What is the treatment for erythromelalgia?

Treatment of Erythromelalgia

Aspirin 325 mg daily should be the first-line systemic treatment for erythromelalgia, particularly in cases associated with myeloproliferative disorders. 1, 2

Step-by-Step Treatment Algorithm

First-Line Therapy

1. Evaluate for underlying causes

   • Screen for myeloproliferative disorders (polycythemia vera, essential thrombocythemia) 1, 3
   • Monitor blood counts periodically as erythromelalgia can precede myeloproliferative disorders by years 3

2. Implement lifestyle modifications

   • Avoid triggers such as heat and strenuous exercise 2
   • Limit cooling measures (ice/water immersion) to 10 minutes, maximum 4 times daily to prevent tissue damage 1, 2

3. Topical treatments (trial each for 4 weeks)

   • Lidocaine patches (4% OTC or 5% prescription) applied to affected areas for 12-24 hours 1, 2
   • Compounded amitriptyline 1-2% with ketamine 0.5-5% applied up to 3 times daily 1, 2
   • Compounded midodrine 0.2% applied 3 times daily for erythema management 1, 2
   • Topical capsaicin cream (0.025-0.075%) applied 3-4 times daily for 6 weeks (warn patients about initial burning sensation) 1, 2

4. Systemic treatment

   • Aspirin 325 mg daily for at least 1 month 1, 2
   • Particularly effective for secondary erythromelalgia associated with myeloproliferative disorders 1, 3, 4

Second-Line Therapy (if first-line fails after adequate trial)

1. Alternative NSAIDs (for aspirin-allergic patients)

   • Ibuprofen, indomethacin, nabumetone, naproxen, or sulindac 1
   • Piroxicam has also shown success in primary erythromelalgia 1

2. Neuropathic pain medications (trial each for 3-4 months)

   • Gabapentin starting at 300 mg at bedtime, up to 2400 mg daily divided into 3 doses 1
   • Pregabalin 75-300 mg every 12 hours 1
   • Venlafaxine up to 75 mg daily 1

3. Other medications

   • Selective serotonin reuptake inhibitors (sertraline preferred over fluoxetine) 1
   • Amitriptyline (oral) 1
   • Sodium channel blockers (mexiletine, carbamazepine) 1, 4

4. Corticosteroids

   • Consider early in disease course (history <1 year or sudden onset with clear precipitant) 1
   • Methylprednisolone 1000 mg IV daily for 5 days or prednisone at least 40 mg daily for 5 days 1

Third-Line Therapy (for refractory cases)

1. Referral to pain rehabilitation center 1

2. Experimental treatments (limited evidence)

   • Sodium channel blockers targeting Nav1.7 1
   • Ketamine infusion (controversial due to adverse effects and abuse potential) 1
   • Sodium nitroprusside infusions (for cases with concomitant hypertension, especially in children) 1

Special Considerations

Primary vs. Secondary Erythromelalgia

• Primary (idiopathic) erythromelalgia may be associated with SCN9A gene mutations affecting sodium channel Nav1.7 1, 4
• Secondary erythromelalgia is often associated with myeloproliferative disorders and responds dramatically to aspirin 1, 3, 5

Treatment Pitfalls to Avoid

• Excessive cooling: Can lead to tissue damage, ulcerations, and worsening symptoms when discontinued 1, 2
• Premature treatment discontinuation: Ensure adequate trial periods (4 weeks for topicals, 3-4 months for systemic medications) 2
• Missing underlying disorders: All patients with erythromelalgia should be monitored with periodic blood counts 3
• Intravenous lidocaine: Safety concerns include neurologic effects such as slurred speech and altered mental status 1

Treatment Based on Disease Type

• For secondary erythromelalgia due to myeloproliferative disorders, aspirin is remarkably effective and should be first-line therapy 1, 3, 6
• For primary erythromelalgia, a combination of topical treatments and neuropathic pain medications may be required 4, 7