












































Journal of Enam Medical College
Vol 11 No 2 May 2021

120

Review Article

Chronic Diarrhea in Children
Fahmida Begum1, Khan Lamia Nahid2, Md. Wahiduzzaman Mazumder3,  

Md. Rukunuzzaman4, ASM Bazlul Karim5
Received: 4 April 2020        Accepted: 18 March 2021

doi: https://doi.org/10.3329/jemc.v11i2.65194

1. Professor, Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University, 
Shahbag, Dhaka

2. Assistant Professor, Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical 
University, Shahbag, Dhaka

3. Associate Professor, Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical 
University, Shahbag, Dhaka

4. Professor, Department of Pediatric Gastroenterology and Nutrition, Bangabandhu Sheikh Mujib Medical University, 
Shahbag, Dhaka

5. Fellow, Pediatric Gastroenterology, Liver Diseases (Australia)
Correspondence Fahmida Begum, Email: fahmidalily@gmail.com

Abstract

Chronic diarrhea (CD) is a common but challenging clinical scenario in pediatric medicine. It 
has several hundred disorders in the differential diagnosis and can create a complex situation for 
practitioners and families. Some of the disorders cause failure to thrive but some are not. This 
article focuses on important aetiologies of CD, their clinical features, diagnostic approach as 
well as treatment approaches.

Key words: Chronic diarrhea; Osmotic diarrhea; Secretory diarrhea

J Enam Med Col 2021; 11(2): 120−127

Introduction

Diarrhea is defined as stool volume >10 g/kg per 
day in infants and toddlers, and >200 g/day in older 
children.1 Chronic diarrhea (CD) is one which lasts 
for more than 14 days, is usually noninfectious and 
associated with malabsorptive features. Some experts 
also refer CD for episodes lasting more than 4 weeks.2 
On the other hand persistent diarrhea (PD) is an 
episode of diarrhea of presumed infectious etiology, 
which starts acutely but lasts for more than 14 days 
and excludes recurrent diarrheal disorders such as 
tropical sprue, gluten sensitive enteropathy or other 
hereditary disorders.3

Epidemiology

According to the World Health Organization, 

diarrheal illness is the second leading cause of death 
in developing countries in children younger than 5 
years of age and is responsible for 1.7 million child 
morbidities and 760,000 child mortalities.4 In 2002, 
the World Health Organization estimated that 13.2% 
of all childhood deaths worldwide were caused 
by diarrheal diseases, 50% of which were chronic 
diarrheal illnesses.5 Among children aged 1 to 4 years, 
persistent diarrhea accounted for more than 25% of 
diarrheal deaths in Bangladesh, Ethiopia and Uganda.6 
Large-scale studies indicate that the prevalence of 
chronic diarrheal illnesses worldwide ranges from 3% 
to 20%, and the incidence is ≈ 3.2 episodes per child 
year.7



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Pathophysiology

The basic pathophysiology of CD is incomplete 
absorption of water from the intestinal lumen. This 
occurs either because of a reduced rate of net water 
absorption (related to impaired electrolyte absorption 
or excessive electrolyte secretion) or because of 
osmotic retention of water in the lumen. Reduction 
of net water absorption as little as one percent is 
sufficient to cause diarrhea.8

The four principal pathophysiologic mechanisms of 
CD are osmotic, secretory, dysmotility associated, and 
inflammatory. Often, a single disorder may involve 
multiple overlapping mechanisms. 

Osmotic diarrhea is caused by a failure to absorb a 
luminal solute. As a result, there are secretion of fluids 
and net water retention across an osmotic gradient. 
This may occur from either congenital or acquired 
diseases such as lactose malabsorption.9

Secretory diarrhea occurs when there is a net secretion 
of electrolyte and fluid from the intestine without 
compensatory absorption. Endogenous substances, 
often called “secretagogues,” induce fluid and 
electrolyte secretion into the lumen even in the absence 
of an osmotic gradient. Typically, secretagogues 
affect ion transport in the large and small bowel both 
by inhibiting sodium and chloride absorption and 
by stimulating chloride secretion via cystic fibrosis 
(CF) transmembrane regulator activation. Multiple 
congenital diarrheal disorders associated with identified 
genetic mutations that affect gut epithelial ion transport 
are the example of secretory diarrhea.10 Congenital 
chloride diarrhea (CCD) is one such disorder. Children 
with a pure secretory diarrhea will therefore continue 
to experience diarrhea even while fasting.

