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Overview of the causes of chronic diarrhea in children in resource-abundant settings

Overview of the causes of chronic diarrhea in children in resource-abundant settings
Literature review current through: Jan 2024.
This topic last updated: Mar 01, 2023.

INTRODUCTION — While diarrhea is among the most common ailments affecting children, chronic diarrhea is relatively unusual in resource-abundant countries. It may be the manifestation of a broad group of disorders, ranging from an intolerance to a specific food (or food component) to an indication of a much broader multisystem condition.

This review will outline causes of chronic diarrhea in children that first present beyond early infancy (ie, after six months of age), organized by general pathophysiologic categories. A clinical approach to evaluating children with chronic diarrhea is presented separately:

(See "Approach to chronic diarrhea in children >6 months in resource-abundant settings".)

(See "Approach to chronic diarrhea in neonates and young infants (<6 months)".)

DEFINITIONS

Diarrhea – Objective definitions of diarrhea are based on stool weight or volume. However, because assessment of daily stool weights/volumes is difficult in the outpatient clinic setting, changes in the frequency and consistency of stool compared with baseline can also be used as a convenient gauge of diarrhea. Thus, one or both of the following measures can be used:

Stool weight – Daily stool weight greater than 250 g in children that weigh more than 10 kg is considered diarrhea. In young children (<10 kg), stool in excess of 20 g/kg/day is abnormal.

Stool consistency – The Bristol stool chart is a useful tool to define stool consistencies [1,2]. Diarrheal stools typically correspond to types 6 and 7 on the Bristol stool chart [3] (or its slightly modified versions for children [4] or infants [5]). Low-volume loose stools are not a significant predictor of underlying disease in the absence of other symptoms such as weight loss, dehydration, or significant changes in biochemical/nutritional indicators.

Chronic diarrhea – Chronic diarrhea is generally defined as diarrhea lasting greater than four weeks [6]. This timeline is selected to distinguish between the acute diarrheal episode, which tends to be self-limited, and more prolonged diarrheal disease that warrants further evaluation and possibly intervention.

Persistent diarrhea – The term persistent diarrhea is sometimes defined as diarrhea lasting longer than two weeks, but sometimes this term is used interchangeably with chronic diarrhea.

EPIDEMIOLOGY — Globally, the prevalence of diarrhea in children varies widely. Large-scale studies report that 3 to 20 percent of children under five years old have at least one episode per year, with an incidence of approximately 2.7 episodes per child-year in children younger than five years [7]. In resource-limited settings, chronic diarrhea is common and associated with significant mortality and morbidity.

In resource-abundant countries such as the United States, the prevalence of acute diarrhea is high, with 15 to 20 episodes per child-year in young children. However, the incidence of chronic diarrhea is substantially lower (less than 0.2 episodes per child-year) and is rarely severe, with less than 1 percent of episodes resulting in hospitalization [8,9].

CATEGORIZATION OF DIARRHEA — For clinical purposes, it is helpful to categorize chronic diarrhea by its proximate cause and other clinical characteristics, as outlined in the table (table 1):

Physiologic (lactase nonpersistence)

Infection-related

Drug-induced

Functional

Immune-mediated

Fat malabsorption

Neuroendocrine disorders and tumors

Congenital anomalies with bowel obstruction

Other mechanisms

Other schemes classify diarrheas by the physiologic mechanism, ie, diet-induced (osmotic), electrolyte transport-related (secretory), motility-related, or inflammation-related. This framework is also important at certain steps in the evaluation process. These mechanisms are discussed in a separate topic review. (See "Pathogenesis of acute diarrhea in children", section on 'Diarrhea classification'.)

PHYSIOLOGIC

Lactase nonpersistence — Lactase nonpersistence (also called acquired lactose intolerance or hypolactasia) is a genetically determined phenotype that is particularly common in children of African, Hispanic, and Asian descent, typically developing in early to mid-childhood. Typical symptoms are abdominal pain, flatulence, nausea, bloating, and diarrhea after ingestion of milk or milk-containing products. Management is tailored to the symptoms and consists of dietary lactose restriction and/or taking a lactase enzyme preparation with lactose-containing foods. Children who avoid dairy products should be monitored and supplemented as needed to ensure adequate intake of calcium and vitamin D. (See "Lactose intolerance and malabsorption: Clinical manifestations, diagnosis, and management".)

