4/21/2020 Approach to chronic diarrhea in children >6 months in resource-rich countries - UpToDate

Authors: Richard Kellermayer, MD, PhD, Robert J Shulman, MD

Section Editor: B UK Li, MD
Deputy Editor: Alison G Hoppin, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Mar 2020. | This topic last updated: Nov 04, 2019.

INTRODUCTION

In resource-rich countries, a wide variety of disorders cause chronic diarrheas in children. The
causes range from developmental and dietary factors (eg, excessive consumption of juice) to
diseases causing malabsorption or maldigestion, disordered immune regulation, or enteric
infections (particularly in immunocompromised patients) (table 1) [1,2].

In resource-limited settings, chronic diarrhea typically is associated with serial enteric infections
and malnutrition [3,4]. This common pathophysiology calls for a distinct algorithmic approach to
diagnosis and treatment, which is discussed separately. (See "Malnutrition in children in
resource-limited countries: Clinical assessment".)

The diagnostic approach to diarrheal diseases in resource-rich countries will be reviewed here.
The causes of these diarrheal diseases and the approach to chronic diarrhea in young infants
are discussed separately. (See "Overview of the causes of chronic diarrhea in children in
resource-rich countries" and "Approach to chronic diarrhea in neonates and young infants (<6
months)".)

DEFINITION

Diarrhea is defined as stool volume of more than 20 grams/kg/day in young infants, 10

grams/kg/day in infants and toddlers, or more than 200 grams/day in older children [5]. This
typically translates to symptoms of persistent loose or watery stools occurring at least three
times a day, where the change in stool consistency is more important than stool frequency [3]. To
be considered chronic, the symptom must be present for four weeks [6,7].

OVERVIEW

Selection of the appropriate strategy to diagnose the cause of chronic diarrhea in a child
depends on the age and presentation of the patient and, in some cases, the population setting

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(eg, the genetic predisposition of the population).

For children living in resource-rich countries, common causes of chronic diarrhea include celiac
disease and functional diarrhea. In young children (typically one to four years of age), functional
diarrhea, also known as chronic nonspecific diarrhea or "toddler's diarrhea," may be seen. In
older children and adolescents, lactose intolerance and functional diarrhea associated with
irritable bowel syndrome (further defined by pediatric Rome IV criteria) are seen frequently [7-
10]. Celiac disease and food allergy may present in any age group; the former can be evaluated
with a simple serologic screening test. (See 'Initial diagnostic approach' below.)

It is appropriate to consider these entities early in the evaluation before embarking on extensive
laboratory testing. In most cases, the initial evaluation consists of a thorough history and
physical examination, with serologic testing for celiac disease. If these steps do not establish a
diagnosis, then further laboratory or short-term dietary intervention testing can be selected
based on history, physical examination, and the stool type. This stepwise strategy is outlined
below (algorithm 1).

HISTORY AND EXAMINATION

The first step in evaluating chronic diarrhea is an abdominal examination and detailed history,
which often provide clues to the diagnosis or diagnostic category of the chronic diarrhea (table
2).

● Abdominal examination – In a child with a history of chronic diarrhea, the presence of acute
severe abdominal pain or abdominal distension raises the possibility of acute intestinal
obstruction or enterocolitis, particularly if blood is present in the stools. These symptoms call
for an urgent evaluation for obstruction, infection, or acute presentation of chronic
inflammatory bowel disease. (See 'Inflammation-induced' below.)

● Timing of onset

• Neonatal onset of watery diarrhea strongly suggests one of the congenital diarrheas;
the causes and evaluation are discussed separately. (See "Approach to chronic
diarrhea in neonates and young infants (<6 months)".)

• Abrupt onset of chronic diarrhea suggests that it was triggered by an infectious insult
(including postinfectious lactose intolerance or antibiotic-associated diarrhea). (See
"Overview of the causes of chronic diarrhea in children in resource-rich countries",
section on 'Infectious causes'.)

• Gradual onset of a mild chronic diarrhea in an otherwise healthy toddler suggests

functional diarrhea (chronic nonspecific diarrhea of childhood) [8]. (See "Overview of

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the causes of chronic diarrhea in children in resource-rich countries", section on

'Functional diarrhea'.)

