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DESCRIPTIONSkin biopsy is used to assess the density of epidermal (intraepidermal) and sweat gland (sudomotor) nerve fibers using antibodies to a marker found in peripheral nerves. This procedure is being investigated as an objective measure of small fiber neuropathy by identifying a reduction in the density of nerve fibers.
The majority of patients with peripheral neuropathy exhibit evidence of large fiber involvement, characterized by numbness, tingling, loss of deep tendon reflexes, and abnormal electrophysiologic studies. In contrast, damage to small fibers is not detected by routine nerve conduction studies. Patients with small fiber neuropathy, involving myelinated A delta and unmyelinated C fibers, may complain of severe pain and exhibit diminished thermal and pain perception. The pain, which is frequently reported in the feet, is described as burning, prickling, stabbing, jabbing, or tight band-like pressure. If there is involvement of autonomic C fibers, symptoms such as coldness, discoloration, and hyper- or hypohidrosis may be present. Small fiber neuropathy occurs most often in patients with diabetic neuropathy, but may also be found in patients with impaired glucose tolerance, severe hypertriglyceridemia, the metabolic syndrome, HIV infection, and toxic neuropathy from antiretroviral drugs. For many patients, no specific etiology is identified.
Small fiber neuropathy is diagnosed clinically, but has traditionally been a diagnosis of exclusion based on clinical findings and the absence of large fiber involvement as determined by electrophysiologic studies. The disparity between subjective complaints and objective signs increases the difficulty of diagnosis. In addition, conditions other than nerve fiber damage, including venous insufficiency, spinal stenosis, myelopathy and psychosomatic disturbances may mimic small fiber neuropathy. There is no treatment to cure small fiber peripheral neuropathy. Medications may be provided for pain management, and for some etiologies treatment of the underlying condition (e.g., glucose control, intravenous immunoglobulin or plasma exchange) may be given to reduce progression of the disease and its symptoms.
In the last decade, a specific test to assess intraepidermal nerve fiber (IENF) density and sweat gland nerve fiber (SGNF) density using skin biopsy and immunostaining of the tissue has been developed that allow the identification and counting of intraepidermal and sudomotor nerve fibers. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the calf (and sometimes foot or thigh). After sectioning by microtome, the tissue is immunostained with anti-protein-gene-product 9.5 (PGP 9.5) antibodies and examined with immunohistochemical or immunofluorescent methods. This technique has improved research and contributed greatly to the understanding of small fiber neuropathy. Skin biopsy with measurement of IENF density has also been investigated as an objective measure for the diagnosis of small fiber neuropathy. SGNF density can be assessed from the same tissue that has been prepared for IENF density testing, provided that the biopsy sample is of sufficient depth. Tissue samples may also be counterstained to better identify the boundaries of the sweat glands.
Assessment of IENF and SGNF density with PGP 9.5 is commercially available from Therapath (New York) with a biopsy kit, although IENF-density measurement (i.e., tissue preparation, immunostaining with PGP 9.5 and counting) may also be done by local research pathology labs.
Indications for Quantitative Sensory Testing are discussed in a separate policy.
POLICYSkin biopsy with epidermal nerve fiber density measurement for the diagnosis of small-fiber neuropathy may be considered medically necessary when all of the following conditions are met:
Skin biopsy with epidermal nerve fiber density measurement is considered investigational for all other conditions, including, but not limited to, the monitoring of disease progression or response to treatment.
Measurement of sweat gland nerve fiber density is investigational.
POLICY GUIDELINESThe coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member’s specific benefit plan language.
POLICY HISTORY10/13/2009: Policy added.
11/19/2009: Approved by MPAC
12/30/2010: Policy reviewed; no changes.
01/17/2012: Added a policy statement to indicate that skin biopsy with epidermal nerve fiber density measurement for the diagnosis of small-fiber neuropathy may be considered medically necessary when certain conditions are met.
01/09/2013: Policy title changed from "Intraepidermal Nerve Fiber Density" to "Nerve Fiber Density Testing." Added the following investigational policy statement: Measurement of sweat gland nerve fiber density is investigational.
12/13/2013: Policy reviewed; no changes.
11/17/2014: Policy reviewed; description updated regarding sweat gland nerve fibers. Policy statements unchanged.
SOURCESBlue Cross Blue Shield Association # 2.04.58
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.