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Dermatology Online Journal is an open-access, refereed publication intended to meet reference and education needs of the international dermatology community since 1995. Dermatology Online Journal is supported by the Department of Dermatology UC Davis, and by the Northern California Veterans Administration.

Volume 22, Issue 9, 2016

Review

The history of open access medical publishing: a comprehensive review

Dermatology Online Journal became the first medical open access journal in the early 1990’s. Today, thousands of open access medical journals are available on the Internet. Despite criticisms surrounding open access, these journals have allowed research to be rapidly available to the public. In addition, open access journal policies allow public health research to reach developing countries where this research has the potential to make a substantial impact. In the future, open access medical journals will likely continue to evolve with technology, changing how medical research is accessed and presented.

Psoriasis in Latin America

During the last few decades, management of psoriasis has changed worldwide, owing to a better understanding of its pathophysiology and the introduction of new treatments. As experts in the field of dermatology, specialists from Latin America collaborated to develop this review and further provide an update on the current state of psoriasis management in Latin America. With the goal of summarizing the latest information on psoriasis in most countries in Latin America, we conducted a literature search to obtain relevant articles published in the medical/scientific literature in Latin American countries over the last 10 years; in addition, we completed a questionnaire comprised of 20 questions on important issues related to psoriasis. The aim of this final document isto help improve understanding and management of the disease and to help patients gain better access to new approaches and medical solutions.

Clinical applications of topical ivermectin in dermatology

Ivermectin (IVM) is a broad-spectrum anti-parasitic drug with significant anti-inflammatory properties. The emergence of treatment resistance to lindane, permethrin, and possibly malathion complicates the global strategy for management of common parasitic skin diseases such as scabies and head lice. In this regard. IVM has been safely and effectively used in the treatment of these common human infestations. In addition, IVM may be useful in inflammatory cutaneous disorders such as papulopustular rosacea where demodex may play a role in pathogenesis. Herein, we review the current applications of topical IVM in dermatology.

Case Report

Multiple mucocutaneous ulcers associated with cocaine-induced midline destructive lesions

Cocaine-induced midline destructive lesions (CIMDL) occur in a small subset of cocaine users, who clinically present with inflammation and necrosis of facial midline structures such as the palate, nasal septum, turbinates, and sinuses. We present a patient with CIMDL occurring concomitantly with ulcers on the cheek and upper trunk. Multiple biopsy specimens from the cutaneous and mucosal lesions consistently showed a dense dermal/submucosal infiltrate of neutrophils and plasma cells, without vasculitis or thrombosis. The ulcers resolved following cessation of cocaine use.

Atypical lymphoproliferative disorder-clinical and pathological features

Definitive diagnosis of cutaneous lymphoproliferative disorders is one of the most challenging issues in dermatopathology owing to the broad spectrum of clinical and histopathological presentations. We report a case of a 73-year-old woman who presented with a single, asymptomatic plaque limited to her left collarbone. This was followed by the appearance of several plaques and patches in addition to a tumor. Her initial biopsy suggested a CD4/CD8 double negative mycosis fungoides (MF). However, the rapidly progressive course of her disease is worrisome for peripheral T-cell lymphomas-not otherwise specified (PTCL-NOS). Subsequent biopsies revealed epidermal spongiosis with subepidermal edema and possible nodal involvement by cutaneous T-cell lymphoma. The rare combination of these pathologic features demonstrates the difficulty of diagnosing atypical lymphoproliferative disorders.

Case Presentation

Microcystic Adnexal Carcinoma of the scalp in an african-american male

Microcystic adnexal carcinoma (MAC) is a rare adnexal neoplasm that typically presents in Caucasians. We report a rare case of MAC in a 68 year old African American male that presented as a large asymptomatic scalp mass. The clinical and histologic features of MAC are discussed. A summary of all reported cases of MAC in African American patients is presented, and treatment options are discussed.

Generalized woolly hair with diventricular arrythmogenic cardiomyopathy: a rare variant of Naxos disease

Woolly hair may occur as an isolated problem of cosmetic concern or can be a part of a systemic disease (woolly hair syndrome) with underlying fatal cardiomyopathy. Two characteristic associations of woolly hair syndrome are Naxos disease and Carvajal syndrome. Naxos disease is characterized by woolly hair, palmoplantar keratoderma, and arrythmogenic right ventricular cardiomyopathy.In this report we describe a case of a young girl who presented with heart failure and was subsequently diagnosed as a case of generalized woolly hair with biventricular arrythmogenic cardiomyopathy.Our case represented a rare variant of Naxos disease in the advanced stage of arrythmogenic right ventricular cardiomyopathy; biventricular failure may occur with involvement of the interventricular septum and left ventricle causing congestive heart failure.

Terapêutica Fotodinâmica com metil-aminolevulinato no tratamento de lesões refractárias de Micose Fungóide: resposta clínica e histológica mantida em dois doentes

According to the guidelines proposed by the National Comprehensive Cancer Network, early-stage Mycosis Fungoides (MF) should be treated with skin-directed therapies such as topical steroids or retinoids, topical chemotherapy (carmustin and nitrogen mustard), photochemotherapy, and superficial radiotherapy. Patients with refractory lesions to these therapeutic options are particularly challenging. Photodynamic Therapy (PDT) has been approved to treat cutaneous neoplastic and pre-neoplastic lesions such as superficial basal cell carcinoma, Bowen disease and actinic keratosis. Recently, several small studies have demonstrated the efficacy of PDT with methyl-aminolaevulinate (MAL) in the treatment of early-stage MF. We report two patients diagnosed with IA and IB MF, previously treated with conventional treatments (topical steroids and photochemotherapy) with short-term recurrence that were treated with PDT with MAL with complete and maintained response for one year. Our findings confirm that PDT with MAL can be one more palliative option in the treatment of early-stage MF, especially in pauci-lesional disease or in lesions resistant or inaccessible to conventional therapies.

Aquagenic wrinkling of the palms: a case report and literature review

Aquagenic wrinkling of the palms (AWP) is an unusual and rare dermatological condition characterized by excessive palmar wrinkling, occurring within a few minutes of water exposure. Cystic fibrosis (CF) or CF carrier state associated forms, drug induced cases, and idiopathic forms have been described. We report the case of a 27-year-old woman with a 7-year history of transient excessive wrinkling of her palms after brief exposure to water. We present also a comprehensive review of the literature. We believe that AWP has been underdiagnosed thus far and we would like to encourage investigations such as sweat chloride test or genetic studies in these patients because of the association with CF or CF carrier state, particularly when AWP appears in younger ages.

Elastólisis de la dermis media diseminada

Mid-dermal elastolylis (MDE) is an uncommon skin disorder characterized by a loss of elastic fibers in the mid dermis. The pathogenesis of MDE still remains unclear. This entity usually affects the neck, trunk, and upper extremities. Three clinical patterns have been described: patches of fine wrinkles, perifollicular papular protusions, and persistent reticular erythema. We report a patient with disseminated MDE.

Dyschromatosis universalis hereditaria: report of six cases from a family

Dyschromatosis universalis hereditaria (DUH) is a rare pigmentary disorder characterized by the presence of mottled hyperpigmented and hypopigmented macules over the trunk, extremities, and face. We have presented a case series comprised of six members of a family who had numerous hyperpigmented and hypopigmented macules distributed all over the body. Histological findings were suggestive of dyschromatosis universalis hereditaria.

Necrolytic migratory erythema associated with fatty liver disease and the psuedoglucagonoma syndrome

We report a 48-year-old woman with a past medical history of psoriasis, nonalcoholic steatohepatitis (NASH), and type II diabetes mellitus, who presented to the emergency department with a 1 week history of erosive annular plaques with associated atrophy and telangiectasias on her legs bilaterally, thighs and buttock, histopathologically consistent with necrolytic migratory erythema. Although classically associated with a pancreatic glucagonoma, this patient experienced this figurate erythema in the setting of fatty liver disease with no glucagonoma. The rarity of pseudoglucagonoma syndrome, or necrolytic migratory erythema occurring in the absence of a glucagonoma, warranted the discussion of this case.

Photo Vignette

A chronic, bleeding, and painful nodule on the chest

An 81-year-old man presented to the dermatology clinic with a painful lesion on his chest. The nodule would occasionally bleed and leak serous fluid for 10 years. Physical examination revealed an unspecified nodule with two superimposed nodules. A deep shave biopsy of the lesion was obtained and expressed a solid-cystic dermal neoplasm that was comprised of an admixture of cell types. Through the presenting clinical and histological features seen, a final diagnosis of nodular hidradenoma was made.

Extensive unilateral nevus comedonicus without genetic abnormality

Nevus comedonicus is considered a genodermatosis characterized by the presence of multiple groups of dilated pilosebaceous orifices filled with black keratin plugs, with sharply unilateral distribution mostly on the face, neck, trunk, upper arms. Lesions can appear at any age, frequently before the age of 10 years, but they are usually present at birth. We present a 2.7-year-old girl with a very severe form of nevus comedonicus. She exhibited lesions located initially at the left side of the body with a linear characteristic, following Blascko lines T1/T2, T5, T7, S1 /S2, but progressively developed lesions on the right side of the scalp and left gluteal area.

Oral focal mucinosis: review of the literature and two case reports

Oral focal mucinosis is a rare condition, clinically characterized by an asymptomatic swelling, without distinct, specific features, which occurs predominantly in adults of the female gender. Its clinical aspect leads to various differential diagnoses, and final diagnosis is only possible by means of histopathological exam, in which a well-delimited myxomatous area containing mucinous material is observed. In the present study, a review of the English-language literature about the lesion, was conducted, covering the period from 1974 to March 2015. We report two new cases, thereby contributing to the knowledge and differential diagnosis of this entity.

Letter

Bitemporal hair loss related to traction alopecia

We present a 24-year-old woman that had received a diagnosis of alopecia areata in the past and was treated with topical 19 corticosteroids with little improvement. Instead, the patient exhibited bitemporal alopecia of one year of evolution related to 20 traction alopecia. Traction alopecia is characterized by localized hair loss related to persistent excessive traction. Although it is 21 initially a reversible condition, if this excessive traction is not removed permanent alopecia may develop.

Acitretin amelioration of Acrokeratosis Paraneoplastica (Bazex Syndrome) in cases of incurable squamous cell carcinoma of the hypopharynx

BACKGROUNDAcrokeratosis paraneoplastica (Bazex Syndrome) is a rare paraneoplastic syndrome and dermatosis that only arises in patients with underlying malignancy and uncommonly resolves with systemic therapy.OBJECTIVE/METHODSWe present a patient with acrokeratosis paraneoplastica that improved significantly with acitretin. We present evidence to justify costs of therapy for insurance purposes. Additionally, there is a single report of acitretin use for Bazex syndrome in the French language.RESULTSWe present a case of acrokeratosis paraneoplastica in a patient with incurable stage IV squamous cell carcinoma of the hypopharynx that significantly improved on acitretin.CONCLUSIONAlthough acrokeratosis paraneoplastica most often is cured by treatment of the underlying squamous cell carcinoma, this case highlights the potential benefit of early initiation of acitretin during malignancy work up and staging. This therapy may also be valuable for patients in which the primary malignancy is unresectable or incurable.