• Many different patterns of onset are consistent with celiac disease. Symptoms may
develop within weeks or many years after gluten-containing foods are first introduced
into the diet and may be gradual, semi-acute, or intermittent. (See "Epidemiology,
pathogenesis, and clinical manifestations of celiac disease in children".)

• Diarrhea that has a consistent temporal relationship (eg, within 24 hours) to eating a
specific food may reflect lactose intolerance or food allergy. Food allergy may be either
immediate-type hypersensitivity (immunoglobulin E [IgE]-mediated) or delayed-type
hypersensitivity (non-IgE-mediated, such as food-induced enteropathy/proctocolitis).
(See "Clinical manifestations of food allergy: An overview", section on 'Gastrointestinal
manifestations'.)

• Medications should also be considered as more than 700 drugs are implicated in
causing diarrhea [11]. These include many antibiotics, acid-suppressant medications,
sugar substitutes, vitamin C, antineoplastic agents, and some antihypertensives.
Excessive administration of laxatives also should be considered.

● Stool characteristics

• Stools that become looser as the day progresses are typical of functional diarrhea.

• Diarrheal stools that are passed at night are more concerning for an underlying organic
disorder.

• Stools that contain visible or occult blood or mucus suggest an inflammatory diarrhea,
which may be caused by a dietary protein intolerance (common in infants),
inflammatory bowel disease, or (rarely) chronic infection with an enteric pathogen.
Visible or occult blood also may come from perianal lesions (including, rarely, obscure
perianal vascular injury) resulting from frequent bowel movements and or straining
during bowel movements. This is a common source for the visible blood on stool or on
the toilet paper after wiping.

• A history of small-volume fecal incontinence should prompt questions to determine if

occult constipation might be present. This is sometimes misinterpreted as diarrhea
[12,13]. (See "Functional fecal incontinence in infants and children: Definition, clinical
manifestations and evaluation".)

● Other symptoms

• A history of failure to thrive or weight loss suggests the possibility of malabsorptive

disease (celiac disease, cystic fibrosis, or other cause of pancreatic exocrine

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insufficiency), hyperthyroidism, or anorexia nervosa in the school-age child or

adolescent. Weight loss is also a common feature of inflammatory bowel disease [14].

• A history of recurrent infections suggests underlying immunodeficiency or cystic

fibrosis.

• Dyspepsia and vomiting may be related to several different underlying causes,

including unrecognized constipation [12,13,15].

● Family history – A family history of disease affecting the bowel may provide clues to
heritable diseases, but a negative family history does not exclude monogenic disorders or
diseases with genetic predisposition, such as celiac disease or inflammatory bowel disease.

INITIAL DIAGNOSTIC APPROACH

Exclude celiac disease — Given the high prevalence of celiac disease in most populations and
the availability of noninvasive, sensitive, and specific testing, all children with chronic diarrhea in
resource-rich countries should be screened for celiac disease.

We suggest screening with serum testing for immunoglobulin A antibodies against tissue
transglutaminase (IgA-tTG), which is highly sensitive, specific, and more cost-effective than
other antibody tests. Serum IgA level should be tested at the same time to avoid the possibility if
there is concern for IgA deficiency, which can cause a false-negative result [16]. False-positive
and false-negative results may still occur with some frequency in populations with a low risk for
celiac disease. (See "Diagnosis of celiac disease in children".)

Consider functional diarrhea — Children with functional diarrhea (sometimes called chronic
nonspecific diarrhea of childhood or toddler's diarrhea) typically present with the following
characteristics (which constitute the "Rome IV" diagnostic criteria) [7]:

● Daily painless, recurrent passage of four or more large, unformed stools

● Symptoms last more than four weeks
● Onset of diarrhea between 6 and 60 months of age
● No failure to thrive (if caloric intake is adequate)

Previous guidelines suggested that stools are passed only during waking hours [17]. However,
this is no longer considered a diagnostic criterion, because approximately 25 percent of children
with functional diarrhea pass stools while they are asleep [7]. After exclusion of celiac disease,
children with these characteristics can be given a provisional diagnosis of functional diarrhea.
Giardiasis should also be excluded in children with risk factors, including international adoptees,
international travelers, immunocompromised individuals, and those living in unsanitary
conditions. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis".)

