Small-Fiber Neuropathy: A Diabetic Microvascular Complication of Special Clinical, Diagnostic, and Prognostic Importance

Angiology. 2016 Jan;67(1):49-57. doi: 10.1177/0003319715583595. Epub 2015 May 8.


Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may decrease quality of life. It also contributes to the poor prognosis of diabetic neuropathy because it plays a key role in the pathogenesis of foot ulceration and autonomic neuropathy. Impairment of small nerve fibers is considered the earliest alteration in the course of diabetic neuropathy. Therefore, assessment of functional and morphological abnormalities of small nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical significance of small-fiber neuropathy are considered in the present review. An apparently more complex interaction between small-fiber impairment and microcirculation is extensively discussed. Diagnostic modalities include morphometric and functional methods. Corneal confocal microscopy and punch skin biopsy are considered gold standards, but noninvasive functional tests are also diagnostically useful. However, in routine clinical practice, small-fiber neuropathy is diagnosed by its typical clinical presentation. Finally, prompt treatment should be initiated following diagnosis.

Keywords: corneal confocal microscopy; diabetic neuropathy; microcirculation; punch biopsy; quantitative sensory testing; small-fiber neuropathy.

Publication types

  • Review

MeSH terms

  • Biopsy
  • Diabetic Angiopathies / complications*
  • Diabetic Angiopathies / diagnosis
  • Diabetic Neuropathies / diagnosis*
  • Diabetic Neuropathies / etiology
  • Humans
  • Microscopy, Confocal
  • Nerve Fibers / pathology*
  • Prognosis
  • Skin / pathology