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Causes of chronic diarrhea in children

Physiologic

Lactase nonpersistence (hypolactasia)*

Infection-related

Postinfectious malabsorptive diarrhea*

Lactose or other specific carbohydrate intolerance without residual inflammation*

Generalized malabsorption with residual inflammation

Persistent or recurrent infection

Primary immunodeficiency (SCID, IPEX, CVID)^¶

Secondary immunodeficiency (eg, transplant patient on immunosuppressive drugs or child with malnutrition)^¶

No underlying immunodeficiency – Caused by organisms that are difficult to eradicate, such as C. difficile or S. typhi

Drug-induced

Antibiotic-associated diarrhea*

Non-antibiotic-associated

Without mucosal injury (eg, laxatives, SSRIs, orlistat)

With mucosal injury (eg, 5-FU, NSAIDs, olmesartan)

Functional diarrhea

Functional diarrhea in young children*^Δ

Often associated with excessive sugar or carbohydrate intake

Irritable bowel syndrome (diarrhea-predominant)

Immune-mediated

Common causes

Celiac disease*

Inflammatory bowel disease*

Food protein-induced allergic proctocolitis (eg, due to cow's milk)*^◊

Uncommon causes

Food protein-induced enterocolitis

Eosinophilic gastroenteritis

Microscopic lymphocytic or collagenous colitis

Autoimmune enteropathy

Primary immunodeficiencies (see above)

Polyglandular autoimmune syndrome

Cutaneous or systemic mastocytosis

Fat malabsorption

Pancreatic exocrine insufficiency

Cystic fibrosis*

Shwachman-Diamond syndrome

Bile acid insufficiency

Resection of the terminal ileum

Bile salt deconjugation (eg, in small intestine bacterial overgrowth)

Mucosal malabsorption

Short bowel syndrome

Severe and diffuse small intestinal Crohn disease

Neuroendocrine tumors and related disorders

Neurofibromatosis (associated with several types of neuroendocrine tumors)

Neuroblastoma and ganglioneuroblastoma (eg, VIPoma)

Multiple endocrine neoplasia type 2b

Congenital anomalies associated with bowel obstruction

Chronic intestinal pseudo-obstruction

Hirschsprung disease, with enterocolitis

Malrotation with intermittent volvulus

Other mechanisms

Small intestine bacterial overgrowth

Bile acid malabsorption

Protein-losing enteropathy/gastropathy

Factitious diarrhea

Congenital diarrheas and enteropathies (eg, sucrase-isomaltase deficiency)

Vasculitis

SCID: severe combined immunodeficiency; IPEX: immune dysregulation, polyendocrinopathy, enteropathy, X-linked; CVID: common variable immunodeficiency; C. difficile: Clostridioides difficile; S. typhi: Salmonella typhi; SSRIs: selective serotonin reuptake inhibitors; 5-FU: 5-fluorouracil; NSAIDs: nonsteroidal antiinflammatory drugs; VIPoma: vasoactive intestinal polypeptide-secreting tumor; G. lamblia: Giardia lamblia; E. coli: Escherichia coli; IgE: immunoglobulin E.

* Relatively common causes (although prevalence varies with age group).

¶ Pathogens that tend to be involved in persistent or recurrent enteric infections in immunocompromised patients include parasites (C. difficile, Cryptosporidium, Isospora, Cyclospora, G. lamblia), viruses (rotavirus, norovirus, astrovirus, adenovirus, and cytomegalovirus), and bacteria (Salmonella spp, Campylobacter, E. coli).

Δ In some toddlers, low-volume loose stools may also be physiologic; these are not related to excessive carbohydrate intake and often do not meet criteria for diarrhea.

◊ The term "food protein-induced proctocolitis/enteritis" is now preferred. Previously used terms (eg, milk protein intolerance, cow's milk sensitivity, and soy intolerance) are no longer recommended. The new terminology helps to distinguish these non-IgE-mediated disorders from classical food allergies/hypersensitivities that are mediated by IgE. It also distinguishes them from food intolerances that do not involve immunologic mechanisms (eg, lactose intolerance).

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