To report a case of overlap myositis in a patient with genetically confirmed oculopharyngeal muscular dystrophy (OPMD), emphasizing the important role of muscle biopsy in differentiating these two conditions.

A 65-year-old woman with a family history and genetically confirmed OPMD experienced a rapid worsening of leg weakness 13 months after initial symptom onset. Her ability to walk deteriorated significantly, going from being able to hike, to having difficulty walking a city block. Her OPMD symptoms began four years prior, with dysphagia, ptosis, and proximal muscle weakness, making it hard to climb stairs and exit cars. Initially, her worsening condition was attributed to OPMD, but new symptoms like eyelid discoloration, facial swelling, and "mechanic hands" signaled an inflammatory myopathy. Positive ANA, U1-RNP, and MRI of the thighs revealing bilateral perifascial and epimysial edema with fatty atrophy suggested myositis. A right vastus lateralis biopsy confirmed perimysial inflammation consistent with overlap myositis in mixed connective tissue disease and dystrophic changes with rimmed vacuoles in OPMD. Treatment with IVIg, high-dose corticosteroids, and mycophenolate mofetil led to improvement of her muscle strength.

Identifying overlap myositis in a patient with existing OPMD is difficult. A high index of suspicion is important in a patient with accelerating muscle weakness and additional systemic symptoms. Muscle biopsy was essential for confirming overlap myositis in this patient with a confirmed genetic myopathy.