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Purpose of Review <p>Acute Generalized Exanthematous Pustulosis (AGEP) and its localized variant (ALEP) are severe T cell–mediated hypersensitivity reactions, most commonly triggered by β-lactam antibiotics. This review aims to update the allergological approach for identifying the culprit drug in AGEP/ALEP, contrasting it with immediate-type (IgE-mediated) hypersensitivity reactions. β-lactam antibiotics serve as a model to highlight the differing diagnostic pathways, including clinical assessment, histopathology, and immunological testing, to facilitate prompt recognition and safe management.</p> Recent Findings <p>The latest European consensus on AGEP diagnosis recommends delayed patch testing and intradermal testing (10–30% in petrolatum) ≥ 4 weeks after resolution. Histopathology and EuroSCAR scoring enhance diagnostic accuracy. Recent studies have identified IL36RN and CARD14 mutations in severe or atypical AGEP, supporting pathophysiological overlap with pustular psoriasis. Emerging therapies targeting IL-17 and IL-36 pathways, such as secukinumab and spesolimab, show promise in refractory cases, particularly in genetically susceptible patients.</p> Summary <p>Early clinical suspicion of AGEP is essential to ensure timely drug withdrawal and prevent complications. Understanding the immunopathogenesis and applying appropriately timed allergological testing optimizes diagnostic reliability and patient safety. Recognition of cross-reactivity patterns within β-lactams and the careful differentiation from other pustular dermatoses are critical for guiding therapeutic decisions and avoiding unnecessary drug avoidance.</p>

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Acute Generalized Exanthematous Pustulosis (AGEP): A Review Focusing on Allergological Approach and Comparison with Immediate Beta-Lactam Allergy

  • 期刊论文

  • 发表日期：

    2025年11月8日

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  • Olga Villarreal Balza de Vallejo

摘要

Purpose of Review

Acute Generalized Exanthematous Pustulosis (AGEP) and its localized variant (ALEP) are severe T cell–mediated hypersensitivity reactions, most commonly triggered by β-lactam antibiotics. This review aims to update the allergological approach for identifying the culprit drug in AGEP/ALEP, contrasting it with immediate-type (IgE-mediated) hypersensitivity reactions. β-lactam antibiotics serve as a model to highlight the differing diagnostic pathways, including clinical assessment, histopathology, and immunological testing, to facilitate prompt recognition and safe management.

Recent Findings

The latest European consensus on AGEP diagnosis recommends delayed patch testing and intradermal testing (10–30% in petrolatum) ≥ 4 weeks after resolution. Histopathology and EuroSCAR scoring enhance diagnostic accuracy. Recent studies have identified IL36RN and CARD14 mutations in severe or atypical AGEP, supporting pathophysiological overlap with pustular psoriasis. Emerging therapies targeting IL-17 and IL-36 pathways, such as secukinumab and spesolimab, show promise in refractory cases, particularly in genetically susceptible patients.

Summary

Early clinical suspicion of AGEP is essential to ensure timely drug withdrawal and prevent complications. Understanding the immunopathogenesis and applying appropriately timed allergological testing optimizes diagnostic reliability and patient safety. Recognition of cross-reactivity patterns within β-lactams and the careful differentiation from other pustular dermatoses are critical for guiding therapeutic decisions and avoiding unnecessary drug avoidance.