Úlceras por hidroxiurea en paciente con policitemia vera / Ulcers to hydroxyurea in a patient with polycythemia vera

La hidroxiurea es un agente citostático que inhibe la síntesis de ADN. Se considera el tratamiento de primera línea para algunos trastornos mieloproliferativos, enfermedad de células falciformes, casos severos de psoriasis refractaria y como adyuvante en la terapia de VIH. Se ha informado de que algunos pacientes tratados con hidroxiurea pueden tener úlceras en las extremidades inferiores. Paciente femenino de 67 años de edad con antecedentes de policitemia vera tratada con hidroxiurea durante un año, se deriva a dermatología por presentar úlceras bilaterales en extremidades inferiores. Al examen físico se evidencian dos lesiones ulceradas en la región calcánea. Se realiza una biopsia de piel, y muestra signos no específicos de inflamación. Se decide la interrupción de la hidroxiurea y se inicia la terapia adyuvante con pentoxifilina. Las lesiones se resolvieron en dos meses, dejando una pequeña cicatriz residual. Es importante recordar esta rara complicación inducida por el uso prolongado de la hidroxiurea y, de esta manera, realizar un diagnóstico precoz y tratamiento adecuado, que hasta el momento es básicamente la suspensión de la hidroxiurea.

Hydroxyurea is a cytostatic agent that inhibits DNA synthesis. It is considered the first line treatment for some myeloproliferative disorders, sickle cell disease, severe cases of refractory psoriasis and as adjuvant in VIH therapy. It has been reported that some patients treated with hydroxyurea may have leg ulcers. A 67 year old female patient with a history of polycythemia vera treated with hydroxyurea for a year, is derived to dermatology for presenting bilateral lower extremity ulcers. Physical examination demonstrated two ulcerated lesions in the calcaneal region. A skin biopsy is performed, and it shows non-specific signs of inflammation. Discontinuation of hydroxyurea is decided and initiate adjuvant therapy with pentoxifylline. These ulcerative lesions were resolved within two months, leaving a small residual scar. It is important to remember this rare complication induced by prolonged use of hydroxyurea and thus, early diagnosis and appropriate treatment can be made, which so far is basically the suspension of hydroxyurea.

Efeitos colaterais cutâneos após uso prolongado de hidroxiuréia na Policitemia Vera / Cutaneous effects after prolongaded use of hydroxyurea in Polycythemia Vera

A hidroxiureia é um derivado hidroxilado da ureia utilizado em diversas desordens hematológicas. Inúmeras alterações cutâneas, porém raras, são relatadas após seu uso prolongado. A patogênese das mesmas não está bem esclarecida, porém, sugere-se que a droga tenha uma ação tóxica direta sobre a pele. Descrevemos um homem de 75 anos, branco, com diagnóstico de Policitemia Vera que, ao longo de 11 anos de tratamento com hidroxiureia, evoluiu com várias lesões cutâneas: hiperpigmentação da pele, lesões atróficas em antebraços, melanoníquia longitudinal das 20 unhas, úlcera em antebraço direito, xerose cutânea, ictiose em pernas e carcinoma espinocelular no pavilhão auricular direito. Até o momento, os relatos na literatura descrevem pouca diversidade de lesões nos pacientes acometidos.

Hydroxyurea is an hydroxylated urea derivative used in many myeloproliferative disorders. Many, but unusual cutaneous disorders are related after its prolonged use. Their pathogenesis is not clear, but it is suggested that there is direct toxicity of the drug on the skin. We described a white, 75-year old man with diagnosis of Polycythemia Vera that in 11 years of treatment developed many cutaneous lesions: skin hyperpigmentation, atrophic lesions on forearms, longitudinal melanonychia of 20 nails, right forearm ulcer, cutaneous xerosis, ichthyosis and auricular spinocellular carcinoma. At this moment, the literature reports describe little diversity of lesions in affected patients.

Úlceras acrales por hidroxiurea en paciente con policitemia vera: comunicación de un caso / Acral ulcers associated with hydroxyurea therapy in a patient with polycythemia vera

La hidroxiurea (HU) es una droga antitumoral utilizada principalmente en enfermedades hematológicas. Es generalmente bien tolerada; sin embargo, puede asociarse a efectos adversos mucocutáneos severos, como úlceras acrales. La patogenia de estas úlceras es desconocida, y su aparición se relaciona a la patología de base, tiempo y dosis administrada. Son muy dolorosas, frecuentemente múltiples y por lo general revierten en forma espontánea al suspender el medicamento. La región maleolar es la más comúnmente comprometida. Presentamos el caso de una paciente de sexo femenino, de 64 años, en tratamiento con HU por policitemia vera, que presentó úlceras acrales a los tres años de tratamiento, con excelente evolución tras la suspensión del fármaco. Es fundamental conocer la existencia de estos efectos adversos para sospecharlos precozmente y realizar un oportuno diagnóstico y tratamiento.

Hydroxyurea (HU) is an antitumor drug commonly used in haematological diseases. It is usually well tolerated, however, it may be associated with severe muco-cutaneous side effects such as acral ulcers. The pathogenesis of these ulcers is unknown, and their appearance is related to the main disease, time and dosage. They are very painful, often multiple, an spontenous resolution after drug suspension is observed. The malleolus region is the most common site affected. We present the case of a 64-year-old woman with polycythemia vera treated with HU who developed acral ulcers after 3 years of treatment, with excellent response after drug discontinuation. For an opportune diagnosis and treatment of these side effects, it is very important to know of their existence and suspect that they may appear in advance.

Hydroxyurea Induced Perimalleolar Ulcers

Hydroxyurea (HU) is an antineoplastic drug commonly used to treat chronic myeloproliferative disorders. Common dermatological side effects include hyperpigmentation, scaling, erythema, alopecia, desquamation of face and hands. Leg ulceration following HU therapy is less common and very few cases have been reported so far. Objective of this paper is to increase the awareness of hydroxyurea induced leg ulcers which will aid in the early diagnosis and appropriate treatment. The first case was a chronic myeloid leukemia (CML) patient on HU 1.5 g/day for 5 yr, who had bilateral painful perimalleolar ulcers for 6 months. The second case was a CML patient on HU 1.5 g/day for 3 yr who developed bilateral lateral malleolar ulcers. Third case was a polycythemia vera (PV) patient on HU 1 g/day for 5 yr who presented with painful medial malleolar ulcer of 2 months. The last case of our report was an elderly PV patient on HU 1.5 g/day for 2 yr and presented with lateral malleolar ulcer which persisted on reducing the dose of HU. In all the 4 cases the ulcers healed on stopping HU. Our report confirms the association of chronic hydroxyurea therapy and perimalleolar ulcers which respond promptly after discontinuation of the drug. The heightened awareness among the physicians will promote early diagnosis and prompt relief from the agonizing ulcers.