech, Guidepoint LLC, and Techspert outside the submitted work. Dr Rosenbach reported receiving consultant fees from Merck, consulting and research grants from Processa Pharma: for the necrobiosis lipoidica clinical trial; Janssen, Eli Lilly, and Novartis outside the submitted work. Dr Shields reported being an assistant section editor at JAMA Dermatology. Dr Noe reported receiving grants from Boehringer Ingelheim outside the submitted work. Dr Mostaghimi reported receiving consulting fees from Pfizer, Lilly, AbbVie, Concert, hims & hers, and Digital Diagnostics outside the submitted work; and is an associate editor, JAMA Dermatology. No other disclosures were reported.

Disclaimer: Dr Cruz-Diaz is an Assistant Section Editor of JAMA Dermatology. Dr Micheletti is Images in Dermatology Editor for JAMA Dermatology. Dr Rosenbach is an Editorial Board member of JAMA Dermatology. Dr Shields is an Assistant Section Editor of JAMA Dermatology. Dr Shinkai is Chief Editor of JAMA Dermatology. Dr Mostaghimi is an Associate Editor of JAMA Dermatology. They were not involved in any of the decisions regarding review of the manuscript or its acceptance.

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