An Approach to Chronic Diarrhea in Children

Educational Objectives

The goal of this program is to improve management of chronic diarrhea in the pediatric population. After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate osmotic vs secretory diarrhea.
2. Manage persistent diarrhea in pediatric patients with presence of enteropathogenic Escherichia coli.
3. Optimize use of probiotics in patients with prolonged diarrhea.

Summary

Chronic diarrhea: the World Health Organization defines diarrhea in children as stool output of >10 mL/kg per day, with prolonged diarrhea lasting 7 to 14 days, and chronic diarrhea lasting >14 days

Etiology: inflammatory — inflammatory bowel disease (IBD), allergic colitis, celiac disease, infections, and autoimmune disease; noninflammatory — divided into secretory diarrhea (actively moving water and osmotic load into the intestine), osmotic diarrhea, and motility or anatomic issues; osmotic vs secretory diarrhea — secretory diarrhea has a significantly larger stool volume (200 mL) and does not respond to fasting; the hallmark of secretory diarrhea is that children who have been given nothing by mouth continue to have high volumes of stool output; stool studies show elevated stool sodium and low osmotic gap; osmotic diarrhea demonstrates positive reducing substances and low stool pH

Causes of secretory diarrhea: infants usually present with severe diarrhea with electrolyte abnormalities ≤2 wk of life; congenital chloride diarrhea, congenital sodium diarrhea, tufting enteropathy, and microvillous inclusion disease are some causes; endoscopy with electron microscopy is important; biopsy specimens should be handled differently to examine villous structures; in older children, carcinoid factors, pancreatic vasoactive intestinal peptide tumors, neuroblastoma, thyroid medullary carcinoma, and gastrinoma are some causes; diarrhea not responding to fasting and lasting >14 days in older children should be evaluated for these conditions

Osmotic diarrhea

Carbohydrate malabsorption: lactase deficiency or lactose intolerance; may have primary or secondary disaccharidase deficiencies; primary deficiencies are related to genetics; congenital lactase deficiency is rare; most humans have progressive loss of lactase activity, which is normal; a genetic mutation can cause lactase persistence; secondary disaccharidase deficiencies are secondary to factors that cause villous injury; limit dairy products or milk intake after an episode of acute gastroenteritis; congenital sucrase–isomaltase deficiency (CSID); milder presentations of CSID in older age may overlap with IBS; fructose malabsorption may be related to inability to transport fructose; glucose galactose malabsorption is a rare presentation

Diagnosis: low stool pH and positive reducing substances; caution is needed, especially in older children; breath testing is helpful; speaker uses empirical elimination for 2 wk; some patients could be given a big load and assessed for symptoms

Treatment: dietary avoidance and enzyme supplementation

Fat malabsorption: characterized by fatty, oily, foul-smelling diarrhea; associated with poor growth; pancreatic insufficiency (secondary to various genetic syndromes) is most common; fecal elastase is the initial test; fecal fat may be elevated, but fecal fat is sensitive to dietary intake; consider pancreatic imaging if an abnormal fecal elastase is observed; endoscopic pancreatic function test directly measures pancreatic function in response to secretin stimulation; pancreatic enzyme supplements are considered for pancreatic insufficiency

Protein malabsorption: often coexists with pancreatic insufficiency; patients may become hypoalbuminemic

Bile acid malabsorption: rare congenital bile acid malabsorption diseases and secondary deficiencies (bowel resection, especially distal ileum); a common presentation after cholecystectomy; these patients respond well to cholestyramine

Small intestinal bacterial overgrowth (SIBO): increased production of osmotically active byproducts of bacterial fermentation; presents with postprandial bloating, abdominal pain, diarrhea, and upper gastrointestinal symptoms (nausea); a lactulose breath test is used for diagnosis; antibiotics (rifaximin, metronidazole, and amoxicillin) may be used for treatment

Irritable bowel syndrome: diagnosis requires recurrent abdominal pain on average ≥1 day/wk lasting 3 mo, and having ≥2 of symptoms including 1) signs related to defecation, 2) a change in frequency of stool, and 3) a change in the appearance of stool; rifaximin is a Food and Drug Administration approved treatment for IBS with diarrhea in adults; the speaker also uses rifaximin in teenagers; a 2-wk course can be used as first-line treatment; increased soluble fiber (eg, Psyllium husk) may help in IBS with diarrhea or IBS mixed type; selective serotonin reuptake inhibitors and tricyclic antidepressants may help with abdominal pain and slow gut transit; a biopsychosocial approach helps reduce symptom frequency; loperamide can be used in certain cases

Toddler diarrhea: nonspecific diarrhea affecting children 1 to 3 yr of age, characterized by increased frequency and variable consistency of stools; non-bloody; undigested food particles are common; associated diaper rashes; normal growth is the hallmark; causes — rapid small bowel transit time, impaired carbohydrate absorption, unbalanced diet delivering a high osmotic load (in absence of fat and fiber), and excessive fluid intake; treatment — decreasing fructose and sorbitol intake, increasing fat and fiber intake, and reassurance

