Davis R L, Bohlke K
Department of Paediatrics, University of Washington School of Medicine, Seattle, Washington 98103, USA.
Drug Saf. 2001;24(13):939-46. doi: 10.2165/00002018-200124130-00001.
The increasing incidence of Crohn's disease has lead to speculation about changes in exposures to environmental or infectious agents. Considerable attention has focused on the role of measles infection and/or vaccination in the pathogenesis of Crohn's disease and ulcerative colitis. Current evidence regarding the association between measles vaccination and inflammatory bowel disease (IBD) comprises analytic epidemiological studies, a case-series report and ecological studies. The first of these, a 1995 cohort study, found an association between measles vaccination and Crohn's disease and ulcerative colitis, but was widely questioned on methodological grounds. This was followed by a 1997 case-control study showing no association between measles vaccination and IBD. In 1998, public concern was rekindled by a report of 12 children with nonspecific colitis, ileal-lymphoid-nodular hyperplasia, and developmental disorders largely attributed to measles-mumps-rubella vaccine, but the nature of the report limited its scientific conclusions. Two additional studies, one case-control and one cohort, then followed and neither found an association with measles vaccination. Of the several ecological studies of measles vaccine coverage or measles schedule changes, none found an association with rates of IBD. The role of measles infection in IBD has been examined more extensively with studies of in utero measles exposure, measles infection early in life, and laboratory based investigations. An initial report of high rates of Crohn's disease among pregnancies affected by measles infection was followed by negative studies. Numerous case-control and ecological studies of children with measles infections early in life have also had discordant findings. Of three recent cohort studies, two showed no relationship between infection with early measles exposure and risk for IBD, while one found an approximate 3-fold elevation in risk. Laboratory investigations into persistent measles infection and IBD have been contentious. While some investigators have claimed to find persistent measles infection among patients with IBD, others, using highly sensitive polymerase chain reaction techniques, have not been able to replicate the findings. Recent controversy has centred on whether there is any evidence for molecular mimicry in the pathogenesis of IBD. In summary, available evidence does not support an association between measles-containing vaccines and risk of IBD, nor between measles infection and IBD. While further research is necessary into the causal factors underlying Crohn's disease and ulcerative colitis, continued public education efforts are needed to reassure the public about vaccine safety and to prevent declines in vaccine coverage.
克罗恩病发病率的上升引发了人们对环境暴露因素或感染原变化的猜测。相当多的注意力集中在麻疹感染和/或疫苗接种在克罗恩病和溃疡性结肠炎发病机制中的作用上。目前关于麻疹疫苗接种与炎症性肠病（IBD）之间关联的证据包括分析性流行病学研究、病例系列报告和生态学研究。其中第一项研究是1995年的队列研究，发现麻疹疫苗接种与克罗恩病和溃疡性结肠炎之间存在关联，但该研究在方法学上受到广泛质疑。随后在1997年进行了一项病例对照研究，结果显示麻疹疫苗接种与IBD之间无关联。1998年，一份关于12名患有非特异性结肠炎、回肠淋巴结节增生和发育障碍的儿童的报告重新引发了公众的关注，这些症状大多归因于麻疹-腮腺炎-风疹疫苗，但该报告的性质限制了其科学结论。随后又进行了另外两项研究，一项病例对照研究和一项队列研究，均未发现与麻疹疫苗接种有关联。在几项关于麻疹疫苗接种覆盖率或麻疹接种程序变化的生态学研究中，均未发现与IBD发病率有关联。关于麻疹感染在IBD中的作用，已经通过对子宫内麻疹暴露、生命早期麻疹感染的研究以及实验室研究进行了更广泛的探讨。最初有报告称，受麻疹感染影响的孕妇中克罗恩病发病率较高，但后续研究结果为阴性。针对生命早期感染麻疹的儿童进行的大量病例对照研究和生态学研究也得出了不一致的结果。在最近的三项队列研究中，两项研究表明早期麻疹暴露感染与IBD风险之间无关联，而另一项研究发现风险升高了约3倍。关于持续性麻疹感染与IBD的实验室研究一直存在争议。虽然一些研究人员声称在IBD患者中发现了持续性麻疹感染，但其他研究人员使用高灵敏度聚合酶链反应技术却未能重复这一发现。最近的争议集中在IBD发病机制中是否存在分子模拟的证据。总之，现有证据不支持含麻疹疫苗与IBD风险之间存在关联，也不支持麻疹感染与IBD之间存在关联。虽然有必要对克罗恩病和溃疡性结肠炎的病因进行进一步研究，但仍需要持续开展公众教育工作，以使公众放心疫苗的安全性，并防止疫苗接种覆盖率下降。
