Erythromelalgia and Thrombocytosis: Clinical Features and Management
Erythromelalgia is a rare debilitating disorder characterized by episodic burning pain associated with erythema and warmth of the extremities (primarily feet and hands), while thrombocytosis is an elevated platelet count that can occur as a primary condition or secondary to myeloproliferative disorders, and these conditions can be related as thrombocytosis is a known cause of secondary erythromelalgia. 1, 2
Erythromelalgia
Clinical Features
- Characterized by episodic burning pain with redness and warmth, primarily affecting feet and hands
- Often triggered by physical activity and exposure to warm temperatures
- Pain is characteristically relieved by cooling the affected areas
- May present with swelling of extremities during symptomatic episodes
- Can significantly impact quality of life, with increased morbidity, mortality, and suicide risk 1
Classification
- Primary erythromelalgia: Two-thirds of cases with no identifiable cause, often starting in childhood
- Secondary erythromelalgia: Associated with underlying conditions such as:
Diagnosis
- Clinical diagnosis based on history and physical examination during symptomatic episodes
- No specific diagnostic test exists
- Skin biopsy may be considered to evaluate for small-fiber neuropathy
- Assessment for underlying autoimmune markers is recommended 2, 4
Thrombocytosis and Its Relationship to Erythromelalgia
Thrombocytosis (elevated platelet count) can be:
- Primary: Associated with myeloproliferative disorders like essential thrombocythemia or polycythemia vera
- Secondary/Reactive: Due to inflammation, infection, or other conditions
When associated with myeloproliferative disorders, thrombocytosis can lead to erythromelalgia through:
- Platelet-mediated inflammation and arteriolar thrombosis
- Formation of platelet thrombi in the arterial microvasculature 5, 6
The estimated incidence of erythromelalgia in polycythemia vera is approximately 3%, often associated with thrombocythemia 1.
Management of Erythromelalgia
Patient Education and Lifestyle Modifications
- Maintain normal activities while avoiding excessive heat exposure and vigorous exercise
- Limit cooling measures and elevate extremities during symptom flares
- Avoid excessive ice or cold water immersion (can lead to tissue damage) 2
Pharmacologic Treatment
For Secondary Erythromelalgia (especially with thrombocytosis)
Aspirin 325 mg daily is first-line therapy with approximately 50% of patients reporting improvement
Treatment of underlying myeloproliferative disorder is crucial when thrombocytosis is present 2, 7
For Primary or Refractory Erythromelalgia
- Sodium channel blockers: mexiletine, carbamazepine, lidocaine
- Gabapentin (300 mg at bedtime, titrated up to 2400 mg daily) or Pregabalin (75-300 mg every 12 hours)
- Venlafaxine up to 75 mg daily
- Systemic corticosteroids for acute presentations 2
Topical Therapy Options
- Midodrine 0.2% compounded in Vanicream (3 times daily)
- Oxymetazoline 0.05%, brimonidine tartrate 0.33%, or timolol maleate 0.5%
- Amitriptyline-ketamine compound 2
Important Clinical Pearls
Diagnostic challenge: Symptoms are intermittent and extremities may appear normal between episodes, leading to missed diagnoses 1
Aspirin response: The prompt and lasting relief of burning pain by low-dose aspirin is considered diagnostic of thrombocythemic erythromelalgia 5, 3
Platelet consumption: Studies show increased platelet consumption in erythromelalgia patients with thrombocythemia, which normalizes with aspirin therapy 6
Associated complications: Erythromelalgia can be a warning sign of more serious vascular complications in patients with myeloproliferative disorders 7
Treatment response differences: Secondary erythromelalgia (especially with thrombocytosis) typically responds well to aspirin, while primary forms often don't respond to aspirin therapy 3