Small fiber neuropathy G63.1 - G63.8

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).

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

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

Systemic diseases are often present, resulting in generalized damage to small, epidermal, unmyelinated C-fibers. Blamed systemic diseases include:

• Diabetes mellitus (E14.90), probably the most common cause.
• lupus erythematosus
• hyperlipidaemia (E78.9)
• Amyloidosis
• Sarcoidosis
• viral infections such as HIV and hepatitis C (B17.1).

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

Patients primarily experience burning pain symptoms, especially in the lower extremity (distal symmetric neuropathic syndrome), but also paresthesias or burning itching(burning feet). The disease is usually slowly progressive. In addition, patients may present with restless leg syndrome, hypo- or hyperhidrosis, diarrhea, constipation, sicca syndrome, flushing, and erectile dysfunction.

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

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.

Identification and treatment of a systemic cause.

Cold reduces (as with other forms of itching) 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.). If insufficient effect, combination of the anticonvulsant with an antidepressant (e.g. paroxetine 20mg/day, mirtazapine 15mg/day or amitriptyline 50mg/day).

Antiepileptic drugs: The antiepileptic drug lacosamide works by blocking the sodium channels Nav1.3, Nav1.7 and Nav1.8. A recently published Dutch study therefore investigated the compound in terms of pain management, safety and tolerability in patients with Nav1.7-SFN. The 24 study participants received double-blind, randomized treatment for eight weeks with 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 intensity numerical rating scale. A pain reduction of at least one scale point was considered effective.

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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
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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
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