Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features

AIM: Juvenile idiopathic inflammatory myopathies (IIM) have been recently reclassified into clinico-serological subgroups. Myopathological correlates of the subgroups are incompletely understood. METHODS: We studied muscle biopsies from 101 children with clinically and serologically-defined juvenile IIM from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review, and C5b-9 complement analysis. RESULTS: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti-TIF1γ, 15/90 anti-NXP2, 11/90 anti-MDA5, 5/90 anti-Mi2, and 6/90 anti-PmScl. JDM biopsy severity scores were consistently low in the anti-MDA5 group, high in the anti-Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage-rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101), and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b-9-deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b-9 deposition. CONCLUSION: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. This article is protected by copyright. All rights reserved

Muscle biopsy in combination with myositis-specific autoantibodies aids prediction of outcomes in juvenile dermatomyositis

OBJECTIVE: Juvenile dermatomyositis (JDM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. We investigated whether histopathology and myositis-specific autoantibodies (MSA) have prognostic significance. // METHODS: Muscle biopsy samples (n=101) from the UK JDM Cohort and Biomarker Study were stained, analyzed and scored. Autoantibodies were measured (n=90) and longitudinal clinical data were collected (median follow-up 4.9 years). Long-term treatment status was modelled using generalized estimating equations. // RESULTS: Muscle biopsy scores differed according to MSA. When effects of MSA were accounted for, increased severity of muscle pathology predicted increased risk of remaining on treatment over time: 1.48-fold higher odds (1.12-1.96, p=0.0058) for the global pathology score (hVAS) and 1.10-fold higher odds (1.01-1.21, p=0.038) for the total biopsy score for the standardized score tool. A protective effect was identified in patients with anti-Mi2 autoantibodies, who had 7.06-fold lower odds (1.41-35.36, p=0.018) of remaining on treatment, despite displaying more severe muscle pathology at biopsy. For patients with anti-NXP-2, anti-TIF1γ autoantibodies or no-detectable autoantibody, increased severity of muscle pathology alone could predict the risk of remaining on treatment, without adjustment for MSA: 1.61-fold higher odds (1.16-2.22, p=0.0040) for hVAS and 1.13-fold higher odds (1.03-1.24, p=0.013) for total biopsy score. // CONCLUSION: Muscle pathology, in combination with MSA, predicts the risk of remaining on treatment in JDM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease

Validation of a score tool for measurement of histological severity in juvenile dermatomyositis and association with clinical severity of disease.

OBJECTIVES: To study muscle biopsy tissue from patients with juvenile dermatomyositis (JDM) in order to test the reliability of a score tool designed to quantify the severity of histological abnormalities when applied to biceps humeri in addition to quadriceps femoris. Additionally, to evaluate whether elements of the tool correlate with clinical measures of disease severity. METHODS: 55 patients with JDM with muscle biopsy tissue and clinical data available were included. Biopsy samples (33 quadriceps, 22 biceps) were prepared and stained using standardised protocols. A Latin square design was used by the International Juvenile Dermatomyositis Biopsy Consensus Group to score cases using our previously published score tool. Reliability was assessed by intraclass correlation coefficient (ICC) and scorer agreement (α) by assessing variation in scorers' ratings. Scores from the most reliable tool items correlated with clinical measures of disease activity at the time of biopsy. RESULTS: Inter- and intraobserver agreement was good or high for many tool items, including overall assessment of severity using a Visual Analogue Scale. The tool functioned equally well on biceps and quadriceps samples. A modified tool using the most reliable score items showed good correlation with measures of disease activity. CONCLUSIONS: The JDM biopsy score tool has high inter- and intraobserver agreement and can be used on both biceps and quadriceps muscle tissue. Importantly, the modified tool correlates well with clinical measures of disease activity. We propose that standardised assessment of muscle biopsy tissue should be considered in diagnostic investigation and clinical trials in JDM

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

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