The Role of Histopathology in Diagnosing Protracted Diarrhea of Infancy

Abstract

Protracted diarrhea is used to describe infants with loose and frequent stools of sufficient severity to require nutritional support, most commonly parenteral nutrition. Despite similar clinical presentations, the causes of protracted diarrhea in infants are varied and diverse in management and prognosis. The following cases represent the two more common causes of protracted diarrhea in young infants in the developed world - allergic and autoimmune enteropathy. Both patients demonstrate diagnostic challenges related to clinical and/or laboratory features. These cases illustrate the important role histological assessment plays in determining the correct diagnosis, treatment course and prognosis in infants with protracted diarrhea.

Autoimmune Enteropathy: A Review and Update of Clinical Management

“…Individuals generally have refractory diarrhea with malabsorption and anorexia leading to severe weight loss that requires treatment with total parenteral nutrition [2]. While some have proposed that AIE is more common in males, a relatively large series in adults found no sex predominance and an average age at diagnosis of 55 [1, 4]. …”

“…Crypt abscesses may also be seen [4]. There may be apoptotic bodies and lymphocytic infiltration in the crypt epithelium with relative paucity of surface lymphocytosis (<40 lymphocytes per 100 epithelial cells), whereas an intra-epithelial distribution of lymphocytes predominates in celiac disease [1, 17–19].…”

“…The presence of AEA is not specific for AIE, as they may be found in other diseases such as inflammatory bowel disease, HIV infection, and allergic enteropathy [2, 4, 21–23]. Titer levels may increase after there is mucosal damage, and may normalize with treatment before there is histological remission [2].…”

“…Furthermore, Scurfin, a transcription factor encoded by the FOXP3 gene that is necessary for regulatory T cell development and function, is associated with dysfunction or loss of effect of these cells [2, 4, 6, 14, 30]. In one study, 7/11 children with AIE had mutations that resulted in lost or reduced FOXP3 protein expression, while 2/11 demonstrated decreased T regulatory cell activity [17].…”

The Spectrum of Autoimmune Enteropathy

“…Cryptitis and crypt abscesses have been reported in severe AIE. Crypt enterocytes commonly show an increased expression of HLA-A, -B, -C molecules [8,55,56]. (See Table 2.2; Fig.…”