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RENAL TRANSPLANTATION AND THE SKIN
1312 the shoulder. The patient must be made fully aware of the likely outcome-pain relief but a variable postoperative range of movement. However, it is clear from the limited follow-up data that the results of shoulder arthroplasty do not as yet parallel the success of the same procedure in the hip and knee.
RENAL TRANSPLANTATION AND THE SKIN FOR patients on renal dialysis awaiting an appropriately matched donor kidney, the prospect of dermatological problems many years post-transplant will no doubt seem a very minor inconvenience at most. However, for long-term survivors-and the number of such individuals is rising steadily—the reality may be somewhat different. The cutaneous disorders are of three main types-persistent viral warts, premalignant actinic keratoses, and frank cutaneous malignancy. There is keen interest in the possible aetiological relation between the viral and malignant lesions, and the role of exposure to natural sunlight in facilitating the development of all three types of skin disorder. The earliest reports of an increased incidence of cutaneous malignancy in transplant patients came from Australiawell recognised as the skin cancer capital of the world even for those who are not immunosuppressed. It was also noted that there was a relation between the incidence of cutaneous malignancy and the time since transplantation. These studies were followed by reports from Scandinavia3 and Scotland4 indicating that even in areas with relatively low solar intensity, cutaneous malignancy was a posttransplantation hazard. A report by Shuttleworth and colleagues from Wales5 confirms these findings. Of 85 transplant recipients, 45 had survived 80 months or more after transplantation and 17 (38%) of these had preneoplastic or neoplastic lesions. Only nine lesions were frankly neoplastic-seven squamous cell carcinomas and two basal cell carcinomas. This ratio is a reversal of the usual ratio of two or three basal cell carcinomas to one squamous cell carcinoma and is also a feature of other reported series of malignancies in transplant patients. In all, Shuttleworth et al found nineteen solar keratoses in 21 patients; they defined these lesions as pre-neoplastic without discussion. This definition must be challenged in view of an Australian study suggesting that less than 5% of actinic keratoses progress and that over an observation period of 12 months 25% actually regress.6 However, it must be remembered that the Australian figures relate to normal, non-immunosuppressed individuals. The highincidence of viral warts noted in the Scandinavian’ and Scottish’ studies is also confirmed in the Welsh report: 45 (53%) of the Welsh patients had such lesions. In patients who receive therapeutic 1. Najarian JS, So SKS, Simmons RL, et al The outcome of 304 primary renal transplants in children (1968-1985). Ann Surg 1986; 204: 246-58 2. Shell AGR, Mahoney JF, Horvath JS, et al Cancer following renal transplantation Aust NZJ Surg 1979; 49: 617-20 3. Blohmé I, Larko O Premalignant and malignant skin lesions in renal transplant patients Transplantation 1984; 37: 165-67 4 Boyle J, MacKie RM, Briggs JD, Junor BJR, Aitchison TC. Cancer, warts, and sunshine in renal transplant patients Lancet 1984; i 702-05 5. Shuttleworth D, Marks R, Griffin PJA, Salaman JR Dysplastic epidermal change in immunosuppressed patients with renal transplants Quart J Med 1987, 64: 609-16 6 Marks R, Foley P, Goodman G, Hage BH, Selwood TS. Spontaneous remission of solar keratoses The case for conservative management Br J Dermatol 1986; 115: 649-55 7
Spencer ES, Andersen HK Viral infections in renal allograft recipients long-term immunosuppression Br Med J 1979, ii: 829-30.
