Familial empiric risk estimates of inflammatory bowel disease in Ashkenazi Jews

Genetic factors have been implicated in the etiology of inflammatory bowel disease (IBD) because of the increased occurrence of IBD in relatives. To further characterize the familial aggregation of IBD, we obtained family histories by interview on 188 IBD patients, including 154 Ashkenazi Jews (82%), ascertained through a Los Angeles gastroenterology practice. Thirty-three index cases (17.6%) had at least one affected first-degree relative; an additional 11 had more distant affected relatives. Thus, 23.4% of our sample had a positive family history. The quantification of empiric risk estimates for various classes of relatives has been quite limited and has been reported in only a few series. An important goal of our study was the determination of the specific empiric risk figures for relatives. We obtained uncorrected risk estimates of 2.5% to off-spring, 5.2% to siblings, and 2.9% to parents. Although the highest risk we observed is to siblings, IBD has a variable and often late age of onset, and it is likely that many relatives, particularly offspring, of patients in this sample have not reached the age at which they will manifest clinical disease. Thus, these uncorrected risks as well as those reported in the literature are an underestimate of the true empiric risks. To provide an estimate of the true lifetime risks, we utilized age-specific incidence data to calculate the following age-corrected empiric risk estimates for IBD: 8.9% to offspring, 8.8% to siblings, and 3.5% to parents. It is these latter age-corrected estimates that are most appropriate for both genetic counseling and genetic modeling.     

Familial occurrence of inflammatory bowel disease in celiac disease

BACKGROUND: The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM: The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS: One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital records. Two hundred twenty-two controls matched for age and sex (111 from the general population and 111 from orthopedic wards) were also interviewed regarding the possible occurrence of IBD in first-degree relatives. The chi2 test was used to evaluate the difference in proportion of familial occurrence of IBD among individuals with celiac disease and controls. RESULTS: Among 600 first-degree relatives of patients with celiac disease, 10 cases of IBD were identified among first-degree relatives (7 cases of ulcerative colitis and 3 cases of Crohn's disease), whereas only 1 case of IBD was identified among the 1,196 first-degree relatives of control patients (p < 0.01). When ulcerative colitis and Crohn's disease were analyzed separately, only the prevalence of ulcerative colitis was statistically significant (p 相似文献   

Familial occurrence and inheritance studies in inflammatory bowel disease

A number of studies have demonstrated aggregation of cases of ulcerative colitis or Crohn's disease in families, and of cases of both diseases within the same families, suggesting that patients share a genetic background. Perhaps because of differences in the selection of patients, study design and diagnostic criteria, different patterns of occurrence of inflammatory bowel disease (IBD) have been found among relatives of patients with these disorders. In recent years, however, several studies have been carried out, aiming by epidemiological methods to reveal (1) the frequency of familial occurrence of IBD among patients with ulcerative colitis and Crohn's disease, and (2) the prevalence of IBD among 1⁰ relatives to patients with these diseases. Results from these studies show a relatively uniform pattern of family occurrence in about 10% of patients with ulcerative colitis and Crohn's disease, and a prevalence among 1⁰ relatives of about 10 times that of the background population. A twin study reported a significantly higher concordance rate for Crohn's disease than for ulcerative colitis in monozygotic twins. By use of complex segregation analyses in 3 different studies, a very similar model of inheritance was found to fit for ulcerative colitis, namely a major dominant or additive gene with a low penetrance. For Crohn's disease the best-fitting model was a major recessive gene, with a high penetrance. This difference strongly supports the concept of ulcerative colitis and Crohn's disease as two separate disease entities. The occurrence of both diseases within the same families in certain members of the affected families is difficult to explain. The search for distinct associations of HLA genes with inflammatory bowel disease has shown a positive correlation between DR2 and ulcerative colitis and a negative association with DR4 and DRw6, compared with ethnically matched controls. In contrast, in Crohn's disease a positive association with the combination of DR1 and DQw5 alleles was revealed, thus indicating genetically different disease susceptibility for the two disorders. In general, however, no consistent pattern has been revealed from studies of association of HLA-A or -B antigens or blood group and serum protein markers. In two French families with several members affected with Crohn's disease no evidence for an HLA haplotype association could be revealed. Possible inherited markers of ulcerative colitis or Crohn's disease have been sought but without convincing success. Increased intestinal permeability, presence of anticolon antibodies and presence of antineutrophil leukocyte antibodies have been proposed, but not proved. Thorough studies are now needed of multimember families with disease for linkage studies to identify loci which contribute to increased liability. Such studies are in progress in different centres.     