INFECTION-RELATED CAUSES — Diarrhea caused by bacterial or viral infections are often associated with constitutional symptoms of nausea, vomiting, fever, and, occasionally, dysentery. Most episodes of infectious diarrhea in an immunocompetent host resolve within two weeks since they either resolve spontaneously or are treatable with targeted antimicrobial therapies. (See "Diagnostic approach to diarrhea in children in resource-abundant settings", section on 'Common conditions'.)

Persistence of symptoms beyond two to four weeks may be related to underlying mucosal damage (postinfectious malabsorptive diarrhea including secondary lactose intolerance). If the infectious agent persists or recurs, an underlying primary or secondary immunodeficiency should be considered (table 1).

Postinfectious malabsorptive diarrhea — Postinfectious malabsorptive diarrhea is characterized by mucosal dysfunction that persists beyond four weeks after an acute enteric infection. This pattern is sometimes called postinfectious irritable bowel syndrome (IBS). In some cases, this is associated with residual mucosal inflammation and altered mucosal permeability and motility, which can cause diarrhea or upper gastrointestinal symptoms such as vomiting and dyspepsia [10,11]. As an example, one study in children who were followed for at least six months after acute bacterial gastroenteritis found a significantly higher risk (36 versus 11 percent of controls; relative risk 3.2) of developing abdominal pain that met criteria for IBS (87 percent) or dyspepsia (24 percent) [12].

More commonly, postinfectious diarrhea is caused by transient loss of lactase and other abnormalities that cause macro- and micronutrient malabsorption. This condition may persist for weeks or months after the infection resolves, particularly in malnourished children [12,13]. Lactose intolerance is the most common manifestation, but symptoms may include intolerance to a broad range of foods, and diarrheal symptoms may last for months.

Persistent or recurrent infection

With immunodeficiency — If the infectious agent persists or recurs, an underlying primary or secondary immunodeficiency should be considered. These disorders are characterized by persistence of infection beyond the infectious period that would be expected in a normal host and/or unexplained recurrences of infectious diarrhea. These recurrent and prolonged infections are often caused by parasitic or viral agents and lead to severe and prolonged symptoms in a lymphopenic host.

Specific pathogens that tend to be involved in these cases include:

Parasites – Cryptosporidium, Isospora, Cyclospora, and Giardia lamblia.

Viruses – Rotavirus (with or without history of receiving the vaccine (see "Clinical manifestations and diagnosis of rotavirus infection")), norovirus, astrovirus, adenovirus, and cytomegalovirus. These viruses tend to cause prolonged or non-self-resolving diarrhea in an immunocompromised host, in contrast with the self-resolving episodes in an immunocompetent host.

Bacteria – Clostridioides difficile, Salmonella, Campylobacter, and Escherichia coli.

T cell defects are associated with recurrent or persistent viral or parasitic infection, while B cell disorders are more often associated with bacterial infections. Important causes of primary and secondary immunodeficiency to consider include:

Primary immunodeficiency

Cellular and humoral

-Severe combined immunodeficiency

-Regulatory T cell (Treg) dysfunction, including IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) and other disorders

-Wiskott-Aldrich syndrome

(See "Severe combined immunodeficiency (SCID): An overview" and "IPEX: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked" and "Wiskott-Aldrich syndrome".)

Humoral

-Selective immunoglobulin A (IgA) deficiency

-Common variable immunodeficiency

(See "Selective IgA deficiency: Clinical manifestations, pathophysiology, and diagnosis" and "Common variable immunodeficiency in children".)

Secondary immunodeficiency

Organ transplant recipients (due to immunosuppressants)

Human immunodeficiency virus (HIV) infection (due to opportunistic infection in patients with active disease, or medication-induced)

Malnutrition

(See "Evaluation of the patient with HIV and diarrhea" and "Malnutrition in children in resource-limited settings: Clinical assessment" and "Persistent diarrhea in children in resource-limited settings".)

Without immunodeficiency — Many children with recurrent gastrointestinal infections have no identifiable immunodeficiency. These children are typically asymptomatic between bouts of infections, whereas those with immunodeficiency are more likely to have persistent symptoms.

