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

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, Nonresponsiveness 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 nonresponsiveness, 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.