Alberto Rubio-Tapia, MD and Joseph A Murray, MD
Division of Gastroenterology and Hepatology, Departments of Medicine and Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota
Corresponding Author: Joseph A Murray, MD, The Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA,
CD affects ~1% of most populations but remains largelyunrecognized. In the last year, work has shown that the prevalence of CD has increased dramatically, not simply due to increased detection. Also, undiagnosed CD may be associated with increased mortality. Significant progress has been made in understanding how gliadin peptides can cross the intestinal border and access the immune system. New genetic loci and candidate genes that may contribute to therisk of CD and its overlap with type 1 diabetes mellitus have been identified. New deamidated gliadin peptides antibodies have better diagnostic accuracy over native gliadin-based tests. The inclusion of duodenal bulb biopsy specimens may increase the rate of CD detection. The spectrum of CD likely includes a minority of patients with mild enteropathy. A practical 7-item instrument may facilitatestandardized evaluation of gluten-free diet adherence. Finally, refractory CD, whilst rare, is associated with a poor prognosis.
Celiac disease (CD) now affects ~1% of most populations. This was not always so. In fact, at least two studies have shown that over time there has been a substantial increase in background prevalence of the disease.1, 2 In addition to anincrease in background prevalence, serologic testing for CD has impacted the rate of diagnosis as well as our understanding of the epidemiology of CD. The incidence of CD in children <2 years of age showed an epidemic pattern in Sweden during the period of 1984–1996.3 A population-based incidence register of CD covering epidemic and post-epidemic birth cohorts revealed that the cumulative incidenceat 2 years of age was almost 3 times higher during the epidemic, compared to the years before and after the epidemic.4 Also, a significant successive increase in incidence rates among children <2 years of age was once again revealed during the last years of follow-up monitoring rising the question of a new epidemic approaching.4 Furthermore, a study that followed up the fate of children bornduring the Swedish epidemic of infant CD showed an increasing prevalence of CD in these children reaching 3% by the age of 12.
Why the prevalence of celiac disease may have increased over time is not clear. This is too short a time period for substantial changes in human genetics and likely represents some major and pervasive environmental influence. Concepts such as the hygiene hypothesis,perhaps changes in wheat or other cereals may influence this. One study suggesting a pervasive environmental influence identified a higher rate of celiac disease in Finland compared to the adjacent, but less developed, Karelia.8 Immunoreactivity to dietary proteins in CD appears to be age-related; specifically IgA immunoreactivity to bovine milk caseins was lower in CD patients under 2 years of age thanolder children or young adults suggesting that the proteins in infant formulas and foods could be associated with the risk for CD prevalence.
Celiac disease results from innate and adaptive immune system dysregulation. Activation of the adaptive immune system implies that gliadin (the toxic component of gluten) cross the intestinal epithelium. It has been hypothesized thatincreased intestinal permeability is an early event in CD pathogenesis. Lammers et al15 demonstrated that gliadin bind to the chemokine receptor CXCR3, the interaction gliadin-CXCR3 may induce release of zonulin that may lead to tight junction disassembly and subsequent paracellular passage of gliadin to the gut mucosa. Other mechanisms of gliadin transport in CD have been postulated. Matysiak-Budnik et...