Primary Sclerosing Cholangitis-Associated Inflammatory Bowel Disease
Primary sclerosing cholangitis (PSC) is closely associated with inflammatory bowel disease (IBD). Although there is a clear genetic association between PSC and IBD, the underlying pathogenesis linking these diseases remains unclear. Many studies describe
- PDF / 496,885 Bytes
- 12 Pages / 504.57 x 720 pts Page_size
- 27 Downloads / 213 Views
Primary Sclerosing CholangitisAssociated Inflammatory Bowel Disease Blair Fennimore, Emilie H. Regner, and Mark E. Gerich
Epidemiology of PSC-Associated IBD (PSC-IBD) Approximately 60–80 % of PSC cases in North American and Western European populations are associated with IBD; generally, over two-thirds of the IBD cases are diagnosed as ulcerative colitis (UC) [1, 2]. It has been suggested that the prevalence of IBD among PSC patients of nonCaucasian background may be lower. For instance, IBD prevalence rates of 20–34 % have been reported in studies of Asian PSC patients; however, these studies were either very small or relied on provider surveys without rigorous methods of IBD case ascertainment [3–6]. The diagnosis of IBD precedes that of PSC in the majority of patients with concomitant PSC and IBD. Indeed, the diagnosis of PSC may be made many years after the diagnosis of IBD and can even occur after proctocolectomy [7–15]. The prevalence of PSC in population-based studies of UC patients ranges from 2 to 8 %. Among patients with Crohn’s disease (CD), the prevalence of PSC approaches 1 %, and it appears to occur much less frequently among patients with CD that is isolated
B. Fennimore, MD (*)• E.H. Regner, MD M.E. Gerich, MD Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, 12700 E. 19th Ave. MS B-146, Aurora, CO 80045, USA e-mail: [email protected]; emilie. [email protected]; [email protected]
to the small bowel [1, 15–17]. It has been reported that no statistically significant differences were seen in the prevalence of PSC among AfricanAmerican, Hispanic, and non-Hispanic white patients with IBD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Inflammatory Bowel Disease Genetics Consortium (IBDGC) repository; however, only 20 patients with PSC were in this study [18].
Pathophysiology of PSC-IBD Although a variety of hypothesis-generating associations have been identified between PSC and IBD, the specific underlying pathophysiology has yet to be elucidated. The strong heritability of disease coupled with identification of multiple shared genetic risk loci between PSC and IBD suggests a significant genetic contribution. Familial occurrence of PSC has been well documented [19]. PSC also confers greater than a threefold increased risk of UC among first-degree relatives [20]. This risk exists even in the absence of concomitant IBD in the proband, strongly suggesting a shared genetic susceptibility between the diseases [20]. Interestingly, although a variety of HLA- and non-HLA-associated risk loci have been described for both PSC and UC [21–23], specific HLA haplotypes [24] and major IBD-associated genes such as CARD15 and MDR1 [25] do not appear to be shared between the two. While overlap involving various non-HLA-associated risk
© Springer International Publishing Switzerland 2017 L.M. Forman (ed.), Primary Sclerosing Cholangitis, DOI 10.1007/978-3-319-40908-5_3
29
30
loci does
Data Loading...
