Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands.
Inflamm Bowel Dis. 2011 Sep;17(9):1837-45. doi: 10.1002/ibd.21582. Epub 2010 Dec 22.
Immune suppressant medications such as thiopurines and anti-tumor necrosis factor agents are important for maintaining disease control in most patients with inflammatory bowel diseases (IBDs); however, their use has been associated with the development of malignant lymphoma. The purpose of this Dutch nationwide study was to estimate the relative risk of malignant lymphoma in IBD patients.
IBD patients who developed a lymphoma between 1997 and 2004 were identified using the Dutch National Database of PALGA. Data from confirmed cases were collected from individual hospitals, including data on Epstein-Barr virus (EBV). The age-adjusted 8-year incidence of malignant lymphoma in the Netherlands was retrieved from the Central Bureau of Statistics.
Forty-two hospitals were visited and 285 matches evaluated in the total cohort of 17,834 IBD patients. Forty-four lymphomas were observed, resulting in a relative risk of 1.27 (95% confidence interval [CI]: 0.92-1.68). Only 19 of 44 patients (43%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP). Remarkably, 92% of patients (11/12) with EBV-positive lymphoma used AZA/6-MP, in contrast to only 19% patients (4/21) with EBV-negative lymphoma, suggesting a strong relation between EBV-positive lymphoma and thiopurine use.
This nationwide study does not suggest a significant overall increased risk for lymphoma in IBD patients. A distinct correlation between EBV-positive lymphoma and AZA/6-MP use was observed.
免疫抑制剂如硫嘌呤和抗肿瘤坏死因子制剂对于大多数炎症性肠病（IBD）患者维持疾病控制非常重要；然而，它们的使用与恶性淋巴瘤的发展有关。本项荷兰全国性研究的目的是评估 IBD 患者恶性淋巴瘤的相对风险。
通过荷兰全国性 PALGA 数据库确定 1997 年至 2004 年间发生淋巴瘤的 IBD 患者。从各医院收集确诊病例的数据，包括 EBV 数据。从中央统计局检索到荷兰恶性淋巴瘤的 8 年年龄调整发病率。
在总共 17834 例 IBD 患者的队列中，访问了 42 家医院，评估了 285 例匹配。观察到 44 例淋巴瘤，相对风险为 1.27（95%置信区间[CI]：0.92-1.68）。仅 44 例患者中的 19 例（43%）暴露于硫唑嘌呤/6-巯基嘌呤（AZA/6-MP）。值得注意的是，92%的 EBV 阳性淋巴瘤患者（11/12）使用了 AZA/6-MP，而 EBV 阴性淋巴瘤患者仅为 19%（4/21），这表明 EBV 阳性淋巴瘤与硫嘌呤使用之间存在很强的相关性。
本项全国性研究并未提示 IBD 患者淋巴瘤的总体风险显著增加。观察到 EBV 阳性淋巴瘤与 AZA/6-MP 使用之间存在明显的相关性。
