Assessment of steatorrhoea

Reported to have 100% sensitivity in children with cystic fibrosis and severe pancreatic maldigestion, and 100% specificity in children with history of gastrointestinal diseases plus normal pancreas on ultrasound examination. However, the specificity calculated on children with small intestinal diseases dropped to 86%.[60]Carroccio A, Verghi F, Santini B, et al. Diagnostic accuracy of fecal elastase 1 assay in patients with pancreatic maldigestion or intestinal malabsorption: a collaborative study of the Italian Society of Pediatric Gastroenterology and Hepatology. Dig Dis Sci. 2001 Jun;46(6):1335-42. http://www.ncbi.nlm.nih.gov/pubmed/11414313?tool=bestpractice.com ​​

In adults, the sensitivity in detecting pancreatic insufficiency has been reported as 100% in patients with severe chronic pancreatitis, 77% in those with moderate disease, and 22% in those with mild disease.[50]Gullo L, Ventrucci M, Tomassetti P, et al. Fecal elastase 1 determination in chronic pancreatitis. Dig Dis Sci. 1999 Jan;44(1):210-3. http://www.ncbi.nlm.nih.gov/pubmed/9952246?tool=bestpractice.com ​​

The sensitivity of faecal elastase as a screening test for pancreatic insufficiency in patients presenting with steatorrhoea was 70% in another study.[61]Symersky T, van der Zon A, Biemond I, et al. Faecal elastase-I: helpful in analysing steatorrhoea? Neth J Med. 2004 Sep;62(8):286-9. http://www.ncbi.nlm.nih.gov/pubmed/15588069?tool=bestpractice.com ​​

CT and MRI/MRCP are considered first-line for the diagnosis of chronic pancreatitis along with clinical history and physical examination.[58]Gardner TB, Adler DG, Forsmark CE, et al. ACG clinical quideline: chronic pancreatitis. Am J Gastroenterol. 2020 Mar:115(3):322-39. https://journals.lww.com/ajg/Fulltext/2020/03000/ACG_Clinical_Guideline_Chronic_Pancreatitis.9.aspx http://www.ncbi.nlm.nih.gov/pubmed/32022720?tool=bestpractice.com ​​​ Also useful to exclude complications of chronic pancreatitis such as pseudocysts or cancer.[5]Conwell DL, Lee LS, Yadav D, et al. American Pancreatic Association practice guidelines in chronic pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014 Nov;43(8):1143-62. https://journals.lww.com/pancreasjournal/Fulltext/2014/11000/American_Pancreatic_Association_Practice.6.aspx http://www.ncbi.nlm.nih.gov/pubmed/25333398?tool=bestpractice.com

CT and MRI/MRCP are considered first-line for the diagnosis of chronic pancreatitis along with clinical history and physical examination.[58]Gardner TB, Adler DG, Forsmark CE, et al. ACG clinical quideline: chronic pancreatitis. Am J Gastroenterol. 2020 Mar:115(3):322-39. https://journals.lww.com/ajg/Fulltext/2020/03000/ACG_Clinical_Guideline_Chronic_Pancreatitis.9.aspx http://www.ncbi.nlm.nih.gov/pubmed/32022720?tool=bestpractice.com ​ Also useful to exclude complications of chronic pancreatitis such as pseudocysts or cancer.[5]Conwell DL, Lee LS, Yadav D, et al. American Pancreatic Association practice guidelines in chronic pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014 Nov;43(8):1143-62. https://journals.lww.com/pancreasjournal/Fulltext/2014/11000/American_Pancreatic_Association_Practice.6.aspx http://www.ncbi.nlm.nih.gov/pubmed/25333398?tool=bestpractice.com ​​

A simple inexpensive test that helps to diagnose chronic pancreatitis and pancreatic cancer, but both can have a similar appearance.

This test is done if CT/MRI is unavailable.

