Biomedical subjects

Angelo Ravelli

Publications and source records attributed to Angelo Ravelli.

28 records · Page 2Linked to original sources

PubMed2004

Health-related quality of life in juvenile-onset systemic lupus erythematosus and its relationship to disease activity and damage.

OBJECTIVE: To assess the health-related quality of life (HRQL) of patients with juvenile-onset systemic lupus erythematosus (JSLE) and its relationship with disease activity and accumulated damage. METHODS: In this cross-sectional study, HRQL was assessed using the Child Health Questionnaire (CHQ), disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and accumulated damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: A total of 297 patients were included. The mean +/- SD physical and psychosocial summary scores of the CHQ were 40.2 +/- 15.0 and 44.8 +/- 10.7, respectively. The most impaired CHQ subscales were global health, general health perceptions, and parent impact-emotional. The SLEDAI score was significantly correlated with both the physical summary score (r = -0.29, P < 0.0001) and psychosocial summary score (r = -0.25, P < 0.0001), whereas the SDI score was significantly correlated only with the physical summary score (r = -0.23, P = 0.0001). CONCLUSION: We found that patients with JSLE have significant impairment of their HRQL, particularly in the physical domain. HRQL may be affected by both disease activity and accumulated damage, particularly in the renal, central nervous, and musculoskeletal systems.

Adolescent↗

PubMed2004

Serum level of KL-6 as a marker of interstitial lung disease in patients with juvenile systemic sclerosis.

OBJECTIVE: Serum KL-6 has been found to be elevated in diseases characterized by diffuse interstitial lung involvement. The purpose of this study was to evaluate serum KL-6 as a marker of interstitial lung disease (ILD) in patients with juvenile systemic sclerosis (JSS). METHODS: Serum concentrations of KL-6 were measured with an immunoassay in 39 serum samples from 12 children with diffuse cutaneous form of JSS (6 patients with and 6 patients without ILD) and from 20 healthy controls comparable for age. In patients sampled serially, the relationship of KL-6 concentrations with the severity of ILD and its response to treatment were evaluated. RESULTS: Serum concentrations of KL-6 were significantly higher in patients with ILD (1687 +/- 979 IU/ml) than in patients without (345 +/- 95 IU/ml, p < 0.01) and healthy controls (311 +/- 114 IU/ml, p < 0.001). Serum KL-6 concentrations of patients without ILD were not statistically different from those of healthy controls. We found a significant correlation of serum KL-6 concentrations with vital capacity and with diffusing capacity for carbon monoxide (DLCO). Analysis of individual patients showed that serum concentrations of KL-6 were correlated with ILD severity and its response to treatment. CONCLUSION: Measurement of serum KL-6 concentration is a useful noninvasive marker of pulmonary fibrosis in children with JSS. Its advantages over conventional methods of ILD assessment, such as pulmonary function test and high-resolution computerized tomography, are that it is easy to quantify and to measure repeatedly and it does not need children's cooperation.

Adolescent↗

PubMed2003

Positive family history of psoriasis does not affect the clinical expression and course of juvenile idiopathic arthritis patients with oligoarthritis.

OBJECTIVE: In the 1997 revision of the International League of Associations for Rheumatology (ILAR) criteria for juvenile idiopathic arthritis (JIA), a family history of psoriasis is an exclusion for the oligoarthritis category. We investigated whether psoriasis in a first or second degree relative influences the clinical expression and course of JIA patients with oligoarthritis. METHODS: In a cross-sectional study, consecutive oligoarticular-onset JIA patients were investigated. Clinical evaluations included confirmation of a family history of psoriasis and assessment of nail abnormalities, dactylitis, psoriatic rash, variables of JIA activity, and laboratory indicators of inflammation. Retrospective assessments included sex, onset age, disease duration, antinuclear antibodies, HLA-B27, uveitis, ocular complications, second-line therapies, intraarticular corticosteroid injections, radiographic joint lesions, joint involvement over time, and laboratory investigations at disease presentation and first observation. RESULTS: A total of 185 patients were included. Thirty-three had a positive family history of psoriasis (group 2) and 139 did not (group 1). Thirteen patients fulfilled the ILAR criteria for juvenile psoriatic arthritis (group 3). Patients in groups 1 and 2 were comparable for all parameters, except for a higher frequency of females in group 1 (P = 0.04). As compared with group 2, patients in group 3 were less frequently antinuclear antibody positive and had a more severe arthritis and a different distribution of joint involvement. CONCLUSION: We found close similarities in the clinical features and course among patients with oligoarthritis who had a positive family history for psoriasis and those who did not. These findings argue against the exclusion of the former patients from the oligoarthritis category of JIA.

Arthritis, Juvenile↗

PubMed2003

Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study.

