1
Coeliac disease: changing views

https://doi.org/10.1016/j.bpg.2005.01.006Get rights and content

A continuing flow of new scientific developments concerning coeliac disease in the last decade asks for the formulation of new concepts of pathophysiology and clinical considerations. Immunogenetic studies have shown a correlation of the disease to the HLA region on the short arm of chromosome 6, immunological research has led to the concept of a T-cell driven immunologic response of the small intestine, with the identification of highly sensitive and specific antibodies. The understanding of the histopathology of coeliac disease has changed dramatically, initiated by the proposition of a spectrum of gluten sensitive enteropathy by Marsh in 1992. Clinical studies report a significant change in patient characteristics and epidemiology. The incidence of the disease has shifted to a majority of adult coeliacs, the disease may present with less severe symptoms of malabsorption and the screening studies suggest an overall prevalence of up to 1 in 200–300.

Histopathology has been standardized; lymphocytic enteritis (Marsh I), lymphocytic enteritis with crypthyperplasia (Marsh II), and villous atrophy, subdivided in partial, subtotal and total (Marsh IIIABC). Special attention is given to a subgroup of ‘refractory coeliacs’, including the identification of pre-malignant T-cells in the intestinal mucosa. The management of coeliacs primarely consists of monitoring for compliance and complications. Dietetic and medical associations need to establish protocols and offer additional training to undergraduetes, internships, general practitioners and other allied health professionals.

It might be relevant to have a low threshold for intestinal biopsies. However, screening asymptomatics may be harmful for individuals. Research is needed to assess the benefits of mass-screening in the future. HLA analysis can contribute towards recognising populations at increased risk.

Section snippets

Diagnostic criteria (1969–2001)

Until the 1950s, the diagnosis of coeliac was made when a child or adult had malabsorption in the absence of infection. When techniques for peroral small bowel biopsy were introduced during the 1960s, patients with malabsorption were found to have either a normal or a grossly abnormal jejunal biopsy. It is now more than 35 years since the diagnostic criteria for coeliac disease (CD) were proposed at the Interlaken Meeting of the European Society of Paediatric Gastroenterology and Nutrition

The coeliac spectrum according to Marsh

The spectrum of gluten sensitive enteropathy as Marsh described, consists of consecutive stages of progressive abnormalities of the small intestinal mucosa, comprising infiltration of the epithelium with lymphocytes, hyperplasia of crypts, progressive loss of surface epithelial cells and, ultimately, VA. In the Marsh I lesion (lymphocytic enteritis) the architecture of the mucosa appears normal and the mucosal epithelium is invaded by lymphocytes. Marsh II (lymphocytic enteritis with

Intestinal biopsies from the distal duodenum

Traditionally, the diagnosis of CD is made by the recognition of villous atrophy in mucosal specimens from the jejunum. Reliable mucosal specimens could be taken from the distal duodenum, this allows us to take biopsies in patients with less obvious symptoms and signs of CD.11

The Marsh spectrum of gluten sensitive enteropathy in vivo

When looking more carefully to the intestinal biopsies the consecutive stages of intraepithelial lymphocytosis, crypthyperplasia and VA have been recognized.7 Additional criteria for the distinct stages have been introduced.12 In Marsh I (lymphocytic enteritis) we assume intraepithelial lymphocytosis is present when more than 30 lymphocytes per 100 epithelial cells are counted. In Marsh II (lymphocytic enteritis with crypthyperplasia) we recognise intraepithelial lymphocytosis and

Histological follow-up

According to the diagnostic criteria, mucosal pathology in coeliacs should normalise in response to a gluten-free diet. Scientific reports on histological recovery, including time schemes and end-stage histology are limited. Histological recovery in coeliacs after starting a gluten-free diet takes its time, is incomplete in a substantial subgroup of patients and recovery is correlated to the degree of initial mucosal pathology.17, 18

Serological studies

Coeliac related serological tests have had great attention in the last decade. Formerly, antibodies to reticulin and gliadin were introduced, but their sensitivity proved to be disappointing. The introduction of antibodies to endomysium and recently tissue trans-glutaminase was welcomed with great enthusiasm. Reports suggested a sensitivity and specificity of up to nearly 100%, implicating those small intestinal biopsies would become obsolete. However, sero-negative coeliac disease seems a

Refractory coeliac disease

Although reports on the prevalence of refractory coeliac disease (RCD) are scarce, it is assumed to be 0–5% in adults. We consider coeliacs to be refractory, when symptoms of malabsorption due to villous atrophy are seen, persisting or regressing after a former good response despite a strict adherence to a gluten-free diet. All other causes of malabsorption must be excluded and additional features supporting the diagnosis of coeliac disease must be looked for, including the presence of

Epidemiology

The clinical presentation of CD is proven to be diverse, varying from severe, debilitating malabsorption states to mild symptoms as fatigue, abdominal complaints and isolated iron deficiency. At present, more than 60% of newly diagnosed patients are adults; 15–20% are over 60 years of age.23 Still, in society and among general practitioners and internists it generally remains to be considered a disease of children. Due to scientific research and increasing attention in postgraduate teachings