Two or more abnormal signs would indicate mild chronic pancreatitis and ≥3 would indicate severe disease.[62]Axon AT, Classen M, Cotton PB, et al. Pancreatography in chronic pancreatitis: international definitions. Gut. 1984 Oct;25(10):1107-12. https://gut.bmj.com/content/gutjnl/25/10/1107.full.pdf http://www.ncbi.nlm.nih.gov/pubmed/6479687?tool=bestpractice.com ​​

Consider if cross-sectional imaging or EUS is non-confirmatory and the clinical suspicion remains high.[58]Gardner TB, Adler DG, Forsmark CE, et al. ACG clinical quideline: chronic pancreatitis. Am J Gastroenterol. 2020 Mar:115(3):322-39. https://journals.lww.com/ajg/Fulltext/2020/03000/ACG_Clinical_Guideline_Chronic_Pancreatitis.9.aspx http://www.ncbi.nlm.nih.gov/pubmed/32022720?tool=bestpractice.com ​​

Elevated in autoimmune pancreatitis.

Total IgA is often routinely requested to assess for IgA deficiency, since the presence of IgA deficiency renders tTG-IgA insensitive.[63]Hill ID, Dirks MH, Liptak GS, et al. Guideline for the diagnosis and treatment of celiac disease in children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. 2005 Jan;40(1):1-19. https://journals.lww.com/jpgn/Fulltext/2005/01000/Guideline_for_the_Diagnosis_and_Treatment_of.1.aspx http://www.ncbi.nlm.nih.gov/pubmed/15625418?tool=bestpractice.com ​​ IgA deficiency is more common in people with coeliac disease than in the general population.[64]Kumar V, Jarzabek-Chorzelska M, Sulej J, et al. Celiac disease and immunoglobulin a deficiency: how effective are the serological methods of diagnosis? Clin Diagn Lab Immunol. 2002 Nov;9(6):1295-300. https://journals.asm.org/doi/10.1128/cdli.9.6.1295-1300.2002?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed http://www.ncbi.nlm.nih.gov/pubmed/12414763?tool=bestpractice.com ​ All diagnostic serological testing should be done with patients on a gluten-containing diet.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

tTG-IGA test is the preferred single test for detection of coeliac disease, including in children younger than 2 years who are not IgA deficient.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com ​ The test should be ordered in any case of suspected coeliac disease. Higher titres have increased positive predictive value. All diagnostic serological testing should be done with patients on a gluten-containing diet.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

Small bowel histology is the most specific and sensitive test. If the suspicion of coeliac disease is high, small bowel biopsy should be pursued even if serology tests are negative.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

EMA is an alternative to tTG-IgA, with greater specificity but lower sensitivity.[65]Sheppard AL, Elwenspoek MM, Scott LJ, et al. Systematic review with meta-analysis: the accuracy of serological tests to support the diagnosis of coeliac disease. Aliment Pharmacol Ther. 2022 Mar;55(5):514-27. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305515 http://www.ncbi.nlm.nih.gov/pubmed/35043426?tool=bestpractice.com ​ A combination of high-level tTG-IgA (>10 times upper limit of normal) with a positive EMA in a second blood sample can be used to diagnose coeliac disease in children. In symptomatic adults unwilling or unable to undergo upper gastrointestinal endoscopy, the same criteria may be considered as a diagnosis of likely coeliac disease.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com ​​ All diagnostic serological testing should be done with patients on a gluten-containing diet.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

tTG-IgA and EMA-IgA may be less sensitive in children younger than 2 years. Therefore, guidelines recommend that testing for coeliac disease in this age group include both tTG-IgA and DGP-IgG. Testing for coeliac disease in children with IgA deficiency should be performed using IgG-based antibodies (DGP-IgG or tTG-IgG).[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com ​​ All diagnostic serological testing should be done with patients on a gluten-containing diet.[16]Rubio-Tapia A, Hill ID, Semrad C, et al. American College of Gastroenterology guidelines update: diagnosis and management of celiac disease. Am J Gastroenterol. 2023 Jan 1;118(1):59-76. https://journals.lww.com/ajg/Fulltext/2023/01000/American_College_of_Gastroenterology_Guidelines.17.aspx http://www.ncbi.nlm.nih.gov/pubmed/36602836?tool=bestpractice.com

