Active Juvenile Rheumatoid Arthritis Research Articles

PMS25 Evaluation of Direct Costs for the Treatment of Active Juvenile Rheumatoid Arthritis Using Biologics

Evaluate direct costs for the treatment of patient with active juvenile rheumatoid arthritis (JRA) in the inefficiency of conventional therapy. Direct costs applied to patient, health care and society in process of medical care provision were evaluated. In the study direct costs included cost of biologics for the treatment of active JRA, therapy cost of the most common side effects caused by biologics use, cost of inpatient care and cost of out-patient diagnostic and treatment of JRA patients. Therapy cost with Etanercept and Abatacept was evaluated on the first stage including spending on one patient treatment with active JRA with body weight 15 till 65 kg. during one year after three months of inefficient conventional therapy. Biologics doses and dosing regimen were defined on the basis of application sheet. Calculated annual therapy cost for Etanercept varied from 11,752 EUR to 23,503 EUR depending on body weight and for Abatacept from 8,879 EUR to 26,638 EUR respectively. During cost analysis authors considered only very often (>1/10) and often (>1/100, < 1/10) occurred side effects. Thus, cost of side effects treatment caused by Etanercept use resulted in 44 EUR and for Abatacept – 69 EUR. Next stage of cost analysis was evaluation of therapy cost for patients with JRA according standard of inpatient treatment è standard of out-patient treatment. Cost of 30 days of inpatient care and 14 months of out-patient care was considered during cost analysis for the treatment of patients with JRA. Cost of inpatient and out-patient care for patient with JRA excluding biologics cost amounted to 33585 EUR. Finally total direct costs for the treatment of patient with JRA during one year with body weight from 15 till 65 kilogram varied from 45,380 EUR to 57,132 EUR for Etanercept and from 42,534 EUR to 60,292 EUR for Abatacept respectively.

Asymptomatic celiac sprue in juvenile rheumatic diseases children

Celiac disease (CD) is the most frequent enteropathy in adults and its coexistence with other autoimmune diseases is frequent. To detect asymptomatic CD in children with rheumatic diseases by measuring tissue transglutaminase (tTG) antibodies and finding any relation to disease activity. Setting and study design: The study included 60 children with juvenile rheumatic diseases consecutively from those attending the Rheumatology Clinics of Cairo University Hospitals: 30 juvenile rheumatoid arthritis (JRA), 10 juvenile systemic lupus erythematosus (SLE), 12 juvenile seronegative spondyloarthropathy and eight juvenile systemic sclerosis/polymyositis (SSc/PM) overlap syndrome were recruited during 2010. There were 22 male and 38 female patients. Thirty matched healthy controls were included. All children were subjected to thorough history taking, clinical examination and laboratory investigations. The body mass index (BMI) for age was used. All subjects had no gastrointestinal tract symptoms suggestive of CD and the tTG antibodies (IgA and IgG) were assessed. The mean age of patients was 12.03 ± 3.3 years and disease duration 4.18 ± 3.24 years. The demographic, clinical and laboratory features of the children were studied and compared. The tTG was positive in 32 (53.3%) patients compared to 20% of the controls (P = 0.03), being higher in females. In tTG-positive patients, the BMI was significantly lower, while white blood cell count, erythrocyte sedimentation rate and disease activity were significantly higher. tTG antibodies may be used as a screening test to identify asymptomatic CD associated with juvenile rheumatic diseases, especially those with active JRA or marked reduction in BMI.

Adalimumab with or without Methotrexate in Juvenile Rheumatoid Arthritis

Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis. Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously received treatment with nonsteroidal antiinflammatory drugs underwent stratification according to methotrexate use and received 24 mg of adalimumab per square meter of body-surface area (maximum dose, 40 mg) subcutaneously every other week for 16 weeks. We randomly assigned patients with an American College of Rheumatology Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a double-blind fashion every other week for up to 32 weeks. Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares (the primary outcome) occurred in 43% of those receiving adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo (P=0.02). At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Response rates were sustained after 104 weeks of treatment. Serious adverse events possibly related to adalimumab occurred in 14 patients. Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.)

