Pain associated with juvenile rheumatoid arthritis

Despite a comprehensive approach to the treatment of JRA patients, pain remains a largely underdeveloped area of research and an undertreated clinical problem. Pain is a highly prevalent condition in JRA patients, one that in adults has been shown to be highly predictive of current medication usage and future disability. This recurrent or chronic pain syndrome is currently treated primarily with nonsteroidal anti-inflammatory drugs, but inclusion of pain management specialists on the interdisciplinary team will allow for greater use of nonpharmacologic means of pain management.     

Neutropenia associated with chrysotherapy for juvenile rheumatoid arthritis.

Severe neutropenia, in the absence of generalized bone marrow depression, is a rare complication in adults receiving chrysotherapy for rheumatoid arthritis and has not been described in children. Isolated, severe neutropenia developed in five children with systemic onset JRA while they were receiving gold injections. This potentially fatal complication occurred within eight weeks of beginning therapy in four patients, and after 24 weeks of well-tolerated therapy in the fifth. Leukopenia preceded neutropenia in two children. Localized infection was successfully treated in one child; septicemia was fatal to a second child. Neutropenia resolved within eight to 14 days of its onset in the four survivors; chelation with dimercaprol in one child did not appear to alter the recovery time. It is suggested that a systemic onset of JRA in children less than 6 years of age identifies a higher risk group developing severe neutropenia during chrysotherapy. Cessation of gold therapy upon recognition of a decreasing neutrophil count may prevent or ameliorate a developing neutropenia; careful observation for, and early treatment of, infection may alter its outcome.     

Epstein-Barr virus associated Hodgkin lymphoma in a 9-year-old girl receiving long-term methotrexate therapy for juvenile idiopathic arthritis

We describe a case of Hodgkin lymphoma developing in a 9-year-old girl with polyarticular, rheumatoid factor-positive juvenile idiopathic arthritis treated with methotrexate (MTX), prednisone, and naproxen for 5 years. Pathologic and molecular analyses revealed that the Hodgkin cells contained Epstein-Barr virus and the viral DNA was monoclonal. She achieved complete remission after MTX withdrawal, chemotherapy, and radiation. To the best of my knowledge, this is the sixth report of Hodgkin lymphoma in patients with juvenile idiopathic arthritis receiving low dose MTX therapy.     

Consumption coagulopathy associated with systemic juvenile rheumatoid arthritis

A coagulopathy resembling disseminated intravascular coagulation may occur in systemic juvenile rheumatoid arthritis. We have seen this in seven patients with three different circumstances of disease activity or drug treatment. In one patient, a coagulopathy was not associated with drug therapy, and required corticosteroid therapy for control. A second group of patients was receiving orally nonsteroidal anti-inflammatory drugs during an acute flare-up of disease associated with low serum albumin concentrations. Coagulopathy in these patients may be a result of reduced vascular endothelial cell cyclooxygenase activity secondary to increased levels of unbound nonsteroidal anti-inflammatory drug. In these children, corticosteroid therapy was required for control. A third form of coagulopathy was seen in patients receiving a second injection of aurothiomalate. This form appears to be idiosyncratic, self-limiting, and relatively benign.     

Factors associated with response to methotrexate in systemic-onset juvenile chronic arthritis

We retrospectively investigated, in 19 children with systemic-onset juvenile chronic arthritis (SoJCA), the possible influence on the outcome of methotrexate (MTX) therapy of several independent variables, including age at onset of juvenile chronic arthritis, disease duration and severity of the disease at baseline. The dosage of MTX ranged from 7.5 to 11.O mg/m*/week (median 9.3 mg/m²/week) and was given as a single, oral weekly dose. After 6 months of treatment, 12 (63%) patients were judged as responders on grounds of a 50% reduction in the number of joints with active arthritis and/or an articular severity score; 7 (37%) did not respond to therapy. When the baseline values of the selected variables were compared, we found that the responder group had, with respect to the non-responder group, a lower percentage of radiographic lesions ( p < 0.005), a shorter duration of the disease ( p < 0.05) and a lower number of joints with limitation of motion ( p < 0.01), functional limitation score ( p < 0.05) and articular severity score ( p < 0.05). A threshold value of disease duration of two years and the presence/absence of radiographic lesions gave a correct classification with respect to the treatment outcome of 73.7% and 83.3%, respectively. The predictive value of these two variables was confirmed by a multivariate analysis. We conclude that earlier treatment with MTX, possibly before the appearance of radiographic changes, may favourably influence the outcome of MTX treatment in those patients with SoJCA who require a second-line drug.     

