Amyloid myopathy: A primarily microangiopathic and neurogenic disease

Amyloid myopathy is an etiologically heterogeneous group of disorders associated with amyloid deposition in skeletal muscle. The great majority of cases reflect muscle involvement in systemic amyloidosis, particularly immunoglobulin light-chain amyloidosis and hereditary amyloidosis. Occasionally, amyloid myopathy presents as an isolated myopathy associated with muscle proteinopathies. Clinical manifestations are generally nonspecific. Muscle weakness is the most common presentation; however, many patients with biopsy-confirmed amyloid deposition lack objective weakness, as amyloid within muscle does not necessarily equate to clinically significant myopathy. Amyloid myopathy is probably underdiagnosed due to the limited use of muscle biopsies and potential under-detection of amyloid deposition in muscle specimens. Histopathologically, it is characterized by amyloid deposition predominantly within the perimysial and endomysial blood vessel walls and perivascular regions. Neurogenic features are also frequently observed in muscle biopsies from patients with systemic amyloidosis-associated or isolated myopathy. While amyloid microangiopathy and neurogenic features seem to dominate amyloid myopathy pathology, the pathogenesis remains elusive. In this article, we comprehensively review amyloid myopathy pathogenesis and histopathological correlates including specific workup for detection of amyloid deposition, as well as clinical manifestations, diagnostic approach, and management. This review reveals that amyloid myopathy may represent a microangiopathic-neurogenic-myopathic process.