Initial Management and Treatment of Erythromelalgia
Begin with topical therapies as first-line treatment for 4 weeks, combined with aspirin 325 mg daily for at least 1 month in all patients without contraindications, particularly those with myeloproliferative disease where dramatic improvement occurs within days. 1
Immediate Non-Pharmacologic Interventions
Critical safety counseling is essential to prevent tissue damage:
- Strictly limit ice or water immersion to maximum 10 minutes, 4 times daily to avoid immersion foot, trench foot, swelling, and ulceration 1
- Avoid continuous fan use, which causes windburn-equivalent damage and rebound flushing 1
- Encourage extremity elevation during flares 1
- Substitute swimming for running if exercise triggers flares 1
- Counsel patients to maintain normal lifestyle and activities, as precipitating episodes does not worsen long-term outcomes 1
First-Line Pharmacologic Treatment
Topical Therapies (Trial each for 4 weeks)
For pain control:
- Lidocaine patches (4% OTC or 5% prescription) applied to affected areas for 12-24 hours, particularly effective on dorsal/plantar foot surfaces (up to 3 patches) 1
- Compounded amitriptyline with ketamine 1
- Capsaicin for receptor desensitization 1
For erythema reduction:
- Compounded midodrine 0.2% in Vanicream, applied 3 times daily (evidence-based preferred treatment) 1
- Alternative vasoconstrictor options: oxymetazoline 0.05%, brimonidine tartrate 0.33%, or timolol maleate 0.5% (warn about rebound erythema risk) 1
Systemic First-Line Therapy
Aspirin 325 mg daily for minimum 1 month trial:
- Particularly effective in secondary EM from myeloproliferative disease (essential thrombocytosis, polycythemia vera) with dramatic improvement within days 1
- Works through prostaglandin synthesis inhibition and platelet aggregation blockade 1
- Approximately 50% of patients report symptom improvement 1
- Most common initial systemic therapy due to safety, accessibility, and cost 1
Second-Line Systemic Therapy (If First-Line Fails After 3-4 Months)
For aspirin-allergic patients:
- Other NSAIDs (ibuprofen, indomethacin, nabumetone, naproxen, sulindac) - nearly 50% report benefit 1
- Piroxicam for primary EM 1
Sodium channel blockers (particularly for SCN9A-related primary EM):
- Mexiletine (oral) - safer alternative to IV lidocaine, which causes slurred speech and altered mental status 1
- Dosing: 1-2 mg/kg bolus or 50-100 mg fixed dose, with 1 mg/kg/hour continuous infusion 1
Corticosteroids:
- Consider early in disease course before irreversible nociceptive remodeling and central sensitization occur 1
- Mechanism: suppression of inflammatory neuropathy 1
Gabapentin:
- Starting 300 mg at bedtime, titrating up to 2400 mg daily divided into 3 doses 2
- Note: Lower limb edema is a frequent side effect that may counteract topical medication benefits 3
Third-Line Management
For severe, refractory, or disabling EM:
- Referral to comprehensive pain rehabilitation center 1
- Multidisciplinary team approach addressing pain control, psychological concerns (anxiety), and functional restoration 1
Critical Diagnostic Considerations
Screen for secondary causes:
- Myeloproliferative disease (5% of cases) - essential thrombocythemia, polycythemia vera 1
- Small fiber neuropathy present in ~90% on thermoregulatory sweat testing 1
- Large fiber neuropathy in ~50% on EMG/nerve conduction studies 1
- Autoimmune conditions, medications (bromocriptine, calcium channel blockers) 4
Common Pitfalls to Avoid
- Do not recommend IV lidocaine infusions due to unclear safety profile and common neurologic adverse effects 1
- Avoid ketamine infusions except as controversial adjunctive therapy, given limited evidence, adverse effects, and abuse potential 1
- Do not delay aspirin trial in myeloproliferative-associated EM, where response is rapid and dramatic 1
- Recognize that skin biopsy shows decreased epidermal nerve fiber density in only a minority of cases despite high prevalence of small fiber neuropathy 1