Background:
Anti-HMGCR immune-mediated necrotizing myopathy (IMNM) is a rare autoimmune disease characterized by proximal weakness and myofiber necrosis with minimal inflammation. While often associated with statin use in older adults, it may also present in younger patients as a chronic, progressive phenotype mimicking hereditary muscular dystrophies.
Objective/Results:
A 27-year-old male presented for evaluation of suspected limb girdle muscular dystrophy (LGMD). Symptoms began at age 12 with acute onset bilateral leg weakness, and progressive involvement of truncal and shoulder weakness. He denied family history of myopathy. Neurological examination revealed prominent weakness in hip flexors, adductors, and mild weakness in shoulder abductors. Outside workup at symptom onset included creatine kinase (CK) 11,100 U/L and myopathic changes on EMG in the proximal bilateral lower extremities. Prior genetic testing (for DMD, CAPN3, FKRP) was negative, and prior quadriceps muscle biopsy was reported to show regenerative and degenerative changes with subtle inflammation and intact staining for dystrophin-associated proteins. Our diagnostic evaluation, considering a wide differential of LGMD and acquired myopathies, revealed elevated HMGCR antibodies. Electrodiagnostic testing confirmed evidence of an irritable myopathy in the proximal upper and lower extremities. Repeat quadriceps muscle biopsy demonstrated myopathic changes with some regenerative and necrotic fibers, and rare perivascular inflammation. Additional genetic testing was unrevealing. The patient was treated with prednisone and IVIG, resulting in significant clinical improvement in ambulation and strength. His CK improved from 859 U/L before treatment to 275 U/L after treatment. He remains stable on low-dose prednisone and IVIG.
Conclusion:
Anti-HMGCR myopathy and other immune mediated necrotizing myopathies are important to consider in the differential diagnosis for LGMD, especially in the absence of a definite genetic diagnosis. Distinguishing IMNM from genetic dystrophies is critical, as IMNM is a treatable condition.