Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years.

OBJECTIVE: To investigate the relationships between systemic onset juvenile idiopathic arthritis disease activity, course of the disease, and functional class according to Steinbrocker. METHODS: The records of all children with systemic onset juvenile arthritis (JA) according to the American College of Rheumatology criteria attending our center since 1971 with a minimum followup period of 3 years were reviewed. A cohort of 80 consecutive patients entered the study: 42 males, 38 females, mean age at onset 6.3 years (range 0.7-16), mean followup period 10.7 years (range 3-33). The cumulative duration of the active periods (CDAP) in months was calculated for every patient. RESULTS: Three patterns of disease course were apparent: monocyclic (subtype I), intermittent (subtype II), and persistent (subtype III). At the last control the functional class and disease activity status were evaluated. In all subtype I patients (9 cases) the disease was in remission and no patient was in class II, III, or IV. In subtype II patients (27 cases), 16 were inactive or in remission and 6 in class III. In subtype III (44 cases) 21 were inactive or in remission and 17 were in class III or IV. The equation relating the Steinbrocker class to the CDAP was calculated considering the functional outcome as the dependent variable. The linear regression equation y = 0.0083 x + 1.266 was found with a correlation coefficient r = 0.586 (p < 0.0001). The majority of our patients were treated with disease modifying antirheumatic drugs, which in many cases were effective in reducing the duration of the active phases of disease. CONCLUSION: Systemic onset JA may present with different clinical courses; the functional outcome is always good in subtype I (monocyclic), but can be poor in subtypes II and III. The severity of disability evaluated according to Steinbrocker classes is dependent on the cumulative duration of the active periods of the disease.

Validation of the Italian version of the Stanford Childhood Health Assessment Questionnaire for measuring functional status in children with chronic arthritis.

The Stanford Health Assessment Questionnaire developed by Singh et al. to measure functional status in children with chronic arthritis (CHAQ) was translated into Italian (I-CHAQ), with minor modifications to obtain cross-cultural equivalence. This version was evaluated in a series of 96 patients with juvenile rheumatoid arthritis (JRA), both males and females ranging in age from 3 to 19 years (mean age 9.9 years). All three onset subtypes and all four classes of disability were represented in the sample. The questionnaire was filled in by the parents if the children were less than 8 years of age (23 cases), and by the children themselves in all other cases; a health professional was always present to provide assistance. As expected, JRA patients with a systemic or polyarticular disease onset had higher scores than those with a pauciarticular onset, and there were statistically significant differences in disability index values between patients from different Steinbrocker functional classes. The instrument showed good reproducibility in a test-retest over a two-week period, a high correlation between the child and parent scores, excellent internal reliability, and good convergent and discriminant validity.

Lung function and diffusing capacity for carbon monoxide in patients with juvenile chronic arthritis: effect of disease activity and low dose methotrexate therapy.

OBJECTIVE: We measured lung function, in terms of lung volumes, forced expiratory flow-volume curves and diffusing capacity of carbon monoxide (DLCO), in a group of 61 patients with juvenile chronic arthritis (42 female; age range 5 to 33 years) to ascertain whether disease activity and treatment with low dose methotrexate (MTX) influenced these parameters. The whole population was divided into subgroups based on onset type (systemic, n = 27; pauciarticular, n = 12; polyarticular, n = 22), disease activity (active, n = 42; inactive, n = 19), and MTX treatment (treated, n = 27; not treated, n = 34). RESULTS: We found that maximal-mid expiratory flow (MMEF) was significantly reduced in patients with active disease (p < 0.025). The mean DLCO value, expressed as a percentage of the predicted value, and DLCO corrected for the hemoglobin value were lower than expected (67% and 80%, respectively). Multiple regression analysis showed that the forced vital capacity (FVC), forced expiratory flow in one second (FEV1) and DLCO were all correlated to the clinical subtype of the disease (p < 0.05, p < 0.02, p < 0.02, respectively), and MMEF was related to disease activity (p < 0.025). There was no evidence of any effect of MTX treatment on the pulmonary parameters. CONCLUSION: This study confirms that JCA is characterized by an impairment of lung function, mainly involving the small airways, and by interstitial damage. These changes are related to the clinical subtypes of the disease and to disease activity.

The anticytokine neuropeptide alpha-melanocyte-stimulating hormone in synovial fluid of patients with rheumatic diseases: comparisons with other anticytokine molecules.

The aim of this study was to determine if the anticytokine neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) occurs, along with interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFr), in synovial fluid of patients with rheumatoid arthritis (RA), juvenile chronic arthritis (JCA), or osteoarthritis. The data show that alpha-MSH does occur in the synovial fluid and its concentrations are greater in patients with RA than in those with osteoarthritis. Synovial fluid concentrations of IL-1ra and sTNFr were likewise greater in RA. Further, concentrations of alpha-MSH, IL-1-ra, and sTNFr were greater in patients with polyarticular/systemic-onset JCA than in those with pauciarticular disease, that is in patients with greater joint inflammation. Concentrations of alpha-MSH were greater in synovial fluid than in plasma in a substantial proportion of patients, suggesting local production of the peptide; this is the first indication that the anticytokine molecule alpha-MSH is produced within a site of inflammation. Further, it appears that local production of alpha-MSH is induced particularly in those arthritic joints that have more intense inflammatory reactions. This finding, combined with previous evidence of the marked anti-inflammatory activity of alpha-MSH, suggests that the peptide acts locally to modulate proinflammatory influences in rheumatic diseases.

Clonal expansions of V delta 1+ and V delta 2+ cells increase with age and limit the repertoire of human gamma delta T cells.

We have investigated the complexity of the human gamma delta T cell repertoire by means of a VJ heteroduplex analysis method. cDNA obtained from peripheral blood mononuclear cells was amplified with V delta 1-C delta or V delta 2-C delta primers. The product was denatured and renatured to allow random reannealing of the strands and the heteroduplexes carrying mismatched junctional sequences were separated from the homoduplexes on polyacrylamide gels. Whenever one or more T cell clones were expanded to over 10% of the polyclonal background, discrete bands of homo- and heteroduplex appeared. This method was applied to the analysis of the peripheral gamma delta compartment from healthy donors and rheumatoid arthritis patients of different ages. While samples from young individuals showed a polyclonal pattern, a clear tendency towards oligoclonality appeared with increasing age, both in normal individuals and rheumatoid arthritis patients. We also show that the VJ junctional sequence derived from the heteroduplex fragments can be successfully used to isolate and characterize the corresponding T cell clones in vitro, even after a period of 1 year. In conclusion, our findings indicate that the complexity of the gamma delta T cell repertoire decreases with age as a consequence of the expansion of a few T cell clones.