目的:硫嘌呤可有效治疗炎症性肠病(IBD)患者,但使用硫嘌呤与皮肤癌(包括非黑素瘤皮肤癌[NMSC]和黑素瘤皮肤癌)风险之间的关联已经得到充分报道.然而,这些研究的结果是不一致的,因此,我们分析的目的是探讨硫嘌呤是否会导致IBD患者患皮肤癌的额外风险.
方法:MEDLINE,EMBASE,我们检索了Cochrane图书馆,以确定评估使用硫嘌呤治疗的IBD患者患皮肤癌风险的相关研究.进行随机效应荟萃分析以计算合并的发病率比率以及风险比率(RR)。进行亚组分析以探索异质性的潜在来源。
结果:纳入了13项研究,包括149.198名参与者。结果表明,硫嘌呤显著增加IBD患者整体皮肤癌的风险(随机效应:RR=1.80,95%置信区间[CI]1.14-2.87,P=0.013)。其中NMSC显示与使用硫嘌呤相关的额外风险(随机效应:RR=1.88,95%CI1.48~2.38,P<0.001),而未观察到黑色素瘤皮肤癌的风险增加(随机效应:RR=1.22,95%CI0.90~1.65,P=0.206).关于皮肤癌的样本量和地理分布以及NMSC的随访时间的亚组分析达到统计学意义。而其他亚组无显著性。
结论:IBD患者中硫嘌呤的暴露与皮肤癌的高风险相关。建议对这些患者进行常规皮肤筛查和每日皮肤保护实践。
OBJECTIVE: The
thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between
thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether
thiopurines can lead to an excess risk of skin cancer in IBD patients.
METHODS: MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity.
RESULTS: Thirteen studies comprising 149 198 participants were included. The result suggested that
thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance.
CONCLUSIONS: Exposition of
thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.