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Dendritic cells were enriched from synovial fluids (SF) of patients with inflammatory arthritis and studied by immunogold labelling and electron microscopy for expression of histocompatability antigens of the HLA-D locus. Dendritic cells from SF were larger than most of these from peripheral blood with a more extensive Golgi region and more lysosomes and microfilaments. Class II histocompatability antigens HLA-DR, -DP, -DQ and that labelled by the antibody RFDI were abundant on the dendritic cells. The macrophages in the enriched cells showed labelling for DR but little labelling with the other antibodies. DR, DP and RFDI were often concentrated at areas of contact between dendritic and other cells (other dendritic cells, macrophages or lymphocytes). On incubating labelled cells at 37°C for 30 min many macrophages lost their DR label but dendritic cells always retained some surface label. Some gold labelling DR and DP was found in characteristic channels between the veils and became internalized in membrane-bound structures. A small proportion of the RFDI label internalized in areas resembling coated pits. Less DQ label internalized and appeared on vesicles inside vacuoles. Material bound to different class II molecules may thus be internalized or processed differently by dendritic cells. The presence in inflammatory lesions of large activated dendritic cells with high expression of class II antigens suggests that these cells could be presenting antigen to lymphocytes within the joints. [ABSTRACT FROM AUTHOR]

Mental health was evaluated early in the course of juvenile rheumatic disease; 106 parents of children (aged 1-17 yrs) were interviewed and 98 of the children were assessed when the child was hospitalized. Instruments included the Child Assessment Schedule (CAS), the Children's Global Assessment Scale (CGAS) and the Child Behavior Checklist (CBCL). Half the patients received a psychiatric diagnosis; psychosocial dysfunction of at least mild severity was found in 64% of the patients. In the polyarthritic group there was a negative correlation between CGAS and severity of disease. CBCL behaviour scores did not differentiate between patients and siblings when corrected for somatic components. [ABSTRACT FROM AUTHOR]

A 25-year-old woman with recurrent pronounced enlargement of the iliopsoas bursae is described; her hips were evaluated by ultrasonography and MRI. They appeared normal and communications to the iliopsoas bursae were demonstrated. During the preceding 8 years she had intermittent seronegative non-erosive arthritis of the knee and finger joints and her disease was classified as juvenile chronic arthritis. [ABSTRACT FROM AUTHOR]

Physiotherapy and occupational therapy are widely accepted as being of central importance for the treatment of juvenile chronic arthritis (JCA). However, these approaches have rarely been subject to critical scrutiny. The aims of this report are to highlight some of the inter-centre similarities and differences observed in the implementation of physical and occupational therapy for JCA, and to emphasize the need for scientifically controlled research in this area. During a series of visits to several paediatric rheumatology units in the UK, USA and Canada, three aspects of the service were noted: treatment philosophy, physical interventions used for the treatment of JCA and quality-of-life and independence training activities. There was general consensus with the philosophy that early physical intervention was a vital part of the treatment plan for JCA, although all therapists were concerned that compliance with treatment modalities was poor. Differences between units in the approach to acute arthritis, the use of foot orthoses and wrist splints, the treatment of joint contractures and the use of general quality-of-life training activities were noted. Although it was widely recognized that controlled research into the efficacy of physical intervention was needed, no centre had a co-ordinated plan for such investigations. [ABSTRACT FROM PUBLISHER]

The intestinal microflora was indirectly evaluated in juvenile chronic arthritis (JCA) by analysing enzyme activities-urease, β-glucosidase and β-glucuronidase—in faeces. In 18 out of 26 JCA patients, the illness had been diagnosed during the past year. The control group was composed of eight age-matched control patients and 18 family members of JCA patients (3–36 yr). The mean [95% confidence interval (CI)] urease activity, but not the activities of β-glucosidase and β-glucuronidase, in faeces from the JCA group differed from that in the control group: 32.3 (26.6–38.1) nmol/min/mg protein vs 24.0 (16.8–31.6), P = 0.07. The difference was more marked in a comparison of JCA patients with family members (P = 0.03). In a subgroup of subjects, the effect of 10 days oral bacteriotherapy with Lactobacillus GG on faecal enzyme activities was then investigated (n = 8 JCA patients, n = 8 control patients). This short-term oral bacteriotherapy reduced the increased urease activity in faeces of JCA patients. Keeping in mind the small number of subjects, it may be inferred from the present results that the increased urease activity in JCA is specific for the disease, suggesting altered intestinal microflora in JCA. [ABSTRACT FROM PUBLISHER]

