Objectives: Cow's milk protein allergy (CMPA) is very frequent in infants. Presentation is variable, and symptoms fluctuate in intensity. Diagnosis can be challenging as it is mostly clinical. In severe cases, patients can present with anasarca secondary to protein-losing enteropathy (PLE). The exact mechanism underlying PLE is incompletely understood. Here we report four cases of severe PLE caused by CMPA warranting endoscopic workup in whom histological expression was characterized by variable features along the gastrointestinal (GI) tract.

Methods: We report four cases of severe CMPA with PLE requiring extensive workup including endoscopy to exclude immune deficiency or congenital enteropathy. The different histological expressions along the GI tract are presented.

Results: Histology ranged from the expected eosinophilia, observed in all cases, to severe mucosal atrophy with subtotal loss of colonic glands. Correlation between endoscopy and histology was poor.

Conclusion: CMPA can affect any segment of the GI tract and the intensity of the histological findings varies among patients and localizations. Food protein allergy should be considered in infants and children with hypoalbuminemia.