関節リウマチ(RA)の治療において生物学的製剤であるエタネルセプトが近年使用されているが,その効果減弱例に対して関節鏡視下滑膜切除を施行した7例88関節,男性2例,女性5例,平均年齢62(48～75)歳について術前c-reactive protein(CRP)とdisease activity scores(DAS)28を経時的に48週まで調べ,術中採取した滑膜を組織学的にtumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)およびreceptor activator of nuclear kappa B ligand(RANKL)の発現について調べた.その結果CRPは術前3.8±0.5mg/dlから術後48週で0.7±0.4mg/dlに有意に低下し,DAS28は術前6.3±0.6から術後48週で2.7±0.9に有意に低下した.エタネルセプト効果減弱例の滑膜はリンパ球浸潤,血管増生を示し,滑膜表層に多核の組織球の発現を認めた.免疫組織化学的検討ではTNF-αの発現は滑膜全体の細胞に見られ,IL-6は滑膜細胞は抑制され血管のみ発現していた.破骨細胞の分化を促進するRANKLは滑膜に発現していなかった.以上よりエタネルセプト効果減弱例のRAでは組織学的にTNF-αの発現が見られる滑膜を切除することにより,局所からのサイトカイン産生を抑制する関節鏡視下滑膜切除は有効であり,エタネルセプトの効果を持続できる一つの手段として考えられる.In order to investigate whether arthroscopic synovectomy is effective for rheumatoid arthritis (RA) patients who exhibit an incomplete response to etanercept treatment, we assessed 7 subjects who underwent 8 arthroscopic synovectomies in the knee joint, shoulder joint and elbow joints. We compared c-reactive protein (CRP) and disease activity scores (DAS) 28 before and at 4, 24 and 48 weeks after surgery. Immunohistochemical examination was performed whether tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and receptor activator of nuclear kappa B ligand (RANKL) expressed in synovial cells besides lymphocytes invasion and vascular proliferation occurred in hematoxylin and eosin (HE) staining. After arthroscopic synovectomy we continued etanercept treatment with or without methotrexate (MTX) in a routine manner. We detected synovium proliferation with a vascular increase in the patella femoral (PF) joint, around the meniscus and also on the femoral and tibial side of the anterior cruciate ligament (ACL) in the knee joints. We also found synovium proliferation in the rotator interval (RI) in the glenohumeral joint and fatty change in the subacromial bursa (SAB) in the shoulder. In the elbow joint we found synovium proliferation with white fibrous tissue around the radioulner joint which had developed into bone erosion. The average of CRP at preoperation, 3.8 ± 0.5 mg/dl, was improved to 1.3 ± 0.3 mg/dl at 6 weeks, 0.6 ± 0.2 mg/dl at 24 weeks and 0.7±0.4 mg/dl at 48 weeks after surgery. There were no side effects, not even post surgical infection from arthroscopic synovectomy, during etanercept treatment. DAS28 was improved from 6.3±0.6 to 3.5 ± 1.2 at 6 weeks, 2.8±0.7 at 24 weeks and 2.7±0.9 at 48 weeks after surgery. Histological examination revealed that lymphocyte proliferation, multi-nuclear cells and hyper vascularity emerged in etanercept toleration cases. TNF-α and IL-6 were expressed in the synovium, however RANKL was not expressed. Therefore, it is possible that arthroscopic synovectomy, in order to remove the synovium which produces TNF-α and IL-6, can be an effective method for the continuation of etanercept treatment when its efficacy is decreased in or attenuated for RA patients
