Small fiber neuropathy

Small fiber neuropathy (SFN) is a condition involving the small nerve fibers of the peripheral nervous system, specifically the thinly myelinated Aδ and unmyelinated C fibers. It is an increasingly acknowledged condition within the spectrum of neuropathic pain disorders, leading to a rise in diagnosed patients. SFN is characterized by neuropathic pain, that is often described as burning, and typically presents in the hands and feet ascending proximally. Since small nerve fibers are involved in the autonomic nervous system, SFN can also lead to autonomic dysfunction. In the clinical setting, SFN diagnosis is frequently based on the Besta Criteria, which include skin biopsy and quantitative sensory testing. For clinical trials, the ACTTION criteria are also recommended. However, the diagnostic process is often complex, prompting research towards more accessible diagnostic methods. The pathophysiology of SFN remains unclear, thereby challenging therapeutic strategies. A large variety of underlying conditions has been associated with SFN, including metabolic, immune-mediated, infectious, toxic and hereditary conditions. The discovery of genetic sodium channelopathies in SFN provides insight into its underlying mechanisms. Newly discovered mutations within these genes reveal that SFN often shows overlapping clinical presentations with other sodium channelopathies. This chapter provides an in-depth look at SFN, including its clinical features, diagnostic methods, underlying conditions and possible therapeutic strategies.