Resolution of Food Protein–Induced Enterocolitis Syndrome—A Long-Term Follow-Up Study of 113 Swedish Children

Food protein–induced enterocolitis syndrome (FPIES) is a non–immunoglobulin E–mediated food allergy primarily affecting infants and young children. Allergy skin tests or blood tests are typically negative. In the acute form of FPIES, symptoms typically include significant repetitive vomiting 2 to 4 hours following ingestion of a triggering food, and there can be lethargy and hypotension. Although the condition is usually outgrown, the time course of resolution is not well established. To determine resolution, a medically supervised oral food challenge (OFC) test is required. This study aimed to provide data on the resolution of FPIES in a large Swedish cohort.The cohort included 113 children with physician-diagnosed acute FPIES, recruited from 25 pediatric centers in Sweden.This was a prospective long-term follow-up study using a combination of retrospective medical record review and caregiver interviews. Investigators collected data on food triggers, timing of tolerance development, and results of OFCs. Resolution was defined as either successful hospital-based OFC or reintroduction at home (planned or by accident) without symptoms.The median age at diagnosis was 7.7 months, and median age at last follow-up was 5.6 years (range: 8.7 months to 16.5 years). A total of 137 food triggers were reported across the cohort, with 83% of children having a single trigger and the remainder having 2 to 4. Overall, 83 of 113 children (73%) developed tolerance to at least 1 previously reactive food, accounting for 96 of 137 food triggers (70%). Tolerance rates were highest for cow’s milk (93%) and oat (92%) and lowest for fish (46%). The median age of tolerance was 24 months for cow’s milk, 30 months for oat, and 49 months for fish. The median age for tolerance overall was 36 months. Tolerance was determined by OFCs in 45% of the cases and through report of home introduction for the remainder.Most Swedish children with FPIES achieved tolerance to common trigger foods by the age of 3 to 4 years. Tolerance to cow’s milk and oat generally occurred earlier, whereas fish-induced FPIES persisted longer. These findings support individualized timing of OFCs, with earlier reintroduction attempts for milk and oat and delayed OFCs for fish.It should be noted that the prevalence of FPIES trigger foods varies regionally. For example, 25% of this cohort had fish as a trigger, whereas in the United States, the rate is less than 5%. It is also important to consider that the timing of OFC could be influenced by severity of the prior reaction, the perceived importance of the food, and other factors. However, this well-designed, multicenter study offers important insight into the long-term prognosis of FPIES in a Scandinavian population that is likely applicable to other populations on a food-specific basis. Its strengths include a large cohort, national representation, and inclusion of multiple food triggers. However, some tolerance data were based on caregiver report alone, which could lead to misdiagnosis. Additionally, the wide range in follow-up age introduces variability. Despite these limitations, the study reinforces the typically favorable prognosis of FPIES and highlights the need for food-specific reintroduction strategies. Prospective standardized protocols for OFCs would enhance future research.