Hydroxyurea Associated Cutaneous Lesions: A Case Report

Abstract

Background: Hydroxyurea (HU) is an antimetabolite agent that interferes with the S-phase of cellular replication and inhibits DNA synthesis, with little or no effect on RNA or protein synthesis. It is used in the treatment of many myeloproliferative disorders (MD) and is particularly a first line treatment drug for intermediate to high-risk essential thrombocythemia. Although safe and very well tolerated by the patients suffering from MD, there have been numerous reports of a broad palette of cutaneous side effects associated with prolonged intake of the medication. These may include classical symptoms such as xerosis, diffuse hyperpigmentation, brown-nail discolouration, stomatitis and scaling of the face, hands, and feet or more serious side effects such as actinic keratosis lesions, leg ulcers and multiple skin carcinomas.

Case report: We report a case of a 52-year-old man, on long-term therapy with HU for essential thrombocytosis, with several concurrent skin lesions. Despite the perennial use of HU, the cutaneous changes were neglected. The local dermatological examination revealed oval perimalleolar ulcer on the right leg, with dimensions 6 x 4 cm, clearly demarcated from the surroundings with regular margins, periulcerous erythema, with very deep and highly fibrinous bed of the ulcer, positive for bacterial infection. The ulcer was treated with topical wound therapy with alginate and parenteral antibiotics. The extended dermatological screening also showed two nummular lesions in the right brachial region, presenting as erythematous papules with sharp margins from the surrounding skin, gritty desquamation and dotted hyperpigmentations inside the lesion. Further dermoscopy and biopsy investigations confirmed a diagnosis of basal cell carcinoma. Nasal actinic keratosis was also noted. The patient was advised for discontinuing or substituting the HU therapy.

Conclusion: We present this case to draw attention to the various cutaneous side effects that occur with perennial HU use and suggest an obligatory reference to a dermatological consult.

Keywords: Basal cell carcinoma; Cutaneous side effects; Hydroxyurea therapy; Leg ulcer.

Figure 1

a), b) Oval perimalleolar ulcer on the right leg, with dimensions 6 x 4 cm, clearly demarcated from the surroundings with regular margins and definite limits, periulcerous erythema. The bed of the ulcer appears very deep and highly fibrinous. The a and b figures are respectively time framed to cover 5 months, from initial examination (Fig. 1a) to last control (Fig. 1b). We see no significant change in the course of treatment

Figure 2

a), b) and c) Two nummular lesions (Fig. 2b upper lesion, Fig. 2c lower lesion) in the right brachial region, presenting as erythematous papules with sharp margins from the surrounding skin, gritty desquamation and dotted hyperpigmentations inside the lesion

Figure 3

a), b) (upper lesion), c), d) (lower lesion) Dermoscopic findings of cancer like lesions: shiny white to red areas, short fine telangiectasias, leaf-like areas and small surface erosions

Figure 4

Nasal actinic keratosis lesion