Up to one-half of patients with anterior uveitis suffer from related systemic diseases. The common associations are the seronegative arthropathies and, in children, juvenile chronic arthritis. Anterior uveitis may also occur in the context of sarcoidosis or Behçet's disease. Syphilis and tuberculosis remain a significant problem for specific populations and may be the cause of anterior uveitis in these groups. By thorough clinical history and the correct selection and interpretation of simple investigations, it is generally possible for the ophthalmologist to make or exclude a systemic diagnosis, predict the ocular prognosis and direct selected patients to the appropriate physician. Diseases that threaten the patient's wellbeing must certainly be recognized. In the present review we present a method for identifying the systemic associations of anterior uveitis. [ABSTRACT FROM AUTHOR]

Over a 22-year period, eith patients affected with severe systemic or polyarticular juvenile chronic arthritis (JCA) developed systemic amyloidosis with nephrotic syndrome. They were treated with chlorambucil over 5-192 months (mean=44 months). With treatment, an abrupt decrease in the severity of JCA was observed in six patients but two patients were chlorambucil resistant. After a mean follow-up period of 10 years from onset of renal symptoms, one chlorambucil-resistant patient died of end-stage renal failure; two patients have a persistent nephrotic syndrome; and five patients are free from proteinaria, of whom one has developed hypertension. A good correlation was observed between the response of the rheumatic disease to chlorambucil treatment and the clinical course of renal symptoms. Fourteen renal biopsies were performed in these eight patients. In all, amyloid deposits were of the AA type, which persisted on repeat biopsies. In addition, 15%-60% of glomeruli had become globally sclerotic by the second or third biopsies. At the ultrastructural level, modifications in the structure of amyloid deposits and reparative changes of the glomeruli, characterized by partial restoration of glomerular architecture, were observed in three patients with a favourable clinical course. [ABSTRACT FROM AUTHOR]

Forty-six patients with juvenile chronic arthritis maintained on glucocorticoid therapy have been reviewed retrospectively for evidence of vertebral collapse. The 23 patients who had sustained vertebral fractures had received a daily dose 2.3 times higher than those without. No patients sustained a vertebral collapse until they had received a prednisolone cumulative dose of at least 5 g. It would appear that the ideal dose, if collapse of vertebrae is to be avoided, should be not more than 5 mgs daily, probably best given as 10 mg on alternate days; unfortunately, some children with serious systemic disease cannot be controlled on these low doses. In such cases it seems justified to investigate the possible use of the oxazoline derivative of prednisolone (deflazacort) in view of its reported bone-sparing properties in adults. [ABSTRACT FROM AUTHOR]

The effect of dietary therapy with a human Lactobacillus strain GG (ATCC 53103), bovine colostrum, or bovine immune colostrum with specific antibodies against anaerobic intestinal bacteria on gut defence mechanisms were studied in juvenile chronic arthritis. Thirty patients with juvenile chronic arthritis were randomly allocated to receive a freeze-dried powder of Lactobacillus GG, or bovine colostrum, or bovine immune colostrum, for a two-week period. Immunologic and non-immunologic gut defence mechanisms were indirectly investigated in blood and faecal samples. In patients receiving Lactobacillus GG, the median (interquartile range) frequency of immunoglobulin-secreting cells, determined by enzyme-linked immunospot assay, increased in the IgA class from 1840 (690–2530) to 3480 (1030–13 170)/106 cells; p=0.02. Likewise the median (interquartile range) frequency of specific antibody-secreting cells against dietary antigens increased during the Lactobacillus GG therapy in the IgM class from 3.8 (1.4–5.0) to 11.2 (5.0–30.0)/106 cells; p=0.02. In addition, Lactobacillus GG therapy decreased the median (interquartile range) activity of faecal urease, which has been associated with mucosal tissue damage, from 40.3 (21.7–54.3) to 28.6 (24.5–49.4) nmol. min−1 (mg protein)−1; p=0.10, while, in patients receiving bovine colostrum, faecal urease activity increased (from 42.2 to 80.6; p=0.04). All findings were transient. We suggest that gut defence mechanisms are disturbed in juvenile chronic arthritis and we further suggest that orally administered Lactobacillus GG has a potential to reinforce the mucosal barrier mechanisms in juvenile chronic arthritis. [ABSTRACT FROM AUTHOR]

