Sulphasalazine in the treatment of pauciarticular-onset juvenile chronic arthritis

Summary Sulphasalazine in a dose of 50 mg/kg/day was administered to ten patients with pauciarticular-onset juvenile chronic arthritis (JCA), with active disease not adequately controlled by nonsteroidal anti-inflammatory drugs (NSAID). The treatment was initiated with 1/4 of this dose and increased by weekly increments of 250–500 mg until the total dose was reached. In all patients sulphasalazine was the first disease-modifying agent tried. Among nine of the ten patients there was significant improvement in all clinical scores, including the number of active joints and the severity grading (tenderness and limitation of motion). Within 3 months of sulphasalazine therapy the laboratory measurements revealed marked improvement in the erythrocyte sedimentation rate (ESR) and haemoglobin values. One patient, in whom the ESR and haemoglobin were normal at onset, had no change in clinical scores. Transient skin rash and elevated liver enzyme levels developed in one patient. These preliminary data suggest that sulphasalazine is an effective and safe second-line agent in the management of pauciarticular-onset JCA. More trials with this drug are needed, including double blind, to study efficacy and safety of sulphasalazine in JCA.     

Sulphasalazine versus penicillamine in the treatment of rheumatoid arthritis

Summary Fifty-four patients with rheumatoid arthritis were randomized to either sulphasalazine or d-penicillamine in order to compare the short- and long-term efficacy of these two agents in the treatment of rheumatoid arthritis. Decisive improvement was observed in both treatment groups over a 1 year period. Side effects were common in both groups and accounted for termination of therapy in 11 patients during the first year. Radiological deterioration was evident in both treatment groups. A trend toward greater radiological deterioration was observed in patients receiving sulphasalazine, but this was not statistically significant. Only 11 of the 38 patients who completed 1 year of therapy were continuing to take the same drug 5 years later. Eight patients were continuing d-penicillamine and three were still taking sulphasalazine. Among the patients who completed 1 year of therapy, treatment was subsequently terminated because of loss of effective disease control in a significantly higher proportion of patients receiving sulphasalazine (P<0.01). The radiological data and the latter observations suggest that d-penicillamine may be a more effective agent for long-term treatment.     

Class I associations and frequencies of class II HLA-DRB alleles by RFLP analysis in children with rheumatoid-factor-negative juvenile chronic arthritis

Summary A total of 94 patients with juvenile chronic arthritis (JCA) was tested for HLA class I by serology and for class II by RFLP typing. Early onset JCA (EOPA) is associated with HLA-A2, DR5 and DR8 in both males and females. The combination (joint occurrence) of these JCA associated alleles (A2, DR5, DR8) is frequently seen in patients with chronic iridocyclitis. Late onset pauciarticular disease has an increased frequency of HLA-B27, especially in males. Our data confirm that polyarticular JCA with early childhood onset (4 years) is associated with DR5 and DR8 and has a different immunogenetic background from polyarticular JCA with later childhood (>4 years) onset (associated with DR4).     

Efficacy of methylprednisolone pulse therapy in children with rheumatoid arthritis

Pulse therapy is one of the most well-known methods used in the treatment of juvenile rheumatoid arthritis. This study assessed the outcome of methylprednisolone pulse therapy, its rate of efficacy, and its associated complications in patients with juvenile rheumatoid arthritis (JRA). This cross-sectional study was performed on 120 children with JRA who attended the Pediatric Ward of Imam Khomeini Hospital from 1994 to 2004 and who had undergone around 500 cycles of methylprednisolone pulse therapies. Clinical signs, including signs of improvement, complications, or recurrence of disease, were noted. SPSS version 11.5 and paired t test were used to compare the variables prior to and after treatment. Clinical signs observed included: feeling of weakness (100%), malaise (98.3%), loss of appetite (93.3%), fever (88.3%), skin rash (28%), lymphadenopathy (18.3%), serositis (4.2%), splenomegaly (3.3%), and hepatomegaly (1.7%); however, none of these findings were present after pulse therapy. The number of swollen and tender joints, duration of morning stiffness, erythrocyte sedimentation rate, C-reactive protein, and hemoglobin levels showed significant improvement after pulse therapy. Complications of pulse therapy included tachycardia (n = 16, 13.3%), hypertension (n = 10, 8.3%), headache (n = 2, 1.7%), and flashing (n = 2, 1.7%). The mean duration of remission was 3.3 ± 0.7 months.     

