02OBrachio-cervical inflammatory myopathy: evidence for a distinct form of inflammatory muscle disease

Brachio-cervical inflammatory myopathy (BCIM) is a rare and underrecognized type of idiopathic inflammatory myopathy (IIM). It stands out due to its unusual pattern of muscle weakness, affecting the upper arms and neck, often in an asymmetric and severe way. BCIM frequently overlaps with other autoimmune diseases, such as scleroderma, but its exact biological basis has remained unclear. As a result, it’s still debated whether BCIM represents a unique disease or a variation of other known IIM subtypes. Diagnosing BCIM can be challenging, as its clinical presentation can resemble that of genetic muscle disorders, e.g., facioscapulohumeral muscular dystrophy (FSHD). This underlines the importance of thorough diagnostic work-up, including muscle biopsy and molecular studies, to avoid misdiagnosis. In this study, we examined 23 patients with BCIM and available muscle biopsies. Most patients (87%) were women and showed pronounced and asymmetric upper limb weakness. Other frequent signs included dropped head, dysphagia, scapular winging, and facial involvement. Interestingly, more than half (56%) also showed signs of proximal lower limb weakness. While many patients initially responded to immunosuppressive therapy, most experienced only partial recovery, and progressive muscle fibrosis with persistent axial weakness was common. Polyclonal antibody production was found in 80% of patients, including AChR antibodies in the absence of clinical myasthenia. Integrating clinical, histopathological, transcriptomic, and proteomic data, we observed a consistent pattern of B cell-driven inflammation with local antibody production, alongside clear evidence of mitochondrial dysfunction, which is at variance with other types of IIM. Together, these findings support the hypothesis that BCIM is a distinct form of inflammatory myopathy. Improved recognition of its clinical and molecular features is essential for accurate diagnosis and may open the door to more tailored treatment approaches, including early B-cell depleting strategies.