Stimulated skin wrinkling as an indicator of limb sympathetic function

Clin Neurophysiol. 2015 Jan;126(1):10-6. doi: 10.1016/j.clinph.2014.08.007. Epub 2014 Sep 2.


Skin wrinkling upon water immersion has been used as an indicator of limb nerve function for more than 80years. Until recently, routine use of the test has been hampered by a poor understanding of the physiology and lack of standardization. The process underlying stimulated skin wrinkling has been recently identified as dependent on digital vasoconstriction mediated via sympathetic nerve fibers. Vasoconstriction is postulated to drive wrinkling through loss of digit volume, which induces a negative pressure in the digit pulp and exerts a downward pull on the overlying skin and ultimately results in wrinkles. Improved test standardization has been achieved through substituting water with EMLA for inducing skin wrinkling. This has made testing much easier and has helped implement stimulated skin wrinkling as a practical routine clinical bedside test. A literature search identified 10 studies of sufficient quality for evaluating stimulated skin wrinkling as a diagnostic test of sympathetic under or over function. Seven studies provide level 1 or 2 evidence as a diagnostic test of small fiber neuropathy and three provide level 1 or 2 evidence for cystic fibrosis. There is reasonable evidence allowing the test to be employed as a simple and effective marker for small fiber neuropathy and cystic fibrosis.

Keywords: Aquagenic wrinkling; Small nerve fiber test; Stimulated skin wrinkling; Sympathetic function; Vasoconstriction; Water-immersion skin wrinkling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autonomic Nervous System Diseases / diagnosis
  • Autonomic Nervous System Diseases / physiopathology
  • Extremities / innervation
  • Extremities / physiology*
  • Humans
  • Skin / innervation
  • Skin Aging / physiology*
  • Skin Physiological Phenomena
  • Sympathetic Nervous System / physiology*
  • Vasoconstriction / physiology
  • Water*


  • Water