Photosensitive drug eruption induced by bicalutamide within the UVB action spectrum

ARTICLE

ejd.2012.1719

Auteur(s) : Kumiko Sasada, Jun-ichi Sakabe, Aiko Tamura, Akira Kasuya, Takatoshi Shimauchi, Taisuke Ito, Satoshi Hirakawa, Yoshiki Tokura tokura@hama-med.ac.jp

Department of Dermatology, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu 431-3192, Japan

Bicalutamide is a non-steroidal, anti-androgenic drug used for the treatment of prostatic carcinoma. Flutamide, another anti-androgen, preceded bicalutamide in the market and has been reported to cause photosensitivity as an adverse effect [1, 2]. However, there has been only one report in the English literature describing a photoallergic reaction with bicalutamide [3]. We report another case, focusing on its action spectrum.

A 59-year-old Japanese man was referred to us for a 2-week history of a skin eruption on a sun-exposed area. He had been treated for prostatic carcinoma with 80 mg bicalutamide daily for 2 months and 11.25 mg of leuprorelin acetate once, 2 months before. He had pruritic, scaly, erythematous lesions on the face (figure 1A), ears, posterior neck (figure 1B), and dorsum of the hands. Antinuclear antibodies, blood protoporphyrin, and urine uroporphyrin and coproporphyrin were normal. Bicalutamide-induced photosensitivity was highly suspected based on the history of drug administration. He was treated with topical corticosteroids and a SPF50+ sunscreen with beneficial effects. Since the condition of patient's prostatic cancer did not allow us to discontinue biculutamide, we advised him to avoid sun exposure and to strictly use sunscreens, with good results.

During administration of bicalutamide, phototests with ultraviolet A (UVA) and UVB were performed. While no reaction was observed with UVA at 4 J/cm², minimal erythemal dose with UVB was 40 mJ/cm² at 48 h. Furthermore, UVB doses higher than 60 mJ/cm² produced marked erythema, edema and pigmentation, and the response prolonged even 14 days after UVB exposure. A biopsy specimen was taken 7 days after the phototest from the site irradiated with 100 mJ/cm² UVB. Histologically, there was remarkable perivascular infiltration of lymphocytes in the upper dermis with epidermal invasion (figure 1C). Immunohistochemical staining revealed that CD8⁺ T cells (figure 1D) outnumbered CD4⁺ cells.

The absorption spectrum of bicalutamide (Tocris Bioscience, Bristol, UK) was measured with a spectrometer [4]. Bicalutamide was dissolved in absolute DMSO at 1 mM. The absorption peak of non-irradiated bicalutamide was 285 nm (figure 1E). To examine the UV-stability of bicalutamide, the solutions were irradiated with UVA at 1.3 J/cm² or UVB at 200 mJ/cm². Whereas the absorption spectrum of bicalutamide was not substantially changed by UVA, it was dramatically altered by UVB (figure 1E), suggesting that bicalutamide is easily photo-degraded by UVB but not UVA.

Our patient developed photosensitivity after a 2-month administration of bicalutamide. The diagnosis of bicalutamide photosensitivity was also suggested by the many case reports on flutamide photosensitivity [1, 2]. In general, drug photosensitivity is evoked by UVA [4], and drugs possessing UVB action spectrum, such as ranitidine [5], have been rarely reported. Ours, and the reported cases [3], show that UVB is the action spectrum of bicalutamide photosensitivity, while flutamide exerts photosensitive dermatitis in concert mainly with UVA [1]. The peak absorption wavelength of bicalutamide is 285 nm, which is shorter than that of flutamide (303 nm) [1]. Moreover, bicalutamide shows virtually no absorption in wavelengths longer than 305 nm, whereas flutamide absorbs the UVA range (320-400 nm) as well as UVB. The remarkable photo-degradation of bicalutamide by UVB but not UVA is in accordance with its UVB action spectrum.

Our case was also characterized by persistency of the photo-provoked skin lesions and the CD8⁺ T cell infiltrate. The eruption might have been prolonged by the occurrence of a photoallergic lichenoid reaction induced by CD8⁺ T cells. However, discontinuation of the drug was not necessarily required for prevention of photosensitivity, as reported in other cases [3]. It is considered that the efficacious cut-off effect of sunscreens on UVB contributes to easier control of the photosensitivity than other photosensitive drugs.

Disclosure

Financial support: none. Conflict of interest: none.

References

1. Yokote R, Tokura Y, Igarashi N, et al. Photosensitive drug eruption induced by flutamide. Eur J Dermatol 1998; 8: 427-9.

2. Rafael JP, Manuel GG, Antonio V, et al. Widespread vilitigo after erythroderma caused by photosensitivity to fultamide. Contact Dermatitis 2004; 50: 98-100.

3. Kurumaji Y. Photosensitivity Due to Bicalutamide. J Environ Dermatol Cutan Allergol 2007; 1: 189-95.

4. Tokura Y. Photoallergy. Expert Rev Dermatol 2009; 4: 264-70.

5. Kondo S, Kageyama M, Yamada Y, et al. UVB photosensitivity due to ranitidine. Dermatology 2000; 201: 71-3.