Gómez-Puerta José A, Martín Helena, Amigo Mary-Carmen, Aguirre Maria A, Camps Maria T, Cuadrado Maria J, Hughes Graham R V, Khamashta Munther A
From Lupus Research Unit (JAGP, HM, MJC, GRVH, MAK), Rayne Institute, St Thomas' Hospital, London, United Kingdom; Hospital Clinic, (JAGP), Barcelona; Fundación Hospital Alcorcón (HM), Madrid; Hospital Reina Sofía (MAA), Córdoba; Hospital Regional Universitario Carlos Haya (MTC), Málaga, Spain and Instituto Nacional de Cardiología Ignacio Chávez (MCA), Mexico City, Mexico.
Medicine (Baltimore). 2005 Jul;84(4):225-230. doi: 10.1097/01.md.0000172074.53583.ea.
We retrospectively studied a large cohort of patients with primary antiphospholipid syndrome (APS) from 4 different referral centers to analyze the clinical and serologic features and, specifically, to determine the number of patients going on to develop systemic lupus erythematosus (SLE) or other autoimmune disease after long-term follow-up. The study included 128 unselected patients with primary APS who fulfilled the Sapporo International Criteria from 4 different tertiary hospitals in the United Kingdom, Mexico, and Spain. The patients had attended the referral centers between January 1987 and July 2001. We reviewed clinical and serologic characteristics according to a pre-established protocol. We used univariate analysis with the chi-squared or Fisher exact test and logistic regression to analyze possible factors related to the coexistence of SLE and APS. Ninety-seven female and 31 male patients fulfilled the criteria, with a median age of 42 +/- 12 years (range, 16-79 yr), and with a mean follow-up of 9 +/- 3 years (range, 2-15 yr). The main manifestations included deep vein thrombosis in 62 patients (48%), arterial thrombosis in 63 (49%) patients, pregnancy loss in 177/320 (55%) cases, and pulmonary embolism in 37 (30%) patients. Other clinical manifestations were migraine in 51 (40%) patients, thrombocytopenia in 48 (38%), livedo reticularis in 47 (37%), and valvular disease in 27 (21%). Serologic findings were anticardiolipin antibodies (aCL) IgG positive in 110 (86%) patients, aCL IgM in 36 (39%), lupus anticoagulant in 71 (65%), antinuclear antibodies in 47 (37%), and positive Coombs test in 5 (4%) patients. During the follow-up and after a median disease duration of 8.2 years (range, 1-14 yr), 11 (8%) patients developed SLE, 6 (5%) developed lupus-like disease, and 1 (1%) developed myasthenia gravis. The remaining 110 patients (86%) continued to have primary APS. After the univariate analysis, a family history of lupus, the presence of Raynaud phenomenon, migraine, psychiatric features, multiple sclerosis-like features, hemolytic anemia, low C3 and C4, and Coombs positivity conferred a statistically significant risk for the subsequent development of SLE (p < 0.05). Only the presence of Coombs positivity had statistical significance (odds ratio, 66.4; 95% confidence interval, 1.6-2714; p = 0.027) after the logistic regression evaluation. The current study confirms that progression from primary APS to SLE or lupus-like disease is unusual, even after a long follow-up. Only 3 patients developed anti-dsDNA antibodies. The presence of a positive Coombs test might be a marker for the development of SLE in patients with primary APS.
我们对来自4个不同转诊中心的一大群原发性抗磷脂综合征（APS）患者进行了回顾性研究，以分析其临床和血清学特征，特别是确定经过长期随访后发展为系统性红斑狼疮（SLE）或其他自身免疫性疾病的患者数量。该研究纳入了128例符合 Sapporo 国际标准的原发性 APS 患者，这些患者来自英国、墨西哥和西班牙的4家不同的三级医院。患者于1987年1月至2001年7月期间就诊于这些转诊中心。我们根据预先制定的方案回顾了临床和血清学特征。我们使用卡方检验或 Fisher 精确检验进行单因素分析，并采用逻辑回归分析与 SLE 和 APS 共存相关的可能因素。97例女性和31例男性患者符合标准，中位年龄为42±12岁（范围16 - 79岁），平均随访时间为9±3年（范围2 - 15年）。主要表现包括62例（48%）患者发生深静脉血栓形成，63例（49%）患者发生动脉血栓形成，177/320例（55%）妊娠丢失，37例（30%）患者发生肺栓塞。其他临床表现为51例（40%）患者出现偏头痛，48例（38%）患者出现血小板减少，47例（37%）患者出现网状青斑，27例（21%）患者出现瓣膜病。血清学检查结果显示，110例（86%）患者抗心磷脂抗体（aCL）IgG 阳性，36例（39%）患者 aCL IgM 阳性，71例（65%）患者狼疮抗凝物阳性，47例（37%）患者抗核抗体阳性，5例（4%）患者 Coombs 试验阳性。在随访期间，疾病中位持续时间为8.2年（范围1 - 14年）后，11例（8%）患者发展为 SLE，6例（5%）患者发展为狼疮样疾病，1例（1%）患者发展为重症肌无力。其余110例（86%）患者继续患有原发性 APS。单因素分析后，狼疮家族史、雷诺现象、偏头痛、精神症状、多发性硬化样症状、溶血性贫血、低 C3 和 C4以及 Coombs 试验阳性与随后发生 SLE 的风险具有统计学意义（p < 0.05）。逻辑回归评估后，只有 Coombs 试验阳性具有统计学意义（比值比，66.4；95%置信区间，1.6 - 2714；p = 0.027）。当前研究证实，即使经过长期随访，原发性 APS 进展为 SLE 或狼疮样疾病也不常见。只有3例患者出现抗双链 DNA 抗体。Coombs 试验阳性可能是原发性 APS 患者发生 SLE 的一个标志物。
