How do you manage erythromelalgia?

Management of Erythromelalgia

Aspirin 325 mg daily should be the first-line treatment for erythromelalgia, particularly effective in secondary forms associated with myeloproliferative disorders, with approximately 50% of patients reporting symptom improvement. 1, 2

Initial Evaluation and Management

Diagnostic Workup

• Evaluate for underlying causes or associations, especially myeloproliferative disorders
• Monitor with periodic blood counts as erythromelalgia can precede myeloproliferative disorders by a median of 2.5 years 3
• Assess for small-fiber neuropathy and autoimmune markers when appropriate

First-Line Therapy

1. Patient education and lifestyle modifications:

   • Maintain as normal a lifestyle as possible
   • Cool affected areas safely (limit ice/water immersion to 10 minutes at a time, maximum 4 times daily)
   • Avoid excessive cooling which can lead to tissue damage and worsening disability 2

2. Topical therapy (4-week trial for each):

   • Midodrine 0.2% compounded in Vanicream applied 3 times daily 1
   • Amitriptyline-ketamine compound (75% of patients report improvement) 2
   • Other options: oxymetazoline 0.05%, brimonidine tartrate 0.33%, timolol maleate 0.5% 1
   • Caution: advise patients about risk of rebound erythema with continued use

3. Systemic therapy:

   • Aspirin 325 mg daily for at least 1 month trial 1, 2
   • Dramatic improvement often occurs within days for secondary EM, particularly with myeloproliferative disorders 3, 4

Second-Line Therapy

If first-line therapy is inadequate after appropriate trials:

Alternative Systemic Medications

• For aspirin allergy: Other NSAIDs (ibuprofen, indomethacin, nabumetone, naproxen, sulindac) 1
• Neuropathic pain medications:
  • Gabapentin (start 300 mg at bedtime, titrate up to 2400 mg daily in 3 divided doses) 2
  • Pregabalin (75-300 mg every 12 hours) 2
  • Venlafaxine (up to 75 mg daily) 2

For Primary Erythromelalgia

• Sodium channel blockers (especially for primary/genetic forms) 5:
  • Mexiletine (safer oral alternative to IV lidocaine) 1
  • Carbamazepine 1, 5
  • Lidocaine (topical formulations preferred over IV) 1, 5

Third-Line Therapy

For Early Disease (<1 year duration)

• Systemic corticosteroids if sudden onset, clear precipitant, or disease duration <1 year 1, 2:
  • Methylprednisolone 1000 mg IV daily for 5 days (5000 mg total) OR
  • Prednisone at least 40 mg daily for 5 days (200 mg total)

For Refractory Cases

• Referral to a pain rehabilitation center 1
• Consider procedural interventions in a multidisciplinary setting 6:
  • Sympathetic ganglion blocks
  • Spinal cord stimulation
  • Dorsal root ganglion stimulation

Special Considerations

Secondary Erythromelalgia

• Always treat the underlying condition (particularly myeloproliferative disorders) 1, 3, 4
• Intravenous immunoglobulin (IVIG) for underlying autoimmune connective tissue disease 2

Pediatric Patients

• Children with primary erythromelalgia may have limited response to aspirin 7
• Sodium channel blockers may be more effective in genetic forms

Common Pitfalls and Caveats

1. Failure to identify underlying conditions: Always screen for myeloproliferative disorders, as erythromelalgia can precede diagnosis by years 3

2. Excessive cooling: Patients often discover that cold water immersion relieves symptoms, but this can lead to tissue damage, ulcerations, and worsening disability 1, 2

3. Inadequate trial periods: Each medication should be tried for an adequate duration (4 weeks for topicals, 1 month for aspirin, 3-4 months for other systemic therapies) 1

4. Overlooking genetic causes: Primary erythromelalgia, especially in younger patients, may be related to SCN9A gene mutations affecting sodium channels, requiring targeted therapy 5