Rheumatoid Arthritis: Magni-Manzoni S

Ravelli A, Magni-Manzoni S, Pistorio A, Besana C, Foti T, Ruperto N, Viola S, Martini A. · Department of Pediatrics, Division of Pediatrics II, University of Genoa, Istituto G. Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy. · J Pediatr. · Pubmed #15870661 No free full text.

Abstract: OBJECTIVE: To develop diagnostic guidelines for macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (S-JIA). STUDY DESIGN: We followed the classification criteria approach that is based on the comparison of patients with the index disease with patients with a "confusable" disease. The former group included 74 patients with S-JIA-associated MAS reported in the literature or seen by the authors; the latter group included 37 patients with S-JIA who had 51 instances of "high disease activity" seen by the authors. The relative power of clinical, laboratory, and histopathologic variables in discriminating patients with MAS from patients with high disease activity was evaluated by calculating the sensitivity rate, specificity rate, area under the receiver operating characteristic curve, and diagnostic odds ratio (DOR). The combinations of variables that led to best separation between patients and control subjects were identified through "the number of criteria present" method. RESULTS: The strongest clinical discriminators were hemorrhages (DOR = 67) and central nervous system dysfunction (DOR = 63); the strongest laboratory discriminators were decreased platelet count (DOR = 1092), increased aspartate aminotransferase (DOR = 247), leukopenia (DOR = 70), and hypofibrinogenemia (DOR = 165). The best separation between patients and control subjects occurred when any 2 or more laboratory criteria (DOR = 1309) were simultaneously present; the second best performance was provided by the presence of any 2, 3, or more clinical and/or laboratory criteria (DOR = 765 and 743, respectively). CONCLUSION: We identified preliminary diagnostic guidelines for MAS complicating S-JIA. These guidelines deserve prospective validation.

Bartoli M, Tarò M, Magni-Manzoni S, Pistorio A, Traverso F, Viola S, Magnani A, Gasparini C, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy. · Ann Rheum Dis. · Pubmed #17660217 No free full text.

Abstract: OBJECTIVE: To investigate the relationship between the magnitude of clinical response in the first 6 months of methotrexate (MTX) therapy and long-term outcome in children with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts of 125 JIA patients who were started with MTX and then followed for at least 5 years were reviewed. Based on the level of American College of Rheumatology (ACR) Pediatric response at 6 months, patients were divided in four mutually exclusive groups: (1) non-responders, (2) responders at 30%, (3) responders at 50%, and (4) responders at 70%. The long-term outcome in each response group was evaluated by calculating the percentage change in active and restricted joint counts from baseline to 1, 2 and 5 years and the frequency of inactive disease at 5 years. RESULTS: At 6 months, 42 patients were classified as non-responders, 24 as 30% responders, 26 as 50% responders, and 33 as 70% responders. Patients who had achieved a 70% response showed a significantly greater percentage improvement in active joint count between baseline to 5 years compared with non-responders and 30% responders, and a significantly greater percentage improvement in restricted joint count between baseline to 5 years compared with 30% responders. The 70% responders also had a greater frequency of inactive disease at 5 years compared with 30% responders, CONCLUSIONS: Our results show that the achievement of an ACR Pediatric 70 response at 6 months after start of MTX therapy predicts a more favorable long-term outcome of patients with JIA.

Ravelli A, Moretti C, Temporini F, Rossi F, Magni-Manzoni S, Pistorio A, Martini A. · Pediatria II, IRCCS G. Gaslini, Università di Genova, Italy. · Clin Exp Rheumatol. · Pubmed #12175118 No free full text.

Abstract: OBJECTIVE: To investigate the efficacy and safety of a combination therapy with methotrexate (MTX) and cyclosporine A (CyA) in patients with juvenile idiopathic arthritis (JIA) who were refractory to MTX as a single second-line agent. METHODS: Seventeen consecutive patients with JIA who had refractory polyarthritis despite a minimum of 6 months of MTX as a single second-line agent at the dose of 15 to 25 mg/m2/week were continued with MTX with the addition of CyA (4 mg/kg/day) for 6 to 30 months (median 10 months) were analyzed. The clinical response to therapy was assessed through the preliminary definition of improvement in JIA. RESULTS: At the end of the treatment, as compared to the time when CyA was added to MTX, 8 patients (47%) met the 30% definition of improvement; among them 5 (29%) met the 70% definition of improvement, and 2 (12%) achieved complete disease control. Seven patients (41%) experienced side effects: 4 gastrointestinal discomfort, 1 liver transaminase elevation, and 2 increase > or = 30% in the serum creatinine concentration. No patients was discontinued from combination therapy due to adverse events. CONCLUSION: In our JIA patients who were refractory to MTX as a single second-line agent, the addition of CyA was associated with a significant clinical improvement in roughly half of the patients.

