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.     

Sulphasalazine in the treatment of children with chronic arthritis

The ainich of study was to investigate the efficacy and toxicity of sulphasalazine (SASP) in the treatment of children with chronic arthritis. The medical records of 36 children (25 boys, 11 girls) who received SASP for the treatment of chronic arthritis were reviewed. Twenty-one patients had juvenile spondyloarthropathies (JSA) (eight juvenile ankylosing spondylitis (JAS), 13 undifferentiated JSA (uJSA) and 15 had juvenile rheumatoid arthritis (JRA). The patients received SASP therapy for a mean of 2.5 years (range 3 weeks to 8.1 years). Clinical and laboratory data were reviewed retrospectively to determine the effects of treatment. A clinically significant response occurred in 23 (64%) children: remission in 14 (39%) (JRA 5, JSA 9) and improvement (25% reduction in joint count) in nine (25%) (JRA 4, JSA 5). There was no difference in response rate between JR and JSA patients (p=0.11), but the time to remission shorter in JSA patients (mean 5 months) JRA patients (mean 25 months) (p=0.024). Twelve of the 36 patients discontinued non-steroidal anti-inflammatory drugs, and six of eight patients discontinued prednisolone. A significant fall in erythrocyte sedimentation rate and rise in haemoglobin occurred in SASP-treated patients (p<0.005) comparing most recent results with pretreatment levels. Side-effects occurred in four of 36 patients (11%); only one patient who had persisting severe diarrhoea required discontinuation of SASP. It was concluded that SASP appears to be effective and safe in the treatment of JRA and JSA patients. As a second-line agent, SASP is the drug of first choice for patients with JSA; for JRA patients SASP may be a useful, possibly less toxic alternative to methotrexate.     

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.     

Lack of association between the HLA-DRB1 locus and post-streptococcal reactive arthritis and acute rheumatic fever in Italian children

OBJECTIVE: Post-streptococcal reactive arthritis (PSReA) may be a variant of acute rheumatic fever (ARF), but there still is debate on the relationship between the 2 entities. Possible associations with HLA class II antigens of PSReA (DRB1*01) and ARF (DRB1*16) were described previously in white Americans. To confirm these findings, we studied DRB1 alleles in a group of Italian children with PSReA and ARF. METHODS: We performed low-resolution HLA-DRB1 typing by a sequence-specific primer polymerase chain reaction method in 33 children with PSReA and 25 children with ARF. We also compared the DRB1 genotypes of our patients with 200 normal subjects from the same geographic area and typed in the same laboratory with the same methods. RESULTS: The allele distributions at the DRB1 locus observed in PSReA patients, ARF patients, and controls were not significantly different from each other (chi-square test with small numbers, P = .65). The positivity for each of the 13 HLA-DRB1 alleles was compared in disease groups (PSReA and ARF) and controls, and failed to show any significant association. Comparisons of the frequency of the DRB1*01 allele among PSReA, ARF, and controls did not show any statistical differences. No significant difference in the frequency of DRB1*16 was present between ARF vs the control group, between ARF vs PSReA, and in PSReA patients when compared with controls. CONCLUSIONS: Our data do not confirm in Italian patients the previously reported associations of DRB1*01 and DRB1*16 with PSReA and ARF, respectively.     

HLA-DRB1 alleles encoding the shared epitope associated with rheumatoid arthritis confer additional susceptibility to seronegative spondyloarthropathies in HLA-B27-positive Japanese individuals

Although the crucial role of HLA-B27 for the development of seronegative spondy-loarthropathies (SpA) has been established, family and twin studies indicated the presence of additional genetic factors. To determine whether HLA-DRB1 gene acts as an additional susceptibility factor for SpA in HLA-B27-positive Japanese individuals, complete HLA-DRB1 allele typing of 23 HLA-B27-positive patients (21 with ankylosing spondylitis, one with Reiter’s syndrome, and one with uveitis and sacroiliitis) and 17 HLA-B27-positive healthy individuals was performed using polymerase chain reaction-microtiter plate hybridization (PCR-MPH) assay. Twenty-two of patients’ 46 HLA-DRB1 alleles (47.8%) were those that encode the shared epitope associated with rheumatoid arthritis, as compared with eight of 34 DRB1 alleles of healthy HLA-B27-positive individuals (23.5%). This difference was statistically significant [odds ratio (OR)=2.98.P=0.036]. Seventeen of 23 patients were positive for one or two alleles coding for the shared epitope, as compared with seven of 17 healthy individuals (73.9 versus 41.2%, OR=4.04,P=0.053). These results suggest that HLA-DRB1 alleles encoding the shared epitope may act as an additional susceptibility factor for the development of SpA in HLA-B27-positive Japanese individuals.     

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     

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.     

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.     

Only weak association between disease severity and HLA-DRB 1 genes in a Swiss population of rheumatoid arthritis patients

This study analyses the prognostic value of HLA-DRB 1 genes for Swiss patients with rheumatoid arthritis (RA). HLA-DRB 1 genotyping was performed in 83 patients using the polymerase chain reaction and subsequent oligonucleotide hybridisation. They were categorised according to the presence of one or two putatively relevant genes (DRB 1^*01 and/or DRB 1^*04) and retrospectively evaluated for sex, age at disease onset, seropositivity, erosive disease and extraarticular manifestations. Sixty-one patients (73%) had disease-associated alleles. Twenty-four patients showed HLA-DRB 1^*04 variants on both alleles or combined an HLA-DRB 1^*04 variant with HLA-DRB 1^*01, while 37 patients expressed only one relevant allele. Interestingly, 22 patients did not express any relevant allele. Some 52% of patients had nodular disease, 88% were seropositive, 96% had joint erosions and I I% expressed vasculitis and/or rheumatoid organ disease. A significant difference was observed only for the number of seropositive individuals, which was slightly higher in the group of patients expressing a double dose of disease-associated alleles than in patients who had no relevant alleles. Moreover, patients expressing homozygous DRB 1 alleles had a significantly earlier onset of disease than those who were heterozygous. We conclude from these findings that HLA-DRB 1 genotyping in a Swiss population of RA patients only weakly identifies clinical subsets with distinct profiles of disease manifestations and is not of strong prognostic value to determine disease severity in individual patients.     

