Case Report Dermatology 1992;185:307-308
N. Vandeghinste J. Dc Bersaques M.L. Geerts A. Kint Department of Dermatology, University Hospital. Ghent. Belgium
Key Words Renal transplantation Cutaneous malignancy Retinoids
Acitretin as Cancer Chemoprophylaxis in a Renal Transplant Recipient
Abstract The use of acitretin in a renal transplant recipient who had been treated for sev eral premalignant and malignant skin lesions is the subject of this case report. During the treatment period no new dysplastic lesions developed.
Renal transplant recipients have an increased suscepti bility to both viral infections, including human papilloma virus infection, and cutaneous cancers [1]. When the num ber of lesions is limited, local therapy may be satisfactory. But often widespread or recurrent lesions necessitate a gen eral treatment. Vitamin A was identified long ago as essential in the normal differentiation of epithelial tissues, but its use is lim ited by its systemic toxicity in the required supraphysiologic doses [2J. Several more recent studies showed that the analogues of vitamin A, the retinoids, exert a prophylactic action on the development of epithelial cancers [2],
When the patient was examined at the beginning of 1989. multiple dysplastic lesions were diagnosed: two new basal cell carcinomas, a keratoacanthoma, a squamous cell carcinoma and a lesion of Bowen's disease on sun-exposed areas. The verrucous papules had increased in number and size. Because of the appearance of multiple precancerous and cancerous lesions, a therapy with acitretin at a dose of 0.5 mg/kg/day was started. Side effects were limited to a well-tolerated xerosis of skin and muco sae. There were no alterations of biochemical parameters. During a 15-month period of acitretin intake, no new dysplastic lesions were observed. The existing verrucosities disappeared or shrunk to flat keratotic lesions. Four months after stopping treatment, many of the verrucous lesions had reappeared and a small recurrence of Bowen’s disease was treated locally.
Case Report Discussion In patients receiving immunosuppressive drugs for a renal transplant, the frequency of developing malignancy is 100 times higher than in a control population, and lies between 1.6 and 5.6% [3], Cutaneous carcinomas account for about 50% of these cancers [3], Duration of immuno suppression and sun exposure are the most important risk factors [4]. In the past decade, several studies have demon-
Dr. N. Vandeghinste Department of Dermatology University Hospital IX* Pintciaan 185. B-9000 Ghent (Belgium)
© 1992 Karger ACi. Basel 1018-8665/92/1854-0307 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:23:13 AM
In 1971. a male patient, born in 1924. received a renal transplant for an end-stage renal insufficiency due to chronic glomerulonephritis. He was treated with prednisolone 10 mg/day and azathioprine 50 mg/ day. In 1983, he was seen in our department with progressive verru cous papules on the limbs and the trunk. A biopsy of a lesion on the back showed small nests of koilocytes in the upper layers of the epider mis. Cryotherapy was used to treat the lesions. Two years later, a basal cell carcinoma on the forehead was excised, followed by the removal of two lesions of Bowen’s disease, one oil the left wrist and one in the right retroauricular region, and of a cornu cutaneum on the dorsum of the left hand.
stratcd the effectiveness of retinoids in the prevention of skin cancer in certain risk groups, namely patients with extensive keratosis actinica [5], xeroderma pigmentosum [6], basal cell naevus syndrome |6], and also in renal trans plant recipients [7|. Although a minor influence was noted on existing tumors, there was an evident tumor-preventive effect as long as the retinoid was given. A few months after discontinuation of treatment, tumors reappeared with the same frequency as before [8]. Retinoids were also used systemicaily in the treatment of extensive verrucae in immunodepressed patients, mostly with a temporary result [9.
10]. The patient presented here is an illustration of the use fulness of systemic retinoids in the prevention of cutaneous cancers in certain risk groups. The mechanisms of the anticancer action of retinoids remain incompletely understood. Recent studies have shown their influence on enzyme and protein synthesis, ccll-to-ccll contacts, cell membrane structure, cellular and humoral immunity, growth factors, cytokines, gene tran scription and postgcnomic events |11]. By these mech anisms, theoretically, retinoids may interact with different steps of tumor development.
