Small fiber neuropathy: Diagnosis, causes, and treatment

Joint Bone Spine. 2018 Oct;85(5):553-559. doi: 10.1016/j.jbspin.2017.11.002. Epub 2017 Nov 16.


Small fiber neuropathy, which affects the sensory Aδ and C fibers, is now a major diagnostic and therapeutic challenge. Nearly 7% of the general population have chronic neuropathic pain responsible for severe quality-of-life impairments. Awareness must therefore be raised among clinicians of the somatosensory and autonomic symptoms that can reveal small fiber neuropathy, appropriate diagnostic investigations, most common causes, and best treatment options for each patient profile. To help achieve this goal, the present review article discusses the clinical presentation of neuropathic pain and paresthesia and/or autonomic dysfunction due to involvement of nerves supplying exocrine glands and smooth muscle; normal findings from standard electrophysiological investigations; most informative diagnostic tests (epidermal nerve fiber density in a skin biopsy, laser-evoked potentials, heat- and cold-detection thresholds, electrochemical skin conductance); main causes, which consist chiefly of metabolic diseases (diabetes mellitus, glucose intolerance), dysimmunity syndromes (Sjögren's syndrome, sarcoidosis, monoclonal gammopathy), and genetic abnormalities (familial amyloidosis due to a transthyretin mutation, Fabry disease, sodium channel diseases); and the available symptomatic and etiological treatments.

Keywords: Amyloidosis; Diabetes; Dysautonomia; Fabry disease; Neuropathic pain; Sarcoidosis; Sjögren's syndrome; Small fiber neuropathy; Sodium channel disease.

Publication types

  • Review

MeSH terms

  • Analgesics / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Biopsy, Needle
  • Chronic Pain / drug therapy
  • Chronic Pain / physiopathology
  • Electromyography / methods
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Neurologic Examination / methods
  • Pain Measurement*
  • Prognosis
  • Risk Assessment
  • Sarcoidosis / complications*
  • Sarcoidosis / diagnosis
  • Sjogren's Syndrome / complications*
  • Sjogren's Syndrome / diagnosis
  • Small Fiber Neuropathy / diagnosis*
  • Small Fiber Neuropathy / drug therapy*
  • Small Fiber Neuropathy / pathology
  • Treatment Outcome


  • Analgesics
  • Antidepressive Agents