🔬 Diagnostic Process
1. Clinical Evaluation
Your doctor will conduct a thorough medical history and physical examination, focusing on:
- Symptom patterns and progression
- Family medical history
- Current medications and supplements
- Lifestyle factors and exposures
- Neurological examination
2. Skin Biopsy (Gold Standard)
The most definitive test for SFN involves taking small skin samples to examine nerve fiber density:
- Quick, minimally invasive procedure
- Usually taken from the leg and sometimes thigh
- Measures intraepidermal nerve fiber density (IENFD)
- Results compared to age-adjusted normal values
3. Laboratory Tests
Blood work to identify potential underlying causes:
- Glucose tolerance test (diabetes screening)
- Vitamin B12, B6, and other vitamin levels
- Thyroid function tests
- Autoimmune markers (ANA, ANCA)
- Heavy metal screening
- Celiac disease markers
4. Specialized Testing
Additional tests that may be recommended:
- Quantitative Sensory Testing (QST): Measures response to heat, cold, and vibration
- Sudomotor Testing: Evaluates sweat gland function
- Heart Rate Variability: Assesses autonomic nervous system
- Corneal Confocal Microscopy: Non-invasive nerve imaging
📋 Preparing for Your Appointment
Symptom Journal
Keep a detailed log of symptoms, including timing, triggers, and severity on a scale of 1-10.
Medication List
Bring a complete list of all medications, supplements, and dosages you're currently taking.
Medical Records
Gather previous test results, imaging studies, and reports from other healthcare providers.
Questions List
Write down questions about your symptoms, treatment options, and prognosis beforehand.
🏥 Finding the Right Specialist
SFN is typically diagnosed by neurologists, but other specialists may also be involved:
Neurologist
Primary specialist for nerve disorders and neuropathy diagnosis
Endocrinologist
If diabetes or metabolic causes are suspected
Rheumatologist
When autoimmune conditions may be involved
Pain Specialist
For comprehensive pain management approaches
⏳ Why Diagnosis Is Often Delayed
Although the testing pathway for small‑fiber neuropathy is fairly well‑defined, many people face long delays—sometimes years—before receiving a diagnosis. Irregular or fluctuating symptoms, overlapping conditions (comorbidities), and variability from day to day can cloud the clinical picture. In addition, access to knowledgeable clinicians is uneven, and some tests commonly used for other neuropathies (for example, EMG/NCS) may be normal in SFN, which can mislead workups.
Insurance hurdles, out‑of‑pocket costs, and—at times—dismissive or negligent medical professionals further slow evaluation. These barriers are systemic, not individual failings. Change is needed: better clinician education, clearer care pathways, and equitable coverage for essential testing (including skin biopsy and appropriate laboratory workups) can reduce diagnostic delay and improve outcomes.
Laboratory Tests Commonly Considered in Small-Fiber Neuropathy Workups
General Screening Tests
- Basic metabolic and chemistry panel
- Complete blood count
- Liver function tests (AST, ALT)
- Hemoglobin A1c
- Thyroid-stimulating hormone (TSH)
- Vitamin B12 level (with methylmalonic acid if results are borderline)
- Erythrocyte sedimentation rate (ESR)
- Antinuclear antibody (ANA) screen
- SSA (Anti-Ro) and SSB (Anti-La) antibodies
- C-reactive protein (CRP)
- Complement levels C3 and C4
- Hepatitis C antibody testing
- Lyme disease antibody testing (Western blot or equivalent)
- Serum protein electrophoresis (SPEP) or immunofixation
- Free kappa and lambda light-chain analysis
- Tissue transglutaminase IgA (for celiac screening)
Targeted or Follow-Up Testing (as indicated by history or findings)
- Oral glucose-tolerance test (2-hour, 75 g)
- HIV screening
- Methylmalonic acid (if B12 is low-normal)
- Thiamine (vitamin B1) level
- Pyridoxine (vitamin B6) level
- Anti-double-stranded DNA and anti-Smith antibodies
- Cryoglobulin and cryofibrinogen studies
- Serum viscosity (if hyperviscosity suspected)
- Urine protein electrophoresis (Bence-Jones protein detection)
- 24-hour urine for heavy metals (arsenic, lead, mercury, cadmium)
- Angiotensin-converting enzyme (ACE) level
- Genetic testing guided by phenotype or family history (e.g., SCN9A mutations)
- Abdominal fat-pad biopsy (for amyloidosis evaluation)