The role of skin biopsy in differentiating small‐fiber neuropathy from ganglionopathy

Background and purpose We aimed to test the clinical utility of the leg:thigh intraepidermal nerve‐fiber (IENF) density ratio as a parameter to discriminate between length‐dependent small‐fiber neuropathy (SFN) and small‐fiber sensory ganglionopathy (SFSG) in subjects with signs and symptoms of small‐fiber pathology. Methods We retrospectively evaluated thigh and leg IENF density in 314 subjects with small‐fiber pathology (173 with distal symmetrical length‐dependent SFN and 141 with non‐length‐dependent SFSG). A group of 288 healthy subjects was included as a control group. The leg:thigh IENF density ratio was calculated for all subjects. We used receiver operating characteristic curve analyses to assess the ability of this parameter to discriminate between length‐dependent SFN and SFSG, and the decision curve analysis to estimate its net clinical benefit. Results In patients with neuropathy, the mean IENF density was 14.8 ± 6.8/mm at the thigh (14.0 ± 6.9/mm in length‐dependent SFN and 15.9 ± 6.7/mm in patients with SFSG) and 7.5 ± 4.5/mm at the distal leg (5.4 ± 3.2/mm in patients with length‐dependent SFN and 10.1 ± 4.6/mm in patients with SFSG). The leg:thigh IENF density ratio was significantly ( P < 0.01) lower in patients with length‐dependent SFN (0.44 ± 0.23) compared with patients with SFSG (0.68 ± 0.28). The area under the curve of the receiver operating characteristic analysis to discriminate between patients with length‐dependent SFN and SFSG was 0.79. The decision curve analysis demonstrated the clinical utility of this parameter. Conclusions The leg:thigh IENF ratio represents a valuable tool in the differential diagnosis between SFSG and length‐dependent SFN.