On the work-up of (Refractory) Coeliac Disease

Coeliac disease is a gluten-sensitive enteropathy that affects people of all ages worldwide. This disease has emerged a major health-care problem, as advances in diagnostic and screening methods have revealed its global prevalence. Environmental factors such as gluten introduction at childhood, infectious agents and socioeconomic features, as well as the presence of HLA-DQ2 and/or HLA-DQ8 haplotypes or genetic variations in several non-HLA genes contribute to the development of coeliac disease. Growing insight into the variable clinical and histopathological presentation features of this disease has opened new perspectives for future research. A strict life-long gluten-free diet is the only safe and efficient available treatment, yet it results in a social burden. Alternative treatment modalities focus on modification of dietary components, enzymatic degradation of gluten, inhibition of intestinal permeability and modulation of the immune response. A small group of patients with coeliac disease (2–5%), however, fails to improve clinically and histologically upon elimination of dietary gluten. This complication is referred to as refractory coeliac disease, and imposes a serious risk of developing a virtually lethal enteropathy associated T-cell lymphoma. R1 R2 R3 R4 R5 R6 R7 R8 R9 R10 R11 R12 R13 R14 R15 R16 R17 R18 R19 R20 R21 R22 R23 R24 R25 R26 R27 R28 R29 R30 R31 R32 R33 R34 R35 R36 R37 R38 R39 Spectrum of CD | 19 InTRODuCTIOn Coeliac disease (CD) is the most common food intolerance in the Western population, and currently represents a major health-care issue. CD has an ancient history, first described in the 1st and 2nd century AD. In 1887, Samuel Gee described typical symptoms of CD in children, including irritability, chronic diarrhoea and failure to thrive, and cure by means of a diet was suggested for the first time.1 Since then, insight into CD has undergone a revolutionary development regarding epidemiology, diagnostics and treatment. Coeliac disease is a chronic, small intestinal enteropathy, which is triggered by gluten proteins from wheat, barley and rye. It is characterised by an autoimmune response in genetically susceptible individuals resulting in small intestinal mucosal injury. As a consequence, malabsorption develops which results in malnutrion-related problems including anaemia, vitamin deficiencies, osteoporosis and neurological disorders. Withdrawal of dietary gluten usually leads to prompt healing of the damaged small intestinal mucosa and improvement of nutrient absorption. A gluten-free diet (GFD) is sufficient to treat the overwhelming majority of patients with CD and clinical improvement is usually evident within a few weeks.2 A small percentage (2–5%) of patients with adult-onset CD, especially those diagnosed above the age of 50, does not respond to a GFD and is seen as suffering from refractory coeliac disease (RCD). The occurrence of an enteropathy associated T-cell lymphoma (EATL) is the major complication associated with RCD and is the main cause of death in this patient group.3, 4 Early identification of patients with RCD enables early intervention, which results in reduction in morbidity and mortality.4, 5 This review gives an overview of the latest trends in epidemiology, clinical presentation, diagnosis, treatment and complications with respect to the spectrum of CD. EPIDEMIOlOGY Global population trends Until the 1970s the estimated global prevalence of CD in the general population was 0.03%. 6 The currently estimated prevalence is 1%, with a statistical range of probability of 0.5–1.26% in the general population in Europe and the USA.7 Even taking into account that the actual occurrence rate of CD has been underestimated for many decades, the prevalence of this disease is increasing. Advances in diagnostic methods and improvement in screening have played a part in this increase observed, but environmental factors have also been important. Trends in diagnosis and screening The introduction of gastro-intestinal endoscopic techniques in the 1970s, which provided the opportunity to take routine biopsy samples, opened new horizons in CD case-finding and diagnosis. In addition, identification of human leukocyte antigen (HLA) molecules typically