3/19/23, 10:20 AM Approach to chronic diarrhea in children >6 months in resource-rich countries - Uptodate Free

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Approach to chronic diarrhea in children >6

months in resource-rich countries
Approach to chronic diarrhea in children >6 months in resource-rich countries
Authors:
Martin G Martin, MD, MPP
Jay R Thiagarajah, MD, PhD
Section Editor:
B UK Li, MD

Deputy Editor:
Alison G Hoppin, MD

Literature review current through: Dec 2022. | This topic last updated: Mar 28, 2022.

INTRODUCTION — Although diarrhea is among the most common

ailments affecting children, chronic diarrhea is unusual in resource-rich countries. Chronic
diarrhea can be caused by a wide variety of disorders, ranging from an intolerance to a
specific food (or component, eg, lactose) to a symptom of a broader multisystem condition.
Many children with mild or intermittent symptoms can ultimately be classified as having
functional diarrhea after an appropriate clinical evaluation.

This review describes a clinical approach to evaluating children with chronic diarrhea that
first presents after six months of age. Other aspects of chronic diarrhea in children are
presented separately:

●(See "Overview of the causes of chronic diarrhea in children in resource-rich settings".)

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●(See "Approach to chronic diarrhea in neonates and young infants (<6 months)".)
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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 indicator of diarrhea. Thus, diarrhea can be defined by one or
both of the following measures:

•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 helps define stool consistencies [1-3]. Diarrheal
stools typically correspond to types 6 and 7 on the Bristol stool chart [4]. However, if the
stool volume is low, isolated loose stools are not a significant predictor of underlying
disease in the absence of weight loss, dehydration, or significant changes in
biochemical/nutritional indicators [5].

●Chronic diarrhea – Chronic diarrhea is generally defined as diarrhea lasting more 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 – Persistent diarrhea is sometimes defined as diarrhea lasting longer

than two weeks, but, other times, this term is used interchangeably with chronic diarrhea.

OVERVIEW OF THE CAUSES OF CHRONIC

DIARRHEA IN CHILDHOOD — The causes of chronic diarrhea in
children are shown in the table, grouped by the underlying mechanism (table 1). These
include several common and benign causes, including excessive sugar intake; physiologic
lactase nonpersistence (hypolactasia); diarrhea-predominant irritable bowel syndrome (IBS-
D); and drug-induced, infectious, and postinfectious diarrheas. Other less common causes
include immune-mediated conditions, alterations in pancreatic function, and
neuroendocrine abnormalities. These causes are discussed in more detail in a separate
topic review. (See "Overview of the causes of chronic diarrhea in children in resource-rich
settings".)

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INITIAL EVALUATION — Chronic diarrhea is typically evaluated

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outpatient setting. Selected patients with warning signs may require more extensive or
urgent evaluation, sometimes in the inpatient setting.

Warning signs — The first step is to identify any warning signs or symptoms

suggesting a rapidly progressive or severe systemic disorder (table 2). Children with
warning signs may require hospital admission and an expedited evaluation. Key warning
signs are:

●Fever

●Gross blood in stool

●Growth faltering or weight loss

●Nausea, vomiting

●Severe abdominal distension or tenderness

●Hepatosplenomegaly or mass

History and physical examination — The next step is to perform a

focused history (table 3) and physical examination (table 4) to investigate common causes of
chronic diarrhea.

Initial laboratory testing — In addition, perform basic laboratory

screening:

●Celiac disease – All children with chronic diarrhea should be screened for celiac disease by
measuring immunoglobulin A antibodies to tissue transglutaminase antibodies (tTg-IgA),
usually in conjunction with total IgA to exclude the possibility of IgA deficiency. This screen
is only valid if the child's diet includes gluten. (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".)

●Other tests – Other tests depend on the child's presenting characteristics and prior
testing, as outlined in the table (table 5). For most children, we include a complete blood
count and fecal calprotectin or lactoferrin at this stage of the workup, often with stool
cultures and Clostridioides difficile testing if not already done.

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PROVISIONAL DIAGNOSIS AND INITIAL Your activity: 7 p.v.

