Dermatomyositis-like eruption after long-term hydroxyurea therapy for polycythemia vera

ARTICLE

Hydroxyurea (HU) is a hydroxylated derivative of urea commonly used to treat a variety of myeloproliferative disorders such as chronic myeloid leukemia, polycythemia vera, or essential thrombocythemia as well as refractory psoriasis. HU is usually well tolerated, but long-term HU therapy can produce several cutaneous abnormalities [1-5]. Although the occurrence of dermatomyositis-like changes during long-term HU therapy are well known, they are rarely described in patents with polycythemia vera [4, 6-8].

We report a patient with polycythemia vera who developed a dermatomyositis-like eruption after long-term HU therapy.

Case report

A 69-year-old man was referred from the department of Internal Medicine for evaluation of skin lesions. He had an 8-year history of polycythemia. His condition was initially managed with venesection, and he was subsequently put on continuous HU therapy at a dose of 1-1.5 g per day for 6 years. He reported photosensitivity and pruritic skin lesions two years after HU therapy. The complaints gradually worsened, becoming especially bad one year before referral. There was no personal or family history of connective tissue disease or photosensitivity.

Dermatologic examination revealed telangiectasia and scaly, reddish purple patches together with swelling of the eyelids on his face. There were violaceous erythema, atrophy and telangiectasia and hyperpigmentation on the dorsal aspects of both hands as well as periungual telangiectasia (Fig. 1). He was also noted to have plantar keratoderma and polygonal scaling eruption of acquired ichthyosis on the extremities, trunk and buttocks. His skin eruption did not improve with potent topical steroids.

The hemoglobin value was 16.2 g/L, the white blood cell count was 17,900 mm³, and platelets were 233,000 mm³. Results of blood biochemistry analysis and urinalysis were within normal limits. Immunologic investigations such as antinuclear antibodies, single and double stranded DNA were found to be negative. Muscle enzymes including aldolase and CPK were also normal.

A skin biopsy specimen demonstrated an epidermis show-ing hyperkeratosis and minimal irregular acanthosis along with focal vacuolization at the dermo-epidermal junction. The dermis showed mononuclear inflammatory infiltration around the capillaries with a few melanophages and extravasated erythrocytes (Fig. 2). Direct immunofluorescence study revealed positive staining of cytoid bodies for IgM. The clinical differential diagnosis was of a connective tissue disorder or of a chronic cutaneous adverse reaction to HU.

Since we thought HU might be responsible for the skin lesions, it was decided to change the patient's treatment to interferon alpha-2a. After interruption of HU administration, the skin lesions almost completely improved within 2 months. The clinical course strongly suggested that the lesions were induced by long-term HU therapy. Follow-up of the patient continues.

Discussion

Drug-induced dermatomyositis-like skin changes are rare and interesting. Various drugs, including d-penicillamine, NSAIDs, anti-infectious agents, as well as lipid lowering drugs, the HMG-CoA reductase inhibitors are known to cause skin lesions of dermatomyositis [9].

Long-term HU therapy is known to cause adverse hematologic side effects, including reversible dose dependent cytopenia and megaloblastosis as well as cutaneous disorders. Even though the mechanism for the cutaneous changes caused by long-term HU therapy is not clear, these are thought to result from cumulative toxicity of HU on the basal layer of the epidermis due to inhibition of DNA synthesis and repair. It may induce vacuolar degeneration of the basal cells, colloid bodies and epidermal atrophy [1-5].

Dermatomyositis-like skin changes have been noted in patients on long-term treatment with HU for myeloproliferative conditions and psoriasis [3-5, 10-13]. Even though dermatomyositis-like changes have been already fully described in several chronic myeloid leukemia affected patients, they have rarely been reported in patients treated with HU for polycythemia vera.

Kennedy et al., first reported the long-term effects of high dose HU therapy such as lichen planus-like lesions for treatment of chronic myeloid leukemia in seven of 20 patients in 1975 [11]. Several authors have previously termed to similar eruptions as "dermatomyositis-like" [12], "pseudo-dermatomyositis" [13] and "simulating chronic dermatomyositis" [14]. Daoud et al. also described a unique lichenoid eruption which developed on the dorsae of the hands in six patients after an average of 60 months for myeloproliferative disease as hydroxyurea dermopathy and suggested that cessation of treatment is necessary for healing or improvement of the eruption [15]. Recently, Eming et al. have reported five patients as lichenoid chronic graft-versus-host-disease-like acrodermatitis induced by HU [8]. Other dermatologic manifestations of HU include nonspecific lesions such as alopecia, leg ulcers, fixed drug eruption, diffuse hyperpigmentation, photosensitization, nail changes, stomatitis, solar keratoses, skin tumors, and cutaneous vasculitis [3-7, 11].

The clinical presentation of our case is peculiar, because changes affecting the face, such as a true dermatomyositis have been rarely described in the literature. HU related dermatomyositis-like changes typically present months or years after initiation of therapy with the culprit drug, and this case conforms to this pattern. In addition to skin lesions of dermatomyositis, several of the long-term effects of HU on the skin have been reported together with it [3, 11-14]. In addition to dermatomyositis-like eruption, our patient had plantar keratoderma and acquired ichthyosis.

Although all reported cases have typical dermatomyositis-like eruption induced by HU, muscle abnormalities are noted to be absent as in our case. On cessation of HU therapy, the clinical course of dermatomyositis-like changes shows different results [10-14]. However, our patient displayed improvement of the lesions within two months of HU withdrawal. The rapid improvement following discontinuation of HU implicated this drug as a possible etiological factor in the development of cutaneous features of dermatomyositis in our patient. As HU continues to have a prominent role in the treatment of various diseases, clinicians should be aware of delayed adverse drug reaction to avoid unnecessary investigations, morbidity and therapy.

Article accepted on 23/7/02

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