Systemic Lupus Erythematosus (SLE)
With the incidence of systemic lupus erythematosus (SLE) increasing, anesthesiologists are more likely to be exposed to patients with the disease. Next weeks we'll be discussing various aspects of SLE, and This week, we'll be discussing the treatment of SLE.
1. What is the basic treatment regimen for SLE?
2. Given the effectiveness of corticosteroids in the treatment of SLE inflammation, why should they not be used continuously?
3. Can thalidomide play a role in the treatment of SLE?
随着SLE发生率的增高，麻醉科医生也越来越多的接触到此类疾患。本周我们将讨论SLE的治疗。
1、SLE的基本治疗方法？
2、使用皮质激素治疗SLE炎症产生作用后，为什么不能继续使用？
3、反应停（镇静剂）能否用于SLE的治疗？
参考答案：
1、SLE的基本治疗方法？
对SLE进行有规律的医学评估，这对充分诊断非常重要，因为这可以指导药物治疗。对于轻微的关节炎症，可选用非甾体类抗炎药；而对于全身性炎症而言，谨慎的使用皮质激素常是主要的治疗手段[1]。抗疟药如羟氯喹可减低SLE的活动，有助于降低皮肤和关节症状。对于严重的SLE表现，可使用更强的免疫抑制剂如硫唑嘌呤、环磷酰胺。由于SLE具有周期性缓解的特性，因此即使对于严重的患者，也常采用逐渐减量或停止药物治疗的方法[1]。
2、使用皮质激素治疗SLE炎症产生作用后，为什么不能继续使用？
除了可显著减轻临床症状，偶尔可达到临床治愈，应避免使用皮质激素的持续使用，因为其具有潜在的永久性器官损害的作用。Zonana-Nacach等[2]使用全身性红斑狼疮国际合作机构/美国大学风湿病损害指数对器官损害的发生率进行了评价。作者表示，累积强的松剂量36.5gm（如每天使用强的松10mg达10年）造成器官损害的风险与以下发展显著相关：
骨质疏松性骨折（相对风险[RR]2.5，95%可信区间[95%CI]1.7，3.7）
有症状的冠心病（RR 1.7，95% CI 1.1，2.5），及
白内障（RR 1.9，95% CI 1.4，2.5）
此外，每两月接受大剂量强的松治疗的患者，其发生无血管性坏死（95% CI 1.1，1.4）和中风（95% CI 1.0，1.5）的几率增加1.2倍。需要更进一步的研究以判断SLE疾患的相对影响，以及皮质激素器官特定损害的作用机制。新的控制性（节制）激素疗法用于治疗活动性SLE，从而最大程度的降低强的松的累积性和大剂量性损害。
3、反应停（镇静剂）能否用于SLE的治疗？
反应停的致畸性和明显的神经损害限制了其使用。然而，对于红斑狼疮皮肤损害其他治疗方法无效时，反应停似乎非常有效。虽然停药之后经常出现复发，但是缓慢降低药物剂量可降低其发生，有时甚至可逆转疾病的发展。现在反应停的这种作用的机制尚不清楚。因为其具有潜在的严重的副作用，因此选择合适患者并采取可靠的避孕措施正在研究中。近期有临床和神经生理学研究推荐使用神经传导监测。
What is the basic treatment regimen for SLE?
Regular medical evaluations to monitor SLE are vital for a good prognosis, as this allows for the tailoring of drug regimens. For mild joint inflammation, nonsteroidal anti-inflammatory medications are appropriate, and with progression towards generalized systemic inflammation, judicious use of corticosteroids are often the mainstay of therapy (1). Anti-malarials such as hydroxychloroquine reduce SLE activity and are helpful for moderate skin and joints symptoms. With severe SLE symptoms, stronger immunosuppressive drugs such as azathioprine and cyclophosphamide can be utilized. Even with severe disease, SLE is known for its periodic remissions, so tapering and/or discontinuing of medications can occasionally be considered (1).
Given the effectiveness of corticosteroids in the treatment of SLE inflammation, why should they not be used continuously?
Despite their dramatic reduction of symptoms and occasional ability to achieve clinical remission, corticosteroids should be avoided on a continuous basis due to the potential for permanent organ damage. Zonana-Nacach et al. (2), evaluated the occurrence of organ damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The authors noted that the risk of organ damage for a cumulative prednisone reference dose of 36.5 gm (e.g., 10 mg of prednisone daily for 10 years) was significantly associated with the development of:
• osteoporotic fractures (relative risk [RR] 2.5, 95% confidence interval [95% CI] 1.7, 3.7),
• symptomatic coronary artery disease (RR 1.7, 95% CI 1.1, 2.5), and
• cataracts (RR 1.9, 95% CI 1.4, 2.5).
Moreover, each 2-month exposure to high-dose prednisone was associated with a 1.2-fold increase in the risk of both avascular necrosis (95% CI 1.1, 1.4) and stroke (95% CI 1.0, 1.5). Additional research is required to determine the relative contributions of SLE disease activity and corticosteroids to the pathogenesis of specific types of organ damage. New steroid-sparing therapies are being developed (to be discussed in tomorrow's Answerpage) to treat disease activity and minimize cumulative and high-dose prednisone exposure.
Can thalidomide play a role in the treatment of SLE?
The teratogenicity and significant neuropathy associated with thalidomide has limited its use. However, thalidomide appears to be an effective treatment for the cutaneous forms of lupus erythematosus refractory to other therapies. Although recurrence after discontinuation of treatment frequently occurs, moderate doses are effective in slowing and sometimes reversing the progress of the disease. Currently, the mechanism by which thalidomide exercises its effects remains unclear. As the potential for severe thalidomide side effects is known, identification of suitable patients and the use of reliable contraceptive measures are strictly observed. Close clinical and neurophysiological supervision using nerve conduction studies has been recommended.
References:
1. http://www.rheumatology.org/patients/factsheet/sle.html
2. Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000 Aug;43(8):1801-8.
3. Karim MY, Ruiz-Irastorza G, Khamashta MA, Hughes GR. Update on therapy--thalidomide in the treatment of lupus. Lupus 2001;10(3):188-92
编辑：ache