Facial pigmentation with demodex Mite; a mere coincidence or an association?

Demodex mites may induce inflammatory cutaneous reactions such as papulopustular rosacea and demodex folliculitis; both may lead to post inflammatory pigmentation. A 59-year-old man presented with an asymptomatic, hyperpigmented plaque on his face. Histological and clinical findings displayed Riehl-like facial pigmentation. Multiple demodex mites at the follicular infundibulum in the biopsy material were remarkable. There are limited publications about demodex-associated pigmentation. We report this case to point out that various hyperpigmentation disorders may occur simultaneously with demodex mites.

Hypothyroidism in Patients with Psoriasis or Rosacea: A Large Population Study

Hypothyroidism is a common disease, and there may be a link between hypothyroidism and inflammatory skin disease. The purpose of this study is to assess whether hypothyroidism is more prevalent in psoriasis or rosacea patients. We utilized a large claims-based database to analyze rates of hypothyroidism in patients with psoriasis and rosacea compared to other patients with skin diseases. Participants were patients between 20-64 years of age with ICD-9 diagnosis codes for psoriasis, rosacea, and hypothyroidism. We found that rates of hypothyroidism in rosacea and psoriasis patients were similar to rates of hypothyroidism in those without rosacea or psoriasis.

Oral ponesimod for psoriasis compared to other investigational therapies

Oral ponesimod is a new therapy for the treatment of moderate-to-severe plaque psoriasis. Vaclavkova et al conducted a phase 2 trial that demonstrated moderate efficacy of ponesimod in the treatment of psoriasis. Here we discuss various biologic agents with alternative mechanisms of action, that have demonstrated superior efficacy in psoriasis, and call into question the risks versus benefits of ponesimod therapy.

Abstracts from the 7th Int. Dermato-Epidemiology Assoc. (IDEA) Congress/2nd Keratinocyte Carcinoma Consortium (KeraCon)

Actinic keratoses progress more quickly to squamous cell carcinoma than basal cell carcinoma

Actinic keratoses (AK) are common, costly, and may evolve to keratinocyte carcinoma (KC): basal cell (BCC) and squamous cell carcinoma (SCC) of the skin. Time to malignant transformation is controversial. We used data from the placebo arm (n=166) of a randomized trial of veterans with multiple prior KCs. Study dermatologists examined participants’ faces/ears at enrollment and semiannual visits. Clinically diagnosed AKs were marked, photographed, and treated with cryotherapy (starting at 6 months). Lesions suspicious for KC were marked, photographed, and biopsied. AKs were tracked using these photographs. For each AK that progressed to KC (n=23), the time between the first appearance of the AK and the biopsy resulting in a KC diagnosis was measured. Among all 4,231 tracked AKs, the difference in time to progression of AKs that progressed to BCC (12/4,231) vs. SCC (11/4,231) was not statistically detectable (Cox proportional hazards analysis). However, among the 23 AKs that progressed to KC, AKs progressed more quickly to SCC compared to BCC (two-sided Wilcoxon test; p=0.01) with respective mean progression times of 13 and 25 months. This may be due to clinical misdiagnosis of early BCCs as AKs, as BCCs are known to grow slowly; or perhaps SCCs become more rapidly clinically distinguishable. Differences in progression could also indicate differences in sensitivity to cryotherapy, as lesions progressed despite this treatment. Alternatively, if these were true AKs, then certain events—with different likelihoods and timing—may be needed for AKs to progress to BCC vs. SCC.

Advanced basal cell carcinomas appear preferentially on the scalp of patients with Basal Cell Carcinoma Nevus Syndrome

Basal Cell Carcinoma Nevus Syndrome is a rare condition in which patients need to meet certain major or minor diagnostic criteria or test positive for chromosome 9 or PTCH1 mutations to be diagnosed. The results of an internet based survey of self-identified adults with BCCNS which was launched through SurveyMonkey with access provided by the Basal Cell Carcinoma Nevus Syndrome Life Support Network (www.BCCNS.org). Of 45 respondents, 11 individuals reported having locally advanced BCCs and 6 individuals reported having both locally advanced and metastatic BCCs. Of the 11 individuals with locally advanced BCCs, 8 reported having lesions on the scalp. Of the 6 patients with locally advanced BCCs, 3 reported having abnormally thick hair distribution. There were 6 individuals with both locally advanced and metastatic BCCs and 5 reported having BCCs on their scalp. Thick hair distribution was reported by 3 of 4 patients with locally advanced and metastatic BCCs. Overall, it was determined that patients with BCCNS develop aggressive BCCs on their scalp despite thick hair distribution. Patients with BCCNS have an overactive hedgehog signaling pathway. This pathway is also known to play a role in follicle cycling and is believed to lead to increased rates of malignancy.1,2 Despite the presence of thick hair, patients with BCCNS should have their scalp skin closely examined to identify and treat BCCs at early stages of development.

Associations between indoor tanning and risky health-related behaviors among high school students in the United States

Understanding of the associations between indoor tanning and risky health related behaviors such as sexual activity and substance abuse among adolescents across the United States is incomplete. The purpose of this study is to identify risky health related behaviors among high school students utilizing indoor tanning according to region. We analyzed the results from surveys of adolescents in 14 different states administered as part of the Youth Risk Behavior Surveillance System (YRBSS) 2013. Data were collected and analyzed over a 4-month period from January 2016 to April 2016. Participants were 90,414 high school students. Sexual activity and use of substances including tobacco, alcohol, marijuana, cocaine, ecstasy, steroids, and prescription drugs was assessed.Our data indicate that females were more likely than males to utilize indoor tanning. Multivariate analysis identified sexual activity in the past 30 days as a variable strongly associated with indoor tanning in Nebraska (adjusted odds ratio, 3.8; 95% CI, 2.4-6.2; p<0.001), South Dakota (adjusted odds ratio, 3.0; 95% CI, 1.8-5.1; p<0.0001), Maryland (adjusted odds ratio, 2.4; 95% CI, 2.1-2.8; p<0.0001), Alabama (adjusted odds ratio, 2.2; 95% CI, 1.4-3.3; p<0.0001), Florida (adjusted odds ratio, 2.2; 95% CI, 1.6-3.1; p<0.0001), Idaho (adjusted odds ratio, 2.2; 95% CI 1.4-3.2; p<0.0001), Colorado (adjusted odds ratio, 2.1; 95% CI 1.5-3.1; p<0.0001), Montana (adjusted odds ratio, 2.0; 95% CI, 1.5-2.6; p<0.0001), North Carolina (adjusted odds ratio, 1.8; 95% CI, 1.0-3.3; p=0.04), and Wisconsin (adjusted odds ratio, 1.7; 95% CI, 1.0-3.0; p=0.04). A weak association was seen in Ohio (adjusted odds ratio, 1.2; 95% CI 0.7-2.0; p=0.58), and three states did not report this data. In Colorado, students were 7.5 times more likely to use steroids (adjusted odds ratio, 7.5; 95% CI, 4.7-11.9; p<0.0001) if they also participated in indoor tanning. Any alcohol consumption within the prior 30 days was also associated with indoor tanning with the greatest association in North Dakota (adjusted odds ratio, 3.3; 95% CI, 2.4-4.6; p<0.0001). Multivariate analysis identified marijuana use in the past 30 days as a variable associated with indoor tanning with the strongest association in New Hampshire (adjusted odds ratio, 2.3; 95% CI, 1.4-3.9; p=0.0011). Associations were also found between indoor tanning and use of ecstasy, cocaine, prescription medications, and a history of smoking cigarettes in the past month.When present, use of indoor tanning should raise clinical concern that warrants further screening for substance abuse and counseling of safe sex practices.

Association of atopic dermatitis with tobacco smoke exposure: a systematic review and meta- analysis

Previous studies found conflicting results about whether exposure to tobacco smoke is associated with increased atopic dermatitis (AD). We examined this association by systematic review and meta-analysis of MEDLINE, EMBASE, Scopus, and Cochrane Library and identified 86 studies, including 680,176 patients from 39 countries. A meta-analysis was performed using random-effects models to estimate pooled odds ratios (OR). Subset analyses were performed for different ages (children or adult), regions, study designs (cross-sectional vs. longitudinal), sizes (<5,000 or ≥5,000) and quality (Newcastle-Ottawa Score [NOS] <6 or ≥6), and amount of smoking (mild or extensive). Overall, 17,969 (12.9% [range 1.2–50.0%]) were active smokers, 33,200 (15.3% [range 0.9–56.8%]) were passively exposed to tobacco smoke in the home and 14,004 (15.4% [range 2.3–34.4%]) of children born to mothers who smoked during pregnancy, respectively, had a previous and/or current history of AD. Atopic dermatitis was associated with higher odds of active smoking (random-effects OR [95% CI]: 1.87 [1.32–2.63]) and exposure to passive smoke (1.18 [1.01–1.38]), but not maternal smoking during pregnancy (1.06 [0.80–1.40]). In sensitivity analyses, the association between active smoking and AD remained significant in children and adults, in all continents studied and study sizes, but all studies were cross-sectional designs and had a NOS score ≥6. Exposure to passive smoke was associated with AD in children and adults, cross-sectional studies, South/Central American and African studies, study size <5,000 and NOS <6. This study demonstrates that active smoking and passive exposure to smoke are associated with increased AD prevalence.

Attitudes and predictors of sunless tanning in a sample of young adults

Given the popularity of a tan appearance, sunless tanning may play a role in skin cancer prevention as a substitute for ultraviolet (UV) tanning. Few studies have comprehensively assessed attitudes toward sunless tanning or predictors of use.Demographic, phenotypic, and lifestyle characteristics were ascertained during in-person interviews of 385 non-Hispanic whites (75 sessions vs no indoor tanning OR=3.30, 95% CI=1.52-7.16), a tendency to burn with first summer sun exposure (OR=1.89, 95% CI=1.03-3.47), higher public body consciousness (OR=1.09, 95%CI=1.02-1.18), and believing sunless tanning was useful for tanning when weather is not optimal for sunbathing (OR=5.08, 95% CI=2.11-12.22).Results suggest young adults find sunless tanning to be an acceptable method of achieving a tanned appearance. Sunless tanning may prove useful in reducing UV exposure, particularly among females who engage in sunbathing or indoor tanning.

