Sensory predominant peripheral neuropathy is a common disorder, affecting as many as 10% of individuals older than 40 years.1 Many of these patients have small fiber neuropathy (SFN). Despite 3 decades of intense study, SFN remains an enigmatic condition that is often difficult to diagnose and manage successfully. In addition, SFN is extremely frustrating for patients who experience pain, disrupted sleep, gait imbalance, autonomic disturbances, and fall-related injuries, all of which lead to a profoundly reduced quality of life. The precise diagnostic criteria for SFN are debated, and the relative role of specific symptoms, signs, specialized investigations (eg, quantitative sensory testing and quantitative sudomotor axon reflex testing), and skin biopsy for measurement of intraepidermal nerve fiber density (IENFD) is uncertain and somewhat controversial.2,3 Approximately half of patients with SFN have diabetic neuropathy, and most of the remainder have cryptogenic sensory peripheral neuropathy (CSPN). Although half of patients with CSPN also have prediabetes and even more are obese,4-6 the lack of a specific cause is difficult for many patients to accept, especially when they learn that treatment often involves only diet and exercise, which they find difficult to sustain, and symptomatic pain management, which is often only modestly effective.6 An uncertain prognosis increases frustration, with many patients experiencing relatively stable symptoms for many years and others progressing to involvement of large nerve fibers.