RESUMO
INTRODUCTION: The mortality-to-incidence ratio (MIR) can be used to approximate healthcare inequities and is helpful to understand/compare cancer survival between geographic regions/jurisdictions. We investigated cutaneous melanoma (CM) outcomes through MIR analysis in Canadian jurisdictions and census divisions (CDs) between 1992 and 2016. METHODS: Data were obtained from the national databases from 1992 to 2016 for all Canadian jurisdictions, except Quebec. Age-standardized overall and median MIRs were calculated per province per year, while crude MIRs were calculated for CDs. Generalized linear regression models were conducted to study the effect of province and year on MIR, while a mixed effect regression model was used to determine how healthcare and socioeconomic factors affect MIR, while accounting for possible clustering effects (eg, year and province). RESULTS: We identified 106,015 CM cases and 20,570 CM deaths between 1992 and 2016. National MIR from 1992 to 2016 demonstrated a significant linear decrease (P value < .0001). The national median MIR was 15.4 (ie, 0.154 × 100), whereby Manitoba (19.9), Ontario (19.5), Saskatchewan (18.5), British Columbia (16.1), and Newfoundland and Labrador (15.9) demonstrated higher MIRs than the Canadian average. CDs with the highest MIRs were commonly identified in the southern regions of provinces. No healthcare or socioeconomic factors were found to be significantly associated with higher MIR at the provincial level. CONCLUSION: MIRs have decreased at the national and provincial levels in recent decades, which is reassuring. Higher MIRs were noted in select rural CDs and in the Canadian territories, reinforcing the importance of proper dermatological care in all parts of the country.
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Melanoma , Neoplasias Cutâneas , Fatores Socioeconômicos , Humanos , Melanoma/mortalidade , Melanoma/epidemiologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/epidemiologia , Incidência , Canadá/epidemiologia , Melanoma Maligno Cutâneo , Feminino , Disparidades em Assistência à Saúde , MasculinoRESUMO
BACKGROUND: Consensus about the definition and classification of 'plaque' in mycosis fungoides is lacking. OBJECTIVES: To delineate a comprehensive view on how the 'plaque' entity is defined and managed in clinical practice; to evaluate whether the current positioning of plaques in the TNMB classification is adequate. METHODS: A 12-item survey was circulated within a selected panel of 22 experts (pathologists, dermatologists, haematologists and oncologists), members of the EORTC and International Society for Cutaneous Lymphoma. The questionnaire discussed clinical and histopathological definitions of plaques and its relationship with staging and treatment. RESULTS: Total consensus and very high agreement rates were reached in 33.3% of questions, as all panellists regularly check for the presence of plaques, agree to evaluate the presence of plaques as a potential separate T class, and concur on the important distinction between plaque and patch for the management of early-stage MF. High agreement was reached in 41.7% of questions, since more than 50% of the responders use Olsen's definition of plaque, recommend the distinction between thin/thick plaques, and agree on performing a biopsy on the most infiltrated/indurated lesion. High divergence rates (25%) were reported regarding the possibility of a clinically based distinction between thin and thick plaques and the role of histopathology to plaque definition. CONCLUSIONS: The definition of 'plaque' is commonly perceived as a clinical entity and its integration with histopathological features is generally reserved to specific cases. To date, no consensus is achieved as for the exact definition of thin and thick plaques and current positioning of plaques within the TNMB system is considered clinically inadequate. Prospective studies evaluating the role of histopathological parameters and other biomarkers, as well as promising diagnostic tools, such as US/RM imaging and high-throughput blood sequencing, are much needed to fully integrate current clinical definitions with more objective parameters.
