Evidence-based diagnosis and treatment of macrophage activation syndrome in systemic juvenile idiopathic arthritis.

BACKGROUND: Macrophage activation syndrome (MAS) is a severe and potentially lethal complication of several inflammatory diseases but seems particularly linked to systemic juvenile idiopathic arthritis (sJIA). Standardized diagnostic and treatment guidelines for MAS in sJIA are currently lacking. The aim of this systematic literature review was to evaluate currently available literature on diagnostic criteria for MAS in sJIA and provide an overview of possible biomarkers for diagnosis, disease activity and treatment response and recent advances in treatment. METHODS: A systematic literature search was performed in MEDLINE, EMBASE and Cochrane. 495 papers were identified. Potentially relevant papers were selected by 3 authors after which full text screening was performed. All selected papers were evaluated by at least two independent experts for validity and level of evidence according to EULAR guidelines. RESULTS: 27 papers were included: 7 on diagnosis, 9 on biomarkers and 11 on treatment. Systematic review of the literature confirmed that there are no validated diagnostic criteria for MAS in sJIA. The preliminary Ravelli criteria, with the addition of ferritin, performed well in a large retrospective case-control study. Recently, an international consortium lead by PRINTO proposed a new set of diagnostic criteria able to distinguish MAS from active sJIA and/or infection with superior performance. Other promising diagnostic biomarkers potentially distinguish MAS complicating sJIA from primary and virus-associated hemophagocytic lymphohistiocytosis. The highest level of evidence for treatment comes from case-series. High dose corticosteroids with or without cyclosporine A were frequently reported as first-line therapy. From the newer treatment modalities, promising responses have been reported with anakinra. CONCLUSION: MAS in sJIA seems to be diagnosed best by the recently proposed PRINTO criteria, although prospective validation is needed. Novel promising biomarkers for sJIA related MAS are in need of prospective validation as well, and are not widely available yet. Currently, treatment of MAS in sJIA relies more on experience than evidence based medicine. Taking into account the severity of MAS and the scarcity of evidence, early expert consultation is recommended as soon as MAS is suspected.

Body composition and adipokines in patients with juvenile idiopathic arthritis and systemic glucocorticoids.

OBJECTIVES: The aim of this cross-sectional study was to explore body composition, and the relationship of serum adipokines with bone mass and disease activity, in a cohort of JIA patients with at least three months' exposure to systemic glucocorticoids (GC). METHODS: Fifty patients with JIA (34 girls, median age 12.4 years and disease duration 6.3 years) and 88 controls matched for gender and age participated in this study. Bone mineral content (BMC) and areal bone mineral density (BMD) of the lumbar spine and whole body, as well as body composition were assessed with dual-energy x-ray absorptiometry. Fasting serum leptin and adiponectin were measured. RESULTS: Fat and lean mass were similar between patients and controls, but patients had slightly decreased BMD Z-scores. Serum leptin and adiponectin concentrations were similar. Disease activity was low, and no correlation with adipokines was observed. Patients with bone age-corrected lumbar spine BMD Z-score ≤-1.0 ("low BMD") did not show alterations in body composition, GC exposure or current disease activity, but had decreased BMC-to-lean mass ratio (p<0.001) and tendency for increased serum leptin (p=0.064). However, no association of leptin with BMD in multivariate analysis existed in patients or controls. An inverse association between adiponectin and whole body BMD was observed in both groups. CONCLUSIONS: Normal body composition was observed in a JIA cohort with low-dose GC exposure. Patients with "low BMD" tended to have increased serum leptin, but leptin did not associate with BMD. In this cohort with low disease activity, no correlation between adipokines and disease activity was present.

Anti-tumor necrosis factor treatment in cherubism--clinical, radiological and histological findings in two children.

