Chronic Active Epstein-Barr Virus Myopathy Mimicking Idiopathic Inflammatory Myopathies: A Diagnostic Pitfall, Differentiating Features, and Clinical Impact Revealed in the 10-year Case Series

Systemic chronic active Epstein-Barr virus disease (sCAEBVD) can primarily involve skeletal muscle to form CAEBV-myopathy (CAEBV-M), which may resemble idiopathic inflammatory myopathies (IIMs). This study reports an 11-patient, 10-year cohort of CAEBV-M to summarize clinicoseropathologic features. CAEBV-M typically affects young adults (median: 29 years), with universal limb swelling, frequent disseminated muscle involvement (73%), and systemic symptoms like fever (82%), splenomegaly (82%), and hemophagocytic lymphohistiocytosis (55%). Heliotrope-like rash and myositis-specific antibodies each occurred in 18%. Histology showed endomysial (82%) and perimysial (91%) lymphoid infiltration in an angiocentric pattern (82%), with NK-cell component in 64%. EBER-ISH-positive cells varied in muscle samples but were more abundant in skin lesions. Median survival was 6.6 months. Compared to IIMs, CAEBV-M affects younger patients, has more systemic symptoms, positive plasma EBV-DNA, angiocentric histology, and EBER-ISH positivity. These features provide practical diagnostic clues. Clinicians should consider testing for EBV-DNA and EBER-ISH in patients with atypical myositis presentations to avoid misdiagnosis and inappropriate immunosuppressive therapy.