Basal Cell Carcinoma Nevus Syndrome: Population of patients negative for Chromosome 9 mutations

Patients with Basal Cell Carcinoma Nevus syndrome are assumed to have a chromosome 9 mutation, such as a PTCH1 [9q22] mutation, despite the majority of patients with BCCNS being diagnosed through the presence of major and minor diagnostic criterion. The main treatment for BCCNS, Hedgehog inhibitors (HhI), targets these mutations. The results of an internet based survey of self-identified adults with BCCNS which was launched through SurveyMonkey with access provided by the Basal Cell Carcinoma Nevus Syndrome Life Support Network (www.BCCNS.org). Of a total of 395 participants, 282 and 289 individuals responded to questions regarding PTCH1 and chromosome 9 genetic testing, respectively. Those who reported having been genetically tested for either PTCH1 and/or chromosome 9 mutations, were limited to 14-28 % of all BCCNS patient respondents. Of those genetically tested, 12% reported they were negative for PTCH1 and 11% were negative for chromosome 9 mutations. Biogenetic pathway testing needs to be performed on a higher percentage of phenotypical BCCNS patients and the results correlated with HhI treatment responses. These results suggest the need to recognize that phenotypical BCCNS consists of multiple subpopulations of patients with differing biogenetic signaling mutations making current treatment less than adequate for phenotypical BCCNS individuals.

Body mass index, height and early-onset basal cell carcinoma in a case-control study

BackgroundBasal cell carcinoma (BCC) is the most common malignancy in the US. Body mass index (BMI) and height have been associated with a variety of cancer types, yet the evidence regarding BCC is limited. Therefore, we evaluated BMI and height in relation to early- onset BCC and explored the potential role of ultraviolet (UV) radiation exposure as well as estrogen-related exposures in the BMI-BCC relationship.MethodsBCC cases (n=377) diagnosed under age 40 were identified through a central dermatopathology facility in Connecticut. Control subjects (n=389) were randomly sampled from the same database and frequency matched to cases on age, gender, and biopsy site. Participants reported weight (usual adult and at age 18), adult height, sociodemographic, phenotypic, and medical characteristics, and prior UV exposures. We calculated multivariate odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models.ResultsAdult BMI was inversely associated with early-onset BCC (obese vs. normal OR=0.43, 95% CI=0.26-0.71). A similar inverse association was present for BMI at age 18 (OR=0.54, 95% CI=0.34-0.85). Excluding UV exposures from the BMI models and including estrogen-related exposures among females only did not alter the association between BMI and BCC, indicating limited mediation or confounding. We did not observe an association between adult height and BCC (OR per cm=1.00, 95% CI=0.98-1.02).ConclusionWe found a significant inverse association between BMI and early-onset BCC, but no association between height and BCC. This association was not explained by UV exposures in this population or estrogen-related exposures among only the females

The burden of keratinocyte cancer: occurrence, multiplicity and predicting risk

The costs of diagnosing and treating basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) are the highest of all cancers in Australia. However, information regarding incidence, multiplicity and risk are scarce as keratinocyte cancers (KCs) are not captured by most registries. To address these gaps, we initiated the QSKIN Study in 2010 recruiting 43,794 Queensland residents from a population register (participation 24%). Participants self-completed a baseline survey recording information on residential history, sun exposure, phenotype and medical and family history. We identified keratinocyte cancers through linkage to the national insurance register, confirming histopathology where possible. During the first three years of follow-up, 6936 (17%) participants had at least one KC excised; 1626 (4%) had 3 or more excisions. Of lesions with known histology, there were 9713 BCCs (in 4080 people) and 3505 SCCs (in 1782 people). We developed a tool to predict the risk of developing KC using backwards stepwise logistic regression models. The primary model retained terms for 10 items, including history of >20 prior skin cancers excised (OR 8.6), >50 skin lesions destroyed (OR 3.4), age >70 years (OR 3.5) and fair skin color (OR 1.8). Discrimination was high (Area under ROC 0.80, 95%CI 0.79-0.81) and the model appeared well calibrated. Among those reporting no prior history of skin cancer, a model with 10 factors (including age, sex, ethnicity and phenotypic factors) predicted KC events with reasonable discrimination (AUROC 0.72, 95% CI 0.70-0.75). The tool is undergoing external validation in primary care skin cancer clinics.

Cigarette smoking and the risks of incident basal cell carcinoma and squamous cell carcinoma in a large population-based cohort study

Tobacco smoking is a strong risk factor for cancer, but associations with basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) of the skin have been inconsistent. We prospectively investigated the associations between cigarette smoking and 3-year incidence of first primary BCC or SCC in the QSkin cohort (n=43765). Smoking history was self-reported at baseline; newly diagnosed and surgically treated BCCs and SCCs were ascertained through linkage to the national health insurance scheme and verified by histopathology reports. We restricted our analyses to white participants who at baseline reported no past history of skin cancer excisions or cutaneous melanoma (registry-confirmed) and no more than 5 destructively-treated skin lesions (n=18830). Cox proportional hazards regression analysis was used to examine the association between smoking status and risk of BCC and SCC, adjusted for demographic and phenotypic characteristics and sun exposure history. Current smokers had significantly lower risks of BCC (HR 0.6; 95% CI, 0.4-0.9) but significantly increased risks of SCC (HR 1.9; 95% CI, 1.1-3.1) compared with never smokers. Former smoking was not associated. In analyses restricted to people with no past history of destructively-treated lesions (n=13323), we found a non-significant decreased risk of BCC (HR 0.8; 95% CI, 0.5-1.3) and a significant increased risk of SCC (HR 2.3; 95% CI, 1.3-4.4) among current smokers compared to never smokers. Future analyses will investigate associations with age at initiation, duration and intensity of smoking, and time since quitting. These findings suggest current smoking is a risk factor for cutaneous SCC but not BCC.

Comorbidities of Hospitalized Pemphigus Patients in the United States

We sought to determine the comorbid health conditions and inpatient mortality associated with pemphigus in a U.S. inpatient cohort. The 2002-2012 Nationwide Inpatient Sample, which contains a representative 20% stratified sample of all inpatient hospitalizations in the US, was analyzed. Comorbidities were determined through ICD-9-CM codes. Survey weighted multivariate logistic regression models controlling for demographic factors were constructed to determine the association of pemphigus with various comorbidities. Multivariate logistic regression models controlling for socio- demographic factors were constructed to determine predictors of mortality.Of 87,039,711 hospital discharges captured in the NIS between 2002-2012, there were 1,185 and 5,221 admissions with a primary or secondary diagnosis of pemphigus. The comorbid health conditions most strongly associated with pemphigus were Cushing syndrome (17.23 [2.41-122.90]), adrenal insufficiency (4.08 [1.71-9.73]), myasthenia gravis (6.92 [2.55-18.79]), fungal infections (4.03 [3.60-4.52]), insomnia (18.02 [2.46-131.88]), leukemia (1.56 [1.08-2.24]), non-Hodgkin’s lymphoma (1.52 [1.15-2.03]), and diabetes mellitus (1.30 [1.20-1.40]). Mean mortality for patients with a primary or secondary diagnosis of pemphigus was 1.70% [1.29-1.91] and 3.20% [2.71-3.69], respectively, while patients without a diagnosis of pemphigus had a mean mortality of 1.78% [1.78-1.78]. Predictors of mortality included Asian race, Medicare or Medicaid insurance status, and increasing number of chronic conditions. The present study found significantly higher odds of comorbidities in US children and adults with pemphigus, including infections, autoimmune, malignancy, cardiovascular and endocrine disorders. Patients with pemphigus have higher rates of mortality and necessitate meticulous care given the associations with a wide array of comorbid health conditions.

Comparing survival of patients with single or multiple primary melanoma in The Netherlands: 1994- 2009

There is conflicting literature as to whether the survival of patients with multiple melanoma is worse that this of single melanoma cases. We used extended Cox-proportional hazard models to estimate hazard-ratios (HR) of patients with multiple melanomas against single melanomas. Data from the nationwide Dutch Cancer Registry was used to retrieve cutaneous melanoma cases between 1994 and 2009 and linked with municipal records to assess the vital status. To account for the longer survival in the multiple melanoma cases we modelled multiple melanoma as time-varying variable, as well as Breslow thickness, histological subtype and nodal/distant metastasis. In total, 42,733 melanoma cases were identified, of which 1210 (3%) developed a new primary melanoma during a total follow-up of 11 years. The adjusted HR for multiple melanoma was 1.32 (95 %CI: 1.17-1.50) adjusting for age, sex, Breslow thickness, histological subtype and presence of nodal and distant metastasis . Our study showed that patients with multiple melanomas have an increased risk of dying when compared with single melanoma cases, and suggests that the improved survival of patients with multiple melanoma shown in previous studies was an artefact due to survival bias. Based on our findings we advise, within the guideline of five years of follow-up, to focus on high-quality patient-education about skin self-examination and the risks of subsequent melanomas.

Compliance with indoor tanning laws for minors among salons and business in the United States

Indoor tanning is an established risk factor for skin cancer, yet indoor tanning is quite common among adolescents. Laws exists in some states to limit access to indoor tanning by minors, but there is limited research on industry compliance with these laws.

We conducted a telephone survey with a random sample of businesses (n=412) offering indoor tanning in the 14 states with indoor tanning bans for minors as of May 2015. Female research assistants posing as minors conducted telephone interviews with employees using a standardized script.

The majority of businesses (73.5%) told the minor caller that she could not use the tanning facilities. However, 12.6% told her she could tan and 13.9% gave other inaccurate information related to parental permission. Among the businesses (n=368) that completed the full interview, when asked about dangers from indoor tanning 52.2% identified burning and 20.1% mentioned skin cancer. However, 21.7% said dangers were no worse than the sun, 11.4% said the booths in their business were safer than others, and 10.3% said there were no dangers. Many businesses stated benefits when asked, including vitamin D (27.7%), social/cosmetic (27.2%), and treatment of skin diseases (26.4%), with only 4.9% indicating no health benefits.

While three-quarters of businesses followed the indoor tanning bans when a minor called, one- quarter were noncompliant. Many of the businesses made inaccurate health claims about indoor tanning. Additional enforcement may be necessary to increase compliance and other regulations are needed to penalize businesses from stating health benefits and presenting false risk information.

Correlation between cancer incidences and Google searches in the United States

IntroductionDespite being highly prevalent, keratinocyte carcinomas (basal cell and squamous cell carcinomas lack nationwide registries. Internet search data has emerged as a new method to evaluate previously difficult to quantify public health outcomes and may be useful in keratinocyte carcinoma research.

ObjectiveWe aimed to evaluate whether Google search density correlated with known incidences of common cancers in the United States.

MethodsWe used the Center for Disease Control’s National Program of Cancer Registries ageTadjusted cancer incidences (2008T2012 . We collected Google search data, normalized for total search volume, using Google trends (google.com/trends . We collected data on the ten most incident cancers in the United States: lung, breast, colon, prostate, melanoma, endometrial, bladder, thyroid, NonTHodgkin’s lymphoma, kidney/renal pelvis. We utilized Pearson’s correlation coefficient to evaluate the relationship between known cancer incidence and Google search density by state.