MANAGEMENT — After the above evaluation, the cause of the diarrhea

usually can be narrowed to one of the following categories (algorithm 1):

Celiac disease — A provisional diagnosis of celiac disease can be made based on

positive IgA antibodies to tissue transglutaminase antibodies (tTG-IgA). Further evaluation is
required to confirm the diagnosis. (See "Diagnosis of celiac disease in children".)

Inflammatory diarrhea — Inflammatory diarrhea is likely if there is gross

blood in the stool and is further confirmed by testing the stool for calprotectin or
lactoferrin. Patients with inflammatory diarrhea should be further evaluated for (algorithm
2):

●Infection – Children with inflammatory diarrhea should also be evaluated for enteric
pathogens (including Giardia lamblia) and C. difficile toxin. Several enteric pathogens cause
acute inflammatory diarrhea, but these infections are rarely chronic unless the patient is
immunocompromised. (See "Overview of the causes of chronic diarrhea in children in
resource-rich settings", section on 'Persistent or recurrent infection'.)

●Inflammatory bowel disease (IBD) – Children with inflammatory diarrhea should also be
evaluated for IBD, starting with a clinical evaluation and basic laboratory screening,
including a complete blood count, erythrocyte sedimentation rate or C-reactive protein, and
albumin. Children with abnormal results suggesting IBD or severe symptoms should
undergo a full evaluation, including small bowel contrast radiographs, colonoscopy, and
upper endoscopy. (See "Clinical presentation and diagnosis of inflammatory bowel disease
in children".)

Drug-related diarrhea — A history that the onset of diarrhea coincided with

antibiotic or other drug use should prompt consideration of diarrhea due to drug side
effect. The initial evaluation should include an empiric trial of drug removal/dose reduction
if possible. Drugs that are commonly associated with diarrhea are summarized in the table
(table 6) and discussed separately. (See "Overview of the causes of chronic diarrhea in
children in resource-rich settings", section on 'Drug-induced causes'.)

Diet-induced diarrhea — Diet-induced diarrhea refers to diarrhea that is

caused or exacerbated by osmotic load in the intestinal lumen. The primary cause may be a
specific dietary component or impaired digestion and absorption of nutrients, including
food protein-induced intestinal injury (algorithm 3).

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Clues that diarrhea is diet induced (ie, related to the osmotic load in the intestinal lumen)
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include mild or moderate severity and predominantly postprandial pattern. Conversely,
diarrheal symptoms that persist while asleep (nocturnal diarrhea) suggest that a
component of the watery stools is secondary to abnormal electrolyte absorption and
intestinal secretion and less dependent on the osmotic load provided by luminal nutrients.
One exception is that young children with functional diarrhea sometimes have very low-
volume nocturnal episodes of diarrhea.

Supportive evidence from the dietary history may include (table 3):

●Onset coincided with a change in diet, such as changing from formula to unmodified cow's
milk or calorically denser formulas or an increase in dietary sugars.

●Excessive consumption of fruit juice or other source of simple sugars (fructose) or poorly
absorbed carbohydrates (sorbitol or xylitol) and/or episodes of diarrhea coincide with
ingesting certain foods, including lactose or common allergens.

●Diarrheal symptoms associated with the consumption of sucrose (and/or starch) may be
attributable to congenital sucrase-isomaltase deficiency [7,8]. Although this defect is
present from birth, it does not become apparent until sucrose or starches are introduced
into the diet (eg, in some infant formulas or in solid foods introduced in later infancy).

●Unexplained aversion to certain foods that most children like.

If a dietary trigger seems likely, initial testing should include an empiric dietary elimination
trial and, potentially, a more detailed diet history and food diary. Specifically, a brief two- to
three-day trial of a low-lactose diet should be routinely suggested because new-onset
lactose intolerance is a common cause of chronic diarrhea in school-aged children; this may
be physiologic lactase nonpersistence (hypolactasia) or postinfectious. (See 'Dietary
changes' below.)

Postinfectious diarrhea — Diarrhea that began abruptly after an acute

enteric infection is often related to residual mucosal damage, causing temporary loss of
lactase and other abnormalities that cause malabsorption. Therefore, postinfectious
diarrhea often has a diet-induced component (eg, exacerbated by lactose). (See "Overview
of the causes of chronic diarrhea in children in resource-rich settings", section on
'Postinfectious malabsorptive diarrhea'.)

