[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: Basal cell carcinoma (BCC) is the most common form of skin cancer; however, few data are available relating to patients' perspectives and experiences of this disease. This study explored the spectrum of BCC symptoms and their impact by disease stage to determine how BCC affects the overall health-related quality of life (HRQL) of patients.
This study comprised a cross-sectional, qualitative approach involving telephone interviews with patients with BCC who had been divided into two groups: group 1 (G1), patients with stage 1, non-advanced BCC (and of superficial or nodular histology); and group 2 (G2), patients with locally advanced or metastatic BCC. Patients were recruited from three clinical sites in the USA based on a separate qualitative interview study (I4J-MC-HHBB [1.3]) over a 10-month period. Techniques in qualitative methodology were used by applying 'open-ended' questions and probing techniques intended to elicit patients' own description of their experiences with BCC. Telephone interviews lasted between 60 and 90 mins.
Thirty-four interviews were conducted (G1: N = 13; G2: N = 21). The majority of patients were aged either 55-64 years (32%, N = 11) or 76+ years (32%, N = 11) and were primarily male (82%, N = 28); most (75%, N = 24) patients were actively receiving BCC treatment. Both groups reported similar symptoms, with the most common being red lesions or open sores that failed to heal (41%, N = 14) and cancer-related stress (41%, N = 14). G2 reported more frequent and severe HRQL impact as a result of their cancer condition because most were affected in their daily activities (76%, N = 16) or emotional well-being (71%, N = 15). Cosmetic and functional impacts were relevant and important aspects of HRQL for both patient groups (G1: 31%, N = 4; G2: 48%, N = 10).
Patients with non-advanced or locally advanced and metastatic BCC experience disease-related symptoms that affect their HRQL, activities of daily living, emotional well-being, and social and/or leisure activities. Qualitative descriptions of patient experiences can help healthcare providers and caregivers better understand the impact of BCC from the patient perspective.
Eli Lilly and Company.
[Show abstract][Hide abstract] ABSTRACT: Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked U.S. transplant-cancer registry data (1987-2010). We used standardized incidence ratios (SIRs) to compare incidence to the general population, and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (N=182) and non-recipients (N=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (N=519) was elevated (SIR=2.20, 95%CI 2.01-2.39), especially for regional stage tumors (SIR=4.11, 95%CI 3.27-5.09). Risk of localized tumors was stable over time after transplantation, but higher with azathioprine maintenance therapy (IRR=1.35, 95%CI 1.03-1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95%CI 1.02-2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (HR 2.98, 95%CI 2.26-3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with ultraviolet radiation, while T-cell depleting induction therapies may promote late stage tumors. Our findings support sun safety practices and skin screening for transplant recipients.Journal of Investigative Dermatology accepted article preview online, 13 August 2015. doi:10.1038/jid.2015.312.
Journal of Investigative Dermatology 08/2015; DOI:10.1038/jid.2015.312 · 7.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
American Journal of Transplantation 08/2015; DOI:10.1111/ajt.13431 · 5.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Psoriasis patients have relatively infrequent cutaneous viral infections compared to atopic dermatitis patients. Increased expression of four antiviral proteins (MX1, BST2, ISG15 and OAS2) has been reported in psoriatic skin and genetic studies of psoriasis have identified susceptibility genes in antiviral pathways.Objective
To determine if psoriasis is associated with pervasive expression of antiviral genes in skin and blood.Methods
We performed RNA sequencing on skin samples of 18 subjects with chronic plaque psoriasis and 16 healthy controls. We examined the expression of a predefined set of 42 antiviral genes, each of which has been shown in previous studies to inhibit viral replication. In parallel, we examined antiviral gene expression in atopic dermatitis, non-lesional psoriatic skin and psoriatic blood. We performed HIV-1 infectivity assays in CD4+ peripheral blood T cells from psoriatic and healthy individuals.ResultsWe observed significant overexpression of 16 antiviral genes in lesional psoriatic skin, with a greater than two-fold increase in ISG15, RSAD2, IRF7, MX2 and TRIM22 (P < 1E-07). None of these genes was overexpressed in atopic dermatitis skin (P < 0.0001) or non-lesional psoriatic skin. In contrast to the skin compartment, no differences in antiviral gene expression were detected in the peripheral blood of psoriasis cases compared to healthy controls. CD4+ T cells from both psoriatic and healthy patients supported HIV-1 infection at a similar rate.Conclusion
Our findings highlight psoriasis as an inflammatory disease with cutaneous but not systemic immune activation against viral pathogens.
Journal of the European Academy of Dermatology and Venereology 03/2015; 29(10). DOI:10.1111/jdv.13091 · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Basal cell carcinoma (BCC), the most common cancer in the United States, is primarily treated with local excision. In some cases, lesion size, location, or extent prevent complete resection. Locally advanced BCC responds to systemic therapy with the Hedgehog (Hh) pathway inhibitor vismodegib, but withdrawal of treatment may result in disease relapse. Here we present a case of locally advanced auricular BCC treated with induction vismodegib and radiation resulting in durable local control and an acceptable level of acute toxicity. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
British Journal of Dermatology 02/2015; 173(2). DOI:10.1111/bjd.13748 · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Fungal infections remain a substantial cause of mortality in lung transplant (LTx) recipients, yet no comprehensive consensus guidelines have been established for antifungal prophylaxis and treatment of Aspergillus infection in these patients.MethodsA cross-sectional study surveyed the directors from 27 of 64 (45.5%) active LTx centers in the United States to examine clinical practice variations in Aspergillus prophylaxis and treatment of colonization and invasive aspergillosis (IA) in LTx recipients.ResultsAntifungal prophylaxis increased from 52.3% in 2011 to 77.8% in 2013, with the most common agent being inhaled amphotericin B (61.9%), followed by oral voriconazole (51.9%). A total of 74.1% of centers treat Aspergillus airway colonization, with 80.0% of centers using oral voriconazole. All centers treat IA, with 92.6% using oral voriconazole. The duration of Aspergillus prophylaxis and treatment of colonization or IA varied widely across centers from 3 months to >1 year. A total of 51.9% of centers reported internal practice variations in the treatment of IA. Factors guiding treatment decisions included microbiologic culture and sensitivity (74.1%), ease of administration (59.3%), interaction with other medications (55.5%), side effect profile (51.8%), and center guidelines (48.1%). Although 85.2% of LTx centers recommended routine skin cancer screening for LTx recipients, only 44.4% of LTx centers reported having a dedicated transplant dermatologist.Conclusion
Most active US LTx centers currently employ antifungal prophylaxis and treat Aspergillus colonization and IA, although choice of agent, route of administration, and duration of therapy across and within centers continue to differ substantially. The number of transplant dermatologists available among US LTx centers is limited. Overall, a strong need exists for more comprehensive consensus guidelines to direct antifungal prophylaxis and treatment of Aspergillus infection in LTx recipients.
[Show abstract][Hide abstract] ABSTRACT: Background
Psoriasis is a multifactorial, chronic disease of skin affecting 2-3 % of the world¿s population. Genetic studies of psoriasis have identified a number of susceptibility genes that are involved in anti-viral immunity. Furthermore, physiological studies have also found an increase in anti-viral proteins in psoriatic skin. These findings suggest the presence of an anti-viral state in psoriatic skin. However, the triggers for this anti-viral cascade and its consequences for host immunity are not known. Endogenous retroviruses have previously been described in many autoimmune diseases including psoriasis.Methods
In the present study we examined the humoral immune response against human endogenous retrovirus-K (HERV-K) proteins and the cutaneous expression levels of multiple HERV-K genes in psoriasis patients and healthy controls.ResultsIn psoriatic sera we observed a significant decrease in IgM response against three HERV-K proteins: Env surface unit (SU), Env transmembrane protein (TM), and Gag capsid (CA) in comparison to sera obtained from blood bank healthy controls. A decrease in IgG response was also observed against CA. Furthermore, using quantitative RT-PCR we observed a decrease in the expression of HERV-K Env, Gag, Pol and Rec as well as ERV-9 genes in lesional psoriatic skin as compared to healthy skin.Conclusions
Together, our results suggest that the pro-inflammatory, anti-viral state in psoriasis is associated with diminished expression of HERV-K gene transcripts and a concomitant decrease in humoral responses to HERV-K. Our results indicate that a simple model where continuous, minimally changing HERV-K expression serves as an antigenic trigger in psoriasis might not be correct and further studies are needed to decipher the possible relationship between psoriasis and HERVs.