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Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Humanos , Estudos Prospectivos , Micose Fungoide/patologia , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , BiópsiaRESUMO
BACKGROUND: For dermatology to effectively address the ever-growing medical needs, longstanding communication barriers across investigators working in different research pillars and practicing clinicians must be improved. To address this problem, trainee-specific programs are now evolving to align their educational landscape across basic science, translational and clinical research programs. OBJECTIVES: To establish a Skin Investigation Network of Canada (SkIN Canada) training roadmap for the career and skill development of future clinicians, clinican scientists and basic scientists in Canada. This Working Group aims to strengthen and harmonize collaborations and capacity across the skin research community. METHODS: The Working Group conducted a search of established international academic societies which offered trainee programs with mandates similar to SkIN Canada. Societies' program items and meetings were evaluated by use of an interview survey and/or the collection of publicly available data. Program logistics, objectives and feedback were assessed for commonalities and factors reported or determined to improve trainee experience. RESULTS: Through the various factors explored, the Working Group discovered the need for increasing program accessibility, creating opportunities for soft skill development, emphasizing the importance of current challenges, collecting and responding to feedback, and improving knowledge sharing to bridge pillars of skin research. CONCLUSIONS: Although improvements have been made to trainee education in recent years, a plurality of approaches exist and many of the underlying roadblocks remain unresolved. To establish fundamental clinician-basic scientist collaboration and training efforts, this Working Group highlights important factors to include and consider in building a trainee program and emphasizes the importance of trainee education.
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Pesquisa Biomédica , Humanos , Canadá , Inquéritos e Questionários , EscolaridadeRESUMO
BACKGROUND: Sex and gender have increasingly been recognized as significant risk factors for many diseases, including dermatological conditions. Historically, sex and gender have often been grouped together as a single risk factor in the scientific literature. However, both may have a distinct impact on disease incidence, prevalence, clinical presentation, severity, therapeutic response, and associated psychological distress. OBJECTIVES AND PROJECT DESCRIPTION: The mechanisms that underlie differences in skin diseases between males, females, men, and women remain largely unknown. The specific objectives of this review paper are:To highlight the biological differences between males and females (sex), as well as the sociocultural differences between men and women (gender) and how they impact the integumentary system.To perform a literature review to identify important sex- and gender-related epidemiological and clinical differences for various skin conditions belonging to a range of disease categories and to discuss possible biological and sociocultural factors that could explain the observed differences.To discuss dermatological skin conditions and gender-affirming treatments within the transgender community, a population of individuals who have a gender identity which is different than the gender identity they were assigned at birth. FUTURE IMPACT: With the rising number of individuals that identify as non-binary or transgender within our increasingly diverse communities, it is imperative to recognize gender identity, gender, and sex as distinct entities. By doing so, clinicians will be able to better risk-stratify their patients and select treatments that are most aligned with their values. To our knowledge, very few studies have separated sex and gender as two distinct risk factors within the dermatology literature. Our article also has the potential to help guide future prevention strategies that are patient-tailored rather than using a universal approach.
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Dermatologia , Pessoas Transgênero , Recém-Nascido , Humanos , Masculino , Feminino , Identidade de Gênero , Pessoas Transgênero/psicologia , Fatores de RiscoRESUMO
BACKGROUND: The Skin Investigation Network of Canada (SkIN Canada) is a new national skin research network. To shape the research landscape and ensure its value to patient care, research priorities that are important to patients, caregivers, and health care providers must be identified. OBJECTIVES: To identify the Top Ten research priorities for 9 key skin conditions. METHODS: We first surveyed health care providers and researchers to select the top skin conditions for future research within the categories of inflammatory skin disease, skin cancers (other than melanoma), and wound healing. For those selected skin conditions, we conducted scoping reviews to identify previous priority setting exercises. We combined the results of those scoping reviews with a survey of patients, health care providers, and researchers to generate lists of knowledge gaps for each condition. We then surveyed patients and health care providers to create preliminary rankings to prioritize those knowledge gaps. Finally, we conducted workshops of patients and health care providers to create the final Top Ten lists of research priorities for each condition. RESULTS: Overall, 538 patients, health care providers, and researchers participated in at least one survey or workshop. Psoriasis, atopic dermatitis and hidradenitis suppurativa (inflammatory skin disease); chronic wounds, burns and scars (wound healing); and basal cell, squamous cell and Merkel cell carcinoma (skin cancer) were selected as priority skin conditions. Top Ten lists of knowledge gaps for inflammatory skin conditions encompassed a range of issues relevant to patient care, including questions on pathogenesis, prevention, non-pharmacologic and pharmacologic management. CONCLUSIONS: Research priorities derived from patients and health care providers should be used to guide multidisciplinary research networks, funders, and policymakers in Canada and internationally.
