BSR2013：干燥综合征或引起癌症等多种长期并发症

一项为期25年的单中心病例综述研究发现，干燥综合征患者的长期并发症呈现多样化和发生率高的特点。在1986~2011年英国伦敦大学医学院收治的152例原发性干燥综合征(pSS)患者中，超过一半的患者出现血清学异常(51.3%)，紧接着49.3%和28.3%的患者分别出现其他自身免疫性疾病和全身性恶性肿瘤。
在英国风湿病学会2013年会上，英国伦敦大学五年级医学生Esha Abro女士报告称，“我们发现并发症多累及腺体外器官，71%的患者出现腺体外临床症状，20%出现腮腺肿大等局部或腺体并发症，如腮喉痈等。”
Abrol女士提示，需要注意的是上述结果意味着pSS或许并非大家所认为的那样温和，非霍奇金淋巴瘤(NHL)风险增加也不是唯一值得提防的问题。
这项研究的大多数受试者为女性(91.4%)和白人(86.8%)，抗核抗体、抗-Ro/SS-A抗体、抗- La/SS-B抗体和类风湿因子阳性率分别为75.7%、55.9%、35.5%和54.6%，高丙种球蛋白血症患者占36.8%，确诊时平均年龄54.4岁。
研究者在病例回顾分析时发现，患者平均随访时间为12.4年。55.9%的患者仍然存活，26.6%失访(主要是由于年龄太大)，18.5%死亡，平均死亡年龄72岁。
Abrol女士报道说，“最常见腺体外临床表现之一为其他自身免疫性疾病”。15.8%的患者为自身免疫性甲状腺疾病(如桥本甲状腺炎和Graves病)，其他自身免疫疾病累及血管(10.5%为血管炎)、皮肤(10.5%)、胃肠道系统(10.5%)、肺部(7.2%)和肾脏(6.5%)等。
Abrol女士观察到，发生自身免疫疾病的患者多为女性、抗- Ro/SS-A或抗- La/SS-B抗体阳性以及高丙种球蛋白血症患者。19%的患者除SS外还出现1种以上的其他自身免疫性疾病，1例患者出现另外4种自身免疫性疾病。
一如预期，最常见的恶性肿瘤为NHL，其发生率约为1/10(10.5%)。还观察到其他一系列的癌症，随手举几个例子如卵巢和宫颈癌(3.3%)、膀胱癌(2.6%)、皮肤癌(2.6%)、肺癌(2.0%)和口咽癌(2.0%)等。
研究者称，50岁以上的患者恶性肿瘤风险更高，比值比(OR)为9.6(P=0.03)。癌症并发者也多为抗-RNP抗体阴性(OR，4.9；P=0.06)。血管炎(OR，10.5；P<0.001)和有腺体临床表现患者(OR,3.4；P=0.041)NHL风险增加。
还有其他数种并发症，包括血清学改变(51.3%，主要为高丙种球蛋白血症)、雷诺综合征(30.9%)和关节炎(19.7%)。部分患者还出现外周(15.8%)和中枢神经系统并发症(9.2%)。
Abrol女士总结道，这些数据突出显示原发性干燥综合征患者疾病负担高于既往预期，在与患者沟通长期结局时需提供这些信息。Abrol女士声明无利益冲突。

原文阅读：Sjögren's syndrome has high long-term complication rate
BIRMINGHAM, ENGLAND – Patients with Sjögren’s syndrome had a diverse and high rate of long-term complications over the course of a 25-year review of cases seen at a single center.
Between 1986 and 2011, 152 patients with primary Sjögren’s syndrome were treated at University College London (UCL), England. More than half of the patients developed serological abnormalities (51.3%), followed by additional autoimmune diseases in 49.3% and systemic malignancy in 28.3%.
“We found that the main complications were extraglandular,” Ms. Esha Abrol, a fifth-year medical student at UCL, reported at the British Society for Rheumatology annual conference. Extraglandular manifestations occurred in 71% of patients, and 20% of patients experiencing local or glandular complications, such as parotid swelling.
These data highlight that primary Sjögren’s syndrome is perhaps not as benign as people might think, Ms. Abrol suggested, and that an increase in the risk of non-Hodgkin’s lymphoma (NHL) is not the only problem to watch out for.
The majority of the study population was female (91.4%) and white (86.8%); three-quarters (75.7%) had antinuclear antibodies, 55.9% had anti-Ro/SS-A antibodies, 35.5% anti-La/SS-B antibodies, 54.6% were rheumatoid factor positive, and 36.8% had hypergammaglobulinemia. The mean age at diagnosis was 54.4 years.
At the time of the case review, at a mean of 12.4 years’ follow-up, 55.9% of patients were still alive; 26.6% had been lost to follow-up, which was mainly from old age, and 18.5% had died. The mean age at death was 72 years.
“One of the most common extraglandular manifestations was additional autoimmune diseases,” Ms. Abrol reported. These included autoimmune thyroid disease (for example, Hashimoto’s thyroiditis and Graves’ disease) in 15.8% of patients. Other autoimmune diseases included those affecting the blood vessels (vasculitis occurred in 10.5% of patients), skin (10.5%), gastrointestinal system (10.5%), lungs (7.2%), and kidneys (6.5%).
Ms. Abrol observed that patients who developed autoimmune diseases were more likely to be female than male, have anti-Ro/SS-A or Anti-La/SS-B antibodies, and hypergammaglobulinemia. Nineteen percent of patients had more than one autoimmune disease in addition to Sjögren’s, with one patient having four additional autoimmune diseases.
As expected, the most common type of malignancy seen was NHL, which occurred in approximately one in ten patients (10.5%). A range of other malignancies was seen, including ovarian and cervical (3.3%), bladder (2.6%), skin (2.6%), lung (2.0%), and oropharyngeal (2.0%) cancers, to name a few.
The risk for malignancy was higher in patients older than 50 years, with an odds ratio (OR) of 9.6 (P = .03). Patients who developed cancer were also more likely to be negative for Anti-RNP antibodies (OR, 4.9; P = .06).
The risk for NHL was increased in patients who had vasculitis (OR, 10.5; P less than .001) and in those with glandular manifestations (OR, 3.4; P = .041).
There were other numerous complications, including serologic alterations (51.3%), principally hypergammaglobulinemia, Raynaud’s syndrome (30.9%), and arthritis (19.7%). Peripheral and central nervous system complications were also seen in 15.8% and 9.2% of patients.
These data highlight that primary Sjögren’s syndrome carries a higher disease burden than previously suggested, Ms. Abrol concluded, noting that they can be used to inform patients on what may happen to them long-term.