Longitudinal melanonychia has been associated with a range of drugs, especially chemotherapeutic agents. We report 7 cases of melanonychia associated with the use of hydroxycarbamide for essential thrombocythemia. Of a patient population of 27, 7 (26%) developed melanonychia over a period of 2–7 years, and was not dose dependent. The high incidence of melanonychia in Chilean patients may be in part due to their Hispanic descent or to the high levels of UV radiation found in Santiago.
We present 7 cases, five men and two women, all with a diagnosis of essential thrombocythemia, who presented with longitudinal dark pigmentation of the nails after a period of 3 to 5 years of treatment with hydroxyurea. Acquired longitudinal melanonychia is characterized by the presence of longitudinal brown or black lines in the nail plate as a result of increased melanin deposits. They originate in the nail matrix and are the result of an increased production of melanin by matrix melanocytes or of an increased number of melanocytes in the nail matrix.
Of 27 patients currently being followedup for essential thrombocythemia and being treated with hydroxycarbamide, 7 (26%) patients have developed melanonychia.
The clinical details of the 7 patients are shown in Table
Clinical features of nail pigmentation.
Age | Sex | Mean dose/day | Time using hydroxyurea | Number of nails affected hands (feet) | Skin hyperpigmentation |
---|---|---|---|---|---|
78 | M | 1500 mg | 2 years | 3 (0) | No |
84 | M | 2500 mg | 5 years | 10 (10) | Yes |
63 | M | 500 mg | 6 years | 2 (0) | No |
59 | M | 1000 mg | 3 years | 5 (2) | No |
81 | M | 500 mg | 4 years | 10 (10) | No |
64 | F | 1500 mg | 5 years | 8 (4) | No |
73 | F | 2000 mg | 7 years | 6 (10) | Yes |
All patients did not have significant comorbidities and the use of other drugs was limited to aspirin 100 mg and in four patients the use of allopurinol 100 mg/day.
Nail examination (Figures
(a) Close of longitudinal melanonychia. (b) Melanonychia of the thumb nail.
Seven patients (6 men and 1 woman) with polycythemia rubra vera and treated with venesection for a median of 5 years were evaluated for melanonychia, and none of the 7 patients showed this condition. Fifty patients with atrial fibrilation attending an outpatient oral anticoagulant Clinic were also evaluated to assess the frequency of melanonychia in a general Chilean population, and 3 (6%) of these patients were identified as having this nail condition. The melanonychia involved 3 to 4 nails and was found in the hands but not in the feet.
A healthy adult has approximately 200 melanocytes per mm2 in the nail matrix, of which the majority remain dormant [
The largest reported series of melanonychia in patients with essential thrombocythemia and associated with hydroxycarbamide is of 9 cases [
Hydroxycarbamide is a cytostatic agent used in the treatment of myeloproliferation, inhibiting cellular DNA synthesis and promoting cell death in the S phase of the cell cycle [
It has been postulated that one cause is photosensitivity, and in Santiago, Chile, the levels of UV radiation are high during most of the year, and this may be a contributing factor for the relatively high incidence of melanocytic in the patients taking hydroxycarbamide, apart from the racial influence of being of a Hispanic origin. The high UV radiation levels may also explain why the melanonychia was more common in the hands than in the feet and was only found in the hands of the control patients, reflecting total UV radiation exposure.
In the reported cases, it has been estimated that the risk of developing melanonychia in patients receiving treatment with hydroxycarbamide is 4%, more commonly in women and after a long period of treatment [
Longitudinal melanonychia of a single nail unit in an adult is concerning, and a biopsy of the nail unit can evaluate the possibility of melanoma, which cannot be differentiated from benign causes of longitudinal melanonychia solely based on clinical examination [
The authors declare that they have no conflict of interests.
The authors would like to thank Mrs. Ana Maria Palazuelos for her help in writing this paper.