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Pesquisa Biomédica , Dermatite Atópica , Hidradenite Supurativa , Psoríase , Neoplasias Cutâneas , Humanos , Hidradenite Supurativa/epidemiologia , Hidradenite Supurativa/terapia , Dermatite Atópica/epidemiologia , Dermatite Atópica/terapia , Prioridades em Saúde , Canadá/epidemiologiaRESUMO
Actinic keratosis (AK) is among the most commonly diagnosed skin diseases with potentially life-threatening repercussions if left untreated. Usage of pharmacologic agents represents one of many therapeutic strategies that can be used to help manage these lesions. Ongoing research into these compounds continues to change our clinical understanding as to which agents most benefit particular patient populations. Indeed, factors such as past personal medical history, lesion location and tolerability of therapy only represent a few considerations that clinicians must account for when prescribing appropriate treatment. This review focuses on specific drugs used in either the prevention or treatment of AKs. Nicotinamide, acitretin and topical 5-fluorouracil (5-FU) continue to be used with fidelity in the chemoprevention of actinic keratosis, although some uncertainty persists in regard to which agents should be used in immunocompetent vs. immunodeficient/immunosuppressed patients. Topical 5-FU, including combination formulations with either calcipotriol or salicylic acid, as well as imiquimod, diclofenac and photodynamic light therapy are all accepted treatment strategies employed to target and eliminate AKs. Five percent of 5-FU is regarded as the most effective therapy in the condition, although the literature has conflictingly shown that lower concentrations of the drug might also be as effective. Topical diclofenac (3%) appears to be less efficacious than 5% 5-FU, 3.75-5% imiquimod and photodynamic light therapy despite its favorable side effect profile. Finally, traditional photodynamic light therapy, while painful, appears to be of higher efficacy in comparison to its more tolerable counterpart, daylight phototherapy.
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Ceratose Actínica , Fotoquimioterapia , Humanos , Ceratose Actínica/patologia , Ácido Aminolevulínico , Diclofenaco , Imiquimode/uso terapêutico , Fotoquimioterapia/efeitos adversos , Fluoruracila/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Over 90% of skin cancers including cutaneous melanoma (CM) are related directly to sun exposure. Despite extensive knowledge on ultraviolet radiation's (UVR) detrimental impact, many still fail to implement sun protection/sun avoidance. Human behavior, attitudes, and cultural norms of individuals and communities heavily depend on the surrounding climate/environment. In many instances, the climate shapes the culture/norms of the society. Canada has vast geographic/environmental differences. METHODS: In the current ecological study, we sought to examine the relationship between various geographic and environmental factors and the distribution of CM incidence by Forward Sortation Area (FSA) postal code across Canada. CM incidence data were extracted from the Canadian Cancer Registry, while environmental data were extracted from the Canadian Urban Environmental Health Research Consortium (greenspace, as measured by the normalized difference vegetation index; annual highest temperature; absolute number and average length of yearly heat events; annual total precipitation [rain and snow]; absolute number and average length of events with precipitation [rain and snow]; and summer UVR index). The above geographic/environmental data by FSA were correlated with the respective CM incidence employing negative binomial regression model. RESULTS: Our analysis highlights that increases in annual average temperature, summer UVR, and greenspace were associated with higher expected incidence of CM cases, while higher number of annual heat events together with highest annual temperature and higher average number of annual rain events were associated with a decrease in CM incidence rate. This study also highlights regional variation in environmental CM risk factors in Canada. CONCLUSIONS: This national population-based study presents clinically relevant conclusions on weather/geographic variations associated with CM incidence in Canada and will help refine targeted CM prevention campaigns by understanding unique weather/geographic variations in high-risk regions.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/epidemiologia , Melanoma/etiologia , Melanoma/prevenção & controle , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Incidência , Raios Ultravioleta/efeitos adversos , Canadá/epidemiologia , Melanoma Maligno CutâneoRESUMO