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In some cases, functional diarrhea is caused by excessive intake of osmotically active

carbohydrates (eg, apple, prune, or pear juices; "sugar-free" foods containing sorbitol; or high
quantities of fructose) and/or restriction of fat from the diet [8,18]. If the diet history suggests this
possibility, we suggest an empiric trial of restricting juices and liberalizing dietary fat to 35 to 50
percent of total calories. Response to this dietary intervention supports the diagnosis of
functional diarrhea, and no further intervention is necessary. (See "Overview of the causes of
chronic diarrhea in children in resource-rich countries", section on 'Functional diarrhea'.)

In school-age children or adolescents, chronic diarrhea may be caused by lactose intolerance or

be a component of irritable bowel syndrome, which is a functional gastrointestinal disorder
characterized by chronic abdominal pain and changes in either stool consistency or frequency
[10]. (See "Chronic abdominal pain in children and adolescents: Approach to the evaluation",
section on 'Functional disorders'.)

SUBSEQUENT TESTING IF THE DIAGNOSIS REMAINS UNCLEAR

Testing according to stool type — If the diagnosis remains unclear after the above
maneuvers, the next step is to narrow the diagnostic possibilities with clues from the history and
by categorizing stool type.

The clinical appearance of the stool typically falls into categories that inform further diagnostic
testing (table 3). Thus, a first step in the evaluation of chronic diarrhea is to determine whether
the stool is watery, fatty, or inflammatory. Gross inspection of stool may be helpful, but laboratory
testing usually will be necessary to categorize the stool accurately. In some cases, the stool will
have a mixed appearance, requiring an evaluation that spans more than one category. As an
example, diarrheal diseases of infectious origin commonly have watery and inflammatory
components.

Watery — Many chronic diarrheas are watery in nature. If this is the case and the initial
evaluation suggests that functional diarrhea and celiac disease are unlikely, the next step is to
attempt to categorize the watery diarrhea into a diet-induced (osmotic) versus electrolyte
transport-related (secretory) type. Although these categories help to narrow the possible causes,
some diarrheal diseases involve a combination of both processes. (See "Pathogenesis of acute
diarrhea in children", section on 'Diarrhea classification'.)

Diarrhea can be characterized as a diet/substrate-induced (osmotic) or electrolyte transport-

related (secretory) mechanism by doing a trial of fasting and measuring fecal electrolytes, pH,
reducing substances, and calculation of the osmotic gap:

● Trial of fasting – Diarrhea that stops during a 12- to 24-hour trial of fasting is likely to be
diet/substrate-induced (osmotic), whereas diarrhea that persists during fasting suggests an
electrolyte transport-related (secretory) component.
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● Stool pH, electrolytes, and osmolarity – For watery stools, fecal electrolyte
concentrations and pH are measured in stool water after homogenization of a fresh
specimen (by manual stirring or in a mechanical blender) and centrifugation of an aliquot to
obtain supernatant for analysis. Fecal pH is measured with nitrazine paper on a fresh stool
sample.

The results can be used to calculate the osmotic gap, which reflects the relative
contributions of electrolytes and nonelectrolyte osmoles in the sample. The presence of
excessive nonelectrolyte osmoles suggests a diet/substrate-induced (osmotic) diarrhea
because these osmotic particles cause water retention in the intestinal lumen.

We prefer to calculate the osmotic gap from electrolyte concentrations in stool water using
the following formula:

Stool osmotic gap = 290 - 2([Na+] + [K+]) (table 4)

The osmotic gap is best calculated using the factor 290 (which is the expected osmolality of
freshly passed diarrheal stool) rather than measured stool osmolality because measured
stool osmolalities may be falsely elevated due to post-collection bacterial fermentation or to
contamination of the sample with concentrated urine.

