Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

BACKGROUND: Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life. RESULTS: A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups. CONCLUSIONS: In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

Dermatological Disease in Australian Heart and Lung Transplant Recipients.

BACKGROUND: Research examining skin disease in heart and lung transplant recipients in Australia is limited. This study aims to determine the spectrum of skin diseases encountered in Australian heart and lung transplant recipients, their effect on quality of life, and potential risk factors for skin cancer. METHODS: Ninety-four participants were recruited from an Australian heart and lung transplant centre between March and December 2016. The participants were asked to fill out a questionnaire which included the Dermatology Life Quality Index and were examined for malignant and non-malignant skin disease. The association of study variables with the presence of skin cancer and Dermatology Life Quality Index score were examined using logistic regression analysis. RESULTS: A dermatological diagnosis was made in 82 patients (87%). Actinic keratosis was the most common diagnosis, affecting 50 participants (53%), followed by skin cancer (41; 44%) and warts (14; 15%). Other non-malignant skin diseases were less common. Risk factors associated with skin cancer on multivariate modelling included age at transplantation and a history of ≥5 post-transplant skin cancers. Skin disease had a negative effect on the quality of life of a minority of patients. CONCLUSION: Actinic keratosis and skin cancer are very frequent in Australian heart and lung transplant recipients and more common than non-malignant skin diseases. Routine dermatological surveillance at regular intervals is advised.

Nephrogenic systemic fibrosis in a gadolinium-naïve patient: successful treatment with oral sirolimus.

A 52-year old woman with chronic renal failure presented with tender buttock nodules, bilateral non-tender periocular papules and yellow scleral plaques. The patient then developed sclerodermoid changes of the hands, as well as woody induration, oedema and hyperpigmentation of lower limbs. There was no previous exposure to gadolinium contrast. Her histology and clinical features were consistent with nephrogenic systemic fibrosis. Treatment with oral sirolimus resulted in a marked reduction of induration and oedema, and an improvement in distal upper limb and lower limb joint mobility.

Nonmelanoma Skin Cancer Frequency and Risk Factors in Australian Heart and Lung Transplant Recipients.

Importance: There is limited research examining the incidence of nonmelanoma skin cancer (NMSC) in heart and lung transplant recipients in Australia. Objective: To determine the frequency of and risk factors for NMSC in a cohort of Australian heart and lung transplant recipients. Design, Setting, and Participants: A retrospective cohort study was conducted at an Australian tertiary center where heart and lung transplants are performed between March 21 and December 14, 2016. A consecutive sample of 94 patients who underwent heart and/or lung transplant presenting for outpatient dermatologic review were evaluated. Data analysis was conducted between April 18 and October 30, 2017. Exposures: Risk factors examined for association with posttransplantation NMSC included age at the time of transplantation, sex, skin phenotype, UV radiation exposure, history of allograft rejection, history of smoking, history of skin cancer prior to transplant, and transplant type. Main Outcomes and Measures: The primary outcome measure was the occurrence of posttransplantation NMSC. The probabilities of developing NMSC in general, and squamous cell carcinoma and basal cell carcinoma specifically, were separately summarized based on Kaplan-Meier analysis. Association of risk factors with development of NMSC was examined using univariable and multivariable Cox proportional hazards regression analysis. Results: Of the 94 study participants, 58 (62%) were men; median age at transplantation was 51.9 years (range, 15.1-69.7 years). There were 801 posttransplantation skin cancers in 57 (61%) of the patients who underwent heart and/or lung transplant. The probabilities for NMSC were 41% (95% CI, 31%-53%) at 5 years and 67% (95% CI, 55%-78%) at 10 years; for basal cell carcinoma, 27% (95% CI, 18%-38%) at 5 years and 53% (95% CI, 40%-67%) at 10 years; and for squamous cell carcinoma, 33% (95% CI, 24%-45%) at 5 years and 62% (95% CI, 50%-74%) at 10 years. On multivariable analysis, older age at transplantation was associated with the development of NMSC (hazard ratio [HR], 1.07/1 year; 95% CI, 1.04-1.10; P < .001) and history of pretransplant skin cancer was associated with development of basal cell carcinoma (HR, 4.56; 95% CI, 1.67-12.42; P = .003). A Fitzpatrick skin type III to VI was associated with a decreased risk of NMSC (HR, 0.42; 95% CI, 0.24-0.74; P = .003). Sex, transplanted organ, UV radiation exposure, and history of allograft rejection were not associated with an increased risk of skin cancer. Conclusions and Relevance: In this study of Australian heart and lung transplant recipients, there was a probable high frequency of NMSC. Routine dermatologic surveillance at frequent intervals is advised for similar populations.

ECMO-dependent respiratory failure after snorting speed associated with anti-GBM antibodies.

A previously well 20-year-old man with a history of nasal inhalation of "speed" was retrieved on extracorporeal membrane oxygenation for respiratory failure. Anti-glomerular basement membrane (anti-GBM) antibody was positive in the absence of renal disease. We postulate a hitherto unreported causal link between snorting "speed" and lung disease associated with anti-GBM antibody formation.