类风湿关节炎伴恶性实体瘤(文献综述)

欧美国家有很多关于类风湿关节炎(RA)肿瘤风险的大样本研究，有的认为，比总体人群相比，RA总的肿瘤风险没有增加[1-5]，有的甚至认为肿瘤风险还较低[6-7]。hakravarty等人的一项-分析发现RA患者的肿瘤风险没有增加[8]。但依然有相当数量的研究认为肿瘤风险是增加的[9-12]，Smitten等对观察性研究进行的-分析也发现RA患者的肿瘤风险增加[13]。很多研究都得出RA患者血液系统肿瘤风险增加，而结肠肿瘤风险下降的结论[1-4，9-11, 14-18]。亚洲国家中日本和韩国在2011年和2012年也先后发表了RA并肿瘤的大样

本研究结果，RA患者相较总体人群肿瘤风险没有增加[19-20]。2011年台湾地区阳明大学的Chen YJ研究发现RA患者的肿瘤风险增加，尤其是造血系统及肾肿瘤，随访时间延长，肿瘤相对风险降低[21]。2014年发表的台湾地区的Huang WK等根据台湾健保资料进行研究发现，台湾的RA患者总体肿瘤风险与总体人群相比没有显著增高，但造血系统肿瘤发病风险轻度增加，结肠肿瘤风险轻度下降[22]。A合并肿瘤的发病机制不明。疾病本身和治疗措施都有可能增加肿瘤的风险。英国的Mercer LK等发现：使用非生物DMARD治疗的RA患者的肺癌、霍奇金淋巴瘤和非霍奇金淋巴瘤风险增加，而前列腺与女性生殖道肿瘤风险降低[12]，并指出肿瘤坏死因子不增加英国RA人群肿瘤风险[23]，而荷兰的Ramiro S等进行了系统回顾，发现生物DMARDs不增加总体肿瘤风险，轻度增加黑色素瘤风险，而原有的化学药物DMARDs没有发现新的安全问题[24] 。Lopez-Olivo MA等对2012年以前的随机对照研究进行分析发现，对比一般DMARD和安慰剂，生物制剂治疗患者至少随访6个月不增加肿瘤风险[25]。Moulis G等进行-分析后也得出相同结论，推荐剂量下使用抗肿瘤坏死因子治疗RA短期内不增加肿瘤风险[26]。在亚洲人群方面，2014年发表的文献中台湾地区阳明大学医学院的Chun-Ying Wu等人研究发现抗肿瘤坏死因子治疗RA不增加肿瘤风险[27]而美国的andersen CL等发表在著名杂志PLOS ONE上的论文指出，与总体人群相比，RA患者的肿瘤风险没有增加，且与病程无关，意味着治疗措施并不增加肿瘤风险[28]。

笔者认为：RA患者免疫系统功能活跃，但其他系统却表现出功能缺陷，因此对一些治疗药物的致癌作用很敏感，持续激活的淋巴细胞最终可能转化成恶性肿瘤。当RA患者突然出现病情进展迅速且治疗效果不佳时，应警惕可能并发恶性肿瘤。

RA自身的肿瘤发病率是研究RA治疗药物致肿瘤风险的基础，英国的Mercer LK等指出判定生物制剂增加肿瘤风险时应对RA自身的肿瘤风险加以考虑[12]。不同的国家和地区，人群存在人种、卫生状况、教育程度等差异，流行病学资料可能存在差异。国内关于RA与恶性肿瘤的研究仅有少量病例报道[29，30]，尚未有大样本的调查研究。本文希望能起到抛砖引玉的作用，期待国内也能有大样本的研究获得符合我们大陆地区的数据，从而更好地指导RA的治疗与研究。

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