Bone mineral density in children with juvenile chronic arthritis

The aim of this study was to evaluate bone mineral density changes in patients with juvenile chronic arthritis (JCA) and to determine the most likely causes of osteoporosis in these patients. Eighteen (11 male, 7 female) patients suffering from JCA and 14 healthy controls (10 male, four female) were included in this study. The mean age of the patients and control groups were 11.0±3.2 and 10.9±2.9 years respectively. Disease activity was determined by clinical and laboratory evaluation and Articular Disease Severity Score (ADSS). Bone mineral density (BMD) of the femoral neck and lumbar spine was measured by dual photon absorptiometry.BMD of the patients at the lumbar spine was significantly lower than the control group (p<0.05). This difference was more marked in patients treated with steroids. Femoral neck BMD was also lower in the patient group but this difference was not statistically significant. There was a negative correlation between ADSS and BMD at the spine. In conclusion, trabecular bone loss is characteristic for osteoporosis in JCA. Our results indicate that steroid treatment and disease severity are important factors in the development of osteoporosis in JCA.     

Predicting pain among children with juvenile rheumatoid arthritis

Objective. Children and adolescents with juvenile rheumatoid arthritis (JRA) often report pain as a major symptom that affects their daily activities. Little is known about the factors that contribute to pain, however. Demographic, disease status, and social-psychologic variables were used to predict pain of JRA. Methods. Participants were 37 girls and 23 boys who were 7 to 17 years old. Measures included the Hopelessness Scale for Children, the Sadness Scale from the Differential Emotions Scale—IV, and the Social Support Questionnaire-Revised. A pain visual analogue scale served as the criterion measure. Results. Reported pain was modestly correlated with disease duration and age. A hierarchical regression indicated that the predictor variables accounted for a modest amount of variance in pain scores. Conclusions. The results suggest that the factors contributing to pain in children with JRA are different from those in adults with rheumatoid arthritis (RA). Research is needed to identify the psychologic and socioenvironmental variables that influence pain among children with JRA.     

A descriptive study of foot problems in children with juvenile rheumatoid arthritis (JRA)

In this study, we evaluated the feet of 144 consecutive children with juvenile rheumatoid arthritis (JRA) during a routine outpatient visit to discover patterns of foot problems. We found that all but nine subjects had at least 1 of 21 foot problems, categorized as inflammation, limitation of motion, and abnormal alignment. Overall, pronated rearfoot and midfoot were observed in 73% and 72% of JRA patients, respectively. Additionally, 36% had splayfoot, whereas 35% of subjects had ankle limitation of motion. Other common foot problems included pronated forefoot, rearfoot and forefoot synovitis, forefoot limitation of motion, and toe valgus. Significant differences in the occurrence of various foot problems were observed among JRA onset/course subgroups and were influenced by both age and disease duration. Specifically, subjects with polyarticular JRA had more forefoot limitation and toe valgus, whereas subjects with pauciarticular JRA had pronated forefoot more often. Ankle limitation of motion, although unrelated to the JRA subgroup, was related to the duration of JRA. Subjects with longer disease histories also had toe valgus more often. Conversely, forefoot limitation of motion seemed to be more a function of age than of disease duration. These results indicate that foot problems are common in the JRA population, and they underscore the need for thorough evaluation and physical therapy management.     

