What is the appropriate workup and treatment for a patient presenting with peripheral neuropathy?

Workup and Management of Peripheral Neuropathy

The appropriate workup for peripheral neuropathy should include a thorough assessment for underlying causes, with treatment focused on addressing the etiology and managing symptoms with medications like pregabalin, duloxetine, or gabapentin for neuropathic pain.

Initial Evaluation

History and Physical Assessment

• Ask specifically about numbness and tingling in hands and/or feet, and characterize these symptoms 1
• Assess for pain using a simple pain scale and obtain a comprehensive history of the complaint 1
• Evaluate for potential contributing factors:
  • Diabetes mellitus 1
  • Vitamin B12 deficiency 1, 2
  • Thyroid dysfunction 1, 2
  • Alcohol use 2
  • Toxin exposure 2
  • Chemotherapy history 1
  • Hereditary factors 1, 2

Physical Examination

• Assess temperature or pinprick sensation (small-fiber function) 1
• Test vibration sensation using a 128-Hz tuning fork (large-fiber function) 1
• Perform 10-g monofilament testing to identify feet at risk for ulceration 1
• Check for distal weakness or atrophy 2
• Evaluate deep tendon reflexes 3

Laboratory Testing

First-Line Laboratory Tests

• Complete blood count 2, 4
• Comprehensive metabolic profile 2, 4
• Fasting blood glucose 1, 2
• Hemoglobin A1c 1
• Vitamin B12 level 2, 4
• Thyroid-stimulating hormone 2, 4
• Serum protein electrophoresis with immunofixation 2

Additional Testing Based on Clinical Suspicion

• ESR and CRP (for inflammatory conditions) 2
• Autoimmune markers (ANA, ANCA) if vasculitis is suspected 2
• Hepatitis B, C, and HIV testing if indicated 1, 2
• Anti-ganglioside antibodies for suspected GBS 1
• Anti-MAG antibodies if demyelinating neuropathy is suspected 1

Specialized Testing

Electrodiagnostic Studies

• Nerve conduction studies (NCS) and electromyography (EMG) to differentiate between:
  • Axonal neuropathy 5
  • Demyelinating neuropathy 5
  • Mixed neuropathy 5
• These studies help narrow the differential diagnosis and guide further testing 5, 3

Additional Specialized Testing

• Skin biopsy for intraepidermal nerve fiber density assessment in suspected small-fiber neuropathy 5
• Lumbar puncture and CSF analysis for suspected inflammatory demyelinating neuropathies 4
• Nerve biopsy in select cases where diagnosis remains unclear 4, 5

Treatment Approach

Treating Underlying Causes

• Optimize glucose control in diabetic neuropathy to prevent progression 1
• Correct nutritional deficiencies (B12, folate) 2, 4
• Treat thyroid dysfunction if present 2
• Address alcohol use disorder 2
• Remove offending toxins or medications 2

Pharmacological Management of Neuropathic Pain

• First-line medications for neuropathic pain:
  • Pregabalin (FDA-approved for diabetic peripheral neuropathy) 1, 6
  • Duloxetine (FDA-approved for diabetic peripheral neuropathy, 60 mg once daily) 1, 7
  • Gabapentin 1

Non-Pharmacological Interventions

• Regular physical activity (improves neuropathic symptoms) 1
• Acupuncture for pain management 1
• Referral for physical therapy or rehabilitation 1
• Cognitive behavioral therapy for pain management 1

Special Considerations

Diabetic Neuropathy

• Annual screening for all patients with type 2 diabetes and after 5 years in type 1 diabetes 1
• Assess for autonomic neuropathy (orthostatic hypotension, gastroparesis, etc.) 1
• Monitor for development of foot ulcers 1

Chemotherapy-Induced Peripheral Neuropathy

• Assess for numbness, tingling in hands/feet 1
• Offer physical activity for symptom management 1
• Consider duloxetine for neuropathic pain, numbness, and tingling 1

When to Refer to Specialists

• Rapidly progressive or severe neuropathy 5
• Asymmetric or multifocal neuropathy 5
• When diagnosis remains unclear after initial evaluation 2
• For specialized testing (nerve biopsy, skin biopsy) 5
• For management of complex neuropathic pain 8

Common Pitfalls to Avoid

• Failing to screen for treatable causes before labeling neuropathy as idiopathic 2, 4
• Not considering non-diabetic causes in patients with diabetes 1
• Inadequate pain management 8
• Missing autonomic features of neuropathy 1
• Overlooking small-fiber neuropathy when nerve conduction studies are normal 5