A total of 433 children, hospitalized in the Rheumatic Children's Hospital Garmisch-Partenkirchen, were followed on average for 15 years (range 10-22 years) after the onset of definite juvenile chronic arthritis. This paper reveals clearly that the different subgroups of chronic rheumatic disease in childhood with their different complications have a definite relationship to prognosis. Severe limitation with inability to attend normal school or employment occurred in 13.4% of children with systemic polyarticular arthritis (Still's syndrome) and 11.4% of the non-systemic cases, but not in the pauci-articular group. In the latter group 82.5% of the children remained without disability or with only slight impairment: this is significantly better than in the systemic or non-systemic polyarticular groups. Although the high incidence of chronic rheumatic iridocyclitis is common in children with pauci-articular arthritis, none of this group had been handicapped by severe eye complications or blindness, in contrast to several early cases with systemic or non-systemic polyarthritis. This might be due to regular eye checks in the pauci-articular group. Of the children in the systemic polyarticular group 10% were dwarfed. Mortality in the systemic group was 13.8%, in contrast to 1% in the non-systemic polyarticular and 0% in the pauci-articular arthritis group. Secondary amyloidosis was the most important cause of death, mainly in systemic cases. Of the children whose amyloidosis had been verified, 44% died in their second or third decades, mostly with uraemia. [ABSTRACT FROM AUTHOR]

Antiphospholipid antibodies (APA) are often associated with severe clinical manifestations, especially in the setting of systemic lupus erythematosus (SLE). Here we have investigated the prevalence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) in paediatric patients affected with SLE, JCA and overlap syndromes (OS) and correlated the presence of aCL and LA with clinical features. aCL were assayed by enzyme-limited immunoassay; LA was determined by activated partial thromboplastin time and the kaolin clotting time test. aCL and LA assays were performed in parallel on at least two occasions over a 7–30-month follow-up. Fifteen out of nineteen (79%) SLE patients had aCL and 8/19 (42%) had LA. Six SLE patients displayed manifestations that were APA-related: deep venous thromboses, autoimmune haemolytic anaemia, pulmonary hypertension, neurological alterations. Five out of six symptomatic patients had both LA and high-titre aCL. In contrast, JCA and OS patients had usually low-titre aCL, no detectable LA and no APA-related manifestations. aCL persisted at high titre over time in SLE patients, but was only transiently detected in JCA and OS patients. This study shows that the simultaneous positivity for LA and high-titre aCL allows the identification of paediatric SLE patients who are at risk not only for thrombosis, but also for other APA-related clinical features. [ABSTRACT FROM PUBLISHER]

This study aimed to measure IgG reactivities to DNA-free nucleosome subparticles (H2AH2B, H3H4) and nucleosome subparticles (H2AH2B–DNA, H3H4–DNA) and to evaluate the temporal relation of these reactivities, as well as those to single core histones, with iridocyclitis (IC) in patients with antinuclear antibody positive (ANA +) pauciarticular juvenile chronic arthritis (JCA). Reactivities to nuclear substrates were determined by enzymatic immunoassays in 120 sera from 45 children with ANA + pauciarticular JCA. Significantly elevated IgG levels to H3 and H4, to DNA-free nucleosome subparticles, and to the nucleosome subparticle H3H4–DNA were present in patients with ANA + pauciarticular JCA; no evidence of recognition of conformational epitopes was found. In both horizontal and follow-up studies, no relation between the reactivities studied and the development, presence, or history of IC was found. Our results show the absence of a relation of antibodies to histone molecules or to nucleosome subparticles with IC in patients with ANA+ pauciarticular JCA. [ABSTRACT FROM PUBLISHER]

Twenty-nine children with juvenile chronic arthritis, aged from 7 to 16 yr were studied using the Juvenile Arthritis Functional Assessment Report for Children and Parents questionnaires (JAFAR-C and JAFAR-P). The results showed that JAFAR-C and JAFAR-P were highly correlated { <0.001) with each other and also with a predicted JAFAR score( <0.05). The JAFAR score correlated with the arthritic joint count at the time of the study ( <0.01), Steinbrocker classification ( <0.001), pain score ( <0.01) and stiffness score ( <0.005). Evidence of psychological dysfunction was found in eight of the 29 children (27%). Six children (21%) scored 13 or more on the Rutter A(2) for parents and one patient scored more than nine on the Rutter B(2) for teachers. Only one child had a score on the Birleson self-rating scale that was high enough to suggest a likely diagnosis of depression. The median Lipsitt self-concept scale score was 86, that expected for a healthy population. There was no correlation between the psychological scores and any of the other functional measurements, although the numbers affected were small. There was no significant difference between type of arthritis at onset with regard to any of the scores obtained. [ABSTRACT FROM PUBLISHER]