● Reducing substances – The watery component of the stool should be tested for reducing
substances, which if present, suggest carbohydrate malabsorption. The test detects any
carbohydrate that can be metabolized into a reducing sugar, including glucose, lactose, and
fructose. Sucrose is not a reducing sugar, so malabsorbed sucrose does not cause a
positive result for reducing substances. However, malabsorbed sucrose also can be
degraded by colonic bacteria to glucose and fructose, resulting in a positive test for reducing
substances.

● Interpretation

• Diet/substrate-induced – Diet/substrate-induced (osmotic) diarrhea improves or

resolves during a trial of fasting and is usually driven by an unabsorbed dietary
carbohydrate. It is characterized by relatively low sodium concentration (<70 mEq/L)
and a high osmotic gap (>75 mOsm/kg [19]) (table 4). This type of diarrhea typically is
less voluminous than secretory diarrhea (eg, <200 mL/day). The presence of reducing
substances or low fecal pH (ie, pH <6) suggest carbohydrate malabsorption (algorithm
2A).

• Electrolyte transport-related – Electrolyte transport-related (secretory) diarrhea

usually is associated with large volumes of watery stools and persists during fasting as
it is driven by electrolyte secretion by intestinal mucosa [1]. The osmotic gap is

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generally <50 mOsm/kg. A low osmotic gap also may be caused by contamination of
the stool sample with dilute urine or water.

Pure electrolyte transport-related diarrheas are uncommon but can occur in the setting
of certain enteric infections (eg, cholera and enterotoxigenic Escherichia coli), some
congenital diarrheas, and some neuroendocrine tumors (algorithm 2B). Enteric
infections typically cause acute diarrhea but may become persistent if mucosal injury
causes a postinfectious lactose intolerance. Electrolyte transport-related diarrhea also
may be caused by excessive bile acids entering the colon (cholerheic diarrhea), which
can occur in patients with ileal resection or disease. (See "Overview of the causes of
chronic diarrhea in children in resource-rich countries".)

• Mixed – Diarrheas with mixed diet/substrate-induced and electrolyte transport-related

mechanisms often have intermediate osmotic gaps: between 50 and 75 mOsm/kg.
These can be associated with a number of bacteria and viruses and even chronic
inflammatory disorders, such as inflammatory bowel disease (where chronic
inflammation can lead to mucosal malabsorption). (See 'Inflammation-induced' below.)

Inflammation-induced — Chronic diarrhea with gross or occult blood in the stool suggests
an inflammatory diarrhea (algorithm 2C). Inflammation-induced diarrhea can be confirmed by the
finding of elevated fecal calprotectin.

● Fecal calprotectin – Fecal calprotectin levels are increased in intestinal inflammation and
often are useful for distinguishing inflammatory from noninflammatory causes of chronic
diarrhea. However, test characteristics vary depending on the prevalence of inflammatory
bowel disease in the study population. Thus, the test may be used to focus the next stage of
the investigation, but results should not be interpreted to firmly include or exclude any
disease or disease category. (See "Approach to the adult with chronic diarrhea in resource-
rich settings", section on 'General laboratory tests'.)

If fecal calprotectin is elevated, further evaluation is indicated to determine whether the

cause is infectious or related to a chronic inflammatory disease (eg, dietary protein
intolerance or inflammatory bowel disease). (See 'Specific testing' below.)

● Occult blood – Occult blood in the stool also raises the possibility of an inflammation-
induced diarrhea (eg, inflammatory bowel disease, enteric infection, or food protein-induced
proctocolitis), but this test is less specific than calprotectin. As an example, a substantial
number of individuals with diarrhea due to rotavirus infection also test positive for occult
fecal blood. This may be caused by dermal blood from skin breakdown or anal fissures
rather than intestinal inflammation. Functional diarrhea or diarrhea caused by laxative abuse
is less likely to contain occult blood. The American Gastroenterological Association (AGA)
technical review on the evaluation and management of chronic diarrhea (including a

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discussion on occult blood) [20], as well as other AGA guidelines, can be accessed through
the AGA website.

