Abstract Details

To describe clinical and laboratory features and long-term outcomes in patients with iRMD.

Nine patients were identified (3 females). Median age at symptom onset was 53 years (range: 18-76), median time to diagnosis was 2 years (range: 0.5-10) and median follow-up was 0.5 years (range: 0.1-2.5). Presenting symptoms included muscle rippling (4, focal; 2, diffuse), myalgia (8), and/or proximal weakness (3). Co-existent autoimmune disease was present in 3. Breast cancer was diagnosed in one patient 6 months after iRMD developed. Examination identified percussion-induced rippling and muscle mounding in all patients and mild proximal weakness (MRC 4-5) in 4. Median creatine kinase was 534 U/L (range: 132-2625). Genetic testing identified no mutations in CAV3 (8/9) and CAVIN1 (2/9). Acetylcholine receptor binding antibodies were elevated in 3 patients, 2 of whom had electrophysiological evidence of a neuromuscular transmission defect.  Electromyography demonstrated increased insertional activity (9), fibrillation potentials (8), and myopathic motor unit potentials (9). Rippling was electrically silent (6) or active (3), resembling post-percussion trains of fibrillation potentials, shorter in duration than the observed muscle rippling. Muscle biopsies (8) demonstrated myopathic features (6), endomysial or perimysial perivascular inflammation (2), mosaic caveolin-3 sarcolemmal immunoreactivity (7), varying degrees of major-histocompatibility complex I upregulation and C5-b9 deposition on sarcolemma of non-necrotic muscle fibers and capillaries. Transcriptomics analysis evaluating for gene dysregulation is ongoing. Six patients with adequate follow-up received immunotherapy (6 IVIG, 3 prednisone, 2 IV methylprednisolone, 3 azathioprine) with remission (4) or stabilization (2) of rippling.