Erythromelalgia due to thrombocytosis or polycythemia

Specialty: Hematology.

• Hematologic erythermalgia
• acromelalgia
• erythromelalgic Mitchell syndrome

Why it occurs

• Essential thrombocythemia (chronic myeloproliferative neoplasm with megakaryocytic proliferation and microvascular platelet dysfunction)
• Polycythemia vera (myeloproliferative neoplasm characterized by primary erythrocytosis that increases viscosity and favors occlusion of microcirculation)
• Primary myelofibrosis (initial megakaryocytic cell hyperproliferation phase)
• Hereditary primary erythromelalgia (mutation in the SCN9A gene for nociceptive sodium channels, idiopathic presentation)
• Systemic lupus erythematosus or autoimmune vasculitis (secondary rheumatological cause with immune complex-mediated microthrombosis)

Initial workup

Complete blood count with automated differential count (preferential attention to platelet numbers greater than 450,000/μL and elevated hematocrit above 49% in men or 48% in women); peripheral blood smear to evaluate platelet morphology (macroplatelets, platelet aggregates) and cellularity; molecular profile that includes determination of the JAK2 V617F mutation in peripheral blood (present in >95% of polycythemia vera and >50% of essential thrombocythemia), as well as mutations in the CALR (calreticulin) gene and MPL if JAK2 is negative; serum erythropoietin levels (characteristically decreased in polycythemia vera to differentiate it from secondary erythrocytosis); bone marrow biopsy to confirm WHO criteria for chronic myeloproliferative neoplasms.

Standard management

• Acetylsalicylic acid / Aspirin — low doses of 75 to 100 mg orally every 24 hours; It acts through the irreversible acetylation of platelet cyclooxygenase-1, inhibiting the synthesis of thromboxane A2 and almost immediately resolving pain and erythema of thrombotic microvascular origin.
• Hydroxycarbamide / Hydroxyurea — oral cytoreductive chemotherapeutic agent, indicated to maintain platelet count <400,000/μL or normalize hematocrit in patients at high risk of thrombosis; requires strict monitoring of blood count to avoid iatrogenic cytopenias
• Anagrelide — selective phosphodiesterase-3 inhibitor that alters the maturation of megakaryocytes, used as a second line in essential thrombocythemia if there is intolerance to hydroxyurea
• Pegylated interferon alfa-2a (cytoreductive immunomodulatory agent of choice in young patients of childbearing age or pregnant women with chronic myeloproliferative neoplasms).