Consolaro A, Ruperto N, Bazso A, Pistorio A, Magni-Manzoni S, Filocamo G, Malattia C, Viola S, Martini A, Ravelli A, Anonymous00061. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, and the Università degli Studi di Verona, Verona, Italy. · Arthritis Rheum. · Pubmed #19405003 No free full text.

Abstract: OBJECTIVE: To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). METHODS: The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). RESULTS: The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. CONCLUSION: The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.

Magnani A, Pistorio A, Magni-Manzoni S, Falcone A, Lombardini G, Bandeira M, Rossi F, Sala I, Martini A, Ravelli A. · Istituto G. Gaslini, Largo G. Gaslini 5, 16147 Genova, Italy. · J Rheumatol. · Pubmed #19208600 No free full text.

Abstract: OBJECTIVE: To investigate whether the achievement of inactive disease in the first 5 years predicts a more favorable outcome of children with juvenile idiopathic arthritis (JIA). METHODS: We reviewed clinical charts of 123 patients who started taking methotrexate, were followed for at least 5 years, and received a yearly assessment in the first 5 years. At each yearly visit, the presence of inactive disease was assessed. Patients were divided into 3 groups: (1) patients who never reached inactive disease; (2) patients who reached inactive disease in only 1 visit; and (3) patients who reached inactive disease in > or = 2 visits. Outcome was evaluated after 6 to 18 years (median 7.1 yrs) by assessing the following clinical measures: restricted joint count, Childhood Health Assessment Questionnaire (CHAQ), Juvenile Arthritis Damage Index (JADI), and Poznanski score of radiographic damage. RESULTS: In the first 5 years, 62 patients (50.4%) were noted to have active disease at their yearly visit, 40 patients (32.5%) were noted to have inactive disease only once, and 21 patients (17.1%) were noted to have inactive disease in > or = 2 visits. Patients who achieved inactive disease 1 or more times had lower restricted joint count (p = 0.007) and JADI-Articular score (p = 0.004) at last followup visit than those who never reached such a state. A similar trend, although not significant, was observed for CHAQ and Poznanski score of radiographic damage. CONCLUSION: Attainment of the state of inactive disease at least once in the first 5 years was found to be associated with less longterm joint damage and with a trend toward less functional impairment.

Bazso A, Consolaro A, Ruperto N, Pistorio A, Viola S, Magni-Manzoni S, Malattia C, Buoncompagni A, Loy A, Martini A, Ravelli A, Anonymous00093. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Largo G. Gaslini 5, 16147 Genova, Italy. · J Rheumatol. · Pubmed #19208532 No free full text.

Abstract: OBJECTIVE: To develop and test reduced joint counts in children with juvenile idiopathic arthritis (JIA). METHODS: Four reduced joint counts including 45, 35, 27, and 10 joints were devised by a panel of experienced pediatric rheumatologists, who selected the joints to be included based on the ease of technical assessment, functional relevance, and frequency of involvement. Three large samples of patients with JIA (total n=4353) who had a detailed joint assessment available were used to develop and test reduced joint counts. Performance of reduced counts was examined by comparing their Spearman correlation with the standard (i.e., complete) joint count. Construct validity was evaluated by calculating Spearman correlation with other JIA outcome measures. Responsiveness to clinical change was determined through the standardized response mean (SRM). RESULTS: Spearman correlations of reduced joint counts with the whole joint count and with the other JIA outcome measures were comparable, revealing that they had similar ability to serve as surrogate for the whole joint count and construct validity. Responsiveness to clinical change was also comparable across reduced counts (SRM 0.83-1.09 for active joint counts and 0.63-0.81 for restricted joint counts). Based on these results and considering the relative feasibility of the different counts, the 27-joint reduced count is proposed for use in JIA. This joint count includes the cervical spine and the elbow, wrist, metacarpophalangeal (from first to third), proximal interphalangeal, hip, knee, and ankle joints. CONCLUSION: Reduced joint counts appear to be as reliable as standard joint counts in assessment of the severity of joint disease and its change over time in children with JIA.

Solari N, Viola S, Pistorio A, Magni-Manzoni S, Vitale R, Ruperto N, Ullmann N, Filocamo G, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #18975357 No free full text.