1 Harr BB. Benton EC. McLaren K. Bunncy MIL Smith IV. Blessing K: Human papilloma virus infection and skin cancer in renal allograft recipients. Lancet 1989;i: 124-129. 2 l.ippman SM. Mcyskens FL: Results of the use of vitamin A and retinoids in cutaneous malig nancies. Pharmacol Titer 1989:40:107—122. 3 Euvrard S. Chardonnet Y. Hcrmier C. ViacJ. Tltivolcl J: Verrues et carcinomes épidermoï des après transplantation rénale. Ann Derma tol Vénéréol 1989:116(3):201-211. 4 Boyle J. MacKie RM. Briggs JD. Junor BJR: Cancer, warts and sunshine in renal transplant patients. Lancet 1984;i:702—704.
308
5 Moriarty M. Dunn .1. Darragh A. Lambc R: Etretinate in treatment of actinie keratosis. Lancet 1982:i:304-365. 6 Schnitzlcr L. Schubert B. Verret JL: Essai de prévention des epitheliomas cutanés par le réti noïde aromatique. Ann Dermatol Vénéréol 1980:107:657-663. 7 Shuttleworth D. Marks R. Griffin PJA. Salaman JR: Treatment of cutaneous neoplasia with etretinate in renal transplant recipients. O J Med 1988:257:717-724. 8 Peck GL. Gross EG. Butkus D. DiGiovanna JJ: Chemoprcvention of basal cell carcinoma with isotretinoin. J Am Acad Dermatol 1982: 6:815-823.
9 Cobb MW: Human papillomavirus infection. .1 Am Acad Dermatol 1990:22:547-566. 10 Jablonska S. Obalek S. Wolska H: Follow-up of patients with epidermodysplasia verrucifor mis treated with etretinate. Dermatológica 1986:173:196-199. 11 Gollnick HPM. Orfanos CE: Theoretical aspects of the use of retinoids as anticancer agents: in Marks R (cd): Retinoids in Cuta neous Malignancy. Oxford. Blackwell Scien tific Publications 1991. chap 3. pp 41-65.
Vandcghinstc/Dc Bersaques/Geerts/Kint
Cancer Chemoprophylaxis with Acitrctin
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:23:13 AM
References
N. Vandeghinste J. Dc Bersaques M.L. Geerts A. Kint Department of Dermatology, University Hospital. Ghent. Belgium
Key Words Renal transplantation Cutaneous malignancy Retinoids
Acitretin as Cancer Chemoprophylaxis in a Renal Transplant Recipient
Abstract The use of acitretin in a renal transplant recipient who had been treated for sev eral premalignant and malignant skin lesions is the subject of this case report. During the treatment period no new dysplastic lesions developed.
Renal transplant recipients have an increased suscepti bility to both viral infections, including human papilloma virus infection, and cutaneous cancers [1]. When the num ber of lesions is limited, local therapy may be satisfactory. But often widespread or recurrent lesions necessitate a gen eral treatment. Vitamin A was identified long ago as essential in the normal differentiation of epithelial tissues, but its use is lim ited by its systemic toxicity in the required supraphysiologic doses [2J. Several more recent studies showed that the analogues of vitamin A, the retinoids, exert a prophylactic action on the development of epithelial cancers [2],
When the patient was examined at the beginning of 1989. multiple dysplastic lesions were diagnosed: two new basal cell carcinomas, a keratoacanthoma, a squamous cell carcinoma and a lesion of Bowen's disease on sun-exposed areas. The verrucous papules had increased in number and size. Because of the appearance of multiple precancerous and cancerous lesions, a therapy with acitretin at a dose of 0.5 mg/kg/day was started. Side effects were limited to a well-tolerated xerosis of skin and muco sae. There were no alterations of biochemical parameters. During a 15-month period of acitretin intake, no new dysplastic lesions were observed. The existing verrucosities disappeared or shrunk to flat keratotic lesions. Four months after stopping treatment, many of the verrucous lesions had reappeared and a small recurrence of Bowen’s disease was treated locally.
