Utility of Skin Biopsy to Evaluate Peripheral Neuropathy

Abstract

Skin biopsy for epidermal nerve fiber analysis provides an important objective test for the diagnosis of peripheral neuropathy, particularly small fiber sensory neuropathy (SFSN). The determination of epidermal nerve fiber density (ENFD) is reliable, with high diagnostic specificity and good sensitivity. Because of false negatives, biopsy results must be interpreted in conjunction with neurologic findings and laboratory results, including objective tests of sensory and autonomic function. SFSN most commonly is length dependent and is idiopathic in about half the patients. Biopsy of a proximal site (thigh) and a distal site (calf) typically shows greater abnormality of ENFD distally than proximally. More severe abnormality of ENFD in the thigh than in the calf raises the possibility of a non-length-dependent SFSN. The causes of this type of neuropathy, such as Sjögren's syndrome, sarcoidosis, and celiac disease, may be treatable.

Sarcoidosis and Small-fiber Neuropathy

“…Patients often report unilateral flank numbness, chest tingling, thigh pain, or constant facial paresthesias; many of them describe a crawling, vibrating sensation in and around their lips. In our experience and that of others, SSFN is commonly non-length-dependent and is manifested as prominent sensory disturbances in the trunk, face, or more proximal portions of the limbs [9,10]. In addition, the involved areas may be exquisitely tender to temperature extremes.…”

“…Other cases may present in a subacute manner and then rapidly evolve into diffuse, generalized paresthesias. In many instances, the distribution of neuropathic pain does not follow a length-dependent pattern as is usually seen with large-fiber disease, in which the distal portion of the limbs are affected before the proximal sites; symptoms typically begin in the feet and slowly ascend to the level of the knees, at which point the hands may become affected [9,10].…”

Causes of neuropathy in patients referred as “idiopathic neuropathy”

“…In most patients with small‐fiber neuropathy symptoms and normal nerve conduction results, skin biopsy was performed from 2 standard sites (distal leg and proximal thigh). Specimens included 3‐mm punch biopsies that were processed in a standard fashion . Epidermal nerve fiber density (ENFD) was measured and compared with normative data by an expert neuropathologist using a method described by McArthur etal .…”

Clinical Approach to Peripheral Neuropathy

“…33 The high specificity indicates that IENFD is a good tool to verify a neuropathy, but a normal IENFD does not exclude neuropathy. 29 The literature on the agreement between QST and IENFD is conflicting. 33 IENFD is correlated with objective SFN signs.…”