狼疮患者使用强的松3年会使白内障风险翻倍

美国约翰霍普金斯大学对2,109例患者开展的一项回顾性分析表明，如果系统性红斑狼疮（SLE）患者使用强的松10 mg/d或等效物3年或以上，其发生白内障的风险会增加1倍以上。

 根据年龄、性别以及其他潜在混杂因素进行校正之后，研究者发现如果患者使用该剂量强的松长达10年或以上，那么白内障风险会增加两倍（相对风险，3.1；95%置信区间，1.6~5.7；P = .0005）；如果使用强的松10 mg/d或等效物3~10年，那么发生白内障的风险会增加一倍（RR，2.3；95% CI，1.3~4.3；P = .0065）。使用强的松不足3年者，白内障风险没有增加（Rheumatol. Int. 2014 Sept. 26 [doi:10.1007/s00296-014-3129-5]）。

约翰霍普金斯大学风湿病学博士后研究员Khaled Alderaan及其同事报告称，所有患者均来自“霍普金斯狼疮患者队列”；这些患者每季度看一次风湿病科医生，每半年看一次眼科医生。入选研究时大约一半的患者年龄不足40岁，其余患者也不超过60岁。大部分患者（93%）都是女性，以白种人（54%）和黑人（39%）为主。加入这个研究队列时所有患者都没有白内障病史。

在总共11,887患者-年中，这个队列的白内障发生率约为13.2/1,000患者-年。

分析显示，白内障与狼疮病程、糖尿病、吸烟史、高胆固醇、肾损害、免疫系统状况以及除强的松外的其他用药史均无关。而在一般人群中，我们已知糖尿病、吸烟史和高胆固醇会增加白内障风险。

 Alderaan博士说，我们早就知道长期使用强的松会导致白内障，但这项研究明确了到底使用多长时间、多大剂量会导致问题出现。总的来看，对于SLE患者来说，“强的松的累积剂量是白内障最重要的危险因素。”此外，如果在4.1年的中位随访期内患者的平均收缩压超过140 mm Hg，那么其发生白内障的风险会增加一倍（RR，2.2；95% CI，1.4~3.3；P = .0006）；根据SELENA–SLEDAI（系统性红斑狼疮疾病活动度评分，根据红斑狼疮雌激素安全性全国评估研究进行修订）测得的疾病活动度每增加2分，白内障风险增加30%（RR，1.3；95% CI，1.1~1.5；P=0.0005）。

作者总结道：“上述结果进一步强调了控制SLE患者血压和疾病活动度的重要性。”

研究者指出：“疾病活动度高可能是增加皮质类固醇剂量的指征之一。不过，我们的多因素分析显示，在针对皮质类固醇剂量进行校正之后，疾病活动度与白内障之间的相关性依然存在。对于这一相关性，另一种可能的解释是SLE对眼内细胞因子和生长因子的免疫影响。正如在一般人群中得到的结果一样，这些细胞因子失衡有可能促进白内障的形成。

研究者写道：“在一般人群中，高血压与白内障之间的关系尚无一致的定论。而且，高血压诱导白内障的病理生理学机制仍不明确。有人认为两者间的潜在相关性可能是受到了糖尿病、吸烟史等混杂因素的影响。在这项研究中，我们针对其他所有混杂因素进行校正之后，高血压与白内障之间的相关性依然存在。”

研究者还指出，在这项研究中，男性发生白内障的风险比女性低20%。“虽然这一结果没有统计学意义，但的确与在一般人群中得到的研究结果相吻合。”至于导致这一性别差异的潜在原因，目前尚不清楚。

这项研究由美国国立卫生研究院资助。研究者声明无相关经济利益冲突。

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The risk of cataracts more than doubles if patients with systemic lupus erythematosus have been on 10 mg/day of prednisone, or its equivalent, for 3 or more years, according to a retrospective review of 2,109 patients at Johns Hopkins University in Baltimore.

After the researchers controlled for age, sex, and other potential confounders, they found that the risk triples when patients have been on that dose for 10 or more years (relative risk, 3.1; 95% confidence interval, 1.6-5.7; P = .0005). The doubling of risk was found in those who had been on 10 mg/day, or its equivalent, for 3-10 years (RR, 2.3; 95% CI, 1.3-4.3; P = .0065). Shorter courses did not increase the risk of cataracts (Rheumatol. Int. 2014 Sept. 26 [doi:10.1007/s00296-014-3129-5]).

  It’s not news that long-term prednisone causes cataracts, but the findings give an idea of how long it takes – and how much drug is needed – for problems to emerge. Overall, in patients with systemic lupus erythematosus (SLE), “the cumulative prednisone dose was the most important risk factor for cataract[s],” concluded Dr. Khaled Alderaan, a postdoctoral fellow in rheumatology at Johns Hopkins University, and his team. Also, the risk of cataracts doubled if patients had a mean systolic blood pressure above 140 mm Hg over a median of 4.1 years of follow-up (RR, 2.2; 95% CI, 1.4-3.3; P = .0006 ), and the risk increased 30% for every 2-point increase in disease activity, as measured on the SELENA–SLEDAI (Systemic Lupus Erythematosus Disease Activity Index, as modified for the Safety of Estrogens in Lupus Erythematosus National Assessment) (RR, 1.3; 95% CI, 1.1-1.5; P = .0005).

  “These results provide further incentive for controlling blood pressure and disease activity in SLE,” the authors concluded.

The patients, all members of the Hopkins Lupus Cohort, were seen quarterly by their rheumatologists and examined every half year by their ophthalmologists. About half were under 40 years old when they enrolled, and the rest were under 60 years old. Most of the patients (93%) were women, and most were either white (54%) or black (39%). They had no cataract history when they joined the cohort.

Cataracts were not associated with lupus duration, diabetes, smoking, high cholesterol, renal involvement, immunological profile, and medication history other than prednisone. Diabetes, smoking, and high cholesterol are all known to increase the risk of cataracts in the general population.

During a total of 11,887 persons-years, the cohort had a cataract incidence of 13.2/1,000 persons-years.

 “High disease activity would be an indication for higher corticosteroid doses. However, in our multivariate analysis, the association of disease activity with cataract persisted after we controlled for corticosteroid doses. Another potential explanation of the association between disease activity and cataract is an immunological impact of SLE on ocular cytokines and growth factors. Imbalance between these cytokines can facilitate the formation of cataract, as proposed in the general population,” the investigators noted.

 “In the general population, the relationship between hypertension and cataract has been inconsistent. Moreover, the pathophysiological mechanism of hypertension-induced cataract remains uncertain. Some have debated the potential association may be affected by confounding factors such as diabetes or smoking. In our study, the association persisted after controlling for all other confounding factors,” they wrote.

Men in the study had a 20 % lower risk of cataracts than did women. “Although this finding was not statistically significant, it is consistent with general population studies.” The reasons for the sex differences are unknown, the researchers wrote.

The work was funded by the National Institutes of Health. The investigators have no competing financial interests.