In an immunocompetent host, risk factors for recurrent or chronic infection include:

Infection with C. difficile, which is notoriously difficult to eradicate. Similarly, children infected with Salmonella typhi frequently become carriers.

Underlying inflammatory bowel disease (IBD), which predisposes the patient to recurrent infections such as cytomegalovirus and C. difficile.

(See "Clostridioides difficile infection in children: Clinical features and diagnosis" and "Clostridioides difficile infection in children: Treatment and outcome" and "Enteric (typhoid and paratyphoid) fever: Epidemiology, clinical manifestations, and diagnosis".)

DRUG-INDUCED CAUSES — Drug-induced diarrhea is relatively common and may be caused by a wide variety of drugs (table 2). Mechanisms may involve alteration of intestinal fluid, electrolyte and nutrient transport, or direct mucosal damage [14].

Antibiotic-associated — Antibacterial agents are particularly common causes of drug-induced diarrhea [15]. The risk of diarrhea depends on the type of antibiotic; it is particularly common with broad-spectrum antibiotics that are poorly absorbed, such as amoxicillin-clavulanate.

Watery diarrhea following antibiotic use is generally benign, self-limiting, and requires no intervention. It usually results from the drug-induced microbial and metabolomic dysbiosis that eventually resolves [16]. Probiotics may help to prevent or shorten the course of antibiotic-associated diarrhea, based on limited information [17-20].

Bloody diarrhea (indicating colitis) associated with antibiotic use is infrequent but problematic. It is caused by loss of normal bowel flora and subsequent C. difficile infection. Very rarely, this can progress to a fulminant colitis with multisystem failure [21]. (See "Clostridioides difficile infection in children: Clinical features and diagnosis" and "Clostridioides difficile infection in children: Treatment and outcome".)

Non-antibiotic-associated — Diarrhea associated with nonantimicrobial drug therapies is common [22].

Drugs that do not injure the mucosa – For these drugs, diarrhea tends to start shortly after the drug is started and is often mild.

Laxatives (either prescribed or surreptitiously used) may result in an osmotic diarrhea in a dose-dependent manner.

Promotility agents such as metoclopramide, macrolides, and erythromycin shorten transit time and impair nutrient assimilation, leading to diarrhea.

Certain antidepressants (selective serotonin reuptake inhibitors) and anticholinergic agents reduce gastrointestinal motility, which may predispose to diarrhea due to bacterial overgrowth or by altering the microbiome [23]. The time course of onset may vary.

Drugs that impair assimilation of nutrients, such as orlistat (a pancreatic lipase inhibitor), acarbose, and miglitol (an alpha-glucosidase inhibitor), frequently result in diarrhea.

Certain antineoplastic agents (eg, tyrosine kinase inhibitors) can result in severe diarrhea without significant mucosal injury [24].

Drugs that injure the mucosa – Drugs that are associated with significant alterations of the mucosa may take longer for clinical symptoms to appear.

Antineoplastic drugs such as fluorouracil and others are commonly associated with diarrhea that results from minor mucosal injury.

The purine synthesis inhibitor mycophenolic acid is commonly used in renal transplant patients. It frequently causes diarrhea, associated with leukopenia and with villous atrophy and apoptosis in the crypt.

Other drugs, such as the angiotensin II receptor blocker olmesartan, are associated with a sprue-like enteropathy that results in chronic diarrhea that can be severe [25]. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'ARBs'.)

Microscopic colitis is a chronic inflammatory colitis that is seen almost exclusively in adults but has been reported in children. Risk factors include chronic use of nonsteroidal antiinflammatory drugs and proton pump inhibitors, among other drugs. (See "Microscopic (lymphocytic and collagenous) colitis: Clinical manifestations, diagnosis, and management", section on 'Medications'.)

Numerous immunotherapies are specifically associated with an immune-related adverse effect that includes diarrhea. For instance, ipilimumab (CTLA-4) and anti-PD-1 antibodies may result in a clinical course resembling both celiac disease and inflammatory bowel disease (IBD) [26].