Effect on lung function of methotrexate and non-steroid anti-inflammatory drugs in children with juvenile rheumatoid arthritis

We evaluated lung function in a group of patients affected by juvenile rheumatoid arthritis (JRA), without clinical and/or radiological signs of respiratory involvement. We compared the effects on pulmonary function of methotrexate (MTX) therapy combined with non-steroid anti-inflammatory drugs (NSAIDs) to those of NSAIDs alone and correlated lung function to subtype onset, disease duration and disease activity. Our patients were 27 JRA children, subdivided into two groups according to the therapy (group A=14 patients, treated with a low dose of MTX and NSAIDs; group B=13 patients, treated with NSAIDs alone). Clinical evaluation, haematological data and pulmonary function tests (PFTs) were obtained in each group at baseline (time 0) and at 1 year (time 1). At time 0 and time 1 PFTs were altered in 51.8% of JRA patients. The restrictive pattern (reduced forced vital capacity, FVC) was the most frequent feature, observed in 22.2% of patients. In group A the mean values of FVC, FEV1 (forced expiratory flow in 1 s), FRC (functional residual capacity), TLC (total lung capacity) and DLCO (diffusing lung capacity of carbon monoxide) were significantly lower compared to those of group B, at time 0 and at time 1. No functional parameter was correlated to subtype, duration or activity of the disease. Our study confirms that abnormalities in PFTs may be detected in JRA patients, even in the absence of clinical and/or radiological signs of lung disease; MTX in combination with NSAIDs does not seem to affect lung function at 1 year more than NSAIDs alone. Received: 3 November 1997 / Accepted: 21 December 1997     

Sulphasalazine (Salazopyrin) in the treatment of enterogenic reactive synovitis and ankylosing spondylitis with peripheral arthritis

Summary Sulphasalazine was administered to 48 patients with reactive synovitis (RS) and ankylosing spondylitis (AS) with peripheral arthritis, resistent to nonsteroidal antiinflammatory drugs. Thirty-seven patients underwent an ileocolonoscopy and in 33 patients signs of chronic or active inflammation of the ileum and/or ileocecal valve were found. Forty-two patients improved after 3 to 12 months of treatment; 50 per cent of them went into remission. In most of the patients improvement failed to occur in the first 2 months of treatment. There was no recurrent disease activity in patients responding to the treatment. Adverse reactions were rare and did not necessitate interruption of treatment. The beneficial effect of sulphasalazine in the treatment of RS and AS with peripheral arthritis needs to be confirmed in double-blind controlled studies.     

Successfully treated sulphasalazine-Induced fulminant hepatic failure, Thrombocytopenia and Erythroid Hypoplasia with intravenous immunoglobulin

We report the simultaneous development of fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia in a child treated with sulphasalazine. A 12-year-old girl with juvenile rheumatoid arthritis developed fulminant hepatic failure, thrombocytopenia and erythroid hypoplasia, which was confirmed by liver histology and bone marrow examination, 2 weeks after initiation of sulphasalazine therapy. The patient recovered after administration of high doses of intravenous immunoglobulin. this is the first reported case of the concurrent development of these complications associated with sulphasalazine hypersensitivity. The use of intravenous immunoglobulin may have helped in the treatment of this rare adverse effect of sulphasalazine.     

Physical activity in children with juvenile rheumatoid arthritis: Quantification and evaluation

Objective. To measure daily physical activity in patients with juvenile rheumatoid arthritis (JRA) and in healthy controls, and to identify variables that may influence physical activity in JRA patients. Methods. Twenty-three prepubertal children, ages 5-11 years, with mild to moderate JRA and no prior exposure to systemic glucocorticosteroids, were compared to 23 healthy children of similar age. Physical activity was measured for 3 days (minimum of one weekend day) using 3 standardized methods simultaneously. Total body movement was assessed by the Caltrac accelerometer and the University of Cincinnati Motion Sensor (UCMS). The Caltrac measured movement in the vertical plane; the UCMS measured movement of 10° or more from the horizontal plane. The type and intensity of daily physical activity was measured by the 3-day activity record, which also recorded the number of hours of daily sleep. Participation and duration of involvement in organized sports was ascertained by questionnaire. Results. The mean physical activity was significantly lower in JRA patients than in controls for the activity diary (P = 0.05). However, daily body movement measured by the Caltrac and UCMS were similar for both groups. Differences were seen in the number of hours of sleep per day (P = 0.02) and participation in strenuous activities (P < 0.01). JRA patients had significantly less participation in organized sports (P = 0.01). Conclusion. There was less daily physical activity by this group of JRA patients than for healthy age-and sex-matched control subjects.     

