What is the role of intravenous immunoglobulin (IVIG) in treating peripheral neuropathy, particularly in patients with autoimmune or inflammatory causes, and what is the prognosis for these patients?

Role of Immunoglobulin in Peripheral Neuropathy and Prognosis

IVIG should be considered for acute inflammatory demyelinating polyneuropathy (AIDP)-type peripheral neuropathy, while steroids are appropriate for mild cases; prognosis varies significantly based on underlying etiology, with autoimmune causes generally responding better than paraproteinemic neuropathies. 1

Treatment Algorithm by Clinical Presentation

Acute Inflammatory Demyelinating Polyneuropathy (AIDP/Guillain-Barré Syndrome)

• IVIG is first-line therapy for severe GBS (grade 3-4), equally effective as plasmapheresis 2, 3
• Standard dosing: 2 g/kg body weight administered intravenously 4, 5
• Combined treatment with corticosteroids and IVIG may be promising, though corticosteroids alone do not significantly hasten recovery 3
• Both IVIG and plasma exchange are equally effective as first-line therapies 2, 3

Mild Peripheral Neuropathy

• Steroids should be considered as initial treatment for mild symptoms 1
• Dexamethasone 10 mg daily is a reasonable starting dose 1
• This applies to CAR T-cell therapy-related neuropathy (median onset 57 days) and other mild inflammatory neuropathies 1

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

• Corticosteroids, IVIG, and plasma exchange are equally effective 3
• IVIG is established as first-line therapy with proven long-term efficacy 6
• Subcutaneous immunoglobulin may be a more patient-friendly alternative with better tolerability, though long-term efficacy requires further validation 6

Multifocal Motor Neuropathy (MMN)

• IVIG is the first-choice therapy; corticosteroids and plasma exchange are ineffective or detrimental 3
• This represents a critical distinction where steroids should be avoided 3

Vasculitic Peripheral Neuropathy

When Conventional Treatment Fails

• IVIG (2 g/kg body weight) should be considered for steroid-resistant or immunosuppressive-resistant vasculitic neuropathy 4, 5
• Response rates are favorable in Sjögren's syndrome, SLE, Churg-Strauss vasculitis, and vaccination-induced vasculitis 4, 5
• Treatment may require 1-13 cycles depending on severity and response 4

Poor Response Conditions

• Mixed cryoglobulinemia associated with hepatitis C shows limited response to IVIG 4, 5
• Sarcoidosis-associated neuropathy may not respond adequately 4
• Close monitoring of HCV or HBV infection is necessary after apheresis, especially when combined with immunosuppressants 2

Paraproteinemic Neuropathy

IgM-Associated Neuropathy

• Plasmapheresis should be considered for aggressive IgM-related neuropathy with rapid progression 1, 2
• Initial course: 2-3 months of weekly plasmapheresis before symptomatic improvement is typically seen 1
• Plasmapheresis must be consolidated with chemotherapy; IgM levels return to baseline in 4-6 weeks without ongoing treatment 1

Waldenström Macroglobulinemia-Related Neuropathy

• Single-agent rituximab for mild, slowly progressive neuropathy 1
• Cyclophosphamide/prednisone/rituximab or rituximab/cyclophosphamide/dexamethasone for moderate-to-severe or aggressive neuropathy 1
• Symptomatic improvement more likely with: non-amyloid neuropathy (48.5% vs 15.4%), major response (≥50% IgM reduction; 79% vs 35.5%), earlier therapy (≤24 months; 57.3% vs 42.5%), and rituximab combinations (59.3% vs 37.0%) 1

Critical Caveat

• Bortezomib-based regimens should be avoided in patients with pre-existing disease-related peripheral neuropathy 1
• When bortezomib is necessary, use subcutaneous administration once weekly to reduce neuropathy risk 1
• Grade 3 peripheral neuropathy occurred in 30% with twice-weekly IV bortezomib, leading to premature discontinuation in 61% 1

Prognosis by Etiology

Favorable Prognosis

• Vasculitic neuropathy from Sjögren's syndrome, SLE, Churg-Strauss, and vaccination-induced vasculitis: neuropathy resolved or significantly improved with IVIG 4, 5
• CIDP with major response to IVIG: sustained improvement with ongoing therapy 3, 6
• GBS/AIDP: IVIG and plasma exchange equally effective for recovery 2, 3

Guarded Prognosis

• SLE-related optic neuritis: only 30% maintain visual acuity >20/25 despite treatment 1
• IgM paraproteinemic neuropathies: known to be intractable with slow disease progression 3
• Peripheral neuropathy in SLE: significant predictor of damage, though NCS parameters remained unchanged in 67% over 7 years 1

Poor Prognosis Indicators

• Mixed cryoglobulinemia with hepatitis C: limited IVIG response 4
• Sarcoidosis-associated neuropathy: poor IVIG response 4
• Anti-myelin-associated glycoprotein antibody-positive neuropathy: often intractable despite immunotherapy 3

Special Populations

CAR T-Cell Therapy-Related Neuropathy

• Approximately 7% incidence with ciltacabtagene autoleucel 1
• Types include lower motor neuron facial paralysis, cranial nerve palsy, peripheral sensory and motor neuropathy 1
• For AIDP-type picture, consider IVIG in line with current AIDP treatment guidelines 1

Systemic Lupus Erythematosus

• Peripheral neuropathy occurs in 2-3% of SLE patients 1
• Glucocorticoids alone or with immunosuppressive therapy: 60-75% response rate 1
• IVIG, plasma exchange, and rituximab reserved for severe cases 1

Monitoring and Supportive Care

After Immunoglobulin Therapy

• Monitor IgG trough levels, blood counts, and serum chemistry 2
• Follow-up duration: 1-5 years documented in vasculitic neuropathy studies 4, 5

Adjunctive Symptomatic Treatment

• Gabapentin, pregabalin, and duloxetine for symptomatic improvement during plasmapheresis or immunotherapy 1
• These agents provide symptomatic relief while addressing underlying pathology 1