Ciclosporin is an effective immunosuppressant that is widely used not only in transplant recipients, but also to treat chronic inflammatory diseases such as psoriasis. In organ transplant recipients, ciclosporin use has been associated with an increased risk of squamous-cell carcinoma, a type of skin cancer. This is a worrying observation because psoriasis is often treated with another carcinogen — psoralen and ultraviolet-A light (PUVA) — in combination with ciclosporin. Isabelle Marcil and Robert Stern, in the 29 September issue of The Lancet, now show that ciclosporin and PUVA are a particularly carcinogenic combination.

Marcil and Stern found that ciclosporin users had a threefold higher incidence of squamous-cell carcinoma than nonusers, whereas patients who had experienced high PUVA exposure as well as being ciclosporin users had a sevenfold higher incidence of squamous-cell carcinoma than ciclosporin users who had not been exposed to PUVA. After adjustment for ageing (which, in itself, increases cancer incidence) during the study and use of other treatments, the incidence of squamous-cell carcinoma was ninefold higher in individuals who had received both ciclosporin and high exposure to PUVA compared with nonusers with a low PUVA exposure. Incidence of tumours increased most in regions of the body not usually exposed to sunlight but exposed to PUVA. Perhaps most significantly, even only brief or minimal use of ciclosporin greatly increases the risk of squamous-cell carcinoma in individuals who have also received long-term PUVA exposure.

There is, therefore, a potential safety issue for patients receiving ciclosporin, and possibly also other immunosuppressants used for severe psoriasis, when they are used in conjunction with other known carcinogens. These findings indicate that further investigations into the cancer-causing potential of other immunosuppressants used to treat psoriasis should be undertaken.