Etretinate treatment of severe cutaneous dysplasia in renal transplant recipients

Abstract

It is well recognized that patients who have undergone renal transplantation are at an increased risk of developing cutaneous malignancy. The incidence of this problem rises as survival time increases, and multiple dysplastic lesions may develop, especially on sun‐exposed sites. Conventional treatment by excision, curettage, cryotherapy or topical cytotoxic agents is often unsatisfactory because of the number and extent of lesions present. In non‐immunosuppressed patients, treatment with etretinate has been shown to be helpful in treating both basal cell carcinomas and solar keratoses. There are, however, no previous studies of its safety or efficacy in renal transplant patients who have developed dysplastic lesions, and the immuno‐adjuvant effect of retinoids is a potential limitation to this type of treatment. We have therefore undertaken a study in which patients with functioning renal allografts who had developed multiple dysplastic lesions were treated with etretinate, 1 mg/kg/day for a period of 6 months. Six patients (five males, one female), who had been immunosuppressed for between 166 and 240 months (mean 210 months), were entered into the study. All patients had histological evidence of severe epidermal dysplasia, and four patients had previously developed invasive squamous cell carcinomas. In addition, all patients had numerous viral warts, some of which showed evidence of dysplastic change. No deterioration of renal function was detected in any of the patients during treatment, as measured by serial plasma creatinine estimations. Circulating lymphocyte numbers were unaffected by treatment and there was no consistent change in the relative numbers of T helper or suppressor cells. Intradermal challenge with multiple antigens was undertaken at o and 6 months, and all patients remained completely anergic. Serum cholesterol and triglyceride levels were monitored throughout the study, and only one patient had a rise in lipid values which did not respond to dietary manipulation. Four patients had almost complete clearing of hyperkeratotic lesions, one patient had a partial response, and one patient developed two further squamous cell carcinomas during treatment. Side‐effects were no more severe than those normally encountered with retinoid therapy. Etretinate appears to be a safe and useful treatment in this group of patients. Fears concerning its immuno‐modulating effects proved groundless, and its effects on a heavily suppressed immune system appear to be negligible.

Low-Dose Retinoids in the Prevention of Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

“…Eleven patients were treated for at least 4 years, and although the mean reduction was still 1.63 SCCs, this did not quite achieve statistical significance (P=.09; 95% CI, 0.32 to −3.59). For individuals who had received at least 5,6,7,8,9, and 16 years of continuous treatment (n = 6, 6, 4, 4, 2, and 1, respectively), the mean difference in SCCs continued to show an overall reduction, but this was no longer statistically significant (Table 2, Figure 1). Responses for selected individual patients are shown in Figure 2.…”

“…Previous studies have also shown such a relapse in tumor development, 6,15,18,19,22 such that continuous treatment appears to be required to maintain a chemopreventive effect. It therefore seems most appropriate to regard retinoid chemoprevention as a potentially lifelong treatment in OTRs, and this must be considered before the patient embarks on such treatment.…”

“…The use of systemic retinoids in prevention of transplant-related skin malignancy was first described more than 15 years ago. 6 Retinoids are vitamin A analogues that interact with 2 groups of nuclear receptors, the retinoic acid receptors and retinoid X receptors, to influ- …”

Potentiating effect of dietary vitamin A on photocarcinogenesis in hairless mice

“…1), and synthetic retinoids are currently used in the treatment of cancer, including both pre-malignant and malignant tumours of the skin (2)(3)(4). This concept of a favourable effect of exogenous vitamin A is supported by findings in animal experiments that pharmacological doses of both synthetic retinoids (5,6) and natural retinyl palmitate (7) inhibit chemical carcinogenesis in the skin.…”

Low‐dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients

“…Conventional treatment may be difficult due to the wide area of dysplastic skin. Etretinate 1 mgkglday was shown to have a beneficial role in a small group of RTRs (n = 6) by Shuttleworth et al [9]. The objectives of this study were to examine the therapeutic effects of low dose etretinate (0.3 mgkgl day) on the rate of skin cancer development in RTRs who had a history of excision of two or more skin cancers, to assess patient acceptability of this therapy, and to monitor retinoid toxic effects at this dose.…”