Small Fiber Neuropathy

Disorder of the peripheral nerves that primarily impair small nerve fibers. The affected small nerve fibers include myelinated A-delta fibers (see A FIBERS) and unmyelinated C FIBERS. Because these small fibers innervate skin and help control autonomic function, their neuropathy presents with neuropathic pain, reduced thermal and pain sensitivity, and autonomic dysfunction (e.g. abnormal sweating or facial flushing). Small fiber neuropathy can be idiopathic or associated with underlying diseases (e.g., AMYLOIDOSIS; DIABETES MELLITUS; SARCOIDOSIS; or VASCULITIS).

Also Known As:

Networked: 287 relevant articles (20 outcomes, 28 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Sarcoidosis (Schaumann Disease)
2.	Pain (Aches)
3.	Neuralgia (Stump Neuralgia)
4.	Neurodegenerative Diseases (Neurodegenerative Disease)
5.	Type 2 Diabetes Mellitus (MODY)

Experts

1.	Faber, Catharina G: 20 articles (01/2022 - 06/2012)
2.	Merkies, Ingemar S J: 16 articles (10/2021 - 11/2012)
3.	Hoeijmakers, Janneke G J: 15 articles (10/2021 - 11/2012)
4.	Waxman, Stephen G: 12 articles (01/2021 - 11/2012)
5.	de Greef, Bianca T A: 11 articles (10/2021 - 06/2015)
6.	Lauria, Giuseppe: 11 articles (01/2021 - 11/2012)
7.	Geerts, Margot: 9 articles (01/2022 - 01/2016)
8.	Dib-Hajj, Sulayman D: 6 articles (01/2020 - 11/2012)
9.	Gerrits, Monique M: 6 articles (01/2020 - 11/2012)
10.	Sopacua, Maurice: 5 articles (10/2021 - 01/2019)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Small Fiber Neuropathy:

