Studies have shown that enteric microflora is important in the pathogenesis and severity of inflammation and disease phenotype. Additionally, there is an upregulation of mucosal addressin cellular adhesion molecule-1 (Mad-CAM1) on the endothelium of mucosal blood vessels which promotes leukocyte adhesion and extravasation into mucosal tissue. There is an upregulated release of the chemoattractant CXCL8 in ulcerative colitis so that leukocytes are recruited to the mucosa from systemic circulation. Leukocyte recruitment is affected on two fronts. Levels of IgM, IgA, and IgG are elevated in inflammatory bowel disease however, a disproportionate increase in IgG1 antibodies is found in patients diagnosed with ulcerative colitis. Other immune-related factors that play a role in the pathophysiology of ulcerative colitis include tumor necrosis factor-alpha (TNF-alpha), interleukin 13, and natural killer T-cells. There also seems to be an atypical T-helper (Th) cell response in patients with ulcerative colitis, specifically Th2, which exerts a cytotoxic response against epithelial cells. The lamina propria of the mucosa also has an increased number of activated and mature dendritic cells which include a large number of toll-like receptors (TLR), specifically TLR2 and TLR4. The epithelial barrier has a defect in colonic mucin, and possibly tight junctions, leading to increased uptake of luminal antigens. The pathophysiology of ulcerative colitis involves defects in the epithelial barrier, immune response, leukocyte recruitment, and microflora of the colon. In fact, appendectomy has been shown to reduce the risk of developing ulcerative colitis by 69%. There is also an association of inflammatory bowel disease with the removal of an inflamed appendix. Appendectomy before the age of twenty is associated with a decreased incidence of ulcerative colitis whereas the opposite is true for Crohn disease. There is evidence, though weak, that non-steroidal anti-inflammatory drug use is associated with the onset or relapse of ulcerative colitis. Additionally, smokers diagnosed with ulcerative colitis tend to have milder disease, fewer hospitalizations, and need for less medication. There is an increased prevalence of ulcerative colitis in nonsmokers or those who recently quit smoking. Though some studies show a slight predilection for men, most studies note no preference regarding sex. A second, and the smaller peak of incidence occurs between the age of 50 and 70 years. The main onset peaks between the age of 15 and 30 years. Ulcerative colitis has a bimodal pattern of incidence. When considering the pediatric population however, ulcerative colitis is less prevalent than Crohn disease. Compared to Crohn disease, ulcerative colitis has a greater prevalence in adults. Its prevalence is 156 to 291 cases per 100,000 persons per year. Ulcerative colitis has an incidence of 9 to 20 cases per 100,000 persons per year. Worldwide, the highest incidence and prevalence of inflammatory bowel diseases are seen in Northern Europe and North America. Inflammatory bowel disease is closely linked to a westernized environment and lifestyle.
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