Viral infections: evaluate for Giardia lamblia infection; caution should be exercised when sending stool pathogen panels; enteropathogenic Escherichia coli (EPEC) — frequently detected in asymptomatic hosts; most common pathogen in children with persistent diarrhea; reassure the patient, especially if the symptoms have resolved; speaker uses azithromycin for 3 days in patients with persistent diarrhea who are EPEC positive; a test of cure is not recommended and will likely not change treatment; Clostridium difficile — difficult to interpret; ≈35% of enzyme immunoassays (EIA) being false positives, especially in children, compared with culture (gold standard); false positive rates are higher in younger children; children <2 yr of age have immature or diminished receptor sites for C difficile toxin, so true C difficile infection is uncommon; a positive PCR and EIA indicate a true C difficile infection; patients with a positive PCR and negative EIA are considered carriers; a negative disease state if both are negative; tests should be avoided unless the patient has concerns about C difficile exposure or severe diarrhea (commonly bloody diarrhea)

Management strategies for prolonged diarrhea: initial evaluation of complete blood count (anemia, thrombocytopenia, or thrombocytosis), erythrocyte sedimentation rate, c-reactive protein tests, comprehensive metabolic panel (CMP; for albumin and liver enzymes), stool calprotectin test (colon inflammation), a fecal occult blood test (bloody diarrhea), and fecal alpha-1-antitrypsin (A1AT); A1AT is not ingested in food; presence in stool indicates leakage and mucosal injury, especially in the absence of colonic disease; reassure for persistent symptoms lasting 7 to 14 days; alteration in the gut microbiome, villous atrophy (secondary to inflammation), and high gut mucosal permeability could be the cause; a Cochrane review concluded probiotics shortened the duration of diarrhea and reduced stool frequency; studies have shown zinc helps with the resolution of small bowel damage and can shorten the duration of diarrhea (most effective with vitamin A); empiric antimicrobials have very limited evidence; amoxicillin and metronidazole, for eg, have no data suggesting effectiveness in limiting duration of diarrhea; dietary factors (eg, decreased sugar, increased fat, soluble fiber) are helpful; not unusual for patients to stay on BRAT diet for 10 to 14 days

Speaker’s stepwise diagnostic approach: blood tests for inflammation and celiac disease; stool tests for inflammation and malabsorption; a growth assessment to determine further workup; diet assessment; if the evaluation is normal or treatment fails, proceed with sugar breath testing, an empiric elimination diet, or lactulose breath test for SIBO; if diarrhea persists, evaluate for other causes (eg, stool osmolarity and electrolytes, neuroendocrine markers, endoscopy)

Readings

Bernaola AG, Bada MCA, Carreazo NY, et al. Probiotics for treating persistent diarrhoea in children. Cochrane Database Syst Rev. 2013 Aug;2013(8):CD007401; Burgers K, Lindberg B, Bevis ZJ. Chronic diarrhea in adults: evaluation and differential diagnosis. Am Fam Physician. 2020;101(8):472-480; Giannattasio A, Guarino A, Vecchio AL. Management of children with prolonged diarrhea. F1000Research. 2016 Feb 23;5(F1000 Faculty Rev):206; Hensgens MPM, Dekkers OM, Demeulemeester A, et al. Diarrhoea in general practice: when should a Clostridium difficile infection be considered? Results of a nested case-control study. Clinical Microbiology and Infection. 2014 December;20(12):O1067-O1074; Hu J, Torres AG. Enteropathogenic Escherichia coli: foe or innocent bystander? Clin Microbiol Infect. 2015 Aug;21(8):729-34; Johnston BC, Shamseer L, da Costa BR, et al. Measurement issues in trials of pediatric acute diarrheal diseases: A systematic review. Pediatrics. 2010;126(1):e222–e231; Poddar U, Agarwal J, Yachha SK, et al. Toddler’s diarrhea: Is it an under-recognized entity in developing countries? Journal of Tropical Pediatrics, 2013 December;59(6)470–475; Sadovsky R. Management of chronic diarrhea. Am Fam Physician. 2005;71(9):1797; Toltzis P, Nerandzic MM, Saade E, et al. High proportion of false-positive Clostridium difficile enzyme immunoassays for toxin A and B in pediatric patients. Infect Control Hosp Epidemiol. 2012 Feb;33(2):175-9.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Danialifar is a consultant for QOL medical. Members of the planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Danialifar was recorded at Pediatrics in the Islands: Clinical Pearls 2023, held June 24-30, 2023, on Maui, HI, and presented by Children’s Hospital Los Angeles Medical Group. For information on future CME activities from this presenter, please visit https://www.chla.org/continuing-medical-education-department. Audio Digest thanks Dr. Danialifar and the Children’s Hospital Los Angeles Medical Group for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

PD694101

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.