Chronic Inflammatory Demyelinating Polyneuropathy(CIDP)

CIDP is distinguished from GBS by its chronic course. In other respects, this neuropathy shares many features with the common demyelinating form of GBS, including elevated CSF protein levels and findings of acquired demyelination. Most cases occur in adults, and males are affected slightly more often than females.

Clinical Manifestations

Onset is usually gradual over a few months or longer, but in a few cases the initial attack is indistinguishable from that of GBS. An acute-onset form of CIDP should be considered when GBS deteriorates >9 weeks after onset or relapses at least three times. Symptoms are both motor and sensory in most cases.
Weakness of the limbs is usually symmetric but can be strikingly asymmetric in multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy variant in which discrete peripheral nerves are involved. Tremor occurs in 10% and may become more prominent during periods of subacute worsening or improvement. A small proportion have cranial nerve findings, including external ophthalmoplegia. CIDP tends to ameliorate over time with treatment; the result is that many years after onset, nearly 75% of patients have reasonable functional status. Death from CIDP is uncommon.

Diagnosis

The diagnosis rests on characteristic clinical, CSF, and electrophysiologic findings. The CSF is usually acellular with an elevated protein level. As with GBS, a CSF pleocytosis should lead to the consideration of HIV infection, leukemia or lymphoma, and neurosarcoidosis. Nerve conductionstudies findings reveal variable degrees of conduction slowing, prolonged distal latencies, distal and temporal dispersion of CMAPs, and conduction block as the principal features.Serum protein electrophoresis with immunofixation is indicated to search for monoclonal gammopathy and associated In all patients with presumptive CIDP, it is also reasonable to exclude vasculitis, collagen vascular disease (especially SLE), chronic hepatitis, HIV infection, amyloidosis, and diabetes mellitus. Other associated conditions include inflammatory bowel disease and lymphoma.
Pathogenesis
Although there is evidence of immune activation in CIDP, the precise mechanisms of pathogenesis are unknown. The response to therapy suggests that CIDP is immune-mediated; CIDP responds to glucocorticoids, whereas GBS does not. Approximately 25% of patients with clinical features of CIDP also have a monoclonal gammopathy of undetermined significance (MGUS). Cases associated with monoclonal IgA or IgG kappa usually respond to treatment as favorably as cases without a monoclonal gammopathy. Patients with IgM monoclonal gammopathy tend to have more sensory findings and a more protracted course, and usually have a less satisfactory response to treatment.

Treatment:

Most authorities initiate treatment for CIDP when progression is rapid or walking is compromised. If the disorder is mild, management can be expectant, awaiting spontaneous remission. Controlled studies have shown that high-dose IVIg, PE, and glucocorticoids are all more effective than placebo. Initial therapy is usually with IVIg, administered as 2.0 g/kg body weight given in divided doses over 2–5 days; three monthly courses are generally recommended before concluding a patient is a treatment failure. If the patient responds, the infusion intervals can be gradually increased or the dosage decreased (e.g., 1 g/kg per month). PE, which appears to be as effective as IVIg, is initiated at two to three treatments per week for 6 weeks; periodic re-treatment may also be required.
Treatment with glucocorticoids is another option (60–80 mg prednisone PO daily for 1–2 months, followed by a gradual dose reduction of 10 mg per month as tolerated), but long-term adverse effects including bone demineralization, gastrointestinal bleeding, and cushingoid changes are problematic.
As many as one-third of patients with CIDP fail to respond adequately to the initial therapy chosen; a different treatment should then be tried. Patients who fail therapy with IVIg, PE, and glucocorticoids may benefit from treatment with immunosuppressive agents such as azathioprine, methotrexate, cyclosporine, and cyclophosphamide, either alone or as adjunctive therapy. Early experience with anti-CD20 (rituximab) has also shown promise. Use of these therapies requires periodic reassessment of their risks and benefits. In patients with a CIDP-like neuropathy who fail to respond to treatment it is important to evaluate for POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes.