The geoepidemiology of autoimmune intestinal diseases
Introduction
Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders of the digestive tract. The majority of the cases of IBD can be classified as either ulcerative colitis (UC) or Crohn's disease (CD) based upon clinicopathologic features, however a portion are atypical of either disease and fall within the category of indeterminate colitis (IC). UC is characterized by superficial continuous ulceration of the large bowel, whereas CD is typified by transmural lesions that can occur throughout the gastrointestinal tract and sometimes form strictures and fistulous tracts. Although the pathogenesis of IBD is incompletely understood, numerous hypothesis have been presented proposed including abnormalities in apoptosis and cell damage [1], [2], micro-RNAs [3], [4], adhesion molecules [5], and humoral response to self and foreign antigens [6], [7]. In addition, there is strong evidence for genetic susceptibility to dysregulation of the innate immune system leading to gastrointestinal inflammation with the central premise being an inappropriate response to normally benign gut antigens [8], [9], [10], [11].
Unlike IBD where a specific antigen has not been identified, celiac disease is an autoimmune intestinal disease that involves a break in immune tolerance to gluten, a protein found in wheat, barley and rye. Celiac disease occurs primarily in genetically susceptible hosts, particularly those carrying an HLA-DQ2 or DQ8 allele. A wide variety of presentations are possible, ranging from the typical malabsorptive diarrhea to iron deficiency, abdominal pain, liver disease, or neuropsychiatric problems. Classically mucosal atrophy of the small intestine is present, however pathologic changes of the small bowel mucosa can range from a mild increase in intraepithelial lymphocytes all the way to complete villous atrophy. The development of highly sensitive and specific serologic tests including anti-endomesial and anti-tissue transglutaminase have allowed accurate estimates celiac disease incidence and prevalence with non-invasive methods.
The purpose of this paper is to review the global epidemiology of IBD and celiac disease with an emphasis on trends over time and geography and the potential explanations for these trends.
Section snippets
Epidemiology of IBD
Traditionally, both UC and CD have been found to have a higher incidence in developed countries such as North America and northern and western Europe than in Asia, Africa, and South America (Fig. 1). However, the incidence of IBD and other immune mediated disorders has been noted to be rising with urbanization and development. The rise of IBD seen with development is often quite dramatic and cannot be explained by either random effects or migration mediated changes in genetic susceptibility.
Potential explanations for the changing epidemiology of IBD
Despite the now well-established changing global incidence of IBD, epidemiologic studies to date have not identified specific factors responsible for these changes (Table 1). Although smoking has been clearly identified as a risk factor for CD and protective against UC, the prevalence of smoking does not correlate with the prevalence or incidence of either CD or UC on a global scale. Urbanization has been suggested as an environmental risk factor for IBD, as a change to a Western lifestyle
Celiac disease
As in IBD, celiac disease occurs in a genetically susceptible host. The incidence of celiac is higher in those with specific haplotypes — HLA DR3-DQ2 and DR4-DQ8, as well as other non-HLA genes. However in the case of celiac disease, the exposure to a specific environmental factor (dietary gluten) is essential to develop disease. Therefore the disease is typically seen in populations who not only have genetic susceptibility but also consume gluten. The disease has typically been described to be
Conclusion
Inflammatory bowel disease is a group of incompletely understood disorders that appear to be related to dysregulation of the innate immune system in the genetically susceptible host leading to gastrointestinal inflammation. Numerous genetic and environmental factors have been suggested to play in role in the development of disease but few have been confirmed. Classically, the prevalence of IBD has been higher in developed countries than those which are less developed. In developed countries,
Take-home messages
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The prevalence of inflammatory bowel disease is higher in developed countries than under-developed countries.
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In developed countries, the overall prevalence and incidence of inflammatory bowel disease has leveled but the rates of Crohn's disease have increased and ulcerative colitis have decreased.
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As under-developed countries have modernized, the incidence of inflammatory bowel disease increases to the levels of developed countries. A similar phenomenon occurs with migration of populations to
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