Abstract: OBJECTIVE: To investigate the disease outcomes of a cross-sectional sample of children with longstanding juvenile idiopathic arthritis (JIA) seen between September 2002 and December 2006, and to provide a benchmarking of outcomes obtained with current treatment. METHODS: All consecutive patients were included if they met the following criteria: diagnosis of JIA, disease duration > or = 5 years, and informed consent. Outcome assessments included disease activity, inactive disease, minimal disease activity, pain, physical function, health-related quality of life (HRQOL), auxometric measurements, and articular and extraarticular damage. RESULTS: A total of 310 patients were included. At study visit, patients had on average a low level of disease activity. However, only 21.8% met the criteria for inactive disease, and less than 50% met the definition of minimal disease activity. Additionally, 19.2% had moderate to severe Childhood Health Assessment Questionnaire disability and 3.6% were in Steinbrocker class III-IV. Approximately 10% had major impairment in HRQOL. A total of 34.2% had damage in > or = 1 joint or joint group and 26.1% showed extraarticular damage. Of the 125 patients who underwent a wrist radiograph, 35.2% had significant structural damage and 8.7% had growth retardation. CONCLUSION: Our patients had on average a low level of disease activity, little or no physical disability, and a satisfactory HRQOL. However, a sizable proportion of patients had persistently active disease, impaired function, and damage. These findings underscore the critical need for treatments and treatment strategies that have the ability to better control disease activity and to reduce the development of disease-related morbidities.

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.

Magni-Manzoni S, Ruperto N, Pistorio A, Sala E, Solari N, Palmisani E, Cugno C, Bozzola E, Martini A, Ravelli A. · Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy. · Arthritis Rheum. · Pubmed #18668599 No free full text.

Abstract: OBJECTIVE: To develop and validate a definition of minimal disease activity (MDA) in patients with juvenile idiopathic arthritis (JIA). METHODS: The clinical charts of JIA patients followed over a 16-year period were reviewed to identify visits with high disease activity and MDA, defined on the basis of therapeutic decisions made by the attending physician. For each JIA activity measure recorded at the time of the visit, the cutoff value that best identified states of MDA was calculated by means of the area under the receiver operating characteristic curve analysis. A definition of MDA for oligoarthritis and polyarthritis was set up after testing the relative power of each variable in a multivariate analysis. Validation procedures included assessment of discriminant and construct validity. RESULTS: The definition that resulted from the analyses led to establish that a state of MDA could be defined as the presence of a physician global assessment < or =2.5 cm and a swollen joint count of 0 in patients with oligoarthritis; and as the presence of a physician global assessment < or =3.4 cm, a parent global assessment < or =2.1 cm, and a swollen joint count < or =1 in patients with polyarthritis. Validation procedures demonstrated that the MDA definition had good discriminant and construct validity in the context of both observational studies and controlled trials. CONCLUSION: We developed a preliminary definition of MDA in patients with JIA that represents a useful treatment target state and is proposed for inclusion as an outcome measure in future observational studies and clinical trials in patients with JIA.

Magni-Manzoni S, Pistorio A, Labò E, Viola S, Garcia-Munitis P, Panigada S, Visconti C, Buoncompagni A, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico S. Matteo, Pavia, Italy. · Ann Rheum Dis. · Pubmed #17965116 No free full text.

Abstract: OBJECTIVE: To describe the longitudinal course of physical functioning in children with juvenile idiopathic arthritis (JIA) and identify predictors of long-term functional impairment. METHODS: Between January 1987 and December 2002, 227 patients had two or more functional ability questionnaires completed by a parent. The total number of questionnaires was 1356 and the follow-up between first and last questionnaire administration was 949.7 patient years. At each questionnaire administration, patients were assigned to one of three functional disability states (1 = no disability; 2 = mild to moderate disability; 3 = severe disability), based on their functional ability score. Predictor variables included sex, onset age, JIA category, age at visit, disease duration, presence of antinuclear antibodies, joint counts, acute phase reactants and initial disability state. RESULTS: Despite patient variability in the course of physical functioning, the following three longitudinal patterns were observed: (1) a stable state of disability throughout the entire study period, with continued absence of disability in 27.8% of patients and persistently moderate disability in 3.5% of patients; (2) a steady improvement (22.9% of patients) or deterioration (5.7% of patients) in disability over time; (3) a fluctuating course of disability, with deterioration and improvement (40.1% of patients). Younger age at disease onset and a greater restricted joint count were the strongest predictors of long-term functional impairment. CONCLUSION: A wide within-patient and between-patient variability in the longitudinal course of functional disability was found. Children with early disease onset and a greater number of restricted joints had the highest risk of developing long-term physical disability.