CD associated with intestinal dysmotility typically 
occurs in the setting of intact absorptive abilities. 
Intestinal transit time is decreased, the time allowed for 
absorption is minimized, and fluid is retained within 
the lumen. High-amplitude propagated contractions 
cause diarrhea predominant irritable bowel syndrome 
(IBS) in older adolescents and changes in small 
intestinal motility results chronic nonspecific diarrhea 
(CNSD) in toddlers.11

Inflammatory diarrhea may include all of the 
pathophysiologic mechanisms. Inflammation that 
results injury to the intestine may lead to malabsorption 
of dietary macronutrients which, in turn, creates 
a luminal osmotic gradient. Moreover, particular 
infectious agents may induce secretion of fluid into 
the lumen, and blood in the gut may alter intestinal 
motility. Diseases such as inflammatory bowel 
disease (IBD) and celiac disease are the example of 
this inflammatory mechanism.9

Common causes of chronic diarrhea in 
children

Causes of chronic diarrhea can also be divided into 
following subgroups (Table II).

Table II: Causes of chronic diarrhea

Infective
Due to exogenous substances
Abnormal digestive processes
Nutrient malabsorption
Immune and inflammatory
Structural defects
Defects of electrolytes and metabolite transport
Motility disorders
Neoplastic
Chronic non-specific diarrhea

Table I: Differences between osmotic and secretory diarrhea

Variables Secretory diarrhea Osmotic diarrhea
Volume of stool >200 ml/24 hours <200 mL/24 hours
Response to fasting Diarrhea continues Diarrhea stops
Stool Na >70 mEq/L <70 mEq/L
Reducing substances Negative Positive
Stool pH  >6 <5
Stool osmotic gap
{Stool osmolarity – 2 (stool Na+ K )}

< 100 >100



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Infective causes: Infective causes of chronic diarrhea 
can be seen in any age and common organisms 
implicated includes Salmonella, Yersinia, E.coli, 
Campylobacter, Aeromonas, Plesiomonas, Giardia, 
Cryptosporidium, viral causes (Rota, Entero, 
Norwalk). They have associated fever, abdominal 
pain, exposure history, blood/mucus in stool.
Giardia causes both osmotic and secretory diarrhea. 
Microscopic examination of a freshly passed stool on 
three consecutive days is recommended for detection 
of Giardia trophozoites. Antimicrobial therapy for 
giardiasis is metronidazole, tinidazole, or nitazoxanide. 
Non typhoidal Salmonella organisms typically cause 
gastroenteritis with diarrhea, abdominal cramping, 
and fever. Salmonella organisms typically are detected 
in routine stool culture for up to 5 weeks but may 
be excreted in stool for >1 year in 5% of patients.12 
Antibiotic therapy for uncomplicated nontyphoidal 
serotypes is not indicated as it does not shorten the 
disease duration but may prolong the duration of 
excretion of bacteria in the stool.13 Antibiotic is 
indicated only for children younger than 3 months of 
age or those with immunosuppressive diseases.14

Small bowel bacterial overgrowth: There are 
overgrowths of aerobic and anaerobic bacteria in 
the small bowel such as in short bowel syndrome, 
bowel strictures, pseudo-obstruction, malnutrition. 
Osmotic diarrhea occurs due to enhanced bile acid 
deconjugation and fatty acid hydroxylation by 
bacteria. The patients present with abdominal pain 
and diarrhea. The diagnosis can be made by breath 
hydrogen with lactulose testing. Metronidazole or non 
absorbable rifaximin is the treatment of choice.15

Whipple’s disease: Whipple’s disease is caused 
by Gram +ve bacteria: Tropheryma whipplei. The 
patients have malabsorption, central nervous system, 
joints and cardiovascular involvement. It is a rare 
condition and carries a poor prognosis.

