What is the initial treatment for Erythromelalgia?

Initial Treatment for Erythromelalgia

The initial treatment for erythromelalgia should include topical therapies as first-line pharmacologic management, along with aspirin 325 mg orally daily for a trial of 1 month, particularly for patients with secondary erythromelalgia due to myeloproliferative disorders. 1, 2

Evaluation and Non-Pharmacologic Management

• Evaluate for underlying causes or associations, particularly myeloproliferative disorders (e.g., essential thrombocythemia, polycythemia vera), which may underlie erythromelalgia in approximately 5% of patients 1
• Provide patient counseling to maintain as normal a lifestyle as possible while minimizing known triggers 1
• Implement safe cooling measures for affected areas, limiting ice and water immersion to 10 minutes at a time and no more than 4 times daily to prevent tissue damage 1, 2
• Encourage alternative cooling strategies such as elevation of extremities during symptoms 1
• Advise patients that excessive cooling with ice water or fans can lead to tissue damage, ulcerations, and worsening symptoms when discontinued 2

First-Line Pharmacologic Treatment

Topical Therapies (Trial for 4 weeks)

• Lidocaine patches (4% OTC or 5% prescription) applied to affected areas for 12-24 hours 2
• Compounded amitriptyline-ketamine mixture applied to affected areas up to 3 times daily 2
• Compounded midodrine 0.2% in Vanicream applied 3 times daily for reducing redness 1
• Capsaicin cream (0.025-0.075%) applied 3-4 times daily for 6 weeks (warn patients about initial burning sensation) 2
• Other topical options with anecdotal evidence: oxymetazoline 0.05%, brimonidine tartrate 0.33%, or timolol maleate 0.5% (with caution regarding rebound erythema) 1

Systemic Therapy

• Aspirin 325 mg orally daily for at least 1 month trial 1, 2
• Aspirin is particularly effective for secondary erythromelalgia due to myeloproliferative disorders, with dramatic improvement often occurring within days of initiation 1, 3
• In a case series of 57 patients, approximately half reported that aspirin helped their symptoms 1

Second-Line Therapy (If First-Line Fails)

• For aspirin-allergic patients, consider other NSAIDs such as ibuprofen, indomethacin, nabumetone, naproxen, or sulindac 1, 2
• Systemic corticosteroids should be considered early in the disease course to prevent possible irreversible nociceptive remodeling and central sensitization 1, 2
• Sodium channel blockers (e.g., lidocaine, carbamazepine, mexiletine) may be beneficial, especially for primary erythromelalgia 4
• Each systemic medication should be tried for 3-4 months before considering it ineffective 1

Third-Line Therapy

• Referral to a comprehensive pain rehabilitation center for multidisciplinary management 1, 2
• Consider procedural interventions for refractory cases, though evidence is limited to case reports and small case series 5

Special Considerations

• For secondary erythromelalgia due to myeloproliferative disorders, treatment should focus on addressing the underlying condition 1
• Monitor all patients with erythromelalgia with periodic blood cell counts, as symptoms of erythromelalgia may precede the onset of myeloproliferative disease by a median of 2.5 years 3
• Primary erythromelalgia may be associated with mutations in the SCN9A gene, which encodes the Nav1.7 sodium channel, making sodium channel blockers potentially more effective in these cases 4
• Topical therapies are generally preferred due to their limited side effects compared to systemic options 2, 6

Common Pitfalls to Avoid

• Discontinuing treatments too quickly before adequate trial periods (4 weeks for topicals, 3-4 months for systemic medications) 2
• Failing to evaluate for underlying myeloproliferative disorders, which could significantly impact treatment approach 1, 3
• Allowing patients to use excessive cooling measures, which can lead to tissue damage and worsen symptoms long-term 1, 2