Ravelli A, Ioseliani M, Norambuena X, Sato J, Pistorio A, Rossi F, Ruperto N, Magni-Manzoni S, Ullmann N, Martini A. · Università degli Studi di Genoa, and IRCCS, Istituto G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17763418 links to  free full text

Abstract: OBJECTIVE: To develop adapted versions of the Sharp/van der Heijde radiographic scoring system for use in juvenile idiopathic arthritis (JIA), and to investigate their validity in JIA patients with polyarticular disease. METHODS: The study group comprised 177 patients with polyarticular JIA. Radiographs of the wrist/hand of each patient were obtained at baseline (first observation) and then at 1, 3, 5, 7/8, and 10 years and were assessed independently by 2 pediatric rheumatologists according to different adaptations of the Sharp/van der Heijde method. To facilitate score assignment, the radiograph for each patient was compared with a bone age-related standard. Validation procedures included analysis of reliability, construct validity, and score progression over time. RESULTS: Interobserver and intraobserver agreement on longitudinal score values and score changes was good for all of the adapted scoring versions (intraclass correlation coefficient >0.85). Score changes over time were moderately to strongly correlated with the clinical indicators of long-term joint damage and with the amount of long-term radiographic damage as measured with the carpo:metacarpal ratio, thereby demonstrating good construct validity. A steady increase in scores over time was observed, with joint space narrowing being the most common form of damage throughout the disease course. The inclusion of 5 new areas appeared to increase the overall construct validity of erosion scores. CONCLUSION: Our results show that the adapted versions of the Sharp/van der Heijde score are reliable and valid for the assessment of radiographic progression in patients with JIA.

Filocamo G, Sztajnbok F, Cespedes-Cruz A, Magni-Manzoni S, Pistorio A, Viola S, Ruperto N, Buoncompagni A, Loy A, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17665481 links to  free full text

Abstract: OBJECTIVE: To develop and validate a new short and simple measure of physical function in children with juvenile idiopathic arthritis (JIA). METHODS: The Juvenile Arthritis Functionality Scale (JAFS) is a 15-item questionnaire that explores physical function in 3 body areas (lower limbs, hand/wrist, and upper segment). Validation of the Italian version of the instrument was accomplished by evaluating 211 consecutive JIA patients ages 2.2-18 years. The instrument's feasibility, face and content validity, construct and discriminative ability, internal consistency, interrater reliability, and responsiveness to clinical change were examined. JAFS psychometric properties were compared with those of the Childhood Health Assessment Questionnaire (C-HAQ). RESULTS: The JAFS was found to be feasible and to possess both face and content validity. The JAFS score correlated with most of the other JIA outcome measures in the range predicted, thereby demonstrating good construct validity, and discriminated well among different levels of disability. The internal consistency (Cronbach's alpha) was 0.82. The intraclass correlation coefficients between raters (mothers, fathers, and children) and between reported and observed level of function ranged from 0.65 to 0.84. The JAFS revealed fair responsiveness, with a standardized response mean ranging from 0.42 to 0.56. Comparison with the C-HAQ indicated that the JAFS may be superior in terms of construct validity and reliability, and at least as good in terms of discriminant validity and responsiveness. CONCLUSION: The JAFS exhibited good reliability, construct validity, and discriminative ability and fair responsiveness, and is therefore a valid instrument for the assessment of physical function in children with JIA.

Palmisani E, Solari N, Magni-Manzoni S, Pistorio A, Labò E, Panigada S, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17139659 links to  free full text

Abstract: OBJECTIVE: To compare the correlation between juvenile idiopathic arthritis (JIA) measures of disease activity and damage in patients with early and late disease. METHODS: Three cohorts of patients with JIA disease duration < or =1 year (early disease, n = 70), 5-9.9 years (advanced disease, n = 114), and > or =10 years (longstanding disease, n = 39) were studied. Measures included physician's global assessment of overall disease activity (MD global), parent's global assessment of the child's well-being (parent global) and pain (parent pain), joint counts, Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate, C-reactive protein level, and Poznanski score of radiographic damage. RESULTS: In all cohorts, the MD global assessment was generally well correlated with the other variables, except the Poznanski score. The parent global assessment was correlated strongly with the parent pain assessment and moderately with the CHAQ irrespective of disease duration. Correlations between the CHAQ and the joint counts were low in early disease, moderate in advanced disease, and high to moderate in longstanding disease. Correlation between the CHAQ and the Poznanski score was low in early and advanced disease and moderate in longstanding disease. The Poznanski score was highly correlated with the number of joints with restricted motion in longstanding disease. CONCLUSION: We found important differences in the level of correlation between JIA measures of activity and damage in patients with different lengths of disease duration. These findings have important implications for clinical trials because they indicate that the responsiveness of some variables and their correlation with other variables change as disease duration changes.

