Duodenal biopsy site for diagnosing coeliac disease: D1, D2, or both?

Summary

Current best practice, in line with BSG, ESPGHAN and ACG guidance, is to take biopsies from both the duodenal bulb (D1) and the distal duodenum (D2 / D3), placed in separate pots. At least one (preferably two) bulb biopsies plus four or more distal duodenal biopsies is the standard recommendation. D2 remains the principal diagnostic site, but adding D1 increases diagnostic sensitivity, particularly for ultra-short coeliac disease and paediatric cases.

Historical position: D2 only

Traditional teaching was to biopsy the second part of the duodenum and to avoid the bulb. The rationale was that the bulb is architecturally complex — Brunner glands distort villous architecture, peptic injury and gastric metaplasia are common, and orientation in the histology laboratory is often poor. These features were felt to give unreliable assessment of villous atrophy and to risk false-positive interpretations of Marsh 1–3 change.

Why D1 was added: ultra-short coeliac disease

A series of studies in the 2000s and 2010s showed that a meaningful minority of coeliac patients have disease that is confined to, or most marked in, the bulb. Bonamico and colleagues demonstrated that taking bulb biopsies in addition to distal duodenum increased the diagnostic yield in children, and identified the 9 o’clock and 12 o’clock positions as the most informative bulb sites. Evans et al. and subsequent adult series have confirmed that around 5–10% of adult coeliac patients have lesions limited to or more severe in the bulb (ultra-short coeliac disease), and that omitting D1 would miss these cases.

Practical protocol

  • At least 1–2 biopsies from the duodenal bulb (ideally from the 9 o’clock and 12 o’clock positions, per Bonamico).
  • At least 4 biopsies from the distal duodenum (D2 / D3).
  • Bulb biopsies should be submitted in a separate, clearly labelled pot so the pathologist can apply appropriate caution when interpreting villous architecture around Brunner glands.
  • Single-biopsy-per-pass technique is preferred for orientation; multiple biopsies in one bite increase tangential sectioning and false-positive villous blunting.

Caveats with bulb biopsies

Bulb mucosa is intrinsically harder to assess. Brunner gland lobules push villi apart and shorten them, gastric metaplasia is common, and peptic duodenitis can produce IEL increases unrelated to gluten. Bulb-only abnormalities should therefore be interpreted in the context of serology, HLA status, and the distal duodenal appearances before a confident coeliac diagnosis is made.

Bottom line

Biopsy both. D2 remains the principal diagnostic site, but the addition of separately-potted bulb biopsies materially improves sensitivity, particularly for ultra-short coeliac disease and in children. This is the position of the BSG, ESPGHAN and ACG guidelines.

Key references

  • Ludvigsson JF, Bai JC, Biagi F, et al. Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut 2014;63:1210–1228.
  • Husby S, Koletzko S, Korponay-Szabó I, et al. European Society Paediatric Gastroenterology, Hepatology and Nutrition Guidelines for Diagnosing Coeliac Disease 2020. J Pediatr Gastroenterol Nutr 2020;70:141–156.
  • Rubio-Tapia A, Hill ID, Kelly CP, et al. ACG Clinical Guidelines: Diagnosis and Management of Celiac Disease. Am J Gastroenterol 2013;108:656–676 (and updated 2023 ACG guideline, Am J Gastroenterol 2023;118:59–76).
  • Bonamico M, Mariani P, Thanasi E, et al. Patchy villous atrophy of the duodenum in childhood celiac disease. J Pediatr Gastroenterol Nutr 2004;38:204–207.
  • Bonamico M, Thanasi E, Mariani P, et al. Duodenal bulb biopsies in celiac disease: a multicenter study. J Pediatr Gastroenterol Nutr 2008;47:618–622.
  • 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;106:1837–1842.
  • Mooney PD, Kurien M, Evans KE, et al. Clinical and immunologic features of ultra-short celiac disease. Gastroenterology 2016;150:1125–1134.
  • Lebwohl B, Kapel RC, Neugut AI, et al. Adherence to biopsy guidelines increases celiac disease diagnosis. Gastrointest Endosc 2011;74:103–109.
  • Latorre M, Lagana SM, Freedberg DE, et al. Endoscopic biopsy technique in the diagnosis of celiac disease: one bite or two? Gastrointest Endosc 2015;81:1228–1233.