Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE-mediated food allergy that typically presents in infancy with delayed gastrointestinal symptoms. While cow’s milk and soy are common triggers globally, fish appears to be a significant culprit in Mediterranean regions, including Greece. Objective: To describe the clinical characteristics, natural history, and follow-up outcomes of fish-induced FPIES in a pediatric Greek population. Methods: A retrospective review was conducted on 96 children, diagnosed with acute fish-induced FPIES at a tertiary pediatric allergy unit in Greece between October 2014 and June 2024. Data collected included demographics, atopic comorbidities, multiple food triggers and outcomes of oral food challenges (OFCs). Results: The median age at first reaction to fish was 11 months, and diagnosis was confirmed by 2 years. Most children (73%) experienced multiple FPIES episodes before diagnosis. Codfish was the most common offending fish and was used in all OFCs. During follow-up, 73% of patients developed tolerance at a median age of 5.5 years. The mean amount of fish protein tolerated during the OFC was 10 grams. Children with more pre-diagnostic episodes were significantly less likely to develop tolerance (p<0.001). Mild abdominal discomfort post-tolerance was noted in a subset of children resulting in consuming small portions of fish. No patients developed IgE sensitization to fish. Atopic comorbidities, particularly allergic rhinitis, were common. Conclusions: Fish-induced FPIES is a prevalent and underrecognized condition in Greek children as in other Mediterranean countries. Early diagnosis and avoidance of the trigger may improve outcomes. Tolerance in the offending food can be acquired in early childhood. Further prospective studies are needed to assess species-specific reactivity and long-term prognosis in Mediterranean populations.

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a non-IgE-mediated food allergy that typically presents in infancy with delayed gastrointestinal symptoms. While cow’s milk and soy are common triggers globally, fish appears to be a significant culprit in Mediterranean regions, including Greece. Objective: To describe the clinical characteristics, natural history, and follow-up outcomes of fish-induced FPIES in a pediatric Greek population. Methods: A retrospective review was conducted on 96 children, diagnosed with acute fish-induced FPIES at a tertiary pediatric allergy unit in Greece between October 2014 and June 2024. Data collected included demographics, atopic comorbidities, multiple food triggers and outcomes of oral food challenges (OFCs). Results: The median age at first reaction to fish was 11 months, and diagnosis was confirmed by 2 years. Most children (73%) experienced multiple FPIES episodes before diagnosis. Codfish was the most common offending fish and was used in all OFCs. During follow-up, 73% of patients developed tolerance at a median age of 5.5 years. The mean amount of fish protein tolerated during the OFC was 10 grams. Children with more pre-diagnostic episodes were significantly less likely to develop tolerance (p<0.001). Mild abdominal discomfort post-tolerance was noted in a subset of children resulting in consuming small portions of fish. No patients developed IgE sensitization to fish. Atopic comorbidities, particularly allergic rhinitis, were common. Conclusions: Fish-induced FPIES is a prevalent and underrecognized condition in Greek children as in other Mediterranean countries. Early diagnosis and avoidance of the trigger may improve outcomes. Tolerance in the offending food can be acquired in early childhood. Further prospective studies are needed to assess species-specific reactivity and long-term prognosis in Mediterranean populations.