Small Fiber Neuropathy: Making the Diagnosis
Small Fiber Neuropathy: Making the Diagnosis
Abstract & Commentary
By Norman Latov, MD, PhD, Professor of Neurology and Neuroscience, and Director of the Peripheral Neuropathy Center, Weill Medical College of Cornell University. Dr. Latov reports that he received grants/research support from Talecris Biopharmaceuticals, is a stockholder in Therapath LLC, is a retained consultant for Quest Diagnostics, and received royalty payments from Athena Diagnostics.
Synopsis: In the setting of chronic pain in a pattern consistent with polyneuropathy, determination of intraepidermal nerve fiber density (IENFD) is the most sensitive diagnostic test.
Source: Devigili G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain 2008 Jun 4 (Epub ahead of print).
Small fiber neuropathy (SFN) is increasingly recognized as a cause of neuropathic pain, but there are no generally accepted diagnostic criteria. The authors examined the sensitivity of 3 diagnostic procedures, including clinical examination, Quantitative Sensory Testing (QST), and determination of intraepidermal nerve fiber density (IENFD) by skin biopsy, in 67 patients in whom 2 of the 3 measures were abnormal. Symptoms included: burning, sharp, sunburn-like, pruritic, aching, cold, or paroxysmal pains; in a distribution consistent with polyneuropathy, mononeuropathy multiplex, or sensory neuronopathy. Clinical findings included pinprick and thermal sensory loss and/or allodynia and/or hyperalgesia.
The sensitivity of each of the 3 procedures were as follows: skin biopsy 88.4%, clinical examination 54.6%, and QST 46.9%. There was a statistically significant inverse correlation between IENFD and cold or warm thresholds on QST, but not between IENFD and severity of the neuropathic pain. Seventy percent of patients had signs of peripheral vascular autonomic dysfunction by laser Doppler flowmetry.
At initial evaluation, the etiology of the SFN was unknown in 41.8% of patients, but at 2-year follow-up, a potential cause was determined in 25% of these patients. Over the same period, 13% of the patients' SFN progressed to also involve large fibers, and 45.6% remained unchanged. The neuropathic pain spontaneously remitted in 10.9% and worsened in 30.4%. Identified causes included: diabetes (46%), glucose intolerance (23%), Sjogrens syndrome (13%), monoclonal gammopathy (8%), hypothyroidism (6%), psoriasis (2%) and celiac disease (2%).
Our understanding of neuropathic pain has historically evolved from studies in patients with defined lesions of the central or peripheral nervous system, but the diagnosis can be problematic in the absence of a demonstrable deficit or lesion, with many patients remaining undiagnosed, or said to have other pain syndromes such as fibromyalgia, RSD (reflex sympathetic dystrophy) or psychosomatic illness instead.
Devigili and colleagues report that determination of IENFD by skin biopsy, a relatively new diagnostic procedure, can demonstrate a lesion, or abnormally low value, in approximately 90% of patients with small fiber neuropathy. This is significantly more sensitive than a clinical examination or QST in identifying patients with this condition.
IENFD correlated with cold or warm thresholds, but not with the severity of the neuropathic pain. This is consistent with clinical observations, where disease progression can be associated with either greater or lesser pain; this results from such factors as spread of the neuropathy or development of numbness instead of pain. Accordingly, determination of IENFD can provide an independent quantitative measure for assessing and following the severity of the underlying neuropathy.
Making a diagnosis of SFN helps direct testing for possible causes, the most common of which are diabetes and glucose intolerance. Other causes identified in the current and previously reported patients include Sjogren's syndrome, celiac disease, hypothyroidism, monoclonal gammopathy, nutritional deficits, systemic lupus erythematosus, amyloid, Fabry disease, Lyme disease, infection with HIV-I or hepatitis C, or toxins. SFN also may be an early manifestation of a more generalized mixed axonal neuropathy, in which case follow-up and evaluation may reveal a cause at a later date.In the setting of chronic pain in a pattern consistent with polyneuropathy, determination of intraepidermal nerve fiber density (IENFD) is the most sensitive diagnostic test.
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