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).     

Bone mineral density in Indian women with rheumatoid arthritis

Osteoporosis (OP) is being increasingly recognized in inflammatory rheumatic diseases like rheumatoid arthritis (RA). Ethnicity influences bone mineral density (BMD) and fracture risk. Due to paucity of data on this aspect of RA from Asian countries including India, we prospectively studied 84 premenopausal women with RA of at least 2 years duration and 247 healthy, age (within 5 years) and sex-matched controls. A significant difference in BMD between patients and controls was observed only at the femoral neck. As many as 22% patients with RA exhibited osteoporosis at least one site in contrast to 9% controls. Nearly 40% of patients exhibited osteopenia at all the three sites. Modified Sharp score, disease duration and DMARD naive period were found to correlate with low BMD. However, on multivariate analysis, only modified Sharp score was shown to be significantly associated with low BMD. Our study draws attention to the poor bone health in Asian Indian women with RA.     

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.     

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.     

HLA B27: A prognostic factor in juvenile chronic arthritis

This study was performed to assess the frequency of HLA B27 in patients with juvenile chronic arthritis (JCA) of varying severity and outcome by studying three patient categories: those in whom cytostatic treatment with azathioprine had been started, those with secondary amyloidosis, and those with arthroplasty of the knee or hip joints. In the first category the frequency of the HLA B27 allele was compared between those who had attained remission and those who had not. In the second and third categories the rate at which amyloidosis developed and the timing for the need of arthroplasty, were compared for HLA B27-positive and-negative patients. A control group consisted of 37 patients with uncomplicated seronegative polyarthritis. Ten of the 37 patients in the control group (27%) were HLA B27 positive as opposed to 84 out of 190 (44%) in the three study groups. Of the 101 patients treated with azathioprine, two out of 15 in remission were HLA B27 positive, whereas as many as 41 out of 86 with still active disease were HLA B27 positive (p=0.013). Of the secondary amyloidosis patients, 29 out of 51 carried HLA B27. The HLA B27-positive patients contracted amyloidosis on average 5.9 (median 6.7) years earlier than the HLA B27-negative patients (p=0.038). Of the arthroplasty patients, 39 out of 91 carried HLA B27. The HLA B27-positive patients underwent arthroplasty on average 2.9 (median 3.5) years earlier than the HLA B27-negative patients (p=0.050). We conclude that HLA B27-positive cases are accumulated among the most severe cases of 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.     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Analysis of childhood reactive arthritis and comparison with juvenile idiopathic arthritis

There is currently no agreement on how to classify and diagnose reactive arthritis (ReA) and what kind of clinical and laboratory findings are specific for the diagnosis. This study retrospectively analyzed the initial clinical manifestations and laboratory findings in children diagnosed with ReA and juvenile idiopathic arthritis (JIA). A comparison was also made between these two groups to see if there were differences. A retrospective chart review was performed and 44 patients diagnosed with ReA and 80 patients with JIA were enrolled in this study. Their initial clinical manifestations and laboratory findings were also analyzed and compared. The initial clinical manifestations in ReA were analyzed including the demographic data, the preceding infection history, the duration of the infectious episode to the onset of arthritis, the duration of arthritic symptoms, and the involved joint pattern. Comparison of the initial laboratory findings between patients with ReA and JIA showed significant differences between erythrocyte sedimentation rates (ESR) in the first hour, platelet counts (p<0.05), and ESR in the second hour (p=0.052). Further, comparing ReA with the subtypes of JIA, significant differences were noted between ReA and the systemic type in terms of hemoglobin level, platelet counts, C-reactive protein, and first and second hour ESR (p<0.05). However, if compared with the polyarticular or pauciarticular type, only the platelet counts showed any significant statistical difference (p<0.05). This study summarizes clinical experiences in ReA. The differences in laboratory findings of ReA and JIA may provide a clue in making a differential diagnosis.     

Association of bone mineral density and vertebral deformity in patients with rheumatoid arthritis

The aim of this study was to investigate the association of vertebral deformities developed as a result of osteoporosis in female patients with rheumatoid arthritis (RA) with bone mineral density (BMD) and disease activity parameters. In the study, 100 female patients with the diagnosis of RA and 56 healthy subjects were recruited. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and rheumatoid factor (RF) tests were performed and the number of swollen and tender joints, level of pain and health assessment questionnaire (HAQ) were recorded in order to evaluate disease activity. Anteroposterior and lateral thoracic and lumbosacral roentgenograms of all patients were taken for radiological examination and deformities of vertebrae were assessed. BMD measurements of patients were performed on vertebrae L1–4 of lumbar region and on total hip, femur neck, trochanter and Ward’s triangle of the right side. Vertebral deformity was established in 30% of RA patient group and 7.1% of control group and this was statistically significant. In the statistical analysis, no statistically significant difference was found between BMD measurements of RA and control groups. Patients with RA were divided into two subgroups with regard to using corticosteroids (CS) or not. Vertebral deformity was 32.4% in the subgroup using CS and 24.1% in the subgroup not using CS, and the difference was not statistically significant. There was a correlation between number of deformed joint and age and vertebral deformity incidence. RA is a risk factor on its own for the development of osteoporosis and vertebral deformity and this risk increases by age, excess number of deformed joints and severe course of disease. We think that precautions should be taken immediately to suppress the disease activity as well as to protect the quality and density of bone and to prevent the development of vertebral deformity and fracture while planning the treatment of patients with RA.     