Tropical sprue: It is a rare condition in children 
and coliform organisms are implicated in its etio-
pathogenesis.

Abnormal digestive processes
Cystic fibrosis 

Pancreatic insufficiency is common in approximately 
90% of patients with CF and this causes diarrhea in 
this disorder.16 Loss of exocrine pancreatic function 
leads to malabsorption of carbohydrates, fat, and 
protein because of dysfunctional amylases, lipases, 
and proteases, respectively. Pancreatic exocrine 
function can be assessed by fecal elastase, and low 
levels indicating possible pancreatic insufficiency. 
Pancreatic enzyme replacement therapy may improve 
malabsorptive diarrhea in patients with CF. 

Nutrient malabsorption

Carbohydrate malabsorption: Intestinal lactase 
deficiency causes carbohydrate malabsorption that 
can be congenital, adult-onset and secondary lactase 
deficiency. Congenital lactase deficiency is a rare 
entity. Adult onset is relatively common and ‘normal’ 
for most humans. Secondary lactase deficiency is 
seen after infectious gastroenteritis or injury to small 
intestinal mucosa caused by gluten or other sensitizing 
substances, Crohn’s disease, and other enteropathies.

Symptoms of lactose intolerance are independent of 
the cause. Incompletely digested lactose reaches the 
dense colonic microbial population, which ferments 
the sugar to hydrogen and other gases, thereby 
causing gassy discomfort and flatulence. The no 
absorbed lactose serves as an osmotic agent, resulting 
in an osmotic diarrhea. Diagnosis can be made by 
a successful lactose-free diet trial of 2 weeks or by 
hydrogen breath-testing. Minimizing lactose intake 
is the treatment of choice, as the symptoms are dose 
dependent and so complete removal of dietary lactose 
is not necessary.17

Lipid malabsorption: Lipid malabsorption is seen in 
diseases like cystic fibrosis, Shwachman- Diamond 
syndrome, Pearson syndrome, Johanson-Blizzard 
Syndrome, celiac disease, cholestatic liver disease, 
beta lipoproteinemia, lymphangectasia and short 
bowel syndrome.

Protein malabsorption: Protein malabsorption is 
seen in condition like pancreatitis, cystic fibrosis, 
trypsinogen deficiency, enterokinase deficiency, 
hartnup disease, lymphangectasia, lowes syndrome 
and lysinuric protein intolerance.



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Cow’s milk protein allergy (CMPA): Cow’s milk 
protein allergy presents in first year of life, but may 
present up to two years of age. The child present with 
streaks of blood and mucus in stool, in otherwise 
healthy infant. It typically occurs in child on top milk, 
however 0.5% may present in exclusive breast-fed 
infants. Withdrawal of cow’s milk from diet is the 
treatment of choice.

Inflammatory bowel disease21

Inflammatory bowel diseases (IBD) can present in 
children and adolescents with chronic diarrhea along 
with passage of blood or mucus in stools. The child 
can have weight loss, anemia, tenesmus, joint pains, 
and redness of eyes. In Crohn’s disease, stool may 
contain microscopic blood but may not be grossly 
bloody. In ulcerative colitis, diarrhea is a more 
consistent presenting feature. 

Immune and inflammatory
Celiac disease: Celiac disease is an immune-
mediated systemic disease that occurs due to gluten 
ingestion in a genetically susceptible individual. With 
its prevalence in adults and children approaching 1% 
worldwide.18 It is most common cause of chronic 
diarrhea and malabsorption in more than 2 years age 
group patients.19

The typical presentation of celiac disease in children 
is failure to thrive, diarrhea and abdominal distension. 
The presence of raised anti-tissue transglutaminase 
antibody/anti endomysial antibody make the 
suspicion of celiac disease and is confirmed by 
histologic findings in the duodenum which is graded 
according to Marsh Criteria.20 The management of 
celiac disease is lifelong restriction of food containing 
gluten in diet which includes wheat, rye, and barley. 
Multivitamin and mineral deficiency should also be 
managed appropriately.

