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Background: The development of painful leg ulcers in the ankle area is a rare and only partially described complication in patients receiving high-dose, long-term hydroxyurea treatment for myeloproliferative diseases. Several reports have described treatments for chronic wound management with this type of lesion., Observations: We describe 2 patients who were diagnosed as having hydroxyurea-induced leg ulcers that were successfully treated with a freeze-dried sponge containing oxidized regenerated cellulose and bovine purified collagen. This dressing is able to modulate the activity of proteases such as plasmin, neutrophil-derived elastase, and matrix metalloproteinase by physically entrapping them and thus inhibiting their activity., Conclusion: This case demonstrates that topical application of a matrix metalloproteinase modulator can be a successful and safe treatment option for patients with hydroxyurea-induced recalcitrant leg ulcers.

Introduction: Causes of leg ulcers vary widely, although venous insufficiency and peripheral arteriopathy are most common. Ulcers are much rarer in patients treated by hydroxyurea., Case: A 66-year-old woman who had been treated with hydroxyurea for polycythemia vera for four years came to our consultation a month after ulceration of the left lateral malleolus had begun. Symmetric peripheral pulses were present and there was no patent venous insufficiency. After two months of local symptomatic treatment, the size of the ulcer had increased. The possible involvement of hydroxyurea in the genesis and maintenance of this leg ulcer was then considered. Hydroxyurea was stopped, and the ulcer progressively grew smaller, finally healing completely two months later., Discussion: We conclude that hydroxyurea was the primary cause of the malleolar ulcer, for it healed rapidly when this treatment stopped. Hydroxyurea causes cutaneous atrophy; when followed by microtrauma, associated with deterioration in DNA repair mechanisms, it may lead to the formation of persistent cutaneous ulcers. Hydroxyurea can also affect the microcirculation and induce tissular anoxia, which may also explain both the occurrence of cutaneous ulcers after microtrauma and their often painful character.

Hydroxyurea (HU) is effective in controlling thrombocytosis while reducing the risk of thrombosis in essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). However, HU may carry more or less severe side-effects. Rare cases of patients with painful leg ulcers have been published. We report our experience on such a side-effect in a large cohort of patients with ET and PV treated with HU and review the literature on the topic. Five (4%) out of our 124 patients (69 ET, 51 PV, 4 MF; 49 males, 75 females; mean age at diagnosis 59.1+/-11.8 years) treated with HU developed painful leg ulcers. Sixty-one other patients affected with Phmyeloproliferative disorders (Ph- MPD) developing HU-related painful leg ulcers are described in the English literature. All our five patients were women and developed leg ulcers over the age of 75. Sixty-five percent of all described cases are women; 59% were over 65 years of age and 45% over 70. Most cases received over 1 gr HU per day for at least 1 year. The pathogenesis of HU-induced skin ulcers remains elusive. Treatment is difficult and requires prompt cessation of HU therapy.

We report the case of a 73-year-old man who had been on hydroxyurea for essential thrombocythemia since 1988. After 12 years of treatment he developed a symmetrical dermatomyositis-like eruption together with a leg ulceration and five squamous cell carcinomas of the face. The possible pathogenetic mechanisms of these known side effects are discussed.

The association of lower leg ulcer development and hydroxyurea therapy in patients with myeloproliferative disorders has been reported previously. In most of these cases the ulcers healed with cessation of the hydroxyurea together with meticulous attention to wound care. We report a patient who developed painful vasculitic ulcers secondary to hydroxyurea on both lower legs whilst on long-term hydroxyurea therapy for idiopathic thrombocytosis. The ulcers extended relentlessly despite stopping hydroxyurea, maximizing topical therapies and starting intensive systemic treatment. We discuss the association of hydroxyurea therapy with the development of painful ulceration.

Hydroxyurea is a common cancer chemotherapy agent that inhibits ribonucleotide reductase, an enzyme essential to DNA synthesis. It is considered the drug of choice in the treatment of chronic myelogenous leukemia and essential thrombocythemia. The occurrence of leg ulcers have been described in 8.5% of patients receiving continuous treatment with hydroxyurea, but the cause of this complication is unknown. We report two additional patients and suggest that macroerythrocytosis, which occurs in almost all the patients taking hydroxyurea, may be a pathogenic factor. Macroerythrocytosis can be considered as an 'acquired' blood dyscrasia, and similar leg ulcers have long been known to occur with certain hereditary blood dyscrasias, such as sickle cell anemia, thalasemia, and spherocytosis.