Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) is a rare, potentially life-threatening hypersensitivity reaction characterized by fever, rash, eosinophilia, and internal organ involvement. Its delayed onset and variable presentation complicate diagnosis. The pathophysiology involves genetic predisposition, drug metabolism alterations, and possible herpesvirus reactivation. The RegiSCAR scoring system is used to standardize and validate diagnosis, supporting therapeutic decision-making.

A six-year-old male, previously healthy, hospitalized in a tertiary pediatric center for pneumonia, developed persistent fever, diffuse maculopapular rash, facial edema, lymphadenopathy, marked eosinophilia (18%), and elevated transaminases two weeks after completing vancomycin therapy, with no new infectious evidence. Based on RegiSCAR criteria, the case was classified as “definite” DRESS. Vancomycin was promptly discontinued, and symptomatic management was initiated, including antipyretics, antihistamines, beta-2 agonists, and systemic corticosteroids.

DRESS represents a diagnostic challenge in pediatric populations, where fever and rash are common to many conditions. Although vancomycin-associated DRESS is rare, it warrants attention in pharmacovigilance of widely used antibiotics. This case underscores the importance of early recognition of the characteristic clinical triad and objective scoring tools such as RegiSCAR. Long-term follow-up is crucial given risks of viral reactivation, relapse, or autoimmune sequelae. Early diagnosis and timely management are key to favorable outcomes and reduced risk of severe complications.