Polysomnography and Self-reported Sleep, Pain, Fatigue, and Anxiety in Children with Active and Inactive Juvenile Rheumatoid Arthritis

To compare polysomnography (PSG) and self-reported sleep, symptoms (pain and fatigue), and anxiety between children with active and inactive juvenile rheumatoid arthritis (JRA) and examine relations among sleep, symptoms, and anxiety. Two consecutive nights of PSG, self-reported sleep, and symptoms were obtained in 70 children 6-11 years of age with active (n = 35) or inactive (n = 35) JRA. On the second (study) night, PSG and self-reported sleep variables were not different, but pain and fatigue were significantly higher (both p <.02) in children with active compared to inactive disease. In a stepwise regression, age, medications, disease status, anxiety, evening pain, total sleep time, and arousals explained 36% of the variance in fatigue and age, disease status, and evening pain were significant (all p <.04) predictors of fatigue. All children showed longer sleep latency and reduced sleep efficiency on the first night in the laboratory. Sleep was not altered in children with active JRA, however, the "first night effect" suggests that valid laboratory sleep assessments require an adaptation night.

Long‐term safety and efficacy of etanercept in children with polyarticular‐course juvenile rheumatoid arthritis

Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.

Evidence for chronic, peripheral activation of neutrophils in polyarticular juvenile rheumatoid arthritis

Although strong epidemiologic evidence suggests an important role for adaptive immunity in the pathogenesis of polyarticular juvenile rheumatoid arthritis (JRA), there remain many aspects of the disease that suggest equally important contributions of the innate immune system. We used gene expression arrays and computer modeling to examine the function in neutrophils of 25 children with polyarticular JRA. Computer analysis identified 712 genes that were differentially expressed between patients and healthy controls. Computer-assisted analysis of the differentially expressed genes demonstrated functional connections linked to both interleukin (IL)-8- and interferon-γ (IFN-γ)-regulated processes. Of special note is that the gene expression fingerprint of children with active JRA remained essentially unchanged even after they had responded to therapy. This result differed markedly from our previously reported work, in which gene expression profiles in buffy coats of children with polyarticular JRA reverted to normal after disease control was achieved pharmacologically. These findings suggest that JRA neutrophils remain in an activated state even during disease quiescence. Computer modeling of array data further demonstrated disruption of gene regulatory networks in clusters of genes modulated by IFN-γ and IL-8. These cytokines have previously been shown to independently regulate the frequency (IFN-γ) and amplitude (IL-8) of the oscillations of key metabolites in neutrophils, including nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and superoxide ion. Using real-time, high-speed, single-cell photoimaging, we observed that 6/6 JRA patients displayed a characteristic defect in 12% to 23% of the neutrophils tested. Reagents known to induce only frequency fluctuations of NAD(P)H and superoxide ion induced both frequency and amplitude fluctuations in JRA neutrophils. This is a novel finding that was observed in children with both active (n = 4) and inactive (n = 2) JRA. A subpopulation of polyarticular JRA neutrophils are in a chronic, activated state, a state that persists when the disease is well controlled pharmacologically. Furthermore, polyarticular JRA neutrophils exhibit an intrinsic defect in the regulation of metabolic oscillations and superoxide ion production. Our data are consistent with the hypothesis that neutrophils play an essential role in the pathogenesis of polyarticular JRA.

Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations.

