Combe B, Didry C, Gutierrez M, Anaya J M, Sany J
Service de Rhumatologie, Hôpital Caremeau, Nîmes, France.
Eur J Med. 1993 Mar;2(3):153-6.
Methotrexate is successfully used in the treatment of arthritis but little is known about its effects on extra-articular manifestations of rheumatoid arthritis. We focused this work on the incidence and clinical course of extra-articular manifestations during long-term treatment with methotrexate.
The effect of methotrexate on extra-articular manifestations was investigated in 176 patients with rheumatoid arthritis who had obtained, in a prospective study, a good clinical response to methotrexate (10 mg/week) taken for 33 months (range 4-68).
Before taking methotrexate, 44 patients (25.1%) had extra-articular manifestations: nodules (n = 40) and vasculitis (n = 9). With methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and worsened in 10 (23%). Among the 132 patients without extra-articular manifestations before methotrexate therapy, 15 (11%) developed accelerated nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a pericarditis during methotrexate therapy. Extra-articular manifestations occurred between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was positive in 88% of the patients with extra-articular manifestations. No relationship was noted between extra-articular manifestations and HLA type or antinuclear antibodies. In 3 out of 4 patients who developed accelerated nodulosis while taking methotrexate, the addition of hydroxychloroquine (400 mg/day) resulted in a significant reduction in the number and size of the nodules within 3 to 10 months after starting combined therapy.
These data suggest that methotrexate is not effective in the treatment of extra-articular manifestations in rheumatoid arthritis and that nodulosis may occur in about 11% of patients taking methotrexate therapy for rheumatoid arthritis. The combination of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis that needs to be evaluated.
甲氨蝶呤成功用于治疗关节炎，但其对类风湿关节炎关节外表现的影响却鲜为人知。我们将这项工作聚焦于甲氨蝶呤长期治疗期间关节外表现的发生率及临床病程。
在一项前瞻性研究中，对176例类风湿关节炎患者进行了甲氨蝶呤（10毫克/周）治疗33个月（范围4 - 68个月）且临床反应良好的研究，以调查甲氨蝶呤对关节外表现的影响。
在服用甲氨蝶呤之前，44例患者（25.1%）有关节外表现：结节（n = 40）和血管炎（n = 9）。使用甲氨蝶呤后，31例结节病和血管炎病情稳定，3例改善，10例（23%）恶化。在甲氨蝶呤治疗前无关节外表现的132例患者中，15例（11%）出现了以手指为主的加速性结节病，7例出现血管炎，3例出现心包炎。关节外表现在开始甲氨蝶呤治疗后的1至24个月出现。88%有关节外表现的患者类风湿因子呈阳性。未发现关节外表现与HLA类型或抗核抗体之间存在关联。在4例服用甲氨蝶呤时出现加速性结节病的患者中，有3例在联合使用羟氯喹（400毫克/天）后，在联合治疗开始后的3至10个月内结节数量和大小显著减少。
这些数据表明，甲氨蝶呤对类风湿关节炎的关节外表现治疗无效，且在接受甲氨蝶呤治疗类风湿关节炎的患者中约11%可能发生结节病。羟氯喹和甲氨蝶呤联合使用可能对结节病有有益作用，有待评估。
