Background/Purpose: The pain associated with fibromyalgia is classically described as deep, muscular, aching and flu-like; however, a significant percentage of patients with fibromyalgia also describe neuropathic symptoms. The pain in these patients can be categorized and burning, tingling or stabbing.  These clinical descriptors may raise the concern for a coexistent neuropathy. Yet, EMG/NCS in fibromyalgia patients are typically unrevealing. The constellation of neuropathic pain with normal nerve conduction studies, raises the possibility of a neuropathy confined purely to the small unmyelinated nerve fibers: a small fiber neuropathy. These small fiber neuropathies can be diagnosed through a 3-mm punch biopsy and may offer insight into the pathogenesis of some cases of fibromyalgia. 

Methods: We retrospectively examined 56 patients referred for neurological evaluation who met diagnostic criteria for fibromyalgia. The patients were seen in neuromuscular consultation at  the Ohio State University or at Phoenix Neurological Associates. Patients were included if they met either the ACR criteria or the revised criteria of 2010 for  fibromyalgia. Patients underwent 3 mm punch biopsies at a proximal and a distal site of one lower limb.  PGP 9.5 immunolabelling was performed and the epidermal nerve fiber density was counted on 50 micron sections. The patients who were found to have reduced epidermal nerve fiber density underwent a standard serologic evaluation looking for identifiable causes for their neuropathy. 

Results: 34/56 (61%) of the cases were diagnosed with small fiber neuropathy on the basis of reduced epidermal nerve fiber density. Of these 34 patients only 5 had evidence for neuropathy on EMG/Nerve conduction studies. Further, this evidence was subtle enough as to be inconclusive for diagnosis.  24/34, 71%, of the patients with fibromyalgia and small fiber neuropathy had serologic evidence of an underlying etiology for their neuropathy that had not been detected prior to identification of the neuropathy: errors of glucose metabolism (n=11), vitamin D deficiency (n=5), elevated ESR (n=2), B6 deficiency (n=1), B12 deficiency (n=1), Sjogrens (n=2), elevated ANA (n=1), mutation in alpha galactosidase (Fabry’s Disease) (n=1).

Conclusion: In this retrospective series, 61% of patients with fibromyalgia and neuropathic pain were found to have small fiber neuropathy based on reduced epidermal nerve fiber density on a standard 3-mm punch biopsy. In 71% of these patients,  a diagnosis was made based on serologic evaluation. These results suggest that testing for small fiber neuropathy in patients with fibromyalgia  will allow for earlier diagnosis of underlying conditions such as glucose dysmetabolism, toxicities, connective tissue disorders, and others. Further, identification of patients who have both fibromyalgia and small fiber neuropathy may suggest earlier therapeutic trials of neuropathic agents in treating the pain in these patients. It is unclear whether our patients had two separate disorders or whether patients had small fiber neuropathy and not fibromyalgia as the cause of their symptoms. A larger, prospective study is needed to answer this question.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/presence-of-small-fiber-neuropathy-in-a-cohort-of-patients-with-fibromyalgia/