Elsevier

The Lancet

Volume 391, Issue 10115, 6–12 January 2018, Pages 70-81
The Lancet

Seminar
Coeliac disease

https://doi.org/10.1016/S0140-6736(17)31796-8Get rights and content

Summary

Coeliac disease occurs in about 1% of people in most populations. Diagnosis rates are increasing, and this seems to be due to a true rise in incidence rather than increased awareness and detection. Coeliac disease develops in genetically susceptible individuals who, in response to unknown environmental factors, develop an immune response that is subsequently triggered by the ingestion of gluten. The disease has many clinical manifestations, ranging from severe malabsorption to minimally symptomatic or non-symptomatic presentations. Diagnosis requires the presence of duodenal villous atrophy, and most patients have circulating antibodies against tissue transglutaminase; in children, European guidelines allow a diagnosis without a duodenal biopsy provided that strict symptomatic and serological criteria are met. Although a gluten-free diet is an effective treatment in most individuals, a substantial minority develop persistent or recurrent symptoms. Difficulties adhering to a gluten-free diet have led to the development of non-dietary therapies, several of which are undergoing trials in human beings.

Introduction

Coeliac disease is an autoimmune disorder that occurs in genetically predisposed individuals who develop an immune reaction to gluten. The disease primarily affects the small intestine; however, the clinical manifestations are broad, with both intestinal and extra-intestinal symptoms. Coeliac disease is notable because of its broad clinical spectrum of presentations, large age range at which onset can occur (which can precede diagnosis by several years), and the increased morbidity and mortality that has been found in most studies. The disease also provides a model of an immune-based disease with both strong genetic and environmental risk factors. Coeliac disease has been the topic of previous Seminars in The Lancet,1, 2 and we aim to provide the most current information to clinicians with this Seminar.

Section snippets

Gluten

The major environmental factor responsible for the development of coeliac disease is gluten. Gluten (from the Latin “glue”) is the term for the prolamin storage proteins of the cereal grains wheat, rye, and barley. Gluten is favoured in breadmaking for its elasticity; however, it is enriched in glutamines and prolines and, as a result, is incompletely digested by gastric, pancreatic, and brush border peptidases, leaving large peptides up to 33 aminoacids long.3 These peptides enter the lamina

Epidemiology

Coeliac disease affects about 1% of the population.56, 57 Worldwide, there are differences in prevalence that are not explained by the known genetic and environmental risk factors. For example, in Europe, Germany has a lower prevalence of coeliac disease than other countries, with the highest prevalence being in Sweden and Finland.58 Within the USA, the prevalence in African Americans is low compared with those of white ethnic background;59 similarly, in Brazil, Brazilians of African descent

Clinical manifestations

Over the past 10 years, attempts have been made to bring consensus to the terminology of the clinical stages of coeliac disease (panel 1).70 The common presentation of coeliac disease has shifted from the historically classic symptoms of malabsorption in childhood to non-classic symptoms, which can be present in childhood or adulthood. Classic symptoms include chronic diarrhoea, weight loss, and failure to thrive,71 which are quite rare. The more common, non-classical symptoms include iron

Diagnosis

A combination of coeliac disease serology testing and duodenal biopsy sampling is required for the diagnosis of coeliac disease in adults. The current American College of Gastroenterology,73 British Society of Gastroenterology,74 and NICE guidelines71 recommend testing high-risk adults with coeliac serology. Measurement of the concentration of IgA-TTG antibodies should be done as a first-line screening test because of its high sensitivity and negative predictive value, and because it is less

Controversies in testing for coeliac disease

There is controversy as to whom to test for coeliac disease. A central tenet of this issue is the ethical difference between population screening and case-finding. If a patient seeks medical help then the physician is attempting to diagnose an underlying condition; for example, patients with coeliac disease can present with symptoms of irritable bowel syndrome or with osteoporosis. This behaviour would be classified as case-finding and, evidently, the patient has initiated the consultation and,

Treatment

The mainstay of treatment of coeliac disease remains adherence to a gluten-free diet. Improvement and resolution of symptoms typically occurs within days or weeks, and often precedes normalisation of serological markers and of duodenal villous atrophy.107 Despite its effectiveness in achieving normalisation of these parameters in most patients, the gluten-free diet has numerous difficulties. Gluten-free substitute foods are substantially more expensive than their gluten-containing counterparts.

Non-responsive and refractory coeliac disease

About 20% of patients with coeliac disease have persistent or recurrent symptoms despite a gluten-free diet.121 These cases are caused by heterogeneous conditions (panel 3). An essential first step in assessing these patients is to confirm the accuracy of the initial diagnosis of coeliac disease. If a patient did not originally have a duodenal biopsy showing villous atrophy while on a gluten-containing diet, or if the patient had a negative coeliac disease result from serological testing

Malignancy and mortality risk

In addition to enteropathy-associated T-cell lymphoma, coeliac disease is associated with an increase in other types of non-Hodgkin lymphoma.132, 133 In a population-based study, the risk of increased malignancy was increased for adenocarcinoma of the oesophagus, small intestine, colon, liver, and pancreas, although only estimates for the small intestine and liver remained significant after excluding the first year after coeliac disease diagnosis.134 The risk of colorectal cancer was found to

Conclusions

Despite the increase in the prevalence of coeliac disease and improved recognition and rates of diagnosis, numerous avenues of investigation are necessary to better understand the pathogenesis and improve the treatment of patients with this condition. Advances in the pathophysiology of coeliac disease could enable preventive strategies in individuals at high risk for disease development. The development of non-dietary therapies might alleviate symptoms among patients with coeliac disease and

Search strategy and selection criteria

We searched PubMed for articles published from Jan 1, 1990, to Jan 31, 2017, with no language restrictions, using the terms “celiac”, “coeliac”, and “gluten”. In our selection of articles, we emphasised those published since 2010, but included older publications of scientific and historical relevance. We mostly selected cohort and case-control studies and the few randomised trials performed in this subject area, but also selected guidelines and systematic reviews and smaller, non-controlled

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