Immunopathogenesis and Cytokine Pathways in Reactive Infectious Mucocutaneous Eruption (RIME) in Pediatric Population: Infectious Triggers and Molecular Insights.

Authors

Filippos Filippatos, Konstantinos Kakleas, Athanasios Michos

Published in

Clinical reviews in allergy & immunology. Volume 69. Issue 1. Jun 25, 2026. Epub Jun 25, 2026.

Abstract

Reactive infectious mucocutaneous eruption (RIME) is increasingly recognized as a pediatric syndrome in which severe mucositis follows a recent infection and cutaneous involvement is usually limited. Although Mycoplasma pneumoniae remains the prototype trigger, influenza, SARS-CoV-2, adenovirus, respiratory syncytial virus, and other respiratory pathogens can produce a similar clinical phenotype. This narrative review summarizes pediatric RIME/MIRM literature and selected adult or comparator-disease evidence when direct pediatric data are unavailable, explicitly distinguishing direct RIME evidence from extrapolated mechanisms. This review synthesizes current evidence on the immunopathogenesis of RIME in children, with emphasis on how pathogen-specific factors intersect with innate and adaptive immune pathways to drive mucosal injury. We discuss the central roles of epithelial sensing, inflammasome activation, cytokine amplification, neutrophil recruitment, and T-cell polarization, and we relate these mechanisms to the severe oral, ocular, and anogenital disease that often defines pediatric presentations. We also integrate emerging proteomic data showing recurring molecular programs, including acute-phase and complement activation, neutrophil-associated epithelial injury, and interferon-inducible antiviral responses. In addition, we review the possible contribution of genetic susceptibility, especially variation in innate immune sensors and cytokine signaling pathways, to disease severity and recurrence. Finally, we address the main diagnostic challenges, histopathologic and imaging findings, differential diagnosis from Stevens-Johnson syndrome, erythema multiforme, and Kawasaki disease, and the implications of these insights for risk stratification and treatment. Taken together, current evidence supports RIME as a pathogen-triggered, mucosa-predominant inflammatory syndrome in which exaggerated host responses, rather than pathogen presence alone, shape the clinical phenotype.

PMID:
42350880
Bibliographic data and abstract were imported from PubMed on 26 Jun 2026.

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