Psoriatic arthritis (PsA) can affect a diverse range of anatomical sites and its heterogeneous presentation contributes to misdiagnosis and delayed treatment with conventional and biologic disease-modifying antirheumatic drugs (DMARDs). Up to 15% of psoriasis (PsO) patients affected by PsA remain undiagnosed. Early detection and referral to a rheumatologist are crucial to optimize care and minimize irreversible erosive joint damage. To improve the rheumatology referral process, the authors propose a risk stratification tool to identify and triage patients with possible psoriatic arthritis. With the aim of ultimately assisting in early treatment initiation, this risk stratification algorithm can be used in both dermatology and primary care clinics. It is based on the Psoriasis Epidemiology Screening Tool (PEST) combined with the ClASsification criteria for Psoriatic Arthritis (CASPAR). This article intends to provide a rationale for further prospective studies whose objective would be to validate this screening algorithm.
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Artrite Psoriásica , Psoríase , Humanos , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/epidemiologia , Estudos Prospectivos , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Encaminhamento e Consulta , Medição de RiscoRESUMO
Type 2 immunity, illustrated by T helper 2 lymphocytes (Th2) and downstream cytokines (IL-4, IL-13, IL-31) as well as group 2 innate lymphoid cells (ILC2), is important in host defense and wound healing.1 The hallmark of type 2 inflammation is eosinophilia and/or high IgE counts and is best recognized in atopic diathesis. Persistent eosinophilia, such as seen in hypereosinophilic syndromes, leads to fibrosis and hence therapeutic Type 2 inhibition in fibrotic diseases is of high interest. Furthermore, as demonstrated in cutaneous T cell lymphoma, advanced disease is characterized by Th1 to Th2 switch allowing cancer progression and immunosuppression. Development of targeted monoclonal antibodies against IL-4Rα (eg, dupilumab) led to a paradigm shift for the treatment of atopic dermatitis (AD) and stimulated research to better understand the role of Type 2 inflammation in other skin conditions. In this review, we summarize up to date knowledge on the role of Type 2 inflammation in skin diseases other than AD and highlight whether the use of Type 2 targeted therapies has been documented or is being investigated in clinical trials. This manuscript reviews the role of Type 2 inflammation in dermatitis, neurodermatitis, IgE-mediated dermatoses (eg, bullous pemphigoid, chronic spontaneous urticaria), sclerodermoid conditions and skin neoplasms.
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Imunidade Inata , Imunoterapia/métodos , Dermatopatias/imunologia , Dermatopatias/terapia , Cicatrização/imunologia , Citocinas/imunologia , Humanos , Células Th2/imunologiaRESUMO
Moderate to severe chronic plaque psoriasis may be difficult to control using current therapies, which has led to development of a novel class of therapy, selective tyrosine kinase 2 (TYK2) inhibitors, to address this unmet need. Oral deucravacitinib is a first-inclass selective TYK2 inhibitor, which has shown efficacy in moderate to severe chronic plaque psoriasis from two phase III pivotal trials (POETYK PSO-1 and PSO-2), whereby response rates were significantly higher with deucravacitinib vs. placebo or apremilast for Psoriasis Area Severity Index (PASI) 75 and static Physician's Global Assessment (sPGA) 0/1. Deucravacitinib was generally well tolerated and safe compared to placebo and apremilast. Although deucravacitinib is a type of Janus kinase (JAK) inhibitor, it only blocks specific cytokine-driven responses, potentially reducing off-target effects more commonly associated with other JAK inhibitors on the market. Incidence rates of serious adverse events, such as serious infections, malignancies, thrombosis, cardiovascular events, creatinine kinase elevation, hematologic changes, and lipid profile abnormalities were absent or low.