About 95% of coeliac patients are positive for HLA-DQ2.[66]Sciurti M, Fornaroli F, Gaiani F, et al.​ Genetic susceptibility and celiac disease: what role do HLA haplotypes play? Acta Biomed. 2018 Dec 17;89(9-S):17-21. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6502200 http://www.ncbi.nlm.nih.gov/pubmed/30561391?tool=bestpractice.com

Confirms diagnosis.[Figure caption and citation for the preceding image starts]: A scanning electron micrograph of an in vitro Giardia lamblia culture. The image shows trophozoites and a cluster of maturing cysts (bottom right)Courtesy of CDC/ Dr Stan Erlandsen; used with permission [Citation ends].

Nucleic acid amplification test (NAAT) diagnostics offer greater sensitivity than microscopy for Giardia detection.[67]Garcia LS, Arrowood M, Kokoskin E, et al. Laboratory diagnosis of parasites from the gastrointestinal tract. Clin Microbiol Rev. 2018 Jan;31(1):e00025-17. https://journals.asm.org/doi/10.1128/CMR.00025-17 http://www.ncbi.nlm.nih.gov/pubmed/29142079?tool=bestpractice.com ​ Polymerase chain reaction (PCR) of stool samples detects parasite concentrations as low as 10 parasites/100 microlitres of stool.[68]Ghosh S, Debnath A, Sil A, et al. PCR detection of Giardia lamblia in stool: targeting intergenic spacer region of multicopy rRNA gene. Mol Cell Probes. 2000 Jun;14(3):181-9. http://www.ncbi.nlm.nih.gov/pubmed/10860716?tool=bestpractice.com A single stool sample is often sufficient for complete parasitological diagnosis.​

Two methods in use - enzyme-linked immunosorbent assay and direct fluorescent antibody test.

Alternative to stool microscopy.

Testing of saliva, stool and, if possible, joint fluid.[69]Herbette M, Cren JB, Joffres L, et al. Usefulness of polymerase chain reaction for diagnosing Whipple's disease in rheumatology. PLoS One. 2018;13(7):e0200645. https://www.doi.org/10.1371/journal.pone.0200645 http://www.ncbi.nlm.nih.gov/pubmed/30020975?tool=bestpractice.com

Steatorrhoea may occur due to opportunistic infections or HIV infection of small bowel.

This test is done if patient cannot receive contrast for CT.

Likely that mass of this location is within reach of an enteroscope.

Only suitable if mass is within reach of an enteroscope.

Appears more sensitive than fat biopsy in patients with secondary amyloidosis due to chronic arthritis.[70]Breedveld FC, Markusse HM, MacFarlane JD. Subcutaneous fat biopsy in the diagnosis of amyloidosis secondary to chronic arthritis. Clin Exp Rheumatol. 1989 Jul-Aug;7(4):407-10. http://www.ncbi.nlm.nih.gov/pubmed/2591113?tool=bestpractice.com ​​[Figure caption and citation for the preceding image starts]: Congo red stain blood vessel in a bone marrow biopsy demonstrating green birefringence pathognomonic of amyloidosisCourtesy of Morie A. Gertz, MD/Mayo Clinic; used with permission [Citation ends].

TSH should be the initial test. If this is border-line or suppressed, additional testing such as free thyroid hormones should be requested.

Sensitivity ranges from 17% to 68%; specificity from 44% to 86%.[71]Saad RJ, Chey WD. Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy. Clin Gastroenterol Hepatol. 2014;12:1964-72. http://www.ncbi.nlm.nih.gov/pubmed/24095975?tool=bestpractice.com

Helps in localisation of the disease.[Figure caption and citation for the preceding image starts]: CT scan demonstrating thickening of the terminal ileum in a patient with Crohn's disease exacerbationCourtesy of Drs Wissam Bleibel, Bishal Mainali, Chandrashekhar Thukral, and Mark A. Peppercorn; used with permission [Citation ends].[Figure caption and citation for the preceding image starts]: CT scan demonstrating thickening of the terminal ileum in a patient with Crohn's disease exacerbationCourtesy of Drs Wissam Bleibel, Bishal Mainali, Chandrashekhar Thukral, and Mark A. Peppercorn; used with permission [Citation ends].