ResultsFour cancers (endometrial, bladder, thyroid, kidney/renal pelvis had insufficient Google search quantity among individual states to be evaluated. Lung cancer (R2=0.70, p<0.001 , colon cancer (R2=0.60, p<0.001 , melanoma (R2=0.42, p=0.002 , and NonTHodgkin’s lymphoma (R2=0.47, p=0.006 had statistically significant correlations between actual incidences and Google searches. Breast and prostate cancer incidences were not correlated (p>0.05 .

DiscussionFour of the six highly incident cancers evaluated had statistically significant correlations between known incidence and Google search density. Internet search data may be a novel tool to estimate geographical incidence and prevalence of disease. This methodology may be particularly useful for keratinocyte carcinomas, which currently lack nationwide registries

Dermatological screening of an elderly population: the Rotterdam Study

BackgroundThe recent WHO burden of disease project showed that the non-fatal skin disease related burden is high, but also that prevalence rates of many common skin diseases are not well documented. The aim of this study is to give an overview of (untreated) skin diseases in a population based sample of elderly.

MethodsIn 2010, a full body skin examination (FBSE) was embedded in the Rotterdam Study, a prospective population based cohort study of an elderly white-skinned population in the Netherlands. The examination was conducted by a dermatology-trained physician and focused on most common skin diseases (e.g. skin (pre)malignancies, eczema, psoriasis, seborrheic dermatitis, varicose veins). Age- and sex-adjusted standardized prevalence rates (PR) were calculated per 100,000 persons aged 50 years or older, standardized to the World Standard Population 2000.

ResultsIn total, 5,365 participants with a median age of 67.2 (range: 52-99) were examined and 2,462 had a skin condition (45.9%, PR male: 48,519/100,000, female: 33,442/100,000), including 218 (4.1%) participants with one or more cutaneous malignancies (BCC: 136, SCC: 10, melanoma: 8, mycosis fungoides: 1, without histological confirmation: 63), 1,399 (26.1%) with (multiple) actinic keratosis, 411 (7.7%) with eczema, 175 (3.3%) with psoriasis and 713 (13.3%) with seborrheic dermatitis. Several differences were found between men and woman, e.g. in cutaneous malignancies (PR male: 4,305/100,000, female: 2,825/100,000) and actinic keratosis (PR male: 23,338/100,000, female: 13,610/100,000). In addition to skin diseases, 1466 (27.3%) participants had clinical varicose veins.

ConclusionDuring FBSE of this elderly population , a high proportion of elderly had a skin diagnosis.

Developing a continuous quality improvement assessment using a patient-centered approach in optimizing SLE disease control.

Systemic lupus erythematous is a multi-organ autoimmune disease in which the patient has “lost” self- tolerance and developed immune-complexes containing self-antigen that cause disease through tissue inflammation and multi-organ damage. Patients often have unpredictable flares in symptoms with poorly identified triggers. However, it has been suggested in other literature that exogenous exposures, including ingested beef, cigarette smoke, UV radiation, metal-complexing agents, and infections can contribute to exacerbations and improvements in SLE symptoms. New continuous quality improvement assessment survey platform will be develop and utilized to reach out to SLE patients across the globe. This new platform will allow participants to log in and out of the survey enabling them to address 20-50 pages of questions at baseline as well as to edit this delving into the minutia of the activities of daily living as well as lifestyle, diet, and exposures. These exposures can be helpful or harmful to SLE patients. Patients will be asked to update survey responses monthly to capture changes in lifestyle and health as data points over time. Statistical analysis array using complex adaptive systems methodology will be performed on de- identified patient surveys in order to determine if patterns exist in subgroups of SLE patients who experience fluctuations in their disease state over time. Feedback will be given to patients who are then able to adapt accordingly while they participate in the study. Interpretations of this data will then be used to identify which exogenous exposures influence SLE symptoms in specific subgroups of SLE patients. This information will then be used to make improvements in treatment plans for systemic lupus erythematous, and will ultimately result in enhancing the value of SLE patient care.

Development and validation of the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire

Health-related quality of life is increasingly important in the management of patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). A few disease-specific questionnaires exist, but all with substantial flaws. We developed and validated a quality of life questionnaire suitable for use in all BCC and SCC patients. In an extensive four-phase trajectory, as recommended by the European Organisation for Research and Treatment of Cancer (EORTC), 33 items were selected and rephrased into a preliminary questionnaire. A population-based sample of 1173 patients from the Dutch Cancer Registry were invited to complete the questionnaire. The questionnaire was reduced using exploratory factor analysis and item response theory (IRT). Subsequently, individual item performance was assessed using 8 features of the classical test theory (CTT).

The 33-item preliminary questionnaire was completed by 721 patients, of whom 15% had SCC. The number of items in the questionnaire was reduced to 16, covering five subscales: “Worries”, “Appearance”, “Behaviour”, “Diagnosis & Treatment” and “Other People”. Confirmatory factor analysis showed a good fit. Cronbach’s α (range 0.67 – 0.82) were reasonable to high and demonstrated good internal consistency. Of the 8 CTT item performance features, only 1 item was suboptimal for 6 out of 16 items and only 2 for 2 items, suggesting a valid Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire.

Diagnostic parameters of children with basal cell carcinoma nevus syndrome

Basal Cell Carcinoma Nevus Syndrome (BCCNS) is a multi-system genetic disease characterized by the development of multiple basal cell carcinomas (BCCs), macrocephaly, medulloblastomas, jaw keratocysts, and coarse facial features, amongst other symptoms. The major and minor criteria for adults with BCCNS are often extrapolated for children, however, little is known about the disease presentation of children with BCCNS. Our study focused on bringing the pediatric presentation of BCCNS to light. To the best of our knowledge, we are the first to investigate BCCNS and its medical impact on children. Using an internet accessible survey, we asked parents and guardians about the presenting symptoms of BCCNS in their children. It was found that at least 75% of children were diagnosed with BCCNS by the age of ten or earlier, which suggests that the presentation of disease starts much earlier than previously reported. Moreover, at least 19% of parents or guardians reported that their children had 50 or more BCCs by the age of diagnosis. It is our hope that these results will help clinicians be aware of the possible diagnosis of BCCNS at earlier ages in these children. An earlier diagnosis could provide the medical specialty-specific support services that may prevent the development of other medical consequences that arise from the burden of disease of BCCNS.

Differences in incidence and persistence of atopic dermatitis by race/ethnicity

BackgroundMost studies on racial disparities in childhood atopic dermatitis (AD) did not consider persistent AD or account for differences in vitamin D status.

MethodsAmong 1418 children recruited from a Massachusetts HMO into the pre-birth Project Viva cohort, we examined associations of child’s race/ethnicity with maternal report of child’s AD diagnosis by annual questionnaires. We used multivariable logistic regression adjusted for socio- demographics (maternal education, household income, smoking exposure, parental atopy, breastfeeding duration, child sex) and cord blood 25-hydroxyvitamin D, to estimate odds ratios (OR) of incident AD by early childhood (median age 3.3 years), and, among young children with AD, OR of persistence through mid-childhood (median age 7.7 years).

Results68% of children were non-Hispanic white, 13% were black, and 19% were other race/ethnicities. By early childhood, 497/1418 (35%) had incident AD. Among those with both AD and follow- up to mid-childhood, 58/389 (15%) had persistent AD. Black children were more likely than white children to have incident AD (OR 2.21; 95% CI 1.60, 3.04), even after adjustment for socio-demographics (2.64; 1.79, 3.89) and vitamin D levels (1.93; 1.07, 3.48). Black children also had higher odds of persistent AD (3.21; 1.63, 6.32; fully adjusted 4.60; 1.24, 17.13). Children with other race/ethnicities had non-significantly higher risk for AD incidence and persistence than white children.

ConclusionIn this cohort, compared with white children, black children and children with other race/ethnicities were at higher risk for incident and persistent AD, even after accounting for differences in socio-demographic characteristics and vitamin D levels.

Effect of antibiotic exposure on Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN)

BackgroundAntibiotics are commonly implicated in Stevens-Johnson syndrome (SJS), overlap syndrome (SJS-TEN), and Toxic Epidermal Necrolysis (TEN), rare disorders of skin and mucosal membranes, often the result of adverse drug reactions. The objective of this study is to examine associations between SJS, SJS-TEN, and TEN and antibiotic exposure overlapping diagnosis, and 3, 6, and 12 months before diagnosis.

MethodsA case-control study was conducted using PharMetrics LifeLink® Health Plan Claims Database (2001-2013). Cases had ≥1 diagnoses of SJS/TEN identified using ICD-9 codes, and ≥1 year of continuous health plan enrollment before earliest diagnosis. Controls were randomly selected from patients with no diagnoses of SJS/TEN, and matched to cases 4:1 on age, gender, and amount of continuous health plan enrollment. Multivariate logistic regression was used to estimate odds ratios for varying antibiotic exposures.

Results192 cases and 768 controls were included. Odds of an antibiotic fill overlapping diagnosis was ten times higher for cases than controls (OR=10.4; 95% CI 5.1, 21.1). Most common antibiotics overlapping diagnosis were aminopenicillins and cephalosporins, however associations between specific antibiotics and SJS/TEN were not significant (OR=1.03; 95% CI 0.6, 1.9). Unadjusted ORs for 3 (OR=1.05; 95% CI 1.03-1.07), 6 (OR=1.03; 95% CI 1.02, 1.04), and 12 months (OR=1.02; 95% CI 1.01, 1.02) before diagnosis show lower associations further in the past between antibiotics and reaction.

ConclusionsA significant association was found between overlapping antibiotic exposure and SJS/TEN. Likely due to small sample sizes, associations between specific antibiotic classes and SJS/TEN were not significant; further studies should be pursued to examine specific antibiotics.

Epidemiology of lentigo maligna and lentigo maligna melanoma in the Netherlands, 1989 –2013

Lentigo maligna (LM) is considered a precursor to LM melanoma (LMM). We assessed trends in LM and LMM incidence rates between 1989 and 2013 in the Netherlands, and estimated the risk of a LMM after LM. Data on newly diagnosed LM and LMM were obtained from the Netherlands Cancer Registry and PALGA (Dutch Pathology Database). Age-standardized incidence rates (European standardized rate [ESR]), estimated annual percentage changes (EAPC), and the cumulative incidence of LMM after LM were calculated. Between 1989-2013, 10,545 patients were diagnosed with a primary LM and 2,898 with a primary LMM in the Netherlands. The ESR for LM increased from 0.72 to 3.84 per 100,000 person-years, and for LMM from 0.24 to 1.19 between 1989-2013. LM incidence increased from 2002-2013 with 6.8% annually, prior to the – even steeper – rise in LMM incidence from 2007-2013 (EAPC: 12.4%). The cumulative incidence of LMM after a primary LM after 25 years follow-up was 2.0% for males and 2.6% for females. The increased incidence of LM and LMM in the Netherlands seems, besides increased awareness, increased histological confirmation, diagnostic drift and changed market forces, to reflect a true increase. The absolute risk of a LMM (at any location) after a histologically confirmed LM was low (2.0 – 2.6%).

