Small fiber neuropathy G63.1 - G63.8

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 29.10.2020

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Microfibre neuropathy; OMIM:133020; SFN

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Generalised or localised disease caused by direct damage to the small non-myelinated nerve fibres of the skin and various other organs (so-called C-fibres and Ad-fibres) with consecutive dysfunction. C-fibres (so-called somatic fibres) serve for the innervation of the skin and are involved in the regulation of various organs. Organs (autonomous fibres).

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The cause is often not clear (idiopathic small fiber neuropathy).

In autosomal dominant inherited SFN, mutations in the sodium channel coding SCN9A gene (sodium channel, voltage-gated, type 9, alpha subunit) located on chromosome 2q24.3 can be detected (OMIM:133020).

Often systemic diseases are present, which lead to generalized damage of the small epidermal non-myelinated C-fibers. Systemic diseases like:

Further neurotoxic drugs, especially antibiotics such as metronidazole, linezolid, antiretroviral drugs, statins, chemotherapeutic drugs and chronic alcoholism (F10.2).

Clinical features
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Patients primarily experience burning pain symptoms, especially in the lower extremities (distal-symmetric neuropathic syndrome), but also paresthesia orburning itching(burning feet). The disease usually progresses slowly. In addition, patients may have restless leg syndrome, hypo- or hyperhidrosis, diarrhea, constipation, sicca syndrome, flush and erectile dysfunction.

Even in isolated neuropathic pain such as "burning-mouth syndrome" without further sensory symptoms, a small-fibre neuropathy can be detected via reduced intraepidermal nerve fibre density (IENFD).

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Small Fiber Neuropathy" can be detected by determining the intraepidermal nerve fiber density (IENF). All nerve fibres crossing the epidermal boundary layer are counted. In small fiber neuropathy, the density of the intradermal nerve fibers is reduced. Occasionally, morphological changes such as swelling of the nerve endings are found.

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Determination and treatment of a systemic cause.

Cold (as with other forms of itching) reduces neuropathic itching.

Capsaicin cream in increasing concentration - alternatively capsaicin patches

anticonvulsants (e.g. gabapentin - maximum dose 3,600mg/day p.o.); alternatively pregabalin (maximum 600mg/day p.o.)

Leg insufficient effect Combination of anticonvulsant with an antidepressant (e.g. paroxetine 20mg/day, mirtazapine 15mg/day or amitriptyline 50mg/day)

The antiepileptic drug lacosamide works by blocking the sodium channels Nav1.3, Nav1.7 and Nav1.8. A recently published Dutch study therefore examined the substance in terms of pain management, safety and tolerability in patients with Nav1.7-SFN. The 24 study participants received double-blind, randomized, for eight weeks either 2 x 200 mg lacosamide (n=12), followed by eight weeks of placebo (n=12) or vice versa (first placebo, then lacosamide). Pain was measured using a pain scale ("Pain Intensity Numerical Rating Scale"). Pain reduction by at least one scale point was considered effective.

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  1. Buonocore M (2014) Unilateral peripheral neuropathic pain: The role of neurodiagnostic skin biopsy. World J Clin Cases 2:27-31
  2. Cortez M et al (2014) Glucose intolerance, metabolic syndrome, and neuropathy. Hand Clin Neurol 126:109-122
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  4. Kosmidis ML et al (2014) Reduction of Intraepidermal Nerve Fiber Density (IENFD) in the skin biopsies of patients with fibromyalgia: A controlled study. J Neurol Sci 347:143-147
  5. Morkavuk G et al (2014) Small fiber neuropathy associated with hyperlipidemia: utility of cutaneous silent periods and autonomic tests. ISRN Neurol 19: doi: 10.1155/2014/579242.
  6. Oomatia A et al (2014) Peripheral neuropathies in systemic lupus erythematosus: clinical features, disease associations, and immunologic characteristics evaluated over a twenty-five-year study period. Arthritis Rheumatol 66:1000-1009
  7. Pereira MP et al (2016) Small Fibre Neuropathy as a possible cause of chronic pruritus. Dermatologist 67: 615-621
  8. Skorna M et al (2014) Small nerve fiber pathology in critical illness documented by serial skin biopsies. Muscle Nerve doi: 10.1002/mus.24489
  9. Tzatha E et al (2014) Small fiber abnormalities in skin biopsies of patients with benign fasciculations. J Clin Neuromuscul Dis 16:12-14


Please ask your physician for a reliable diagnosis. This website is only meant as a reference.


Last updated on: 29.10.2020