Small Fibre Neuropathy
Burning feet, autonomic symptoms, and the workup that gets to the answer. A specialist diagnostic pathway in Sydney.
You do not need a referral from your doctor. Request an appointment online in about two minutes, and we will call you to arrange a time. Testing takes 40–60 minutes.
Request an appointment →Please note the tests themselves are not covered by a Medicare rebate. Questions? Call 02 9388 0615.
Small fibre neuropathy (SFN) is a disorder of the smallest nerve fibres in the body. These are the unmyelinated and thinly myelinated fibres that carry pain and temperature signals from the skin, and that supply autonomic functions like sweating, blood-pressure regulation, gut motility, and bladder function.
The most common picture is burning, stinging, or electric pain in the feet — often worse at night, often disproportionate to anything visible on examination. Some patients have additional autonomic symptoms: orthostatic intolerance, abnormal sweating, gastrointestinal symptoms, or unexplained heart-rate variations.
One of the reasons SFN is sometimes missed is that standard nerve conduction studies are usually normal — they only assess the larger fibres. Diagnosing SFN means using tests built for the smaller fibres: autonomic function testing, SudoScan, and the gold-standard test, skin biopsy with intraepidermal nerve fibre density.
Symptoms
Small fibre neuropathy can present in many ways. Most patients have some combination of these features.
🔥 Burning or stinging feet
The most common symptom. Often worst at night. May feel like the feet are on fire, or like walking on hot sand.
⚡ Electric or stabbing pain
Sudden, sharp pains in the feet or legs — sometimes triggered by light touch (allodynia).
🧊️ Temperature sensitivity
Feet feel abnormally hot or abnormally cold, sometimes despite normal skin temperature. Difficulty tolerating heat or cold.
🫦 Sensitivity to bedclothes
Even the weight of a sheet may feel painful or unbearable on the feet at night.
💦 Abnormal sweating
Sweating too much, too little, or in unusual distribution. Dry hands or feet, or excessive sweating elsewhere.
📊 Orthostatic intolerance
Lightheadedness on standing, palpitations, brain fog — from autonomic-fibre involvement in blood-pressure regulation.
🪥 Gastrointestinal symptoms
Bloating, constipation, early satiety, or unexplained nausea — from autonomic-fibre involvement in gut motility.
💙 Patchy or unusual distribution
SFN can present in a length-dependent pattern (starting in the feet) or, less commonly, in a non-length-dependent or patchy pattern affecting the trunk, face, or upper limbs.
If this list resonates, you are not imagining it. SFN is real, common, and increasingly recognised — but it is often missed because routine nerve studies look normal. Specialist testing is what brings the picture into focus.
What Causes Small Fibre Neuropathy?
Identifying the underlying cause matters — some are treatable, and the right treatment depends on knowing what's driving the neuropathy.
Diabetes & impaired glucose tolerance
The most common identified cause. Small fibres are damaged years before the larger fibres — often before diabetes is formally diagnosed. Glycaemic control reduces progression.
Autoimmune disease
Sjögren's syndrome, sarcoidosis, lupus, and other autoimmune conditions can cause SFN. Recognition matters because immune therapy can help.
Vitamin deficiencies
Vitamin B12 deficiency in particular — common, easily missed, and easily treated. B6 toxicity can also cause SFN.
Thyroid disease
Hypothyroidism (and rarely hyperthyroidism) can contribute to SFN. Often part of standard screening.
Alcohol
Excess alcohol is directly toxic to small fibres and depletes B vitamins. Reduction can stabilise or improve symptoms.
Medications & chemotherapy
Several chemotherapy agents (taxanes, platinum compounds, bortezomib), and a small number of other medications, can cause SFN.
Post-viral & post-COVID
SFN can follow viral illness. Long-COVID-associated SFN is increasingly described and often overlaps with dysautonomia.
Genetic
Sodium-channel mutations (SCN9A, SCN10A, SCN11A), Fabry disease, and familial amyloid polyneuropathy — less common but important when there is a family history or atypical features.
Amyloidosis
Both hereditary transthyretin amyloidosis (hATTR) and AL amyloidosis can present with small fibre neuropathy. Time-sensitive to diagnose because effective treatments exist.
Idiopathic
In about a third of cases no specific cause is identified after thorough workup. This does not change the diagnosis or rule out symptomatic management — but it is something to revisit periodically as new causes are recognised.
How Small Fibre Neuropathy Is Diagnosed
Diagnosis combines the clinical picture with quantitative tests of small-fibre function and structure. Standard nerve conduction studies are part of the workup but cannot rule SFN out.
Clinical assessment
Detailed history of the symptoms, the timeline, family history, medications, alcohol intake, and any conditions known to cause SFN. Neurological examination assesses pinprick and temperature sensation in addition to the standard examination.
Standard nerve conduction studies
Usually normal in pure SFN — but the test is done to make sure there is no large-fibre involvement that would change the diagnosis. A normal study in someone with burning feet does not rule out SFN.
