Rheumatoid Arthritis: Cortis E

Cortis E, Insalaco A. · Department of Medicine, Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, Scientific Institute (IRCCS), Rome, Italy. · Acta Paediatr Suppl. · Pubmed #16801165 No free full text.

Abstract: Macrophage activation syndrome (MAS) is a rare and potentially lethal complication of chronic rheumatic diseases of childhood, in particular of systemic-onset juvenile idiopathic arthritis (s-JIA), resulting from uncontrolled activation and proliferation of T lymphocytes and macrophages. The onset, acute and dramatic, may mimic a flare of the underlying disease or a severe sepsis. Diagnosis is difficult and, until now, no specific criteria have been developed. Laboratory data show pancytopenia, coagulopathy, low ESR and low concentrations of serum albumin, and high levels of ferritin, liver enzymes and triglycerides. Activated macrophages are found in various organs, particularly in bone marrow. Most hypotheses on the mechanism underlying MAS are based on the data obtained in primary haemophagocytic lymphohistiocytosis (HLH), a genetic disease very similar to MAS. Prompt diagnosis is essential because prognosis is highly related to early treatment. The first approach was to use intravenous methylprednisolone pulse therapy; cyclosporin A was proposed in patients resistant to steroids. We describe nine patients affected by haemophagocytosis: seven patients developed MAS and two patients developed HLH. A child with s-JIA developed three episodes of MAS. After the third episode, as there was no improvement with pulses of methylprednisolone and cyclosporine, he was successfully given etanercept. CONCLUSION: Our data, together with a similar, published observation, suggest that the TNF inhibitor etanercept is potentially useful for obtaining remission in children not responding to steroids and cyclosporin A.

Ruperto N, Ravelli A, Falcini F, Lepore L, Buoncompagni A, Gerloni V, Bardare M, Cortis E, Zulian F, Sardella ML, Giovanni Strano C, Alessio M, Alpigiani MG, Migliavacca D, Pistorio A, Viola S, Martini A. · Laboratorio di Informatica Medica, IRCCS S. Matteo, Pavia, Italy. · Rheumatology (Oxford). · Pubmed #10342633 links to  free full text

Abstract: OBJECTIVE: To examine the responsiveness of the disease activity measures more commonly used in juvenile chronic arthritis (JCA) clinical trials. METHODS: Data were obtained from an open-label, non-controlled, multicentre trial designed to investigate the efficacy of methotrexate (MTX) in children with JCA. Outcome measures, including physician and parent global assessments, functional ability measures, articular variables, and laboratory indicators of systemic inflammation, were assessed at baseline and after 6 months of MTX treatment in 132 patients. Responsiveness of endpoint variables was evaluated by assessing the effect size (ES) and the standardized response median (SRM). RESULTS: Physician and parent global assessments were the more responsive instruments, showing ES and SRM above 1.0. Erythrocyte sedimentation rate, C-reactive protein, functional status measures and articular variables showed intermediate responsiveness. Morning stiffness, haemoglobin and platelet count were the least responsive instruments. CONCLUSION: The results of our analysis indicate that subjective estimations of the disease activity, either by the physician or parents, are the most responsive instruments in the assessment of the therapeutic response in children with JCA. The responsiveness of outcome measures in JCA should be further investigated in prospective controlled studies.

Nielsen S, Ruperto N, Gerloni V, Simonini G, Cortis E, Lepore L, Alpigiani MG, Zulian F, Corona F, Alessio M, Barcellona R, Gallizzi R, Rossi F, Magni-Manzoni S, Lombardini G, Filocamo G, Raschetti R, Martini A, Ravelli A, Anonymous00024. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genova, Italy. · Clin Exp Rheumatol. · Pubmed #18799107 No free full text.

Abstract: OBJECTIVE: To investigate the rate of radiographic progression, as measured with the carpo-metacarpal ratio (Poznanski score), during etanercept (ETN) therapy in children with polyarticular juvenile idiopathic arthritis (JIA). METHODS: Patients included in the Italian ETN registry who had a standard radiograph of both hands and wrists in the posteroanterior view made at start of treatment and after 1 year were included in the study. The clinical response was assessed by means of the ACR Pediatric definition of improvement. Radiographic progression was determined by calculating the change in the Poznanski score between the baseline and the 1-year radiographs. RESULTS: A total of 40 patients were studied. The frequency of ACR pediatric 30, 50, and 70 response at 1 year was 77%, 72%, and 50%, respectively. The median change in the Poznanski score between baseline and 1 year was + 0.3 units, meaning that, on average, patients experienced improvement in radiographic progression. CONCLUSION: Our pilot study provides evidence that ETN is potentially capable of reducing the progression of radiographic joint damage in JIA. This finding deserves confirmation in a controlled trial.

Céspedes-Cruz A, Gutiérrez-Suárez R, Pistorio A, Ravelli A, Loy A, Murray KJ, Gerloni V, Wulffraat N, Oliveira S, Walsh J, Penades IC, Alpigiani MG, Lahdenne P, Saad-Magalhães C, Cortis E, Lepore L, Kimura Y, Wouters C, Martini A, Ruperto N, Anonymous00360. · IRCCS G Gaslini, Pediatria II, Reumatologia, PRINTO, Largo Gaslini, 5, 16147 Genova, Italy. · Ann Rheum Dis. · Pubmed #17875547 No free full text.

Abstract: OBJECTIVES: To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX). METHODS: Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included. RESULTS: A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p<0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status. CONCLUSIONS: MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Chini L, Bardare M, Cancrini C, Angelini F, Mancia L, Cortis E, Finocchi A, Riccardi C, Rossi P. · Division of Immunology and Infectious Disease, Department of Pediatrics, Children's Hospital 'Bambino Gesù'- Tor Vergata University, School of Medicine, Rome, Italy. · Scand J Immunol. · Pubmed #12410801 No free full text.

Abstract: Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site.

Ruperto N, Ravelli A, Pistorio A, Malattia C, Viola S, Cavuto S, Alessio M, Alpigiani MG, Buoncompagni A, Corona F, Cortis E, Falcini F, Gerloni V, Lepore L, Sardella ML, Strano CG, Zulian F, Gado-West L, Tortorelli A, Fantini F, Martini A, Anonymous00072. · Laboratorio di Informatica Medica, IRCCS S. Matteo, Università di Pavia, Italy. · Clin Exp Rheumatol. · Pubmed #11510339 No free full text.

Abstract: We report herein the results of the cross-cultural adaptation and validation into the Italian language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Italian CHAQ was already published in the literature and was therefore revalidated while the Italian CHQ was fully cross culturally adapted with 3 forward and 3 backward translations, and than validated. A total of 1,192 subjects were enrolled: 404 patients with JIA (16% systemic onset, 31% polyarticular onset, 21% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 788 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Italian version of the CHAQ-CHQ are reliable, and valid tools for the functional, physical and psychosocial assessment of children with JIA.

Nobili V, Devito R, Comparcola D, Cortis E, Sartorelli MR, Marcellini M. · No affiliation provided · Ann Rheum Dis. · Pubmed #15608319 links to  free full text

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