Phagocytes are extensively involved in the synovial inflammation associated with chronic arthritis. The aim of our study was to determine neutrophil activation in juvenile rheumatoid arthritis (JRA) by analyzing S100A12 (EN-RAGE; calgranulin C), a proinflammatory protein secreted by human neutrophils. S100A12 serum concentrations were determined in 124 patients with chronic active polyarticular-, oligoarticular-, or systemic-onset JRA. S100A12 was also analyzed in synovial fluid obtained from 22 patients. Changes in S100A12 levels in response to anti-tumor necrosis factor alpha (anti-TNF alpha) therapy, intraarticular injections of corticosteroids, and methotrexate (MTX) treatment were analyzed. Forty-five patients were followed up after successful antiinflammatory treatment, for a mean period of 2.8 years. The mean serum level of S100A12 was 395 ng/ml in patients with active polyarticular JRA and 325 ng/ml in patients with active oligoarticular JRA (normal <120 ng/ml). The level of S100A12 was approximately 10-fold higher in synovial fluid than in serum, indicating release at sites of local inflammation. In patients with systemic-onset JRA, the mean level of S100A12 was 3,700 ng/ml. Moreover, serum levels decreased in response to different antiinflammatory therapies (i.e., intraarticular injections of corticosteroids, MTX, or etanercept). S100A12 levels were elevated in 20 patients who experienced disease flares after the initial induction of remission, even weeks before the relapses became clinically apparent. S100A12 serum concentrations indicate neutrophil activation in JRA and correlate with disease activity. S100A12 may indicate synovial inflammation even when other signs of arthritis are absent. Its function as a proinflammatory factor secreted by activated neutrophils makes this protein a potential target for future therapies.

Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis.

To analyze which cellular compartments are involved in the initial phase of systemic-onset juvenile rheumatoid arthritis (JRA), and to investigate the role that myeloid-related protein 8 (MRP-8) and MRP-14, two S-100 proteins that are primarily expressed in phagocytes, play in the disease. Skin biopsy samples obtained during patients' acute episodes of systemic-onset JRA were analyzed by immunohistochemistry and in situ hybridization. Concentrations of MRP-8/MRP-14 in serum were determined by enzyme-linked immunosorbent assay. By analyzing biopsy samples from cutaneous rashes during the initial phase of systemic-onset JRA, we discovered infiltration of leukocytes expressing MRP-8 and MRP-14. Surprisingly, keratinocytes also showed de novo synthesis of these proinflammatory proteins, indicating activation of epithelial cells during systemic-onset JRA. Serum concentrations of MRP-8/MRP-14 were 120-fold higher compared with healthy controls and approximately 12-fold higher compared with patients with other inflammatory diseases. Concentrations of MRP-8/MRP-14 in patients with systemic-onset JRA fell dramatically after remission was induced. The exceptionally high serum levels of MRP-8 and MRP-14 in active systemic-onset JRA make them prime candidates as markers for monitoring disease activity and response to treatment. Since MRP-8/MRP-14 exhibit direct effects on leukocyte adhesion to the vascular endothelium, their extensive expression in the epidermis indicates an active role for these S-100 proteins in the initial phase of this systemic autoimmune disease.

Tumor suppressor protein p53 and anti-p53 autoantibodies in pediatric rheumatological diseases.

The tumor suppressor protein p53 plays an important role in cell cycle regulation. One of the major features in rheumatic diseases is the abnormal proliferation of lymphocytes. p53 expression in peripheral blood mononuclear cells (by flowcytometry) and serum anti-p53 antibodies (by ELISA) were therefore measured in 18 children and adolescents with juvenile rheumatoid arthritis (JRA) and 17 with systemic lupus erythematosus (SLE) in comparison to 20 healthy controls, to determine their role. p53 expression in patients was insignificantly higher than that of controls (2.28 +/- 2.71% vs. 1.08 +/- 1.02%, respectively, p > 0.05) with 29.4% of the patients showing values above a cut-off level of 2.55% (95th percentile of controls). SLE patients with active disease had significantly higher p53 expression compared to controls and to patients with quiescent disease although no significant correlation with ESR or complement 3 was detected. Seropositivity to anti-p53 antibodies was observed in none of controls but in 22.8% of patients, all of whom, except one, had active disease. Seropositivity to anti-p53 antibodies was more prominent in lupus nephritis than in other presentations of SLE (p < 0.05). The mean p53 expression in seropositive patients was insignificantly higher than in seronegatives. p53 expression and seropositivity to anti-p53 were slightly higher in SLE than in JRA and were not significantly affected by the mode of therapy. Thus, the overexpression of p53 in some patients with active SLE and JRA might explain the abnormal proliferation of autoreactive lymphocytes that perpetuates the inflammatory response. The presence of anti-p53 antibodies might cause malfunctioning of p53 protein interfering with its regulatory functions.

