Pitfalls of diagnostic criteria for small fiber neuropathy

This Practice Point commentary discusses a retrospective study conducted by Devigili et al. that sought to establish gold standard diagnostic criteria for small fiber neuropathy (SFN). The chosen gold standard for SFN requires abnormalities on two out of three tests (clinical findings, skin biopsy [epidermal nerve fiber density] and quantitative sensory testing), with nerve conduction studies being normal. A total of 150 patients with sensory symptoms met study inclusion criteria, and 67 were determined to have SFN on the basis of the gold standard criteria. Epidermal nerve fiber density was the single most useful test for SFN with a diagnostic efficiency of 88.4%. This commentary argues in favor of a hierarchical system of levels of diagnostic certainty for SFN, depending on the number and type of abnormal diagnostic tests, in contrast to the dichotomous approach used by Devigili et al. We further highlight methodological limitations of the present study, such as the confounding of diagnostic-efficiency estimates for individual SFN tests through incorporation bias.