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Angelo Ravelli

Publications and source records attributed to Angelo Ravelli.

At least 19 recordsLinked to original sources
PubMed2025

Stochastic epigenetic mutation profiles as biomarkers of clinical activity in juvenile idiopathic arthritis: a multi-omic machine learning approach for gene prioritization.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a rare autoimmune disease arising from a complex interplay between genetic and environmental factors. Epigenetic modifications such as DNA methylation (DNAm) have been described as potential mediators in gene-environment interactions, contributing to immune system dysregulation. Emerging evidence suggests that DNAm profiles also predict therapeutic responses in autoimmune diseases. This study aims to identify epigenetic biomarkers and epigenetic-driven gene expression changes associated with JIA clinical activity. METHODS: We reanalyzed a publicly available dataset of 44 JIA patients, with whole-genome DNAm and gene expression from CD4 + T cells measured at two points: at anti-TNF therapy withdrawal (T0) and eight months later (Tend). At Tend, 30 patients maintained inactive disease (ID) while 14 did not (NO ID). We investigated differences between ID and NO ID patients in the epigenetic mutation load and various epigenetic clocks through linear regression models, and prioritized genomic regions with significantly higher number of epimutations in NO ID patients through machine learning. RESULTS: We found a higher mutation load in NO ID than ID patients, both at T0 and at Tend, with the differences at Tend reaching statistical significance (p = 0.02). In contrast, we found no evidence of association between epigenetic clocks and JIA clinical activity. Using a multi-omic approach, we identified a List of candidate epigenetically-driven differentially expressed genes, 80 up-regulated and 77 down-regulated, in NO ID patients. Finally, comparing our candidate gene list with the Connectivity Map database, we identified new candidate potential therapeutic targets. Key findings were validated in independent datasets: DNAm profiles from CD4 + T cells (56 JIA patients, 57 controls) and transcriptomic data from PBMCs of JIA patients with active or inactive disease, confirming dysregulation of pathways such as TNF-α signaling via NF-kB and TGF-β signaling among others. CONCLUSIONS: We described a significant association of epigenetic mutations with JIA clinical activity, indicating that epigenetic changes might precede clinical symptoms and may serve as biomarkers for early disease monitoring. Further, our results shed light on biomolecular mechanisms of JIA, supporting the development of more effective treatments.

Humans↗
PubMed2006

Correlation between juvenile idiopathic arthritis activity and damage measures in early, advanced, and longstanding disease.

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.

Adolescent↗
PubMed2006

Use of the Sharp and Larsen scoring methods in the assessment of radiographic progression in juvenile idiopathic arthritis.

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.

Age Factors↗
PubMed2006

The Pediatric Rheumatology International Trials Organization/American College of Rheumatology provisional criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the definition of improvement.

OBJECTIVE: To use the Pediatric Rheumatology International Trials Organization (PRINTO) core set of outcome measures to develop a validated definition of improvement for the evaluation of response to therapy in juvenile systemic lupus erythematosus (SLE). METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries, each of whom had specific experience in the assessment of juvenile SLE patients, achieved consensus on 128 patient profiles as being clinically improved or not improved. Using the physicians' consensus ratings as the gold standard measure, the chi-square, sensitivity, specificity, false-positive and false-negative rates, area under the receiver operating characteristic curve, and kappa level of agreement for 597 candidate definitions of improvement were calculated. Only definitions with a kappa value greater than 0.7 were retained. The top definitions were selected based on the product of the content validity score multiplied by its kappa statistic. RESULTS: The definition of improvement with the highest final score was at least 50% improvement from baseline in any 2 of the 5 core set measures, with no more than 1 of the remaining worsening by more than 30%. CONCLUSION: PRINTO proposes a valid and reproducible definition of improvement that reflects well the consensus rating of experienced clinicians and that incorporates clinically meaningful change in core set measures in a composite end point for the evaluation of global response to therapy in patients with juvenile SLE. The definition is now proposed for use in juvenile SLE clinical trials and may help physicians to decide whether a child with SLE responded adequately to therapy.