Excludes large-fibre involvementAutonomic function testing
The five-test autonomic protocol (active stand test with recovery blood pressure, paced-breathing HRV, Valsalva, isometric handgrip, SudoScan) detects autonomic-fibre involvement and characterises which autonomic domains are affected. This is particularly useful when autonomic symptoms (orthostatic intolerance, abnormal sweating) are part of the picture.
Tests small-fibre autonomic functionSudoScan
A rapid, non-invasive measure of sudomotor (sweating-fibre) function. Particularly sensitive to early small-fibre involvement — including in diabetic autonomic neuropathy before nerve conduction studies become abnormal. A useful supportive test that helps build the case for biopsy.
Quantifies sudomotor small fibresSkin biopsy with intraepidermal nerve fibre density (IENFD)
A small (3 mm) punch biopsy of skin from the lower leg, stained for nerve fibres and counted under microscopy. A reduced intraepidermal nerve fibre density (IENFD) is the gold-standard test for confirming small fibre neuropathy. Heals with a tiny scar, well tolerated, done as an outpatient procedure.
Gold standard for SFN diagnosisCause workup
Once SFN is confirmed, the cause is investigated. Blood tests cover glucose / HbA1c, B12, thyroid function, autoimmune screen (ANA, ENA, anti-SSA/SSB for Sjögren's), and protein electrophoresis. Further tests — including genetic testing or biopsy of fat or other tissues for amyloid — are done where the clinical picture suggests them.
Not every patient needs every test. Your specialist tailors the workup to what fits your story. The aim is the right tests, in the right order, to get to the answer — not a fishing expedition.
Treatment
Treatment has two arms: address the underlying cause if one is identified, and manage the symptoms in their own right.
Treat the underlying cause
Where a cause is identified, treating it can stabilise or improve the SFN:
- Glycaemic control for diabetic SFN
- B12 replacement for B12 deficiency
- Thyroid replacement for hypothyroidism
- Immune therapy for Sjögren's-related and other autoimmune SFN
- Alcohol reduction for alcohol-related SFN
- Specific treatments for amyloidosis — substantial advances in recent years
Manage the symptoms
Whether or not a cause is identified, the symptoms themselves can be managed:
- Neuropathic pain: duloxetine, pregabalin, gabapentin, amitriptyline, topical lidocaine or capsaicin — often used in combination
- Orthostatic symptoms: hydration, salt, compression, graded exercise; medications such as fludrocortisone or midodrine when needed
- Sweating abnormalities & GI symptoms: targeted management
- Sleep: addressing pain at night significantly improves quality of life
Even idiopathic small fibre neuropathy is manageable. The combination of carefully chosen neuropathic-pain medication, lifestyle measures, and ongoing review usually brings the symptoms to a level where they no longer dominate daily life.
Frequently Asked Questions
What is small fibre neuropathy?
Small fibre neuropathy is a disorder of the smallest nerve fibres in the body — the unmyelinated and thinly myelinated fibres that carry pain and temperature signals from the skin, and that supply autonomic functions like sweating, blood-pressure regulation, and gut motility. Damage to these fibres typically causes burning, stinging or electric pain (most often starting in the feet), abnormal temperature sensation, and sometimes autonomic symptoms such as orthostatic intolerance, abnormal sweating, or gastrointestinal symptoms.
How is small fibre neuropathy diagnosed?
Diagnosis combines the clinical picture with quantitative tests of small-fibre function and structure. Skin biopsy with intraepidermal nerve fibre density (IENFD) is the gold-standard test. Autonomic function testing — including SudoScan and the cardiovascular autonomic protocol — detects autonomic-fibre involvement. Standard nerve conduction studies are usually normal because they only assess the larger fibres. Blood tests look for underlying causes.
Why are my normal nerve conduction studies not enough to rule small fibre neuropathy out?
Standard nerve conduction studies only assess the large, myelinated fibres. The smaller fibres affected in SFN are below the resolution of nerve conduction studies — which is precisely why dedicated small-fibre testing exists. A normal nerve conduction study in someone with burning feet does not rule SFN out; it is part of the workup, not the answer.
What causes small fibre neuropathy?
The most common identified causes are diabetes and impaired glucose tolerance, autoimmune disease (especially Sjögren's syndrome and sarcoidosis), thyroid disease, vitamin B12 deficiency, alcohol-related neuropathy, and certain medications (including chemotherapy). Genetic causes (such as sodium-channel mutations and Fabry disease) and amyloidosis are less common but important to look for. In about a third of cases no specific cause is identified — this is called idiopathic SFN.
Can small fibre neuropathy be treated?
Yes. Treatment has two arms. First, treat any underlying cause where one is identified — glycaemic control for diabetes, immune therapy for autoimmune causes, replacement for vitamin deficiencies. Second, manage the symptoms — pain is treated with neuropathic-pain medications (such as duloxetine, pregabalin or gabapentin), and autonomic symptoms (orthostatic intolerance, abnormal sweating, gastrointestinal symptoms) are managed individually. Even idiopathic SFN typically becomes manageable with the right combination.
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