Muco-cutaneous changes during long-term therapy with hydroxyurea in chronic myeloid leukaemia

Abstract

Hydroxyurea is an antimetabolite agent used in the treatment of myeloproliferative disorders and sickle cell anaemia. Although hydroxyurea is relatively well tolerated, adverse effects often involve skin and mucous membrane during long-term therapy. A group of 510 patients affected by chronic myeloid leukaemia from 1977 to 1998 has been considered. Only 158 patients were treated with hydroxyurea and fulfilled inclusion/exclusion criteria of this study. A spectrum of severe cutaneous and mucosal changes (inflammatory and neoplastic) was seen in about 13% of patients (21 patients out of 158) and was studied in detail. Cutaneous and mucosal atrophy were observed in all 21 patients. Skin atrophy was often characterized by numerous telangiectases, especially on legs and on sun-exposed sites (16/21). Cutaneous, mucosal and nail hyperpigmentation was evident, albeit with variable extent, in 10 of the 21 patients. Severe stomatitis and glossitis with flattening of papillae were another common finding. Five patients, who received a particularly long treatment with hydroxyurea, developed squamous-cell neoplasms on sun-exposed sites (both squamous-cell carcinomas and keratoacanthomas). Acral changes were characteristic and constant, including acral erythema (21/21), dermatomyositis-like changes on the dorsa of hands (7/21), ulcers localized on acral areas of legs, on genitalia and oral mucosae (20/21). The frequency and the variety of these muco-cutaneous changes are reported and the mechanisms by which hydroxyurea may induce this muco-cutaneous syndrome-like group of changes, are proposed.

Squamous Cell Carcinoma Accompanying Chronic Myeloid Leukemia: Case Report and Review of the Literature

“…21 In this study, the frequency and clinical variety of severe cutaneous and mucosal side effects of long term hydroxyurea therapy was observed in a group of 21 out of 158 patients (13%) affected by chronic myelogenous leukemia. The median age was 58 years (range 25-79 years) with male to female ratio of 3.5:1.…”

“…The patients who developed these squamous cell neoplasms, had recieved hydroxyurea therapy for the median time of 76.5 months (range 60-120 months) but the cumulative dose was not available. None of the patients developed metastases (21) .…”

“…20 It is also reported that hydroxyurea has intrinsic mutogenic actvity. 21 Since Hydroxyurea therapy is a commonly used treatment modality in CML, the patients with CML can also present with such clinical findings as others, who are recieving hydroxyurea therapy.…”

“…The cutaneous changes that Vasallo et al have reported include; acral erythema (in all 21 patients), xerosis (in 19 patients), ichthyosiform lesions (in 16 patients), telangiectasies (in 16 patients), malleolar ulcers (in 13 patients), heel ulcers (in 1, patient), oral mucosa ulcers (in 1 paticat), glans penis ulcers (in 1 patients), dermatomysitis-like changes (in 7 patients), hyperpigmentation (in 10 patients), squamous cell carcinoma (in 3 patients), livedoid fixed erythema of heels (in 6 patients), glossitis (in 2 patients), upper lip (in 1 patient) and lower lip (in 1 patient) ulcers, scrotum ulcers (in 1 patient), keratoacantomas (in 2 patients), stomatitis (in 4 patients), vasculitis (in 1 patient), ulcer on the toes (in 1 patient). 21 Because of severe mucocutaneous changes, hydroxyurea was discontinued in all patients. Among neoplastic lesions three squamous cell carcinomas (on lower lip, left auricle and forehead), and two keratoacantomas (on left cheek and dorsum of right hand) were observed.…”

Hydroxycarbamide‐induced dermopathy

“…An estimated 13% of patients with chronic myelogenous leukemia have mucocutaneous changes with long-term hydroxycarbamide therapy [4]. Myriad cutaneous adverse effects from long-term hydroxycarbamide therapy have been noted in the medical literature, including a dermatomyositis-like erythematous eruption on the hands, mucositis and oral ulceration, hair loss, nail pigmentation, and hyperpigmentation of the face [5].…”