Chronic Inflammatory Demyelinating Polyneuropathy: How Pathophysiology Can Guide Treatment.

Abstract

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune demyelinating neuropathy that is most commonly characterized clinically by progressive proximal and distal weakness affecting the upper and lower extremities, sensory loss, and reduced or absent reflexes. These symptoms evolve over the time course of 8 weeks or more. While the majority of CIDP demonstrates this clinical phenotype, there are CIDP variants as well. The milieu of the underlying pathophysiology and immunologic factors involved is complex and involves components of both the innate and adaptive immune systems. As more is understood about the underlying pathophysiology, novel targets and patterns have emerged guiding further classification and management. This is most notable in the discovery of antibodies targeting paranodal and nodal regions related to anti-neurofascin-155 and anti-contactin-1 antibody-mediated disease resulting in a reclassification as demyelinating nodo-paranodopathies. Triggering antigens and correlative antibodies for CIDP are otherwise undiscovered. While first-line therapies for CIDP currently are broad and non-targeted, a shift in approach has been to develop specific targeted treatments guided by what is understood about the underlying pathophysiology. Some of these targets include specific types of B-cell depletion, complement inhibition, immunoglobulin G (IgG) reduction via inhibition of the neonatal Fc receptor (FcRn) recycling of IgGs, treatments related to T-cell dysfunction, and macrophage inhibition.