FUNCTIONAL DIARRHEAL DISORDERS

Functional diarrhea in young children — Functional diarrhea in young children (sometimes known as "toddler's diarrhea") refers to chronic diarrhea or loose stools in an otherwise healthy young child with no underlying disease. This disorder can present as early as six months of age and is characterized by four or more large, painless stools per day, progressing in consistency from semi-solid in the morning to loose as the day progresses. Stools can contain undigested food and be watery. Intercurrent illness and stressors (excitement) may be triggers for exacerbations that last more than four weeks. The symptoms usually resolve by four to five years of age.

This disorder is thought to be common, with survey studies indicating prevalence among young children between 0.9 and 6.4 percent [27,28]. However, in many cases, the stools are simply loose and do not meet the formal definition of diarrhea in terms of volume, frequency, or severity (ie, no predisposition to dehydration or weight loss), so the true prevalence of diarrhea caused by this mechanism may be lower.

In some children, the symptoms appear to be associated with the excessive use of fructose- or sorbitol-based juices or diets high in sugar or other carbohydrates. In these cases, the severity of the diarrhea is dose-dependent and improves with restricting the intake of carbohydrate-rich food or beverages. However, in other cases, the diarrhea or loose stools continue regardless of dietary restriction. If the toddler is growing well and is otherwise healthy, no diagnostic testing or elimination diet is recommended. The parent/caregiver(s) can be reassured that the symptoms will likely have a benign course and eventually resolve by age five.

Diarrhea-predominant irritable bowel syndrome — Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by recurrent abdominal pain and a change of stool form or frequency. It is more common in adolescents compared with younger age groups. The estimated prevalence of IBS is between 1 and 3 percent among children in the United States [29]. As with other functional disorders, the diagnosis is based on symptoms and excluding other disorders. (See "Functional abdominal pain in children and adolescents: Management in primary care" and "Clinical manifestations and diagnosis of irritable bowel syndrome in adults".)

A subset of IBS is associated with mild diarrhea, known as diarrhea-predominant IBS or IBS-D. IBS-D can be seen at most ages, but it is more prevalent in adolescent females and generally is associated with low-volume loose stools, abdominal pain, urgency, and sensation of incomplete evacuation.

IMMUNE-MEDIATED CAUSES — Immunologic mechanisms are responsible for several causes of chronic diarrhea, including some common disorders (table 1):

Common causes

Celiac disease – Celiac disease is relatively common and may present at any age with failure to thrive, diarrhea, or, occasionally, with constipation. Many cases are now detected by testing asymptomatic children who have risk factors for celiac disease (eg, children who have type 1 diabetes or first-degree relatives with celiac disease). Celiac disease is a gluten-sensitive enteropathy that leads to an immune-mediated enteropathy that reduces the nutrient-absorptive capacity of the small bowel. A lifelong strict elimination of dietary gluten is required and is effective in the majority of cases. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children" and "Diagnosis of celiac disease in children" and "Management of celiac disease in children".)

Inflammatory bowel disease (IBD) – IBD (ulcerative colitis or Crohn disease) typically presents with a prolonged history of diarrhea, generally associated with mucous and, occasionally, blood. While the peak incidence of IBD is during adolescence or mid-adulthood, it can occur at any age. When IBD begins in infancy, it tends to have more protracted course that is less responsive to medical therapy and is more likely to result from a genetic basis. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children".)

Food protein-induced allergic proctocolitis – Food protein-induced allergic proctocolitis, sometimes known as food-protein intolerance, is a common cause of diarrhea or loose stools in infants. It usually resolves before one year of age but can rarely extend to toddlers and school-aged children. The most common food triggers are cow's milk, egg, or soy in the diet. (See "Food protein-induced allergic proctocolitis of infancy".)

Uncommon causes

Food protein-induced enterocolitis – Food protein-induced enterocolitis is a non-IgE-mediated food hypersensitivity syndrome that presents during infancy and typically resolves by three years of age. It is characterized by acute onset of profuse, repetitive vomiting with or without diarrhea following exposure to the offending food antigen. This leads to dehydration and lethargy. Chronic symptoms may include watery diarrhea with intermittent vomiting, leading to weight loss, failure to thrive, dehydration, and metabolic derangements ’ [30]. The diagnosis of food protein-induced enterocolitis is based upon the history, constellation of typical clinical symptoms with clinical improvement following elimination of the suspected causal protein, exclusion of other etiologies, and, if necessary, results of an oral food challenge. (See "Food protein-induced enterocolitis syndrome (FPIES)".)