OBJECTIVE: To investigate the prevalence of cumulative organ damage in patients with juvenile-onset systemic lupus erythematosus (SLE) and its association with demographic and clinical variables, medication use, and quality of life. METHODS: The occurrence of organ system damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was determined for 387 patients consecutively enrolled in pediatric rheumatology centers from Europe, the US, Mexico, and Japan. Risk factors for damage included demographic variables; clinical manifestations at diagnosis; previous corticosteroid, immunosuppressive, and antimalarial therapies; disease activity; and quality of life. RESULTS: Overall, 195 (50.5%) patients had damage within a mean of 5.7 years after disease onset. Renal (21.8%) and neuropsychiatric (15.8%) system involvement were observed most frequently, followed by musculoskeletal (11.7%), ocular (10.9%) and skin (9.6%) system involvement, with a mean SDI score of 1.1. In multivariate models, the occurrence of neuropsychiatric manifestations at diagnosis, a longer disease duration, and a greater number of intravenous cyclophosphamide pulses showed the strongest association with the presence of damage. CONCLUSION: We found evidence of cumulative organ damage, as measured by the SDI, in half of the patients with juvenile-onset SLE. Damage was significantly more likely in patients who had experienced neuropsychiatric manifestations at diagnosis, had a longer disease duration, and had received more intravenous pulses of cyclophosphamide.

Adolescent↗

PubMed2003

Preliminary core sets of measures for disease activity and damage assessment in juvenile systemic lupus erythematosus and juvenile dermatomyositis.

OBJECTIVE: To identify preliminary core sets of outcome variables for disease activity and damage assessment in juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). METHODS: Two questionnaire surveys were mailed to 267 physicians from 46 different countries asking each member to select and rank the response variables used when assessing clinical response in patients with JSLE or JDM. Next, 40 paediatric rheumatologists from 34 countries met and, using the nominal group technique, selected the domains to be included in the disease activity and damage core sets for JSLE and JDM. RESULTS: A total of 41 response variables for JSLE and 37 response variables for JDM were selected and ranked through the questionnaire surveys. In the consensus conference, domains selected for both JSLE and JDM activity or damage core sets included the physician and parent/patient subjective assessments and a global score tool. Domains specific for JSLE activity were the immunological tests and the kidney function parameters. Concerning JDM, functional ability and muscle strength assessments were indicated for both activity and damage core sets, whereas serum muscle enzymes were included only in the activity core set. A specific paediatric domain called 'growth and development' was introduced in the disease damage core set for both diseases and the evaluation of health-related quality of life was advised in order to capture the influence of the disease on the patient lifestyle. CONCLUSIONS: We developed preliminary core sets of measures for disease activity and damage assessment in JSLE and JDM. The prospective validation of the core sets is in progress.

Child↗

PubMed2003

Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis.

OBJECTIVE: To address the functional and prognostic relevance of the -173 single-nucleotide G-to-C polymorphism of the macrophage migration inhibitory factor (MIF) gene in patients with systemic-onset juvenile idiopathic arthritis (systemic-onset JIA) by evaluating its association with serum and synovial fluid levels of MIF, with glucocorticoid requirement, and with the outcome of the disease. METHODS: A total of 136 patients with systemic-onset JIA were studied, including 98 patients from the British Paediatric Rheumatology Study Group's National Repository for JIA and 38 patients who were followed up at the IRCCS Policlinico San Matteo (Pavia, Italy) and the IRCCS G. Gaslini (Genoa, Italy). The MIF-173 polymorphism was genotyped using SnaPshot ddNTP primer extension and capillary electrophoresis. MIF levels were measured by enzyme-linked immunosorbent assay. The evaluation of the association of the MIF-173 polymorphism with outcome was performed only in Italian patients who were followed up for >5 years, by analyzing retrospectively 1) the number of joints with active arthritis and the number of joints with limited range of motion; 2) the score, at the last visit, on the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ); and 3) data concerning the treatment regimens during the disease course. RESULTS: Systemic-onset JIA patients carrying a MIF-173*C allele had serum and synovial fluid levels of MIF significantly higher than those in patients with the GG genotype. The duration of glucocorticoid treatment on a daily regimen was significantly longer in patients carrying a MIF-173*C allele than in MIF-173 GG homozygous patients. Moreover, the duration of clinical response to intraarticular injection of triamcinolone hexacetonide was significantly shorter in patients carrying a MIF-173*C allele. At the last visit, the numbers of joints with active arthritis, the C-HAQ scores, and the numbers of joints with limited range of motion were significantly higher in patients carrying the MIF-173*C allele. CONCLUSION: Our study shows the functional relevance of the MIF-173 polymorphism and suggests that the MIF-173*C allele is a predictor of poor outcome in systemic-onset JIA.

Adolescent↗

PubMed2003

Prognostic factors for radiographic progression, radiographic damage, and disability in juvenile idiopathic arthritis.

