Erythromelalgia in patients with essential thrombocythemia and polycythemia vera

Erythromelalgia is an uncommon neurovascular pain syndrome characterized by periodic attacks with a triad of erythema, increased temperature, and burning pain that primarily affects the feet and hands and leads to markedly diminished quality of life. [1–4] Erythromelalgia exists as either a primary, idiopathic form or secondary to various diseases, especially myeloproliferative neoplasms, essential thrombocythemia (ET), and polycythemia vera (PV). [1–3] Diagnosis should prompt evaluation for myeloproliferative neoplasms because erythromelalgia can precede or be the initial manifestation of an underlying myeloproliferative neoplasm. [1,5,6] The pathogenesis of secondary erythromelalgia is currently not well understood. Prior studies propose that erythromelalgia is caused by arterial microcirculation occlusion from intravascular platelet activation and aggregation, which is supported by the efficacy of aspirin in reducing erythromelalgia symptoms. [2,3,5,7] Although treatment of erythromelalgia is often challenging, erythromelalgia secondary to ET and PV is typically responsive to aspirin. Treatment of the underlying myeloproliferative neoplasm may reduce erythromelalgia symptoms. [3,6] The main objective of our study was to describe the clinical and laboratory characteristics and the results of treatment of patients with erythromelalgia secondary to ET and PV. The Mayo Clinic Institutional Review Board approved this study. We queried the institution’s diagnosis index of patients with erythromelalgia and cross-referenced them with either ET or PV at Mayo Clinic, Rochester, MN, between 1995 and 2012. All patients who received a diagnosis of ET and six of the eight patients who had the diagnosis of PV had bone marrow confirmation of their myeloproliferative neoplasm. Ten patients had ET and erythromelalgia; eight patients had PV with erythromelalgia. For one patient, erythromelalgia was the presenting manifestation of ET, with diagnosis of erythromelalgia approximately 5 years before diagnosis of ET. All other patients had the diagnosis of the myeloproliferative neoplasm at the same time or before the diagnosis of erythromelalgia. Six of the patients in the ET and erythromelalgia group had simultaneous diagnosis of ET and erythromelalgia. Four of the eight patients received a diagnosis of PV and erythromelalgia concurrently. Six patients in the ET and erythromelalgia group were male; two patients in the PV and erythromelalgia group were male. In the ET and erythromelalgia group, the average age at diagnosis of ET and erythromelalgia was 52.9 years and 53.1 years, respectively. By comparison, the patients had the diagnoses of PV or PV with erythromelalgia at older ages, averaging 78.8 years and 83.6 years, respectively. Most commonly, erythromelalgia involved the lower extremities, which is consistent with prior case reports. [3,4] All of our patients had bilateral extremities affected; however, in secondary erythromelalgia, unilateral involvement may be present. [2] Table 1 details the affected site distribution, the laboratory characteristics at the time of myeloproliferative neoplasm diagnosis, and the clinical features. Treatment details were available for five of the 10 patients with erythromelalgia and ET. Consistent with the literature, therapy with aspirin and treatment of the underlying myeloproliferative neoplasm resolved or greatly reduced erythromelalgia symptoms. One patient achieved resolution of erythromelalgia with aspirin 81 mg and another patient with aspirin 325 mg and hydroxyurea. A separate patient taking aspirin 81 mg and hydroxyurea reported an 80% reduction in erythromelalgia symptoms. Another patient receiving a regimen of aspirin 81 mg, hydroxyurea, pregabalin, and hydroxyzine noticed a daily reduction from 30 erythromelalgia attacks to 5. One patient did not achieve platelet control with hydroxyurea or anagrelide treatment but did have excellent control with busulfan, which is thought to provide longer relief by affecting platelet production. [4] This latter patient