Definition and Overview
Small fiber neuropathy (SFN) is a neuropathy in which thin myelinated Aδ fibers (1-6 μm in diameter) and unmyelinated C fibers (diameter <1 μm), which transmit pain and temperature sensations, are selectively damaged among peripheral nerves. Because large fibers (which transmit touch, vibration, and deep tendon reflexes) are preserved, standard electromyography and nerve conduction tests do not show abnormalities, and diagnosis is often delayed.
The prevalence is estimated to be about 53 people per 100,000 people, and it occurs most often in people in their 40s and 60s. Small fiber neuropathy involves not only peripheral pain fibers (sensory fibers) but also autonomic nerve fibers, causing various autonomic symptoms.
Causes and classification
Classification by cause
- Metabolic: diabetic neuropathy, pre-diabetes (impaired fasting glucose or impaired glucose tolerance), hypothyroidism
- Immune/autoinflammatory: Sjögren's syndrome, lupus, rheumatoid arthritis, sarcoidosis, celiac disease
- Heritability: SCN9A (Nav1.7), SCN10A (Nav1.8), SCN11A (Nav1.9) voltage-dependent sodium channel gene mutations
- After infection: HIV, hepatitis B and C, aftereffects of COVID-19 (Long COVID)
- Related to anti-cancer treatment: oxaliplatin, paclitaxel, etc.
- Idiopathic (unknown cause): accounts for approximately 50%
symptoms
sensory symptoms
Symptoms of small fiber neuropathy usually have a glove-stocking distribution that starts in both feet and progresses gradually upward.
- Burning pain: persistent, burning pain in the feet
- Stinging pain, electric shock sensation
- Allodynia: Pain even with light touch (socks, bedding)
- Numbness, numbness, hot and cold paresthesia
Symptoms tend to get worse at night and may be worse with warmth (such as a hot shower) or in the heat.
autonomic symptoms
Since small fibers also include autonomic nerve fibers, the following symptoms appear when autonomic nerve small fibers are damaged.
- Sweating abnormalities (anhidrosis or hyperhidrosis)
- Orthostatic hypotension
- Tachycardia
- Gastrointestinal motility abnormalities (constipation, nausea)
- bladder dysfunction
diagnosis
Skin Fiber Biopsy (Punch Biopsy)
Measurement of intraepidermal nerve fiber density (IENFD) is the gold standard for diagnosing small fiber neuropathy. A small amount of skin is collected from 10 cm above the ankle and upper thigh, stained with PGP9.5 antibody, and the number of nerve fibers is measured. If the IENFD is below the 5th percentile of the normal reference value (relative to age and gender), the diagnosis is consistent.
Quantitative Sensory Testing (QST)
Small-fiber paresthesia is evaluated by quantitatively measuring hot and cold sensations and pain thresholds.
Autonomic function test
Autonomic nerve fiber function is assessed using heart rate variability (HRV) and quantitative sweat axon reflex testing (QSART).
Blood tests and genetic tests
Fasting blood sugar, glycated hemoglobin (HbA1c), 75g oral glucose tolerance test (OGTT), autoantibody (ANA, anti-SSA/SSB), thyroid function, and SCN9A/SCN10A gene analysis are used to identify the cause.
treatment
Cause Treatment
If pre-diabetes is the cause, lifestyle changes (exercise, weight loss) and blood sugar control may help restore nerve fiber density. In immune-mediated small fiber neuropathy, immunoglobulin (IVIG) and steroid treatment may be effective.
Neuropathy Pain Medication Treatment
Primary drug: - Tricyclic antidepressants (amitriptyline): Useful in controlling nighttime pain. - SNRI (duloxetine, venlafaxine): Control of pain and autonomic symptoms - Gabapentin, Pregabalin: Control of neuropathic pain
Topical treatment: - Lidocaine 5% patch or gel - Capsaicin 8% patch: High concentration of capsaicin desensitizes C fibers
Management of autonomic symptoms
For orthostatic hypotension and abnormal sweating caused by autonomic nerve fiber involvement, autonomic nerve function treatment according to the cause is provided in parallel.