Pulmonary function in children with juvenile idiopathic arthritis and effects of methotrexate therapy

Summary Objective To evaluate impairment of lung function as an adverse effect associated with methotrexate therapy in patients with juvenile idiopathic arthritis (JIA). Methods We performed pulmonary function testing including diffusion capacity for carbon monoxide as measured by the single breath method (DLCO-SB) in 89 children with juvenile idiopathic arthritis. Forty (45%) were treated with methotrexate for a median of 24 months (range 3 to 120 months). Except for the presence of asthma in two children, there was no clinical or radiological evidence of pulmonary disease. Results Pulmonary function testing demonstrated moderate airway obstruction in two children with known bronchial asthma. Neither obstructive nor restrictive alteration of ventilation was found in any other patient. Two juvenile idiopathic arthritis patients showed a reduced CO diffusion capacity of 64 and 67%. One of them was treated with methotrexate. Conclusions With regard to lung function impairment treatment with low dose methotrexate appears to be safe even when performed for several years reaching a total amount of up to 3.5 g. In contrast to studies performed in adult rheumatoid arthritis patients, in children with juvenile idiopathic arthritis impairment of lung function is a rare event. Received: 23 February 2001 Accepted: 16 May 2001     

Effect of estrogen replacement therapy on arthritis and bone mineral density in estrogen-replete rats with collagen-induced arthritis

The influence of estrogen therapy on changes in arthritis and bone mineral density (BMD) was evaluated using an estrogen-replete collagen-induced arthritis (CIA) rat model. Seven-month-old female Sprague–Dawley rats (n = 30) were divided into the three groups; control (CONT), collagen sensitization (CIA), and CIA + 17β-estradiol administration for 7 weeks (CIA + E). BMD was measured by peripheral quantitative computed tomography in the proximal tibia every 2 weeks. Eight weeks after the initial sensitization the rats were killed and histomorphometry of tibia was performed. The hind paw thickness increased with time in CIA rats and there was a significant difference between CONT and CIA at 8 weeks after the initial sensitization. Estrogen tended to make the development of arthritis milder. In CIA, BMD at metaphyseal cancellous bone began to decrease with the onset of arthritis and became significantly lower than in CONT after 8 weeks. Compared with the CIA, the deterioration in BMD was inhibited in CIA + E. Histomorphometrical parameters of bone resorption were increased in CIA compared with CONT, and those elevations were reduced by estrogen treatment, but estrogen had no effect on bone formation parameters. In conclusion, estrogen could partially suppress arthritis and bone loss in estrogen-replete rats as well as estrogen-deplete ones.     

Bone mineral density and bone turnover in patients with psoriatic arthritis

Psoriasis is a common inflammatory skin disease, and conflicting data have been published about osteoporosis and bone turnover markers in patients with psoriatic arthritis. The aim of this study was to assess bone mineral density (BMD) and bone turnover markers in psoriatic patients with and without peripheral arthritis and to investigate the relationship between clinical parameters and markers of bone turnover. Forty-seven patients (24 women, 23 men) with psoriasis were included to the study. Demographic data and clinical characteristics were recorded. Erythrocyte sedimentation rate and C-reactive protein were assessed as disease activity parameters. BMD was determined for lumbar spine and total hip by dual X-ray absorptiometry (DXA). Serum Ca, P, alkalen phosphatase (ALP), and serum type I collagen cross-linked C telopeptide (CTX) were measured as bone turnover markers in all patients. The patients were divided into two groups according to their peripheral arthritis status. The clinical and laboratory variables, as well as bone mass status of the groups, were compared with each other. Eighteen patients had peripheral arthritis. All the female patients were premenopausal. None of the patients had radiologically assessed axial involvement. There was no significant difference between the BMD levels of psoriatic patients with and without arthropathy. One patient (5%) had osteoporosis, and nine (50%) patients had osteopenia in arthritic group, while eight (27.5%) patients had osteopenia in patients without arthritis. Serum CTX, ALP, Ca, and P levels were not significantly different in arthritic than in non-arthritic patients (p > 0.05). In patients with psoriatic arthritis, the duration of arthritis was negatively correlated with BMD values of lumbar spine and total femur and serum CTX levels, suggesting an association of increased demineralization with the duration of joint disease. In conclusion, psoriatic patients with peripheral arthritis with longer duration of joint disease may be at a risk for osteoporosis, which can require preventative treatment efforts.     

