专家视点：治疗红斑狼疮需兼顾全身

佛罗里达州德斯坦——匹兹堡大学卓越狼疮中心的Susan Manzi医生在临床风湿病学大会(CCR)上指出，系统性红斑狼疮(SLE)患者在接受治疗的过程中，可能会遇到多种长期健康问题：骨骼疾病、心血管疾病、癌症和感染等，这些风险都是临床医生不可忽视的。

·骨骼健康：已知女性SLE患者面临较高的骨折风险。例如1999年一项回顾性队列研究显示，在700多例女性SLE患者中观察到的非创伤性骨折发病率，超过一般人群的5倍(Arthritis Rheum. 1999;42:882-90)。

在不同年龄段的女性SLE患者中，标化发病率介于2.4~12.1，风险最高的是年龄18~24岁患者(12.1)，其次为45~64岁患者(7.6)，再次为≥70岁患者(4.9)。

Susan Manzi医生

“我们知道患者的骨丢失有相当一部分与我们(实施的治疗)有关；我们知道骨丢失可能是潜在疾病的一部分。不论如何，骨丢失是确实存在的，我们需要进行监测和加以干预。” Manzi医生指出，美国风湿病学会(ACR)指南可以为减少结缔组织病(包括狼疮)患者骨折提供帮助(Arthritis Care Res. 2010;62:1515-26)。

·心血管健康：与骨骼健康相似，1997年弗莱明翰后代研究显示，SLE患者的心肌梗死风险显著高于一般人群。

在这项研究中，Manzi医生及其同事发现，每个年龄段的SLE患者的心肌梗死发病率均高于其同龄对照者。其中年龄35~44岁SLE患者的心肌梗死风险更是高达总体研究人群的50倍(Am. J. Epidemiol. 1997;145:408-15)。

值得一提的是，2011年美国心脏协会(AHA)认定患有狼疮和类风湿性关节炎(RA)的女性属于心血管疾病高危人群，并且针对这类女性提出了治疗和管理建议。AHA认为，SLE和RA可能是尚未被认可的危险因素，患有这两种疾病的女性——即使没有临床相关心血管疾病——应当被视为高危并接受相应筛查。AHA建议“实际上表明，对于任何发生了心血管事件的女性患者，尤其是当事件原因不明确且患者较年轻时，应当筛查狼疮和RA”。

·癌症：2005年一项从30个中心纳入超过1.3万例患者的研究显示，狼疮患者的癌症风险比一般人群升高20%。更近期的数据与之相似，提示风险升高15%~20%(J. Autoimmun. 2013;42:130-5)。

SLE患者的癌症风险升高最明显的是血液肿瘤，如淋巴瘤和白血病。肺癌和甲状腺癌风险也有所升高，SLE患者还有宫颈癌和外阴癌风险升高的趋势，这可能与人乳头状瘤病毒(HPV)感染有关。“这意味着我们应当对SLE患者更多地进行宫颈涂片和盆腔检查。”

有趣的是，女性SLE患者似乎具有较低的乳腺癌、卵巢癌和子宫内膜癌风险，这很可能是其避免接受激素替代治疗的结果(Arthritis Rheum. 2005;52:1481-90)。

·感染：已知狼疮患者具有较高的感染风险，这提示应更谨慎地对狼疮患者使用减毒活疫苗，包括单纯疱疹病毒疫苗、卡介苗、口服伤寒疫苗、麻风腮疫苗、水痘疫苗、口服脊髓灰质炎疫苗、鼻内流感疫苗、黄热病疫苗和地方性斑疹伤寒疫苗等。

对于正在接受免疫抑制剂或生物制剂治疗的SLE患者，免疫球蛋白水平低下或有低补体血症的SLE患者，不建议使用上述疫苗。

Manzi医生是百时美施贵宝、Exagen诊断、基因泰克等多家公司的顾问。

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By: SHARON WORCESTER, Ob.Gyn. News Digital Network

DESTIN, FLA. – Patients with lupus are at increased risk for a number of long-term health issues that should be considered during the course of their care, according to Dr. Susan Manzi.

Bone disease, cardiovascular disease, cancer, and infection are particular areas of concern, Dr. Manzi said at the Congress of Clinical Rheumatology.

·Bone health. Women with systemic lupus erythematosus are known to be at increased risk for fractures. A 1999 retrospective cohort study, for example, showed that the observed number of nontraumatic fractures in more than 700 women with SLE was about fivefold greater than in the general population (Arthritis Rheum. 1999;42:882-90).
 
The standardized morbidity ratios ranged from 2.4 to 12.1 for various age groups, with the greatest risks in those aged 18-24 years (12.1), 45-64 years (7.6), and 70 years and older (4.9).

"We know that we cause a lot of the bone loss; we know that the bone loss may be part of the underlying disease. The fact is it’s there. We need to monitor for it and treat it," Dr. Manzi said. She noted that American College of Rheumatology guidelines are available to help in reducing fracture risk in patients with connective tissue diseases, such as lupus (Arthritis Care Res. 2010;62:1515-26).

·Cardiovascular health. Similarly, myocardial infarctions per 1,000 person-years are significantly greater among those with SLE than in the general population, according to the 1997 Framingham Offspring Study.

In that study, Dr. Manzi and her colleagues found that the incidence of MI was higher in SLE patients in every age category. The risk was 50-fold greater in those with SLE who were aged 35-44 years, compared with the overall study population (Am. J. Epidemiol. 1997;145:408-15).

Of note, in 2011 the American Heart Association officially recognized women with lupus and rheumatoid arthritis as at-risk groups for cardiovascular disease, and developed treatment and management recommendations for these groups, said Dr. Manzi, director of the Lupus Center of Excellence at the University of Pittsburgh. The AHA noted that SLE and RA may be unrecognized risk factors and that women with these conditions, even without clinically relevant cardiovascular disease, should be considered at risk and should be screened accordingly. The AHA recommendations "actually suggested that any woman who comes in with a cardiovascular event, particularly if it’s unexplained and they are young, should be screened for lupus and rheumatoid arthritis," she said.

·Cancer. In a 2005 study of more than 13,000 women from 30 centers, patients with lupus had a 20% increased risk for cancer, compared with the general population. A recent update similarly showed a 15%-20% increased risk (J. Autoimmun. 2013;42:130-5).

The greatest risk was for hematologic cancers, such as lymphomas and leukemia. Lung cancer and thyroid cancer were also increased in the lupus patients. A trend toward an increased risk of cervical and vulvar cancers was also noted, which could be associated with human papillomavirus infection. "This means we should be doing more paps and pelvics," she said.

Interestingly, women with SLE appear to have a reduced risk of breast, ovarian, and endometrial cancers, possibly as a result of avoidance of hormone replacement therapy, she said (Arthritis Rheum. 2005;52:1481-90).

·Infection. Patients with lupus are known to have an increased risk for infection, and it is important to exercise caution when using live attenuated vaccines. These include the herpes zoster vaccine; bacillus Calmette-Guérin tuberculosis vaccine; oral typhoid vaccine; measles, mumps, and rubella vaccine; varicella vaccine; oral polio vaccine; intranasal influenza vaccine; yellow fever vaccine; and endemic typhus vaccine, Dr. Manzi said.

These vaccines are not recommended for SLE patients being treated with immunosuppressive or biologic medications or with low immunoglobulins or hypocomplementemia.

Dr. Manzi has served as a consultant and/or advisory board member for Bristol-Myers Squibb, Exagen Diagnostics, Genentech, and other companies.