Familial occurrence of inflammatory bowel disease in Korea

BACKGROUND: Little information is available about the familial aggregation of inflammatory bowel disease (IBD) in Asian populations. We therefore determined the risk of familial aggregation of IBD among first-degree relatives of patients with ulcerative colitis (UC) or Crohn's disease (CD) in an ethnically distinct Korean population. METHODS: Familial aggregation of IBD was evaluated in terms of family history, prevalence, lifetime risk, and population relative risk in first-degree relatives of 1440 unrelated patients with UC (n = 1043) or CD (n = 397). RESULTS: A positive first-degree family history of IBD was observed in 27 probands (1.88%): 21 of 1043 (2.01%) with UC and 6 of 397 (1.51%) with CD. The crude prevalence of IBD in first-degree relatives of probands with IBD was 0.31%. The lifetime risk of IBD was 0.54% in all first-degree relatives of IBD probands, 0.52% in UC probands, and 0.67% in CD probands, with overall lifetime relative risks of 0.12% in parents, 0.79% in siblings, and 1.43% in offspring. The age- and sex-adjusted population relative risk of IBD was 13.8 in first-degree relatives of probands with IBD. CONCLUSIONS: Although a positive family history, prevalence, and lifetime risk of IBD among first-degree relatives of Korean IBD patients are much lower than among relatives of Western patients, the population relative risk in first-degree relatives is about equal in Koreans and Westerners. This finding indicates that a positive family history is an important risk factor for IBD in Koreans and in Westerners.     

炎症性肠病药物联合治疗的获益与风险

目前炎症性肠病(IBD)的发病机制未完全明确,虽有越来越多的生物制剂问世,但其治疗仍存在难点,有时无法得到令人满意的疗效。在临床实践中,当常规治疗收效不佳时,将几种药物联合应用治疗IBD不失为一种重要的治疗策略,但药物联合治疗提高疗效的同时可能会增加感染及肿瘤等风险。因此应用联合治疗时需结合患者的疾病类型、病情程度、病变范围、高危因素、既往用药情况,对治疗方案进行技巧性地选择和甄别必不可少。     

Malpractice risks associated with colon cancer and inflammatory bowel disease

Analyses of lawsuits against gastroenterologists suggest that the disorders of colon cancer and inflammatory bowel disease are among the more common disorders resulting in malpractice claims, with colon cancer suits receiving some of the highest monetary judgments. Unfortunately, that composite data does not specify the exact alleged wrongdoing, but uses global categories such as "errors of diagnosis." This review will focus on potential legal pitfalls regarding those disorders. The focus is on the legal theories, not the exact medical approach recommended, and is intended as general education, and not legal advice for any specific patient.     

Clinical manifestations of inflammatory bowel disease: East and West differences

Inflammatory bowel disease (IBD) is very common in developed countries, while it is relatively uncommon in Asian countries. However, the incidence of IBD has been increasing in some Asian countries in recent years. Most cases of ulcerative colitis (UC) in Asia are of the chronic relapsing type, run a milder course, and the fulminant type is rarely seen. There is no difference in clinical manifestations between Asian and developed countries. The incidence of Crohn's Disease (CD) is mainly in males in Asia, while it is mainly in females in developed countries. The clinical manifestations of CD are similar between both sets of countries. In China there are less fistulae and perianal diseases, and extraintestinal manifestations of CD are uncommon. In China, 5.6% of patients with UC have a family history, which is lower than 10-20% in developed countries. NOD2/CARD15 variants in the locus of 16q112 (IBD1) are significantly associated with the susceptibility of CD in developed countries, but NOD2/CARD15 variants have not been found in Asian CD patients.     

巨细胞病毒与炎症性肠病的关系

巨细胞病毒（cytomegalovirus，CMV）为机会致病性病毒，多数人呈隐性或潜伏感染，显性CMV感染常发生在免疫功能抑制者。炎症性肠病（1BD）是一种慢性、复发性的肠道炎症疾病，患者常使用激素或免疫抑制剂治疗，因而有很高的CMV易感性。近年研究表明CMV感染可能在炎症性肠病病情发展变化中起关键作用，CMV通过直接或间接作用致组织损伤，目前新发展的检测技术或联合多种检测手段可增加CMV检出的敏感性和特异性，而不少研究表明难治性IBD时应用抗CMV病毒治疗可明显改善病情。本文就CMV在IBD疾病进展中的作用和关系，以及对CMV的最新检测技术和治疗策略的研究进展作一综述。     

Medical therapy for inflammatory bowel disease.

