Enteropathies Associated with Chronic Diarrhea and Malabsorption of Childhood

Diarrheal disorders place an enormous burden on the health of children throughout the world and are associated with significant morbidity and mortality even in industrialized countries, particularly in the infant, who is at greater risk of dehydration. Acute diarrhea is usually infectious in nature and most frequently self-limited in industrialized countries. It is generally diagnosed by a combination of stool cultures, immunologic, and molecular methods and rarely requires endoscopy or biopsies. Chronic diarrhea is generally understood as lasting more than 2 weeks and is often associated with poor nutrition and growth. Chronic diarrhea can be classified as either acquired or congenital. Acquired diarrhea is most often infectious, but may occasionally persist as postinfectious enteritis. Infectious diarrhea may also be chronic in patients with primary or secondary immunodeficiencies (see Chap. 5 ). Other causes of acquired chronic diarrhea include allergic enteropathies (see later in this chapter) and necrotizing enterocolitis leading to short bowel syndrome (Chap. 6 ). Motility disorders (Chap. 7 ) can also cause diarrhea either when motility is increased, as a result of abnormal mediators, or when decreased, by allowing bacterial overgrowth resulting in excessive deconjugation of bile acids. In the most severe cases, diarrhea may even be due to overflow. Congenital diarrheas and enteropathies are rare causes of intestinal failure early in life. Modern genetic analysis and the application of whole-exome sequencing have identified monogenic causes for many of these disorders. Infants with these conditions undergo extensive investigation, almost invariably including intestinal biopsies, the major topic of this chapter. These patients require intensive nutritional and medical support, and in some cases bone marrow or intestinal transplantation, prompting the need for timely and accurate diagnosis. As originally described, most of these disorders were classified as intractable diarrhea of infancy to refer to these cases which, at the time, remained mostly undiagnosed and were associated with a high mortality. The incidence of congenital diarrhea varies in different populations and with methods in ascertainment; one study in Italy estimated an occurrence rate of congenital diarrhea of 1 per 2000 hospitalized newborns (Canani and Terrin, Curr Gastroenterol Rep 13:257–264, 2011). Investigation of these disorders has also led to significant advances in our understanding of gut biology and immunology, sometimes in other fields of medicine. For example, the discovery that mutations in FOXP3 cause the IPEX syndrome with a resulting absence of naturally occurring T regulatory lymphocytes (Tregs) has opened whole new avenues in our understanding of the control of immune response, autoimmunity, and immune tolerance. Numerous entities can result in chronic diarrhea and malabsorption; a partial listing is provided in Table 4.1 by disease category and corresponding major age at presentation. Motility disorders and primary immunodeficiencies are discussed in other chapters in this volume and will not be further elaborated upon here. As pancreatic disorders causing chronic diarrhea rarely require histologic confirmation, they will also not be discussed further.