Functional diarrhea — A functional gastrointestinal disorder is likely if the

above causes are ruled out and if the symptoms are mild or intermittent.

●In young children, mild or intermittent diarrhea that is otherwise unexplained is often
considered functional, although it may be exacerbated by excessive fructose or sorbitol
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consumption [9,10]. This pattern is common in this age group and is sometimes known as
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"toddler's diarrhea." A selective dietary elimination plan to limit the child's intake of fructose
and sorbitol (primarily in fruit juices) often improves the symptoms and serves to confirm
the diagnosis [11]. (See 'Dietary changes' below and "Overview of the causes of chronic
diarrhea in children in resource-rich settings", section on 'Functional diarrhea in young
children'.)

●In older children, a functional diarrheal disorder (termed irritable bowel syndrome, or IBS-
D) is suggested by the presence of inconsistent, intermittent, and/or mild symptoms;
abdominal pain; and no evidence of systemic disease or warning signs. The focus should
shift to empiric management trials with diet or, occasionally, with medications. (See
"Overview of the causes of chronic diarrhea in children in resource-rich settings", section on
'Diarrhea-predominant irritable bowel syndrome'.)

Patients and their caregivers should be counseled regarding the benign nature of functional
disease. Clinical care should be focused on symptom management and on restoring a
balanced diet (if the diet has been restricted), as well as function and quality of life [12]. (See
"Functional abdominal pain in children and adolescents: Management in primary care".)

FURTHER TESTING IF THE DIAGNOSIS IS

UNCLEAR — If the etiology of the diarrhea remains unclear and the diarrhea is
severe or has features suggesting a pathogenic (rather than functional) disorder (table 1),
further evaluation may include (table 5):

●Endoscopic evaluation – Endoscopic evaluation of the upper gastrointestinal tract and/or

colon with biopsies may provide useful insight into the cause of the diarrhea.

Key findings on endoscopic biopsies include the architecture and relative compositions of
epithelial and immune cells and evidence of inflammation. As an example, celiac disease is
characterized by duodenal biopsies with shortened villi, long crypts, and expanded numbers
of intraepithelial lymphocytes. Inflammatory bowel disease (IBD) is characterized by diffuse
or patchy inflammation, often with ulceration. Several rare disorders may be diagnosed on
endoscopy, including eosinophilic gastroenteritis, microscopic colitis, cutaneous and
systemic forms of mastocytosis, and polyglandular autoimmune syndrome. (See "Overview
of the causes of chronic diarrhea in children in resource-rich settings", section on 'Immune-
mediated causes'.)

●Mucosal enzyme tests – In children with diet-induced diarrhea that remains unexplained
after a focused history and dietary trials, endoscopic small bowel mucosal biopsy samples
can be used to measure mucosal enzymes (lactase, sucrase, maltase, isomaltase
[palatinase], and glucoamylase enzyme activity). The results can support the diagnosis of

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primary or secondary lactase and/or sucrase-isomaltase deficiency [13]. However, the

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sensitivity and specificity of these tests is limited, likely due to inadequate sampling and/or
degradation during storage or processing.

●Breath tests – Lactase deficiency (eg, postinfectious or physiologic lactase

nonpersistence) and congenital sucrase-isomaltase deficiency are usually diagnosed
clinically but also may be diagnosed or confirmed by hydrogen breath testing [9]. Small
intestine bacterial overgrowth (SIBO) is primarily a clinical diagnosis based on the presence
of risk factors (eg, dysmotility or anatomic abnormalities that predispose to stasis) with
suggestive signs and symptoms (steatorrhea, abdominal bloating, and macrocytic anemia
due to vitamin B12 deficiency); lactulose breath testing may be used to support the
diagnosis but is not a definitive test. (See "Small intestinal bacterial overgrowth: Clinical
manifestations and diagnosis".)

●Tests for fat malabsorption – Testing for fat malabsorption and pancreatic exocrine
function is warranted for patients with steatorrhea or fat-soluble vitamin deficiencies or
conditions associated with pancreatic insufficiency. (See "Overview of the causes of chronic
diarrhea in children in resource-rich settings", section on 'Fat malabsorption'.)