CD and UC represent a spectrum of chronic IBD that present in protean ways and are accompanied by a variety of systemic sequelae. Sulfasalazine and the newer 5-aminosalicylates are important in the management of mild-to-moderate disease, whereas corticosteroids remain the primary therapy for most patients with moderate-to-severe disease (Tables 2-5). The toxicities associated with long-term steroid therapy, combined with their ineffectiveness as maintenance medications, have led to increased use of immunomodulators, such as azathioprine and 6-MP, for the treatment of steroid-dependent and steroid-resistant IBD. Infliximab is a novel therapeutic adjunct for chronically active and fistulizing CD that will herald a new era of biologic therapy for IBD. Meanwhile, CSA remains an alternative to urgent colectomy in severe UC unresponsive to corticosteroids and also for CD patients with severe disease or refractory fistulas. Finally, continued insights into the etiopathogenic pathways in IBD will provide evolving and innovative approaches until the eventual causes and cures are elucidated. In the meantime, clinicians should remain optimistic regarding current ability to reduce the morbidity and maintain the quality of life for patients suffering with these frustrating diseases.     

Novel therapies for inflammatory bowel disease.

Looking back at successes and failures in newer approaches to treating IBD, it is tempting--although still difficult--to draw conclusions about pathogenesis. When a therapy proves effective, do clinicians truly know how it works? Even with a therapy as specific as anti-TNF antibody, it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage. When a drug appears to be less effective than preclinical models suggest, can failures in effectiveness from delivery or dosing be differentiated? The disappointing results of clinical trials with IL-10--so at odds with the prediction of benefit from animal models--bring into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is judged. The variability of response even to the most narrowly targeted agents suggests that these diseases are far more heterogeneous in humans than in their murine counterparts. Clinicians are only just beginning to recognize subclinical markers of response, and it may soon be possible to predict response on the basis of genetic composition. For the moment, however, the field of pharmacogenetics is embryonic. Challenges in developing new therapeutic strategies include not only identifying novel agents, but also improving the definitions of clinical endpoints and defining efficacy at the biologic level. Only through considered evaluation of clinical evidence may clinicians determine which therapies should remain novelties and which should become an accepted part of the armamentarium.     

Exercise and inflammatory bowel disease.

Crohn's disease and ulcerative colitis are both idiopathic inflammatory bowel diseases (IBDs) that affect 0.5% of Canadians. As yet, there is no known cure for either disease, and symptoms are treated with an array of medicines. The objective of the present review was to present the role of exercise and its impact on all facets of IBD. Exercise has been speculated to be protective against the onset of IBD, but the literature is inconsistent and weak. Preliminary studies reveal that exercise training may be beneficial to reduce stress and symptoms of IBD. Current research also recommends exercise to help counteract some IBD-specific complications by improving bone mineral density, immunological response, psychological health, weight loss and stress management ability. However, the literature advises that some patients with IBD may have limitations to the amount and intensity of exercise that they can perform. In summary, exercise may be beneficial to IBD patients, but further research is required to make a convincing conclusion regarding its role in the management of IBD and to help establish exercise regimens that can account for each IBD patient's unique presentation.     

Chlamydiae and inflammatory bowel disease.

No association was found between inflammatory bowel disease and infection with C. trachomatis or C. psittaci when patients were tested for the presence of these organisms using immunohistological, cell culture isolation, and serological techniques.     

Thrombosis and inflammatory bowel disease.

Interaction between thrombosis and inflammation is increasingly recognized. With this, interest has arisen in the role of thrombosis in inflammatory conditions, including the inflammatory bowel diseases. Although the association between active inflammatory bowel disease and thromboembolic complications has long been known, there has been a resurgence in research into the role of thrombosis and the hemostatic system in the pathogenesis of both ulcerative colitis and Crohn's disease. Here we review the increased frequency of thromboembolic complications occurring in patients with inflammatory bowel disease; whether thrombosis might play a part in the initiation and maintenance of inflammation in inflammatory bowel disease; abnormalities of the coagulation system found in patients with inflammatory bowel disease; platelet dysfunction in inflammatory bowel disease; the mechanisms by which hemostatic processes might be proinflammatory in inflammatory bowel disease; and how these interactions might impact not only on the prevention of complications, but also on the treatment of the underlying inflammation in inflammatory bowel disease.     

白细胞介素23与炎症性肠病

炎症性肠病(IBD)是一类病因不明的胃肠道慢性非特异性炎症,包括克罗恩病(CD)和溃疡性结肠炎(UC).促炎因子和抗炎因子的失衡被视为一个重要的病因[1].白细胞介素23(IL-23)属于前炎性因子,在IBD的发生、发展中起重要作用.此文就近年来IL-23在IBD发生、发展和治疗中的作用作一综述.