Comparative Analysis of Small Nerve Fiber Density in Fibromyalgia Syndrome and Small Fiber Neuropathy

Background/Objectives: Fibromyalgia syndrome is commonly associated with reduced intraepidermal nerve fiber density (IENFD), as assessed by skin biopsy, a finding referred to as small fiber pathology (SFP-FMG). The clinical significance of this abnormality, and how it relates to symptoms in fibromyalgia, remains uncertain. Reduced IENFD also represents the defining feature of small fiber neuropathy (SFN). While previous observations suggest that IENFD reduction is generally less severe in SFP-FMG than in SFN, no study has directly confirmed this finding in a large cohort. This retrospective study aimed to compare the severity of IENFD reduction in patients with SFP-FMG and those with SFN. Methods: To account for age and sex differences, we used the age-and sex-adjusted axonal loss density (ALD), defined as the percentage reduction from normative IENFD values. We retrospectively analyzed skin biopsy data from 73 patients with SFP-FMG and 134 patients diagnosed with SFN. Results: We found that the reduction in IENFD was significantly milder in patients with SFP-FMG than in those with SFN both at distal and proximal sites. Receiver operating characteristic analysis indicated that an ALD threshold of 37.6% provided good specificity for distinguishing SFN from SFP-FMG. Conclusions: These findings indicate that small fiber damage in fibromyalgia syndrome is quantitatively mild compared to patients with SFN. This may explain the absence of detectable sensory deficits on clinical examination and suggests a limited contribution of peripheral nerve damage to the pathophysiology of fibromyalgia syndrome.