What lab tests are used to diagnose chronic diarrhea?

Laboratory Testing for Chronic Diarrhea

Begin with a comprehensive initial laboratory panel including complete blood count, C-reactive protein, erythrocyte sedimentation rate, basic metabolic panel, liver function tests, thyroid function tests, vitamin B12, folate, calcium, ferritin, and serological testing for celiac disease (IgA tissue transglutaminase with total IgA), along with stool studies for fecal calprotectin or lactoferrin and Giardia antigen testing. 1, 2

Initial Blood Work

The first-tier blood tests serve to identify organic disease, assess for malabsorption, and screen for systemic causes:

• Complete blood count (CBC) to detect anemia (particularly iron deficiency, which is highly sensitive for small bowel enteropathy including celiac disease) and inflammatory markers 1, 2
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have high specificity for organic disease, though fecal markers are more sensitive for inflammatory bowel disease 1, 2
• Basic metabolic panel including urea, electrolytes, calcium to assess for dehydration, electrolyte abnormalities, and malabsorption 1, 2
• Liver function tests to evaluate for hepatobiliary causes and associated conditions 1
• Vitamin B12, folate, and ferritin to screen for malabsorption 1
• Thyroid function tests with thyroid-stimulating hormone being the best predictor for hyperthyroidism as a cause of diarrhea 1

Celiac Disease Serological Testing

Celiac disease testing is mandatory in all patients with chronic diarrhea given its prevalence of 3-10% in this population and the significant delays in diagnosis. 1

• IgA tissue transglutaminase (tTG) antibody is the primary screening test 1, 2
• Total IgA level must be checked simultaneously to identify IgA deficiency, which occurs in approximately 2-3% of celiac patients and would cause false-negative results 1, 2
• For IgA-deficient patients, use IgG-tTG or IgG deaminated gliadin peptides as alternative testing 1, 2

Critical Pitfall

Failing to check total IgA levels when testing for celiac disease is a common error that leads to missed diagnoses in IgA-deficient patients. 2

Stool Studies

Inflammatory Markers

• Fecal calprotectin (threshold 50 mg/g) or fecal lactoferrin (threshold 4.0-7.25 mg/g) should be used to screen for inflammatory bowel disease, as these are more sensitive than ESR or CRP for detecting IBD 2
• These markers help distinguish inflammatory from non-inflammatory causes and guide the need for endoscopy 2

Infectious Evaluation

• Giardia antigen testing or PCR is strongly recommended due to high prevalence and excellent test performance in chronic diarrhea 2
• Stool culture for bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia) if infectious etiology suspected 3
• Clostridium difficile toxin testing particularly if recent antibiotic use within 8-12 weeks 1, 3
• Ova and parasites examination for Cryptosporidium, Cyclospora, and Entamoeba histolytica, especially in travelers or immunocompromised patients 3

Stool Characterization Tests

After initial screening, categorize diarrhea type (watery, fatty, or inflammatory) to guide further targeted testing: 4, 5

For Watery Diarrhea

• Stool electrolytes (sodium, potassium, chloride) to calculate osmotic gap and distinguish secretory from osmotic diarrhea 3, 6
• Osmotic gap = 290 - 2(stool Na+ + stool K+); gap >125 mOsm/kg suggests osmotic diarrhea, <50 mOsm/kg suggests secretory diarrhea 6
• Serum 7α-hydroxy-4-cholesten-3-one or 75Se-HCAT scan if bile acid malabsorption suspected 3

For Fatty Diarrhea

• Fecal elastase to assess for pancreatic insufficiency (though moderate-to-severe impairment required for adequate sensitivity) 7, 3
• Qualitative fecal fat if malabsorption suspected 3

For Bloody/Inflammatory Diarrhea

• Stool for occult blood 3
• Culture for Shiga toxin-producing E. coli (STEC) with monitoring of hemoglobin and platelets for hemolytic uremic syndrome 3

Additional Testing Based on Clinical Context

Risk Factor-Directed Testing

• Previous surgery history: Consider bile acid malabsorption testing (particularly after ileal resection or cholecystectomy) 1
• Systemic disease: Thyroid, parathyroid, and adrenal function tests if clinical suspicion 1
• Alcohol abuse: Assess pancreatic function and nutritional deficiencies 1
• Medication review: Up to 4% of chronic diarrhea cases are medication-related (magnesium supplements, ACE inhibitors, NSAIDs, gliptins, antineoplastic agents) 1

Special Populations

• Immunocompromised patients: Additional testing for Cryptosporidium, Cyclospora, Cystoisospora, microsporidia, Mycobacterium avium complex, and cytomegalovirus 3
• Recent travelers: Specific testing for intestinal parasites with multiple specimens if initial testing negative 3

Algorithmic Approach

1. Start with basic blood work and celiac serology (with total IgA) in all patients 1, 2
2. Add fecal calprotectin/lactoferrin and Giardia testing as first-line stool studies 2
3. If initial tests negative and symptoms persist, categorize diarrhea type using stool characteristics and targeted testing 4, 5
4. Consider endoscopy if alarm features present (weight loss, nocturnal symptoms, blood in stool, duration <3 months, age >45 years) or if initial workup negative 1

Key Pitfall to Avoid

Do not rely solely on ESR or CRP to screen for IBD when fecal calprotectin or lactoferrin are more sensitive markers. This is a common error that delays diagnosis. 2