Chronic diarrhea laboratory findings

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Case #1

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:  Omodamola Aje B.Sc, M.D. [2] Anum Ijaz M.B.B.S., M.D.[3]

## Overview

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The laboratory findings in chronic diarrhea include complete blood count to evaluate for anemia and abnormal white blood cell count, electrolytes, thyroid function tests, serology testing for celiac disease, and stool analysis for fecal leukocytes, fecal lactoferrin, and fecal occult blood.

## Laboratory Findings

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### Blood Tests

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Initial laboratory tests should include a complete blood count to evaluate for anemia and an abnormal white blood cell count, as well as electrolytes, thyroid function tests, and serology testing for celiac disease.[1][2][3][4]

### Stool Analysis

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* Fecal leukocytes: The presence of white blood cells in the stool has a sensitivity of 70% and a specificity of 50% for detecting inflammation in studies of infectious diarrhea. Fecal white blood cells can be present in both infectious colitis and inflammatory bowel diseases such as ulcerative colitis, Crohn's disease, and microscopic colitis.
* Fecal occult blood: The sensitivity and specificity of stool guaiac cards for detecting inflammatory or neoplastic causes of diarrhea have not been studied.
* Osmotic gap: Measuring stool potassium and sodium concentrations can determine the stool osmotic gap. For secretory diarrhea, the osmotic gap is less than 50 mOsm/kg. In osmotic diarrhea, the osmotic gap is greater than 50 mOsm/kg.

The table below summarizes common causes of chronic non-infectious diarrhea and laboratory tests for the diagnosis.[5]

Diagnostic Test | Mechanism and Clinical Utility | Diagnostic Thresholds & Findings | Sensitivity | Specificity | Key Clinical Considerations

|
|
|
|
|

Celiac Disease |
IgA-tTG Antibody | Primary screening tool targeting transglutaminase 2; normal ranges vary by ELISA test reference defined by the manufacturer.  | High titers increase positive predictive value [6] ; levels >10x the upper limit of normal (ULN) are 100% specific.  | 93% [7] | 97.9%  | Recommended first-line test. Concurrent total IgA measurement is vital due to higher IgA deficiency prevalence in Celiac patients. Requires active gluten consumption (≥2–4 weeks) [8]. Confirm with duodenal biopsy in adults.
IgG DGP Antibody | Secondary test for patients with IgA deficiency.  | Varies by laboratory reference.  | 80.1%–98.6% [9] | ≥95%  | Use when IgA-tTG is negative but IgA deficiency is suspected. Confirm with duodenal biopsy in adults.
Microscopic Colitis |
Colonoscopy with Biopsy | Histopathologic assessment of intraepithelial lymphocytes (<5 per 100 cells = normal) and collagen band (<5 μm = normal).  | Lymphocytic colitis: ≥20 intraepithelial lymphocytes per 100 epithelial cells. [10]

Collagenous colitis: Subepithelial collagen band >10 μm [10]

| N/A (Standard Reference)  | N/A (Standard Reference)  | Histopathology is the gold standard for diagnosis.
SIBO Evaluation |
Glucose Hydrogen Breath Test | Detects hydrogen and methane in human breadth produced by bacterial fermentation of 75 g of glucose.  | Hydrogen rise ≥20 ppm within 90 min;

Methane rise ≥10 ppm at any point (suggests Intestinal methanogenic overgrowth (IMO)) [11]

| 54.5%[12] | 83.2%  | More accurate than lactulose as glucose is absorbed early; avoid in diabetic patients due to high glucose load.
Lactulose Hydrogen Breath Test | Detects breadth hydrogen and methane produced by bacterial fermentation of 10 g of lactulose.  | Hydrogen rise ≥20 ppm within 90 min; Methane rise by ≥10 ppm at any point (suggests IMO).  | 42% [12] | 70.6%  | Synthetic disaccharide reaches the colon; high risk of false positives due to normal colonic flora fermentation.
Exocrine Pancreatic Insufficiency (EPI) |
Fecal Elastase | Measures pancreatic elastase-1 levels, reflecting overall pancreatic enzyme production.  | Abnormal: Fecal elastase <200 μg/g.

Highly specific for EPI: Fecal elastase <100 μg/g.

| 77% (vs secretin stimulation test) [13] ; 96% (vs quantitative fecal fat).  | 88% (vs secretin stimulation test or quantitative fecal fat).  | Stable in feces at room temp (1 week) or refrigerated at 4 degree celsius (1 month). Test only on solid stool to avoid false positives. Not affected by enzyme therapy or fasting.

