Paraproteinemic Neuropathies

Paraproteinemic neuropathies present with a myriad of phenotypes and associated underlying plasma cell dyscrasias. This article provides a phenotype-driven approach to the evaluation of paraproteinemic neuropathies, guided by an alignment of clinical, electrodiagnostic, and serologic features.

The advent of targeted immunotherapies has improved outcomes for patients with plasma cell dyscrasia. While no US Food and Drug Administration (FDA)-approved therapies exist for the disabling paraproteinemic neuropathies discussed in this article, such as anti-myelin-associated glycoprotein neuropathy or polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS), increased understanding of these neuropathies' pathomechanisms and natural history is paving the way for newer, promising therapies. There are multiple ongoing trials, such as using Bruton tyrosine kinase inhibitors for the treatment of anti-myelin-associated glycoprotein neuropathy.

The evaluating clinician needs to properly order and interpret screening tests for paraproteinemic neuropathy. Red flag features beyond the typical distal symmetric polyneuropathy phenotype, namely, the presence of symmetric distal or proximal weakness, ataxia, autonomic deficits, ophthalmoplegia, demyelination on nerve conduction studies, and IgM or lambda gammopathy (particularly when combined with any of the above features), should prompt added scrutiny and phenotype-driven testing. Early diagnosis can streamline the administration of potentially effective immunotherapies and avoid unnecessary and inappropriate therapies and cost.