Family history of cancer in relation to the risk of keratinocyte carcinoma plus another type of cancer: a case-control study

BackgroundA personal history of keratinocyte carcinoma (KC) is associated with increased risk for other malignancies. To assess the role of inherited cancer predisposition we investigated if family history (FH) of skin cancer plus noncutaneous malignancy is associated with the risk of KC plus another type of cancer.

MethodsThis clinic-based case-control study of non-Hispanic Caucasians had three age- and gender-matched groups: KC plus another cancer (n=49), KC only (n=50), and cancer-free controls (n=50). Patients were interviewed to assess FH in first-degree relatives of “skin cancer” and “cancer other than skin cancer.” Controls were the referent category for the risk of 1) KC only and 2) KC plus another cancer.

ResultsWhen FH was categorized into a four-level variable and evaluated across the 3 study groups, compared to the control group a FH of skin plus noncutaneous malignancy was strongly associated with risk of KC only (OR 9.9; 95% CI 1.7-59.7) and KC plus another cancer (OR 9.8; 95% CI 1.7-57.0). The ORs for FH of skin cancer only were weaker and non-significant for both KC only (OR 4.3) and KC plus another cancer (OR 6.8). FH of noncutaneous malignancy only was null across groups.

ConclusionsThe overall pattern of associations, especially the similar associations in patients with KC only and with KC plus another cancer, reinforce the known association between a family and personal history of KC but do not support a link between FH of skin plus noncutaneous malignancy and the KC cancer-prone phenotype.

Frequent somatic mutations of chromatin remodeling genes in metastatic cutaneous squamous cell carcinoma

Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but is typically correlated with high survival rates and low rates of metastasis. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals are estimated to die yearly from this disease. As it is difficult to predict which cSCCs are more likely to metastasize, and because there are no targeted therapies specifically designated for metastatic cSCC, we performed exome and targeted sequencing of 18 metastatic and 10 primary cSCCs to identify mutations with potential therapeutic benefit. Genes previously shown to be mutated in primary cSCC as well as aggressive tumors such as TP53 and NOTCH pathway genes were mutated at high rates in both metastatic and primary tumors. We compared our results to published sequencing results of an additional 223 primary tumors and 68 aggressive cSCCs. We identified several genes showing higher mutation frequencies in metastatic cSCC relative to primary tumors including the chromatin remodeling gene KMT2D, AKT/PI3K pathway gene PIK3CG, and the classic skin tumor suppressor TP53. These studies uncover potential pathways important in metastatic cSCC that may lead to new therapeutic strategies and understanding of the biology leading to more aggressive tumor behavior.

Histological completeness of BSS Excisions by dermatologists, plastic surgeons and general practitioners

OBJECTIVESFirst to determine the proportion of incompletely excised basal cell carcinomas (BCCs) treated by conventional excision by dermatologists, plastic surgeons and general practitioners. Second to identify characteristics of incomplete excised BCCs.

METHODSAnalysis of pathology reports of 3005 primary BCC excisions by general practitioners (31%), dermatologists (34%) and plastic surgeons (35%) from an urbanized area in the South West of the Netherlands from 2008-2014. Chi-square test and independent T-tests were used to analyze the primary outcome. Logistic regression was used to determine the odds ratio for incomplete excision in the groups corrected for patients age, patients sex, site, size, subtype and specialism.

OUTCOME MEASURESProportion of incompletely excised BCC per specialism, age and sex of patients, anatomical site, excision size (as a proxy for BCC size), and subtype.

RESULTSDermatologists had a complete excision rate of 93.24%, plastic surgeons 83.33% and general practitioners 69.61% (p<.0001). Head neck tumors we more often incompletely excised (OR 2.7; 95% CI: 2.0-3.7; p<.0001) compared to the trunk. Infiltrative BCCs were mere often incompletely excised compared to nodular BCCs (OR 3.8; 95% CI: 2.7-5.4; p<.0001). Plastic surgeons and general practitioners had a higher rate of incomplete excisions compared to dermatologists (OR 2.0; 95% CI: 1.5-2.7; p<.0001, resp. OR 6.1; 95% CI: 4.5-8.3; p<.0001).

CONCLUSIONRegardless of subtype, location and size dermatologists had a significantly higher rate of completely excised basal cell carcinomas compared to general practitioners and plastic surgeons

Hormonal and reproductive factors and incidence of basal cell carcinoma in a population-based cohort

Estrogens have photosensitizing properties, but few prospective studies have examined the relationship between hormonal and reproductive factors and incidence of basal cell carcinoma (BCC) in women. Previous findings have been inconsistent, particularly in relation to parity and use of oral contraceptives (OCs) and menopausal hormone therapy (MHT). Given the heterogeneity in the literature, we sought to examine the association between hormonal and reproductive factors and BCC risk in a cohort of women (n=23,879) enrolled in the QSkin Study in 2011. The baseline survey included questions about use of OCs and MHT, age at menarche, menopausal status, age at menopause and parity. We restricted our analysis to white women with no past history of treatments for skin cancer and less than 6 treatments for actinic keratoses (n=11,204) and used Cox proportional hazards models to estimate the hazards ratio associated with each potential hormonal/reproductive factor and first histologically confirmed BCC, while taking account of the potentially confounding influence of sun exposure history, phenotypic characteristics, body mass index and smoking history. During a median follow-up duration of 2.95 years, 352 women developed BCC. In preliminary analyses, amongst post-menopausal women, ever use of MHT at baseline was associated with an increased risk of developing BCC compared to never users (adjusted HR1.4; 95%CI 1.1-1.9), but risk did not differ by duration of use. We found no association between parity, age at menarche, age at menopause or use of OCs and BCC incidence. Future work will examine whether MHT use is associated with an increased risk of a second primary BCC.

Human papillomavirus infection and squamous cell carcinoma in organ transplant recipients

Organ transplant recipients (OTR) have an increased risk of developing squamous cell carcinomas (SCC). SCC are usually associated with multiple warts and premalignant keratoses. This cohort study investigated the predictive effect of infection with beta papillomaviruses (betaPV) with the later development of cutaneous SCC.

In an earlier prospective and case‐control study, eyebrow hairs and sera of 743 OTR transplanted before 2003 were collected. BetaPV DNA was determined in eyebrow hairs and betaPV antibodies in sera. The OTR were followed‐up for a maximum of 12 years. Hazard ratio (HR) were calculated with Cox proportional hazard analysis.

The age and sex adjusted HR to develop SCC being betaPV‐DNA positive for at least 5 betaPV types was 1.6 (95%CI 1.2 ‐ 2.2) and for the presence of antibodies against betaPV 1.4 (95%CI 1.0 – 1.8). BetaPV serological responses can be against one or more betaPV types which are present (concordant response) or are not present (disconcordant response) in the eyebrow hairs. The HR to develop SCC having a concordant response was 1.5 (95%CI 1.1 – 2.1) and having a disconcordant response 1.0 (95%CI 0.67 – 1.5) compared to patients with a negative serological response.

The presence of betaPV DNA in eyebrow hairs and a concordant antibody response to these betaPV types are predictive for the later development of cutaneous SCC in OTR. This finding suggests that infection with betaPV plays a role in SCC carcinogenesis.

Increased risk of opportunistic infections among patients with moderate-to-severe psoriasis: a population-based cohort study in the United Kingdom

Infection is the second leading cause of death among psoriasis patients on phototherapy or systemic medications. The types of infections associated with psoriasis remain poorly understood. The aim of our study was to determine the risk of opportunistic infection (OI) among patients with psoriasis. We conducted a cohort study of patients with (N=199,700) and without (N=954,315) psoriasis in The Health Improvement Network electronic medical record database. Patients receiving phototherapy or systemic therapy were considered to have moderate-to-severe psoriasis (N=12,442). The OI outcome was defined by a diagnostic code for any one of the following: actinomycosis/nocardia, aspergillosis, BK virus, cytomegalovirus, cryptococcus, systemic mycoses, pneumocystis, progressive multifocal leukoencephalopathy, tuberculosis, and toxoplasmosis. The incidence rates of OI were 1.9, 1.8, and 3.8 per 10,000 person-years for all patients with psoriasis and those with mild and moderate-to-severe disease, respectively, versus 2.1 per 10,000 person-years for those without psoriasis. The most common OI among patients with psoriasis was tuberculosis with an incidence rate of 1.0 per 10,000 person-years. In multivariable Cox proportional hazards regression analyses adjusting for age, gender, body mass index, drinking, comorbid diseases, corticosteroid use, history of infection or hospitalization, and Townsend deprivation score, we found an increased risk of OI among patients with moderate-to-severe psoriasis compared with patients without psoriasis: hazard ratio 1.86 (95% confidence interval, 1.23-2.83). Risk of OI was not increased among patients with mild psoriasis. Our results suggest that increased awareness of OIs, particularly tuberculosis, may be important for psoriasis patients receiving therapies for moderate-to-severe disease.

Infections in children with eczema in UK general practice- a cohort study

BackgroundCase reports and cross-sectional studies suggest increased risks of cutaneous and non-cutaneous infections in eczema; this relationship needs to be assessed in large population-based studies with diagnostic confirmation. The objective was to examine associations between eczema and common childhood infections.

MethodsIndividuals registered prior to age 18 in the Health Improvement Network, a UK general practice database, from 2003 to 2013 were included in this cohort study. We determined the association between eczema and selected infectious outcomes, including cutaneous (dermatophyte, herpes simplex virus, impetigo, molluscum contagiosum and warts), and non-cutaneous infections (otitis media, streptococcal throat infections, and pneumonia).

ResultsEczema was diagnosed in 14.4% (95% confidence interval 14.4, 14.4), and the average age of eczema diagnosis was 7.94 years (7.91, 7.98). All of the infectious illnesses were more prevalent in those with eczema compared to those without, with adjusted odds ratios (95% confidence intervals) as follows: dermatophyte 2.54 (2.47-2.61), herpes simplex virus, 2.08 (2.04-2.12), impetigo 2.61 (2.53-2.68), molluscum contagiosum 3.11 (3.07-3.14) and warts 1.98 (1.96-2.00). For non-cutaneous outcomes, the odds of otitis media, streptococcal throat infections and pneumonia were 2.24 (2.22-2.25), 1.75 (1.69-1.82) and 1.27 (1.23,1.31). Associations were attenuated in sensitivity analyses.