1.	Intravenous Immunoglobulins (IVIG)FDA Link 01/01/2023 - "To our knowledge, this is the first published case report of COVID vaccination-induced FGFR3-associated small fiber neuropathy improving in the context of IVIG administration as demonstrated by normalization of small fiber density measured by skin biopsy accompanied by marked improvement in the patient's symptoms." 01/01/2016 - "Several open-label studies have suggested an immunological basis in small fiber neuropathy and have reported efficacy of treatment with intravenous immunoglobulin. " 11/01/2019 - "Intravenous immunoglobulin efficacy for primary Sjögren's Syndrome associated small fiber neuropathy." 01/01/2020 - "Prior studies have shown that in small fiber neuropathy of autoimmune etiology, intravenous immunoglobulin (IVIg) holds promise as an effective treatment. " 01/01/2016 - "To date, no randomized controlled study with intravenous immunoglobulin in patients with small fiber neuropathy has been performed. "
2.	Insulin (Novolin)FDA Link 01/01/2015 - "Treatment-induced neuropathy in diabetes (also referred to as insulin neuritis) is considered a rare iatrogenic small fibre neuropathy caused by an abrupt improvement in glycaemic control in the setting of chronic hyperglycaemia. " 01/01/2015 - "Corneal confocal microscopy shows an improvement in small-fiber neuropathy in subjects with type 1 diabetes on continuous subcutaneous insulin infusion compared with multiple daily injection."
3.	Biomarkers (Surrogate Marker)IBA 08/01/2008 - "The aim of this study was (1) to investigate whether vasoconstriction-induced microvascular oscillations in the skin are reduced in diabetic patients with peripheral and/or autonomic neuropathy, and (2) whether this method could be used as a non-invasive surrogate marker to assess diabetic small fiber neuropathy. " 01/01/2023 - "We examined putative biomarkers of neuropathy in blood and tissue and quantified levels of small fiber neuropathy, looking for associations between lowered 1-deoxySL and phenotypes. " 01/01/2022 - "Corneal confocal microscopy (CCM) is a non-invasive, in-vivo diagnostic technique that provides an accurate surrogate biomarker for small-fiber neuropathy. " 01/01/2020 - "Recently, there is also interest in the evaluation of IENF via skin biopsy as a biomarker of small fiber neuropathy in the regulatory setting. " 10/15/2015 - "Among the biomarkers for different nerve fiber categories, only the small fiber neuropathy assessments were significantly related to all domains of the WHOQoL. "
4.	LacosamideFDA Link 01/01/2016 - "The Lacosamide-Efficacy-'N'-Safety in Small fiber neuropathy (LENSS) study is a randomized, double-blind, placebo-controlled, crossover trial in patients with SCN9A-associated small fiber neuropathy, with the primary objective to evaluate the efficacy of lacosamide versus placebo. " 01/01/2016 - "This is the first study that will be evaluating the efficacy, safety, and tolerability of lacosamide versus placebo in patients with SCN9A-associated small fiber neuropathy. " 01/01/2016 - "Efficacy, safety, and tolerability of lacosamide in patients with gain-of-function Nav1.7 mutation-related small fiber neuropathy: study protocol of a randomized controlled trial-the LENSS study." 01/01/2020 - "Taken together, these findings begin to unravel biophysical underpinnings that contribute to responsiveness to lacosamide in patients with small fibre neuropathy carrying select Nav1.7 variants." 01/01/2020 - "Differential effect of lacosamide on Nav1.7 variants from responsive and non-responsive patients with small fibre neuropathy."
5.	Glucose (Dextrose)FDA LinkGeneric 08/01/2006 - "The abnormal glucose metabolism rates were found to be similar across the 3 subtypes (sensorimotor, pure sensory, and small-fiber neuropathy) of CIAP (P = .60, .72, and .61). " 05/01/2012 - "We adopted several new methods to evaluate autonomic function accurately for detecting the onset of small-fiber neuropathy, such as laser-Doppler flowmetry, ultrasonography, 123I-MIBG scintigraphy, electrogastrography, cystometry, glucose-tolerance test, near-infrared spectrophotoscopy, blood pressure tests, and evaluation of sweating. " 08/01/2015 - "CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status." 04/01/2011 - "Small-fiber neuropathy is frequently associated with pain, and these patients may present to a neurologist for evaluation before the underlying glucose dysregulation has been diagnosed. " 04/01/2011 - "It is increasingly recognized that individuals with "prediabetes" or impaired glucose regulation can already have a "small-fiber" neuropathy, or mild DSP, in which sensory axons of both small and larger diameter are damaged. "
6.	Capsaicin (Zostrix)FDA Link 01/01/2016 - "The in vivo cutaneous nerve regeneration model using capsaicin is applied extensively to study the regenerative mechanisms and therapeutic efficacy of disease modifying molecules for small fiber neuropathy (SFN). " 01/01/2016 - "This study indicates that capsaicin application results in significant loss of epidermal NRP-1 receptor expression, whereas diabetic subjects presenting small fiber neuropathy show full epidermal NRP-1 expression in contrast to the basal expression pattern seen in healthy controls. " 07/01/2019 - "This case report shows the correlation between clinical improvement, electrochemical skin conductance normalization, and intraepidermal nerve fiber density improvement after a high-dose capsaicin patch in a patient with small fiber neuropathy." 10/01/2013 - "LDI measurements were taken before and longitudinally after a 48-hour application of 0.1% capsaicin (to cause a transient small fiber neuropathy) on the skin of the thigh; placebo cream was placed on the contralateral thigh as a control. " 01/01/2013 - "In conclusion, topical application of capsaicin causes a small fiber neuropathy and is associated with a delay in healing of shallow, but not deep wounds. "
7.	TinIBA 04/01/2021 - "Conclusions TIN was predominantly sensory with normal nerve conduction studies which is the main feature of small fiber neuropathy. " 09/01/2019 - "Treatment-induced neuropathy (TIN) in diabetes is an acute and painful yet completely reversible small fiber neuropathy precipitated by a rapid improvement in glycemic control. "
8.	AntibodiesIBA 01/01/2023 - "We report a case of a patient with confirmed small fiber neuropathy post-COVID-19 vaccination with positive FGFR3 antibodies. " 01/01/2023 - "Four patients had skin biopsy or quantitative sudomotor axon reflex test (QSART)-proven small fiber neuropathy, and five had various positive antibodies at low titers. " 01/01/2020 - "Green shoots but deep roots: New antibodies in small fiber neuropathy." 01/01/2018 - "The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy." 12/01/2017 - "SS patients with certain forms of neurologic involvement, such as small fiber neuropathy and sensory ataxic ganglionopathy, frequently lack anti-SSA and anti-SSB antibodies and other serologic abnormalities. "
9.	SteroidsIBA 03/01/2006 - "We describe four patients with acute small-fiber neuropathy who responded dramatically to steroid therapy. " 01/01/2015 - "Neurological Symptoms of Sarcoidosis-induced Small Fiber Neuropathy Effectively Relieved with High-dose Steroid Pulse Therapy."
10.	Immunoglobulins (Immunoglobulin)IBA 12/01/2020 - "Long-term efficacy of immunoglobulins in small fiber neuropathy related to Sjögren's syndrome." 01/01/2023 - "A double-blind placebo-controlled pilot study of immunoglobulin for small fiber neuropathy associated with TS-HDS and FGFR-3 autoantibodies."

