Sweat Gland Nerve Fiber Density – Interpretation of Results

Skin biopsy for quantitative analysis of autonomic fibers in sweat glands has been recently developed as a diagnosis of small fiber neuropathy (Gibbons et al, 2009). The diagnosis can be made as an adjunct to epidermal nerve fiber density testing or it can be made with the sweat gland analysis without an ENFD testing result. The analysis is performed by determining the sweat gland nerve fiber density (SGNFD) using a counting grid for image analysis. The grid consists of an array of circles of uniform diameter and spacing that is superimposed over the digitized image of a sweat gland. Axons are identified by the same immunohistochemical stain of PGP 9.5 used for epidermal nerve fiber analysis. The number of circles that enclose one or more axons within each circular space are counted, and this value is divided by the total number of circles that fall within the sweat gland. This result is expressed as a percent and is representative of the SGNFD. Sweat glands, that are present in the skin, are exocrine glands, found in the subcutaneous layer of the skin, whose function is to help regulate the body's temperature ( Jablonski 2010). The secretory activity of the gland is controlled by the autonomic nervous system, so that neuroapthy can result in abnormal sweating and impaired thermoregulation (Cheshire and Freeman, 2003). Both ENFs and SGNFs are unmyelinated and often are affected in small fiber neuropathies (Dabby et al, 2007; Gibbons et al, 2009), although either may be more severely affected in particular types of neuropathy or individual patients.

The sweat gland nerve fiber density is compared to the values in specimens found in normal control subjects as determined by Therapath. The 5th percentile for SGNFD is 34.8 fibers per mm in the foot, 36.5 fibers per mm in the calf and 37.8 fibers per mm in the thigh. Testing values that are reported below these values or 5th percentiles are considered to be "reduced sweat gland nerve fiber density (SGNFD), consistent with small fiber neuropathy". In addition, values that fall between the 10th percentile and 5th percentile are defined as low normal in the diagnosis to alert the physician for a possible small fiber neuropathy.

The presence of a normal SGNFD does not, by itself, rule out a diagnosis of small fiber neuropathy. In addition, a diagnosis based on an abnormally low SGNFD cannot predict a response to therapy or indicate a cause for any neuropathy. The diagnosis and treatment of any medical condition depends on the patient's clinical presentation as presented to the treating physician.