Rossi F, Di Dia F, Galipò O, Pistorio A, Valle M, Magni-Manzoni S, Ruperto N, Tomà P, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico G Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #17013855 links to  free full text

Abstract: OBJECTIVE: To investigate the applicability of the Sharp and Larsen scoring methods for radiographic damage in juvenile idiopathic arthritis (JIA). METHODS: Wrist/hand radiographs of 25 patients with polyarthritis obtained at first observation and then yearly for 4-5 years were assessed independently by 2 pediatric rheumatologists according to the Sharp and Larsen methods. To facilitate score assignment, each patient radiograph was compared with a bone age-related standard. A third pediatric rheumatologist measured the Poznanski score, and a pediatric radiologist provided a semiquantitative assessment of radiographic damage severity. RESULTS: Interobserver and intraobserver agreement on longitudinal scores were good for both Sharp and Larsen methods, with intraclass correlation coefficient >0.9. Agreement on change assessment was good for the Sharp method and moderate for the Larsen method. Both methods yielded a steady increase in scores during the study, with score change being more marked in the first year. Sharp and Larsen scores were highly correlated (r(s) = 0.96). Correlations of both scores with the Poznanski score were moderate to high (r(s) from -0.62 to -0.72). Radiologist score was correlated at borderline-high level with both Sharp (r(s) = 0.70) and Larsen (r(s) = 0.71) scores. Sharp and Larsen score change from baseline to final visit was moderately to highly correlated with the number of joints with active arthritis and restricted motion and the Childhood Health Assessment Questionnaire score at final visit. CONCLUSION: Our results demonstrate that the Sharp and Larsen scoring systems are potentially reliable and valid for assessment of radiographic progression in patients with polyarticular JIA.

Garcia-Munitis P, Bandeira M, Pistorio A, Magni-Manzoni S, Ruperto N, Schivo A, Martini A, Ravelli A. · Unità Operativa Pediatria II, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Università di Genova, Largo G. Gaslini 5, 16147 Genoa, Italy. · Arthritis Rheum. · Pubmed #16583392 links to  free full text

Abstract: OBJECTIVE: To investigate the level of agreement between patients, mothers, fathers, and physicians in rating pain intensity in juvenile idiopathic arthritis (JIA), and to identify factors explaining discrepancies between raters. METHODS: Ninety-four children with JIA and their mothers and fathers were asked to rate independently the intensity of present pain and pain in the previous week on a visual analog scale. The physicians rated pain intensity after physical examination. Agreement between raters was determined using intraclass correlation coefficient and Bland and Altman method. Correlations of explanatory variables with discordance in rating pain intensity were determined by univariate and multivariate analyses. Explanatory variables included sex, age, JIA category, disease duration, results of study ratings, joint inflammation measures, and erythrocyte sedimentation rate. RESULTS: Agreement in rating present pain was moderate between children and mothers, but was poor between children and fathers and children and physicians. The agreement in rating pain in the previous week was moderate between children and mothers and children and fathers. Mother-father agreement was good. Parents and physicians agreed at a moderate level. In multiple regression analyses, only intensity of present pain was significantly associated with discordance within child-mother, child-father, and child-physician dyads. CONCLUSION: Children's ratings of pain were only in moderate agreement with those of their parents and were in poor agreement with those of the physicians, whereas the father and mothers agreed at a good level. The intensity of pain was the strongest determinant of discordance between children and other raters.

Bandeira M, Falcone A, Pistorio A, Ruperto N, Magni-Manzoni S, Buoncompagni A, Sala E, Loy A, Martini A, Ravelli A. · Departimento di Pediatria, Università di Genova, Istituto di Ricovero e Cura a Carattee Scientifico G. Gaslini, Genova, Italy. · Rheumatology (Oxford). · Pubmed #16234273 links to  free full text

