Juvenile Chronic Arthritis in Adult Life: A Study of Long-term Outcome in Patients with Juvenile Chronic Arthritis or Adult Rheumatoid Arthritis

We compared the prognostic factors and outcome of 30 patients with juvenile chronic arthritis (JCA) extending into adult life with those of 30 patients with adult rheumatoid arthritis (RA) at a university adult rheumatology clinic; pairs were matched for sex and duration of disease (mean 8 years). One-third of JCA patients had seronegative polyarticular disease and another third had oligoarticular disease. In a third of the JCA patients, the clinical presentation changed during the follow-up. Over half of the RA patients had seropositive polyarticular and a one-third had seronegative polyarticular disease. Fewer seropositive patients were recorded in the JCA group than in the RA group both at the beginning (16.7% versus 56.7%; p = 0.003) and at the end of the follow-up (14.3% versus 59.3%; p = 0.001). JCA patients developed less radiographic changes than RA patients (46.7% versus 76.7%; p = 0.034); oligoarthritis in the JCA group had the best prognosis whereas seropositive polyarthritis in the RA group had the worst prognosis. Significantly more patients with JCA than RA (60% versus 23%; p = 0.009) were in remission at the end of the follow-up. In conclusion, when studied in adult life, the long-term prognosis is better in patients with JCA than in those with RA. Received: 23 March 1998 / Accepted: 3 November 1998     

Detection of Stromelysin and Collagenase in Synovial Fluid From Patients with Rheumatoid Arthritis and Posttraumatic Knee Injury

Objective. To quantify stromelysin and collagenase in synovial fluid (SF) from patients with rheumatoid arthritis (RA) or traumatic knee injury. Methods. Stromelysin and collagenase were measured in the SF of 33 patients with RA or posttraumatic knee injury, using specific double-antibody sandwich enzyme-linked immunosorbent assays. Stromelysin was fractionated from representative SF, and the molecular form was identified by immunoblot analysis. Results. The stromelysin concentration was ˜20-fold higher than the collagenase concentration in the fluids from patients with RA and ˜8-fold higher in the fluids from patients with traumatic injury. For both metalloproteinases, there was a higher enzyme concentration in RA SF than in the SF from patients with trauma (stromelysin 40.1 ± 26 μ/ml [mean ± SD] in RA SF, 8.5 ± 15 μ/ml in trauma SF; collagenase 2.2 ± 3.3 μ/ml in RA SF, 1.1 ± 2.3 μ/ml in trauma SF). The majority of the stromelysin within the SF bound to reactive red—agarose and was identified as prostromelysin based on electrophoretic mobility and immunoblotting with monospecific antibodies. Conclusion. The finding of high levels of stromelysin in SF from patients with RA supports the proposal that this enzyme may play a role in the connective tissue degradation observed in this disease.     

Absence of Lentiviral and Human T Cell Leukemia Viral Sequences in Patients with Rheumatoid Arthritis

Objective. The etiology of rheumatoid arthritis (RA) is unknown, and the possibility that an infectious agent is involved has not been excluded. Lentiviruses can cause chronic arthritis in humans and in animals and have been suggested as candidate agents in RA. We therefore tested for the presence of lentiviruses and also for human T cell leukemia virus type I (HTLV-I)/ HTLV-II in cells from patients with RA. Methods. We used the polymerase chain reaction with degenerate primers designed to recognize highly conserved nucleotide sequences from 5 different pathogenic lentiviruses. This method allowed the detection of at least 1 infected cell/20,000 uninfected cells in control experiments. Results. Testing of synovial cells and blood cells from patients with early RA and patients with established RA did not yield any specific viral product. Conclusion. Our results do not support the presence of lentiviruses or HTLV-like sequences in RA.     