treated with
immunosuppression to prevent organ rejection or who are immunosuppressed as a result of cytotoxic chemotherapy, warts are not banal, mundane, or trivial but are multiple, painful, and frequently extremely resistant to therapy. Moreover, the exact role of the human papilloma virus in the aetiology of a wide range of human malignancies is under investigation. HPV 5 is most consistently reported in cutaneous malignancy. This uncommon HPV type is associated mainly with epidermodysplasia verruciformis, a cutaneous disorder with regularly reported progression to squamous carcinoma. The commonest types of HPV in banal skin warts of non-immunosuppressed individuals are HPV 1 and HPV 3. There have been few studies of HPV types in warts of renal transplant recipients,8-10 most of which appear to contain the commoner non-oncogenic HPV types although some have been reported to contain HPV 5. It remains to be established whether there is a true aetiological association between viral warts and cutaneous malignancy in the transplanted group, and, if so, whether the association is with HPV 5 or other HPVs of known oncogenic potential, or with normally non-oncogenic HPV types behaving with unusual aggression in the immunosuppressed host. The Scottish but not the Welsh study reports that transplant patients with cutaneous malignancy had a history of greater sun exposure than transplant patients without such changes. The role of ultraviolet (UV) exposure in the induction of specific immunosuppression has been extensively studied by Kripke and her colleagues in rriice.11 There is clear evidence of antigen-specific immunosuppression, transferable by adaptive transfer of lymphocytes induced during periods of UV irradiation. Comparable information is lacking for man, but the immunosuppressed environment of the renal transplant patient may interact with a similar mechanism. When the high incidence of cutaneous malignancy in renal transplant recipients was first reported, azathioprine was thought to be an essential factor and there were high hopes for a reduced incidence following the widespread introduction of cyclosporin A. Early work in animals and first results in man do not support this viewY Is there a practical message in these reports for renal transplant recipients and their physicians? Firstly, it is advisable to examine the skin before transplantation and treat any viral warts appropriately. They will be more easily ablated before transplant than after. All renal transplant recipients should be cautioned about excessive sun exposure and given advice about topical sun-screening preparations with an SPF (sun protection factor) of 15 or higher, even for use in the UK and similar temperate countries. All renal transplant recipients should have a full cutaneous examination at regular intervals. Once any signs of premalignant or malignant change have developed the intervals between examinations should be reduced. With this regimen at least some of the long-term cutaneous complications will be avoided. 8 Gassenmaier A, Fuchs P, Schell H, Pfister H Papillomavirus DNA in warts of immunosuppressed renal allograft recipients Arch Dermatol Res 1986, 278: 219-23. 9. Rudlinger R, Smith IW, Bunney MH, Hunter JAA Human papillomavirus infections m a group of renal transplant recipients Br J Dermatol 1986, 115: 681-92 10 Van der Leest RJ, Zachow KR, Ostrow RS, et al Human papillomavirus heterogeneity m 36 renal transplant recipients Arch Dermatol 1987; 123: 354-57 11 Kripke ML Immunology and photocarcinogenesis J Am Acad Dermatol 1986, 14: 149-55. 12. Penn I, First MR Development and incidence of cancer following cyclosporine therapy. Transplant Proc 1986; 18 (suppl 1) 210-13
RENAL TRANSPLANTATION AND THE SKIN FOR patients on renal dialysis awaiting an appropriately matched donor kidney, the prospect of dermatological problems many years post-transplant will no doubt seem a very minor inconvenience at most. However, for long-term survivors-and the number of such individuals is rising steadily—the reality may be somewhat different. The cutaneous disorders are of three main types-persistent viral warts, premalignant actinic keratoses, and frank cutaneous malignancy. There is keen interest in the possible aetiological relation between the viral and malignant lesions, and the role of exposure to natural sunlight in facilitating the development of all three types of skin disorder. The earliest reports of an increased incidence of cutaneous malignancy in transplant patients came from Australiawell recognised as the skin cancer capital of the world even for those who are not immunosuppressed. It was also noted that there was a relation between the incidence of cutaneous malignancy and the time since transplantation. These studies were followed by reports from Scandinavia3 and Scotland4 indicating that even in areas with relatively low solar intensity, cutaneous malignancy was a posttransplantation hazard. A report by Shuttleworth and colleagues from Wales5 confirms these findings. Of 85 transplant recipients, 45 had survived 80 months or more after transplantation and 17 (38%) of these had preneoplastic or neoplastic lesions. Only nine lesions were frankly neoplastic-seven squamous cell carcinomas and two basal cell carcinomas. This ratio is a reversal of the usual ratio of two or three basal cell carcinomas to one squamous cell carcinoma and is also a feature of other reported series of malignancies in transplant patients. In all, Shuttleworth et al found nineteen solar keratoses in 21 patients; they defined these lesions as pre-neoplastic without discussion. This definition must be challenged in view of an Australian study suggesting that less than 5% of actinic keratoses progress and that over an observation period of 12 months 25% actually regress.6 However, it must be remembered that the Australian figures relate to normal, non-immunosuppressed individuals. The highincidence of viral warts noted in the Scandinavian’ and Scottish’ studies is also confirmed in the Welsh report: 45 (53%) of the Welsh patients had such lesions. In patients who receive therapeutic 1. Najarian JS, So SKS, Simmons RL, et al The outcome of 304 primary renal transplants in children (1968-1985). Ann Surg 1986; 204: 246-58 2. Shell AGR, Mahoney JF, Horvath JS, et al Cancer following renal transplantation Aust NZJ Surg 1979; 49: 617-20 3. Blohmé I, Larko O Premalignant and malignant skin lesions in renal transplant patients Transplantation 1984; 37: 165-67 4 Boyle J, MacKie RM, Briggs JD, Junor BJR, Aitchison TC. Cancer, warts, and sunshine in renal transplant patients Lancet 1984; i 702-05 5. Shuttleworth D, Marks R, Griffin PJA, Salaman JR Dysplastic epidermal change in immunosuppressed patients with renal transplants Quart J Med 1987, 64: 609-16 6 Marks R, Foley P, Goodman G, Hage BH, Selwood TS. Spontaneous remission of solar keratoses The case for conservative management Br J Dermatol 1986; 115: 649-55 7
Spencer ES, Andersen HK Viral infections in renal allograft recipients long-term immunosuppression Br Med J 1979, ii: 829-30.