Cherubism is a rare and disfiguring genetic disorder with excessive bone resorption and multilocular lesions in the mandible and/or maxilla. The disease-causing gain-of-function mutations in the SH3-binding protein 2 (SH3BP2) gene result in increased myeloid cell responses to macrophage colony stimulating factor and RANK ligand, formation of hyperactive osteoclasts (giant cells), and hyper-reactive macrophages that produce excessive amounts of the inflammatory cytokine tumor necrosis factor α (TNF-α). Recent findings in the cherubism mouse model suggest that TNF-α plays a major role in disease pathogenesis and that removal of TNF-α prevents development of the bone phenotype. We treated two children with cherubism with the TNF-α antagonist adalimumab for approximately 2.5 years and collected extensive clinical, radiological and histological follow-up data during the treatment. Histologically the treatment resulted in a significant reduction in the number of multinucleated giant cells and TNF-α staining positivity in both patients. As evaluated by computed tomography and magnetic resonance imaging, the lesions in Patient 1 showed either moderate enlargement (mandibular symphysis) or remained stable (mandibular rami and body, the maxilla). In Patient 2, the lesions in mandibular symphysis showed enlargement during the first 8 months of treatment, and thereafter the lesions remained unchanged. Bone formation and resorption markers remained unaffected. The treatment was well tolerated. Based on our findings, TNF-α antagonist may decrease the formation of pathogenic giant cells, but does not result in lesion regression or prevent lesion expansion in active cherubism. TNF-α modulator treatment thus does not appear to provide sufficient amelioration for patients suffering from cherubism.

Validity and predictive ability of the juvenile arthritis disease activity score based on CRP versus ESR in a Nordic population-based setting.

OBJECTIVE: To compare the juvenile arthritis disease activity score (JADAS) based on C reactive protein (CRP) (JADAS-CRP) with JADAS based on erythrocyte sedimentation rate (ESR) (JADAS-ESR) and to validate JADAS in a population-based setting. METHODS: The CRP and ESR values and the corresponding JADAS scores (JADAS10/27/71) were compared in a longitudinal cohort study of 389 children newly diagnosed with juvenile idiopathic arthritis (JIA) in the Nordic JIA study. The construct validity and the discriminative and predictive ability of JADAS were assessed during a median disease course of 8 years by comparing JADAS with other measures of disease activity and outcome. RESULTS: At the first study visit the correlation between JADAS27-CRP and JADAS27-ESR was r=0.99 whereas the correlation between CRP and ESR was r=0.57. Children with higher JADAS scores had an increased risk of concomitant pain, physical disability and use of disease-modifying antirheumatic drugs (DMARDs). A higher JADAS score at the first study visit also significantly predicted physical disability, damage and no remission off medication at the final study visit, and also use of DMARDs during the disease course. Sensitivity to change, demonstrated as change in JADAS score compared with the American College of Rheumatology paediatric measures of improvement criteria, mostly showed excellent classification ability. CONCLUSION: The JADAS-CRP and JADAS-ESR correlate closely, show similar test characteristics and are feasible and valid tools for assessing disease activity in JIA.

Prevention of acute adverse events related to infliximab infusions in pediatric patients.

OBJECTIVE: To study whether premedication with an oral antifebrile agent (acetaminophen) and antihistamine (cetirizine) could decrease the frequency of acute infusion reactions in pediatric patients. METHODS: All pediatric patients scheduled for infliximab infusions at the Helsinki University Central Hospital, a tertiary care center, were prospectively introduced to a standard oral premedication of acetaminophen (20 mg/kg) and cetirizine (10 mg) prior to infliximab infusions for a period of 1 year. All acute adverse events related to infliximab infusions given according to the guidelines of pediatric rheumatologists or gastroenterologists were registered for this time period and retrospectively during the preceding year. RESULTS: During the study period, infliximab infusions with premedication were given to 64 pediatric patients (48 with rheumatic disease and l6 with inflammatory bowel disease, mean age 13 years, n = 34 boys, and n = 30 girls). Infliximab was introduced to 14 children; the rest were on maintenance therapy. Twelve infusion reactions, 4 mild and 8 severe, were observed in 8 (12.5%) of the 64 subjects, and in 1 subject 4 times. During the preceding year, 60 pediatric patients had received infliximab infusions without premedication. In this latter group, infusion reactions occurred in 5 children (8.3%; P > 0.05). The presentation of an acute infusion reaction was not related to the sex or diagnosis of the patient. CONCLUSION: In pediatric patients, acute infusion reactions related to infliximab could not be prevented with premedication with oral acetaminophen and cetirizine.

