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Chapter 2: Refractory Coeliac Disease: An Opportunity to Prevent a T-Cell Lymphoma

W. H. M. Verbeek, M. W. J. Schreurs, A. Al-Toma, J. J. Oudejans, and C. J. J. Mulder, Department of Gastroenterology, VU University Medical Center, Amsterdam, the Netherlands

The Science of Gluten-Free Foods and Beverages
Pages 13-22
DOI: https://doi.org/10.1094/9781891127670.002
ISBN: 978-1-891127-67-0


Coeliac disease (CD) is a lifelong inflammatory condition of the gastrointestinal (GI) tract that affects the small intestine in genetically susceptible individuals. On small bowel biopsy there is a characteristic, although not specific, mucosal trias of villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes (IELs) that impairs nutrient absorption by the involved bowel. Prompt improvement of nutrient absorption and healing of the characteristic intestinal mucosal trias is seen upon withdrawal of gluten from the diet.

Non-responsive coeliac disease (NRCD) can be described in terms of the clinical scenario as a lack of initial response to a prescribed gluten-free diet (GFD) or the recurrence of symptoms despite adherence and maintenance of GFD in a patient who responded initially to the GFD (Schuppan et al., 2006). Although clinical improvement is usually followed by histological improvement, on occasions there is evidence for histological improvement with persistence of clinical symptoms that could be related to other causes (Wahab et al., 2001; Abdulkarim et al., 2002). Clinical improvement is usually evident within the first weeks after starting the GFD; however, it might take up to 2–5 years before a normalisation of the intestinal mucosa is recognised, especially in the elder population (Wahab et al., 2002). We defined refractory CD (RCD) as persisting or recurring villous atrophy with crypt hyperplasia and increased IELs in spite of a strict GFD adherence for more than 12 months, or when severe persisting symptoms necessitate intervention independent from the duration of the GFD (Daum et al., 2005; Marsh, 1992). All other causes of malabsorption must be excluded and additional features supporting the diagnosis of CD must be looked for, including the presence of antibodies (tTGA) in the untreated state and the presence of coeliac-related HLA-DQ markers. Currently, two categories of RCD are being recognised: type I, without aberrant T-cells, and type II, with aberrant T-cells detected by immunophenotyping, flowcytometric analysis or immunohistology of the intestinal mucosa (Wahab et al., 2002). Arbitrarily, a percentage of aberrant cells CD7+CD3- cytoplasmic CD3+% of IEL of ≤10% has been defined as normal, and more than 20% as definitively abnormal.