Synovial fluid levels of E-selectin and intercellular adhesion molecule-1: relationship to joint inflammation in children with chronic arthritis

E-selectin and intercellular adhesion molecule (ICAM)-1 are crucial to the inflammatory response in chronic inflammatory arthritis. Soluble (s) levels of these molecules in sera and synovial fluid (SF) correlate with some clinical parameters and synovial tissue expression of the same molecules in rheumatoid arthritis. Studies of sera from children with chronic inflammatory arthritis corroborate this information; corresponding SF data are relatively lacking. We thus studied SF sE-selectin and sICAM-1 in 28 children with active juvenile rheumatoid arthritis or a spondyloarthropathy. Levels were correlated with erythrocyte sedimentation rate (ESR), SF leukocyte counts, duration of disease, and duration of response to concomitant intra-articular corticosteroid injection. Levels were compared according to use of methotrexate and/or sulfasalazine. Synovial fluid sE-selectin correlated with ESR and SF leukocyte counts. There was a trend toward lower sICAM-1 in patients treated with sulfasalazine and/or methotrexate. We conclude that SF levels of sE-selectin accurately reflect intra-synovial inflammation. Soluble ICAM-1 levels may reflect the effects of disease-modifying agents.

Juvenile rheumatoid arthritis.

The heterogeneous nature of juvenile rheumatoid arthritis is further defined in publications from the past year. Decreased IL-10 production, an anti-inflammatory cytokine, and soluble IL-6 receptor are associated with systemic juvenile rheumatoid arthritis (JRA). IL-4 may have an anti-inflammatory role in the pathogenesis of pauciarticular JRA and may protect, along with IL-10, against the development of joint erosions. Active JRA is associated with lower levels of platelet activating factor acetylhydrolase, which may contribute to the loss of anti-inflammatory activity and increased risk of atherogenesis. The phase 3 clinical trial of etanercept confirmed its efficacy and safety in JRA. Intra-articular steroids are safe and effective in the treatment of JRA. Methotrexate does have disease-modifying effects. The risk of hepatotoxicity with methotrexate use increases with serial transaminase abnormalities and with obesity. Osteoclasts are responsible for joint erosions. Cyclosporine A, mycophenolate mofetil, and methotrexate are effective in the treatment of refractory uveitis. During the past year a number of scientific publications have contributed significantly to our understanding and treatment of juvenile rheumatoid arthritis.

Neuroendocrine immune features of pediatric inflammatory rheumatic diseases.