Eosinophilic gastroenteritis – Eosinophilic gastroenteritis is a relatively rare disorder whose pathogenesis is poorly understood, but most children have elevated serum IgE levels. These patients have a propensity for protein-losing enteropathy and significant asthma and eczema. While a definitive dietary allergen is not usually identified, many patients respond to an elimination diet or elemental diet but frequently require steroid management. (See "Eosinophilic gastrointestinal diseases".)

Microscopic colitis – This disorder occurs primarily in adults and presents with watery, nonbloody diarrhea. Risk factors include chronic use of nonsteroidal antiinflammatory drugs and proton pump inhibitors (see 'Non-antibiotic-associated' above). It is characterized by grossly normal-appearing colonic mucosa, with histologic evidence of either a lymphocytic or collagenous colitis [31]. (See "Microscopic (lymphocytic and collagenous) colitis: Clinical manifestations, diagnosis, and management".)

Polyglandular autoimmune syndrome – This is an autosomal recessive disorder that results in the clinical triad of mucocutaneous candidiasis, hypoparathyroidism, and adrenal failure. Type 1 tends to present during childhood and is rare. Affected patients can also develop either episodic or persistent generalized malabsorptive diarrhea with loss of enteroendocrine cells and poor weight gain [32]. Severe malabsorptive diarrhea may be the first clinical manifestation of this disorder. (See "Causes of primary adrenal insufficiency in children", section on 'Autoimmune disease'.)

Cutaneous and systemic forms of mastocytosis – The majority of patients with this disorder have cutaneous lesions, and many have lymphadenopathy, splenomegaly, gastrointestinal ulcers, and hepatitis. Diarrhea is a common manifestation in either cutaneous or systemic mastocytosis, mediated by histamine release. This may be triggered by certain medicines (eg nonsteroidal antiinflammatory drugs and some antibiotics), infections, or spicy foods. (See "Mastocytosis (cutaneous and systemic) in children: Epidemiology, clinical manifestations, evaluation, and diagnosis".)

FAT MALABSORPTION — Fat malabsorption may be caused by several different mechanisms (table 1):

Pancreatic exocrine insufficiency — Deficiency of pancreatic lipase leads to maldigestion of fat due to lack of micellization in the bowel lumen. Cystic fibrosis is the most common cause of pancreatic exocrine insufficiency. Other causes include Shwachman-Diamond syndrome (MIM #260400; associated with bone marrow failure and skeletal abnormalities), some cases of advanced chronic pancreatitis, and four rare disorders (Pearson syndrome [MIM #557000], Johanson-Blizzard syndrome [MIM #243800], pancreatic lipase deficiency [MIM #614338], and colipase deficiency [also MIM #614338]). (See "Cystic fibrosis: Assessment and management of pancreatic insufficiency" and "Shwachman-Diamond syndrome".)

Bile acid insufficiency — Deficiency of bile acids in the intestinal lumen also leads to maldigestion of fat. This may be seen in patients with bile acid malabsorption due to resection or inflammation of the terminal ileum, which depletes the bile acid pool. Crohn disease is a common cause of terminal ileal disease. Bile acid insufficiency also may be caused by bile salt deconjugation, which is one of several mechanisms that can cause diarrhea in patients with small intestine bacterial overgrowth. (See 'Small intestinal bacterial overgrowth' below.)

Mucosal malabsorption — Extensive mucosal disease or resection of the small bowel can lead to fat malabsorption; this may occur in patients with short bowel syndrome or severe and diffuse small intestinal Crohn disease. (See "Pathophysiology of short bowel syndrome" and "Chronic complications of short bowel syndrome in children", section on 'Nutritional complications'.)

NEUROENDOCRINE TUMORS AND RELATED DISORDERS — Neuroendocrine tumors are rare causes of chronic diarrhea in children (table 1). When they do occur, they usually are associated with one of the following disorders:

Neurofibromatosis – Neurofibromatosis is relatively common and is suspected in children with multiple café-au-lait macules and neurofibromas. A small subset develop tumors that can result in secretory diarrhea, including gastrointestinal stromal tumors, carcinoid tumors, pheochromocytoma, gastrinomas, or somatostatinomas. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis", section on 'Gastrointestinal stromal tumors'.)

