Amyloid Neuropathies

This article reviews the pathophysiology, epidemiology, and clinical features of amyloid neuropathies, with a focus on light chain (AL) amyloidosis and hereditary amyloidogenic transthyretin (ATTRv) amyloidosis, and provides a brief overview of the most common systemic amyloidoses associated with neuropathy.

Minimally invasive biopsies, such as skin punch biopsy and fat aspirate, are reasonable first biopsy sites in the evaluation of amyloid neuropathy with sensitivities of 48% to 83% for amyloid deposits. In the United States, it is recommended that every patient with ATTRv amyloidosis with peripheral neuropathy should have tissue confirmation of amyloid positivity. With the development of daratumumab, a highly effective plasma cell-depleting therapy, the survival rate for AL amyloidosis has increased, and the first-line therapy no longer includes autologous stem cell transplantation. First-generation and second-generation gene silencers are now available for the treatment of ATTRv amyloidosis with peripheral neuropathy and are highly effective in halting disease progression.

The overwhelming majority of amyloid neuropathies are secondary to AL amyloidosis or ATTRv amyloidosis, both treatable disorders that must not be missed. Their progressive nature and associated autonomic dysfunction are the most important clinical features and should always raise the possibility of amyloid neuropathies. The initial diagnostic workup of progressive neuropathies of uncertain etiology should always include monoclonal protein studies (with free light chain assay) and a fat aspirate or skin biopsy.