Matthew Mansh

Voriconazole-Associated Cutaneous Malignancy: A Literature Review on Photocarcinogenesis in Organ Transplant Recipients

This article synthesizes the current data regarding the implication of voriconazole in the development of skin cancer in organ transplant recipients (OTRs) and offers suggestions for additional research. According to Organ Procurement and Transplantation Network data, 28 051 solid organ transplants were performed in 2012. Due to advancements in immunosuppression and management of infectious diseases, survival of OTRs has substantially increased. Voriconazole is a widely prescribed antifungal medication used for prophylaxis and for treatment of invasive fungal infections in OTRs. Case reports describing skin cancer associated with voriconazole exposure emerged shortly after US Food and Drug Administration approval of the drug, and it is now established that voriconazole is an independent risk factor for the development of cutaneous malignancy in lung transplant recipients. The mechanism of voriconazole-induced skin cancer is still unknown and may involve its primary metabolite, voriconazole N-oxide. Here we discuss the current data and potential mechanisms of voriconazole-associated photosensitivity and carcinogenesis and identify areas that require further research.

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all‐cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04–2.88; p = 0.03), with each additional 30‐day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02–1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34–0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all‐cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13–0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient‐specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.

Association of Skin Cancer and Indoor Tanning in Sexual Minority Men and Women

Importance Skin cancer, the most common cancer in the United States, is highly associated with outdoor and indoor tanning behaviors. Although indoor tanning has been suggested to be more common among sexual minority (self-reported as homosexual, gay, or bisexual) men compared with heterosexual men, whether rates of skin cancer vary by sexual orientation is unknown. Objective To investigate whether skin cancer prevalence and indoor tanning behaviors vary by sexual orientation in the general population. Design, Setting, and Participants We performed a cross-sectional study using data from the 2001, 2003, 2005, and 2009 California Health Interview Surveys (CHISs) and the 2013 National Health Interview Survey (NHIS) of population-based samples of the California and US noninstitutionalized civilian population. Participants included 192 575 men and women 18 years or older who identified as heterosexual or a sexual minority. Main Outcomes and Measures Self-reported lifetime history of skin cancer and 12-month history of indoor tanning. Results The study included 78 487 heterosexual men, 3083 sexual minority men, 107 976 heterosexual women, and 3029 sexual minority women. Sexual minority men were more likely than heterosexual men to report having skin cancer (2001-2005 CHISs: adjusted odds ratio [aOR], 1.56; 95% CI, 1.18-2.06, P < .001; 2013 NHIS: aOR, 2.13; 95% CI, 1.14-3.96, P = .02) and having tanned indoors (2009 CHIS: aOR, 5.80; 95% CI, 2.90-11.60, P < .001; 2013 NHIS: aOR, 3.16; 95% CI, 1.77-5.64, P < .001). Sexual minority women were less likely than heterosexual women to report having had nonmelanoma skin cancer (2001-2005 CHIS: aOR, 0.56; 95% CI, 0.37-0.86, P = .008) and having tanned indoors (2009 CHIS: aOR, 0.43; 95% CI, 0.20-0.92, P = .03; 2013 NHIS: aOR, 0.46; 95% CI, 0.26-0.81, P = .007). Conclusions and Relevance Sexual minority men indoor tan more frequently and report higher rates of skin cancer than heterosexual men. Primary and secondary prevention efforts targeted at sexual minority men might reduce risk factors for, and consequences of, skin cancer.

Acne, sexual orientation, and mental health among young adults in the United States: A population-based, cross-sectional study

Age Mean (SE) 21.8 (0.12) 21.7 (0.15) .40 Sex Female 53.1 (0.9) 31.4 (2.4) Male 46.9 (0.9) 68.6 (2.4) \.001 Race White, non-Hispanic 69.4 (3.1) 72.3 (3.4) White, Hispanic 7.5 (1.3) 8.1 (1.6) African American 17.0 (2.5) 11.2 (1.7) Asian or Pacific Islander 3.5 (0.9) 4.6 (1.2) Native American 2.6 (0.6) 3.7 (1.1) .02 Education level \High school 13.4 (1.1) 16.4 (2.1) High school 32.9 (1.4) 27.8 (2.9) Some college 38.6 (1.3) 40.7 (2.5)

Voriconazole exposure regulates distinct cell cycle and terminal differentiation pathways in primary human keratinocytes.

4-y college degree 15.1 (1.5) 15.1 (2.5) .19 Insurance status Insured 76.7 (1.1) 72.1 (2.2) .03 Acnek Yes 3.9 (0.4) 6.2 (1.1) .03

Characteristics and Skin Cancer Risk Behaviors of Adult Sunless Tanners in the United States

Abstract Voriconazole is a second generation triazole antifungal used routinely in the care of solid organ and stem cell transplant recipients to both prevent and treat invasive fungal infections (1) . Voriconazole causes photosensitivity (2) and has been associated with a dose-dependent increased risk of developing cutaneous squamous cell carcinoma (cSCC).(3) Possible mechanisms suggested include direct phototoxicity by voriconazole or one of its metabolites (4) , oxidative stress pathway activation (5) , an indirect retinoid effect, or DNA damage repair inhibition (6) . This article is protected by copyright. All rights reserved.