Juvenile rheumatoid arthritis (JRA) and juvenile systemic lupus erythematosus (JSLE) are the most common autoimmune rheumatic diseases in children associated with high levels of autoantibodies and immune reactivity. JRA and JSLE are more common in girls. Disease activity is worse in the morning, improves during the daytime and worsens at night suggesting that neuroendocrine immune mechanisms are involved in disease pathophysiology. Adult patients with RA and SLE have excessive levels of prolactin (PL) while cortisol (CS) production is down-regulated for the degree of ongoing inflammation. PL has potent proinflammatory properties. Normal to low levels of cortisol have been observed in children with active JRA despite the high serum levels of IL-6, IL-1 beta, and TNF-alpha, which activate the hypothalamic-pituitary-adrenal axis (HPA). The CS levels are in fact subnormal because inflammatory stress activates the HPA. Normal serum PL levels were seen in children with JRA, most of whom were not active with higher levels in those with active ANA +ve JRA complicated by uveitis. A trend toward high PL levels was seen in 33 children with JSLE. High serum PL levels are seen in patients with active juvenile ankylosing spondylitis (JAS) only. Growth retardation is a feature of JRA. Patients with JRA have low to normal levels of growth hormone (GH) and low levels of insulin-like growth factor 1 (IGF-1). IGF-1 mediates the effects of GH. The observation of low IGF-1 in JRA raises the therapeutic possibility with IGF-1. Overall, high levels of follicle stimulating hormone and luteinizing hormone are found in children with JSLE while the levels in JRA tend to be normal. Testosterone levels are low in patients with JRA. No significant differences in estrogen levels have been found between patients with JRA and those with JSLE and matched controls. There is evidence that the autonomic nervous function is defective in patients with JRA.

The inflammatory state in active juvenile rheumatoid arthritis is associated with hypo HDL-emia and reduced lipoprotein-associated PAF-acetylhydrolase activity

The inflammatory state in active juvenile rheumatoid arthritis is associated with hypo HDL-emia and reduced lipoprotein-associated PAF-acetylhydrolase activity

Association of the inflammatory state in active juvenile rheumatoid arthritis with hypo-high-density lipoproteinemia and reduced lipoprotein-associated platelet-activating factor acetylhydrolase activity.

To investigate the relationship between the quantitative and qualitative abnormalities of apolipoprotein B (Apo B)- and Apo A-I-containing lipoproteins and between lipoprotein-associated platelet-activating factor acetylhydrolase (PAF-AH) activity in patients with juvenile rheumatoid arthritis (JRA) as a function of the inflammatory state. Twenty-six JRA patients and 22 age- and sex-matched control subjects with normal lipid levels participated in the study. Fourteen patients had active disease, and 12 had inactive disease. Plasma lipoproteins were fractionated by gradient ultracentrifugation into 9 subfractions, and their chemical composition and mass were determined. The PAF-AH activity associated with lipoprotein subfractions and the activity in plasma were also measured. Patients with active JRA had significantly lower plasma total cholesterol and high-density lipoprotein (HDL) cholesterol levels as compared with controls, due to the decrease in the mass of both the HDL2 and HDL3 subfractions. Patients with active JRA also had higher plasma triglyceride levels, mainly due to the higher triglyceride content of the very low-density lipoprotein plus the intermediate-density lipoprotein subfraction. The plasma PAF-AH activity in patients with active JRA was lower than that in controls, mainly due to the decrease in PAF-AH activity associated with the intermediate and dense low-density lipoprotein subclasses. The lipid abnormalities and the reduction in plasma PAF-AH activity were significantly correlated with plasma C-reactive protein levels and were not observed in patients with inactive JRA. This is the first study to show that patients with active JRA exhibit low levels of HDL2 and HDL3 and are deficient in plasma PAF-AH activity. These alterations suggest that active JRA is associated with partial loss of the antiinflammatory activity of plasma Apo B- and Apo A-I-containing lipoproteins.

Juvenile rheumatoid arthritis. Effects of disease activity and recombinant human growth hormone on insulin-like growth factor 1, insulin-like growth factor binding proteins 1 and 3, and osteocalcin.