•Mechanisms – Fat malabsorption may be caused by (table 1):

-Mucosal disease or short bowel syndrome (ie, loss of absorptive surface area)

-Pancreatic insufficiency

-Bile acid insufficiency (eg, due to lack of reabsorption in the terminal ileum or bile salt
deconjugation)

•Tests – Several tests may be used to assess the severity and cause of fat malabsorption:

-Qualitative (spot) fecal fat is a valuable screening test. Elevated neutral fats (increased
mono-, di-, or triglycerides) indicate fat maldigestion, which is usually due to pancreatic
enzyme deficiency or occasionally due to bile acid deficiency. Elevated split fats (free fatty
acids) suggest impaired intestinal fat absorption due to mucosal injury (eg, celiac disease)
or loss of mucosal surface (eg, short bowel syndrome).

-Quantitative measurement of fat in the stool is more sensitive but cumbersome and
difficult to perform accurately, especially in infants and toddlers.

-Fecal elastase is also an index of pancreatic exocrine function and is commonly used to
assess pancreatic insufficiency in patients with cystic fibrosis. However, falsely abnormal
fecal elastase is common in other diarrheal conditions and does not necessarily indicate
abnormal pancreatic exocrine function.

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-A secretin stimulation test is a direct test of pancreatic function that is performed during
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endoscopy at large institutional centers. However, this test is rarely used.

●Tests for bile acid malabsorption – Risk factors for bile acid-induced diarrhea (cholerheic
diarrhea) include terminal ileal disease or resection, after cholecystectomy, or SIBO due to
deconjugation of the bile salts by small intestinal bacteria. The diagnosis of bile acid
malabsorption is supported by elevated serum C4 bile acid levels and/or responsiveness to
a trial of cholestyramine. (See "Overview of the causes of chronic diarrhea in children in
resource-rich settings", section on 'Bile acid insufficiency' and "Approach to the adult with
chronic diarrhea in resource-abundant settings", section on 'Post-cholecystectomy
diarrhea'.)

●Neuroendocrine tumors – The possibility of a submucosal neuroendocrine tumor should

be considered in a child with predisposing conditions, which include neuroblastomas,
neurofibromatosis, and multiple endocrine neoplasia type 2B. A subset of neuroblastomas
secrete vasoactive intestinal peptide (VIP) and are classified as VIPomas (VIP-secreting
tumors). The diarrhea caused by these tumors is usually high volume and persists during
fasting, indicating that the underlying mechanism is abnormal electrolyte absorption or
secretion (sometimes called "secretory diarrhea").

Patients with these characteristics may be screened with urinary catecholamines and serum
VIP. Radiographic, pathologic, and genomic approaches may be used to establish the
diagnosis. (See "Overview of the causes of chronic diarrhea in children in resource-rich
settings", section on 'Neuroendocrine tumors and related disorders'.)

●Testing for immune-mediated disorders – Autoimmune enteropathies and primary

immunodeficiencies (eg, common variable immunodeficiency [CVID]) are rare disorders that
usually result in chronic diarrhea in children. CVID generally presents after puberty,
although certain forms may present earlier (eg, LRBA deficiency) [14]. Autoimmune
enteropathies can present at any age; when they present in early infancy, they must be
distinguished from primary immunodeficiencies. (See "Approach to chronic diarrhea in
neonates and young infants (<6 months)", section on 'Congenital diarrheas and
enteropathies' and "Autoimmune lymphoproliferative syndrome (ALPS): Clinical features
and diagnosis", section on 'LRBA deficiency disease'.)

These disorders may be suspected in a child with recurrent and/or unusual infections.
Measurement of quantitative serum immunoglobulins and assessment of T and B cell
function are helpful, but these patients require pathologic and genomic approaches to
better characterize the condition. (See "Overview of the causes of chronic diarrhea in
children in resource-rich settings", section on 'Persistent or recurrent infection' and
"Approach to the child with recurrent infections".)

