Objective. Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle-Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome.Methods. Genomic DNA from 13 patients with classic manifestations of NOMID/CINCA syndrome and their available parents was screened for CIAS1 mutations by automated DNA sequencing. Cytokine messenger RNA (mRNA) levels were assessed by real-time polymerase chain reaction on peripheral blood leukocyte mRNA, and serum cytokine levels were assayed by enzyme-linked immunosorbent assay. Protein expression was assessed by Western blotting of lysates from plastic-adherent peripheral blood mononuclear cells.Results. In 6 of the 13 patients, we found 6 heterozygous missense substitutions in CIAS1. Five of the 6 mutations are novel. None of these sequence changes was observed in a panel of >900 chromosomes from healthy controls. Two distinct nucleotide changes in a single codon in unrelated patients resulted in the same amino acid change. In 4 mutation-positive children whose parental DNA was available, no mutation was found in the parental DNA, supporting the conclusion that the mutations arose de novo. Consistent with

The MITAX, MYOACT and MDI tools, which are now undergoing validity testing, should enhance the consistency, comprehensiveness and reliability of disease activity and damage assessment in patients with myositis.

Objective. Vertebral fractures are an under-recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy. Methods. Children were categorized as follows: juvenile dermatomyositis (n ‫؍‬ 30), juvenile idiopathic arthritis (n ‫؍‬ 28), systemic lupus erythematosus and related conditions (n ‫؍‬ 26), systemic arthritis (n ‫؍‬ 22), systemic vasculitis (n ‫؍‬ 16), and other conditions (n ‫؍‬ 12). Thoracolumbar spine radiograph and dual x-ray absorptiometry for lumbar spine (L-spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L-spine BMD Z score, and back pain were analyzed for association with vertebral fracture. Results. Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2-3 fractures. Fractures were clustered in the mid-thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean ؎ SD L-spine BMD Z score was significantly different from zero (؊0.55 ؎ 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 ؎ 1.0, P ‫؍‬ 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1-53.8], P ‫؍‬ 0.004). Conclusion. In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

Objective. To determine the frequency of incident vertebral fractures (IVF) 12 months after glucocorticoid (GC) initiation in children with rheumatic diseases and to identify children at higher risk.Methods. Children with rheumatic diseases initiating GC were enrolled in a prospective observational study. Annual spine radiographs were evaluated using the Genant semiquantitative method. Spine areal bone mineral density (aBMD) was measured every 6 months. Clinical features, including cumulative GC dose, back pain, disease and physical activity, calcium and vitamin D intake, and spine aBMD Z scores, were analyzed for association with IVF. Results. Seven (6%) of 118 children (95% confidence interval 2.9 -11.7%) had IVF. Their diagnoses were: juvenile dermatomyositis (n ‫؍‬ 2), systemic lupus erythematosus (n ‫؍‬ 3), systemic vasculitis (n ‫؍‬ 1), and mixed connective tissue disease (n ‫؍‬ 1). One child was omitted from the analyses after 4 months because of osteoporosis treatment for symptomatic IVF. Children with IVF received on average 50% more GC than those without (P ‫؍‬ 0.030), had a greater increase in body mass index (BMI) at 6 months (P ‫؍‬ 0.010), and had greater decrements in spine aBMD Z scores in the first 6 months (P ‫؍‬ 0.048). Four (67%) of 6 children with IVF and data to 12 months had spine aBMD Z scores less than ؊2.0 at 12 months compared to 16% of children without IVF (P ‫؍‬ 0.011). Conclusion. The incidence of VF 12 months following GC initiation was 6%; most children were asymptomatic. Children with IVF received more GC, had greater increases in BMI, and had greater declines in spine aBMD Z scores in the first 6 months.

At a mean follow-up of 5 yr, the current results show a favourable outcome in most patients with childhood onset jSSc and a significantly better survival than in the adult SSc patients.