Objective Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of pediatric anti-HMGCR-positive myositis patients. Methods The sera of 440 juvenile myositis patients were screened for anti-HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti-HMGCR-positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis-specific autoantibodies (MSAs). Results Five (1.1%) of 440 patients were anti-HMGCR-positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and two patients had immune-mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti-HMGCR-positive subjects was 17,000 IU/L. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR-positive subjects compared to MSA-negative patients or those with other MSAs. Anti-HMGCR-positive patients had only partial responses to multiple immunosuppressive medications and often a chronic course. The DRB1*07:01allele was present in all 5 patients compared to 26.25% of healthy controls (Pcorrected=0.01); none of the 5 pediatric patients had DRB1*11:01. Conclusions Compared to children with other MSAs, muscle disease appeared to be more severe in those with anti-HMGCR autoantibodies. Like adults, children with anti-HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, anti-HMGCR-positive children have a strong association with HLA DRB1*07:01.

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The pediatrician makes a judgment of the degree of illness (toxicity) of a febrile child based on observation prior to history and physical examination. In order to define valid and reliable observation data for that judgment, data from two previous studies were used to construct three-point scales of 14 observation items correlated with serious illness in those reports. Between Nov 1, 1980 and March 1, 1981, these 14 scaled items were scored simultaneously by attending physicians, residents, and nurses prior to history and physical examination on 312 febrile children aged ≤24 months seen consecutively in our Primary Care Center-Emergency Room and in one private practice. Of these 312 children, 37 had serious illness. Multiple regression analysis based on patients seen by at least one attending physician in the Primary Care Center revealed six items (quality of cry, reaction to parents, state variation, color, state of hydration, and response to social overtures) that were significant and independent predictors of serious illness (multiple R = 0.63). The observed agreement for scoring these six items between two attending physicians who saw one third of the patients ranged from 88% to 97%. The chance corrected agreement levels (κw) for these six items were, with one exception, clinically significant (κw = .47 to .73). A discriminant function analysis revealed that these six items when used together had a specificity of 88% and a sensitivity of 77% for serious illness. Individual scores for each of the six key items were added to yield a total score for each patient. Only 2.7% of patients with a score ≤10 had a serious illness; 92.3% with a score ≥l6 had a serious illness. The sensitivity of the six-item model for serious illness when combined with history and physical examination was 92%. In the population studied, this predictive model, when used prior to history and physical examination, was reliable, predictive, specific, and sensitive for serious illness in febnile children. It was most sensitive when combined with history and physical examination. The model wifi need to be validated on a new population of patients.