Introductions/Aims Inclusion body myositis (IBM) typically presents with progressive weakness preferentially involving finger flexors and quadriceps. Atypical presentations have been less commonly reported. Here, we aim to describe the clinical characteristics and long‐term outcomes of IBM patients with atypical presentations. Methods We retrospectively searched the Mayo Clinic medical records to identify IBM patients with atypical disease onset, seen between 2015 and 2020. Results We identified 357 IBM patients, of whom 50 (14%) had an atypical presentation. Thirty‐eight patients were diagnosed with IBM because they fulfilled one of the European Neuromuscular Center diagnostic categories at a later stage, 10 had all IBM histopathological features, and 2 were diagnosed on the basis of clinical and laboratory data. The most common presentation was dysphagia (50%), followed by asymptomatic hyperCKemia (24%; CK, creatine kinase), then foot drop (12%). 6% of patients presented with proximal arm weakness, 4% with axial weakness and 4% with facial diplegia. Median time from symptom onset to diagnosis was 9 y. Median age at diagnosis was 70.5 y. 16% of patients needed a walking aid. When tested, 86.5% of patients had impaired swallowing and 56% had elevated cytosolic nucleotidase‐1A antibodies. Only 1/26 patients who received immunotherapy had minimal improvement. Upon follow‐up, most patients had generalization of their weakness with a decline in their strength summated score of 0.082/mo. Discussion A significant proportion of IBM patients may have an atypical presentation. Recognition of such heterogeneity could improve early diagnosis, prevent unnecessary immunotherapy, and provide insight for future diagnostic criteria development and clinical trials.

Introduction/Aims Intracellular congophilic inclusions within muscle fibers, although nonspecific, are one of the pathological hallmarks of sporadic inclusion body myositis (sIBM). Extracellular amyloid deposits in muscle, on the other hand, are the canonical findings of amyloid myopathies, which occur with or without systemic amyloidosis. Methods We reviewed the muscle biopsy database (1998–2020) to identify sIBM patients with extracellular amyloid deposits. Clinical and laboratory data were reviewed. Results We identified five sIBM patients (three clinicopathologically defined and two clinically defined) with extracellular amyloid deposits in muscle. Mean age at diagnosis was 74.8 y (range, 68–84 y). All patients had a typical sIBM pattern of weakness without associated sensory or autonomic symptoms. None had electrophysiological evidence of peripheral neuropathy. Only one patient had a monoclonal gammopathy (immunoglobulin M‐lambda, IgM‐λ) with normal bone marrow biopsy. This patient with monoclonal gammopathy and three other patients underwent abdominal fat pad aspirate and were negative for amyloid. Cardiac evaluation was unrevealing in the four patients tested. Three patients without monoclonal gammopathy had normal transthyretin gene sequencing and inconclusive mass spectrometry‐based analysis. The patient with monoclonal gammopathy died of pneumosepsis 5 y after diagnosis and autopsy revealed multi‐organ transthyretin amyloidosis. Discussion Detection of extracellular amyloid deposition in muscle should trigger an aggressive search for systemic amyloidosis independently from other associated myopathological abnormalities. Amyloid subtyping is crucial for early therapy and mortality prevention. An isolated monoclonal gammopathy should not halt a search for non‐hematological causes of systemic amyloidosis.