Assuntos
Inibidores de Janus Quinases , Psoríase , Humanos , TYK2 Quinase/uso terapêutico , Psoríase/tratamento farmacológico , Psoríase/patologia , Talidomida/efeitos adversos , Inibidores de Janus Quinases/efeitos adversos , Resultado do Tratamento , Índice de Gravidade de DoençaRESUMO
Warts, Hypogammaglobulinemia, Infections and Myelokathexis (WHIM) is a primary immunodeficiency syndrome. Patients with WHIM syndrome are more susceptible to human papillomavirus (HPV) infections and commonly present to a dermatologist with recalcitrant to treatment warts. Other cardinal features of WHIM syndrome include recurrent sinopulmonary bacterial infections, neutropenia/lymphopenia, low levels of immunoglobulins (IgG, IgA, IgM) and myelokathexis. Research demonstrated that truncating gain-of-function mutations of the C-X-C chemokine receptor type 4 gene (CXCR4) are responsible for this disease. Plerixafor, a specific small molecule antagonist of CXCR4, is currently used for peripheral blood hematopoietic stem cell (HSC) mobilization in stem cell transplant recipients. It has recently shown promise for the treatment of WHIM syndrome in phase I/II clinical trials. In this paper we review the emerging patient clinical data for this medication and highlight the role of CXCR4 in other important skin diseases including keratinocyte carcinomas, psoriasis and cutaneous T-cell lymphoma.
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Agamaglobulinemia , Compostos Heterocíclicos , Neutropenia , Infecções por Papillomavirus , Verrugas , Agamaglobulinemia/tratamento farmacológico , Benzilaminas , Ciclamos , Fantasia , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/uso terapêutico , Humanos , Neutropenia/tratamento farmacológico , Doenças da Imunodeficiência Primária , Receptores CXCR4/uso terapêutico , Síndrome , Verrugas/tratamento farmacológico , Verrugas/patologiaRESUMO
Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that has been used for over 35 years to treat numerous conditions. ECP was initially approved by the US FDA in 1988 for the treatment of Sézary syndrome, a leukemic form of cutaneous T-cell lymphoma (CTCL). Although CTCL remains the only FDA-approved indication, ECP has since been used off-label for numerous other conditions, including graft-versus-host disease (GvHD), systemic sclerosis, autoimmune bullous dermatoses, Crohn's disease, and prevention of solid organ transplant rejection. In Canada, ECP is mainly used to treat CTCL, acute and chronic GvHD, and in some instances systemic sclerosis. Herein, we review the current concepts regarding ECP mechanism of action, treatment considerations and protocols, and efficacy.