Neuroblastomas and ganglioneuroblastoma – Relatively well-differentiated forms of neuroblastomas may be associated with severe secretory diarrhea that is frequently associated with elevated levels of vasoactive intestinal polypeptide. (See "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)

Multiple endocrine neoplasia type 2b – This is an exceedingly rare autosomal dominant disorder characterized by ganglioneuromas, medullary thyroid cancer, and pheochromocytoma. The ganglioneuromas are associated with severe secretory diarrhea and flushing. (See "Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2".)

CONGENITAL CONDITIONS ASSOCIATED WITH BOWEL OBSTRUCTION — Partial bowel obstruction may present with chronic or intermittent diarrhea. The underlying mechanism probably includes dysmotility with small intestine bacterial overgrowth, which in turn causes mucosal injury and malabsorption and/or deconjugation of bile acids with maldigestion. (See 'Small intestinal bacterial overgrowth' below and 'Other' below.)

Congenital conditions that predispose to this complication include (table 1):

Chronic intestinal pseudo-obstruction — Chronic intestinal pseudo-obstruction is a rare disorder that presents during early infancy with severe constipation, abdominal distention, and dilated bowels, with intolerance to luminal feeds that usually requires parenteral nutrition. This disorder can be classified as myogenic (MIM #155310) or neurogenic (MIM #243180) with specific characteristics. Both forms are associated with severe, recurrent bouts of small bowel bacterial overgrowth that may be associated with episodic worsening of abdominal distension and diarrhea. (See "Chronic intestinal pseudo-obstruction: Etiology, clinical manifestations, and diagnosis".)

Hirschsprung disease — Hirschsprung disease is relatively common and results from failure of neural crest cell migration that leads to an absence of enteric ganglion from the rectum extending proximally. The resulting aganglionic segment of the colon fails to relax, causing a functional obstruction. Hirschsprung disease may lead to an associated enterocolitis with fever, abdominal distention, explosive diarrhea, and vomiting that can progress to toxic megacolon. Hirschsprung-associated enterocolitis can occur even after surgery for Hirschsprung disease and in children >6 months old. (See "Congenital aganglionic megacolon (Hirschsprung disease)" and "Emergency complications of Hirschsprung disease", section on 'Enterocolitis'.)

Intestinal malrotation with intermittent volvulus — Intestinal malrotation is a relatively common anatomical abnormality. In some cases, it leads to volvulus that usually presents early in life with sudden-onset emesis, rectal bleeding, and circulatory shock. An intermittent form of volvulus has also been described, which presents with episodic emesis and malabsorptive diarrhea.

OTHER MECHANISMS — Other causes of chronic diarrhea include (table 1):

Small intestinal bacterial overgrowth — Small intestinal bacterial overgrowth (SIBO) is a condition in which the small bowel is colonized by excessive aerobic and anaerobic microbes that are normally present in the colon. This can cause diarrhea by direct mucosal injury, production of enterotoxins, and/or maldigestion because of bile salt deconjugation. Typical symptoms include bloating, flatulence, abdominal discomfort, or watery diarrhea. The incidence of SIBO increases with age. Several disorders predispose to SIBO by altering mucosal defenses. (See "Small intestinal bacterial overgrowth: Clinical manifestations and diagnosis".)

Congenital diarrheas and enteropathies — Chronic diarrhea that presents in early infancy (<6 months) has a unique set of causes, as outlined in the table (table 3). These include congenital diarrheas and enteropathies, which are primarily inherited defects of epithelial function and typically present in the neonatal period. (See "Approach to chronic diarrhea in neonates and young infants (<6 months)".)

Other

Bile acid malabsorption – Bile acids secreted into the intestinal lumen are normally reabsorbed in the terminal ileum. In patients with ileal disease or resection, or those with genetic defects in bile acid transport (eg, MIM #613291), the malabsorbed bile acids enter the colon, where they can cause a secretory diarrhea (this is sometimes called cholerheic diarrhea). Treatment with cholestyramine prevents this process by sequestering bile acids. However, cholestyramine must be used judiciously since some patients may also have bile acid deficiency; in these patients, cholestyramine may bind the remaining bile salts necessary for fat and fat-soluble vitamin absorption, thereby creating additional unwanted nutritional complications.

