This study will enroll patients with small fiber neuropathy (SFN). The study will look at an intravenous immunoglobulin (IVIG) called Panzyga. Panzyga is approved by the FDA as a therapy for Primary humoral immunodeficiency (PI) in patients 2 years of age and older; Chronic immune thrombocytopenia (ITP) in adults and Chronic inflammatory demyelinating polyneuropathy (CIDP) in adults. It has not been approved by the FDA for use in SFN.

There is mounting evidence that Intravenous Immunoglobulin (IVIG) can cause pain reduction and improve objective nerve fiber densities on skin biopsies in great numbers in SFN patients. The primary outcome is quantified improvement in intraepidermal nerve fiber density (IENFD) on repeat skin punch biopsy after 6 months of IVIG treatment.

Small fiber neuropathy (SFN) is an increasingly prevalent diagnosis in neurology and neuromuscular centers. Modern diagnostic techniques, including skin biopsies and autonomic nervous testing are helping to find SFN in many patients with undiagnosed pain syndromes including fibromyalgia. The prevalence is rising for SFN, and an immune etiology may underlie 19%-34% of cases. While there is no standard of care treatment, current treatment strategies for SFN include long-term steroid therapy which come with a host of side effects. There is mounting evidence that Intravenous Immunoglobulin (IVIG) can cause pain reduction and improve objective nerve fiber densities on skin biopsies in great numbers in SFN patients, as well as improving validated questionnaire scores monitoring symptom burden and disability. However, neither IVIG nor any other immunosuppressant has been studied in a sufficiently powered and adequately dosed controlled, randomized clinical trial to demonstrate efficacy.

Inclusion Criteria:

1. Patients ≥ age 18
2. Patient with clinical and biopsy evidence of pure small fiber neuropathy (with or without dysautonomia) as evidenced by reduced IENFD on skin biopsy using PGP 9.5 as the immunostain. Biopsy must have been performed within 12 months of study enrollment. If biopsies were not done at CRL, they will be repeated and done at 3 sites (upper and lower thigh, lower calf), to have consistent and equivalent biopsy data with the follow up biopsy done after 6 mos of treatment
3. Patients must have elevated and/or abnormal titers of autoantibodies to TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 measured by the Washington University Neuromuscular Laboratory (St Louis) within 12 mos of enrollment
4. Patients must have a baseline pain score on a visual analogue scale (VAS) of Greater or equal to 4/10
5. Patients must have a baseline Utah Early Neuropathy Scale (UENS) score of Greater or equal to 4/10
6. Small Fiber Neuropathy Screening List (SFNSL) score of 11/84 or greater
7. Non-pregnant, non-lactating female. Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during treatment

Exclusion Criteria:

1. Any other known cause for small fiber neuropathy other than the presence of the elevated titers of TS-HDS-IgM, FGFR3-IgG, or Plexin-D1 autoantibodies
2. Patients with generalized, severe musculoskeletal conditions other than SFN that prevent a sufficient assessment of the patient by the physician
3. Electromyography/nerve conduction study (EMG/NCS) evidence of large fiber polyneuropathy, to be confirmed by study PI
4. Underlying severe heart, kidney, liver disease, or HIV infection, (Note: If there is no previous HIV test result documented within the last 5 years, a test may be performed in order to confirm eligibility)
5. Patients with a history of deep vein thrombosis within the last year prior to baseline visit or pulmonary embolism ever; patients with susceptibility to embolism or deep vein thrombosis
6. Known significant IgA deficiency with antibodies to IgA
7. History of hypersensitivity, anaphylaxis or severe systemic response to immuno-globulin, blood or plasma derived products, or any component of IVIG 10%
8. Known blood hyperviscosity, or other hypercoagulable states
9. Use of IgG products within six months prior to enrollment
10. Patients with a history of drug or alcohol abuse within the past five years prior to enrollment
11. Patients unable to understand or unwilling or unable to comply with the study protocol

This is a double-blind trial. The participant and the investigator will be masked to the treatment assignment.