来氟米特和甲氨蝶呤联合治疗幼年类风湿性关节炎21例报告

目的　探讨来氟米特和甲氨蝶呤联合治疗幼年类风湿性关节炎的疗效及其安全性。方法　 40例多关节型幼年类风湿性关节炎 (JRA) ,分为治疗组和对照组。治疗组 (来氟米特和甲氨蝶呤 ) 2 1例 ,对照组 (甲氨蝶呤 ) 1 9例 ,各自接受相应药物治疗 2 6周。参与疗效综合评估的指标有关节压痛数、关节压痛指数、关节肿胀数、关节肿胀指数、关节整体功能评分、家长及医生评分、血沉、C 反应蛋白、类风湿因子水平。以总改善百分率对疗效进行综合评估。参与安全性评估的指标有黏膜、皮肤损害、胃肠反应、神经系统反应、血象、肝、肾功能。结果　治疗组用药后 1 2、2 6周的总平均改善率分别为 39 6 %、71 9% ;对照组的总平均改善率分别为 2 7 5 %、49 5 % ,两组差异有显著性 (P <0 0 1 )。治疗组用药后 1 2、2 6周的缓解率分别为 4 76 %、38 1 0 % ;对照组分别为 0、0 ,两组差异有显著性 (P <0 0 1 )。治疗组不良反应的发生率为 9 5 % ,主要表现为轻度白细胞减少和转氨酶升高 ;对照组不良反应发生率为 5 3 % ,主要表现为头晕、皮疹 ,症状轻微 ,两组差异无显著性 (P >0 0 5)。结论　来氟米特和甲氨蝶呤联合治疗幼年类风湿性关节炎的临床疗效显著优于单独使用甲氨蝶呤。但来氟米特有白细胞减少、转氨酶升高的不良反     

Advanced drug therapy for juvenile rheumatoid arthritis

Childhood rheumatic diseases are frequently chronic, painful, and potentially debilitating. They may adversely affect growth and development, compromise future quality of life, and contribute added stress to the patient and family. Awareness of these consequences provides a stimulus to develop more effective therapeutic regimens. There is optimism that new therapeutic strategies will result in the more widespread and earlier use of drugs, including those discussed, that may substantially impede or arrest the underlying disease.     

Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis.

OBJECTIVE: To assess the efficacy of low-dose oral methotrexate (MTX) therapy for children with severe iritis. METHODS: MTX in a weekly dose of 7.25 to 12.5 mg/m2 was administered orally to four patients (two with juvenile rheumatoid arthritis [JRA] and two with sarcoidosis) with severe iritis not adequately controlled by topical and systemic corticosteroid therapy. The treatment was initiated with half of the total dose and increased every 2 weeks until the final dose was reached. Iritis was graded from 0 to +4 according to the density of cells in the anterior chamber of the eye. RESULTS: There were three girls and one boy with a mean age of 10.5 years. Two patients were African American and two were Caucasian. The mean age at onset of iritis was 6 years. The mean duration of MTX therapy was 28.8 months. Significant improvement was noted in two of the four patients in ocular inflammation, demonstrated by reduction of cell density from +4 to +1. Two patients had a mild improvement of the iritis. However, corticosteroids were significantly reduced in all patients. One patient was completely off steroids within 30 months of MTX therapy. In the remaining three cases, the steroid dose was successfully tapered from 0.82 mg/kg/d to 0.15 mg/kg/d (mean doses) within a mean duration of 20 months. No side effects were observed with MTX therapy. CONCLUSION: Low-dose MTX therapy was effective and safe, and displayed steroid-sparing properties in four children with severe iritis.     

Hypohistidinemia in juvenile rheumatoid arthritis.

The mean level of plasma histidine in 86 children with rheumatoid arthritis was found to be significantly lower in comparison with that of controls. The possible influence of various drugs on the plasma histidine concentration is discussed.     

Use of methotrexate in juvenile idiopathic arthritis.

Methotrexate (MTX) has transformed the outlook for children with juvenile idiopathic arthritis (JIA). Most of the evidence from uncontrolled clinical trials suggests that MTX is an effective agent for treating active JIA. Data from controlled clinical trials suggests that MTX has statistically significant effects on patient centred disability measures in JIA patients with active arthritis. Although we would like a much larger study directed evidence base for our use of the drug, the studies that have been done are sound and have been followed by a change in clinical expectations and advice that speak of qualitative evidence from clinical practice, confirming the scientifically acquired data. Randomised controlled multicentre trials using sufficient numbers of patients, including functional assessment and quality of life measures, are needed to confirm the long term efficacy and safety of MTX in JIA.     

Gold nephropathy in juvenile rheumatoid arthritis.

A 2-year-old girl was treated with gold salts for juvenile rheumatoid arthritis. Treatment had to be discontinued when persistent proteinuria was detected. As this case report indicates, close monitoring of the urine is mandatory during treatment with gold salts to detect early signs of toxicity: hematuria followed by casts and then proteinuria as therapy is continued. Histologic examination with electron microscopy will help to differentiate the different forms of gold toxicity. When the findings are consistent with gold-induced renal involvement, therapy should be discontinued. The gold nephropathy usually resolves in time, with no permanent renal damage.     

Thalidomide therapy for recalcitrant systemic onset juvenile rheumatoid arthritis

Systemic onset juvenile rheumatoid arthritis unresponsive to nonsteroidal anti-inflammatory drugs may be controlled with corticosteroids, but these drugs have significant side effects. We report 2 steroid-dependent children with systemic onset juvenile rheumatoid arthritis who did not respond to multiple nonsteroidal anti-inflammatory drugs, methotrexate, azathioprine, cyclosporine, and etanercept. Both children had significant improvement with thalidomide therapy.