If the stools contain substantial amounts of gross blood but fecal calprotectin is normal, the
patient may have a noninflammatory source of blood in the gastrointestinal tract (eg, Meckel's
diverticulum, anal fissures, or perianal excoriations). (See "Lower gastrointestinal bleeding in
children: Causes and diagnostic approach".)

Fatty — Patients with fatty-appearing stools should be further evaluated by a test to detect fat
malabsorption (steatorrhea). A variety of tests can be used for this purpose, but all have limited
sensitivity and specificity.

● Quantitative testing for fecal fat – The gold standard for diagnosis of steatorrhea is
quantitative estimation of stool fat, usually performed over 72 hours, while the patient eats a
diet containing at least 100 grams of fat per day. (See "Approach to the adult patient with
suspected malabsorption", section on 'Stool tests for fat malabsorption'.)

● Qualitative testing for fecal fat – Because 72-hour stool collection is cumbersome, and
especially difficult for a non-toilet-trained toddler, qualitative tests also are used as a
screening tool to detect steatorrhea. These include the Sudan III stain and acid steatocrit, a
rapid gravimetric method. The utility of the Sudan III test is limited by variability in its
performance and interpretation; one study reported a sensitivity of 77 percent and specificity
of 98 percent for this method [21]. The acid steatocrit is rarely available in clinical
laboratories.

Quantitative and qualitative fecal fat tests are reasonably accurate in patients with severe fat
malabsorption caused by pancreatic insufficiency or bile acid secretory defects. Tests of fecal fat
have low sensitivity and specificity for patients with other diarrheal diseases. Thus, these tests
may be used as diagnostic clues to determine the order of an evaluation but are not sufficient to
definitively confirm or exclude fat malabsorption. (See "Clinical manifestations and diagnosis of
chronic and acute recurrent pancreatitis in children".)

Fat malabsorption may be caused by either mucosal disease (ie, loss of absorptive surface area)
or pancreatic insufficiency (ie, insufficient digestion of nutrients). All patients with fatty-appearing
diarrhea should be screened for celiac disease. If fecal fat testing is positive or there is a high
suspicion of fat malabsorption, patients should also be evaluated for specific causes of
pancreatic insufficiency, including cystic fibrosis and Shwachman-Diamond syndrome (algorithm
2D). (See 'Specific testing' below.)

Specific testing — Following the initial categorization of the diarrhea, the differential diagnosis
becomes more manageable and a more focused series of investigations can be pursued (table
3) [20]. Infectious and structural diseases that are consistent with the patient's history should be
excluded first. Consecutively, specific tests guided by the initial categorization should be
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performed, followed by endoscopy and genetic testing if necessary to confirm the diagnosis and
aid management (algorithm 2A-D).

Additional specific testing may be performed based on patient characteristics and/or the
diagnostic considerations raised by the categorization steps outlined below. Clinical suspicion of
the following disease processes calls for specific testing:

● Inflammatory bowel disease – Suggested by grossly bloody stools, growth failure, or family
history of inflammatory bowel disease. Measure complete blood count, serum albumin, C-
reactive protein (CRP), and fecal tests (calprotectin or lactoferrin) for inflammation. Perform
contrast radiography of the small bowel (or magnetic resonance imaging [MRI]), and upper
and lower endoscopy depending on degree of clinical suspicion. (See "Clinical presentation
and diagnosis of inflammatory bowel disease in children".)

● Protein-losing gastroenteropathy – Suggested by reduced serum concentrations of albumin

and gamma globulins or peripheral edema. Perform fecal alpha-1 antitrypsin testing to
measure fecal protein losses. (See "Protein-losing gastroenteropathy".)

● Pancreatic insufficiency – Suggested by marked steatorrhea or other findings that suggest a

disorder associated with pancreatic insufficiency, including:

• Cystic fibrosis – Suggested by pulmonary symptoms, failure to thrive, or family history

of disease. Perform sweat chloride testing (see "Cystic fibrosis: Clinical manifestations
and diagnosis")

• Shwachman-Diamond syndrome – Suggested by neutropenia or bone marrow failure,

exocrine pancreatic insufficiency, and skeletal abnormalities (see "Shwachman-
Diamond syndrome")

Perform indirect tests of pancreatic function, including measurement of fecal elastase-1

and/or chymotrypsin; the stool content of these enzymes is reduced in patients with
pancreatic insufficiency. The diagnostic accuracy of these tests is low and is discussed in
greater detail separately. (See "Exocrine pancreatic insufficiency".)