Activated factor VIIa (FVIIa), von Willebrand factor antigen (vWF:Ag), D-dimer and thombin-antithrombin III complex (TAT) were measured to monitor coagulation status in patients with juvenile chronic arthritis (JCA). Subjects included 14 patients with systemic JCA, 16 with pauciarticular JCA and 16 with polyarticular JCA without disseminated intravascular coagulopathy, thrombosis or liver dysfunction. All types of JCA showed an increase of FVIIa, D-dimer and TAT, indicating enhanced activation of coagulation. In systemic JCA only there was also characteristically an elevation of vWF:Ag. We conclude that all types of JCA constitute a state of subclinical hypercoagulopathy caused by tissue damage and that additionally systemic JCA involves a prothrombotic state associated with or precipitated by vasculitis. [ABSTRACT FROM PUBLISHER]

A panel of 43 early onset pauciarticular (EOPA) juvenile chronic arthritis (JCA) patients have been typed for human leucocyte antigens (HLA) DRB1, DPB1, DQA1 alleles, and DQB10603 status using molecular-based methods. Increased frequencies of DRBl08 [odds ratio (OR) 7.7, 95% confidence interval (CI) 2.6–22.3],DRBlll (OR 3.1, 95% CI 1.2–8.1), DRBl1301 (OR 7.7, 95% CI 2.6–22.3), DPB10201 (OR 3.5, 95% CI 1.6–8.0), DQAl0103 (OR 4.4, 95% CI 1.5–13.3), DQA10501 (OR 2.9, 95% CI 1.3–6.6), DQA10601 (OR 30, 95% CI 3.6–241) and DQB10603 (OR 7.3, 95% CI 3.0–17.6) were foundin the EOPA-JCA group compared with Caucasoid controls. Stratification of the EOPA-JCA group into antinuclear antibody (ANA) positive (n = 18) and ANA negative (n = 25) individuals revealed that ANA positivity was only associated with DRBl1301 (OR 4.2, 95% CI 1.0–17.3), DPBl0201 (OR 4.0, 95% CI 1.0–15.7) and DQB10603 (OR 11.5, 95% CI 2.5–53.4). Further analysis of the relative contributions of HLA antigens to ANA status revealed that DQB10603 determined the primary HLA effect. No apparent interaction between DQBl0603 and DRB11301 or between DQB10603 and DPBl0201 was found to contribute to the association with ANA. We suggest that those ANA positive individuals with a restricted HLA background, DQB10603 positive), defines a group of EOPA-JCA patients which will be especially valuable in the characterization of the ANA associated with EOPA-JCA. [ABSTRACT FROM PUBLISHER]

The inflammatory cytokines interleukin 1β (IL-1β) interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and the anti-inflammatory peptide—the interleukin 1 (IL-1) receptor antagonist—were measured in the plasma of children with juvenile chronic arthritis (JCA). In the two subgroups studied (polyarticular JCA and systemic JCA), there was good correlation between laboratory measures of disease activity C-reactive protein (CRP), erythrocyte sedimentation rate and clinical scores for disease activity. Despite higher levels of CRP in the systemic group IL-1β levels were lower and regression analysis recorded a difference in the relationship between CRP and IL-1β within thetwo clinical groups. In contrast, IL-6 levels were high in the systemic group and correlated with disease activity. No such correlation was observed in the polyarticular group. Five children with systemic JCA were studied during the febrile phase of their illness. IL-6 levels rose and fell with the fever. TNFα levels also rose and fell but out of phase with the fever. In contrast IL-1β levels were either undetectable throughout the febrile episode or only became detectable as the temperature reduced to normal. The IL-1 receptor antagonist was usually found in 1000-fold excess over IL-lβ, levels rising and falling with the fever. These results demonstrate difference in the cytokine profiles and acute phase protein responses in polyarticular and systemic JCA. This would suggest different pathogenic mechanisms for these two groups of JCA with IL-6 being the more important cytokine in systemic JCA. [ABSTRACT FROM PUBLISHER]

