Small nerve fiber neuropathy (SFN) is a disorder of thinly myelinated and unmyelinated nerve fibers recently recognized as a distinct clinical syndrome, with a minimum incidence of 12 per 100.000 and a minimum prevalence of 53 per 100.000. The clinical picture is typically dominated by neuropathic pain, often with a burning quality, and autonomic symptoms. The diagnosis of SFN is usually made on the basis of the clinical picture, no involvement of large nerve fibers at neurological examination and normal nerve conduction studies (NCS), and is confirmed by demonstration of reduced intra-epidermal nerve fiber density (IENFD) or abnormal quantitative sensory testing (QST). Despite intensive search for underlying causes such as diabetes mellitus, impaired glucose tolerance, Fabry's disease, hereditary disorders, celiac disease, sarcoidosis, HIV and other systemic illnesses which may be potentially treatable, the proportion of patients with idiopathic SFN (I-SFN) remains substantial, ranging in different series from 24% up to 93%. It is conceivable that immunological mechanisms play a role in patients with I-SFN, since several immune-mediated diseases, such as sarcoidosis, Sjogren's disease and systemic lupus erythematosis may cause SFN. Auto-antibodies have also been reported in patients with SFN. Moreover, inflammatory changes in nerves have been found. Elevated pro-inflammatory cytokines have been suggested to be involved in the pathophysiology of pain in SFN.~In other immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy, treatment with intravenous immunoglobulin (IVIg) has proven to be efficacious. Moreover, some case studies in patients with SFN and chronic pain have also reported effect of immunomodulating therapy. Pain reduction with IVIg treatment has also been summarized recently.~Intravenous infusion of high doses of pooled immunoglobulin G (IgG) molecules from thousands of donors (IVIg therapy) represents an efficient anti-inflammatory treatment for many autoimmune diseases. Paradoxically, IgG can exert both pro- and anti-inflammatory activities, depending upon its concentration. When administered in high concentrations, IVIg has anti-inflammatory properties. How this anti-inflammatory effect is mediated has not yet been fully elucidated. Several mutually nonexclusive mechanisms have been proposed, including modulation of the expression and function of the Fc fragment of IgG to IgG-specific receptors, interference with activation of the complement cascade and the cytokine network, neutralization of autoantibodies and regulation of cell proliferation. However, the exact mechanism of IVIg in the treatment of inflammatory neuropathies has not been elucidated.~Side effects of IVIg treatment are usually transient (chills, headache, dizziness, fever, vomiting, nausea, arthralgia, low blood pressure and moderate low back pain may occur occasionally).~Sudden fall in blood pressure and anaphylactic shock are rare. More severe side effect are extremely rare (reversible aseptic meningitis, transient cutaneous reactions, reversible haemolytic reactions, haemolytic anemia, and thromboembolic events).~SFN is considered the most common cause of neuropathic pain in peripheral neuropathies. Patients with SFN have reported having excruciating pain, since current anti-neuropathic and other pain drugs do not relief pain substantially. SFN interferes with daily functioning and may lead to a decrement in quality of life expectations. Therefore, a better treatment is warranted. The aim of the current pilot study is to investigate the efficacy and safety of IVIg in patients with I-SFN in a randomized, double-blind, placebo-controlled study.
Small fiber neuropathy (SFN) is the most common cause of neuropathic pain in peripheral neuropathies, with a prevalence of at least 53/100.000. Patients with SFN may have excruciating pain and current anti-neuropathic and other pain drugs do not relief pain substantially.~Several studies suggested an immunological basis in SFN and case studies have reported efficacy of treatment with intravenous immunoglobulin (IVIg) in patients with SFN. It is therefore conceivable that immunological mechanisms play a role in idiopathic SFN (I-SFN). However, to date no randomized controlled study with IVIg in patients with SFN has been performed. The aim of the current study is to investigate the efficacy and safety of IVIg in patients with I-SFN in a randomized, double-blind, placebo-controlled study.~The objective of the study is to evaluate the efficacy of IVIg treatment (4 courses of treatment, 3 weeks apart) compared to placebo on pain alleviation.