Child↗
PubMed2006

Level of agreement between children, parents, and physicians in rating pain intensity in juvenile idiopathic arthritis.

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.

Adolescent↗
PubMed2006

Preliminary validation of clinical remission criteria using the OMERACT filter for select categories of juvenile idiopathic arthritis.

OBJECTIVE: To begin the validation process of the preliminary criteria for inactive disease (ID), clinical remission on medication (CRM), and clinical remission off medication (CR) in children with select forms of juvenile idiopathic arthritis (JIA). METHODS: We used the OMERACT filter paradigm to estimate the validity of the criteria within each of the filter's 3 components: truth, discrimination, and feasibility, in 5 categories of JIA: systemic arthritis, persistent and extended oligoarthritis, and rheumatoid factor-positive and negative polyarthritis. Data sources for determining validity estimates included a Delphi questionnaire survey sent to 246 pediatric rheumatologists in 34 countries, a consensus conference attended by 20 senior pediatric rheumatologists representing 9 countries, a retrospective chart review of 437 patients with JIA from 3 tertiary care clinics who had been followed between 4 and 22 years, and the literature. RESULTS: Truth component: face and content validity. These aspects of validity were largely established via the Delphi questionnaire exercise and the consensus conference. Using an 80% consensus level, participants felt that a set of non-redundant variables could effectively differentiate the clinical states of ID, CRM, and CR. Criterion validity could not be irrefutably established because no gold standard for inactive disease exists for JIA. As an alternative, published investigations of remission in JIA were used to estimate concurrent and convergent validity, as surrogates for criterion validity and as indicators of overall construct validity. Correlational analyses revealed the new criteria to have good construct validity. Discrimination component: the criteria demonstrated moderate to high levels of classification, prognosis, and responsiveness (sensitivity to change) using data from the chart review. Patients who were able to attain CR remained disease-free for substantially longer periods than did those who attained only ID or CRM. Responsiveness was evidenced by the ability of the criteria to allow movement of most patients between the disease states, consistent with what is known of the course of the disease. Feasibility component: Results of the Delphi and consensus conference produced a set of criteria that are easily, quickly, and inexpensively completed in the physician's office, and present minimal or no risk to the patient. CONCLUSION: The preliminary criteria demonstrated moderate to excellent validity characteristics in some, but not all components of the OMERACT filter. Prospective validation studies are under way.

Arthritis, Juvenile↗
PubMed2006

A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus.

OBJECTIVE: To devise a modified version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) for use in children and adolescents with systemic lupus erythematosus (SLE), based on the frequency and distribution of damage in patients with juvenile-onset SLE and the sources of damage that are most suitable for inclusion in a pediatric damage index. METHODS: In this cross-sectional study, damage was assessed through the SDI. Clinical assessments included evaluation of growth failure and delayed puberty, which were believed to be important sources of damage that are not incorporated in the SDI but should be included in a pediatric version of the instrument. RESULTS: A total of 1,015 patients with juvenile-onset SLE in 39 countries were enrolled in the study. Of these, 405 patients (39.9%) had an SDI score of > or =1 (mean +/- SD score 0.8 +/- 1.4). Renal damage (13%), neuropsychiatric damage (10.7%), and musculoskeletal damage (10.7%) were observed most frequently, followed by ocular damage (8.2%) and skin damage (7.6%). Growth failure and delayed puberty were recorded in 15.3% and 11.3% of patients, respectively. A pediatric version of the SDI was devised, with inclusion of growth failure and delayed puberty as new domains. CONCLUSION: We propose a modified version of the SDI for use in patients with juvenile-onset SLE. This new instrument warrants prospective validation in other populations of patients seen in different clinical or research settings.

Adolescent↗
PubMed2006

Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database.