ConclusionSelected infectious illnesses were more prevalent in those with eczema versus those without, with the strength of association varying from 75% increase in streptococcal throat infections to a three-fold increased prevalence for molluscum contagiosum. Findings suggest there may be generalized immune dysfunction in eczema predisposing to increased risk of various infections, which is important for clinical management

The inpatient burden of Psoriasis: A nationwide analysis

Psoriasis is a chronic inflammatory skin disorder associated with substantial morbidity and mortality. Little is known about psoriasis in the inpatient setting. We sought to determine the inpatient burden of psoriasis in the US. We analyzed the 2002-2012 Nationwide Inpatient Sample, containing a representative 20% stratified sample of all hospitalizations in the US. Psoriasis was determined by a validated algorithm using ICD-9-CM codes. Demographics, inflation-adjusted cost, length of stay, comorbidities, and sex- adjusted mortality were analyzed using descriptive statistics and regression analysis. The mean prevalence of a primary diagnosis of psoriasis was 31.7 per million hospitalized patients per year. Hospitalization for psoriasis was associated with race (Asian: 2.08 [1.55-2.78]; Black: 1.65 [1.43-1.89]; Multiracial/other: 1.54 [1.13-2.11]) and insurance status (Medicare: 1.33 [1.26-1.40]; Medicaid: 0.74: [0.66-0.82]; uninsured: 1.94 [1.64-2.30]). Mean cost of care for a primary diagnosis of psoriasis was $7433±254 in comparison to $9956±76 for patients without psoriasis. Length of stay was significantly longer for patients with a primary (5.4±0.2 days; P<.0001) diagnosis of psoriasis compared to no psoriasis (4.6±0.2). After adjusting for demographic factors, psoriasis was associated with obesity (2.15 [2.10- 2.19]), alcohol use disorder (1.73 [1.69-1.77]), depression (1.53 [1.50-1.57]), and HIV/AIDS (2.15 [1.96- 2.37]). Adjusted mortality was 0.28%±0.3 for a primary diagnosis of psoriasis in comparison to 1.78%±0.02 for patients without psoriasis. The burden of psoriasis is substantial and patients with psoriasis had significantly longer length of stays. Although mortality rates were lower, psoriasis was associated with neuropsychiatric and various other comorbidities. Future studies are needed to confirm these findings.

Introducing public health themes in Clinical Dermatology

The ACGME’s Core Competencies comprise six domains, which in turn contain dozens of often overlapping milestones. Several competencies explicitly invoke public health topics – but if one wears the right set of lenses, nearly every milestone, nearly every aspect of health and medicine, can be viewed from a public health perspective. Why then is Dermatology generally taught – and practiced – in an Intensive Care manner, where seemingly unlimited diagnostic & therapeutic efforts focus on single individuals, not the community?

In this presentation, I argue that topics of public health concern should not be relegated to the minor leagues of GME. Instead, dermatology educators can don those public health lenses and identify aspects of clinical cases, common and unusual, that introduce themes that point to larger issues for the public weal.

We will review actual events where dermatologists and dermatologic issues were involved in major public health themes of the day. The presentation explores ways that dermatologists serve as sentinels to monitor emerging infectious diseases (such as HIV & Kaposi sarcoma, Zika, monkeypox in the Midwest, terrorism-associated anthrax) and acute outbreaks of noninfectious diseases (such as those due to environmental changes, drug manufacturing processes, changing trends of human behavior).

From these examples, we will explore ways to re-introduce the basic sciences of public health, including epidemiology and biostatistics, into the daily practice of dermatology.

Keratinocyte carcinoma and risk of all-cause and cancer-related mortality: A systematic review

BackgroundSome reports suggest a history of keratinocyte carcinoma (KC) may be associated with increased mortality. The high prevalence of KC makes the possibility of associated subsequent mortality from other causes important from a clinical and public health perspective. However, the variable methods and findings of existing studies leave the overall significance of these results uncertain. To provide clarity, we conducted a systematic review to characterize the evidence on the associations of KC with: 1) all-cause mortality, 2) cancer-specific mortality, and 3) cancer survival.

MethodsBibliographic databases were searched through February 2016. Studies were included if adequate data were provided to estimate mortality ratios in patients with- vs.-without KC. Data were abstracted from the studies that met inclusion criteria.

ResultsFor all-cause mortality, a significant increased risk was observed for patients with a history of squamous cell carcinoma (SCC) (relative risk estimates (RR) 1.25 and 1.30), whereas no increased risk was observed for patients with a history of basal cell carcinoma (BCC) (RRs 0.96 and 0.97). In one study, cancer-specific mortality was increased for patients with a KC history (RR 1.28; 95% CI 1.22-1.34). With few exceptions, across multiple types of cancer BCC and SCC were consistently associated with poorer survival from second primary malignancies.

ConclusionMultiple studies support an association between KC and fatal outcomes; the associations tend to be more potent for SCC than BCC. Additional investigation is needed to more precisely characterize these associations and elucidate potential underlying mechanisms.

New keratinocyte carcinomas worsen skin-related quality of life

Keratinocyte carcinoma (KC) is the most common malignancy in the U.S. Because KC affects many people but has a low mortality rate, it is important to consider the impact of KC on skin-related quality of life (QoL). We aimed to determine if KCs, actinic keratoses (AKs), and several demographic and health-related factors were associated with skin- related QoL in those at high risk for KC. We used data from a double-blind, placebo- controlled trial in which 932 veterans with multiple prior KCs were randomized to apply topical 5-fluorouracil (5-FU) or vehicle control cream to the face/ears. Skin-related QoL was measured at baseline, 12, 24, and 36 months using Skindex-29 and Skin Cancer Index and participants received skin examinations semiannually. At baseline, worse skin- related QoL was strongly associated (p≤0.01) with younger age and greater functional impairments (e.g. inability to bathe, walk). It was also associated with higher comorbidities, increased sun-sensitivity and prior 5-FU use, but almost entirely unrelated to baseline AKs and prior KCs. However, participants who developed new KCs or more AKs during the trial had worse skin-related QoL, particularly in year 1. Our ability to detect these relationships in longitudinal analyses but not in cross-sectional analyses may indicate the importance of the more precise control of potential confounding factors that is inherent in comparing each individual to their own prior state. These findings suggest that additional KCs and AKs may worsen skin-related QoL in a high-risk population and individuals with worse overall health may need more dermatologic attention, not less.

Pediatric Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the US

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening blistering disorders. Few studies have addressed SJS/TEN in children. We sought to determine risk factors, comorbidities, inpatient burden and mortality in US children with SJS, SJS-TEN and TEN. We analyzed data from the 2009-2012 Nationwide Inpatient Sample (NIS), containing a representative 20% sample of all hospitalizations in the US. SJS, SJS-TEN and TEN were identified by a validated algorithm using ICD-9-CM codes. Socio-demographics, inflation- adjusted cost, length of stay (LOS), comorbidities and mortality were analyzed using descriptive statistics and multivariate regression analysis. The incidences of SJS, SJS-TEN and TEN were a mean 5.5, 0.8 and 0.4 cases per million children per year, respectively. Prolonged LOS and higher costs of care (SJS: 9.3±0.6 days, $24,776±$3,183; SJS-TEN: 15.7±1.5 days, $63,787±8014; TEN: 20.4±6.3 days, $102,243±37,588) were observed compared to all other admissions (4.6±0.1 days, $10,496±424). Mean sex and age-adjusted mortality was 0% for SJS, 3.7% [1.4-6.1] for SJS-TEN and 24.8% [11.8-37.8] for TEN. In multivariate logistic regression models, SJS was associated with Herpes Simplex Virus (odds ratio [95% confidence interval]: 19.18 [7.84-46.91]) and Mycoplasma infection (9.91 [4.54-21.62]). In regression models with stepwise selection, predictors of mortality included renal failure (>999.99 [182.58->999.99]), malignancy (13.58 [2.98-61.99]), septicemia (56.50 [14.41-227.27]), bacterial infection (27.60 [6.71-113.61]), and epilepsy (34.39 [8.32-142.06]). Pediatric SJS-TEN pose a substantial health burden in the US. BSA >30%, renal failure, septicemia, and bacterial infections were the strongest predictors of mortality. Future studies are needed to improve prognostication and reduce the incidence and mortality of SJS-TEN.

Perceptions of indoor vs. outdoor tanning risks among melanoma patients who have a history of indoor UV tanning: an international internet survey

IntroductionA new U.S. FDA regulation categorizes tanning beds as category II¹, and similar global regulatory action require informing users of the “risk of skin cancer” as methods to reverse the growing trend of indoor tanning. However, little is known from the patient’s perspective on whether or not knowledge of risk of cancer is a deterrent to indoor tanning. Also, there is conflicting literature on the relationship between frequency of indoor tanning, age of onset and characteristics of patients’ melanoma diagnoses.

MethodsAn international survey was launched questioning those who are at least 18 years old and self-report being diagnosed with melanoma after indoor tanning. The survey link was made available to university and hospital dermatology departments, private dermatology practices, patient advocacy groups, and social media.

ResultsA total of 448 participants from eleven countries responded to the survey. Among responders, those who perceived indoor tanning as safer than outdoor tanning utilized indoor tanning more frequently than those who don’t (r = -0.224, p < 0.05). Skin cancer warnings failed to influence indoor tanning frequency. Neither the frequency of nor the age of onset of indoor tanning had an effect on the time frame in which melanoma is diagnosed. Moreover, the age of onset of tanning correlated with the Breslow level of melanoma.

ConclusionThose who more frequently tan indoors perceive this method as a safer alternative to outdoor tanning. Knowledge of the risk of skin cancer with tanning results in no decline in the frequency of indoor tanning.

Potential relationship between Rosacea and Parkinson’s disease

Rosacea is a common inflammatory condition characterized by transient or persistent facial erythema, telangiectasias, papules and pustules, for which an association has been reported to exist with Parkinson's disease (PD). We used a large, urban, single center, electronic medical record repository by searching the Northwestern Medicine Enterprise Data Warehouse (NMEDW) (> 4 million patients) for this association. Patients were included if they had an in-person encounter (Jan 2001 to May 2016) and with 1 year documentation of follow-up. Of these, all patients diagnosed with rosacea (ICD-9 codes: 372.31; 695.3, ICD-10 codes: L71.8; L71.9) and with a subsequent diagnosis of PD (ICD-9 code: 332; ICD-10 code: G20) were selected. Data on age, gender, race and tetracycline class therapy were collected. Adjusted odds ratio (OR) was obtained by using logistic regression analysis. A total of 815,210 patients were detected. 18,066 were diagnosed with rosacea, of whom 51 were subsequently diagnosed with PD (mean age: 74.5 years, range 53-89). A significant association between rosacea and PD was detectable after adjusting for age, gender, race and tetracycline class therapy (OR =1.7; 95%CI 1.27-2.22; p<0.001). Moreover, the adjusted odds ratio among untreated patients was higher than for rosacea-treated patients (ORs: 1.64 vs 1.10) and PD remained significantly associated with rosacea for both groups, suggesting that rosacea is an independent factor in the development of PD. These findings warrant further exploration for the relevance of this association between the two disorders.

Predicting the risk of metachronous basal cell carcinomas

A third of basal cell carcinoma (BCC) patients will develop metachronous BCCs, but information is limited on the frequency, timing and predictors of these subsequent BCCs. We aimed to develop a prediction model to assess the absolute risk of metachronous BCCs.