Case Report Discussion In patients receiving immunosuppressive drugs for a renal transplant, the frequency of developing malignancy is 100 times higher than in a control population, and lies between 1.6 and 5.6% [3], Cutaneous carcinomas account for about 50% of these cancers [3], Duration of immuno suppression and sun exposure are the most important risk factors [4]. In the past decade, several studies have demon-
Dr. N. Vandeghinste Department of Dermatology University Hospital IX* Pintciaan 185. B-9000 Ghent (Belgium)
© 1992 Karger ACi. Basel 1018-8665/92/1854-0307 $ 2.75/0
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:23:13 AM
In 1971. a male patient, born in 1924. received a renal transplant for an end-stage renal insufficiency due to chronic glomerulonephritis. He was treated with prednisolone 10 mg/day and azathioprine 50 mg/ day. In 1983, he was seen in our department with progressive verru cous papules on the limbs and the trunk. A biopsy of a lesion on the back showed small nests of koilocytes in the upper layers of the epider mis. Cryotherapy was used to treat the lesions. Two years later, a basal cell carcinoma on the forehead was excised, followed by the removal of two lesions of Bowen’s disease, one oil the left wrist and one in the right retroauricular region, and of a cornu cutaneum on the dorsum of the left hand.
stratcd the effectiveness of retinoids in the prevention of skin cancer in certain risk groups, namely patients with extensive keratosis actinica [5], xeroderma pigmentosum [6], basal cell naevus syndrome |6], and also in renal trans plant recipients [7|. Although a minor influence was noted on existing tumors, there was an evident tumor-preventive effect as long as the retinoid was given. A few months after discontinuation of treatment, tumors reappeared with the same frequency as before [8]. Retinoids were also used systemicaily in the treatment of extensive verrucae in immunodepressed patients, mostly with a temporary result [9.
10]. The patient presented here is an illustration of the use fulness of systemic retinoids in the prevention of cutaneous cancers in certain risk groups. The mechanisms of the anticancer action of retinoids remain incompletely understood. Recent studies have shown their influence on enzyme and protein synthesis, ccll-to-ccll contacts, cell membrane structure, cellular and humoral immunity, growth factors, cytokines, gene tran scription and postgcnomic events |11]. By these mech anisms, theoretically, retinoids may interact with different steps of tumor development.
1 Harr BB. Benton EC. McLaren K. Bunncy MIL Smith IV. Blessing K: Human papilloma virus infection and skin cancer in renal allograft recipients. Lancet 1989;i: 124-129. 2 l.ippman SM. Mcyskens FL: Results of the use of vitamin A and retinoids in cutaneous malig nancies. Pharmacol Titer 1989:40:107—122. 3 Euvrard S. Chardonnet Y. Hcrmier C. ViacJ. Tltivolcl J: Verrues et carcinomes épidermoï des après transplantation rénale. Ann Derma tol Vénéréol 1989:116(3):201-211. 4 Boyle J. MacKie RM. Briggs JD. Junor BJR: Cancer, warts and sunshine in renal transplant patients. Lancet 1984;i:702—704.
308
5 Moriarty M. Dunn .1. Darragh A. Lambc R: Etretinate in treatment of actinie keratosis. Lancet 1982:i:304-365. 6 Schnitzlcr L. Schubert B. Verret JL: Essai de prévention des epitheliomas cutanés par le réti noïde aromatique. Ann Dermatol Vénéréol 1980:107:657-663. 7 Shuttleworth D. Marks R. Griffin PJA. Salaman JR: Treatment of cutaneous neoplasia with etretinate in renal transplant recipients. O J Med 1988:257:717-724. 8 Peck GL. Gross EG. Butkus D. DiGiovanna JJ: Chemoprcvention of basal cell carcinoma with isotretinoin. J Am Acad Dermatol 1982: 6:815-823.
9 Cobb MW: Human papillomavirus infection. .1 Am Acad Dermatol 1990:22:547-566. 10 Jablonska S. Obalek S. Wolska H: Follow-up of patients with epidermodysplasia verrucifor mis treated with etretinate. Dermatológica 1986:173:196-199. 11 Gollnick HPM. Orfanos CE: Theoretical aspects of the use of retinoids as anticancer agents: in Marks R (cd): Retinoids in Cuta neous Malignancy. Oxford. Blackwell Scien tific Publications 1991. chap 3. pp 41-65.
Vandcghinstc/Dc Bersaques/Geerts/Kint
Cancer Chemoprophylaxis with Acitrctin
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:23:13 AM
References
