Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children) new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Sub-classification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) “probable IIM”, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to “definite IIM”. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy) rules out IIM, leaving a probability of ≥50 to <55% as “possible IIM”. Conclusions The EULAR/ACR classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of “definite”, “probable”, and “possible” IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Objective To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. Methods Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. Results Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children) new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Sub-classification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) “probable IIM”, had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to “definite IIM”. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy) rules out IIM, leaving a probability of ≥50 to <55% as “possible IIM”. Conclusions The EULAR/ACR classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of “definite”, “probable”, and “possible” IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Hyperuricemia has long been established as the major etiologic factor in gout. In recent years, a large body of evidence has accumulated that suggests that hyperuricemia may play a role in the development and pathogenesis of a number of metabolic, hemodynamic, and systemic pathologic diseases, including metabolic syndrome, hypertension, stroke, and atherosclerosis. A number of epidemiologic studies have linked hyperuricemia with each of these disorders. In some studies, therapies that lower uric acid may prevent or improve certain components of the metabolic syndrome. There is an association between uric acid and the development of systemic lupus erythematosus; the connection between other rheumatic diseases such as rheumatoid arthritis and osteoarthritis is less clear. The mechanism for the role of uric acid in disorders other than gout is not well established but recent investigations point towards systemic inflammation induced by urate, as the major pathophysiological event common to systemic diseases, including atherosclerosis.

Melorheostosis is a sporadic disease of uncertain etiology characterized by asymmetric bone overgrowth and functional impairment. Using whole exome sequencing, we identify somatic mosaic MAP2K1 mutations in affected, but not unaffected, bone of eight unrelated patients with melorheostosis. The activating mutations (Q56P, K57E and K57N) cluster tightly in the MEK1 negative regulatory domain. Affected bone displays a mosaic pattern of increased p-ERK1/2 in osteoblast immunohistochemistry. Osteoblasts cultured from affected bone comprise two populations with distinct p-ERK1/2 levels by flow cytometry, enhanced ERK1/2 activation, and increased cell proliferation. However, these MAP2K1 mutations inhibit BMP2-mediated osteoblast mineralization and differentiation in vitro, underlying the markedly increased osteoid detected in affected bone histology. Mosaicism is also detected in the skin overlying bone lesions in four of five patients tested. Our data show that the MAP2K1 oncogene is important in human bone formation and implicate MEK1 inhibition as a potential treatment avenue for melorheostosis.