Advances in Evaluation of Chronic Diarrhea in Infants

Abstract

Diarrhea is common in infants (children less than 2 years of age), usually acute, and, if chronic, commonly caused by allergies and occasionally by infectious agents. Congenital diarrheas and enteropathies (CODEs) are rare causes of devastating chronic diarrhea in infants. Evaluation of CODEs is a lengthy process and infrequently leads to a clear diagnosis. However, genomic analyses and the development of model systems have increased our understanding of CODE pathogenesis. With these advances, a new diagnostic approach is needed. We propose a revised approach to determine causes of diarrhea in infants, including CODEs, based on stool analysis, histologic features, responses to dietary modifications, and genetic tests. After exclusion of common causes of diarrhea in infants, the evaluation proceeds through analyses of stool characteristics (watery, fatty, or bloody) and histologic features, such as the villus to crypt ratio in intestinal biopsies. Infants with CODEs resulting from defects in digestion, absorption, transport of nutrients and electrolytes, or enteroendocrine cell development or function have normal villi to crypt ratios; defects in enterocyte structure or immune-mediated conditions result in an abnormal villus to crypt ratios and morphology. Whole-exome and genome sequencing in the early stages of evaluation can reduce the time required for a definitive diagnosis of CODEs, or lead to identification of new variants associated with these enteropathies. The functional effects of gene mutations can be analyzed in model systems such as enteroids or induced pluripotent stem cells and are facilitated by recent advances in gene editing procedures. Characterization and investigation of new CODE disorders will improve management of patients and advance our understanding of epithelial cells and other cells in the intestinal mucosa.

Food protein‐induced enterocolitis syndrome

“…Acute viral gastroenteritis is the most common diagnosis of exclusion for acute FPIES; it is not associated with a specific food trigger and vomiting is often accompanied by diarrhoea and fever . History of sick contacts may help differentiate infectious gastroenteritis from FPIES .…”

“…Other non‐food allergic diseases that can mimic chronic FPIES but are not food allergy related are gastroesophageal reflux, congenital diarrhoea disorders (CDD), primary immunodeficiency and very early onset inflammatory bowel diseases (VEO‐IBD) . .…”

“…64 Acute viral gastroenteritis is the most common diagnosis of exclusion for acute FPIES; it is not associated with a specific food trigger and vomiting is often accompanied by diarrhoea and fever. 65 tract, and often significant peripheral eosinophilia is present. 72 They are almost never responsive to diet and remission is often induced by use of oral steroids.…”

Antidiarrheal Activity of Hydromethanolic Root Extract and Solvent Fractions of Clutia abyssinica Jaub. & Spach. (Euphorbiaceae) in Mice

“…Diarrhea is a symptom of disease marked by rapid and frequent passage of semisolid or liquid fecal materials through the gastrointestinal tract (GIT) along with increased motility and secretions of GIT and decreased fluid absorption [1]. Diarrheal diseases are associated with an estimated 1.3 million deaths annually, with most occurring in resource-limited countries; up to 25% of deaths in young children living in Africa and southeast Asia are attributable to acute gastroenteritis [2,3]. In Ethiopia, diarrheal diseases are major contributors to under-five mortality.…”

Gut dysbacteriosis and intestinal disease: mechanism and treatment

“…Moreover, there will be osmotic diarrhoea when nutrients (especially small‐sized nutrients) produce osmotic force, which causes water to enter the lumen (Thiagarajah et al . 2018). Celiac disease (CD) is an allergic enteropathy, which is also accompanied by osmotic diarrhoea.…”