A retrospective cohort study identifying the principal pathological features useful in the diagnosis of inclusion body myositis.
Brady S., Squier W., Sewry C., Hanna M., Hilton-Jones D., Holton JL.
OBJECTIVE: The current pathological diagnostic criteria for sporadic inclusion body myositis (IBM) lack sensitivity. Using immunohistochemical techniques abnormal protein aggregates have been identified in IBM, including some associated with neurodegenerative disorders. Our objective was to investigate the diagnostic utility of a number of markers of protein aggregates together with mitochondrial and inflammatory changes in IBM. DESIGN: Retrospective cohort study. The sensitivity of pathological features was evaluated in cases of Griggs definite IBM. The diagnostic potential of the most reliable features was then assessed in clinically typical IBM with rimmed vacuoles (n=15), clinically typical IBM without rimmed vacuoles (n=9) and IBM mimics-protein accumulation myopathies containing rimmed vacuoles (n=7) and steroid-responsive inflammatory myopathies (n=11). SETTING: Specialist muscle services at the John Radcliffe Hospital, Oxford and the National Hospital for Neurology and Neurosurgery, London. RESULTS: Individual pathological features, in isolation, lacked sensitivity and specificity. However, the morphology and distribution of p62 aggregates in IBM were characteristic and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for IBM with a sensitivity of 93% and specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for IBM; characteristic p62 aggregates were specific (91%), but lacked sensitivity (44%). CONCLUSIONS: We propose an easily applied diagnostic algorithm for the pathological diagnosis of IBM. Additionally our findings support the hypothesis that many of the pathological features considered typical of IBM develop later in the disease, explaining their poor sensitivity at disease presentation and emphasising the need for revised pathological criteria to supplement the clinical criteria in the diagnosis of IBM.