Patient with suspected IBD

Screen with fecal calprotectin level

                             Negative                                    Positive      

                                                     Urgent endoscopy 

                                Negative                                             Positive

                             Plan other investigation  Start treatment for IBD

Fig 1. Workup for suspected inflammatory bowel disease (IBD) in adults20

Treatment includes anti-inflammatory agents like 
steroids, 5ASA, Azathioprine etc. Nocturnal diarrhea 
with urgency may be a sign of left-sided colonic 
inflammation in either Crohn disease or ulcerative 
colitis. Diarrhea associated with IBD typically 
improves with therapy as mucosal inflammation 
resolves. 
Autoimmune enteropathies: Autoimmune 

enteropathies are rare disorders that may present 
as severe diarrhea during infancy or toddlerhood. 
The diarrhea may be isolated, or may occur in 
association with diabetes mellitus as part of the 
IPEX (Immunodysregulation polyendocrinopathy 
enteropathy X-linked) syndrome. Diagnosis is made 
by documenting antienterocyte, anticolonocyte, or 
antigoblet cell antibodies in the blood. Treatment 



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is difficult but may be accomplished with 
immunosuppressive agents such as corticosteroids, 
6-mercaptopurine, tacrolimus, and infliximab.

Immunodeficiency: Patient with chronic diarrhea 
should be evaluated for primary or secondary 
immunodeficiency such as HIV disease. In this case, 
the evaluation should focus on potential infectious 
causes of the diarrhea, particularly parasites and 
opportunistic infections such as Cryptosporidium, 
Isospora, and Cyclospora.20

Structural defects: These include disease like 
tufting enteropathy, microvillous inclusion disease, 
phenotypic diarrhea, lymphangiectasia, intergrin 
deficiency, heparan sulphate deficiency. These are 
rare diseases and cause neonatal diarrhea and carries 
a poor prognosis.

Defects with effects of electrolytes and metabolite 
transport: It includes congenital chloride diarrhea 
(CCD) and congenital sodium diarrhea (CSD), these 
disorders cause secretory diarrhea and present in 1−2 
week of life and carry a poor prognosis.

Chronic Nonspecific Diarrhea of Childhood or 
Infancy (CNSD)

CNSD is the most common form of chronic diarrhea in 
the first 3 years after birth.21 The typical time of onset 
may range from 1 to 3 years of age and can last from 
infancy until age 5 years. It presents with varied stool 
frequency and consistency without blood or mucus 
and stool contain undigested food particles. There 
is no failure to thrive. Potential pathophysiologic 

mechanisms for CNSD include increased intestinal 
motility and osmotic effects of intraluminal solutes 
(e.g. carbohydrates).12

Reassurance is the cornerstone of therapy for CNSD. 
Treatment includes decreased fruit juices (fructose) 
and reassurance along with liberalization of fat to 
encourage normal caloric intake and to slow intestinal 
transit time is also important.22

Motility disorders
Irritable Bowel Syndrome (IBS)

According to Rome IV Diagnostic Criteria Irritable 
Bowel Syndrome must include all of the followings: 
1. Abdominal pain at least 4 days per month associated 
with one or more of the followings: a. Related to 
defecation; b. A change in frequency of stool; c. A 
change in form (appearance) of stool; 2. In children 
with constipation, the pain does not resolve with 
resolution of the constipation (children in whom 
the pain resolves have functional constipation, not 
irritable bowel syndrome). 3. After appropriate 
evaluation, the symptoms cannot be fully explained 
by another medical condition.23

Criteria fulfilled for at least 2 months before diagnosis 
treatment is often challenging. Antispasmodic agents, 
tricyclic antidepressants, and selective serotonin-
reuptake inhibitors may improve symptoms. Some 
probiotics have been useful in adult and pediatric IBS, 
but results are not consistent.24

Among the causes of CD some are associated with 
failure to thrive and some are not (Table III).