Abstract: OBJECTIVE: To develop a scoring system for juvenile idiopathic arthritis (JIA) in which joints are weighted to reflect their relative importance to children's function and to examine whether weighting increases the correlation of joint counts with subjective and laboratory outcome measures. METHODS: A weighted joint score was devised by a panel of experienced paediatric rheumatologists, who assigned a weight from 1 (not very important) to 10 (essential for key functional activities) to each joint based on its functional importance to children's physical and daily activities. The associations of simple and weighted counts of swollen, tender, limited and active joints with the physician's global assessment of overall disease activity, the parent's global assessment of the child's overall well-being and intensity of pain, the Childhood Health Assessment Questionnaire (C-HAQ), the Child Health Questionnaire (CHQ) and the erythrocyte sedimentation rate were compared using Spearman's correlation analysis in 60 unselected patients seen in the clinic and in 61 consecutive patients with disease duration > or = 5 yr. RESULTS: Weighted counts of swollen and active joints yielded greater correlation with the physician's global assessment than did simple counts. The correlation of weighted counts of swollen, painful and active joints with the parent's assessment of overall well-being and intensity of pain was superior to that provided by simple counts. Weighting increased most of the correlations between joint counts and the C-HAQ score and the physical component of the CHQ. CONCLUSION: Weighting improves the information provided by joint counts on the severity of arthritis and its impact on patients' well-being.

Felici E, Novarini C, Magni-Manzoni S, Pistorio A, Magnani A, Bozzola E, Buoncompagni A, Martini A, Ravelli A. · Dipartimento di Pediatria, Università di Genova, Unità Operativa Pediatria II, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genova, Italy. · J Rheumatol. · Pubmed #16142881 No free full text.

Abstract: OBJECTIVE: To describe the patterns and time course of arthritis in patients with antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA). METHODS: We identified patients followed during a 16-year period who had JIA by ILAR criteria, were ANA-positive (i.e., had >or= 2 positive ANA test results at titer >or= 1:160), and had a disease duration >or= 2 years. Demographic and clinical features, including ILAR category and cumulative number and type of joints affected over time, were recorded. RESULTS: A total of 195 patients were studied. The ILAR category was oligoarthritis in 159 patients and rheumatoid factor-negative polyarthritis in 36 patients. The cumulative rate of polyarticular extension in patients with oligoarticular onset was 26%, 38%, 45%, 49%, and 51% at 1, 2, 3, 4, and 5 years, respectively. At disease onset, most patients had monoarthritis and 95% had <or= 4 joints affected. The knee was the most frequently involved of all joints, followed by the ankle and proximal interphalangeal joints. Among patients with oligoarticular onset, the presence of ankle (in case of monoarticular disease) and/or wrist involvement in the first 6 months was more common in those who progressed to polyarthritis. CONCLUSION: The majority of our ANA-positive patients, including most of those who later developed polyarthritis, had monoarthritis at disease onset. Among patients with oligoarticular onset, polyarticular extension occurred in around 50% of cases within the first 3-4 years after disease onset, and tended to be less likely thereafter. The early occurrence of ankle and/or wrist disease may indicate a higher likelihood of arthritis progression.

Viola S, Felici E, Magni-Manzoni S, Pistorio A, Buoncompagni A, Ruperto N, Rossi F, Bartoli M, Martini A, Ravelli A. · Università di Genova, IRCCS G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #15986372 links to  free full text

Abstract: OBJECTIVE: To develop and validate a clinical measure of articular and extraarticular damage in patients with juvenile idiopathic arthritis (JIA). METHODS: The Juvenile Arthritis Damage Index (JADI), which is derived from physical examination and a brief review of the patient's clinical history, is composed of 2 parts: assessments of articular damage (JADI-A) and extraarticular damage (JADI-E). Instrument validation was accomplished by evaluating 158 JIA patients with disease duration of at least 5 years, seen consecutively over 21 months. The instrument's feasibility, face and content validity, construct and discriminative ability, internal consistency, and interrater reliability were examined. RESULTS: Among the 158 JIA patients, 47% and 37% had articular and extraarticular damage, respectively. The JADI was found to be feasible and to possess both face and content validity. The JADI-A score correlated highly with the number of joints with limited range of motion (Spearman's r [r(S)] = 0.72) and correlated moderately with the Childhood Health Assessment Questionnaire score (r(S) = 0.41), Steinbrocker functional classification (r(S) = 0.50), and Poznanski's score of radiographic damage (r(S) = -0.54), thereby demonstrating good construct validity. Correlations with the JADI-E score were lower, owing to the heterogeneity of its items. The JADI-A discriminated well among different levels of disability. The internal consistency (Chronbach's alpha) of the JADI-A and JADI-E was 0.93 and 0.59, respectively. The intraclass correlation coefficients between pairs of independent observers ranged from 0.85 to 0.97. CONCLUSION: The JADI exhibited good reliability, construct validity, and discriminative ability and is therefore a valid instrument for the assessment of long-term damage in patients with JIA, in the context of both clinical management and research settings.