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●Evaluation for bowel obstruction – Patients with severe abdominal distension and/or
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intermittent vomiting may have partial bowel obstruction; causes include chronic intestinal
pseudo-obstruction, Hirschsprung disease, or intestinal malrotation with intermittent
volvulus. Evaluation for these disorders starts with a conventional radiograph and may
include contrast studies and/or motility testing. (See "Overview of the causes of chronic
diarrhea in children in resource-rich settings", section on 'Congenital conditions associated
with bowel obstruction'.)

●Targeted DNA sequencing – The majority of monogenic disorders associated with chronic
diarrhea in children present during the first several months of life (table 7). However, several
inherited disorders can develop chronic diarrhea after six months of age, either because of
the delay in introducing the offending nutrient (eg, congenital sucrase-isomaltase
deficiency) or because of the normal delay in the manifestation of the condition (eg,
neurofibromatosis or hypolactasia). (See "Approach to chronic diarrhea in neonates and
young infants (<6 months)".)

TREATMENT CONSIDERATIONS — In general, treatment for

chronic diarrhea is directed at the specific cause (see "Overview of the causes of chronic
diarrhea in children in resource-rich settings"). 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 young
children, and therapy should be initiated promptly [15]. 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 [16]. 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 chronic diarrhea, and empiric replacement of zinc is recommended for children with
diarrhea and malnutrition. Zinc deficiency may also impair mucosal recovery as well as
appetite, further exacerbating growth failure.

In resource-rich settings, nutritional rehabilitation can be accomplished by empiric

supplementation with these micronutrients via food or supplements, as well as selective
testing and replacement if a specific deficiency is suspected. In resource-limited settings,
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empiric zinc supplementation is recommended for children with acute or persistent

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diarrhea. (See "Micronutrient deficiencies associated with malnutrition in children" and
"Zinc deficiency and supplementation in children", section on 'Treatment of acute or
persistent diarrhea'.)

Dietary changes — The approach to dietary changes depends upon the

suspected mechanism:

●Dietary sugars – When fructose, sorbitol, sucrose, or lactose intolerance is suspected, we

suggest a trial of avoiding the suspected carbohydrate for at least two days.

Lactose intolerance is the most common, and management focuses on dietary lactose
restrictions and/or the use of over-the-counter lactase enzyme preparations. The child's diet
should be reviewed to ensure adequate intake of calcium and vitamin D, using supplements
if necessary to support bone health. (See "Lactose intolerance and malabsorption: Clinical
manifestations, diagnosis, and management".)

Congenital sucrase-isomaltase deficiency may be managed by dietary restriction of sucrose,

starch, and artificial sweeteners [7,8]. Alternatively, a sucrase enzyme preparation may be
used when it is impossible to avoid dietary sucrose. Given the complexity of such a diet, the
family should work closely with a dietician.

●Postinfectious diarrhea – For school-aged children with suspected postinfectious

diarrhea (eg, the persistence of chronic diarrhea after an acute gastrointestinal illness), a
trial of avoiding lactose may be helpful. Postinfectious diarrhea is often mediated or
exacerbated by lactose intolerance, which typically resolves with time.

●Proctocolitis of infancy – For infants with loose stools (typically with gross blood) who are
otherwise healthy, a common cause is food protein-induced proctocolitis of infancy,
sometimes known as food-protein intolerance. The most common food triggers are cow's
milk, egg, and soy. Symptoms gradually improve when the offending protein is eliminated.
(See "Food protein-induced allergic proctocolitis of infancy".)

●Other food allergies – If another form of food allergy or food protein-induced

enteropathy is suspected, management depends on the certainty and severity of
symptoms. If the symptoms are not severe and an elimination trial is planned, the
suspected food should be removed from the diet for at least 7 to 10 days. (See "Overview of
the causes of chronic diarrhea in children in resource-rich settings", section on 'Immune-
mediated causes' and "Clinical manifestations of food allergy: An overview" and "Food
protein-induced enterocolitis syndrome (FPIES)".)

●Functional diarrhea – Functional diarrhea is a diagnosis of exclusion; it sometimes

responds to modest dietary changes:
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•In young children, functional diarrhea (toddler's diarrhea) often has dietary contributors,
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with or without physiologic hypermotility. The symptom may respond to reductions in
dietary sugars, especially fructose and sorbitol (eg, excessive fruit juice). However, it is
important to maintain a balanced diet and the diet should not be otherwise restricted. The
child should be monitored periodically for growth and any new symptoms.

