Small Fiber Neuropathy (SFN) is a condition that affects the peripheral nervous system, specifically damaging the fine nerve endings that extend throughout the body. These fibers transmit sensory information and regulate automatic bodily functions. Determining how frequently this condition occurs is complicated, largely due to the specialized nature of its diagnosis and the variability in how the disorder is studied.
Defining the Role of Small Nerve Fibers
Small nerve fibers are the thinnest nerve cell projections in the peripheral nervous system, categorized as unmyelinated C-fibers and thinly myelinated A-delta fibers. These fibers are structurally distinct from large nerve fibers, which are thicker and covered in myelin, allowing for rapid signal transmission. Small fibers lack this thick myelin sheath, resulting in slower signal conduction.
These fibers innervate the skin and many internal organs. Small sensory fibers transmit sensations like temperature and pain from the skin to the central nervous system. Autonomic small fibers regulate involuntary bodily processes, including heart rate, blood vessel diameter, digestion, and sweating. Damage to these delicate structures affects both the sensory and automatic systems.
The large nerve fibers are primarily responsible for motor function and transmitting sensations related to vibration, touch, and joint position sense. Standard neurological tests, such as electromyography and nerve conduction studies, evaluate the function of these large, myelinated fibers. Because pure SFN only affects the small fibers, these conventional tests typically return normal results.
Why Measuring SFN Prevalence is Difficult
Accurately determining the number of people with SFN is difficult because the condition often requires specialized testing for confirmation. Unlike large fiber neuropathies identified with standard nerve conduction studies, SFN requires methods that specifically evaluate the integrity and function of the small, unmyelinated fibers.
The current gold standard for diagnosis is a skin punch biopsy, a minimally invasive procedure where a small sample of skin is taken. This tissue is analyzed to measure the intraepidermal nerve fiber density (IENFD), which provides a count of the small sensory fibers present in the skin. A significantly reduced density confirms the diagnosis of small fiber loss.
Another specialized approach involves functional testing of the autonomic small fibers, such as the Quantitative Sudomotor Axon Reflex Test (QSART). This test evaluates the ability of the small fibers to regulate sweating. These specialized diagnostic tools, including IENFD and QSART, are often only available at tertiary care centers or specialized neuropathy clinics.
Limited access to these confirmatory tests in general clinical practice leads to significant underdiagnosis and underreporting of SFN. Individuals who experience symptoms consistent with SFN may not receive the necessary diagnostic workup. This reliance on specialized methods creates a methodological hurdle, resulting in prevalence data that are generally considered an underestimation of the true commonness of the disorder.
Reported Incidence and Primary Risk Factors
Despite the diagnostic challenges, epidemiological studies have provided estimates for SFN prevalence, though the reported figures show variability. One study in the Netherlands reported a minimum incidence of 11.73 cases per 100,000 people per year and a minimum prevalence of 52.95 cases per 100,000 inhabitants. Conversely, a US study reported a lower incidence (1.3 per 100,000 per year) and a prevalence of 13.3 per 100,000, noting that the incidence appeared to be rising over the study period.
This range in figures is largely attributed to differences in study methodologies, including the specific diagnostic criteria used and the population studied. For instance, the US study focused only on pure SFN cases, excluding those with large fiber involvement. Most researchers agree that the true prevalence of SFN is higher than these minimum reported rates.
The prevalence of SFN is strongly linked to underlying medical conditions, primarily Type 2 Diabetes and impaired glucose tolerance. Diabetes was noted as the most common identifiable cause, present in about 15% of SFN patients, with a much higher percentage showing signs of glucose impairment. Metabolic risk factors such as obesity and high triglycerides are significantly more common in SFN patients.
Other identified causes include autoimmune disorders such as Sjögren syndrome and lupus, as well as genetic conditions and infections. Despite these associations, up to 70% of SFN cases remain classified as “idiopathic,” meaning no underlying cause can be identified. The high prevalence of metabolic syndrome and glucose dysregulation in the general population is a primary driver of SFN’s overall frequency. The increasing incidence of SFN is likely connected to the rising rates of these metabolic conditions.