Necrotizing Anogenital Ulcer in a Healthy 8-Month-Old Male

Importance Incidence rates of nonmelanoma and melanoma skin cancers are increasing rapidly in the United States likely because of increased UV light exposure. Sunless tanning is a safe alternative to achieve tanned skin that might help reduce skin cancer incidence by deterring risky behaviors. However, limited data exist on the characteristics and associated skin cancer risk behaviors of sunless tanners in the United States. Objective To assess the demographic characteristics and skin cancer risk behaviors of sunless tanners among adults in the United States. Design, Setting, and Participants This secondary analysis of a cross-sectional study used data from the 2015 National Health Interview Survey, a population-based survey of the US noninstitutionalized civilian population. Participants included 27 353 men and women 18 years or older. Main Outcome and Measures Participant demographics and skin cancer risk behaviors, including indoor tanning, skin cancer screening, sunburn, and sun protection behaviors. Results Of the 27 353 adults (representative of more than 198 million US adults; mean [SE] age, 46.0 [0.2] years) studied, 6.4% (SE, 0.2%) reported sunless tanning. Factors associated with sunless tanning included being young, female, non-Hispanic white, college educated, nonobese, and sun sensitive, living in the western United States, and having a family history of skin cancer. Sunless tanners were more likely to report indoor tanning (adjusted prevalence odds ratio [aPOR], 3.77; 95% CI, 3.19-4.43; P < .001), recent sunburn (aPOR, 1.55; 95% CI, 1.31-1.83; P < .001), use of sunscreen (&bgr; = 0.19; 95% CI, 0.09-0.28; P < .001), and having had a full-body skin examination (aPOR, 1.77; 95% CI, 1.51-2.08; P < .001) but less likely to seek shade (&bgr; = −0.12; 95% CI, −0.19 to −0.04; P = .001) or use protective clothing when outdoors (long pants: &bgr; = −0.18; 95% CI, −0.26 to −0.11; P < .001; long sleeves: &bgr; = −0.10; 95% CI, −0.18 to −0.03; P = .01). Among indoor tanners, sunless tanners compared with those who did not sunless tan reported increased frequency of indoor tanning (mean [SE], 19.2 [1.9] vs 14.9 [1.2] sessions in the past 12 months; P = .04) but no differences in other skin cancer risk behaviors. Conclusions and Relevance This study suggests that sunless tanning is associated with risky skin cancer–related behaviors. Longitudinal studies are needed to assess whether sunless tanning changes UV exposure behaviors to better determine whether sunless tanning represents an effective public health strategy to reduce rates of skin cancer in the United States.

Management of Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients

A healthy 8-month-old male infant was admitted for management of a rapidly progressive, painful anogenital ulcer. The lesion had developed acutely over 48 hours, starting as symmetric pink patches leading to pustules, erosions, and ulceration. Associated symptoms included generalized fatigue, but no fevers, chills, or other systemic symptoms. The child’s parents denied any new topical exposures or medications. The child was born via vaginal delivery at full term. Pregnancy was complicated by gestational diabetes. The child had no major medical issues and met all developmental milestones. There was no relevant family medical history. Broad-spectrum intravenous antibiotics were initiated on admission. Dermatology was consulted prior to scheduled debridement and skin grafting.

Malar Rash in a Stem Cell Transplant Recipient

The lifelong immunosuppression required for maintenance of allograft function in organ transplant recipients (OTR) increases the risk of cutaneous malignancies in this population. Prolonged survival posttransplantation further permits the development of late dermatologic complications of iatrogenic immunosuppression, particularly skin cancer. Cutaneous squamous cell carcinoma (CSCC) is the most common posttransplant malignancy, and in OTR can present as multiple, aggressive, and rapidly metastasizing lesions that are challenging to manage. Due to the high morbidity and potential mortality of CSCC in OTR, close dermatologic surveillance and aggressive treatment are essential. This review will address the challenge of managing posttransplant CSCC in the OTR population with a summary of the current therapeutic strategies in this patient cohort. The management of metastatic CSCC remains challenging, despite promising results from chemotherapeutic agents and novel targeted molecular inhibitors combined with radiation therapy. Ultimately, therapeutic considerations for CSCC in OTR should be determined in a multidisciplinary setting including the dermatologist, the transplant team, and appropriate specialists.

Indoor Tanning, Sunless Tanning, and Sun-Protection Behaviors Among Sexual Minority Men

A 41-year-old white man with a history of myelofibrosis went on a sailing trip during which he was exposed to intense sunlight. Subsequently, he noted development of a nonpruritic rash on his face, trunk, and extremities. The rash was associated with intermittent fever, muscle pain, and weakness. His myelofibrosis had been treated 2 years earlier with a splenectomy and allogeneic peripheral hematopoietic stem cell transplantation from a singleantigen mismatched unrelated donor. A busulfan-based myeloablative regimen was used for preconditioning before the transplant. After the transplant, he experienced acute graft-vs-host disease predominantly manifested by gastrointestinal symptoms. He had received tacrolimus, but that was tapered off 4 months before his current problems began. His only current medication is daily oral acyclovir. Vital signs were normal. There were well-demarcated erythematous to violaceous scaly plaques on his forehead and cheeks, sparing the nasolabial folds and periocular regions (Figure, A). Diffuse areas of reticulated hyperpigmentation were present across his chest and upper back (Figure, B). There were violaceous, thin, flat-topped papules bilaterally on the dorsal surfaces of his hands (Figure, C) and the lateral soles of his feet. Musculoskeletal examination revealed impaired ability to dorsiflex the wrists while bringing the palms together (“prayer sign”). Results of liver function tests revealed an aspartate aminotransferase level of 41 U/L (0.68 μkat/L); alanine aminotransferase, 68 U/L (1.14 μkat/L); alkaline phosphatase, 147 U/L (2.45 μkat/L); and total bilirubin, 0.7 mg/dL (11.97 μmol/L). The result of an antinuclear antibody test was positive (1:320) and had a speckled pattern. Quiz at jama.com A B