OBJECTIVE To evaluate an approach to the clinical, radiographic, and molecular diagnosis of an underlying skeletal dysplasia in adults presenting with early-onset polyarticular osteoarthritis (OA). METHODS We identified a family with 2 adults with polyarticular OA and a child with generalized arthralgia. General, musculoskeletal, ocular, and auditory evaluations were undertaken. Investigations included radiographs of symptomatic joints, analysis of serum inflammatory markers and joint fluid, and mutational analyses of the COL11A2 gene. RESULTS The 3 affected individuals had normal stature, mild mid-face hypoplasia, and hearing impairment, but normal eyes. Radiographs of the affected adults showed severe polyarticular OA but did not reveal diagnostic evidence of an underlying skeletal dysplasia. However, the child's radiographs showed enlarged epiphyses with an advanced bone age. The combination of skeletal, facial, and auditory features together with the absence of ocular features indicated that they had otospondylomegaepiphyseal dysplasia, also known as Stickler syndrome type III. The diagnosis was confirmed by identifying a mutation in the COL11A2 gene that encodes the pre-pro-alpha2(XI) chain of type XI collagen that is involved in type II collagen fibrillogenesis. CONCLUSION Early-onset polyarticular OA may occur in adults without a known or obvious underlying skeletal dysplasia. This study provides an approach to the diagnosis of an underlying skeletal dysplasia in such individuals.

OBJECTIVE To determine the prevalence of anticardiolipin antibodies (aCL), anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies, and lupus anticoagulant (LAC) in a large cohort of children with systemic lupus erythematosus (SLE), and to evaluate the associations with neuropsychiatric manifestations. METHODS A single-center retrospective cohort study with longitudinal followup of antiphospholipid antibodies (aPL) in 137 children with SLE (25 boys and 112 girls, mean age at diagnosis 13.0 years) was performed. Patients were followed up for a mean of 31 months. RESULTS At the time of diagnosis, 65% of the children were aCL positive, 41% had anti-beta(2)GPI antibodies, and 26% were LAC positive. Analysis of the association between presence of aPL and individual neuropsychiatric manifestations at diagnosis showed a statistically significant association of positive LAC with cerebrovascular disease (5 patients; P = 0.015). A persistently positive aCL was observed in 50%, anti-beta(2)GPI antibodies in 29%, and LAC in 16% of children over time. The prevalence of anti-beta(2)GPI antibodies, but not aCL and LAC, was found to be statistically significantly higher in children with neuropsychiatric disease compared with those without (P = 0.02). Comparison for specific neuropsychiatric manifestations showed a statistically significant association between a persistently positive LAC and chorea (2 patients; P = 0.02). CONCLUSION The prevalence of anti-beta(2)GPI antibodies was found to be higher in the group of SLE patients with neuropsychiatric disease compared with those without. Our data suggest an association between LAC and cerebrovascular disease at the time of SLE diagnosis and chorea over the disease course, but not between aPL and other neuropsychiatric manifestations.

In genetically predisposed individuals, viruses, bacteria, or parasitic infectious agents are suspected of inducing autoimmunity and/or exacerbating autoimmune rheumatic diseases (ARD) once self-tolerance is broken. Although direct evidence for this association is still lacking, numerous data from animal models as well as from humans support the hypothesis of a direct contribution of pathogens to the induction of several ARD. This review focuses on the possible role of infectious agents as triggers of autoimmunity in systemic lupus erythematosus, polymyositis-dermatomyositis, antiphospholipid antibody syndrome, and primary vasculitis. Indeed, vasculitis may be a clinical manifestation of an infectious disease (secondary vasculitis). In addition, immune response abnormalities and immunosuppressive medications may be responsible for the high percentage of infectious complications in ARD patients. Recent therapeutic approaches aimed at lowering doses of cytotoxic agents and shortening duration of treatment with the most toxic drugs, have proved to be as effective as conventional regimens. New drugs and strategies aimed at preventing infections could further improve the outcome of ARD patients.

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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.

Nasal septal perforation has been well recognized in patients with various rheumatic diseases. To our knowledge, this condition has not been reported in children with systemic juvenile idiopathic arthritis (SJIA) or patients with adult onset Still's disease (AOSD). We describe 3 patients with persistent SJIA/AOSD who developed nasal septal perforation during the course of their disease. As illustrated by these cases, nasal septal perforation may develop as a rare complication of SJIA/AOSD and can be considered as part of the clinical spectrum of the disease. In one case the nasal septal perforation was associated with vasculitis.

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.

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anti-cardiolipin (aCL) and antiβ2 glycoprotein I (antiβ2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal β2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antiβ2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antiβ2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.

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.