● Factitious diarrhea – Suggested by a history suspicious for laxative abuse, the presence of
hypokalemia or metabolic alkalosis, or elevated magnesium (>90 mEq/L) or phosphorus
(>33 mmol/L) in the stool. Perform a laxative screen if available and measure the stool
osmolality. The measured stool osmolality is elevated in the presence of osmotically active
laxatives (>290 mOsm/kg). However, the osmolality also may be reduced (<290 mOsm/kg)
if the sample is contaminated with water or dilute urine; this finding may indicate intentional
dilution of the sample. (See "Factitious diarrhea: Clinical manifestations, diagnosis, and
management".)

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● Giardiasis – Giardiasis is the most common enteric parasitic infection in the United States. It
can be asymptomatic or can cause chronic diarrhea, typically without blood and sometimes
with malaise, nausea, and weight loss. In areas where the parasite is prevalent or when
patients have visited endemic areas, test the stool for Giardia antigen. (See "Giardiasis:
Epidemiology, clinical manifestations, and diagnosis".)

TREATMENT CONSIDERATIONS

In general, treatment for chronic diarrhea is directed at the specific cause, once it is established
(see "Overview of the causes of chronic diarrhea in children in resource-rich countries"). A few
general approaches are discussed below.

Malnutrition — Chronic diarrhea associated with impaired growth and/or nutritional status
should always be considered a serious disease in infants, and therapy should be promptly
started [22]. Sufficient calories should be provided to allow for catch-up weight gain. When oral
intake is inadequate or malabsorption precludes the necessary intake, continuous enteral
feedings or parenteral nutrition may be required. Parenteral nutrition should be undertaken as
soon as other, less invasive nutritional approaches have been shown to be unsuccessful.

Micronutrient and vitamin supplementation are part of nutritional rehabilitation. Children with
chronic diarrhea and malnutrition are often deficient in vitamin A, zinc, folic acid, copper, and
selenium [23]. Deficiencies in these micronutrients can impair the function of the immune system
and have a direct effect on the structure and function of mucosa. Zinc deficiency is a particular
risk because of increased losses through the gastrointestinal tract during episodes of diarrhea,
and empiric replacement of zinc is recommended for children with diarrhea and malnutrition. In
resource-rich settings, nutritional rehabilitation can be accomplished by empiric supplementation
with these micronutrients via food or supplements, and selective testing and replacement if a
specific deficiency is suspected. (See "Micronutrient deficiencies associated with malnutrition in
children".)

Management of malnutrition with chronic diarrhea in resource-limited settings is discussed in

separate topic reviews. (See "Malnutrition in children in resource-limited countries: Clinical
assessment" and "Management of moderate acute malnutrition in children in resource-limited
countries" and "Management of uncomplicated severe acute malnutrition in children in resource-
limited countries" and "Management of complicated severe acute malnutrition in children in
resource-limited countries".)

Diet — When lactose intolerance, sucrase deficiency, and/or food allergy or food-protein-
induced enteropathy/proctocolitis is suspected, we suggest excluding the suspected offending
food from the diet for 7 to 10 days. If possible, the family should keep a dietary record before and
after the dietary change to assure compliance. A lactose breath hydrogen test usually is not

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helpful, because many individuals have lactose malabsorption (ie, elevated breath hydrogen
indicative of malabsorption) but do not have lactose intolerance (ie, clinical symptoms such as
bloating, diarrhea, or abdominal pain).

A trial of avoiding lactose in school-age children may be appropriate if postinfectious diarrhea is

suspected (eg, onset of chronic diarrhea after an acute gastrointestinal illness). Postinfectious
diarrhea is often mediated or exacerbated by lactose intolerance, which typically resolves with
time.

