Management of skin cancer in solid organ transplant recipients

The incidence of catastrophic skin cancer in the solid organ transplant population continues to rise. As transplant patients are living longer, it is likely that dermatologists will be looking after an increasing number of organ transplant recipients. The key to managing this patient population lies in a multidisciplinary approach encompassing patient education, skin screening in the immediate post-transplant period, regular follow-up, and rapid referral to a dermatologist once skin lesions suspicious for skin cancer are diagnosed. Of paramount importance is discussion with transplant physicians to negotiate reduction of immunosuppression in the setting of catastrophic skin cancer. This article defines the scope of the problem of skin cancer in the solid organ transplant population, defines the nature of the lesions commonly presented, and reinforces the benefit of a multidisciplinary approach in the management of these patients.     

Human papillomavirus infection and skin cancer risk in organ transplant recipients

Warts and squamous cell carcinomas are important cutaneous complications in organ transplant recipients. The role of infection with human papillomaviruses (HPV) in the development of cutaneous squamous cell carcinoma is still unclear. An extremely diverse group of HPV types, mainly consisting of epidermodysplasia-verruciformis (EV)-associated HPV types, can be detected in benign, premalignant, and malignant skin lesions of organ transplant recipients. Frequently, there are multiple HPV types present in single skin biopsies. Typically, the prevalence of viral warts rises steadily after transplantation and a strong association exists between the number of HPV-induced warts and the development of skin cancer. The interval between the transplantation to the development of warts is clearly shorter than the interval from transplantation to the diagnosis of the first skin cancer. A comparison of transplant recipients with and without skin cancer, however, showed an equally high prevalence of EV-HPV DNA in keratotic skin lesions in both groups of patients and the detection rate and spectrum of HPV infection in hyperkeratotic papillomas, actinic keratoses, and squamous cell carcinomas was also similar. HPV DNA can frequently be detected in patients with hyperproliferative disorders like psoriasis and antibodies against HPV in patients with regenerating skin (e.g., after extensive second degree burns). Latent infection with EV-HPV seems to be widespread. The hair follicle region might be the reservoir of EV-HPV. The E6 protein from a range of cutaneous HPV types effectively inhibits apoptosis in response to UV-light induced damage. It is therefore conceivable that individuals who are infected by EV-HPV are at an increased risk of developing actinic keratoses and squamous cell carcinomas, possibly by chronically preventing UV-light induced apoptosis.     

Treatment of nonmelanoma skin cancer in organ transplant recipients: review of responses to a survey

There are approximately 100,000 US organ transplant recipients, many with nonmelanoma skin cancers. To better understand how clinicians treat them, we e-mailed a survey to the International Transplant-Skin Cancer Collaborative and the Association of Academic Dermatologic Surgeons. Twenty-five physicians responded. The majority use topical 5-fluorouracil, cryosurgery, electrodesiccation and curettage, and surgery. We review when these modalities are used.     

Squamous cell carcinoma in organ transplant recipients: approach to management

Skin cancer, particularly squamous cell carcinoma (SCC), continues to be a significant cause of morbidity and even mortality in organ transplant recipients (OTRs). As the number of organ transplant patients continues to increase, dermatologists will be faced with the challenge of diagnosing and managing their skin cancers. Evaluation, management and follow up of organ transplant recipients with high risk SCC will be discussed.     

Skin cancer in organ transplant recipients: Epidemiology,pathogenesis, and management

In the United States more than 100,000 people are living with solid organ transplants. The intense immunosuppressive regimens necessary for prolonged survival of allografts significantly increase the rates of both internal and cutaneous malignancies in recipients of solid organ transplants. Skin cancer is the most common cancer in patients after transplantation. Because of the early onset and high tumor burden in transplant recipients, dermatologists have significant challenges in managing the treatment of these patients. This article describes the epidemiology and clinical presentation of skin cancer during posttransplantation immunosuppression, discusses pathogenic cofactors, and reviews the optimal management for mild and severe skin cancer in transplant recipients.     