Drug survival of the first and second course of anti-tumour necrosis factor agents in juvenile idiopathic arthritis.

OBJECTIVES: To evaluate drug survival (continuation rates on drug) of anti-tumour necrosis factor (TNF) agents in juvenile idiopathic arthritis (JIA) and predictors for treatment discontinuation. METHODS: A retrospective observational study on JIA patients taking etanercept (n = 105) or infliximab (n = 104) with at least one year follow-up. Kaplan-Meier curves and log-rank statistics were used to compare treatments and a proportional hazards model to assess risk factors for discontinuation. RESULTS: Etanercept versus infliximab treatment survival at 12 months was 83% versus 80%, at 24 months 68% versus 68%, at 36 months 64% versus 53%, at 48 months 61% versus 48% (p = 0.194), respectively. Reasons for discontinuing the first biological treatment were inefficacy (etanercept 28% vs infliximab 20%, p = 0.445), adverse events (7% vs 22%, p = 0.002) or inactive disease (10% vs 16%, p = 0.068). Women (hazard ratio (HR) 2.8, 95% CI 1.3 to 5.8), patients with systemic JIA (HR 7.8, 95% CI 1.7 to 34.9) or those taking infliximab (HR 2.0, 95% CI 1.2 to 3.3) were at higher risk of treatment discontinuation. One-third of the patients were switched to the second anti-TNF therapy, which was discontinued less frequently than the first. At 12 months treatment survival of etanercept was 60%, infliximab 58% and adalimumab 66% as the second-line anti-TNF therapy. CONCLUSIONS: Although infliximab was discontinued more often than etanercept because of adverse events, during a 48-month follow-up the overall treatment survival of etanercept and infliximab as the first biological agent in JIA was comparable. A switch from one anti-TNF agent to another appears a reasonable therapeutic option.

Lower extremity isometric strength in children with juvenile idiopathic arthritis.

OBJECTIVE: The aim of this study was to measure lower extremity isometric strength in patients with juvenile idiopathic arthritis (JIA) and to evaluate the usefulness of an adjustable dynamometer chair in the clinical work. METHODS: Twenty-five children with JIA and 25 healthy, age-matched controls, aged 7-12 (mean age 10.1) were studied. The isometric maximal strength of knee and ankle muscles was measured on both sides using the dynamometer chair. Before and after the measurements the Children's Effort Rating Table (CERT) was used to assess physical effort and feelings of exertion during the measurements. RESULTS: In all the tested muscle groups, there was a trend towards lower muscle strength values in the patients with JIA but significant differences were found only in knee extension (at 80 degrees knee angle) on both sides and in ankle plantarflexion if both ankles had had arthritis. No difference was observed in perceived exertion between patients and controls, but both groups significantly sensed the exertion after the muscle strength measurement (mean exertion before, JIA/control 2.2/2.0, and after 5.9/5.8). CONCLUSION: Isometric muscle strength in children with JIA can be close to normal when the disease is not active. However, especially in knee extensors and ankle plantarflexors, muscle weakness may occur. From technical standpoint, an adjustable dynamometer chair can be used for assessment of isometric maximal strength in children with JIA.

Adalimumab in juvenile idiopathic arthritis-associated chronic anterior uveitis.

OBJECTIVE: To evaluate the efficacy of adalimumab in juvenile idiopathic arthritis (JIA)-associated uveitis. METHODS: Retrospective observational study of 20 patients with JIA and chronic uveitis on adalimumab treatment. The ocular inflammation and improvement was assessed according to the Standardization of Uveitis Nomenclature criteria. RESULTS: At the initiation of adalimumab, the mean age of patients was 13.4 yrs and the mean duration of uveitis 8.7 yrs. Seventeen (85%) patients had polyarticular JIA and 19 (95%) had previously been on anti-TNF treatment. The mean duration of adalimumab therapy was 18.7 months. Of the 20 patients, 7 (35%) showed improved activity, 1 (5%) worsening activity and in 12 (60%) no change was observed in the activity of uveitis. Those with improved activity were younger and had shorter disease duration. The mean number of flares/yr decreased from 1.9 to 1.4 during adalimumab treatment. Serious adverse events or side-effects were not observed. Seven patients discontinued adalimumab during the follow-up: six because of inefficacy and one because of inactive uveitis. CONCLUSION: Adalimumab is a potential treatment option in JIA-associated uveitis, even in patients non-responsive to previous other anti-TNF therapy.