Medications

Probiotics — Many diarrheal diseases are associated with alterations in the intestinal
microbiota. An attempt at modifying this altered bacterial population may be worth considering,
even when an infectious cause is suspected but not proven. Randomized studies and meta-
analyses have demonstrated modest efficacy of specific probiotics in the prevention of
Clostridioides (formerly Clostridium) difficile-associated diarrhea (eg, Saccharomyces boulardii
or Lactobacillus acidophilus plus Lactobacillus casei at a dose of 10 to 50 billion colony-forming
units [CFUs] per day) [24] and possibly for treatment of acute gastroenteritis [25-28]. Most
studies of probiotics in treating acute gastroenteritis in children are limited by small sample size
and other issues, making it hard to make firm recommendations regarding their use [28]. There
is limited evidence that probiotics are effective in treating chronic pediatric diarrhea [29]. (See
"Probiotics for gastrointestinal diseases".)

Antidiarrheal drugs — We do not recommend the use of antimotility drugs for children with
chronic diarrhea, except in unusual circumstances to facilitate fluid management when the cause
of the diarrhea has been established (eg, irritable bowel syndrome) and the medication is
administered under careful supervision.

Loperamide and diphenoxylate-atropine may improve symptoms in children with severe and
protracted diarrhea, but these agents have important side effects, including sedation and risk for
toxic megacolon. For example, these agents may prolong excretion of the organism or increase
the risk of developing hemolytic-uremic syndrome in patients with enterohemorrhagic E. coli.
(See "Shigella infection: Treatment and prevention in children" and "Treatment and prognosis of
Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children".)

Somatostatin — In severe secretory diarrheas, for instance (such as in neuroendocrine

tumors, chemotherapy-induced diarrhea, microvillous inclusion disease, and enterotoxin-induced
severe diarrhea), a trial with somatostatin or its analog octreotide may be considered [30,31].
Octreotide has been used in diarrhea caused by neoplastic diseases and in intestinal infections.
It also has been shown to be effective in reducing fecal output in HIV-infected children with
severe cryptosporidiosis. In vitro tests have shown that octreotide has a specific antagonist

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effect against the enterotoxin associated with Cryptosporidium [32]. (See "Management of acute
chemotherapy-related diarrhea".)

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 AND RECOMMENDATIONS

● A wide variety of problems can cause chronic diarrhea in infants and children, including
functional and infectious causes as well as heritable disorders of immune regulation,
macronutrient digestion, mucosal barrier function, and transport (table 1). (See 'Overview'
above and "Overview of the causes of chronic diarrhea in children in resource-rich
countries".)

● To establish a diagnosis within this diverse set of disorders, an algorithmic approach is

helpful (algorithm 1). The first step is a detailed history, which may provide clues to the
diagnosis or diagnostic category (table 2). (See 'History and examination' above.)

● We suggest serologic testing for celiac disease for all children with chronic diarrhea,
provided that their diet contains gluten. (See 'Exclude celiac disease' above.)

● Functional diarrhea accounts for a high proportion of chronic diarrheas in young children.
For children with characteristics typical of functional diarrhea, we suggest a diagnostic trial
of restricting juices and liberalizing dietary fat. (See 'Consider functional diarrhea' above.)

● If the diagnosis is not clear after the above steps, categorizing the diarrhea by stool type will
narrow the diagnostic possibilities and inform the order of further testing (table 3). A
stepwise approach for each stool type is outlined in the algorithms (algorithm 2A-D). (See
'Testing according to stool type' above.)

● Regardless of the cause of the diarrhea, evaluation for and treatment of malnutrition is an
important step in recovery. (See 'Malnutrition' above.)

● We suggest NOT treating children with chronic diarrhea with antidiarrheal drugs such as
loperamide and diphenoxylate-atropine (Grade 2B). In unusual circumstances in which the
cause of the diarrhea has been established, these drugs may be used cautiously to assist
with fluid management and to improve quality of life. There is only limited evidence that
probiotics may provide benefit for treating chronic diarrhea in children. (See 'Medications'
above.)

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