Presentation: Patient with histological evidence of villous atrophy

Example clinical scenario

A young man has had an endoscopy for dyspepsia where distal duodenal biopsies are taken. These show villous atrophy.

HLA-DQ2 and HLA-DQ8 genotype testing will help exclude coeliac disease as a differential diagnosis, if negative.
This test is not currently available through the National Genomic Test Directory, but there are tests available through secondary care laboratories.

Take a history of symptoms, drug history and family history.
Check IgA tissue transglutaminase/antiendomysial antibody/deamidated gliadin peptides as well as IgA levels. Consider IgG testing if the IgA level is low.
Draw blood to test for HLA DQ2 and DQ8 to exclude coeliac disease if the serology is normal
Consider differential diagnoses below:

Immune disorders	Common variable immunodeficiency syndrome Glomerulonephritis Hypogammaglobulaemia IgA deficiency
Autoimmune disease (as these patients may have concurrent coeliac disease)	Autoimmune enteropathy (adults and children) Graves’ disease Haemolytic anaemia Hashimoto’s thyroiditis Multiple sclerosis Psoriasis Rheumatoid arthritis Sjögren’s syndrome Systemic lupus erythematosus Thymoma-associated autoimmune enteropathy Type I diabetes mellitus
Hypersensitivity/ non-gluten protein intolerance	Non-coeliac gluten sensitivity Protein intolerance (cows’ milk, soy, eggs, peanuts, cereals)
Infection	AIDS Cryptosporidium Giardiasis Helicobacter pylori gastritis (common) Postinfectious diarrhoea Small intestinal bacterial overgrowth Tropical sprue Tuberculosis (including atypical TB) Viral Whipple’s disease
Drugs	Chemotherapy Non-steroidal anti-inflammatory drugs Olmesartan Mycophenolate mofetil
Neoplasia	Enteropathy-associated T-cell lymphoma Immunoproliferative small intestinal disease Refractory CD type 2 CD4 T-cell proliferation
Other	Abetalipoproteinaemia Collagenous colitis Collagenous duodenitis Crohn’s disease Eosinophilic gastroenteritis Glycogen storage disease Microscopic colitis Radiation enteritis Small bowel ischaemia

References:

Leonard MM, Lebwohl B, Rubio-Tapia A and Biagi F. ‘AGA Clinical Practice Update on the Evaluation and Management of Seronegative Enteropathies: Expert Review‘. Gastroenterology 2021: 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, issue 8, pages 1,210–1,228. DOI: 10.1136/gutjnl-2013-306578