Management of organ transplant recipients attending a high-throughput skin cancer surgery and surveillance clinic in Queensland

People who undergo organ transplantation are more likely to develop skin cancers, due to long-term immunosuppressive therapy. This is especially concerning for organ transplant recipients (OTRs) living in Queensland, Australia, where skin cancer is more common than elsewhere. In an attempt to address the extreme skin cancer problem in OTRs living in Queensland, a dedicated Transplant Skin Clinic was established in Brisbane. This study aimed to describe the performance of this new clinic, the first of its kind in Queensland, Australia. Clinic attendees were invited to complete two surveys, supplied three months apart, about their health and personal characteristics, and permission was obtained to access participating attendees’ hospital records for details on detected and treated skin cancers over the same three-month period. In total, the authors recruited 101 clinic patients into the study. Over the three months, the authors found that 615 skin lesions were detected in the clinic. Of these, 55 were referred for treatment outside the clinic and 478 were treated in clinic, mostly (78%) with surgery. Of the lesions treated in clinic, 268 were confirmed to be skin cancers, equivalent to nearly 3 skin cancers per patient over the three months. On average, the clinic staff successfully treated one skin cancer for every 1.4 skin lesions they surgically removed. In conclusion, this study found that the clinic is detecting, and efficiently treating, a large number of skin cancers in OTRs and thus effectively contributing to the control of the skin cancer burden in OTRs living in Queensland.     

Skin infections in organ transplant recipients

In contrast to the well‐described high risk of skin cancer in organ transplant recipients, skin infections in these patients are not as well explored.Skin infections caused by viruses, bacteria or fungi represent a growing diagnostic and therapeutic challenge in the dermatological aftercare of organ transplant recipients. Differing immunosuppressive drugs and their variable dosage in chronologic sequence after transplantation probably influence the type and appearance of skin infections. The typical chronology of skin infections are wound infections, pyoderma or the reactivation of herpes viruses in the first month post‐transplant;the main problems in months 2–5 are opportunistic infections and reactivation of varicella‐zoster virus.After 6 months as immunosuppression is reduced, the spectrum of causative organisms approaches that of the general population; mycoses and human papilloma virus (HPV) infections dominate. A causal connection exists between infection with oncogenic viruses such as HPV, Epstein‐Barr virus and human herpesvirus 8 and specific skin cancers (squamous cell carcinoma, Kaposi sarcoma and post‐transplant lymphoprolif‐erative disorders). Dermatological care of organ transplant recipients using appropriate diagnostic methods adapted to the modified clinical pattern may lead to early adequate treatment.     

Defining the clinical course of metastatic skin cancer in organ transplant recipients: a multicenter collaborative study

OBJECTIVE: To evaluate the demographic characteristics, clinical course, and outcome in organ transplant recipients with metastatic skin cancer. DESIGN AND SETTING: An international, multicenter, Internet-coordinated collaborative group retrospectively analyzed data from 68 organ transplant recipients with 73 distinct metastatic skin cancers. MAIN OUTCOME MEASUREMENTS: The Kaplan-Meier method was used to estimate the cumulative incidence of relapse, overall survival, and disease-specific survival after metastatic skin cancer. Univariate Cox proportional hazards models were fit to evaluate factors for an association with survival. RESULTS: Metastasis from skin cancer in organ transplant recipients most commonly consisted of squamous cell carcinoma in regional nodal basins. It was predominantly treated with a combination of surgery and irradiation. By 1 year after metastasis, the cumulative incidence of relapse was 29%, and the 3-year disease-specific survival was 56%. Patients whose initial metastases were distant or systemic had a significantly poorer disease-specific survival than those whose initial metastases were in-transit or regional (risk ratio, 6.5; P<.001). CONCLUSIONS: Metastatic skin cancer in organ transplant recipients has a poor prognosis. Preventive, early, and aggressive therapeutic interventions are required to minimize this serious complication of transplant-associated immunosuppression.     

Keratinocyte carcinoma in organ transplant recipients

Skin cancer commonly affects people who have received a solid organ transplant (heart, lung, liver and kidney). Transplant patients can get multiple skin cancers, some of which can grow very quickly. The commonest types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Immunosuppressant medication is used to prevent rejection of the transplanted organ. This alters the body's immune system, which in turn means that transplant patients are more prone to skin cancers that can grow rapidly. Over the last 20 years, newer immunosuppressants have been introduced which are thought to lessen the risk of skin cancer. Previous studies have shown a lower risk of SCC with the newer medication, but no study to date has looked at BCC rates. This study, from Ireland, aimed to find out if the rate of skin cancer in transplant patients has reduced over the last 20 years, spanning the introduction of newer immunosuppressive medications. The National Cancer Registry of Ireland registers all skin cancers for the Republic of Ireland. The authors looked at the rate of skin cancer in people who received a solid organ transplant and compared this to the rate of skin cancer in the general population. They found that the rate of SCC and BCC in patients who received an organ transplant has significantly reduced over the last two decades. This change in risk of skin cancer coincided with changes in immunosuppressant medication, along with focused education and regular skin cancer screening for transplant recipients.     

