Seven-year prospective study of nonmelanoma skin cancer incidence in U.K. renal transplant recipients.

Nonmelanoma skin cancer (NMSC) causes significant morbidity and mortality posttransplantation. We examined the annual incidence of NMSC in U.K. renal transplant recipients (RTRs). A total of 269 (95% of potential population) RTRs of skin type I-IV were recruited into a prospective study of NMSC incidence between 1998 and 2006. A total of 244 (91% enrolled) RTRs were screened on at least one occasion. The mean incidence per year of NMSC was 7.82% (SD: 1.84), comprising a mean (SD) incidence per year of squamous cell carcinoma 3.45% (1.36), basal cell carcinoma 3.58% (1.17), and Bowen's disease 2.52% (0.91). The risk of developing NMSC increased with duration posttransplantation: the mean incidence per year of NMSC was 3.27% (0.53) in RTRs <5 years posttransplantation, 5.86% (3.1) in RTRs 5-10 years posttransplant, and 11.1% (1.85) in those >10 years posttransplant. Relatively low NMSC incidence rates within the first 5 years posttransplantation suggests that duration posttransplantation may determine the optimum frequency of surveillance of RTRs in the United Kingdom.

Sebaceous hyperplasia and skin cancer in patients undergoing renal transplant.

BACKGROUND: One previous study has shown a higher prevalence of sebaceous hyperplasia (SH) in patients with heart transplant on immunosuppressive drugs as compared with sex-matched control patients. OBJECTIVE: We set out to compare the prevalence of SH in a cohort of patients undergoing renal transplant with age- and sex-matched control patients and to find any association with nonmelanoma skin cancer (NMSC) in these patients. METHODS: In all, 117 patients with renal transplant and 117 age- and sex-matched control patients were screened for the prevalence of SH and NMSC. RESULTS: We found that 29.9% of our patients with renal transplant had SH; 16 of 35 (45.7%) of these patients had a history of NMSC as compared with 6 of 82 (7.3%) patients without SH (P < .001, odds ratio 10.7). In the age- and sex-matched control group, a total of 28 patients (23.9%) had one or more lesions of SH. LIMITATIONS: This study is small and will require confirmation with larger cohort studies. CONCLUSIONS: In our cohort of patients with renal transplant we found a strong association of NMSC with SH. This association remained significant after correction of factors such as age, sex, skin type, and duration of transplant.

Incidence and prediction of nonmelanoma skin cancer post-renal transplantation: a prospective study in Queensland, Australia.

BACKGROUND: Nonmelanoma skin cancer (NMSC) is a significant clinical problem after renal transplantation, particularly in areas of high UV light exposure. A single-center prospective study of a population of Queensland renal transplant recipients was performed with the aims of: (1) establishing NMSC incidence and tumor accrual post-renal transplantation, and (2) developing a clinically derived predictive index to identify transplant recipients at greatest risk. METHODS: Three hundred ten of 398 transplant recipients (78%) who underwent baseline assessment between July 1999 and April 2000 were reassessed a mean of 18 +/- 3.5 (SD) months later. A structured interview, full skin examination, biopsy of suspicious lesions, and review of medical and pathological records were used to determine the number and types of NMSC arising between the two assessments. Incidence (percentage of the population developing NMSC per year) and tumor accrual (number of tumors per person per year) were calculated. A clinically derived predictive index was generated using stepwise logistic regression models. RESULTS: Overall NMSC incidence was 28.1% and increased with duration of immunosuppression therapy: 18.8%, 24.8%, 33.3%, and 47.1% at less than 5, 5 to 10, 10 to 20, and greater than 20 years of immunosuppression therapy, respectively. Mean NMSC accrual was 1.85 +/- 3.84 tumors/person/y, increasing to 3.35 +/- 4.29 tumors/person/y after 20 years of immunosuppression therapy. Renal transplant recipients were stratified into categories of high and low NMSC risk by using predictive indices. CONCLUSION: Clinically derived predictive indices can allow NMSC risk stratification of an Australian transplant population and may provide an evidence-based and cost-effective approach to developing a targeted clinical NMSC surveillance program.

A model for nurse-led skin cancer surveillance following renal transplantation.

Renal transplant recipients are at high risk for multiple non-melanoma skin cancers (NMSC) that occur at a younger age and behave more aggressively. Consequently, the American Society of Transplantation has recommended that physicians conduct annual screenings for NMSC in this population. Few centres currently offer a dedicated surveillance programme. This article discusses a model for skin cancer surveillance in which a trained nurse works within a validated competency programme to provide annual skin surveillance and education in the renal transplant outpatient clinic.

Contact allergy masquerading as seronegative Sjögren's syndrome.

Primary Sjögren's syndrome is an autoimmune disease that presents with xerostomia and keratoconjunctivitis sicca (due to chronic lymphocytic inflammation of the salivary and lacrimal glands) and in some cases extraglandular features. Patients typically have positive antinuclear, anti-Ro, and anti-La antibodies; however, around 20% to 30% do not and are therefore termed seronegative. We present a case of a 58-year-old woman who was originally diagnosed with seronegative Sjögren's syndrome based on the American-European classification system. She had complete resolution of her clinical features on identification and avoidance of relevant contact allergens. Contact allergy should be considered in the differential diagnosis of seronegative Sjögren's syndrome, especially where atypical features such as facial rash, normal salivary gland imaging, or lichenoid histology exist.

Predicting risk of nonmelanoma skin cancer and premalignant skin lesions in renal transplant recipients.

