Work-up for Chronic Diarrhea in Children
Initial Clinical Evaluation
Begin with a focused history targeting age-specific etiologies, stool characteristics, and red-flag symptoms to guide your diagnostic algorithm. 1
Critical History Elements
Age-specific considerations: Neonates and infants <6 months warrant investigation for congenital enteropathies, anatomic abnormalities (e.g., malrotation), and genetic disorders, while older children more commonly have infectious, allergic, or immune-mediated causes 1, 2
Stool characteristics:
- Watery diarrhea suggests osmotic (carbohydrate malabsorption, laxative use) or secretory mechanisms (bile acid malabsorption, microscopic colitis) 3
- Fatty/greasy stools (steatorrhea) with weight loss indicates malabsorption (celiac disease, giardiasis, pancreatic insufficiency) 3
- Bloody or mucoid stools point to inflammatory bowel disease, invasive bacterial/parasitic infections, or cow's milk protein allergy 3, 1
Red-flag symptoms requiring urgent evaluation: Severe weight loss or failure to thrive, fever, bloody diarrhea, severe abdominal pain, signs of malnutrition (edema, muscle wasting), or family history of inflammatory bowel disease or immunodeficiency 1
Physical Examination Priorities
- Growth parameters: Plot weight, height, and weight-for-height on growth charts to identify faltering growth or malnutrition 1
- Signs of malabsorption: Muscle wasting, edema, pallor (anemia), dermatitis, glossitis, or clubbing 1
- Abdominal examination: Distension, organomegaly, masses, or perianal disease (fissures, fistulas, skin tags suggesting Crohn disease) 1
First-Tier Laboratory Investigations
Order these initial tests for all children with chronic diarrhea lasting ≥2 weeks to categorize the mechanism and identify common treatable causes. 1, 4
Stool Studies
- Stool microscopy and culture: Identify bacterial pathogens (Salmonella, Shigella, Campylobacter, pathogenic E. coli) and parasites (Giardia, Cryptosporidium, Entamoeba histolytica) 1, 4
- Fecal calprotectin: Elevated levels (>50 µg/g) indicate intestinal inflammation and help distinguish inflammatory bowel disease from functional disorders 3
- Stool pH and reducing substances: pH <6.0 and reducing substances >0.5% suggest carbohydrate malabsorption, though these findings alone do not mandate dietary changes 5, 4
- Fecal fat (72-hour collection or spot Sudan stain): Quantify steatorrhea to confirm malabsorption; >7 g/day (or >15% of fat intake) is abnormal 4
- Fecal elastase-1: Low levels (<200 µg/g) indicate pancreatic insufficiency 1
Blood Tests
- Complete blood count with differential: Anemia (iron, B12, or folate deficiency from malabsorption), eosinophilia (parasitic infection, allergic enteropathy), or leukocytosis (infection, inflammation) 1
- Inflammatory markers: Elevated ESR or CRP support inflammatory bowel disease or chronic infection 1
- Celiac serology: Tissue transglutaminase IgA (tTG-IgA) with total IgA level; if IgA-deficient, order tTG-IgG or deamidated gliadin peptide antibodies 1, 3
- Electrolytes, albumin, and total protein: Hypoalbuminemia and hypoproteinemia indicate protein-losing enteropathy; electrolyte abnormalities reflect secretory losses 1, 4
- Thyroid function tests: Hyperthyroidism can cause chronic diarrhea in older children 3
Second-Tier Investigations (Based on Initial Results)
Proceed to these tests when first-tier studies are unrevealing or when specific etiologies are suspected. 1
Endoscopy with Biopsy
- Upper endoscopy (esophagogastroduodenoscopy) with duodenal biopsies: Indicated for suspected celiac disease (even with negative serology if clinical suspicion is high), giardiasis, or small bowel mucosal disorders (villous atrophy, microvillus inclusion disease) 1, 3
- Colonoscopy with biopsies: Perform when fecal calprotectin is elevated, bloody diarrhea is present, or inflammatory bowel disease is suspected; biopsies can also diagnose microscopic colitis or allergic colitis 1, 3
Imaging Studies
- Abdominal ultrasound: First-line imaging to detect anatomic abnormalities (malrotation, intussusception), bowel wall thickening, or organomegaly 2, 1
- Upper GI series with small bowel follow-through or MR enterography: Evaluate for malrotation, strictures, fistulas, or Crohn disease when inflammatory bowel disease is suspected 1
Specialized Tests
- Hydrogen breath tests: Diagnose lactose intolerance, fructose malabsorption, or small intestinal bacterial overgrowth (SIBO) 1, 3
- Sweat chloride test: Rule out cystic fibrosis in children with steatorrhea, failure to thrive, or recurrent respiratory infections 1
- Immunodeficiency screening: Measure immunoglobulin levels (IgA, IgG, IgM, IgE), lymphocyte subsets, and HIV testing if recurrent infections, severe diarrhea, or poor growth suggest immune dysfunction 1
Third-Tier Investigations (Refractory or Complex Cases)
Reserve these for children with persistent diarrhea despite initial management or when congenital/genetic disorders are suspected. 1
Genetic Testing
- Targeted gene panels or whole-exome sequencing: Indicated for neonates/infants with severe, intractable diarrhea suggesting congenital diarrheal disorders (e.g., microvillus inclusion disease, tufting enteropathy), monogenic inflammatory bowel disease, or primary immunodeficiency 1
Advanced Functional Studies
- Intestinal permeability tests (lactulose/mannitol ratio): Assess mucosal barrier function in suspected enteropathy 4
- Radionuclide imaging (e.g., SeHCAT scan): Quantify bile acid malabsorption when secretory diarrhea persists without clear cause 1, 3
Common Pitfalls to Avoid
- Do not delay referral to pediatric gastroenterology for infants <6 months with chronic diarrhea, children with severe malnutrition, or those with suspected inflammatory bowel disease or congenital enteropathy—early specialist involvement minimizes morbidity 1
- Do not empirically restrict lactose or other nutrients based solely on low stool pH or reducing substances; true lactose intolerance requires clinical correlation (severe diarrhea upon reintroduction) 5
- Do not order stool cultures for chronic diarrhea without acute onset or travel history unless parasitic infection is suspected; most bacterial pathogens cause acute, not chronic, diarrhea 1
- Do not overlook cow's milk protein allergy in infants with bloody diarrhea and failure to thrive; a 2–4 week trial of extensively hydrolyzed or amino acid-based formula is both diagnostic and therapeutic 1
- Do not perform endoscopy before checking celiac serology unless the child is already on a gluten-free diet, as serology is less invasive and highly sensitive 1, 3
Algorithmic Summary
- Categorize by stool type (watery, fatty, bloody) and age to prioritize differential diagnoses 1, 3
- Order first-tier tests (stool studies, CBC, celiac serology, albumin, fecal calprotectin) for all patients 1, 4
- Proceed to endoscopy if inflammatory markers or fecal calprotectin are elevated, or if malabsorption is confirmed without clear cause 1, 3
- Consider imaging (ultrasound, upper GI series) if anatomic abnormalities or Crohn disease are suspected 2, 1
- Refer for genetic testing in neonates/infants with severe, refractory diarrhea or when congenital enteropathy is suspected 1