What medications can lead to small fiber neuropathy?

Common Medications That Can Lead to Small Fiber Neuropathy

Chemotherapeutic agents, fluoroquinolone antibiotics, and statins are the most common medications that can cause small fiber neuropathy, presenting with painful burning sensations, abnormal temperature perception, and autonomic dysfunction. 1, 2

Chemotherapy Agents

Small fiber neuropathy (SFN) from chemotherapy affects nerve terminals involved in temperature and pain perception, leading to characteristic symptoms:

• Vinca alkaloids (vincristine): Causes painful burning sensations in feet/hands and autonomic dysfunction 1
• Taxanes (paclitaxel): Associated with painful small fiber damage 1
• Platinum compounds (oxaliplatin): Causes transient dysesthesia and axonal polyneuropathy 2, 3
• Bortezomib: Leads to painful small fiber damage with autonomic involvement 1
• Thalidomide: Causes painful axonal sensorimotor neuropathy that often doesn't improve after drug withdrawal 3

Chemotherapy-induced peripheral neuropathy typically presents with:

• Burning pain in hands and feet
• Lancinating (shooting) pain
• Decreased pain perception in affected areas
• Abnormal temperature sensation
• Autonomic symptoms (postural hypotension, bladder disturbances, constipation) 1

Antibiotics

• Fluoroquinolones (ciprofloxacin, levofloxacin): Associated with sensory or sensorimotor axonal polyneuropathy
  • FDA warnings specifically mention "rare cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness" 4, 5
  • Symptoms may occur soon after initiation and can be irreversible 5
  • Requires immediate discontinuation if symptoms develop 4, 5

Other Common Medications

• Statins (HMG-CoA reductase inhibitors): Can cause axonal sensorimotor neuropathy or purely small-fiber neuropathy 3, 6
• Antiretrovirals (Nucleoside reverse transcriptase inhibitors): Associated with sensory neuropathy through effects on mitochondrial DNA replication 3
• Cardiovascular drugs: Various agents have been implicated in peripheral neuropathy 6
• Anticonvulsants and psychotropics: Can cause neuropathic symptoms in some patients 6

Clinical Presentation and Diagnosis

SFN presents with characteristic symptoms:

• Burning pain in extremities (often worse at night)
• Lancinating (shooting) pain
• Paresthesias (tingling, pins and needles)
• Autonomic dysfunction (sweating abnormalities, orthostatic hypotension)
• Normal nerve conduction studies (as large fibers are spared) 7, 8

Diagnosis requires:

1. Clinical symptoms of small fiber involvement
2. Normal nerve conduction studies (as these test only large fibers)
3. Abnormal specialized tests:
   • Skin biopsy showing decreased epidermal nerve fiber density
   • Quantitative sensory testing showing abnormal temperature thresholds
   • Autonomic testing (for sweating abnormalities, heart rate variability) 7

Risk Factors for Medication-Induced SFN

Patients are more likely to develop medication-induced neuropathy if they have:

• Pre-existing neuropathy
• Diabetes mellitus
• Genetic predispositions
• Advanced age 6

Management Considerations

When medication-induced SFN is suspected:

1. Identify and discontinue the offending medication if possible
2. Monitor for improvement after discontinuation (some cases may be irreversible)
3. Consider symptomatic treatment:
   • Duloxetine or gabapentin for neuropathic pain 2, 6
   • Topical treatments for localized symptoms

Important Caveats

• Early recognition is critical as continued exposure may lead to irreversible damage 1, 5
• Small fiber neuropathy significantly impacts quality of life and daily functioning 9
• Standard nerve conduction studies may be normal despite significant symptoms, as these tests primarily assess large fiber function 7
• Some medications (particularly fluoroquinolones) require immediate discontinuation at the first sign of neuropathy symptoms 4, 5