Syndrome of intractable diarrhoea with persistent villous atrophy in early childhood: A clinicopathological survey of 47 cases

Background: The syndrome of intractable diarrhoea of infancy is heterogeneous and includes several diseases with diverse aetiologies. This study determines whether diagnostic categories can be defined on the basis of clinicopathological analysis. Methods: European Society of Paediatric Gastroenterology, Hepatology and Nutrition members were surveyed to identify cases of intractable diarrhoea with persisting small intestinal enteropathy. A retrospective clinicopathological analysis was performed on cases showing life-threatening diarrhoea within the first 24 mo of life and requiring total parenteral nutrition, which were characterized by persistent villous atrophy, and resistance to therapy. Results: Forty-seven infants were identified with intractable diarrhoea. Villous atrophy was of varying degrees with (group I, n = 24) or without (group II, n = 18) lamina propria mononuclear cell infiltration. Group I presented later, had gut autoantibodies, and a higher prevalence of protein-losing enteropathy; a subset (group Ia, n = 12) also had extraintestinal symptoms of autoimmunity associated with a later onset of larger volume diarrhoea. Group II presented early; 8 cases (group IIa) had phenotypic abnormalities and a low birth weight; the remaining 10 (group Ilb) showed mild-to-moderate villous atrophy, epithelial tufting, and abnormal crypts. Group III included five patients in whom no specific features were recognised. Twenty-one (45%) died at a median age of 24 months, 20 (43%) remained dependent on parenteral (n = 16) or enteral tube (n = 4) feeding, 4 (9%) received elimination diets plus other therapies, and 2 (4%) were lost to follow-up. Conclusions: Clinicopathological analysis allowed distinct disease groups to be identified, allowing a provisional classification to be made. This straightforward approach forms a basis for future research in this exceptionally difficult paediatric condition.