Magni-Manzoni S, Cugno C, Pistorio A, Garay S, Tsitsami E, Gasparini C, Viola S, Ruperto N, Martini A, Ravelli A. · Dipartimento di Pediatria, Università di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy. · Clin Exp Rheumatol. · Pubmed #15971436 No free full text.

Abstract: OBJECTIVE: To compare the responsiveness of clinical measures in the assessment of disease flare in patients with juvenile idiopathic arthritis (JIA). METHODS: The clinical records of all consecutive patients with JIA who were diagnosed between 1995 and 2000 were retrospectively reviewed. In each patient, all visits made during follow-up were analyzed and those meeting the criteria for disease flare were recorded. The definition of flare was based on the therapeutic alterations made by the attending physician. Responsiveness of JIA clinical measures to relevant increase in disease activity (a flare) was evaluated by assessing the score change of each measure from a visit made 6 (+/- 3) months before a flare and the flare visit. Responsiveness statistics included the standardized response mean (SRM) and the effect size (ES). RESULTS: A total of 115 patients, who were followed for 0.5 to 6.2 years (mean 2.8 years), were studied. During follow-up, 51 patients (44%) experienced 1 or more disease flares, with the total number of flares being 75. Strong responsiveness (ES and SRM > or = 0.8) to increase in disease activity was demonstrated by the physician's and parent's global assessments, the global articular severity score, and the morning stiffness. The active, swollen and painful joint counts, the swelling, pain on motion/tenderness and limited range of motion (LROM) scores, and the erythrocyte sedimentation rate revealed moderate responsiveness (ES and SRM > or = 0.5). The poorest performances (ES and/or SRM < 0.5) were provided by the parent's assessment of pain, the functional ability tool, the number of joints with LROM, the LROM score, the C-reactive protein, the white blood cell and platelet count, and the hemoglobin level. CONCLUSION: Our analysis suggests that the swollen or painful joint counts are better suited than the count of joints with LROM for the assessment of disease flare in patients with JIA.

Ravelli A, Felici E, Magni-Manzoni S, Pistorio A, Novarini C, Bozzola E, Viola S, Martini A. · IRCCS G. Gaslini, Genoa, Italy. <> · Arthritis Rheum. · Pubmed #15751057 links to  free full text

Abstract: OBJECTIVE: We recently hypothesized that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), the presumably homogeneous patient group characterized by early onset of disease, a female predilection, the presence of antinuclear antibodies (ANA), asymmetric arthritis, and the risk for iridocyclitis is classified into different categories. We sought to investigate whether ANA-positive patients belonging to the ILAR categories of oligoarthritis and rheumatoid factor (RF)-negative polyarthritis share homogeneous features and to compare these features with those of ANA-negative patients with JIA in the same categories. METHODS: We identified patients who were followed up during a 15-year period. All patients had JIA according to the ILAR criteria, with oligoarticular or polyarticular onset. ANA positivity was defined as 2 or more positive results at a titer of >or=1:160. Demographic and clinical features, including the number of joints involved over time and measures of JIA severity at the last followup visit, were recorded retrospectively. RESULTS: A total of 256 patients were included: 190 were ANA positive (109 had persistent oligoarthritis, 48 had extended oligoarthritis, and 33 had RF-negative polyarthritis), and 66 were ANA negative (35 had RF-negative polyarthritis, and 31 had oligoarthritis). All patients who were positive for ANA were similar in terms of age at disease presentation, female-to-male ratio, and frequency of symmetric arthritis and iridocyclitis. Compared with ANA-positive patients with polyarticular disease, ANA-negative patients with polyarticular arthritis were older at disease presentation and had a lower frequency of iridocyclitis, a higher frequency of symmetric arthritis, a greater cumulative number of joints affected over time, and a different pattern of joint disease, with a greater frequency of shoulder and hip involvement. The strong relationship between the presence of ANA and younger age at disease presentation, asymmetric arthritis, and development of iridocyclitis was confirmed by multivariate regression analysis. CONCLUSION: Our results support the hypothesis that patients with similar characteristics are currently classified into different JIA categories. The value of ANA positivity as a possible modifier of the current classification system deserves consideration.