To investigate possible mechanisms of growth impairment in children with juvenile rheumatoid arthritis (JRA). Eighteen prepubertal children with JRA and growth retardation received recombinant human growth hormone (rHuGH) for 1 year. Growth hormone profiles over 24 hours were obtained before treatment in 12 patients; the levels did not differ from those in "short normal" children. Levels of insulin-like growth factor 1 (IGF-1), IGF binding proteins (IGFBPs) 1 and 3, insulin, osteocalcin, and C-reactive protein (CRP), as well as the erythrocyte sedimentation rate were measured serially. Pretreatment levels were compared with control levels. In JRA patients, IGF-1, IGFBP-3, and osteocalcin levels were significantly lower and insulin levels significantly higher than those in controls, but there was no significant difference in the level of IGFBP-1. With rHuGH treatment, height velocity and mean levels of IGF-1, osteocalcin, and insulin increased significantly, while mean levels of IGFBP-1 fell significantly. Levels of IGFBP-3 correlated with those of IGF-1. The height velocity correlated positively with IGF-1 and osteocalcin, and negatively with IGFBP-1. Levels of IGFBP-1 were inversely related to those of insulin and IGF-1. There was a significant negative correlation between the CRP and height velocity, IGF-1 level, and osteocalcin level. IGF-1 production is impaired in children with active JRA. Treatment with a therapeutic dose of rHuGH can rectify the IGF-1 deficiency within 4 days, but its effect is adversely influenced by the acute-phase response, as reflected by an elevated CRP level.

The Autonomic Nervous System and the Immune System in Juvenile Rheumatoid Arthritis

This study demonstrates that juvenile rheumatoid arthritis is associated with a dysregulation of the autonomic nervous system as well as with disturbances in the capacity of the immune system to respond to mediators of the autonomic nervous system. In patients with active disease heart rate at rest is higher than in healthy controls. In addition, 3-hydroxy-4-phenoxyphenylglycol levels in urine are higher in all patients than in the control group. Cardiovascular responses to an orthostatic stress test (tilt up) are reduced in patients with active and nonactive disease. Plasma norepinephrine responses to tilt up are reduced in subjects with active juvenile rheumatoid arthritis. In summary, our data show that patients with juvenile rheumatoid arthritis have an altered function of the autonomic nervous system associated with increased central noradrenergic outflow, presumably leading to increased vasoconstriction, resulting in a decreased response to an orthostatic stressor. The altered function of the autonomic nervous system is associated with changes in the response of leukocytes to mediators of the autonomic nervous system via β2-adrenergic receptors. Leukocytes of patients with active juvenile rheumatoid arthritis have a lower cAMP response to a β2-adrenergic agonist, presumably due to increased cAMP–phosphodiesterase activity in these cells.

Bone mineralization and bone mineral metabolism in children with juvenile rheumatoid arthritis.

To identify mechanisms of the osteopenia associated with juvenile rheumatoid arthritis (JRA) by determining parameters of bone mineralization, and bone mineral content and density (BMC and BMD), in children with JRA. BMC and BMD were measured by dual x-ray absorptiometry in 41 children with JRA and 62 healthy children. Serum samples were analyzed for concentrations of minerals, vitamin D, parathyroid hormone, osteocalcin, bone-specific alkaline phosphatase (BAP), procollagen I carboxy-terminal propeptide, and tartrate-resistant acid phosphatase (TRAP), and urinary excretion of deoxypyridinoline crosslinks and calcium. BMD was decreased in all sites in JRA patients. BMD, corrected for age, height, weight, and bone area, was decreased at cortical bone sites (1/3 radius, upper and lower extremities, and whole body). Low concentrations of osteocalcin and BAP suggested reduced bone formation, and low TRAP levels suggested decreased resorption. Clinical scales of disease severity were negatively correlated with measures of bone mass. Laboratory markers of disease severity were highly correlated with decreases in markers of bone formation, but not with those of resorption. Although laboratory findings were similar for children with oligoarticular and polyarticular disease, differences in bone mass were greater in children with polyarticular disease. These data suggest an association between decreased bone mineralization in JRA and low bone formation that is related to disease severity. Efforts to stimulate bone formation, therefore, need to be considered clinically in prepubertal children with active JRA.

Reduced bone mineral content and normal serum osteocalcin in non-steroid-treated patients with juvenile rheumatoid arthritis.