The functional and psychological outcome of 43 patients with polyarticular juvenile arthritis was assessed in order to evaluate the impact of disease on their quality of life. Mean disease duration was 19.7 yr (range 10–39 yr), mean age 26.7 yr (range 18–54 yr) with sex ratio 1:3 (male : female). Severe disability was present in 8% of systemic onset, 34% of RF negative (Rh – P), 38% of RF positive (Rh + P) and 86% of extended pauci-articular (ExP) juvenile arthritics—this last high percentage was due to ocular impairment. The Rh + P had more hip (100% of the group) and knee prostheses (31%) compared with Rh – P (77 and 11% respectively). The Rh + P and ExP groups were the most disabled with the highest proportions of patients with currently active disease (85 and 71% respectively). Psychological testing showed that 21% of the patients were clinically depressed and the rate increased ( = 0.06) with the degree of disability. The proportion of patients demonstrating an anxious preoccupation with their disease increased ( = 0.002) with the degree of disability. Despite this, 66% of patients were employed and 38% felt that their arthritis had no effect on their ability to form relationships. [ABSTRACT FROM PUBLISHER]

The hip joint is the most important joint as far as surgical management of JCA is concerned. Approximately a third of children will develop hip involvement, leading to pain and deformity. A wide spectrum of hip joint abnormalities may occur, being the result of either under-development or over-development of the bones and erosive change secondary to the synovitis. For the acutely irritable hip with no fixed deformity an intra-articular injection of Triamcinolone Hexacetonide may be beneficial. For those hips with a fixed deformity, resulting in functional impairment in children prior to the closure of the proximal femoral capital epiphysis, a soft tissue release of selected muscles around the hip joint can correct deformity and improve function. For the painful destroyed hip joint, total joint replacement is indicated. Cemented hip replacements have been shown to have a high incidence of loosening in this patient group and consideration is being given to the use of customized uncemented femoral components. [ABSTRACT FROM PUBLISHER]

Juvenile chronic arthritis covers a heterogeneous group of arthritides for which there appears to be a genetically determined susceptibility. The exact events which trigger or perpetuate an arthritic disease have yet to be defined. There is circumstantial clinical evidence that JCA can be initiated by environmental factors such as infection, and indirect laboratory evidence that immune responses to infectious agents are associated with ongoing JCA; such immune responses seem particularly vigorous within the joint space. Although the weight of evidence favours the hypothesis that the intra-articular inflammatory process is antigen-driven, none of the critical antigens have been identified, and it is still unclear whether they are derived from infectious agents or are true auto-antigens. We can however expect progress to be made, since tech niques are now available for defining the antigenic specificity and TCR usage of synovial T cell populations, while PCR allows exquisitely sensitive detection of infectious agents deposited in the synovial space. Application of these techniques should lead to an enhanced understanding of whether (or in what circumstances) infectious agents are involved in the pathogenesis of arthritis in children [ABSTRACT FROM PUBLISHER]

The objective of this study was to determine the prevalence of histone antibodies in early onset pauciarticular juvenile chronic arthritis (JCA), and to assess any association with disease activity in terms of arthritis or uveitis. Forty-four children with early onset pauciarticular JCA have been assessed prospectively using clinical and laboratory parameters. Sera were collected from these patients during clinical follow-up. Some of them had serial measurements during the period of study. Patient sera were analysed for histone antibodies by ELISA. A further study using 30 synthetic peptides of calf thymus core histones was performed by ELISA. Seventy-five per cent of children have IgM antibodies to histone, usually to more than one type. The highest values were anti H3 and H4 antibodies. There was no correlation between the level of anti-histone antibodies and anterior uveitis. There were increased levels of IgG antibodies to histone peptides, in particular the N- and C-terminal peptides of H3 in 70.5% of children. Antibodies to H3 peptides tend to be in patients with chronic anterior uveitis ( = 0.04). [ABSTRACT FROM PUBLISHER]