Therapies and Procedures

1.	Therapeutics 01/01/2021 - "However, studies in murine models and data from small observational studies indicate an association between increased circulating PCSK9 levels and small nerve fibre damage with a protective effect of PCSK9i therapy against small fibre neuropathy. " 10/05/2023 - "Fellows Research Article: Use of Scrambler Therapy to Treat Small Fiber Neuropathy." 05/01/2022 - "[Small Fiber Neuropathy with Inadequate Response to Medical Therapy: Diagnosis and Treatment of Small Fiber Neuropathy]." 05/01/2022 - "[Small Fiber Neuropathy with Inadequate Response to Medical Therapy: Diagnosis of The Etiology of Small Fiber Neuropathy and Treatment Option]." 09/15/2021 - "There is a clinical need for novel techniques for assessing small fibre function to improve detection of small fibre neuropathy and expand the role of available therapies. "
2.	Enzyme Replacement Therapy 06/01/2012 - "Neuropathic pain and small fiber neuropathy characteristics have therefore been considered as appropriate study endpoints in studies on the efficacy of enzyme replacement therapy. " 07/01/2006 - "We prospectively evaluated the effect of enzyme replacement therapy (ERT) on the intraepidermal nerve fiber density (IENFD) and thermal threshold in patients with Fabry disease, an X-linked disorder associated with a painful small-fiber neuropathy and decreased linear IENFD in a length-dependent pattern. " 10/01/2013 - "The diagnostic dilemmas in patients with neuropathic pain and a non-classical disease course are discussed, together with the available diagnostic modalities, pain medication options and the effect of enzyme replacement therapy on small fiber neuropathy." 01/01/2007 - "However, these findings, coupled with the disparity in C-fiber subtype involvement in diabetic small-fiber neuropathy, and the recently reported inability of enzyme replacement therapy in Fabry disease to influence intraepidermal innervation density, while having mixed effects on cold and warm QST thresholds, and beneficial effects on sudomotor findings, when therapeutic benefit was demonstrated, lead one to conclude that the specificity of ancillary testing in neuropathic pain is inadequate at present, and reinforce the aforementioned caveats about inferential conclusions from indirect data. "
3.	Gluten-Free Diet 09/01/2014 - "Nonetheless, progressive multifocal neuropathy, motor neuropathy, small fiber neuropathy, and sensory neuronopathy should be treated early and aggressively with immunosuppression (or the gluten-free diet in appropriate situations) to limit morbidity. " 10/01/2022 - "Improvement in small fiber neuropathy after a gluten-free diet, demonstrated in a patient with celiac disease by measurement of electrochemical skin conductance." 12/01/2008 - "Cerebellar syndrome and small fiber neuropathy may complicate celiac disease (CD) and may be resistant to a strict gluten-free diet. "
4.	Glycemic Control 09/01/2019 - "Treatment-induced neuropathy (TIN) in diabetes is an acute and painful yet completely reversible small fiber neuropathy precipitated by a rapid improvement in glycemic control. "
5.	Lasers (Laser) 06/01/2011 - "Quantitative analysis of epidermal innervation is globally performed for determining the indices of small fiber neuropathy, and recently, laser microscopic evaluation of corneal innervation was proposed as a surrogate technique for skin or nerve biopsy, to serve as a quantitative marker for neuropathy. " 09/24/2002 - "Flare size, but not laser Doppler flux, clearly distinguished patients from controls at both locations (p < 0.01) and may be useful for evaluation of small-fiber neuropathies." 10/01/2012 - "Convergent results were obtained across the different experiments, indicating that the detection rate to brief small-diameter CO(2) laser pulses could be used to estimate IENF density and, hence, to diagnose and quantify denervation in small fiber neuropathies." 12/01/2002 - "Early detection of small-fiber neuropathy in diabetes: a laser-induced pain somatosensory-evoked potentials and pupillometric study." 01/01/2014 - "Thus, we adopted several methods to evaluate autonomic function accurately for detecting the onset of small-fiber neuropathy, such as laser-Doppler flowmetry, sweating tests using capsule type sweating ratemeter, morphological check of sweat gland, electrogastrography, density check of small-fiber and gastrointestinal interstitial cells of Cajal, R-R interval study, (123)I-MIBG myocardial scintigraphy, and head-up tilt test to check the overshoot phenomenon. "