Comparison of peak isometric knee extensor torque in children with and without juvenile rheumatoid arthritis

This study compared peak isometric knee extensor torque in children with juvenile rheumatoid arthritis (JRA) and healthy children. A secondary purpose was to determine the relationship between measures of articular disease severity and peak isometric knee extensor torque. Peak torque was measured with a computerized dynamometer. Twenty-eight children with JRA and 28 children without JRAwere matched for age, sex, and body surface area. Peak isometric knee extensor torque was significantly lower among the children with JRA than their respective control (P < 0.05, paired Student's t-test, one-tailed). There was no relationship between peak torque and measures ofarticular disease severity among the children with JRA. Subjects complained of quadriceps muscle discomfort as a result of the isometric muscle test. One child with JRA complained of increased knee pain and swelling. Peak isometric knee extensor torque appears to be a useful variable for characterizing muscle function deficits in children with JRA. Isometric muscle performance did not correlate with articular disease severity. The results suggest that isometric strengthening programs are indicated for this patient population. We recommend that clinicians monitor patients for joint and muscle symptoms during exercise training sessions.     

An educational needs assessment of children with juvenile rheumatoid arthritis

Objective. Our objective is to describe the use of the PRECEDE model (predisposing, reinforcing, and enabling causes in educational diagnosis and evaluation) to organize needs assessment data in order to define self-management behaviors and plan an educational intervention for children with juvenile rheumatoid arthritis (JRA) and their famihies. Methods. Analysis was done of needs assessment data collected from several sources: 1) literature review, 2) survey of parents of 51 children with JRA, 3) group interview of seven parents of children with JRA, 4) results of pilot programs, and 5) clinical experience of an interdisciplinary pediatric rheumatology team. Results. Two sets of interrelated behavioral factors were identified through the needs assessment: 1) those related to managing the school environment to facilitate optimal participation and to minimize schoolrelated disability, and 2) those related to treating pain and stiffness, intervening in the disease process, and preserving joint function. Conclusion. Both of these sets of behavioral factors may be related to the optimization of children's mobility, joint function, and autonomy of activities of daily living and should be targets of an educational intervention.     

Sulphasalazine in rheumatoid arthritis: Combination therapy with D-penicillamine or sodium aurothiomalate

Summary This open study examined the safety of adding a second slow-acting antirheumatic drug (SARD) — D-penicillamine or sodium aurothiomalate — to the therapy of 38 rheumatoid patients already established on sulphasalazine. Combined anti-rheumatic therapy given in this way was generally well-tolerated and the incidence of adverse reactions was not increased. During the first year none of the reactions were serious although 9 of the 29 patients (31%) given D-penicillamine and 3 of the 9 patients receiving aurothiomalate developed side-effects requiring withdrawal of the second SARD. Reactions attributed to D-penicillamine were: gastro-intestinal-6, rashes-2, and blurring of vision-1. All 3 reactions occurring with gold were rashes, 2 associated with proteinuria and one with increased liver enzymes. During the second year D-penicillamine was withdrawn in 4 patients due to thrombocytopenia-2, and rashes-2. In addition an overall favourable clinical response was achieved in 70% of patients. This approach for combination therapy whereby a second SARD is given to patients already established on a single SARD, appears to minimise the toxicity which is a problem when 2 SARDs are started simultaneously.     