Thirty-four children with juvenile chronic (rheumatoid) arthritis were recruited to a randomized, double-blind study of deflazacort (DFZ) (an oxazolone derivative of prednisone (PDN)) vs prednisone. All had been receiving glucocorticoid therapy for at least 1 year and required at least 5 mg/day of prednisolone (usually as 10 mg every 2 days). Thirty-one children completed the study. Bone density trends were measured in the spine by dual photon absorptiometry and in the forearm by single photon quantitative computed tomography at 3–monthly intervals. Trends(velocities) in bone and soft tissue growth were calculated. In the spine, bone growth correlated well with indices of soft tissue growth, but covariance analysis showed a significant advantage (P<0.007) of DFZ when spinal bone mineral growth was compared to body surface area and weight. In part this was due to a temporary interruption in weight by children receiving DFZ, whose gain in height was comparable with that of the PDN group. Some children in both groups-improved clinically and showed catch-up growth; in these children relative spinal bone mineral growth velocities were about twice those observed for height and weight. It is concluded that during the first year of DFZ, children with active diseases were better able to maintain their spinal bone mineral content at a level that was appropriate for their height and weight. Further observations are required to establish whether this advantage can be maintained subsequently. The anti-inflammatory effects of the two glucocorticoids appeared similar. [ABSTRACT FROM PUBLISHER]

Juvenile chronic arthritis is a heterogeneous disease, having different subtypes. Among our 89 patients with juvenile chronic arthritis, we did not find even one patient with early onset pauciarticular disease with uveitis and antinuclear antibody positivity. Further, the prevalence of anti-nuclear antibodies and anti-histone antibodies was very low whereas the prevalence of rheumatoid factor was similar to that reported from Western countries. Thus, the spectrum of juvenile chronic arthritis in India differs from that seen in the west. Larger population based studies of the disease are thus needed. [ABSTRACT FROM AUTHOR]

Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-α, IL-1α, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active ( n=22) and inactive ( n=14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF-α and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF-α and IL-1α levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF-α concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF-α concentrations may be used as markers of disease activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The immunoinflammatory pathogenesis of juvenile chronic arthritis (JCA) involves the activation of many pathways including various cytokines. We have evaluated the levels of interleukin (IL)-1, IL-6 and IL-8 in 29 JCA patients. The age range was 1–16 with a mean of 10.1. A disease activity score was developed on the basis of: 1.constitutional symptoms and/or morning stiffness, 2.presence of joint swelling, 3.warmth, 4.limited range of motion, and 5.joint pain. This score correlated very significantly with laboratory disease activity markers such as erythrocyte sedimentation rate (ESR) and CRP (both p=0.006) and also correlated with IL-1 and IL-6 levels. The levels of IL-1 decreased in four of the five patients with improved disease activity. IL-6 but not IL-1 correlated significantly with the number of inflamed joints (p=0.013); IL-6 also strongly correlated with rheumatoid factor supporting this cytokine's role in B cell induction (p=0). Haemoglobin values correlated negatively with the activity index, ESR, CRP, IL-1 and IL-6. IL-8 did not correlate with disease activity markers. In the systemic patients all cytokines tended to be higher. Our data suggest that interleukins 1 and 6 are effective in the pathogenesis of JCA. Whether cytokines may be used for monitoring therapy may be clarified with further studies. [ABSTRACT FROM AUTHOR]

Altered levels of high density lipoprotein (HDL), low density lipoprotein (LDL), and very-low density lipoprotein (VLDL), as well as apolipoproteins have been previously described in rheumatoid arthritis patients. We have attempted to evaluate the serum triglyceride, total cholesterol, cholesterol in DHL, LDL, apolipoprotein A1 (apo-A1) and apolipoprotein B (apo-B) levels in juvenile chronic arthritis (JCA) and to correlate them with CRP and ESR in the active and non-active stages of JCA. A total of 37 children who fulfilled ARA criteria for the diagnosis of JCA were studied. There were 18 girls and 19 boys. Age range was 2.5-16 years with a mean of 9.5. The mean duration of disease was 1.8 years. Nineteen patients were accepted to have active disease. Eighteen age and sex matched healty children served as controls. Apo-A1 was significantly lower in the active JCA group when compared to inactive patients and healthy controls (both p<0.05). There were significant inverse correlations between apo-A1 and both ESR and CRP levels in these patients (r=0.67, p<0.05 and r=−0.61, p<0.-05, respectively). Although mean LDL levels were numerically lower in the JCA patients (67.2 mg/dl in the active and 68.6 mg/dl in the inactive patients) the difference with healthy controls (91.7 mg/dl) was not statistically significant. There was no significant differences in regard to triglyceride, total cholesterol, cholesterol in HDL, and apo-B levels between neither of the groups. We conclude that JCA patients have a dyslipoproteinaemic state with already altered metabolism of lipids at different stages of the chronic inflammation from active to inactive disease. [ABSTRACT FROM AUTHOR]

Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46-1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r=0.48 and r=0.55 respectively) (both p<0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA. [ABSTRACT FROM AUTHOR]

In juvenile chronic arthritis (JCA) the indices of disease activity, such as joint swelling, pain, tenderness, and limitation of motion, may poorly correlate with the degree of functional impairment. Since the improvement of functional capacity is one of the main objectives of treatment, we evaluated the effect of methotrexate (MTX) in 29 children with JCA by assessing both the articular indices and a functional status measure. After 6 months of therapy, 15 of the 29 patients had a significant (≥50%) reduction in the number of joints with active arthritis and/or the articular severity score and were then judged as responders, while 14 did not respond to MTX. In the responder group, the median functional index score decreased from 17 (range: 13-27) at baseline to 13 (range: 13-15) at 6 months (p<0.001); the median score of the non-responder group was 20 both at baseline and at 6 months (ranges: 14-27, and 13-36, respectively). These results show an improvement of functional impairment in those patients who respond to MTX according to the conventional indices of articular inflammation. [ABSTRACT FROM AUTHOR]

Among 664 juvenile chronic arthritis patients cared for in the Out-patient Clinic of the Pediatric Rheumatology Unit of the National Institute of Rheumatology and Physiotherapy 11 were found with juvenile psoriatic arthritis, and their data regarding skin, joint, ophthalmological, laboratory and radiological manifestations were analysed. These patients were categorised according to the four subgroups suggested by Truckenbrodt et al. Considering that the occurrence of the disease is rare, the small number of patients investigated in this study can provide additional data to the study of Truckenbrodt. The higher number of patients with JPA thus studied can give more information for a multicentric evaluation. [ABSTRACT FROM AUTHOR]

We evaluated the serum concentrations of zinc., copper and selenium in 125 patients with juvenile chronic arthritis (JCA). Trace element levels showed distinct abnormalities as compared with those of a large group of healthy children. Serum zinc and selenium concentrations were lower and those of copper higher in children with arthritis than in healthy children and, further, patients with polyarthritis had significantly higher copper and lower zinc levels than those with oligoarthritis. Serum zinc levels showed a direct correlation with hemoglobin and an inverse correlation with values for the erythrocyte sedimentation rate (ESR), whereas copper correlated directly with ESR. Selenium values did not correlate with the activity of the disease, but were low in the patients with arthritis of long duration. [ABSTRACT FROM AUTHOR]

Using ELISA antibodies, titres to collagen type I, II and III in sera of patients with juvenile chronic arthritis (JCA) were assayed. Results were compared with titres of patients with rheumatoid arthritis (RA). Increased antibodies titres to all three collagen types were found in comparison with healthy individuals of the same age. Average titres in patients with RA were higher than those of the JCA group. When antibodies titres were correlated with erythrocyte sedimentation rate in 1 hour (ESR/1h) statistical significance was found only in RA group for collagen type II. [ABSTRACT FROM AUTHOR]

One hundred and fifty children with suspected juvenile chronic arthritis (JCA) and a disease duration of 3-6 months entered a prospective study. Diagnosis of JCA could be verified in 107 patients according to the WHO-EULAR criteria. After 5.0±0.9 years 66 of the 107 patients showed no disease activity, 24 of them for more than 2 years, 23 for less than 2 years without any drug therapy. Nineteen patients were still on NSAIDs and/or long acting drugs, 14 patients with unfavourable morphologic outcome (>stage II) and 17 patients with severe functional impairment (≥stage III) all belonged to the 41 children with still active disease after 5 years follow-up. The disease course was polyarticular in 10 of the 14 patients with severe radiologic changes and in 14 of the 17 with unfavourable functional results. The wrist joint proved especially vulnerable since 46% of the severe radiologic changes concerned this joint. All 4 children with positive rheumatoid factor followed a polyarticular course with severe radiologic changes (stage>II), 3 of them together with unfavourable functional outcome. Risk factors for morphologically and functionally unfavourable course are therefore seen in a still active disease after 5 years, a polyarticular joint involvement and a positive rheumatoid factor. Extra-articular complications concerned chronic iridocyclitis in 7 patients, acute iridocyclitis in 2, amyloidosis in 1 and growth retardation in 2 children. - The prospective study is to be continued. [ABSTRACT FROM AUTHOR]