Chitotriosidase activity in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is an inflammatory joint disease of unknown etiology. The pathogenesis is driven by T and B cells. The role of macrophages remains unclear. Chitotriosidase belongs to the chitinase protein family and is secreted by activated macrophages. The chitinases are able to catalyze the hydrolysis of chitin or chitin-like substrates such as 4-methylumbelliferyl chitotrioside. Chitotriosidase activity was determined using the substrate 4-methylumbelliferyl beta-DNN'N'-triacetylchitotrioside (4-MU-TCT, SIGMA Chemical Co.). The substrate and serum were incubated with the serum in a citrate/phosphate buffer. The reaction was stopped by adding a buffer (Na(2)CO(3)). The fluorescence of 4-methylumbelliferone was evaluated by fluorimeter at excitation 360 nm and emission 450 nm. We report about chitotriosidase measurements in patients with JIA. The chitotriosidase level in synovial fluid was up to approximately 1,000 nmol/(h ml) at disease onset before therapy. The level in the sera was below 600 nmol/(h ml). Serum chitotriosidase levels could represent the activity of macrophages in the synovial fluid in JIA.     

Safety and efficacy of once-weekly application of Etanercept in children with juvenile idiopathic arthritis

Etanercept—a recombinant TNF receptor fusion protein—has been approved for the treatment of resistant polyarticular juvenile idiopathic arthritis. In children with JIA, 0.4 mg/kg is given subcutaneously twice weekly. In adult patients efficacy and safety of etanercept, 25 mg twice weekly was comparable to 50 mg once weekly. In the German paediatric Etanercept registry six patients with JIA were identified, who received Etanercept once weekly primarily and six patients who received Etanercept initially twice weekly and later once weekly with increased dose per injection. In both groups, treatment was efficacious and well tolerated. In patients switching from twice to once weekly administration, there was no loss of efficacy and no increase in toxicity. At last observation 10/12 patients achieved an ACR-JRA 30 and 8/12 achieved an ACR-JRA70 response. These data indicate that once weekly application of etanercept is safe and efficacous in children.     

Bone mineral density in patients with early rheumatoid arthritis treated with corticosteroids

The aim of this study was to evaluate the bone mineral density (BMD) in patients with early rheumatoid arthritis (RA) prior to and 6 months after adding low-dose corticosteroid (CS) treatment. Adult patients (>21 years old) with early RA (symptom duration <1 year) and severe joint pain under maximal dose of nonsteroidal anti-inflammatory drugs (NSAIDS) were started on low-dose prednisone (10 mg/day). Patients were evaluated after 1, 3, and 6 months. Disease activity measures including swollen and tender joint count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were documented, and the dose of prednisone was adjusted according to the level of pain at each visit. BMD of the femoral neck (FN) and lumbar spine (LS) was measured using dual energy X-ray absorptiometry prior to and 6 months after starting CS treatment. Calcium supplements, vitamin D, bisphosphonates, or hormonal therapy that may affect BMD were not permitted during the study. Twenty patients were eligible and 16 completed the study; 75% were female. The mean age was 47.2±12 years and mean duration of symptoms was 7±2 months. The mean BMD at the FN prior to and 6 months after starting CS treatment were 0.8080 g/cm²±0.1145 and 0.8242 g/cm²±0.1122, respectively (p=0.04). The mean BMD at the LS prior to and 6 months after starting CS treatment were 0.9429 g/cm²±0.1406 and 0.9490 g/cm²±0.1277, respectively (p=0.423). There was a significant correlation between the mean change of BMD at the FN and mean change of tender joint count (p=0.01), ESR (p=0.008), and CRP (p=0.006) but not with swollen joint count (p=0.099). However, there was no correlation between the change of BMD at the FN or LS and the change of any of the disease activity measures of every patient. Also, no correlation was seen between the cumulative dose of CS and the change in BMD. BMD increases significantly at the FN in early RA patients 6 months after adding low-dose CS to the treatment.     

Bone mineral density and turnover in non-corticosteroid treated African American children with juvenile rheumatoid arthritis

OBJECTIVE: To determine bone mineral content (BMC), bone mineral density (BMD), Z scores, and markers of bone turnover in African American children with juvenile rheumatoid arthritis (JRA). METHODS: Eight children with JRA with no prior exposure to corticosteroids were evaluated. Lumbar spine (L1-L4) and total body and total hip BMC and BMD were determined using dual x-ray absorptiometry (DXA), and Z scores (BMD) were calculated. Serum samples of markers of bone turnover including pyridinoline (PYR), N-terminal propeptide of type I procollagen (P1NP), osteocalcin (OC), and bone-specific alkaline phosphatase (BSAP) were measured. RESULTS: The mean Z score (BMD) at the lumbar spine (L1-L4) in patients with JRA was -1.2+/-0.8. Z scores for total body and total hip were within 1 standard deviation of normal compared with healthy historical controls matched for age, sex, and race. CONCLUSION: BMD was normal for chronological age (defined as Z score >or= 2.0) in African American children with JRA who had not previously been treated with corticosteroids. Further studies are needed on the effects of JRA on skeletal health in African American children.     

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.     

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.