To distinguish the effects of juvenile rheumatoid arthritis (JRA) on bone mineralisation from those possibly caused by steroid therapy. Bone mineral status was evaluated in 20 children (five boys and 15 girls) with active JRA who never received steroids. Seven had oligoarticular, nine had polyarticular, and four had systemic JRA. Bone mineral content (BMC) was assessed by single beam photon absorptiometry and expressed as a Z score relative to normal values in healthy children. Serum calcium, phosphate, and alkaline phosphatase were measured by colorimetric methods. Whole parathyroid hormone was assayed by Immuno Radiometric Assay. Serum osteocalcin was measured by specific radioimmunoassay. Nutrient intake was assessed by a 24 hours dietary recall. BMC and nutrient intake were also assessed in an age and sex matched control group. BMC was -1.5 (SEM 0.8) Z scores in patients and 0.4 (0.3) in the control group (p = 0.02). BMC averaged -4.9 (2) Z scores in the systemic JRA group, -1 (0.6) in the polyarticular group and 0.3 (0.7) in oligoarticular JRA patients. Serum calcium, phosphate and osteocalcin values were normal in all patients. No significant difference was found between JRA patients and controls in calcium, phosphate, energy, and protein intake. JRA subjects have significantly reduced BMC even in the absence of any steroid therapy. Bone demineralisation appears to depend more on disease activity and on reduced motility than on reduced nutrient intake.

A study of prognosis in 52 cases with juvenile rheumatoid arthritis

The prognosis in 52 patients with juvenile rheumatoid arthritis (JRA) was studied. There were 35 cases of systemic onset, 12 of polyarticular onset and 5 of pauciarticular onset. Thirteen systemic cases developed a polycyclic course with chronic polyarthritis. Many monocyclic JRA in systemic cases subsided within 1 year. There were no instances of polyarticular cases or pauciarticular cases that shifted to other type. However, there were many cases with a long active polyarticular JRA and with remission at an early stage in the pauciarticular type. The stage and class were I or II in 90% of cases with a good prognosis for the joints, but there were some serious cases. Transient carditis or iritis which developed at an early stage subsided later. The intractable systemic cases had drug-induced complications. The cases with steroid-induced complications tended to be chronic. One death in a systemic case was caused by hepatic failure.

25-Hydroxyvitamin D therapy in children with active juvenile rheumatoid arthritis: Short-term effects on serum osteocalcin levels and bone mineral density

1. Centers for Disease Control. Food and Drug Administration approval of use of a Haernophilus b conjugate vaccine for infants. MMWR 1990;39:925-6. 2. Centers for Disease Control, Food and Drug Administration approval of use of Haemophilus b conjugate vaccine in infants. MMWR 1990;39:698-9. 3. Boase J, Alexander R. Decline in Haemophilus influenzae type b meningitis--Seattle-King County, Washington, 1984-1989. MMWR 1990;39:924-5. 4. Madore DV, Johnson CL, Phipps DC, et al. Safety and immunologic response to Haemophilus influenzae type b oligosaccharide-CRM197 conjugate vaccine in 1to 6-month old infants, Pediatrics 1990;85:331-7, 5. Madore DV, Johnson CL, Phipps DC, et al. Safety and immunogenicity of Haemophilus influenzae type b oligosaccharideCRM197 conjugate vaccine in infants aged 15 to 23 months. Pediatrics 1990;86:527-34. 6. Anderson P. Intrinsic tritium labeling of the capsular polysaccharide antigen of Haemophilus influenzae type b. J Immunol 1978;120:866-70. 7. K~iyhty H, Peltola H, Karenko V, Miikel/i PH. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis 1983;147:1100. 8. Kgyhty H. Reimmunization with H. influenzae type b conjugate vaccine or capsular polysaccharide vaccine after primary immunization with conjugate vaccine; Presented at Third International Symposium on Epidemiology, Pathogenesis, and Prevention of Haemophilus influenzae Disease. Veldhoven, The Netherlands, Sept 1990.