Incidence of Hepatitis Associated Antigen HAA and Homologous Antibody in Patients with Rheumatoid Arthritis

Abstract. The authors have studied the incidence of hepatitis associated antigen (HAA) and the homologous antibody in sera of patients with rheumatoid arthritis on the basis of (1) arthritis sometimes associated with viral hepatitis, (2) the possible infectious etiology of rheumatoid arthritis, and (3) observation on the possible pathogenetic role of HAA in some cases of polyarteritis nodosa. The presence of HAA and antibody titer gave constantly negative results in all subjects examined with the exception of one case which showed no signs of serological or histological hepatic involvement. On the basis of the results obtained, the negligible role of HAA in the etiopathogenesis of rheumatoid arthritis is underlined. However, the authors emphasize as suggestive the hypothesis that the characteristic histopathological alterations of rheumatoid arthritis may be mediated by an immunological reaction toward an infectious agent other than HAA, but operating through mechanisms similar to those of HAA in polyarteritis nodosa.     

类风湿关节炎患者外周血、滑液及滑膜组织中自然杀伤细胞的特征

目的探讨自然杀伤细胞（NK）在类风湿关节炎（RA）中的特征以及在疗效判断中的作用。方法采用流式细胞仪在单个细胞水平分析RA患者外周血、滑液与滑膜组织中NK细胞的数量。分析NK细胞中信号分子的改变以及产生细胞因子的能力，观察经肿瘤坏死因子（TNF）单克隆抗体治疗后RA患者外周血中NK细胞数量的变化与疗效之间的相关性。结果与健康对照者相比，RA患者外周血中CD3^-CD56^＋NK细胞的数量显著减少（8．95±3．72vs.5．31±5．07，P〈0．05）。RA患者滑液与滑膜组织中CD3^-CD56^＋、CD3^-CD247^＋NK细胞的数量均显著少于相应的外周血（P〈0．05），同时这些细胞中信号分子CD247表达的强度也显著降低。IL-12联合IL-18刺激使1．4％的RA外周血单个核细胞产生干扰素γ，其中1．1％为NK细胞产生；肉豆蔻酸酯和钙离子载体可以使15．33％的单个核细胞产生干扰素γ，其中13．87％为T淋巴细胞产生，NK细胞占1．47％。经TNF单克隆抗体治疗14周后，临床判定为良好反应和中度反应的5例患者中4例外周血中NK细胞数目增加，而治疗反应差的2例患者中NK细胞数量增加或减少各1例。结论RA患者循环与炎症部位中NK细胞的数量显著减少，这些细胞的信号传导和细胞因子产生能力低下；NK细胞的低下状态与所处环境中的炎症程度有关，TNF单克隆抗体治疗在改善患者疾病活动性的同时，使外周血中NK细胞呈增加趋势，NK细胞可能成为疗效判断的一项指标。     

Renal Involvement in Juvenile Rheumatoid Arthritis: Report of Two Cases

Renal involvement is a rare occurrence in juvenile rheumatoid arthritis (JRA). We report on two JRA patients with kidney disease. The first was a 14-year-old African-American female with a 12-month history of polyarthritis. On presentation she was found to have an ESR of 127 mm/h and a positive ANA, rheumatoid factor (RF), perinuclear antineutrophil cytoplasmic antibodies (pANCA), haematuria, proteinuria with normal BUN and creatinine. Renal biopsy showed focal segmental glomerulosclerosis. Her renal function deteriorated to end-stage renal failure requiring dialysis within a few months, despite aggressive treatment with steorids and monthly i.v. pulses of cyclophosphamide. The second patient presented with a 6-week history of polyarthritis and intermittent fever, and had a salmon-coloured evanescent rash. On presentation his laboratory evaluation was significant for elevated ESR and negative ANA, RF and ANCA tests. Within 8 months the patient had developed a persistent microscopic haematuria. Renal biopsy showed mild mesangial glomerulonephritis. On low-dose methotrexate therapy his JRA went into remission and his renal function remained normal. The haematuria persisted for 1 year and then resolved spontaneously. This is the first time that focal segmental glomerulosclerosis and mesangial glomerulonephritis have been described in JRA. Although the association may be just coincidental, further studies are needed to define the role of JRA in these renal conditions. In patients with JRA, urinalysis and renal function should be routinely monitored. Received: 6 April 2000 / Accepted: 20 October 2000     

Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.     