•In older children, functional diarrhea (diarrhea-predominant irritable bowel syndrome [IBS-
D]) is thought to be a motility disorder rather than diet induced. Dietary restriction is not
routinely recommended, but a brief trial of avoiding lactose or sorbitol may be warranted.
For older adolescents with moderate or severe symptoms, the dietary and
pharmacotherapeutic strategies used for adults may be warranted, with nutritional
counseling and monitoring to ensure a balanced diet and healthy eating patterns. (See
"Functional abdominal pain in children and adolescents: Management in primary care",
section on 'Diarrhea' and "Treatment of irritable bowel syndrome in adults".)

If possible, the family should keep a dietary record before and after the dietary change to
document adherence; this record also may identify other potential triggers.

Medications
●Probiotics – For patients with suspected or established antibiotic-related or postinfectious
diarrhea with bothersome symptoms, we suggest a trial of probiotics. Probiotics are
thought to have beneficial effects on the intestinal microbiota, which are altered in many
diarrheal diseases but particularly in infectious or antibiotic-related forms.

This suggestion is based upon the following evidence:

•For antibiotic-associated diarrhea – The use of probiotics for treatment and prevention of
antibiotic-associated diarrhea is supported by randomized trials and meta-analyses [17]. In
a meta-analysis of 33 trials involving 6352 children, probiotics reduced the incidence of
antibiotic-associated diarrhea (8 versus 19 percent; relative risk 0.45, 95% CI 0.36-0.56) and
the duration of symptoms (mean difference 0.9 fewer days, 95% CI 0.4-1.4 fewer days) [17].
Some of the included trials had important methodologic limitations (lack of blinding,
incomplete follow-up). In addition, there was considerable heterogeneity among trials in the
probiotic product and dose used. Nevertheless, the effect on reducing antibiotic-associated
diarrhea remained significant in a subgroup analysis limited to 13 trials deemed to be of
high methodologic quality (relative risk 0.53, 95% CI 0.37-0.77).

•For postinfectious diarrhea – There are fewer data to support the efficacy of probiotics in
the treatment of postinfectious diarrhea. Indirect support is provided by a meta-analysis of
two trials that included a total of 324 children with persistent diarrhea (ie, lasting >14 days),
in which probiotics reduced the duration of symptoms (mean difference four fewer days,

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95% CI 3.4-4.6 fewer days) [18]. However, the trials involved children who were managed in
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resource-limited settings and the etiology of diarrhea was unclear.

•Other uses – Other possible uses for probiotics are discussed separately:

-Irritable bowel syndrome (see "Probiotics for gastrointestinal diseases", section on 'Irritable
bowel syndrome')

-Acute gastroenteritis (see "Probiotics for gastrointestinal diseases", section on 'Infectious

diarrhea' and "Acute viral gastroenteritis in children in resource-rich countries: Management
and prevention", section on 'Probiotics and prebiotics')

-C. difficile infection (see "Clostridioides difficile infection in children: Treatment and
outcome", section on 'Alternative therapies' and "Clostridioides difficile infection in adults:
Treatment and prevention", section on 'Alternative therapies')

●Antidiarrheal drugs – We do not recommend the use of antimotility drugs for children
with chronic diarrhea. A possible exception is to facilitate fluid management when the cause
of the diarrhea has been established (eg, IBS) 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. As examples, these agents may prolong excretion of the
organism or increase the risk of developing hemolytic-uremic syndrome in patients with
enterohemorrhagic Escherichia 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 (eg, in some neuroendocrine tumors,

chemotherapy-induced diarrhea, some forms of congenital diarrheas and enteropathies), a
trial with somatostatin or its analog octreotide may be considered. Octreotide has been
used in diarrhea caused by neoplastic diseases and in intestinal infections that have a
secretory mechanism [19-21]. 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 effect against the enterotoxin associated with
Cryptosporidium infections [22]. (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".)

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SUMMARY AND RECOMMENDATIONS

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●Definition – Diarrhea is often defined as a change in the frequency and consistency of

stool compared with an individual's baseline pattern. It is considered chronic if it lasts more
than four weeks. It has a wide variety of causes, ranging from functional diarrhea to severe
conditions (table 1). (See 'Definitions' above.)

