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Practice Uncertainties Page

Does gluten sensitivity in the absence of coeliac disease exist?

BMJ 2012; 345 doi: (Published 30 November 2012) Cite this as: BMJ 2012;345:e7907
  1. Imran Aziz, clinical research fellow in gastroenterology1,
  2. Marios Hadjivassiliou, consultant neurologist2,
  3. David S Sanders, professor of gastroenterology1
  1. 1Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield S10 2JF, UK
  2. 2Department of Neurology, Royal Hallamshire Hospital, Sheffield
  1. Correspondence to: I Aziz imran.aziz{at}
  • Accepted 13 November 2012

Coeliac disease is a chronic inflammatory disorder of the small bowel which affects 1% of the population.1 The condition can be defined as a state of heightened immunological responsiveness to ingested gluten (from wheat, barley, or rye) in genetically susceptible individuals.2 The gold standard diagnosis of coeliac disease is by the demonstration of villous atrophy on duodenal biopsies, with coeliac serology (endomysial and tissue transglutaminase antibodies) playing a supportive role.2 3 The cornerstone of treatment for coeliac disease is lifelong adherence to a strict gluten-free diet, which leads to improvements in clinical outcome, psychological wellbeing, and quality of life for most patients.2

However, the number of patients consuming a gluten-free diet seems greatly out of proportion to the projected number of patients with coeliac disease. Marketers have estimated that 15-25% of North American consumers want gluten-free foods,4 5 although recently published data from the United States and New Zealand suggest this may be an overestimation.6 7 Nevertheless, this is now “big business,” with Reuters projecting an increased revenue in the US gluten-free food market from $1.31bn for the year 2011 to $1.68bn by 2015.8 In tandem, a growing problem encountered in clinical practice is the diagnosis and management of patients complaining of gluten related symptoms in the absence of diagnostic markers for coeliac disease, such as negative coeliac serology and normal duodenal biopsies. These patients pose a clinical dilemma to gastroenterologists, general practitioners, and dietitians and in the past have been described as belonging to a “no man’s land” because of the diagnostic uncertainty.9

What is the evidence of the uncertainty?

A search of PubMed (“coeliac disease”) yielded over 18 000 citations, with only 170 PubMed citations to papers on gluten sensitivity in the absence of coeliac disease. We limited our search to systematic reviews, case series, case-control studies, and …

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