BACKGROUND: Nonmelanoma skin cancer (NMSC) and associated premalignant lesions represent a major complication after transplantation, particularly in areas with high ultraviolet radiation (UVR) exposure. The American Society of Transplantation has proposed annual NMSC screening for all renal transplant recipients. The aim of this study was to develop a predictive index (PI) that could be used in targeted screening. METHODS: Data on patient demographics, UVR exposure, and other clinical parameters were collected on 398 adult recipients recruited from the Princess Alexandra Hospital, Brisbane. Structured interview, skin examination, biopsy of lesions, and review of medical/pathologic records were performed. Time to presentation with the first NMSC was assessed using Cox's regression models and Kaplan-Meier estimates used to assess detection of NMSC during screening. RESULTS: Stepwise selection identified age, outdoor UVR exposure, living in a hot climate, pretransplant NMSC, childhood sunburning, and skin type as predictors. The PI generated was used to allocate patients into three screening groups (6 months, 2 years, and 5 years). The survival curves of these groups were significantly different (P<0.0001). Jack-knife validation correctly allocated all patients into the appropriate group. CONCLUSION: We have developed a simple PI to enable development of targeted NMSC surveillance strategies.

Polymorphisms in glutathione S-transferases and non-melanoma skin cancer risk in Australian renal transplant recipients.

Caucasian renal transplant recipients from Queensland, Australia have the highest non-melanoma skin cancer (NMSC) risk worldwide. Although ultraviolet light (UVR) exposure is critical, genetic factors also appear important. We and others have shown that polymorphism in the glutathione S-transferases (GST) is associated with NMSC in UK recipients. However, the effect of high UVR exposure and differences in immunosuppressive regimen on these associations is unknown. In this study, we examined allelism in GSTM1, GSTM3, GSTT1 and GSTP1 in 361 Queensland renal transplant recipients. Data on squamous (SCC) and basal cell carcinoma (BCC), UVR/tobacco exposure and genotype were obtained. Associations with both NMSC risk and numbers were examined using logistic and negative binomial regression, respectively. In the total group, GSTM1 AB [P = 0.049, rate ratio (RR) = 0.23] and GSTM3 AA (P = 0.015, RR = 0.50) were associated with fewer SCC. Recipients were then stratified by prednisolone dose (< or =7 versus >7 mg/day). In the low-dose group, GSTT1 null (P = 0.006, RR = 0.20) and GSTP1 Val/Val (P = 0.021, RR = 0.20) were associated with SCC numbers. In contrast, in the high-dose group, GSTM1 AB (P = 0.009, RR = 0.05), GSTM3 AB (P = 0.042, RR = 2.29) and BB (P = 0.014, RR = 5.31) and GSTP1 Val/Val (P = 0.036, RR = 2.98) were associated with SCC numbers. GSTM1 AB (P = 0.016) and GSTP1 Val/Val (P = 0.046) were also associated with fewer BCC in this group. GSTP1 associations were strongest in recipients with lower UVR/tobacco exposure. The data confirm our UK findings, suggesting that protection against UVR-induced oxidative stress is important in NMSC development in recipients, but that this effect depends on the immunosuppressant regimen.

Factors associated with nonmelanoma skin cancer following renal transplantation in Queensland, Australia.

BACKGROUND: Caucasian renal transplant recipients living in Queensland, Australia, have the highest risk of nonmelanoma skin cancer in the world. OBJECTIVE: To determine clinical and environmental factors associated with posttransplantation nonmelanoma skin cancer in Queensland. METHODS: 361 Caucasian adult recipients completed a structured interview and full skin examination. Skin cancer details were obtained from hospital records. RESULTS: Squamous cell carcinoma was strongly associated with blue or hazel eyes, time resident in a hot climate, and pretransplantation squamous cell carcinoma; tumor numbers were associated with birth in a hot climate, childhood sunburn, pretransplantation actinic keratoses, and smoking. The risk of basal cell carcinoma was strongly associated with acute or intermittent sun exposure during childhood and pretransplantation basal cell carcinoma; numbers were associated with blue or hazel eyes, time spent living in a hot climate, and male gender. CONCLUSION: Clinical and environmental factors can be used to identify recipients at risk of nonmelanoma skin cancer in Queensland.

Vascular endothelial growth factor gene polymorphisms are associated with acute renal allograft rejection.

Acute rejection is a major cause of reduced survival of renal allografts. Vascular endothelial growth factor (VEGF) is a mitogen for endothelial cells and is expressed widely by renal tissue and T cells. VEGF influences adhesion and migration of leukocytes across the endothelium. This study investigates whether genetically determined variation in VEGF expression influences the development of renal allograft rejection. VEGF promoter polymorphisms were examined by using sequence-specific primer-PCR in 173 renal transplant recipients. Acute rejection occurred in 38.7%; median time to first rejection episode was 14 d. VEGF in vitro expression was investigated in stimulated leukocytes from 30 controls. The -1154*G and -2578*C alleles were associated with higher VEGF production. VEGF -1154 GG and GA genotypes were significantly associated with acute rejection risk at 3 mo (P = 0.004, odds ration [OR] = 6.8, 95% CI = 1.8 to 25 and P = 0.035, OR = 4.1, 95% CI = 1.1 to 15, respectively). Furthermore, VEGF -2578 CC and CA genotypes were associated with increased rejection risk (P = 0.005, OR = 4.1, 95% CI = 1.5 to 11.3 and P = 0.035, OR = 2.7, 95% CI = 1.1 to 7, respectively). These polymorphisms demonstrate linkage disequilibrium (P = 0.001). These data indicate that the -1154*G and -2578*C containing genotypes, encoding higher VEGF production, are strongly associated with acute rejection and may be useful markers of rejection risk.