We observed 14,628 participants of northwestern European ancestry from a prospective population- based cohort study (Rotterdam Study). BCCs were identified using a linkage with the Dutch Pathology Registry (PALGA). Predictors for subsequent BCCs included 14 patient, lifestyle, and tumor-specific characteristics. The prediction model was developed with Fine and Gray regression analysis to account for the competing risk of death. To correct for within patient correlation, we assessed non-parametric 95% confidence intervals with bootstrapping.

Among 1,077 patients with a first BCC, second to fifth BCCs occurred in 293, 122, 58, and 36 patients, with median follow-up times of 3.0, 2.1, 1.7, and 1.8 years, respectively. The risk of a new BCC was higher for patients with more metachronous BCCs (15% within 3 years after a first BCC; 34% after a second; 45% after a third; and 67% after a fourth). Having >1 BCC at diagnosis was another strong predictor of metachronous BCCs. Discriminative ability of the model was reasonable with apparent c- indices of 0.68, 0.71, and 0.69 at 1, 3 and 5 years, respectively.

We conclude that a combination of readily available characteristics can reasonably identify patients at high risk of metachronous BCCs. After external validation the risk predictions may be used to personalize the follow-up.

Predictors of tanning dependence in white non-hispanic females and males

Growing evidence suggests some individuals may exhibit dependence to ultraviolet light, a known carcinogen; however, few studies have investigated predictors of tanning dependence (TD).A sub-set of early-onset basal cell carcinoma case-control study participants completed an online survey. The modified-Cut down, Annoyed, Guilty, Eye-opener (mCAGE) and a questionnaire based on the addiction criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (mDSM-IV-TR) were used to classify participants having

‘Symptoms of TD’ if they met criteria for TD on both questionnaires, ‘Tendency for TD’ if met criteria on only one questionnaire, or ‘Not TD’. We also assessed lifetime alcohol dependence, nicotine dependence, seasonal affective disorder (SAD), ‘exercise addiction,’ and depression. We compared TD groups with multivariate logistic regression.499 individuals reported volitional tanning and 24.4% were classified as having ‘Symptoms of TD’ and 24.4% as having a ‘Tendency for TD’. Women were more likely to have ‘Symptoms of TD’ (odds ratio (OR)=6.93; 95% Confidence Interval (95% CI)=(3.36-14.27)) or a ‘Tendency for TD’ (OR=2.82; 95% CI=1.59-4.98) than men. Alcohol dependence (OR=6.55; 95% CI=3.19-13.42), alcohol abuse (OR=3.16; 95% CI=1.81-5.51), risk of ‘exercise addiction’ (OR=5.47; 95%=1.15-26.06) and SAD (OR=2.77; 95% CI=1.26-6.09) were all significant predictors for ‘Symptoms of TD’. Alcohol dependence (OR=3.66; 95% CI=1.84-7.31) and alcohol abuse (OR=2.60; 95% CI=1.53-4.41) were significant predictors for ‘Tendency for TD.’Knowledge of associations between TD and gender, alcohol dependence/abuse, SAD, and ‘exercise addiction’ may be helpful to practitioners in treating TD and for targeting skin cancer preventive interventions for those with TD.

Predictors of actinic keratosis count in those with multiple keratinocyte carcinomas

Actinic keratoses (AKs) are frequently treated in the U.S., impacting an estimated 40 million people in 2004 and costing over $1 billion annually. AKs are a major public health concern because of their high prevalence, substantial cost, and potential for malignant transformation to keratinocyte carcinoma (KC). In this analysis, predictors of AK count were explored using pre-randomization baseline data from two large randomized trials of veterans with multiple prior KCs (n=932 and n=1131). Multivariate analyses were conducted to elucidate associations between AK count and several demographic and health related factors. In both trials, greater baseline AK count on the face/ears was strongly associated (p≤0.01) with older age, lower latitude, male sex, greater sun sensitivity, previous 5-FU use, and a higher number of prior invasive SCCs, but was not associated with number of prior BCCs. Additionally, mean baseline AK count was higher on the left side of the face/ear compared to the right, which may be explained by increased UV radiation to the left side while driving. Risk factors for actinic keratoses in a high-risk population are particularly important as actinic keratoses in this group are more likely to progress to keratinocyte carcinoma. Recognizing predictors of AK count in individuals at high risk for KC may help providers tailor AK prevention and treatment efforts. This may in turn lower the risk of KC—perhaps a more important goal—as the keratinocytic dysplasia that gives rise to malignancy, and sometimes appears as an AK, is what actually threatens patient health.

The preneoplastic genome: transcriptomic drivers of squamous cell carcinoma development

Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in the U.S. annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). In order to identify potential targets for molecularly targeted chemoprevention, we performed integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar UV- driven Hairless mouse model. We performed RNA-seq and microRNA-seq on samples from both patients undergoing Mohs surgery and the mouse model. Using cross-species TRANSFAC and linear mixed effects model methodology, we identified the major transcriptional and microRNA drivers of this progression sequence showing that the key genomic changes in cuSCC development occur primarily in the normal skin to AK transition. As a proof of principle validation of our methods, we have shown that MEK is an effective chemoprevention and therapeutic target for cuSCC in cells and in-vivo. Our data validate the use of this UV-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible.

Prognostic Modeling in Desmoplastic Melanoma Using Different Cutpoints for the Proportion of Desmoplasia

Currently, desmoplastic melanomas are commonly divided into “pure” desmoplastic melanoma (at least 90% desmoplasia histologically) and “mixed” (<90%), with pure having a better prognosis, but our understanding of the relationship between percent desmoplasia and prognosis is incomplete. We sought to determine whether a more refined grading system that examined extent of desmoplasia by percent in 10% increments would be a better prognostic model. We also sought to determine the optimal cutpoint for percent desmoplasia if a single cutpoint were used.

We analyzed 103 patients with desmoplastic melanoma confined to the skin at diagnosis and who were followed for at least 6 months. Desmoplasia proportions ranged from 10% to 100%, with forty patients (38.4%) having 100% desmoplasia. Overall, eighteen patients (17.5%) eventually developed metastases. Those with 100% desmoplasia had a statistically significantly decreased likelihood of metastasis compared to those with <100% desmoplasia (OR=0.15, p=0.017). However, there was no trend towards decreased likelihood of metastasis with decreasing percentages below 100% (p=0.658), implying a graduated system did not appear to be a better model than a single cutpoint. We also found that a model for predicting metastasis that incorporated Breslow thickness and the presence or absence of 100% desmoplasia (Akaike information criterion (AIC) = 84.64) was better than a model using 90% desmoplasia as the cutpoint (AIC = 89.35). We determined that a single cutpoint is sufficient in modeling prognosis for desmoplastic melanoma, and that 100% desmoplasia is a better cutpoint than the 90% cutpoint found in the “pure/mixed” model currently in use.

Prospective evaluation of complications in dermatologic surgery associated with hypertension Conroy

BackgroundPoorly controlled hypertension is a known risk factor for surgical complications. Objective: This study examines the incidence of complications in participants undergoing Mohsmicrographic surgery (MMS) based on preoperative blood pressure (BP) measurement and investigates the role of potential confounders in the relationship between preoperative BP and postoperative complications.

MethodsThis 10-month prospective cohort study at the University of California, San Francisco (UCSF) Dermatologic Surgery Center approached all patients undergoing MMS for participation and assessed for the diagnosis of hypertension, anti-hypertensive medication use, use of tobacco or blood thinners, immunosuppression, concomitant diabetes, or previous treatment with radiation therapy at the surgical site.

ResultsPreliminary analysis included 830 people. Overall, 676 patients had their follow up in the Mohs unit. The rate of complications was as follows: postoperative hemorrhage (6, 0.8%), hematoma formation (7, 1.0%), wound infection (16, 2.4%), wound dehiscence (19, 2.8%), flap necrosis (13, 1.9%), graft necrosis (8, 1.2%). Eight patients experienced two complications. There was no significant relationship between a patient’s BP and the presence of complications. In multivariate analyses that include all the potential confounding variables, a self-reported history of diabetes was the only factor that influenced the presence of complications (P=0.039).

ConclusionsOur preliminary analysis showed no relationship between BP and the rate of complications, while the presence of diabetes significantly increased a patient’s risk for a wound complication. This study was limited by a relatively small number of complications and more data will be needed to further investigate the relationship.

Risk factors for facial telangiectasia

BackgroundTelangiectasia or red veins are one of the main features of facial skin aging. To date there are few studies investigating risk factors for telangiectasia. We investigated environmental risk factors in a population‐based cohort study, using a digital continuous outcome measure.

MethodsTelangiectasia were quantified digitally from standardized 3‐dimensional facial photographs of 2886 North‐ European participants (56.8% female, median age 66.9) from the Rotterdam Study, a prospective population‐based cohort study. Age‐ and sex adjusted as well as fully adjusted multivariable linear regressions were performed to investigate associations between potential environmental factors and the amount of telangiectasia. Men and women were analyzed separately.

ResultsThe mean facial area covered by telangiectasia was higher in women (median area 0.95%, interquartile range 0.62‐ 1.4) than in men (median area 0.76%, interquartile range 0.48‐1.2). Besides age (men ß=0.016, P‐value<0.001; women ß=0.016, P‐value<0.001), smoking (men ß=0.29, P‐value<0.001; women ß=0.32, P‐value<0.001), a high susceptibility to sunburn (men ß=0.082, P‐value<0.001; women ß=0.076, P‐value<0.001) and light skin color (pale against olive‐colored skin in men ß=0.26, P‐value<0.001; in women ß=0.23, P‐value<0.001) were independent significant factors contributing to telangiectasia for both sexes. Additionally in men, a lower education also showed an association (medium vs. high ß=0.062, P‐value=0.008). Alcohol showed a negative association with telangiectasia (ß=‐0.028, P‐value<0.001). In women, a higher free androgen index was associated with less telangiectasia (ß=‐0.0053, P‐value<0.001).

ConclusionIn this large cohort study of facial telangiectatic photoaging, environmental factors associated with telangiectasia are described, implicating possible new prevention strategies for this form of skin aging.

Risks of different skin tumor combinations after a first melanoma, squamous cell carcinoma and basal cell carcinoma in Dutch population based cohorts: 1989 – 2009

The aim of this study was to calculate risks of different type of subsequent skin cancers.

All melanoma and squamous cell carcinoma (SCC) patients included in the national Netherlands Cancer Registry (NCR) and all basal cell carcinoma (BCC) patients included in the regional Eindhoven Cancer Registry (ECR) between 1989 and 2009 were followed until diagnosis of a subsequent different skin cancer (melanoma, SCC or BCC), date of death or end of study. Cumulative risk, Standardized Incidence Ratio (SIR) and Absolute Excess Risk (AER) of subsequent skin cancers were calculated.