Two children suffering from systemic juvenile chronic arthritis (JCA) complicated by acute disseminated intravascular coagulation (DIG) are described. One had a fatal outcome with acute renal failure and cerebral haemorrhage; the other recovered. Early recognition and treatment of the underlying cause - usually an infection - as well as replacement of clotting factors are important in management. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Restriction fragment length polymorphism (RFLP) typing of MHC-class II loci DRB, DQA1, DQB1, DQA2 and DPB1 was performed in 94 patients with seronegative juvenile chronic arthritis (JCA) and 184 random controls. Analysis of allele frequencies and MHC-class II 4-loci haplotypes indicate: (1) Susceptibility to JCA is more strongly associated with the HLA-DQ subregion than with the HLA-DR subregion, especially in early onset pauciarticular JCA (EOPA-JCA). (2) Haplotype and sequence analysis show two independent MHC-class II associations for susceptibility to EOPA-JCA, one located in DQA1, the other in DPB1. (3) Two RFLP defined patterns of the DQA1 locus, DQA1.5 (DQA10501) and DQA1.8 (DQA10401, 0601) are strongly associated with the disease. (4) Analysis of amino-acid (AA) sequences coded in exon 2 of DQA1 reveals an AA sequence of six AAs common to all three associated DQA1 alleles. This suggests a model that includes a functional role for HLA-DQ molecules in the pathogenesis of JCA. [ABSTRACT FROM AUTHOR]

Peroxidase-anti-peroxidase (PAP) staining and specific antibodies against cathepsin G and elastase from polymorphonuclear leukocytes (PMN) were applied to pannus-free and microscopically intact superficial articular cartilage. Restricted local deposits containing cathepsin G and elastase were found in three of ten patients with seropositive rheumatoid arthritis (RA), in one of three patients with seronegative RA and in one patient with juvenile chronic arthritis (JCA). Similarly, localized deposits of IgG and C3 were found in the patients with seropositive RA and JCA, but not in the patient with seronegative RA. Adjacent sections exhibited esterase activity in and around the PMN. In proteinase-positive areas from patients with seropositive RA the inhibitors α-proteinase inhibitor (α-PI) and α-macroglobulin (α-MG) were present in two of three and one of three patients, respectively. In JCA only α-proteinase inhibitor was present, and in seronegative RA no inhibitors were found. No staining of articular cartilage was observed in a patient with psoriatic arthritis. One of three cases with osteoarthritis exhibited patchy superficial staining for IgG only. In articular cartilage covered by pannus, in three patients with seropositive RA, in one with seronegative RA and in the patient with JCA a few regions with variably dense PMN infiltrates were observed. Cathepsin G, elastase and esterase activity were found in and around the PMN. In one of the three patients with seropositive RA the adjacent cartilage-pannus junction exhibited distinct staining for cathepsin G and elastase, but not for IgG/C3 and proteinase inhibitors. The findings suggest that cathepsin G and elastase from PMN are involved in the breakdown of rheumatoid articular cartilage in the presence, as well as in the absence, of entrapped immune-complex-like material, and that proteinase inhibitors are often lacking in such regions. [ABSTRACT FROM AUTHOR]

A broad range of autoantibodies have been detected in juvenile chronic arthritis (JCA) patients, although, none of them can be considered specific for this entity. Antinuclear antibody (ANA) is routinely searched in these patients mainly because it is associated with uveitis, a comorbidity that is particularly frequent in the oligoarticular form. Nevertheless, the ANA specific antigen target in JCA is unknown. In this study, we aimed to search for antinucleosome antibodies in 30 adult JCA patients and to study possible associations with clinical profile. Ten individuals (33.3%) were positive for antinucleosome antibodies and seven (70%) were simultaneously ANA positive ( p = 0.01). We did not find any significant association among antinucleosome and JCA form, uveitis, age of onset, gender, or functional index. We conclude that in JCA, there is a prevalence of 33.3% of antinucleosome antibodies. Further investigations are needed to understand the ANA positivity found in this disease as far as the clinical impact of this finding. [ABSTRACT FROM AUTHOR]