●Initial evaluation – The initial evaluation includes assessments for (algorithm 1) (see
'Initial evaluation' above):

•Warning signs (table 2), which raise the possibility of a systemic or rapidly progressing
disorder.

•Focused history (table 3) and physical examination (table 4), which may provide clues to the
etiology.

•Basic laboratory evaluation to screen for common causes, including tissue

transglutaminase (tTg) to screen for celiac disease, complete blood count, and stool
calprotectin or lactoferrin (table 5). In addition, we often perform stool cultures and
Clostridioides difficile testing at this stage.

●Provisional diagnosis and initial management – The above evaluation usually narrows
the cause to one of the following categories (see 'Provisional diagnosis and initial
management' above):

•Celiac disease

•Inflammatory diarrhea (algorithm 2)

•Drugs

•Diet-induced (algorithm 3)

•Postinfectious

A functional gastrointestinal disorder is likely if the above causes are ruled out and if the
symptoms are mild or intermittent. In young children, functional diarrhea may be
exacerbated by excessive fructose or sorbitol consumption. (See 'Functional diarrhea'
above.)

●Further testing if the diagnosis is unclear – If the etiology of the diarrhea remains
unclear and the diarrhea is severe or has features suggesting a pathogenic (rather than
functional) disorder (table 1), further evaluation may include a variety of tests, depending

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on the patient's characteristics and suspected disorder (table 5). (See 'Further testing if the
Your activity: 7 p.v.
diagnosis is unclear' above.)

●Management – Management of chronic diarrhea is directed at the underlying cause. For

functional and postinfectious diarrhea, dietary changes are sometimes helpful. We suggest
a trial of probiotics for patients with antibiotic-associated diarrhea (Grade 2B) and for those
with suspected or established postinfectious diarrhea (Grade 2C). (See 'Treatment
considerations' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges

Richard Kellermayer, MD, PhD, and Robert J Shulman, MD, who contributed to an earlier
version of this topic review.
1. Binder HJ. Causes of chronic diarrhea. N Engl J Med 2006; 355:236.
2. Bhutta ZA, Ghishan F, Lindley K, et al. Persistent and chronic diarrhea and
malabsorption: Working Group report of the second World Congress of Pediatric
Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2004; 39
Suppl 2:S711.
3. Chumpitazi BP, Lane MM, Czyzewski DI, et al. Creation and initial evaluation of a Stool
Form Scale for children. J Pediatr 2010; 157:594.
4. Gibbons T, Fuchs GJ. Chronic enteropathy: clinical aspects. Nestle Nutr Workshop Ser
Pediatr Program 2007; 59:89.
5. Blake MR, Raker JM, Whelan K. Validity and reliability of the Bristol Stool Form Scale in
healthy adults and patients with diarrhoea-predominant irritable bowel syndrome.
Aliment Pharmacol Ther 2016; 44:693.
6. Bhandari N, Bhan MK, Sazawal S, et al. Association of antecedent malnutrition with
persistent diarrhoea: a case-control study. BMJ 1989; 298:1284.
7. OrphaNet disease summary for congenital sucrase-isomaltase deficiency, available at:
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35122 (Accessed on
January 20, 2022).
8. Treem WR. Clinical aspects and treatment of congenital sucrase-isomaltase deficiency. J
Pediatr Gastroenterol Nutr 2012; 55 Suppl 2:S7.
9. Broekaert IJ, Borrelli O, Dolinsek J, et al. An ESPGHAN Position Paper on the Use of
Breath Testing in Paediatric Gastroenterology. J Pediatr Gastroenterol Nutr 2022;
74:123.
10. Jones HF, Butler RN, Moore DJ, Brooks DA. Developmental changes and fructose
absorption in children: effect on malabsorption testing and dietary management. Nutr
Rev 2013; 71:300.
11. Benninga MA, Faure C, Hyman PE, et al. Childhood Functional Gastrointestinal
Disorders: Neonate/Toddler. Gastroenterology 2016.

