Review article: management of patients with non-responsive coeliac disease

Aliment Pharmacol Ther. 1996 Oct;10(5):671-80. doi: 10.1046/j.1365-2036.1996.66237000.x.


A substantial minority of patients with coeliac disease (estimated at anything between 7 and 30%) fail to respond to treatment with a gluten-free diet. Non-responsiveness may be primary, that is when the patient fails to respond to treatment following initial diagnosis, or secondary, when a patient who has previously had a documented response to gluten exclusion becomes non-responsive to therapy. The commonest cause of non-responsiveness is continued gluten ingestion, either voluntary or inadvertent. Other causes to be considered include intolerances to dietary constituents other than gluten (e.g. milk, soya), pancreatic insufficiency, enteropathy-associated T-cell lymphoma and ulcerative jejunitis. There is some evidence that ulcerative jejunitis is, in fact, a manifestation of lymphoma. The most important steps in the management of the non-responsive coeliac patient are (a) to determine whether the patient is indeed coeliac, (b) to exclude lymphoma and (c) to establish the cause of the non-responsiveness. In those coeliac patients with no demonstrable cause for non-responsiveness, a variety of therapeutic stratagems (mostly based on small, uncontrolled studies) have been described; these include elimination diets, dietary supplementation with zinc and copper, and pharmacological therapy in the form of steroids, azathioprine and cyclosporin. In a minority of non-responsive patients, the clinical course is characterized by a rapid decline, and total parenteral nutrition is required. None of the therapies described above has been subjected to rigorous controlled studies. The precise mechanisms of non-responsiveness in coeliac patients need to be unravelled before rational therapeutic approaches can be established.

Publication types

  • Review

MeSH terms

  • Azathioprine / administration & dosage
  • Azathioprine / therapeutic use
  • Celiac Disease / diagnosis
  • Celiac Disease / drug therapy*
  • Celiac Disease / etiology
  • Clinical Trials as Topic
  • Copper / administration & dosage
  • Copper / therapeutic use*
  • Cyclosporine / administration & dosage
  • Cyclosporine / therapeutic use
  • Diet
  • Food, Fortified
  • Glutens / metabolism
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Parenteral Nutrition, Total
  • Steroids / therapeutic use
  • Zinc / administration & dosage
  • Zinc / therapeutic use*


  • Immunosuppressive Agents
  • Steroids
  • Copper
  • Glutens
  • Cyclosporine
  • Zinc
  • Azathioprine