D1.100 - Deciphering Multiple Drug Allergy syndrome: True Allergy or Pro-inflammatory Response ?

Multiple Drug allergy syndrome (MDAS) is defined as an immune-mediated sensitization to two or more chemically unrelated drugs—most frequently antibiotics, though anticonvulsants are also commonly implicated. This often complicates the management of chronic or recurrent infections, as it severely limits first-line antibiotic options. In children, the diagnosis is particularly challenging as viral exanthemas frequently mimic drug eruption, leading to an over-diagnosis allergies. Conversely, severe systemic reactions like drug hypersensitivity syndrome can act as a primer for the immune system, increasing the risk of developing MDAS through massive T-cell activation and cytokine release.

Herein, we report the case of a 13-year-old child with a history of vesico-sphincteric dysgenesis admitted for extensive left cervical cellulitis. The clinical course was complicated by recurrent hypersensitivity reactions to multiple antibiotic classes. Initial treatment with Vancomycin resulted in an immediate pruritic rash. A subsequent switch to Imipenem/Cilastatin (Tienam) triggered a localized pruritic forearm rash during the second infusion. The treatment was maintained by adding anti-histamines. The reaction recurred and became more extensive by the fifth dose. Finally, the introduction of Teicoplanin (Targocid) also elicited an erythematous pruritic reaction, suggesting potential class-wide glycopeptide sensitivity alongside beta-lactam hypersensitivity. Three months later, skin tests were performed and were negative. 

This case illustrates the clinical complexity of MDAS, defined as sensitization to two or more chemically unrelated antibiotics. The diagnosis is challenging and the question remains whether the patient represents MDAS or a pro-inflammatory MDAS, where the massive cytokine release from severe cellulitis lowers the mast cell degranulation threshold. In pediatric patients with extensive cellulitis, clinicians must remain vigilant. Managing extensive pediatric cellulitis with a suspected MDAS requires a delicate balance between infection control and allergy risk. A formal allergy workup, including skin testing and drug provocation tests, is mandatory once the acute inflammatory state has resolved to clarify the patient’s long-term antibiotic safety profile.