Methotrexate improves the health-related quality of life of children with juvenile idiopathic arthritis.

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.

Effects of infliximab on cytokines, myeloperoxidase, and soluble adhesion molecules in patients with juvenile idiopathic arthritis.

OBJECTIVE: Infliximab is effective and well tolerated in the treatment of juvenile idiopathic arthritis (JIA). The aim of the present study was to measure circulating levels of inflammatory mediators in patients with JIA during treatment with infliximab. METHODS: Eight patients with active JIA refractory to standard treatments were treated with infliximab (3-4 mg/kg) at weeks 0, 2 and 6 and thereafter at approximately 6-week intervals up to 24 weeks. RESULTS: All patients (n = 8) responded to the treatment. By 6 weeks of treatment the number of active joints had reduced from 16+/-4 (mean+/-SEM) to 4+/-1 (p<0.01) and C-reactive protein (CRP) levels had fallen from 31+/-8 to 8+/-3 (p<0.001). Infliximab treatment also reduced the serum concentrations of interleukin-6 (IL-6), myeloperoxidase (MPO), and soluble adhesion molecules ICAM-1 (intercellular adhesion molecule-1), and E-selectin. Tumour necrosis factor-alpha (TNFalpha) levels tended to increase while the concentrations of endogenous TNF antagonists (sTNF-RI and sTNF-RII) reduced in most patients during treatment. CONCLUSIONS: Infliximab reduced serum levels of IL-6, MPO and soluble adhesion molecules in JIA patients, producing a good clinical response to the treatment.

Impact of anti-TNF treatment on growth in severe juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the impact of anti-tumour necrosis factor (TNF) treatment on growth and to identify the predictors for the change in growth in severe juvenile idiopathic arthritis (JIA). METHODS: Data from 71 JIA patients (43 on etanercept, 28 on infliximab) were reviewed two years before and two years on the anti-TNF treatment. The patients had polyarticular disease course (48 polyarthritis, 19 extended oligoarthritis, two systemic arthritis, and two enthesitis related arthritis). At the initiation of the anti-TNF treatment, their mean age was 9.6 years and the mean duration of JIA, 5.7 years. RESULTS: In the patients with delayed growth before anti-TNF treatment (n = 53), the growth velocity, measured as the change in height standard deviation score, accelerated +0.45 (95% confidence interval, 0.33 to 0.56) (p<0.001) during the anti-TNF treatment. In the patients with normal or accelerated growth before anti-TNF treatment (n = 18), the change in growth velocity was +0.05 (0.07 to 0.16) (p = 0.39). At two years on anti-TNF treatment, the growth velocity between these two groups was similar. No difference was found between the patients treated with etanercept or infliximab. A decelerating growth rate before the anti-TNF treatment was the strongest predictor for the observed increase in the growth velocity. The change in the inflammatory activity remained a significant predictor of the growth velocity even after the decrease in glucocorticoid dose was taken into account. CONCLUSIONS: In the treatment of polyarticular JIA, the anti-TNF treatment not only suppresses inflammation but also restores growth velocity.

PRINTO/PRES international website for families of children with rheumatic diseases: www.pediatric-rheumatology.printo.it.

OBJECTIVE: To prepare a website for families and health professionals containing up to date information about paediatric rheumatic diseases (PRD). METHODS: Firstly, paediatric rheumatology centres and family self help associations were surveyed to characterise current clinical practice of physicians providing care for children with PRD, research activities, and training facilities of each centre. Secondly, international consensus was reached on the content of the website. Finally, the website was developed and the texts translated. RESULTS: The web page contains three main sections: (a) description for families of the characteristics of 15 PRD; (b) list of paediatric rheumatology centres; (c) contact information for family self help associations. A version for 45 countries in 52 languages (with another three in progress) is now available on the web. 291 surveys from 171 centres and 102 family associations were received from 42 countries. The median proportion of time spent in paediatric practice in the centres examined was 100%, with 70% of this time dedicated to paediatric rheumatology. 90% of the centres were willing to perform clinical trials in the future. CONCLUSIONS: The PRINTO/PRES website provides a well defined and competent set of information about PRD, with appropriate multiple translated versions and easy web navigational direction.