Educational outcomes regarding skin cancer in organ transplant recipients: Randomized intervention of intensive vs standard education

OBJECTIVE: To determine whether an intensive educational program focused on the risk of skin cancer in organ transplant recipients, a population at high risk for development of skin cancer because of immunosuppression, produced measurable improvement in patient knowledge and sun-protective behavior. DESIGN: Patients were randomly assigned to receive standard episode-of-care-based education or intensive repetitive written education about skin cancer after organ transplantation. Preintervention knowledge was assessed and documented through a self-administered educational assessment tool. Retention of knowledge and the effect on sun-protective behavior were assessed with a follow-up questionnaire at 3 and 10 months. SETTING: Transplant center of an academic medical center. PATIENTS: Two hundred two patients presenting for transplant dermatologic consultation.Intervention Randomized intensive, repetitive written educational reinforcement. MAIN OUTCOME MEASURES: Retention of knowledge and the effect on sun-protective behavior were assessed with a follow-up questionnaire at 3 and 10 months. RESULTS: Both intervention groups had similarly high baseline and 3- and 10-month scores on the knowledge portion of the surveys, and they had similar scores on the behavioral assessment portion of the surveys at baseline. Subjects receiving intensive education scored significantly better on the behavioral assessment at 3 and 10 months, although an improvement in knowledge was not documented. CONCLUSIONS: This cohort of transplant recipients was well educated about skin cancer prevention before educational intervention and retained this knowledge. Patients who received the intensive educational intervention were significantly more compliant with recommendations for sun-protective behavior than those who received standard education, although differences in knowledge were not apparent. Lack of time and hassle were the most commonly cited barriers to behavioral compliance with sun protection.     

Iatrogenic skin cancer: induction by psoralen/ultraviolet A and immunosuppression of organ transplant recipients

Photochemotherapy (psoralen/UVA (PUVA)) is an efficient therapeutic tool for a wide range of skin diseases. Concern, however, exists regarding the long-term carcinogenic effects of this treatment modality and, as a consequence, is being used less frequently. PUVA remains an important treatment in our therapeutic armamentarium but must be used with caution in those patients with risk factors and cumulative dose exposure must be limited. PUVA-induced cancers show features in common with skin cancers induced by immunosuppressed organ transplant recipients. Tumours in the latter group of individuals are, however, much more aggressive and difficult to manage.     

Sunlight, keratotic skin lesions and skin cancer in renal transplant recipients

In a retrospective follow-up study, 36 renal transplant recipients with, and 101 without, skin cancer, who had received their first transplant before January 1981 and who were still alive with a functioning graft on 1 August 1989, were assessed to determine the risk of non-melanoma skin cancer in relation to exposure to sunlight during childhood and adolescence. The contribution of the number of keratotic skin lesions to the skin cancer risk was also assessed. The estimated relative risks (odds ratios) of skin cancer in relation to exposure to sunlight and the presence of keratotic skin lesions were calculated by maximum likelihood estimation in a logistic model. The majority of skin cancers and keratotic skin lesions were confined to sun-exposed skin. After adjustment for possible confounding variables, the odds ratios of skin cancer for moderate and high cumulative life-time exposure to sunlight, respectively, compared with low exposure, were 2·4 (95% confidence interval [CI] 0·64-9·3) and 47·6 (95% CI 5·4-418). Exposure to sunlight before the age of 30 contributed more to the risk of developing skin cancer later in life than exposure after the age of 30. No association was found between cumulative life-time exposure to sunlight and the number of keratotic skin lesions. Nevertheless, these lesions behaved as a strong independent risk factor in the development of skin cancer. The adjusted odds ratio of skin cancer for 50-99 lesions compared with >50 lesions was 4·5 (95% CI 1·1-18·2); the adjusted odds ratio for ≥100 lesions compared with >50 lesions was 20·8 (95% CI 5·3-81·7). We conclude that exposure to sunlight before the age of 30 contributes more to the risk of skin cancer in renal transplant recipients than exposure after the age of 30. Cumulative life-time exposure to sunlight does not appear to be associated with an increased number of keratotic skin lesions in these patients. The preferential localization of such lesions on sun-exposed skin suggests a possible role of recently received exposure to sunlight in the development of these lesions.