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12. Lloyd-Still JD. Chronic diarrhea of childhood and the misuse of elimination diets. J
Your activity: 7 p.v.
Pediatr 1979; 95:10.
13. Nichols BL Jr, Adams B, Roach CM, et al. Frequency of sucrase deficiency in mucosal
biopsies. J Pediatr Gastroenterol Nutr 2012; 55 Suppl 2:S28.
14. van Wanrooij RLJ, Bontkes HJ, Neefjes-Borst EA, et al. Immune-mediated enteropathies:
From bench to bedside. J Autoimmun 2021; 118:102609.
15. Evaluation of an algorithm for the treatment of persistent diarrhoea: a multicentre
study. International Working Group on Persistent Diarrhoea. Bull World Health Organ
1996; 74:479.
16. Bhan MK, Bhandari N, Bahl R. Management of the severely malnourished child:
perspective from developing countries. BMJ 2003; 326:146.
17. Guo Q, Goldenberg JZ, Humphrey C, et al. Probiotics for the prevention of pediatric
antibiotic-associated diarrhea. Cochrane Database Syst Rev 2019; 4:CD004827.
18. Bernaola Aponte G, Bada Mancilla CA, Carreazo NY, Rojas Galarza RA. Probiotics for
treating persistent diarrhoea in children. Cochrane Database Syst Rev 2013; :CD007401.
19. Bisset WM, Jenkins H, Booth I, et al. The effect of somatostatin on small intestinal
transport in intractable diarrhoea of infancy. J Pediatr Gastroenterol Nutr 1993; 17:169.
20. Pai V, Porter K, Ranalli M. Octreotide acetate is efficacious and safe in children for
treating diarrhea due to chemotherapy but not acute graft versus host disease. Pediatr
Blood Cancer 2011; 56:45.
21. Mas E, Borrelli O, Broekaert I, et al. Drugs in Focus: Octreotide Use in Children With
Gastrointestinal Disorders. J Pediatr Gastroenterol Nutr 2022; 74:1.
22. Guarino A, Berni Canani R, Spagnuolo MI, et al. In vivo and in vitro efficacy of octreotide
for treatment of enteric cryptosporidiosis. Dig Dis Sci 1998; 43:436.
Topic 5881 Version 29.0

References

1 : Causes of chronic diarrhea.

2 : Persistent and chronic diarrhea and malabsorption: Working Group report of the second
World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.

3 : Creation and initial evaluation of a Stool Form Scale for children.

4 : Chronic enteropathy: clinical aspects.

5 : Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with
diarrhoea-predominant irritable bowel syndrome.

https://pro.uptodatefree.ir/show/5881 15/16
3/19/23, 10:20 AM Approach to chronic diarrhea in children &gt;6 months in resource-rich countries - Uptodate Free

Yourstudy.
6 : Association of antecedent malnutrition with persistent diarrhoea: a case-control activity: 7 p.v.

7 : Association of antecedent malnutrition with persistent diarrhoea: a case-control study.

8 : Clinical aspects and treatment of congenital sucrase-isomaltase deficiency.

9 : An ESPGHAN Position Paper on the Use of Breath Testing in Paediatric Gastroenterology.

10 : Developmental changes and fructose absorption in children: effect on malabsorption

testing and dietary management.

11 : Childhood Functional Gastrointestinal Disorders: Neonate/Toddler.

12 : Chronic diarrhea of childhood and the misuse of elimination diets.

13 : Frequency of sucrase deficiency in mucosal biopsies.

14 : Immune-mediated enteropathies: From bench to bedside.

15 : Evaluation of an algorithm for the treatment of persistent diarrhoea: a multicentre study.

International Working Group on Persistent Diarrhoea.

16 : Management of the severely malnourished child: perspective from developing countries.

17 : Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

18 : Probiotics for treating persistent diarrhoea in children.

19 : The effect of somatostatin on small intestinal transport in intractable diarrhoea of infancy.

20 : Octreotide acetate is efficacious and safe in children for treating diarrhea due to
chemotherapy but not acute graft versus host disease.

21 : Drugs in Focus: Octreotide Use in Children With Gastrointestinal Disorders.

22 : In vivo and in vitro efficacy of octreotide for treatment of enteric cryptosporidiosis.

https://pro.uptodatefree.ir/show/5881 16/16