Cisplatin-induced acral erythema

ARTICLE

Auteur(s) : Shoko Fukamachi, Motonobu Nakamura, Yoshiki Tokura

Department of Dermatology, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka Yahatanishi-ku, Kitakyushu 807-8555, Japan

Chemotherapy-induced acral erythema (CAE) is a cutaneous reaction associated with the use of various systemic chemotherapeutic agents, usually administered at high doses. Since 1982, when CAE was first described, it has been reported under a variety of names, such as palmoplantar erythema, palmoplantar erythrodysaesthesia syndrome and hand-foot syndrome. CAE tends to occur in patients with malignancies, especially those receiving cumulative high-dose chemotherapy with concomitant irradiation and bone-marrow transplantation. The incidence of acral erythema during chemotherapy is about 2% [1] and the main agents responsible are fluorouracil and doxorubicine, followed by docetaxel, pacritaxel, methotrexate, vinorelvine, gemcitabine, cytarabine and cyclophosphamide [1, 2]. We report a patient who developed an erythematous eruption on the palms after systemic administrations of cisplatin, and review the literature of cisplatin as the causative agent of CAE.

A 35-year-old woman was diagnosed as having cervical cancer. After hysterectomy, a combination therapy with irradiation (30 Gy/total) and cisplatin (30 mg/m²) was started. Cisplatin was administered intravenously through her left cephalic vein. At night on the initial day of the treatment, she felt a burning pain in her reddish swollen forearm. The swelling subsided within a day by topical application of betamethasone 1 g per day. However, on the 6^th day of chemotherapy, she again developed swelling on her left upper limb and was referred to us.

On physical examination, her left forearm was swollen and slightly reddish. There was symmetrical erythema on the bilateral palms extending to the palmar surface of the fingers (figures 1A, B). The eruption consisted of multiple, salmon-pink, faintly demarcated, non-tender lesions. No eruption was noted on the dorsum of hands and fingers. Laboratory data revealed no leucocytosis or peripheral eosinophilia. We did not perform any skin tests for ethical reasons, because of the cytotoxic properties. Drug-induced lymphocyte stimulation testing was tried, but it was difficult to evaluate its antigenicity, since lymphocytes were incapable of surviving during culture with cisplatin. A tentative diagnosis of drug eruption was made; she stopped taking cisplatin and her eruption was completely resolved in a week without any treatment.

A biopsy specimen from a palmar lesion revealed a perivascular mild infiltrate of lymphocytes and a few eosinophils in the dermis with mildly acanthotic epidermis. There were no epidermal necrotic cells or dermal inflammatory cells invading into the eccrine glands.

Although cisplatin is widely used for the treatment of various tumors, cisplatin-induced acral erythema has been reported in only four cases [2-4]. All patients developed symmetrical erythema of the palms and fingers and/or soles, and the eruptions were resolved by discontinuing cisplatin. However, there are clinical and histological differences among these cases. First, acral erythema occurred only one day after the initiation of chemotherapy in our case, while it appeared 3 months after the initiation in another patient [2]. Second, the lesional sites were slightly different between the cases. Third, the infiltrates consisted of lymphocytes [2], or neutrophils [4]. Finally, lichenoid or vesicular changes in the epidermis were present in two cases [2, 4] but not in our case.

The occurrence of CAE depends on various factors, which may contribute the typical localization to the palms and soles, including elevated drug concentration in eccrine glands, rapid cell proliferation, regional temperature gradient, gravitational forces, and vasculature anatomy [5]. Thus, it is likely that CAE is a toxic but not allergic reaction. Because the onset of CAE was soon after administration, our case also supports some toxic mechanism underlying CAE.

It may be noted that three out of the four reported cases are Japanese, and some ethnic genetic background might influence on the susceptibility of CAE to cisplatin. The polymorphisms for certain drug transporter genes, such as Multi drug resistance 1, might underlie the ethnic variation [6].

Acknowledgements

Références

2 Vakalis D, Ioannides D, Lazaridou E, et al. Acral erythema induced by chemotherapy with cisplatin. Br J Dermatol 1998; 139: 750-1.

3 Kimura K. Cisplatin-induced acral erythema. Rinsho Derma (Tokyo) 1988; 30: 1379-83.

4 Yamada T, Tanaka R, Kusuda Y, Fujisawa M. Chemotherapy-induced acral erythema with vesicles on soles. Jpn J Dermatol 2005; 115: 1643.

5 Lorusso D, Di Stefano A, Carone V, et al. Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia (’hand-foot’ syndrome). Ann Oncol 2007; 18: 1159-64.

6 Sohn JW, Lee SY, Lee SJ, et al. MDR1 polymorphisms predict the response to etoposide-cisplatin combination chemotherapy in small cell lung cancer. Jpn J Clin Oncol 2006; 36: 137-41.