Table III: Causes of chronic diarrhea

Without failure to thrive With failure to thrive
CNSD IDI (Intractable Diarrhea of Infancy)
Infectious colitis Allergic enteropathy
Lactose malabsorption IBD
Small bowel bacterial overgrowth Celiac disease
IBS Immunodeficiency state (various diseases)

Congenital secretory diarrhea (Chronic chloride and 
chronic sodium diarrhea)
Tufting enteropathy
Microvillous inclusion disease 
Autoimmune enteropathy 
CF



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Evaluation of CD 

History and physical examination

For diagnosis of different causes of CD detailed 
history and examination is a must. Characteristics of 
the stool as well as feeding history are very important 
in assessing the cause and severity of the illness.

There are differences in pattern of stool in small 
and large bowel diarrhea. So, it is important to 
differentiate small bowel diarrhea from large bowel 
type of diarrhea. Small bowel diarrhea differs from 
large bowel diarrhea with its large volume, foul-
smelling stools with undigested food particles 
and often it is associated with features of lactose 
intolerance like explosive diarrhea and bloating. 
On the other hand, large bowel type of diarrhea has 
blood, mucus, tenesmus, urgency and high frequency. 
In toddler’s diarrhea children often have loose stools 
with undigested food particles. Frequent loose 
watery stools may indicate carbohydrate intolerance 
and pasty or loose foul-smelling stools indicate fat 
malabsorption. It is also necessary to take history of 
extraintestinal symptoms like presence or absence of 
weight loss, rash, fatigue, vomiting, joint aches, or oral 
ulcers. A detailed history of source of drinking water, 
family history, complementary feeding and whether 
onset of diarrhea after introduction of specific foods 
like seen in celiac disease and cow’s milk protein 
allergy should be evaluated. There may be history 
of repeated infections in cystic fibrosis or immune 
deficiency syndromes.

In physical examination one should have to look for 
anthropometry assessment and status of dehydration. 
Clubbing may be seen in celiac disease and IBD. 
Extraintestinal manifestations of IBD like joint pain, 
swelling and erythema may also be found. There 
also may be signs of various nutrient and vitamin 
deficiencies like zinc, vitamin D,Vitamin A, Vitamin 
K and B complex. Distended abdomen may be seen 
in malabsorption syndromes or small bowel bacterial 
overgrowth.  Rectal examination is also important as 
it may reveal perianal disease in IBD and perianal 
excoriation in carbohydrate malabsorption.

Laboratory evaluation: A detailed history 
and examination is needed so that unnecessary 

investigations are better avoided. Initial 
investigations include a complete hemogram to 
evaluate anemia, total counts and platelets. Stool 
routine and culture with urine routine should 
be done in all cases of chronic diarrhea. Stool 
may contain RBC, WBC and mucus indicating a 
mucosal inflammation in large bowel and analysis 
of the stool for electrolyte content and osmolarity 
may be helpful in distinguishing an osmotic from 
a secretory diarrhea. Serum electrolytes with renal 
function test should also be done. Serology for celiac 
disease, tTG with total IgA should be done in cases 
of small bowel diarrhea. Upper GI endoscopy and 
when required colonoscopy with mucosal biopsy 
are required in many diseases like celiac disease, 
IBD, eosinophilic enteropathy, microvillous inclusion 
disease, tufting enteropathy, giardiasis, Intestinal 
lymphangiectasia. In special cases, fecal fat estimation, 
fecal elastase, H2 breath test, hormonal assays may be 
required.

Treatment

It depends on primary cause of chronic diarrhea; it 
may vary from just reassurance in cases of chronic 
nonspecific diarrhea to bowel transplant in structural 
enteropathies. In addition to specific disease-oriented 
therapy the patients should be given vitamin and mineral 
supplement. Disease like Cow’s milk protein 
allergy, celiac disease, and giardiasis are easily 
treatable. Celiac disease management includes 
a lifelong strict adherence to gluten free diet 
and nutritional counseling. For CMPA, the ideal 
management it extensively hydrolyzed formula, 
unfortunately they are not still available 
in India and are to be imported 
thereby increasing their cost.

Conclusion

Chronic diarrhea is important cause of morbidity 
in developing countries. Timely evaluation and 
management are of paramount importance to prevent 
complications. The patient should be referred to a 
tertiary care center in time for appropriate diagnosis 
and treatment.



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