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.     

Methotrexate therapy in systemic-onset juvenile rheumatoid arthritis in Saudi Arabia: A retrospective analysis

Eighteen patients (nine girls, nine boys) with systemic onset juvenile rheumatoid arthritis (SO-JRA) treated with methotrexate (MTX) for a mean period of 18 months (range 6–41 months) were analysed to evaluate the safety and efficacy of MTX in this disease subtype. The MTX dose ranged from 2.5 to 15 mg/week with a mean cumulative dose of 684.9 mg/patient at the last follow-up visit. Systemic features were severe in 10 patients before MTX was started. None of these patients showed systemic features at the last follow-up visit. Sixteen patients (89%) showed improvement in both the active joint count (from a mean of 12.0 to 1.3 joints/patient) and function class (from a mean of 3.0 to 1.3) while receiving MTX. Eleven patients (61%) showed a significant decrease in the erythrocyte sedimentation rate (>50% of the initial value), an improvement in anaemia (haemoglobin >2 g) and reduced thrombocytosis (platelets 2×10⁵). Of the patients receiving corticosteroids, three patients (20%) were able to discontinue prednisone and the dose was reduced to less than 50% of the initial dose in seven patients (47%). At these doses of MTX, no gastrointestinal, hepatic or haematological toxicity was encountered and none of the patients withdrew because of toxicity or lack of efficacy. This report suggests that MTX is an effective and safe treatment in controlling systemic and articular features in this subtype of JRA.     

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.     

Lymphokines and soluble interleukin-2 receptors in juvenile chronic arthritis

Summary Serum levels of interleukin (IL)-2, interferon gamma (IFNg) and soluble IL-2 receptors (sIL-2R) were determined in sera from 34 patients with poly-or pauciarticular juvenile chronic arthritis (JCA) by use of enzyme-linked immunosorbent assays (ELISAs). Levels of sIL-2R were elevated in the group of patients compared with those of healthy children and correlated significantly with several parameters of clinical activity, including the functional capacity, joint score, visual-analogue score and erythrocyte sedimentation rate (ESR). Serum IL-2 levels were also elevated in the JCA patients, correlating with the patients functional capacity. Serum levels of IFNg were below the detection limit of the assay. Our data supported the notion that T-cell activation plays a role in the immunopathologic processes leading to clinical JCA.     

Disease and family contributors to adaptation in juvenile rheumatoid arthritis and juvenile diabetes

Objective. Research in the areas of pediatric rheumatology and pediatric chronic illness has emphasized comprehensive models of adaptation involving risk and resistance factors. This study examined adaptation, within this framework, among a large sample of children with chronic illness and children without chronic illness. Methods. A comprehensive battery of adaptation measures was administered to a sample of 107 children with juvenile rheumatoid arthritis, 114 children with insulin-dependent diabetes mellitus, and 88 healthy controls. Results. Medical diagnosis was associated with mothers' depression and a composite measure of parental (mother and father) distress and passive coping. Children's emotional and behavioral functioning was not related to medical diagnosis, but mothers' depression and parental distress were associated with child behavior problems. Conclusion. Because parental distress was associated with child functioning, interventions to ameliorate parental distress may have beneficial effects on the children's behavior and on parents' reactions to their children.     

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.     

Analysis of the HLA-DR gene frequencies in Japanese cases of juveniles rheumatoid arthritis and rheumatoid arthritis by oligonucleotide DNA typing

Summary HLA-DR gene frequencies in 59 Japanese children with juvenile rheumatoid arthritis (JRA) and 62 Japanese adults with rheumatoid arthritis (RA) were analyzed by oligonucleotide DNA typing. As in other studies, the frequency of DRB1*0405 in RA patients was significantly higher than in the Japanese controls. In a comparison of non-calssified JRA patients with Japanese controls, no significant differences were observed in the frequency of DR types. However, when the JRA patients were classified into four clinical types, i.e., a rheumatoid factor-positive [RF(+)] polyarticular type, a rheumatoid factor-negative [RF(-)] polyarticular type, a pauciarticular type, and a systemic onset type, DRB1*0405 was found to be significantly higher in the RF(+) polyarticular JRA patients than in the controls (P>0.05). Thus, the RF(+) polyarticular type of JRA had the same HLA association as RA. This result is consistent with the fact that both RF(+) polyarticular JRA and RA cases have a similar clinical course.     

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.     

Systemic onset juvenile rheumatoid arthritis presenting with absence of B lymphocytes

Juvenile rheumatoid arthritis (JRA) is a complex disease involving the interactions of several cell populations with different mediators. Herein, we report a five-year-old girl with systemic-onset JRA. At admission, peripheral blood flowcytometric analysis showed the percentages of CD19⁺ and CD20⁺ B cells were <1%. These values returned to normal on the tenth day of steroid treatment. This is the first report of JRA presented with absence of B lymphocytes in the literature and suggested that lymphocytes subset analysis could change with treatment in patients with JRA. Different clinical signs and symptoms reflecting aspects of JRA are critical for the etiology of the disease and to identify new strategies for treatment.