May be normal if proximal small-bowel Crohn's disease.

Marker of mucosal inflammation.

Emerging as promising test for early lesions.

Elevated alkaline phosphatase levels suggest cholestasis.

Present in about 95% of patients.[72]Heseltine L, Turner IB, Fussey SP, et al. Primary biliary cirrhosis. Quantitation of autoantibodies to purified mitochondrial enzymes and correlation with disease progression. Gastroenterology. 1990 Dec;99(6):1786-92. https://www.gastrojournal.org/article/0016-5085(90)90488-M/pdf http://www.ncbi.nlm.nih.gov/pubmed/2227292?tool=bestpractice.com ​​[Figure caption and citation for the preceding image starts]: Characteristic auto-antibody patterns in primary biliary cholangitis. White arrow: anti-mitochondrial staining; red arrow: multiple nuclear dot ANA stainingCourtesy of DEJ Jones; used with permission [Citation ends].

Definitive diagnostic and staging test.[Figure caption and citation for the preceding image starts]: Characteristic histological appearances of primary biliary cholangitis: (a) early stage disease; (b) advanced-stage disease; (c) disease with a significant inflammatory componentCourtesy of Professor Alastair Burt, Newcastle University; used with permission [Citation ends].

Useful in patients who are AMA negative. Anti-sp100 and anti-gp210 antibodies are specific to primary biliary cholangitis.

Mildly elevated alkaline phosphatase is common.

Elevated alkaline phosphatase levels suggest cholestasis.

Bilirubin becomes elevated only with significant strictures.

Elevated with biliary obstruction.

MRCP and ERCP are considered equivalent in diagnosis. ERCP allows biopsy of strictures to exclude cholangiocarcinoma, but MRCP is typically preferred because it is non-invasive.[55]Chapman MH, Thorburn D, Hirschfield GM, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019 Aug;68(8):1356-78. https://gut.bmj.com/content/68/8/1356 http://www.ncbi.nlm.nih.gov/pubmed/31154395?tool=bestpractice.com [73]European Association for the Study of the Liver. EASL clinical practice guidelines on sclerosing cholangitis. J Hepatol. 2022 Sep;77(3):761-806. https://www.journal-of-hepatology.eu/article/S0168-8278(22)00326-9/fulltext http://www.ncbi.nlm.nih.gov/pubmed/35738507?tool=bestpractice.com ​​

p-ANCA is positive in 33% to 88% of patients with primary sclerosing cholangitis.[74]Terjung B, Worman HJ. Anti-neutrophil antibodies in primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol. 2001 Aug;15(4):629-42. http://www.ncbi.nlm.nih.gov/pubmed/11492972?tool=bestpractice.com ​ A variety of other auto-antibodies can also be detected at low levels.

Indicated when tissue sampling or therapeutic intervention is required (e.g., brush cytology to evaluate for co-existing malignancy, extraction of bile duct stones, and dilation of prominent bile duct strictures).[55]Chapman MH, Thorburn D, Hirschfield GM, et al. British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis. Gut. 2019 Aug;68(8):1356-78. https://gut.bmj.com/content/68/8/1356 http://www.ncbi.nlm.nih.gov/pubmed/31154395?tool=bestpractice.com [56]Bowlus CL, Arrivé L, Bergquist A, et al. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2023 Feb 1;77(2):659-702. https://journals.lww.com/hep/Fulltext/2023/02000/AASLD_practice_guidance_on_primary_sclerosing.29.aspx http://www.ncbi.nlm.nih.gov/pubmed/36083140?tool=bestpractice.com ​​[Figure caption and citation for the preceding image starts]: Typical endoscopic retrograde cholangiopancreatography (ERCP) findings in a patient with primary sclerosing cholangitis (PSC): multifocal strictures of the intra- and extrahepatic bile ductsCourtesy of Dr Kris Kowdley; used with permission [Citation ends].