Journal of Translational Medicine 09/2014; 12(1):256. DOI:10.1186/s12967-014-0256-4 · 3.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nonmelanoma skin cancer (NMSC) is the most common cancer in the U.S.A. The two most common NMSCs are basal cell carcinoma and squamous cell carcinoma. The associations of single-nucleotide polymorphisms (SNPs) in pigmentation pathway genes with NMSC are not well characterized. There is a series of epidemiological studies that have tested these relationships, but there is no recent summary of these findings. To explain overarching trends, we undertook a systematic review of published studies. The summarized data support the concept that specific SNPs in the pigmentation pathway are of importance for the pathogenesis of NMSC. The SNPs with the most promising evidence include MC1R rs1805007(T) (Arg151Cys) and rs1805008(T) (Arg160Trp), and ASIP AH haplotype [rs4911414(T) and rs1015362(G)]. There are a few other SNPs found in TYR, OCA2 and SLC45A2 that may show additional correlation after future research. With additional research there is potential for the translation of future findings to the clinic in the form of SNP screenings, where patients at high risk for NMSC can be identified beyond their phenotype by genotypically screening for predisposing SNPs.
British Journal of Dermatology 09/2014; 171(4). DOI:10.1111/bjd.13283 · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin. Immunosuppression is associated with increased incidence of MCC. Objective: We sought to determine whether solid organ transplant recipients (SOTR) with MCC had decreased progression-free, disease-specific, and overall survival compared with immunocompetent patients. Methods: We conducted a retrospective cohort study examining 8 SOTR with MCC and 89 immunocompetent control subjects. Cox regression models were generated for outcomes of progression, disease-specific death, and death from any cause, adjusted for patient sex, age at diagnosis, and stage at presentation. Results: SOTR had a 4.1-fold increased hazard for progression (95% confidence interval 1.57-10.95, P = .004), a 10.5-fold increased hazard for all-cause mortality (95% confidence interval 3.06-35.98, P < .0001), and an 11.9-fold increased hazard for MCC-specific death (95% confidence interval 2.67-53.08, P = .001), adjusted for sex, age, and stage at presentation. SOTR had decreased 1-year overall survival, 46.8% versus 88.6%, and decreased 1-year MCC-specific survival, 56.3% versus 95.2%. Limitations: This is a single-center study from a tertiary academic care center, and may not be generalizable to all patient populations. Conclusions: SOTR have a significant reduction in overall, MCC-specific, and progression-free survival compared with immunocompetent patients. Further studies will determine whether aggressive treatment may improve outcomes in this high-risk population.