Intra-articular steroids in radiologically confirmed tarsal and hip synovitis of juvenile idiopathic arthritis.

OBJECTIVE: To estimate the value of MRI or US imaging in the diagnosis of synovitis and the response to local steroid therapy in tarsal and hip synovitis. METHODS: 32 patients with juvenile idiopathic arthritis (JIA), 19 of them with 22 tarsal and 13 of them with 20 hip synovitis, were followed up for 12 months after intra-articular corticosteroid treatment (IAST). MRI was taken from swollen ankles/feet to target the inflamed area before IAST. The synovitis in hip joints was assessed by both clinical and ultrasonographic examination. RESULTS: MRI showed that in the swollen tarsal area the inflammation was distributed widely in the joints and tendon sheaths. In 13/22 (59%) ankles/feet, synovitis was observed in multiple joint spaces. In 17/22 (77%) ankles/feet, tenosynovitis was present. In 32% of cases, the IAST induced clinical remission for up to 12 months. In hip synovitis, ultrasound supplemented clinical assessment. At 12 months after IAST a successful treatment response was seen in 10/20 (50%) hips. CONCLUSION: In unresponsive tarsal arthritis, the synovitic sites should be targeted by radiological imaging to improve the efficacy of corticosteroid injections. For pediatric rheumatologists, easy access to US is preferable to optimize the treatment of hip and tarsal synovitis in JIA.

Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study.

OBJECTIVE: To study infliximab and etanercept in the treatment of refractory juvenile idiopathic arthritis (JIA). METHODS: In a non-randomised, prospective, open label study, 24 patients (mean age 10.2 years, range 3.3-16.3) with polyarticular JIA were treated with either infliximab (n=14) or etanercept (n=10). The patients had had active polyarthritis for at least one year and standard treatment had failed. Anti-tumour necrosis factor (TNF) treatment was added to the current drug treatment. Infliximab (3-4 mg/kg) was given intravenously at weeks 0, 2, and 6, and thereafter at 4 to 8 week intervals. Etanercept (0.4 mg/kg) was given subcutaneously twice a week. Improvement of the patients was assessed at 3, 6, and 12 months according to established JIA response criteria. RESULTS: In intention to treat analyses, patients in both treatment groups improved significantly. ACR Paediatric 50 was achieved at 3, 6, and 12 months by 9/10 (90%), 8/9 (89%), and 8/9 (89%) patients with etanercept and by 8/12 (67%), 10/12 (83%), and 7/9 (78%) with infliximab, respectively. At 12 months, ACR Paediatric 75 was achieved by 67% of patients in both treatment groups. Five withdrawals due to adverse effects or lack of efficacy occurred in the infliximab group and one due to lack of compliance in the etanercept group. CONCLUSION: In this open label clinical study of active JIA, both infliximab and etanercept provided a significant rapid and sustained reduction in disease activity. Adequately powered randomised controlled trials are needed to elucidate the long term safety and efficacy of TNF modulators in the treatment of JIA.

Campylobacter-triggered reactive arthritis: a population-based study.

OBJECTIVE: To study the incidence and clinical picture of Campylobacter-associated reactive arthritis (ReA) and other reactive musculoskeletal symptoms in the population. METHODS: A questionnaire on enteric and extraintestinal, including specifically musculoskeletal, symptoms was sent to 870 consecutive patients with Campylobacter-positive stool culture and 1440 matched controls. Analysis of self-reported musculoskeletal symptoms with clinical examination was performed. RESULTS: Forty-five of the patients (7%) had ReA and eight (1%) had reactive tendinitis, enthesopathy or bursitis. No child had ReA. The arthritis was oligo- or polyarticular, and, in most cases, mild. HLA-B27 was positive in 14% of ReA patients. Of the 45 ReA patients, 37 had C. jejuni and 8 had C. coli infection. No controls had ReA. CONCLUSION: ReA is common following Campylobacter infection, with an annual incidence of 4.3 per 100000. At the population level, acute ReA is mild, more frequent in adults, and not associated with HLA-B27. Besides C. jejuni, C. coli can trigger ReA.