Abbreviations: DGP= Deamidated Gliadin Peptide; ELISA= Enzyme-linked immunosorbent assay; EPI= Exocrine Pancreatic Insufficiency; Ig= Immunoglobulin; NA= not applicable; SIBO= Small Intestinal Bacterial Overgrowth; tTG= Tissue Transglutaminase.

## References

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1. ↑ Fine, K; Schiller, L (1999). "AGA Technical Review on the Evaluation and Management of Chronic Diarrhea☆". Gastroenterology. 116 (6): 1464–1486. doi:10.1016/S0016-5085(99)70513-5. ISSN 0016-5085.
2. ↑ "American Gastroenterological Association medical position statement: Guidelines for the evaluation and management of chronic diarrhea☆, ☆☆". Gastroenterology. 116 (6): 1461–1463. 1999. doi:10.1016/S0016-5085(99)70512-3. ISSN 0016-5085.
3. ↑ Camilleri M (2004). "Chronic diarrhea: a review on pathophysiology and management for the clinical gastroenterologist". Clin Gastroenterol Hepatol. 2 (3): 198–206. PMID 15017602.
4. ↑ Fine KD, Seidel RH, Do K (2000). "The prevalence, anatomic distribution, and diagnosis of colonic causes of chronic diarrhea". Gastrointest Endosc. 51 (3): 318–26. PMID 10699778.CS1 maint: Multiple names: authors list (link)
5. ↑ Singh P, Lee A, Sheth NM, Chey WD (March 2026). "Chronic, Noninfectious Diarrhea: A Review". JAMA. doi:10.1001/jama.2026.0872. PMID 41770539 Check `|pmid=` value (help).
6. ↑ van der Windt DA, Jellema P, Mulder CJ, Kneepkens CM, van der Horst HE (May 2010). "Diagnostic testing for celiac disease among patients with abdominal symptoms: a systematic review". JAMA. 303 (17): 1738–46. doi:10.1001/jama.2010.549. PMID 20442390.
7. ↑ Lewis NR, Scott BB (January 2010). "Meta-analysis: deamidated gliadin peptide antibody and tissue transglutaminase antibody compared as screening tests for coeliac disease". Aliment Pharmacol Ther. 31 (1): 73–81. doi:10.1111/j.1365-2036.2009.04110.x. PMID 19664074.
8. ↑ Leffler D, Schuppan D, Pallav K, Najarian R, Goldsmith JD, Hansen J, Kabbani T, Dennis M, Kelly CP (July 2013). "Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease". Gut. 62 (7): 996–1004. doi:10.1136/gutjnl-2012-302196. PMC 3525791. PMID 22619366.
9. ↑ Giersiepen K, Lelgemann M, Stuhldreher N, Ronfani L, Husby S, Koletzko S, Korponay-Szabó IR (February 2012). "Accuracy of diagnostic antibody tests for coeliac disease in children: summary of an evidence report". J Pediatr Gastroenterol Nutr. 54 (2): 229–41. doi:10.1097/MPG.0b013e318216f2e5. PMID 22266486.
10. ↑ 10.0 10.1 Langner C, Aust D, Ensari A, Villanacci V, Becheanu G, Miehlke S, Geboes K, Münch A (April 2015). "Histology of microscopic colitis-review with a practical approach for pathologists". Histopathology. 66 (5): 613–26. doi:10.1111/his.12592. PMID 25381724.
11. ↑ Rezaie A, Buresi M, Lembo A, Lin H, McCallum R, Rao S, Schmulson M, Valdovinos M, Zakko S, Pimentel M (May 2017). "Hydrogen and Methane-Based Breath Testing in Gastrointestinal Disorders: The North American Consensus". Am J Gastroenterol. 112 (5): 775–784. doi:10.1038/ajg.2017.46. PMC 5418558. PMID 28323273.
12. ↑ 12.0 12.1 Losurdo G, Leandro G, Ierardi E, Perri F, Barone M, Principi M, Leo AD (January 2020). "Breath Tests for the Non-invasive Diagnosis of Small Intestinal Bacterial Overgrowth: A Systematic Review With Meta-analysis". J Neurogastroenterol Motil. 26 (1): 16–28. doi:10.5056/jnm19113. PMC 6955189 Check `|pmc=` value (help). PMID 31743632.
13. ↑ Vanga RR, Tansel A, Sidiq S, El-Serag HB, Othman MO (August 2018). "Diagnostic Performance of Measurement of Fecal Elastase-1 in Detection of Exocrine Pancreatic Insufficiency: Systematic Review and Meta-analysis". Clin Gastroenterol Hepatol. 16 (8): 1220–1228.e4. doi:10.1016/j.cgh.2018.01.027. PMC 6402774. PMID 29374614.

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