Transverse melanonychia: An adverse effect of hydroxyurea

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Melanonychia is a black or dark-brown discolouration of nails. Mucocutaneous hyperpigmentation is a well-known adverse effect of hydroxyurea; however, melanonychia is rarely reported, typically as longitudinal and diffuse involvement of nails.^[1] We report a patient with sickle cell anaemia on hydroxyurea who developed transverse hyperpigmentation of nails.

A 17-year-old male born to a non-consanguineous family presented with easy fatigability, pica and shortness of breath. On investigation, he had anaemia, with haemoglobin 8 g/dL. Serum iron was low. Vitamin B12 levels and thyroid function tests were normal. High-performance liquid chromatography was suggestive of sickle cell anaemia (HbSS pattern). The patient was started on hydroxyurea. After two months of treatment, he developed discolouration of his nails. Knuckle hyperpigmentation was noted with transverse hyperpigmentation of all digits of the hands. In addition, nail bed pallor was present due to persistent iron deficiency anaemia [Figures 1 and 2]. No atrophy or thickening of nails or any other cutaneous lesion was noted. The patient was counselled regarding the benign nature of hyperpigmentation and continued on hydroxyurea.

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Figure 1:

Knuckle hyperpigmentation with transverse hyperpigmentation of all digits of the hands.

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Figure 2:

Closer view of the same showing apparent leukonychia with transverse hyperpigmentation of digits.

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Certain chemotherapeutic agents cause pigmentation of the skin and nails. Common agents include doxorubicin, hydroxyurea and cyclophosphamide. Hydroxyurea is used in the treatment of diseases such as chronic plaque psoriasis and myeloproliferative disorders.^[2]

Many cutaneous changes are associated with the use of hydroxyurea including altered pigmentation, alopecia, lichen planus, ichthyosis, etc. However, nail changes associated with hydroxyurea are rare.^[3] These may be in the form of diffuse hyperpigmentation, transverse bands, longitudinal bands and proximal hyperpigmentation.^[3] Of these, the commonly seen pattern caused by hydroxyurea treatment is longitudinal melanonychia. Transverse melanonychia of nails is uncommon. It may progress to diffuse melanonychia over time if drug intake is continued.^[4]

Melanonychia generally presents after a long time of hydroxyurea treatment; however, cases with onset as early as 6 weeks have been reported. The early onset of nail pigmentation in our patient may be attributed to genetic predisposition and rapid growth of nails in young age, making the changes visible earlier. Fingernails are more commonly involved as compared to toe nails, due to faster growth. The exact pathogenesis is not known. Some of the proposed mechanisms include direct toxicity to the nail matrix and nail bed, genetic predisposition, ethnicity and melanocyte activation due to the drug.^[1] The incidence of hydroxyurea-induced melanonychia is lower in white skin, as compared to Asians.^[3] This pigmentation is asymptomatic and reversible over a few months after stopping the drug.

Melanonychia can be alarming for the patients. However, involvement of multiple nails and absence of Hutchinson’s sign (extension of pigmentation onto the nail folds) are reassuring features against a diagnosis of melanoma. Other causes of transverse melanonychia include systemic diseases such as Addison’s disease and Cushing’s syndrome, and localised nail infections. Knuckle pigmentation may also be seen in cases with Vitamin B12 deficiency. However, serum B12 levels were normal in our patient. No treatment is required for cases with chemotherapy-induced melanonychia.

Hydroxyurea-related melanonychia is uncommon, and transverse pattern is rarer. We present a case of sickle cell anaemia, treated with hydroxyurea who developed transverse melanonychia after two months of treatment. The patient was counselled, reassured and continued on hydroxyurea .