Stimulated skin wrinkling as an indicator of limb sympathetic function

•Stimulated skin wrinkling is a measure of limb sympathetic function.•The underlying vasoconstriction causing stimulated skin wrinkling has been used to standardize and improve testing.•Studies show evidence of diagnostic usefulness for small fiber neuropathy and cystic fibrosis.

Skin wrinkling upon water immersion has been used as an indicator of limb nerve function for more than 80 years. 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.