Coeliac Disease Diagnosis – Biopsy Relevant

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Coeliac disease (CD) is a permanent intolerance to gluten found in wheat, rye and barley. Gluten induces an autoimmune reaction in the small intestinal mucosa resulting in inflammation, villous atrophy and malabsorption. The only effective treatment is a gluten-free diet, which usually leads to healing of the intestinal mucosa and recovery from signs and symptoms.[1]

What about diagnosis?

It is estimated that some 1%-3% of the population has coeliac disease in the USA and UK respectively – this makes this a common diagnosis. The average length of time between symptoms and diagnosis is 11-13 years.[2] Screening studies have shown five to 10 undiagnosed cases for every diagnosed case in some Western European countries.[3]


The gold standard for CD diagnosis is a biopsy post gluten exposure, but biopsies can result in false negatives due to the site of the biopsy, insufficient samples and may lead to continued mis-diagnosis.[4]

The preferred site for accurate diagnosis is the duodenal bulb, which is divided into the proximal and distal section of the small bowl.[5] The proximal section is the recommended area and should include 4-6 samples and also take from the 2nd and 3rd portion of the duodenum to present the best interpretative chance.

Post Biopsy tissue challenge

Challenging biopsied duodenal mucosa with gliadin, the toxic fraction of wheat gluten, can help establish a diagnosis of celiac disease when gluten sensitivity is suspected, but can’t be confirmed with standard diagnostic tests.

“People often start the gluten-free diet before diagnosis, just to see if they feel better (often practitioners give that wrong advice)”. Often such patients “need to return (to) a gluten-containing diet, wait for months, sometimes having symptoms, and repeat blood tests and endoscopy to disclose the presence of coeliac disease.”

However, CD can now be diagnosed by challenging the biopsied mucosa with gliadin. Researchers measured gliadin-induced mucosal expression of seven inflammatory markers: PY99, ICAM-1 (intercellular cell adhesion molecule), HLA-DR, CD3, CD25, CD69, and transglutaminase 2 IgA.[6] Whilst this type of diagnostic work up is only possible in suitably eqipped hospitals, it will be interesting to see if it becomes more widely available in the future.


[1] Di Sabatino A, Corazza GR. Coeliac disease. Lancet. 2009 Apr 25;373(9673):1480-93. View Abstract

[2] Cranney A, Zarkadas M, Graham ID, Butzner JD, Rashid M, Warren R, Molloy M, Case S, Burrows V, Switzer C. The Canadian Celiac Health Survey. Dig Dis Sci. 2007 Apr;52(4):1087-95. Epub 2007 Feb 22. View Abstract

[3] Fasano A, Catassi C. Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology. 2001 Feb;120(3):636-51. Review. View Abstract

[4] Lebwohl B, Kapel RC, Neugut AI, Green PH, Genta RM. Adherence to biopsy guidelines increases celiac disease diagnosis. Gastrointest Endosc. 2011;74:103-109 View Abstract

[5] Evans KE, Aziz I, Cross SS, et al. A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease. Am J Gastroenterol. 2011;10:1837-1842 View Abstract

[6] Tortora R, Russo I, De Palma GD, Luciani A, Rispo A, Zingone F, Iovino P, Capone P, Ciacci C. In Vitro Gliadin Challenge: Diagnostic Accuracy and Utility for the Difficult Diagnosis of Celiac Disease. Am J Gastroenterol. 2011 Sep 27. doi: 10.1038/ajg.2011.311. View Abstract

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