treated with
immunosuppression to prevent organ rejection or who are immunosuppressed as a result of cytotoxic chemotherapy, warts are not banal, mundane, or trivial but are multiple, painful, and frequently extremely resistant to therapy. Moreover, the exact role of the human papilloma virus in the aetiology of a wide range of human malignancies is under investigation. HPV 5 is most consistently reported in cutaneous malignancy. This uncommon HPV type is associated mainly with epidermodysplasia verruciformis, a cutaneous disorder with regularly reported progression to squamous carcinoma. The commonest types of HPV in banal skin warts of non-immunosuppressed individuals are HPV 1 and HPV 3. There have been few studies of HPV types in warts of renal transplant recipients,8-10 most of which appear to contain the commoner non-oncogenic HPV types although some have been reported to contain HPV 5. It remains to be established whether there is a true aetiological association between viral warts and cutaneous malignancy in the transplanted group, and, if so, whether the association is with HPV 5 or other HPVs of known oncogenic potential, or with normally non-oncogenic HPV types behaving with unusual aggression in the immunosuppressed host. The Scottish but not the Welsh study reports that transplant patients with cutaneous malignancy had a history of greater sun exposure than transplant patients without such changes. The role of ultraviolet (UV) exposure in the induction of specific immunosuppression has been extensively studied by Kripke and her colleagues in rriice.11 There is clear evidence of antigen-specific immunosuppression, transferable by adaptive transfer of lymphocytes induced during periods of UV irradiation. Comparable information is lacking for man, but the immunosuppressed environment of the renal transplant patient may interact with a similar mechanism. When the high incidence of cutaneous malignancy in renal transplant recipients was first reported, azathioprine was thought to be an essential factor and there were high hopes for a reduced incidence following the widespread introduction of cyclosporin A. Early work in animals and first results in man do not support this viewY Is there a practical message in these reports for renal transplant recipients and their physicians? Firstly, it is advisable to examine the skin before transplantation and treat any viral warts appropriately. They will be more easily ablated before transplant than after. All renal transplant recipients should be cautioned about excessive sun exposure and given advice about topical sun-screening preparations with an SPF (sun protection factor) of 15 or higher, even for use in the UK and similar temperate countries. All renal transplant recipients should have a full cutaneous examination at regular intervals. Once any signs of premalignant or malignant change have developed the intervals between examinations should be reduced. With this regimen at least some of the long-term cutaneous complications will be avoided. 8 Gassenmaier A, Fuchs P, Schell H, Pfister H Papillomavirus DNA in warts of immunosuppressed renal allograft recipients Arch Dermatol Res 1986, 278: 219-23. 9. Rudlinger R, Smith IW, Bunney MH, Hunter JAA Human papillomavirus infections m a group of renal transplant recipients Br J Dermatol 1986, 115: 681-92 10 Van der Leest RJ, Zachow KR, Ostrow RS, et al Human papillomavirus heterogeneity m 36 renal transplant recipients Arch Dermatol 1987; 123: 354-57 11 Kripke ML Immunology and photocarcinogenesis J Am Acad Dermatol 1986, 14: 149-55. 12. Penn I, First MR Development and incidence of cancer following cyclosporine therapy. Transplant Proc 1986; 18 (suppl 1) 210-13