Recent advances in coeliac disease

Abstract

he management of coeliac disease is an increasing part of a gastroenterologist's workload.Recent prevalence studies suggest ,1% of the general UK population have positive coeliac serology, which combined with increasing population and primary care awareness is leading to more and more referrals.The majority of contemporary referrals are now initially diagnosed by highly sensitive and specific serological tests followed by readily performed endoscopic biopsy (fig 1).Consequently, we now identify many more patients with no or only mild clinical symptoms, making the classical scenario of diarrhoea/steatorrhoea and weight loss a comparative rarity.Much of the early data on clinical aspects of classical coeliac disease (that is, published pre ,1990) may not be applicable to contemporary coeliac disease.These changes in clinical practice have been paralleled by a dramatic increase in our knowledge of disease pathogenesis, making coeliac disease the best understood human ''autoimmune'' disorder.In this review article, we present selected major recent advances in both clinical and basic science aspects of coeliac disease, focusing on the many high quality studies published within the last five years. OCCURRENCE OF COELIAC DISEASE cGeneral population based prevalence studies of undetected coeliac disease Several serological screening studies from Europe, South America, Australasia, and the USA have shown that approximately 0.5-1% of these populations may have undetected coeliac disease.The most consistent estimate reported from the largest population based studies is approximately 1%.The prevalence is even higher in first and second degree relatives of people with coeliac disease. 1 In the five studies shown in table 1, general population based samples of children were recruited for coeliac disease screening.The two earlier Italian studies (using antigliadin antibody testing followed by antiendomysial antibody and small bowel biopsy) suggested a prevalence of 1 in 93 of undetected coeliac disease. 2 3 These findings have been replicated in two further large studies, one from the UK and one from Finland.The recent Bristol study used blood stored anonymously for the Avon Longitudinal Study of Parents and Children (a population based birth cohort study established in 1990). 4This study tested 5470 children for antitissue transglutami- nase antibody and then those who were positive with a further antiendomysial antibody test.Maki et al tested 3654 Finnish students for both serological tests and offered small intestinal biopsy to those who were positive. 5Both of these studies found a prevalence of approximately 1 in 100.The study of Saharawi children by Catassi et al showed the highest coeliac disease prevalence (5%). 6This cohort, comprising refugees living in an Algerian province, was tested for antiendomysial antibody and a sample of positive individuals had small intestinal mucosa biopsy.Reasons for this high prevalence, which is markedly different to all the other general population estimates, are unclear.The authors speculated that coeliac disease might confer some ''protection'' against intestinal infections or parasites.Selected adult general population based screening studies for coeliac disease are shown in table 2. Three of these studies used populations recruited for the World Health Organisation MONICA project (monitoring of trends and determinants in cardiovascular disease) and were similar in design, with samples randomly selected from population registers stratified by age and sex. 7-9All three of these studies (and the Argentinean study) used a combination of antigliadin antibody and antiendomysial antibody testing to identify people with previously undetected coeliac disease, but not all reported small intestinal biopsy.Other studies used antiendomysial antibody as the main test for identifying people with undetected coeliac disease.It is notable that the prevalence of undetected coeliac disease in both children and adults is very similar (approximately 1%) in the two recent large UK based studies. 4 10It therefore seems probable that the coeliac trait starts in early childhood in all cases, even in those who are subsequently diagnosed as adults.The search for the initial trigger resulting in the breakdown of oral tolerance to dietary wheat, rye, and barley therefore needs to focus on in utero events and 1037 www.gutjnl.