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

Abstract

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.

Keywords: Dermatomyositis; Disease Activity; Inflammation.

Figure 1

Features of dermatomyositis including the informative score tool items selected for the modified score tool, illustrated in a quadriceps biopsy (A, C, D, F and H) and in a biceps biopsy (B, E, G and I). Perivascular inflammation was seen, often with a perimysial localisation (A and B, arrows indicate vessels). Perifascicular fibre atrophy was a feature of some biopsies, and other fibre abnormalities including basophilia, indicating regeneration, were often more prominent in perifascicular regions (B, double arrow). CD3 immunoreactive T cells were present in the perimysium (C and E, arrows) and also the endomysium (D, arrow). Macrophage infiltrates were identified by CD68 immunohistochemistry in the endomysium (F and G, arrow) and also around vessels (G, double arrow). Neonatal myosin expression could often be seen to have a characteristic perifascicular pattern (H and I). (A and B) haematoxylin and eosin; (C, D and E) CD3 immunohistochemistry; (F and G) CD68 immunohistochemistry; (H and I) neonatal myosin immunohistochemistry. Bars represent: 50 µm in A, B, C, E and G; 25 µm in D and F; 100 µm in H; 260 µm in I.