Bile acid malabsorption diarrhea occasionally occurs after cholecystectomy. (See "Approach to the adult with chronic diarrhea in resource-abundant settings", section on 'Post-cholecystectomy diarrhea'.)

Protein-losing enteropathies – Protein-losing enteropathy is classically seen in the setting of severe mucosal inflammation and permeability, which may occur in erosive gastrointestinal diseases (inflammatory bowel disease [IBD] or C. difficile infection) or nonerosive disease (celiac disease or eosinophilic gastroenteritis) (table 4). Occasionally, it may be caused by impaired lymphatic drainage or after the Fontan procedure for congenital heart disease. (See "Management of complications in patients with Fontan circulation", section on 'Protein-losing enteropathy'.)

While chronic diarrhea is common in these conditions, significant protein-losing enteropathy may be present even in the absence of diarrhea. Other common features include peripheral edema, hypoalbuminemia, hypogammaglobulinemia, and, sometimes, lymphopenia. (See "Protein-losing gastroenteropathy".)

Factitious diarrhea – Factitious diarrhea may be due to a self-induced true increase in stool volume (eg, from surreptitious laxative abuse) or the creation of an apparent increase in stool volume by the addition of various substances (eg, urine, water) to the stool with the intention of misleading the health professional. Diagnosing factitious diarrhea is often difficult and requires alertness to this possibility and exclusion of other diseases and may be aided by specific testing (eg, stool osmolality or a laxative screen). (See "Factitious diarrhea: Clinical manifestations, diagnosis, and management".)

In children, factitious diarrhea may be contrived by the caregiver in a form of medical child abuse. (See "Medical child abuse (Munchausen syndrome by proxy)".)

Vasculitis – Vasculitides including polyarteritis nodosa or Behçet syndrome may be associated with chronic diarrhea. These disorders usually can be identified by their constitutional symptoms or signs, skin lesions, laboratory evidence of inflammation, and bloody diarrhea. (See "Vasculitis in children: Evaluation overview".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic diarrhea".)

SUMMARY

Definitions – Chronic diarrhea can be defined as daily stool weight of greater than 250 g in children that weigh more than 10 kg and greater than 20 g/kg/day in children that weigh less than 10 kg for longer than four weeks. In the outpatient clinical setting, changes in the frequency and consistency of stool compared with baseline can also be used as a convenient gauge of diarrhea. The Bristol stool chart is a reliable tool to define stool consistencies; diarrheal stools typically correspond to Bristol types 6 and 7. (See 'Definitions' above.)

Causes of chronic diarrhea in children – For clinical purposes, it is helpful to categorize chronic diarrhea by triggers and other clinical characteristics (table 1).

Common causes – Relatively common causes of chronic diarrhea in children include:

-Physiologic lactase nonpersistence (see 'Lactase nonpersistence' above)

-Gastrointestinal infections (especially postinfectious processes) (see 'Infection-related causes' above)

-Drug-induced diarrhea, eg, due to certain antibiotics, laxatives, and antineoplastic medications (table 2) (see 'Drug-induced causes' above)

-Functional disorders such as toddler's diarrhea and diarrhea-predominant irritable bowel syndrome (IBS-D) (see 'Functional diarrheal disorders' above)

-Immune-mediated causes such as celiac disease and inflammatory bowel disease (IBD) (see 'Immune-mediated causes' above)

Less common causes – Less common mechanisms for chronic diarrhea include other immune-mediated disorders, pancreatic exocrine insufficiency, and partial bowel obstruction due to chronic intestinal pseudo-obstruction or other congenital conditions. (See 'Fat malabsorption' above and 'Congenital conditions associated with bowel obstruction' above.)

Causes in young infants – Chronic diarrhea that presents in early infancy (<6 months) has a unique set of causes, which include anatomic defects and heritable disorders of immune regulation, macronutrient digestion, mucosal barrier function, and transport (table 3); these disorders are discussed in a separate topic review. (See "Approach to chronic diarrhea in neonates and young infants (<6 months)".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Richard Kellermayer, MD, PhD, and Robert Shulman, MD, who contributed to earlier versions of this topic review.

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Topic 5877 Version 43.0

References

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