Moretti C, Viola S, Pistorio A, Magni-Manzoni S, Ruperto N, Martini A, Ravelli A. · Dipartimento di Pediatria, Università di Pavia, Istituto di Ricovero e Cura a Carattiere Scientifico, Policlinico S. Matteo, Pavia, Italy. · Ann Rheum Dis. · Pubmed #15647433 links to  free full text

Abstract: OBJECTIVES: To compare the relative responsiveness of condition specific measures with that of a generic health status instrument for outcome assessment of intra-articular corticosteroid (IAC) injection in patients with juvenile idiopathic arthritis (JIA). METHODS: We examined 44 consecutive patients with oligoarticular JIA before an IAC injection and after 6 months. Condition specific measures included physician's and parent's global assessments, the Childhood Health Assessment Questionnaire (CHAQ), the articular indices, and laboratory indicators of systemic inflammation. The generic health status instrument was the Child Health Questionnaire (CHQ), which was divided into two parts: the physical score (PhS) and the psychosocial score (PsS). Responsiveness statistics were the standardised response mean, the effect size, and Guyatt's method. The discriminative ability of the clinical measures in distinguishing improved from non-improved patients was evaluated with the correlation and the receiver operating characteristic methods, using the physician's and the parent's judgements of the treatment outcome as external criteria. RESULTS: All responsiveness statistics and discriminative ability assessments consistently ranked the physician's global assessment of the disease activity as the most responsive measure. The CHQ-PhS revealed superior ability in detecting baseline versus 6 month change compared with the CHAQ and the CHQ-PsS; both summary scales of the CHQ revealed better discriminative ability than the CHAQ. CONCLUSIONS: The physician's global assessment of the disease activity proved the most responsive outcome measure in our patients with JIA. The relative evaluative properties of the generic health status instrument and the CHAQ should be further investigated.

Cassone R, Falcone A, Rossi F, Magni-Manzoni S, Felici E, Buoncompagni A, Martini A, Ravelli A. · Dipartimento di Pediatria, Università di Genova, Pediatria II, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genova, Italy. · Clin Exp Rheumatol. · Pubmed #15485021 No free full text.

Abstract: OBJECTIVE: To describe the clinical and radiographic features of a group of juvenile idiopathic arthritis (JIA) patients who developed unilateral destructive wrist synovitis. METHODS: All wrist radiographs performed yearly between 1986 and 2002 in JIA patients who had wrist involvement were retrospectively reviewed to identify patients who had unilateral erosive wrist synovitis, defined as a difference of at least -3 units in the Poznanski score between the affected wrist and the unaffected wrist, with the Poznanski score in the unaffected wrist being > -2 units throughout the follow-up period. Clinical and radiographic data obtained during follow-up were recorded for all patients. RESULTS: Of a total of 250 patients for whom we had approximately 900 wrist radiographs, 6 patients were found to have unilateral erosive wrist synovitis. The JIA onset subtype was oligoarticular in 5 patients and polyarticular in 1 patient and the disease duration from presentation to the last follow-up visit ranged from 2 to 16 years. The arthritis course was polyarticular in all patients. Five patients had positive antinuclear antibodies (ANA) and 1 had positive rheumatoid factor (RF). At the last follow-up visit, all patients had some impairment of wrist function and 2 patients had wrist subluxation. There was a marked radiographic damage in all affected wrist, with the Poznanski ranging from -8.0 to -8.50 units in 3 patients and being -5.5, -3.1 and -2.4 units, respectively, in 3 patients. The severity of radiographic damage in the ANA-positive patients with the longest disease duration was comparable to that observed in the RF-positive patient. CONCLUSION: Unilateral erosive wrist synovitis seems to be uncommon in JIA. Patients with unilateral wrist synovitis may be at risk of a destructive course irrespective of the JIA onset subtype.

Magni-Manzoni S, Rossi F, Pistorio A, Temporini F, Viola S, Beluffi G, Martini A, Ravelli A. · Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo, Pavia, Italy. · Arthritis Rheum. · Pubmed #14674002 links to  free full text

Abstract: 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.

Tsitsami E, Bozzola E, Magni-Manzoni S, Viola S, Pistorio A, Ruperto N, Martini A, Ravelli A. · IRCCS Policlinico S. Matteo, Università di Pavia, Pavia, Italy. · Arthritis Rheum. · Pubmed #12910554 links to  free full text

Abstract: 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.

Meazza C, Travaglino P, Pignatti P, Magni-Manzoni S, Ravelli A, Martini A, De Benedetti F. · University of Pavia, IRCCS Policlinico San Matteo, Italy. · Arthritis Rheum. · Pubmed #11817596 links to  free full text

Abstract: 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.