Drug-induced enterocolitis syndrome in children: report of two cases and a literature review

Background. Drug-induced enterocolitis syndrome (DIES) is a recently defined clinical entity, first described in 2014. DIES is a hypersensitivity reaction with non-IgE mechanisms involving the gastrointestinal tract, occurring 1 to 4 hours after drug ingestion. Antibiotics are most commonly responsible, particularly amoxicillin or amoxicillin / clavulanic acid (AMX/CL). The main criterion is recurrent, often uncontrollable vomiting occurring 1-4 hours after drug ingestion, without classic IgE-mediated allergic symptoms such as cutaneous or respiratory reactions. To the best of our knowledge, 10 pediatric cases of DIES have been described in the literature. Case Presentations. A 4-year-old male and a 14-year-old male presented to our pediatric allergy clinic with a suspected hypersensitivity reaction to AMX/CL, and their specific IgE tests for penicillin G and penicillin V were negative. The younger patient was also tested for specific IgE against amoxicillin and ampicillin, which were also negative. Skin prick tests and intradermal test with AMX/CL were negative in both patients, but oral provocation testing with AMX/CL resulted in abdominal pain, vomiting and lethargy, confirming the diagnosis of DIES. Conclusions. DIES should be considered in patients presenting with vomiting and lethargy following drug ingestion, particularly when IgE-mediated allergies have been ruled out. Early recognition and appropriate management, including drug provocation testing in a controlled setting, are crucial to ensure optimal patient outcomes. By presenting these two rare cases, we aim to raise awareness and deepen the understanding of DIES among healthcare professionals, which could contribute to earlier diagnosis and better patient outcomes.