OBJECTIVE: To determine the clinical and immunologic features of systemic sclerosis (SSc) in a large group of children and describe the clinical evolution of the disease and compare it with the adult form. METHODS: Data on 153 patients with juvenile SSc collected from 55 pediatric rheumatology centers in Europe, Asia, and South and North America were analyzed. Demographic, clinical, and immunologic characteristics of children with juvenile SSc at the onset, at diagnosis, and during the disease course were evaluated. RESULTS: Raynaud's phenomenon was the most frequent symptom, followed by skin induration in approximately 75% of patients. Musculoskeletal symptoms were present in one-third of patients, and the most frequently involved internal organs were respiratory and gastrointestinal, while involvement of renal, cerebral, and cardiovascular systems was extremely rare. Antinuclear antibodies were present in the sera of 81% of patients. Anti-topoisomerase I (Scl-70) and anticentromere antibodies were found to be positive in 34% and 7.1% of patients, respectively. Involvement of the respiratory, gastrointestinal, and cardiovascular systems was more frequent and occurred earlier in patients who died than in those who survived. Compared with the adult form, juvenile SSc appears to be less severe, with the involvement of fewer internal organs, particularly at the time of diagnosis, and has a less characterized immunologic profile. CONCLUSION: This study provides information on the largest collection of patients with juvenile SSc ever reported. Juvenile SSc appears to be less severe than in adults because children have less internal organ involvement, a less specific autoantibody profile, and a better long-term outcome.

Adolescent↗
PubMed2006

Clinical assessment in juvenile dermatomyositis.

Juvenile dermatomyositis (JDM) is a multisystem inflammatory disease of unknown etiology that affects primarily the skin and muscles. Although the prognosis of JDM has improved considerably in the last three decades, a number of patients may develop irreversible damage due to the disease activity or its treatment. This damage may cause permanent disability and affect the quality of life of patients and their families. In the clinical management of patients with JDM, there is, therefore, the need of monitoring the level of disease activity, the accrual of organ damage, and the impact of the illness on patients' daily living. A reliable assessment of these different aspects of disease requires the availability of well-designed and standardized clinical tools. In the recent years, there has been increasing collaborative effort to devise new assessment measures and these measures have been included into disease activity and damage core sets of outcome variables that have been developed through international consensus. In addition, preliminary definitions of clinical improvement for patients with JDM and other idiopathic inflammatory myopathies have been created. In this review, the latest advances in the development of standardized instruments for the clinical assessment of JDM patients are illustrated and the recent international efforts that have led to the development of core sets of outcome measures and to preliminary definitions of improvement for JDM clinical trials are summarized.

Dermatomyositis↗
PubMed2005

Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease.

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.

Antibodies, Antinuclear↗
PubMed2005

Development and validation of a clinical index for assessment of long-term damage in juvenile idiopathic arthritis.

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.

Arthritis, Juvenile↗
PubMed2005

The Pediatric Rheumatology International Trials Organization criteria for the evaluation of response to therapy in juvenile systemic lupus erythematosus: prospective validation of the disease activity core set.

OBJECTIVE: To validate and promulgate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile systemic lupus erythematosus (SLE). METHODS: In 2001, a preliminary consensus-derived core set of measures for evaluating the response to therapy in juvenile SLE was established. In the present study, the core set was validated through an evidence-based, large-scale data collection process that led to the enrollment of 557 patients from 39 different countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, agreement in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. RESULTS: The following clinical measures were found to be feasible and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) global disease activity measure, 3) 24-hour proteinuria, 4) parent's global assessment of the patient's overall well-being, and 5) health-related quality of life assessment. CONCLUSION: The members of PRINTO propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a patient with juvenile SLE has responded adequately to therapy.

Activities of Daily Living↗
PubMed2005

Patterns of clinical remission in select categories of juvenile idiopathic arthritis.

