Nail pigmentation caused by hydroxyurea: report of 9 cases.

Department of Dermatology, Ospedale S. Giovanni de Dio, University of Cagliari, Via Ospedale 54, 09124-Cagliari, Italy.
Journal of the American Academy of Dermatology (Impact Factor: 4.91). 08/2002; 47(1):146-7. DOI: 10.1067/mjd.2002.120910
Source: PubMed

ABSTRACT We report a series of 9 patients, 6 men and 3 women, who presented nail hyperpigmentation arising between 6 and 24 months from the start of hydroxyurea therapy. The most commonly observed clinical pattern was that of longitudinal melanonychia. In only 1 patient, who was affected in all 20 nails, we observed longitudinal melanonychia, diffuse melanonychia, and hyperpigmentation of the skin.

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    ABSTRACT: Dear Editor, We describe a case of a 72-year-old woman affected by essential thrombocythemia treated with hydroxyurea (HU) at a dosage of 20 mg/kg body weight for 2 years, who was referred to our Department of Dermatology. At her first presentation, clinical examination showed streaky longitudinal pigmentation on fingernails (Fig. 1) and toenails (Fig. 2), with normal periungual skin and absence of other mucocutaneous hyperpigmentations. Hutchinson's sign was absent (Fig. 2). Microscopic examination with potassium hydroxide and culture examinations were negative for dermatophytes, yeasts and molds. According to these data, we made a diagnosis of longitudinal melanonychia in the patient with essential thrombocytosis under treatment with HU. The patient was managed conservatively and she is still taking HU for her hematologic condition. Melanonychia is characterized by tan, brown or black streaks within the nail plate due to the increased melanin deposition (Figs.1 and 2). According to the literature, numerous patterns of nail dyschromia have been described, but the most common pattern is that of longitudinal bands (1). Nowadays, the prevalence of melanonychia has been estimated to 1% in the general population aged 45-65 and this percentage increases to 12% in hospitalized patients, patients with infectious diseases, melanoma and metabolic disorders (2). Two groups of longitudinal melanonychia may be identified: melanocytic activation (melanic pigmentation of the matrix epithelium without any increase in the density of melanocytes) and melanocytic proliferation (lentigo, nevus, or melanoma). Different drugs can often cause melanonychia. The agents more implicated are doxorubicin, cyclophosphamide, antibiotics, psoralens, antimalarials and HU (3). HU is a cytostatic agent used for the treatment of chronic myeloid leukemia, polycythemia vera, essential thrombocythemia or thrombocytosis, sickle cell anemia, and other myeloproliferative disorders. This drug inhibits cellular DNA synthesis, and it promotes cell death in the S phase of the cell cycle through inhibition of the enzyme ribonucleotide reductase (4). HU is generally well tolerated, but it is known to cause several adverse cutaneous reactions including increased pigmentation, hyperkeratosis, skin atrophy, xerosis, alopecia, leg ulceration, and less often nail changes including onychodystrophy, onycholysis and nail dyschromia (1). Nail dyschromia has been described in patients on HU treatment for chronic myelogenous leukemia. Until now, only five cases of longitudinal melanonychia have been described in patients with essential thrombocythemia under treatment with HU (5). Melanonychia in patients under treatment with HU generally occurs after several months of therapy, but the interval greatly varies, from 4 months to 5 years after therapy initiation. Differential diagnosis includes subungual melanoma, Laugier-Hunziker disease, pigmented squamous cell carcinoma, subungual hematoma, nevus, and hyperpigmentation due to other drugs. The pathogenesis of HU-induced melanonychia is unclear and especially the effects on proliferating epithelial cells (such as the ones of nail matrix). Several hypotheses have been proposed, including focal stimulation of nail matrix melanocytes and/or photosensitization (1-3). We report this case because HU-induced melanonychia is rarely described in patients with essential thrombocythemia. It is important to define the correct diagnosis of benign longitudinal melanonychia to exclude acral lentiginous melanoma. Regarding therapy, this "adverse event" is not considered sufficient to stop HU treatment in patients with essential thrombocythemia, according to a unified definition of clinical resistance/intolerance to HU in essential thrombocythemia. However, it may precede the appearance of leg ulcer that is considered an unacceptable mucocutaneous manifestation at any dose of HU, according to the same criteria.
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