Drug-Induced Enterocolitis Syndrome in Children: A Report of Two Cases

Drug-induced enterocolitis syndrome (DIES) is a rare non-IgE-mediated hypersensitivity reaction characterized by delayed-onset gastrointestinal symptoms, typically occurring one to four hours after drug ingestion. It shares clinical features with food protein-induced enterocolitis syndrome and remains underrecognized, with limited reported cases. We present two pediatric cases of DIES triggered by amoxicillin. The first case involves an eight-year-old girl with allergic rhinoconjunctivitis and asthma, who experienced multiple episodes of vomiting and pallor following amoxicillin ingestion. A drug provocation test (DPT) with amoxicillin reproduced the reaction, with vomiting, lethargy, pallor, and diarrhea. The second case concerns a three-year-old girl, initially developing an urticarial rash after amoxicillin exposure at eight months of age. A subsequent DPT led to persistent vomiting, abdominal pain, and leukocytosis with neutrophilia, requiring intravenous fluid therapy. In both cases, DIES was diagnosed based on clinical criteria, and amoxicillin avoidance was recommended. These cases align with previously reported pediatric DIES, reinforcing its association with amoxicillin. Laboratory findings, including leukocytosis, neutrophilia, and thrombocytosis, may support the diagnosis, but clinical recognition remains crucial, requiring high suspicion and increased awareness among clinicians. These cases highlight the diagnostic challenges in differentiating DIES from IgE-mediated drug hypersensitivity, the importance of conducting DPT in a controlled setting, and the need for further research on its pathophysiology, biomarkers, and prognosis.