Recombinant flagellin A proteins from Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii in serodiagnosis of Lyme borreliosis.

Genes for flagellin A (FlaA) proteins from European borrelial strains of Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii were cloned and sequenced. An identity of 92 to 93% was observed in the flaA sequences of the different species. Polyhistidine-tagged recombinant FlaA (rFlaA) proteins were produced in Escherichia coli and used as antigens in Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). In immunoglobulin G (IgG) WB, 71% (10 of 14) of the sera from neuroborreliosis and 86% (12 of 14) of those from Lyme arthritis patients reacted with one to three rFlaAs. In IgG ELISA, 74% (14 of 19) and 79% (15 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. The immunoreactivity in local European patient sera was stronger against rFlaA from B. garinii and B. afzelii than against rFlaA from B. burgdorferi sensu stricto. Neither IgG nor IgM ELISA was sensitive in the serodiagnosis of erythema migrans. Serum samples from patients with syphilis and systemic lupus erythematosus showed mild cross-reactivity in IgG tests. Sera from Yersinia enterocolitica or beta-hemolytic Streptococcus infections showed only occasional responses. With IgM ELISA, 58% (11 of 19) and 37% (7 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. Cross-reactive antibodies to FlaA, especially in serum samples from patients with rheumatoid factor positivity and Epstein-Barr virus infection, reduced the specificity of IgM serodiagnosis. Therefore, rFlaA seems to have a limited role for IgM serodiagnosis, yet rFlaA might be useful in the IgG serodiagnosis of disseminated Lyme borreliosis.

The Finnish version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Finnish 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 Finnish CHAQ-CHQ were validated with 3 forward and 1 backward translations. A total of 161 subjects were enrolled: 89 patients with JIA (9% systemic onset, 44% polyarticular onset, 26% extended oligoarticular subtype, and 21% persistent oligoarticular subtype) and 72 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, polyarticular and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Finnish version of the CHAQ-CHQ is a reliable and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Construct validity of ILAR and EULAR criteria in juvenile idiopathic arthritis: a population based incidence study from the Nordic countries. International League of Associations for Rheumatology. European League Against Rheumatism.

OBJECTIVE: New classification criteria (ILAR) have been proposed for juvenile idiopathic arthritis (JIA). They are more descriptive than those formerly used [American College of Rheumatology (ACR), European League Against Rheumatism (EULAR)], but require validation against classifications already in use. We validated the ILAR criteria in relation to the EULAR criteria in a prospective, incidence, and population based setting, and analyzed their feasibility. METHODS: Construct validity of ILAR and EULAR classification criteria refers to how closely the 2 instruments are related and how each of them operates in classifying subgroups/categories. Twenty doctors in 5 Nordic countries collected data from the incidence cases within their catchment areas during an 18 month period beginning July 1, 1997. Clinical and serological data from the first year of disease were collected. RESULTS: A total of 322 patients were included. Classification according to the ILAR criteria was possible in 321 patients; 290 patients had a disease duration > or = 3 months and were classified according to the EULAR criteria. One child could only be classified according to the EULAR criteria. Thus, 31/322 (9.6%) children were classified according to the ILAR criteria only. Forty-eight of 321 (15%) patients did not fit into any category and 6% (20/321) fulfilled criteria for2 categories. In the ILAR classification 5 out of 7 categories/subgroups have 2 to 5 specified exclusion criteria that highly discriminate the definition of each patient. In our study the exclusion criteria were fulfilled to only a small extent. CONCLUSION: The EULAR and ILAR criteria differ concerning the operational definitions of the subvariables involved, which complicates their comparison. By using ILAR rather than EULAR criteria the number of cases with juvenile arthritis increased by 10%, considering the first half-year after onset. The validity of the ILAR criteria is low since they often exclude patients from subgroup classification and the possibility of having more than one diagnosis is not negligible. The specified exclusion criteria for some of the subgroups are difficult to fulfill in clinical work and variables involved could be questioned with regard to their consistency.