OBJECTIVE: To investigate the rate of radiographic progression and identify prognostic factors of radiographic progression, radiographic damage, and physical disability in juvenile idiopathic arthritis (JIA). METHODS: Ninety-four JIA patients with a median disease duration of 1.1 years were followed up prospectively for a median of 4.5 years. Bilateral wrist radiographs were obtained at baseline, at 1 year, and at the last followup visit. Radiographic damage was assessed by the carpal length (Poznanski score), and physical disability by the Childhood Health Assessment Questionnaire (C-HAQ). Yearly radiographic progression, the Poznanski score at the final visit, and the C-HAQ score at the final visit were used as outcome measures. Baseline parameters included demographic, clinical, laboratory, and radiographic data. RESULTS: The mean +/- SD Poznanski score was -1.2 +/- 1.3 at baseline, -1.7 +/- 1.8 at the 1-year visit, and -1.9 +/- 2.2 at the final visit (P < 0.0001). Radiographic progression was greater during the first year (mean +/- SD -0.5 +/- 1.1) than between the 1-year visit and the final visit (-0.2 +/- 1.3). The mean yearly radiographic progression during the entire study period was -0.1 +/- 0.4. Logistic regression analysis revealed that radiographic progression during the first year was the only baseline parameter that was predictive of all 3 study outcomes. The final Poznanski score was also predicted by the baseline Poznanski score, whereas female sex was protective against radiographic progression. CONCLUSION: We identified the prognostic factors for poorer outcome in polyarticular-course JIA. The changes in the early Poznanski score can be used to predict long-term joint damage and physical disability.

Adolescent↗

PubMed2002

Macrophage migration inhibitory factor in patients with juvenile idiopathic arthritis.

OBJECTIVE: To evaluate serum and synovial fluid (SF) levels of macrophage migration inhibitory factor (MIF) and in vitro MIF production by peripheral blood mononuclear cells (PBMCs) in patients with juvenile idiopathic arthritis (JIA). METHODS: Serum, SF, and culture supernatant levels of MIF were measured by enzyme-linked immunosorbent assay. Production of MIF by PBMCs was investigated by culturing PBMCs in the absence or presence of 2 different concentrations of concanavalin A. RESULTS: Serum MIF levels were increased in patients with JIA, and the highest levels were present in patients with systemic-onset JIA. In systemic-onset JIA, serum levels of MIF correlated with the persistence of systemic features and the number of active joints. PBMCs from patients with systemic-onset JIA, when cultured under unstimulated conditions or at suboptimal stimulation, released higher amounts of MIF compared with those from patients with oligoarticular-onset JIA or healthy controls. MIF levels in the SF of patients with systemic-onset JIA were significantly higher than those in patients with oligoarticular-onset JIA. In individual joints, in both systemic-onset JIA and oligoarticular-onset JIA, SF MIF levels were inversely correlated with the duration of the clinical remission induced by intraarticular administration of triamcinolone hexacetonide. CONCLUSION: MIF appears to be a relevant cytokine in the pathogenesis of JIA, particularly in systemic-onset JIA.

Adolescent↗

PubMed2002

Self epitopes shared between human skeletal myosin and Streptococcus pyogenes M5 protein are targets of immune responses in active juvenile dermatomyositis.

OBJECTIVE: To identify self T cell epitopes associated with proinflammatory immune responses and clinically active juvenile dermatomyositis (juvenile DM). The target of our search for relevant epitopes was represented by amino acid sequences shared between human skeletal myosin and Streptococcus pyogenes M5 protein. The long-term objective of the project is to identify suitable targets for immunotherapy of the disease. METHODS: We used computerized algorithms to identify putative agretopes on both the human myosin and Streptococcus M5 proteins. Direct binding assays for homolog peptides were used to confirm such predictions. Antigenicity and functional cross-reactivity were evaluated by cytotoxicity assays and by measurement of cytokine levels. Specific T cells were isolated by T cell capture, and T cell receptor (TCR) V(beta) gene usage was identified by reverse transcriptase-polymerase chain reaction. RESULTS: We identified peptides that are targets of disease-specific cytotoxic T cell responses. T cell reactivity against the self peptides correlates with clinical signs of early, active myositis. Such reactivity is accompanied by production of proinflammatory cytokines, which may contribute to the damage. T cell cross-recognition of bacterial and human homologs was shown functionally as well as by sorting peptide-specific T cells and identifying oligoclonal and largely overlapping TCR V(beta) gene usage. CONCLUSION: These findings represent the first identification of a self epitope in juvenile DM, providing a potential candidate for antigen-specific immune therapy.

Bacterial Proteins↗

PubMed2002

Macrophage activation syndrome.

Macrophage activation syndrome (MAS) is a serious complication of childhood systemic inflammatory disorders that is thought to be caused by excessive activation and proliferation of T lymphocytes and macrophages. Recent findings in hemophagocytic lymphohistiocytosis, a disease that is clinically similar to MAS, highlight the possible pathogenetic role of a defective function of perforin, a protein involved in the cytolytic processes and control of lymphocyte proliferation. Although the clinical features of MAS have been well documented, early diagnosis can be difficult. Measurement of the serum ferritin level may assist in the diagnosis and may be a useful indicator of disease activity, therapy response, and prognosis. The recognition that MAS belongs to the secondary or reactive hemophagocytic syndromes has led to the proposal to rename it according to the contemporary classification of histiocytic disorders. Cyclosporin A has been found effective in patients with corticosteroid-resistant MAS. A recent report has suggested that etanercept may be a useful adjunctive therapeutic agent.

Arthritis, Juvenile↗