What causes chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)?

Updated: Jun 13, 2018
  • Author: Richard A Lewis, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Answer

Chronic inflammatory demyelinating polyradiculoneuropathy is most frequently an idiopathic illness, but it has been known to occur with several conditions. In those cases, the associated condition is included in the main diagnosis (eg, CIDP with systemic lupus erythematosus, CIDP with HIV infection, CIDP associated with hepatitis B or C) to separate those cases from the idiopathic variety. Most reported conditions associated with CIDP are listed below.

  • CIDP associated with other disorders cannot be distinguished clinically from isolated CIDP except where mentioned in this section. The disease mechanisms for all these disorders are not known. They appear to be immunologic; in some instances, antibody-mediated mechanisms have been shown to play a role.

  • Vasculitis does not seem to be involved; physiologic and pathologic differences can distinguish the multifocal variants of CADP from vasculitic mononeuritis multiplex. Vasculitic neuropathies cause wallerian degeneration with minimal signs, if any, of segmental demyelination on biopsy and electromyographic studies (EMG). The multifocal variants of CADP have prominent conduction block and slowing—hallmarks of segmental demyelination.

  • HIV infection: In these patients, mild lymphocytic pleocytosis and increased gamma globulin level in the CSF are seen frequently. CIDP has been observed with early disease and later on in the course of AIDS.

  • Hodgkin lymphoma: Neuropathy associated with Hodgkin lymphoma is not caused by direct infiltration of the peripheral nerves but is a consequence of the autoimmune cascade that occurs with this disease; the mechanism is not completely clear.

  • Paraproteinemias and/or plasma cell dyscrasias

    • CADP is seen with monoclonal gammopathies (eg, monoclonal gammopathy of unknown significance [MGUS]), most frequently gammopathy of IgM. Evidence exists to suggest that CADP with IgM MGUS has specific clinical and electrophysiologic characteristics. Patients usually have predominance of distal sensory symptoms that are greater than motor symptoms. Conduction slowing on nerve conduction testing is accentuated in distal nerve segments. Fifty percent of patients with IgM-associated neuropathies have antibodies directed against MAG, a protein found in noncompact myelin of peripheral nerves. Whether any clinical difference exists between patients with IgM gammopathy without anti-MAG antibodies and those with anti-MAG antibodies is not clear. In both cases, the response to immunosuppressive and/or immunomodulatory treatment is poor. However, a number of reports, including a double-blind controlled trial, describe a response to rituximab, a monoclonal antibody directed against B cells.

    • Some paraproteinemias occur as isolated phenomena and some are by-products of malignant cells, as in the cases of Waldenström macroglobulinemia and myeloma. In myeloma-associated neuropathy, the abnormal paraprotein usually consists mostly of lambda light chain component. Combination of osteosclerotic myeloma, organomegaly, endocrinopathy, M protein, sensorimotor neuropathy, and pigmentary skin changes is referred to as POEMS syndrome. In POEMS syndrome, the M protein is typically immunoglobulin G (IgG).

    • The association of CIDP with IgG or immunoglobulin A (IgA) gammopathy is less clear. IgG paraproteins can occur in 5% of the population and it is unclear that the incidence of IgG paraproteins is excessive in patients with demyelinating neuropathy. Patients with CIDP and IgG or IgA paraproteins have identical clinical and electrophysiologic features to patients with CIDP and no paraprotein. Response to treatment is also the same.

  • Multiple sclerosis: Reports describe CNS white matter changes in patients with CIDP. Whether a true association exists between CIDP and multiple sclerosis remains unclear.

  • Chronic active hepatitis (B or C): CIDP associated with hepatitis should be differentiated from cryoglobulinemic vasculitis. The latter causes either symmetric distal sensorimotor polyneuropathy or mononeuropathy multiplex but on pathologic examination shows wallerian degeneration and not the segmental demyelination seen in CIDP. Patients can respond to standard CIDP treatments, but in some patients, treatment of the hepatitis infection is associated with remission of the CIDP.

  • Inflammatory bowel disease (IBD): CIDP has been described in association with Crohn disease and other inflammatory bowel conditions, although no direct correlation between the 2 afflictions is known. The mechanism of development of CIDP is presumed to be an autoimmune abnormality that is also causing the primary problem in inflammatory bowel disease, although the details are not known. The situation has become complicated with the recognition that TNF-alpha therapies used for IBD can cause CIDP.

  • TNF-alpha blockers: CIDP, Lewis-Sumner syndrome, and multifocal motor neuropathy have been described in patients with rheumatoid arthritis and IBD who are treated with TNF-alpha blockers, particularly etanercept and infliximab. In some cases, discontinuation of the medication was associated with remission of the inflammatory neuropathy.

  • Diabetes mellitus: Whether an increased incidence of CIDP occurs in patients with diabetes mellitus remains unclear. The most recent literature has not corroborated earlier reports of an association.

  • Pregnancy: Pregnancy is known to exacerbate CIDP. Worsening usually occurs in the third trimester or in the postpartum period.


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