The development of erythema elevatum diutinum in a patient with juvenile idiopathic arthritis under treatment with abatacept

In this case report, we present the first report of erythema elevatum diutinum after treatment of juvenile idiopathic arthritis with abatacept. Although it could also be coincidental, in our case, the appearance of vasculitis was not blocked by the simultaneous administration of a stimulation inhibitor, and alerts to the fact that as effective as a abatacept may be to control of the inflammatory articular symptoms, this might not translate into control of the disease.     

Comparison of serum nitric oxide levels in active juvenile rheumatoid arthritis with those of patients in remission

Thirty-four children with juvenile rheumatoid arthritis were studied for surrogate markers of increased nitric oxide (NO) production by spectrophotometry. Mean levels of reactive nitrogen intermediates and citrulline levels were higher in patients with active disease than in children with partial and complete remission. A significant correlation was also found between clinical indices of inflammation, erythrocyte sedimentation rate, modified Childhood Health Assessment Questionnaire scores, and surrogate markers of increased NO production.     

甲氨蝶呤单用或联合柳氮磺胺吡啶治疗类风湿关节炎的疗效和安全性的再评价

目的：系统评价单独使用甲氨蝶呤(MTX)与联合柳氮磺胺吡啶(SSZ)治疗类风湿关节炎(RA)的疗效及安全性。方法：采用主题词和自由词相结合方法,检索Pubmed、EMBASE、OVID和CNKI全文期刊网,收集疗程大于半年的相关随机及半随机对照临床试验,对其逐个进行质量评价及系统分析。结果：总计纳入4个临床试验,共318例RA患者。MTX单独或联合SSZ治疗RA的总有效性没有差别：采用随机效应模型比较4个试验共306例RA患者,合并后的比值比(OR)为0．75．95% Cl 0．44～1．27;采用美国风湿病学会(ACR)标准进行评价,MTX单独或联合SSZ治疗RA的缓解率没有差异：采用固定效应模型比较208例RA患者的OR为0．77．95% CI 0．43～1．38;采用欧洲风湿病学会联盟(EULAR)标准进行评价,MTX单独或联合SSZ治疗RA的缓解率没有差异,固定效应模型OR为1．04．95%Cl 0．60～1．82;联合治疗的不良事件发生率要远高于单独使用MTX：共3个试验264例RA患者,合并后的OR 0．40,95%Cl 0．20～0．78。其中两种治疗方案在神经系统的不良反应发生率相似,2个试验208例患者合并后的OR为0．56,95%Cl 0．25～1．27;联合用药的消化道不良反应发生率远高于单独使用MTX,2个试验208例患者合并后的OR 0．27,95%Cl 0．15～0．49。结论：联合MTX及SSZ与单用MTX治疗RA相比,联合治疗的不良反应发生率显著增加,而疗效并未相应增加,提示今后临床治疗RA应慎重考虑MTX与SSZ联合治疗的效益和安全性。     

Does sport negatively influence joint scores in patients with juvenile rheumatoid arthritis

Summary The influence of sporting activities performed using joint protective measures on deterioration in hand and lower extremity function was evaluated over 8 years in 62 patients with juvenile rheumatoid arthritis (JRA). Sporting activities usually recommended to patients with JRA, such as cycling and swimming, did not negatively influence hand or lower extremity function as compared to a control group of patients not taking part in sporting activities. Besides cycling and swimming, other sporting activities were only performed by a minority of patients (less than 10%). Decreases in total joint scores of both the hands and lower extremities, showed significant correlations with disease duration in patients taking part and in patients not taking part in sporting activities. Polyarticular onset of disease was associated with higher total joint scores of the hands as compared to pauciarticular onset of disease. In lower extremity function, no difference was found between patients with polyarticular onset and patients with pauciarticular onset. Disease duration of longer than 10 years, accompanied by severe functional deterioration, was followed by low participation in sporting activities. Therefore, we suggest that appropriate sporting activities, such as cycling and swimming, can be advised to patients with JRA regardless of disease duration, since no negative effects were observed in our study over a period of 8 years.