Presentation: Patient with sero-negative coeliac disease

A 19-year-old woman presents with an iron deficiency anaemia. Her IgA-based tests are negative, without IgA deficiency. But, as her sister and first-degree cousin have coeliac disease, she has an endoscopy with distal duodenal biopsies. These demonstrate villous atrophy (Marsh 3b).

• HLA DQ2 and DQ8 genomic testing should be performed (once in a lifetime); under 1% of people with coeliac disease are negative for these causative variants.
  • A positive result does not confirm the disease, as it is also found in 30%–40% healthy Western population.
  • A negative result means that coeliac disease can almost certainly be excluded.
• This is not a test currently available through the National Genomic Test Directory; however, testing is available through secondary care laboratories.

• Ensure eating gluten when testing serology and endoscopy.
• Check HLA DQ2 and DQ8 positivity.
• Exclude other causes of villous atrophy via consulting table 2 by Ludvigsson and colleagues.
• Start the patient on a gluten-free diet, with advice and follow up from a dietitian.
• Re-biopsy to confirm histological response to the gluten-free diet.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.

For clinicians

• Coeliac UK: Seronegative coeliac disease

Resources:

• Leonard MM, Lebwohl B, Rubio-Tapia A and Biagi F. ‘AGA Clinical Practice Update on the Evaluation and Management of Seronegative Enteropathies‘. Gastroenterology 2020: volume 160, issue 1, pages 437–444. DOI: 10.1053/j.gastro.2020.08.061
• Ludvigsson JF, Bai JC, Biagi F and others. ‘Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology‘. Gut 2014: volume 63, pages 1,210–1,228. DOI: 10.1136/gutjnl-2013-306578

For patients

• Coeliac UK: Seronegative coeliac disease