Food allergies are the leading cause of anaphylaxis in children. Cofactors, such as exercise and non-steroidal anti-inflammatory drugs, may influence the occurrence and severity of allergic reactions to food. However, despite their relevance, the underlying mechanisms of cofactor-enhanced food allergies remain poorly understood. We report the case of a 12-year-old girl with mitochondrial DNA depletion syndrome who was referred to an allergy appointment due to suspected ibuprofen hypersensitivity. Detailed anamnesis, laboratory assessment, and negative drug challenge results excluded this diagnosis
however, continued follow-up revealed a crucial pattern on patient reactions that led to the diagnosis of a cofactor-enhanced food allergy with the presumed involvement of soy storage proteins and non-steroidal anti-inflammatory drugs. Our purpose was to highlight the non-negligible role of cofactors in food allergies and the importance of early identification. Moreover, to underscore the relevance of maintaining patient follow-up, as new information may arise and redirect the diagnosis.