In total, 50,510 melanoma patients and 64,054 SCC patients were included (national data NCR). The regional data of the ECR consisted of 5,776 melanoma patients, 5,749 SCC patients and 41,485 BCC patients. The 21-year cumulative risk for a subsequent melanoma after a first SCC or BCC was respectively 1.7% and 1.3% for males and 1.3% and 1.2% for females; SCC after melanoma or BCC was 4.6% and 9.3% (males) and 2.6% and 4.1% (females); BCC after melanoma or SCC was respectively 13.2% and 27.8% (males) and 14.9% and 21.1% (females). SIRs and AERs remained elevated up to 21 years after the first melanoma, SCC or BCC.

The results of this study showed high cumulative risks of mainly BCC and SCC and markedly increased relative and absolute risks of all tumor combinations. These estimates confirm a common carcinogenesis and can serve as information for follow-up guidelines and patient education aiming for an early detection of the subsequent cancers.

Serious Infections are on the rise in US Inpatients with Psoriasis

Psoriasis is a chronic inflammatory skin disorder associated with immune dysregulation and use of systemic immunosuppressive treatments that may predispose toward serious infections. We sought to determine the rates of serious infections in hospitalized patients with psoriasis. We analyzed data from the 2002-2012 Nationwide Inpatient Sample, containing a 20% sample of all US hospitalizations. Psoriasis was determined by a validated algorithm using ICD-9-CM codes. In multivariate logistic regression models adjusting for socio-demographics, psoriasis was associated with multiple serious infections, including methicillin-resistant Staphylococcus aureus (odds ratio [95% confidence intervals] 1.76 [1.52-2.03]), cellulitis (3.21 [3.12-3.30]), herpes simplex virus infection (HSV) (2.21 [1.70-2.89]), infectious arthritis (1.82 [1.58-2.09]), osteomyelitis (1.31 [1.18-1.46]), meningitis (1.31 [1.16-1.47]), encephalitis (1.22 [1.02-1.47]), tuberculosis (1.34 [1.20-1.49]) and meningitis (1.31 [1.16-1.47]). Among patients with psoriasis, rates of overall serious infections increased over all time intervals analyzed (P=0.01) and were significantly higher compared to those without psoriasis across all time intervals (P<0.0001). The mean LOS (6.6±0.1 days) and cost ($13,291±$166) of psoriasis with serious infections was higher than that of psoriasis without serious infections (4.6±0.03 days; $11,003±$96; P<0.0001). Serious infections are increasing in incidence in inpatients with psoriasis. Further research is needed to confirm these findings and understand the mechanisms of these associations in order to develop large-scale interventions aimed at prevention.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in US adults

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening disorders. The incidences, mortality and cost of SJS and TEN in US adults are not well-characterized. We analyzed data from the 2009-2012 Nationwide Inpatient Sample, containing a representative 20% sample of all hospitalizations in the US. SJS, SJS/TEN and TEN were identified by a validated algorithm using ICD-9- CM codes. The mean incidences of SJS, SJS/TEN and TEN were 9.3, 1.6, and 1.9 per million people per year, respectively. Predictors of hospitalization included race (Black, Hispanic, Asian, Native American, other/mixed), insurance status (Medicare, self-pay), and an increasing number of chronic conditions (P<0.05 for all). Significantly prolonged length of stay and higher costs of care (SJS: 9.8±0.3 days, $21,437±807; SJS/TEN: 16.5±1.0 days, $58,954±5,238; TEN: 16.2±1.0 days, $53,695±4,037) were observed in comparison with all other admissions (4.7±0.02 days, $11,281±98). Adjusted mortality was 4.8% for SJS, 19.4% for SJS/TEN and 14.8% for TEN. In multivariate regression models, SJS/TEN were associated with ocular infection/inflammation (30.28 [26.41-34.72]), blindness/vision defects (2.30 [1.83- 2.89]), septicemia (5.73 [5.23-6.27]), renal failure (2.20 [1.98-2.43]), leukemia (2.86 [2.19-3.75]), non- Hodgkin’s lymphoma (2.92 [2.25-3.80]) and HIV/AIDS (3.71 [2.54-5.43]). Predictors of mortality included increasing age, increasing number of chronic conditions, infection (septicemia, pneumonia, tuberculosis), hematological malignancy (non-Hodgkin’s lymphoma, leukemia) and renal failure (P≤0.03 for all). In conclusion, the incidence of SJS appears to be higher than previously reported, though mortality rates are lower. Further studies are needed to confirm mortality findings to improve prognostication of SJS/TEN.

Sun protection behavior and sunburns among Arizona adults

ObjectiveTo examine the prevalence of sun protection behaviors and sunburn history among adults in a region of the United States with high ultraviolet radiation exposure.

Design and SettingData on self-reported sun protection and sunburns were obtained using supplemental questions added to the 2013 Arizona Behavioral Risk Factor Surveillance System survey. 3,370 Arizona adults over the age of 18 years completed questions about use sunscreen and protective clothing and reported sunburns within past 12 months. Weighted analyses were used; odds ratios (OR) and 95% confidence intervals (CI) were calculated.

ResultsApproximately 20% of Arizona adults reported they protected their skin with sunscreen or protective clothing every time when going outdoors; however, among those aged 18-24 years, this percentage dropped to 8%. Additionally, 28% reported they experienced one or more sunburns in the past 12 months. Females were more likely to protect their skin (OR 2.06, 95%CI:1.47-2.87) than males. Binge drinking and heavy alcohol consumption were associated with a decreased likelihood of sun protection in males (OR 0.48, 95%CI: 0.27-0.83 and OR 0.32, 95%CI: 0.14-0.72, respectively), but not females. A recent history of sunburns was associated with being non-Hispanic white and a history of indoor tanning.

ConclusionsA large percentage of Arizona adults are not adequately protecting themselves from the sun. Factors related to use of sun protection are not always the same as those related to sunburns. Comprehensive tailored approaches to skin cancer prevention are needed.

Telomere length, cutaneous beta human papillomavirus infection and cutaneous squamous cell carcinoma

BackgroundCutaneous beta-human papillomavirus (HPV) infection and telomere length have both been associated with cutaneous squamous cell carcinoma (SCC). We examined the interaction between telomere length and beta-HPV in association with SCC.

MethodsA subset of SCC cases and controls, enrolled in a previously conducted case-control study (2007-2008) at the University of South Florida and Moffitt Cancer Center, for whom data was available on telomere length and a) beta-HPV serology (135 cases and 201 controls), b) beta-HPV DNA in eyebrow hairs (EB) (130 SCC cases and 195 controls) and c) beta-HPV DNA in SCC tumors (117 cases), were included in the present analyses. Association between telomere length and SCC, stratified by HPV status, was examined using logistic regression and, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.

ResultsUsing short telomere length (T/S<=1.08) and HPV seronegativity as a reference, the association between long telomere and SCC was found to vary by HPV serostatus, with a stronger inverse association seen among subjects with seronegativity to multiple beta-1 HPV infections (OR long telomere and multiple beta-1 HPV seronegativity = 0.02, 95% CI=0.002- 0.17; OR=0.27 long telomere and multiple beta-1 HPV seropositivity, 95% CI=0.14- 0.51). Long telomere was inversely associated with SCC (OR=0.38, 95% CI=0.25-0.58) among subjects who were EB DNA positive for multiple beta-2 HPV types, with the association being stronger among those with EB DNA negativity for multiple beta-2 HPV infections (OR=0.03, 95% CI=0.01- 0.12).

ConclusionCutaneous HPV infection may modify the association between telomere length and SCC.

Trends of skin cancer incidence following transplantation in the United States

BackgroundSkin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTR), no study has estimated the post-transplant population-based incidence in the US. The objective of this study is to determine the incidence and evaluate the predictors of post-transplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTR receiving a primary transplant in 2003 or 2008.

MethodsDesign: A multi-center retrospective cohort study with 5- and 10-year follow-up periods.Setting: The Transplant Skin Cancer Network (TSCN) comprises 26 transplant centers across the US.Participants: Adult recipients of a primary transplant performed at 26 centers in 2003 or 2008 identified through the Organ Procurement and Transplantation Network (OPTN) database (N=10,649) were selected. Recipients of all organs except intestine were included.Main outcome and measurements: Skin cancer outcomes were determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates (IR) for post-transplant skin cancer overall and for SCC, MM, and MCC were calculated per 100,000 person-years. Potential risk factors for post-transplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR).

ResultsThere were 10,649 organ transplant recipients that contributed 59,923 years of follow-up. The IR for post-transplant skin cancer overall was 1408 per 100,000 person-years. The specific subtype rates for SCC, MM, and MCC were 1328, 122, and 4 per 100,000 person-years, respectively. The statistically significant risk factors for post-transplant skin cancer were: pre- transplant skin cancer (HR 4.69, 95% confidence interval [CI] 3.26-6.73) male gender (HR 1.56, 95% CI 1.34-1.81), white race (HR 9.04, 95% CI 6.20-13.18), age at transplant ≥50 (HR 2.77, 95% CI 2.20-3.48), and being transplanted in 2008 vs. 2003 (HR 1.53, 95% CI 1.22-1.94).

ConclusionPost-transplant skin cancer is common, with elevated risk imparted by increased age, white race, male gender, and thoracic organ transplantation. Understanding the risk factors for post-transplant skin cancer is fundamental to targeted screening and prevention in this high-risk population.

Vitamin D and skin aging

BackgroundThe relationship between 25‐hydroxyvitamin D and different phenotypes of skin aging (e.g., wrinkles, pigmented spots, telangiectasia, perceived age) is unclear. We investigated the association between vitamin D levels and skin aging phenotypes in middle‐aged participants from the Rotterdam Study (RS) and Leiden Longevity Study (LLS).

MethodsStandardized facial photographs were taken of North‐European participants from the RS (N=3,831; 58.2% female, median age 66.5) and the LLS (N=661; 50.5% female, median age 63.1). Facial wrinkles, pigmented spots and telangiectasia (RS only) were quantified either digitally (RS) or by two independent dermatologists (LLS). Perceived age was graded by an average of 27 (range:20‐30) and 60 (range:59‐61) assessors in the RS and LLS respectively. The associations between vitamin D and these phenotypes (all standardized using Z‐scores) were investigated using multivariable linear regression analyses, adjusted for chronological age, sex, self‐reported UV‐exposure, season, smoking, body mass index and skin color, followed by meta‐analysis of the two cohorts.

ResultsHigher circulating 25‐hydroxyvitamin D was associated with more wrinkles (P‐value<0.0001) and a higher perceived age (P‐value<0.0001). However, there was no association between higher circulating 25‐hydroxyvitamin D and pigmented spots or telangiectasia (p‐values>0.05). Self‐reported UV‐exposure was associated with all four phenotypes. In RS, a light skin color was associated with more pigmented spots (P‐value<0.0001) and telangiectasia (P‐value<0.0001), but with less wrinkles (P‐value<0.0001).

ConclusionA higher circulating 25‐hydroxyvitamin D is associated with more facial wrinkles and a higher perceived age in middle‐aged and older individuals. However, although statistically adjusted for questionnaire‐based sun exposure, these two associations could be attributable to residual confounding.