Journal of the American Academy of Dermatology 06/2014; 71(4). DOI:10.1016/j.jaad.2014.05.054 · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Fitzpatrick skin phototype (FSPT) is the most common method used to assess sunburn risk and is an independent predictor of skin cancer risk. Because of a conventional assumption that FSPT is predictable based on pigmentary phenotypes, physicians frequently estimate FSPT based on patient appearance. Objective: We sought to determine the degree to which self-reported race and pigmentary phenotypes are predictive of FSPT in a large, ethnically diverse population. Methods: A cross-sectional survey collected responses from 3386 individuals regarding self-reported FSPT, pigmentary phenotypes, race, age, and sex. Univariate and multivariate logistic regression analyses were performed to determine variables that significantly predict FSPT. Results: Race, sex, skin color, eye color, and hair color are significant but weak independent predictors of FSPT (P < .0001). A multivariate model constructed using all independent predictors of FSPT only accurately predicted FSPT to within 1 point on the Fitzpatrick scale with 92% accuracy (weighted kappa statistic 0.53). Limitations: Our study enriched for responses from ethnic minorities and does not fully represent the demographics of the US population. Conclusions: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by FSPT. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.
Journal of the American Academy of Dermatology 06/2014; 71(4). DOI:10.1016/j.jaad.2014.05.023 · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Targeted therapies for cutaneous squamous cell carcinoma (cSCC) remain limited. Extensive genetic heterogeneity complicates a robust molecular characterization of the evolution of cSCC. Nonetheless, potential targeted therapies for this cancer are under investigation, including the inhibition of epidermal growth factor receptor (EGFR), which may yield promising results. In addition, the emergence of immune checkpoint blockade therapy and vaccine-based methods may provide novel treatment strategies for cSCC that are tailored to the individual patient. Ultimately, a combination of such methods may yield a multi-pronged targeted approach to personalize the treatment of cSCC.
Seminars in Cutaneous Medicine and Surgery 06/2014; 33(2):72-75. DOI:10.12788/j.sder.0083 · 1.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Advanced basal cell carcinomas (BCC) are neoplasms with high-risk clinical characteristics that can develop as locally advanced disease or metastasis. Treatment of advanced BCC may result in significant morbidity due to the technical challenges of size and/or location or in which surgery and radiation therapy may be contraindicated. No standard of care exists for the management of advanced BCC. As such, the difficulty in managing these tumors necessitates a multidisciplinary approach to patient care.
We report four cases of advanced BCC that benefited from a multidisciplinary approach, as well as highlight treatment considerations and factors in the development of advanced BCC.
All four complex cases of advanced BCC presented to a multidisciplinary non-melanoma skin cancer tumor board with extensive tumor involvement. Treatment of disease was effective in preventing recurrence while optimizing aesthetic outcomes.
The multidisciplinary tumor board has a central and important role in the evaluation and management of advanced BCC.
J Drugs Dermatol. 2014;13(5):601-606.
Journal of drugs in dermatology: JDD 05/2014; 13(5):601-6. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The role of human papillomavirus (HPV) in cutaneous squamous cell carcinoma (cuSCC) is not well defined, with past studies showing conflicting results.
We sought to determine if there is a significant association between HPV and cuSCC and whether cuSCC from immunosuppressed patients are more likely to carry HPV than cuSCC from immunocompetent patients.
We performed a systematic review and abstracted data from articles that included: skin samples by biopsy, HPV detection by polymerase chain reaction, and a minimum of 10 cases and 10 controls. Pooled effect size and 95% confidence intervals were calculated using random effects meta-analysis using the inverse variance method.
cuSCC were more likely to carry HPV than normal-appearing skin (pooled effect size [ES] 3.43, 95% confidence interval 1.97-5.98, P < .0001) in all patients. An increase in HPV prevalence was found in tumors from immunosuppressed patients compared with immunocompetent patients (pooled ES 3.01, 95% confidence interval 2.00-4.52, P < .0001).
The greatest limitation is the heterogeneity of the studies included. The association of higher HPV prevalence in squamous cell carcinoma compared with normal-appearing skin does not imply causality.
These results contribute to evidence that HPV is associated with cuSCC. Higher HPV burden in tumors from immunosuppressed patients compared with immunocompetent patients may have therapeutic implications.
Journal of the American Academy of Dermatology 04/2014; 70(4):621–629. DOI:10.1016/j.jaad.2014.01.857 · 4.45 Impact Factor