Adenosine Deaminase Activity and its Isoenzyme Pattern in Patients with Juvenile Rheumatoid Arthritis and Systemic Lupus Erythematosus

Adenosine deaminase (ADA) is involved in purine metabolism and plays a significant role in the mechanisms of the immune system. The aim of this study was to investigate the activity of total ADA (tADA) and its isoenzymes ADA1 and ADA2 in serum and peripheral blood lymphocytes (PBLs) of children with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE) in different phases of the diseases. The study comprised 34 patients with rheumatic disease, 24 with JRA and 10 with SLE, and 64 healthy controls. The tADA activity and its isoenzymes were measured in serum and PBLs of all patients by the method of Giusti and by the presence or absence of EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) during the active phase of the disease (before treatment), as well as during remission and relapse. Our data show that increased tADA activity in the serum and PBLs of patients with JRA and SLE is correlated mainly to increased levels of ADA2 activity in serum and ADA1 activity in PBLs. It also closely correlates with clinical disease activity and relapse. The cause of this increased tADA/ADA2 activity in serum and tADA/ADA1 activity in PBLs in JRA and SLE remains to be elucidated. Nevertheless, it may be noted that the measurement of tADA activity, together with ADA2 activity in serum and tADA with ADA1 activity in PBLs, could offer a biochemical approach to the assessment of the pathophysiology of JRA and SLE. Also, tADA and its isoenzymes could be used as alternative parameters representing disease activity. Received: 31 July 2000 / Accepted: 5 June 2001     

类风湿关节炎患者心血管风险的管理

类风湿关节炎(rheumatoid arthritis,RA)患者心血管病发病率和死亡率的风险增加。吸烟、高血压、血脂异常、胰岛素抵抗、糖尿病、肥胖和体力活动缺乏传统危险因素不能完全解释RA心血管风险。炎性反应在RA和心血管病之间起着重要作用,不仅参与动脉粥样硬化的各个阶段:内皮功能障碍、斑块破裂和血栓形成,而且还能加速传统心血管风险,如血脂异常、肥胖和胰岛素抵抗。目前关于RA和心血管病之间确切的发病机制尚不清楚,对RA心血管风险管理是必要的。     

Non-inflammatory Causes of Pain in Patients with Rheumatoid Arthritis

Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered.     

A Study of Synovial Fluid and Cytology in Arthritis Associated with Herpes Zoster

Summary: A study of synovial fluid and cytology in arthritis associated with herpes zoster. A. L. Cunningham, J. R. E. Fraser, B. J. Clarris and J. B. Hobbs, Aust. N.Z. J. Med., 1979, 9, pp. 440–443.
A case of herpes zoster complicated by acute arthritis with effusions is described. The white cell count in the synovial fluid was low, with a predominance of neutrophils. The synovium showed superficial deposits of fibrin, slight intimal hyperplasia, and subintimal polymorph infiltration. Varicella virus was not detected by culture or electron microscopy, but varicella antigen was demonstrated in the cytoplasm of macrophages in the effusion. Other findings did not determine whether the antigen had appeared in the joint from circulating immune complexes, or following synovial phagocytosis or proliferation of virus.     

类风湿关节炎患者血清破骨细胞相关受体的临床意义

目的通过比较类风湿关节炎患者及正常人血清破骨细胞相关受体(osteoclast-associated receptor,OSCAR)水平,验证破骨细胞相关受体参与类风湿关节炎的炎症过程。方法采用ELISA方法测定类风湿关节炎患者及正常人血清中破骨细胞相关受体水平。结果类风湿关节炎患者血清OSCAR水平为(1.259±0.450)ng/ml,较正常对照组(1.754±0.426)ng/ml低,且与疾病活动性呈负相关,两组比较差异具有统计学意义(P0.05)。结论破骨细胞相关受体参与了类风湿关节炎的炎症过程,在关节损伤及破坏过程中具有重要作用。