OBJECTIVE: To characterize disease activity patterns in a large cohort of children with juvenile idiopathic arthritis (JIA), by applying newly developed preliminary definitions of inactive disease, clinical remission on medication, and clinical remission off medication. METHODS: Children with persistent or extended oligoarthritis, polyarthritis (either rheumatoid factor [RF] positive or RF negative), or systemic JIA who had been followed up for a period of at least 4 years were evaluated for episodes of inactive disease, clinical remission on medication, and clinical remission off medication. Descriptive statistics, correlation analyses, and survival analyses were performed. RESULTS: Four hundred thirty-seven children met the criteria for review. Three hundred ninety-one patients (89%) experienced a total of 878 episodes of inactive disease, with a median episode length of 12.7 months. Two hundred twenty-eight episodes of inactive disease (26%) resulted in clinical remission off medication; it was equally as likely that episodes of inactive disease would or would not follow a period of clinical remission on medication. Thirty-six percent of episodes of clinical remission off medication persisted for at least 2 years, and only 6% of such episodes persisted for 5 years. RF-positive patients were the least likely to achieve clinical remission off medication (5%), and patients with persistent oligoarticular JIA were the most likely (68%). Among patients with persistent oligoarticular JIA, most of the disease course was characterized by inactive disease; in most other patients the majority of the disease course involved active disease. CONCLUSION: Using newly developed preliminary criteria for inactive disease, clinical remission on medication, and clinical remission off medication, we observed that only one-fourth of 878 episodes of inactive disease resulted in clinical remission off medication during followup of at least 4 years. Only a small proportion of episodes of clinical remission off medication were sustained for >5 years. These results highlight the critical need for therapies that have the ability to induce sustained remission of JIA.

Arthritis, Juvenile↗
PubMed2005

Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.

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.

Adolescent↗
PubMed2005

Antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss, accompanied by elevated titers of antiphospholipid antibodies (aPL). APS has been recognized as the leading cause of vascular thrombosis in children. The diagnostic and therapeutic approach to APS in childhood may be different from that for adults and because of the rarity of aPL-related thrombosis in children, the natural history and optimal management of APS can be defined only through large, multicenter, controlled studies.

Adolescent↗
PubMed2005

Outcome in juvenile onset systemic lupus erythematosus.

PURPOSE OF REVIEW: Over the past 2 decades, there has been a marked improvement in survival among patients with juvenile-onset systemic lupus erythematosus. As a result of the increased life expectancy, children and adolescents with systemic lupus erythematosus are now faced with considerable morbidity resulting from sequelae of disease activity, side effects of medications, and comorbid conditions. This morbidity affects physical and psychosocial well-being. Therefore, the need is increasing for monitoring the development of irreversible organ damage and the effect of the disease and its treatment on daily life. This review summarizes the recent advances in the investigation on survival, accumulated damage, and health-related quality of life in patients with juvenile-onset systemic lupus erythematosus. RECENT FINDINGS: The 5-year survival rate of patients with juvenile-onset systemic lupus erythematosus approaches 100%, and the 10-year survival rate is close to 90%. The development of cumulative organ damage has been observed in 50-60% of patients. Children and adolescents with systemic lupus erythematosus have been found to have poorer health-related quality of life, particularly in the physical domain, and lower socioeconomic achievements than their healthy peers. SUMMARY: The prolongation of the life span of patients with juvenile-onset systemic lupus erythematosus has been accompanied by a substantial risk of damage accumulation and has not been paralleled by an improvement in health-related quality of life. This problem highlights the need of measuring cumulative organ damage and health-related quality of life in the long-term follow-up of patients with juvenile-onset systemic lupus erythematosus and of designing new treatments and treatment strategies that are aimed not only at improving control of disease activity but also at minimizing the development of nonreversible damage.

Age of Onset↗
PubMed2005

Course of joint disease in patients with antinuclear antibody-positive juvenile idiopathic arthritis.

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.

Adolescent↗