Characteristics and natural course of neonatal and infantile gastrointestinal milk allergy and the efficacy of oral immunotherapy


Correspondence: H. Arakawa, Department of Pediatrics, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.



The characteristics and natural course of gastrointestinal (GI) allergies, which mainly affect infants and young children, are not fully determined. We investigated the nature of neonatal and infantile GI allergies and the efficacy of slow oral immunotherapy in patients with persistent symptoms. We observed 12 patients (five boys, seven girls) aged at first presentation from 0 days to 8 months after birth. Detailed interviews, peripheral blood eosinophil counts, antigen-specific IgE antibody levels, antigen-specific lymphocyte stimulation tests (LSTs), stool occult blood eosinophil counts and skin tests were performed in combination with milk elimination tests. Five patients underwent an intestinal mucosal biopsy. Provocation testing was used to assess tolerance acquisition. The only clinical symptom in six patients was bloody stool, while vomiting, fever, poor weight gain or hepatic dysfunction developed in six patients. Milk-specific LSTs were positive in 10 of 11 cases tested. Lower GI endoscopy showed large numbers of infiltrating eosinophils in four of five patients with an intestinal mucosal biopsy. Provocation tests to confirm tolerance acquisition were performed in three patients. Interestingly, one patient suffered IgE-mediated GI anaphylaxis during the provocation test. One patient had a sustained high LST index, and elimination of dairy milk products was continued. At 4 years of age, she underwent an oral challenge test. On ingestion of 5 mL of milk, she exhibited fever, loose stool, poor appearance and increased white blood cell counts, which was considered a positive provocation test. Therefore, slow oral immunotherapy was started using 1/20 of the threshold dose, with fat intake at least four times per week. This was steadily increased by 20% over 2 weeks without inducing symptoms. The characteristics of neonatal and infantile GI allergies are diverse, and they generally remit spontaneously. However, patients who do not develop tolerance may be suitable choices for oral immunotherapy.