Genetic and environmental factors

The environmental factor is mainly ingestion of gluten, while several genes contribute to the genetic predisposition.26 The main genetic factors, as mentioned before, are given HLA-DQ genes, i.e. the genes encoding DQ2 or DQ8 in the HLA complex on 6p21.9 Approximately 95% of coeliacs have a DQ2 heterodimer comprised of DQB1*02 and DQA1*05 and most of the remaining 5% have a DQ8 heterodimer comprised of DQB1*302 and DQA1*03. A small number of individuals lacking either of those heterodimers have

Screening issues

Case-finding is the current approach for CD. Efficient case-finding in high-risk groups is more and more accepted as an effective strategy. The accuracy, cost-effectivity and acceptability seem good for individuals diagnosed by this attitude. The question is if the natural course of these high risk groups will be changed by GFD. Epidemiology has to focus which test is the best for disease detection. A combination of DQ typing and serology might be attractive, data about such an approach are

Quality of life

Ever since Dicke's work on the gluten-free diet in the 1930–1940s, striking effect of the GFD on mood and behaviour have been witnessed.30, 31 Even patients without apparent symptoms remark on a new-experienced vitality and perceived well-being, conforming the idea that in CD removal of gluten from the diet leads to ‘full clinical remission’. However, clinical evidence, poorly documented in literature, is accumulating that signs of depression and/or tiredness are typical symptoms of untreated

Living with coeliac disease

It is essential that the physician initiates on immediate referral to a registered dietician with expertise in CD. Because of the limited access of qualified dietician in a lot of countries not only in the second or third world, coeliac societies took on the role of making and revising diet recommendations, restrictions and guidelines unfortunately often without scientific, evidence-based qualifications for the changes. The diet is complicated to implement in daily life in the second and third

Conclusion

Coeliac disease continues to fascinate clinical and basic scientists. The chapters in this volume fall into two distinct groups. First, there are chapters mainly concerned with pathogenesis, and second, chapters describing clinical aspects of coeliac disease. Some authors look into the future and try to predict where these efforts in research might be leading us.

It is timely, therefore, that Best Practice publish a volume on Coeliac Disease. It is ten years since the volume on Coeliac Disease

References (32)

  • M.J. Van Belzen et al.

    A major non-HLA locus in celiac disease maps to chromosome 19

    Gastroenterology

    (2003)
  • K. Karell et al.

    European genetics cluster on celiac disease. HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the european genetics cluster on celiac disease

    Hum Immunol

    (2003)
  • G.W. Meeuwisse

    Diagnostic criteria in coeliac disease

    Acta Paediatr Scand

    (1970)
  • J.K. Visakorpi

    Definition of coeliac disease in children

  • J.A. Walker-Smith et al.

    Revised criteria for diagnosis of coeliac disease

    Arch Dis Child

    (1990)
  • Working Group of the United European Gastroenterology Week in Amsterdam

    When is a coeliac a coeliac?

    Eur J Gastroenterol

    (2001)

    • Cited by (42)

    • Intentional and inadvertent non-adherence in adult coeliac disease. A cross-sectional survey

      2013, Appetite
      Citation Excerpt :

      This change in presentation is partly explained by the increasing use of serological tests for active case-finding and for targeted screening in high risk groups (Collin, 2005; Hin, Bird, Fisher, Mahy, & Jewell, 1999; Jones, 2007; Korponay-Szabo et al., 2005). Advances in diagnostic testing, together with improved recognition of CD (National Institute for Health, 2009), have also resulted in an increased number of individuals diagnosed with atypical, minimal or no symptoms (Mulder & Cellier, 2005). The mainstay of treatment for CD is strict life-long adherence to a gluten-free diet (GFD).

    • Non-dietary therapeutic clinical trials in coeliac disease

      2012, European Journal of Internal Medicine
      Citation Excerpt :

      It is characterized by an excessive immunological reaction against dietary gluten, reaction that starts in the small intestine. This reaction triggers an autoimmune response against several auto-antigens, and results in the development of intestinal and extra-intestinal manifestations [3–6]. Several epidemiological studies have estimated a prevalence of one case per 130–400 individuals in the general population [3,6], with lower prevalence in Asian countries.

    • The Small Bowel

      2010, Brocklehurst's Textbook of Geriatric Medicine and Gerontology

    • Enteroscopy in the Diagnosis and Management of Celiac Disease

      2009, Gastrointestinal Endoscopy Clinics of North America

    • Inflammatory disease processes and interactions with nutrition

      2009, British Journal of Nutrition

    • Biomarkers for the diagnosis and monitoring of celiac disease: Can you count on me?

      2022, Current Opinion in Gastroenterology
    View all citing articles on Scopus
    View full text
    Copyright © 2005 Elsevier Ltd. All rights reserved.