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Dermatologia , Doença Enxerto-Hospedeiro , Linfoma Cutâneo de Células T , Fotoferese , Escleroderma Sistêmico , Neoplasias Cutâneas , Humanos , Fotoferese/métodos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Linfoma Cutâneo de Células T/tratamento farmacológico , Escleroderma Sistêmico/terapiaRESUMO
Retinoids are natural and synthetic vitamin A derivatives that are effective for the prevention and the treatment of non-melanoma skin cancers (NMSC). NMSCs constitute a heterogenous group of non-melanocyte-derived skin cancers that impose substantial burdens on patients and healthcare systems. They include entities such as basal cell carcinoma and cutaneous squamous cell carcinoma (collectively called keratinocyte carcinomas), cutaneous lymphomas and Kaposi's sarcoma among others. The retinoid signaling pathway plays influential roles in skin physiology and pathology. These compounds regulate diverse biological processes within the skin, including proliferation, differentiation, angiogenesis and immune regulation. Collectively, retinoids can suppress skin carcinogenesis. Both topical and systemic retinoids have been investigated in clinical trials as NMSC prophylactics and treatments. Desirable efficacy and tolerability in clinical trials have prompted health regulatory bodies to approve the use of retinoids for NMSC management. Acceptable off-label uses of these compounds as drugs for skin cancers are also described. This review is a comprehensive outline on the biochemistry of retinoids, their activities in the skin, their effects on cancer cells and their adoption in clinical practice.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/patologia , Retinoides/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/prevenção & controle , Vitamina A/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/prevenção & controleRESUMO
BACKGROUND: Non-melanoma skin cancer (NMSC) incidence has been increasing steadily around the world. The aim of the study is to describe geographic trends in incidence and mortality of NMSC in Russia between 2007 and 2017 and compare findings to other European countries. METHODS: We used geospatial analysis to map the incident cases and descriptive statistical analysis to analyze trends. Additionally, we assessed the relationship between ethnicity, geographic latitude/longitude, and NMSC incidence/mortality rates. We retrospectively analyzed the data from the Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, for 2007-2017. Routine methods of descriptive epidemiology were used to study incidence and mortality rates by age groups, years, and jurisdictions (i.e., Federal Districts and Federal Subjects). RESULTS: In total, 733,723 patients were diagnosed with NMSC in Russia over the period 2007-2017, of whom 63% were women. The overall age-standardized incidence and mortality rates were 29.64/100,000 and 0.70/100,000, respectively. There was a consistent increase in age-standardized incidence rates over the study period, with a decreasing mortality rate. Geographic mapping revealed north-to-south and east-to-west gradients for NMSC. CONCLUSIONS: This study demonstrated longitudinal trends for NMSC incidence in Russia documenting that skin phototype, latitude/longitude, climate zones, and cultural practices remain dominant risk factors defining the epidemiology of NMSC. Moreover, this work identified several regions in the country (i.e., Republic of Adygea, Samara, Krasnodar Krai, etc.), where patient education/sun awareness campaigns will be useful to help reduce the risk of this malignancy.
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Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Distribuição por Idade , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Federação Russa/epidemiologia , Distribuição por Sexo , Taxa de SobrevidaRESUMO
Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell activation and subsequent elimination of cancer cells. However, they can also lead to immune intolerance and immune-related adverse event (irAEs) that are new and specific to these therapies. Cutaneous irAEs are the most common, arising in up to 34% of patients on PD-1 inhibitors and 43% to 45% on CTLA-4 inhibitors. The most common skin manifestations include maculopapular eruption, pruritus, and vitiligo-like lesions. A grading system has been proposed, which guides management of cutaneous manifestations based on the percent body surface area (BSA) involved. Cutaneous irAEs may prompt clinicians to reduce drug doses, add systemic steroids to the regiment, and/or discontinue lifesaving immunotherapy. Thus, the goal is for early identification and concurrent management to minimize treatment interruptions. We emphasize here that the severity of the reaction should not be graded based on BSA involvement alone, but rather on the nature of the primary cutaneous pathology. For instance, maculopapular eruptions rarely affect <30% BSA and can often be managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% BSA should be managed aggressively and the immunotherapy should be discontinued at once. There is limited literature available on the management of the cutaneous irAEs and most studies present anecdotal evidence. We review the management strategies and provide recommendations for psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, and other related skin toxicities.
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Toxidermias/terapia , Inibidores de Checkpoint Imunológico/efeitos adversos , Erupções Liquenoides/terapia , Neoplasias/tratamento farmacológico , Penfigoide Bolhoso/tratamento farmacológico , Psoríase/terapia , Alopecia em Áreas/induzido quimicamente , Alopecia em Áreas/tratamento farmacológico , Superfície Corporal , Toxidermias/etiologia , Humanos , Erupções Liquenoides/induzido quimicamente , Penfigoide Bolhoso/induzido quimicamente , Psoríase/induzido quimicamente , Índice de Gravidade de Doença , Síndrome de Stevens-Johnson/etiologia , Síndrome de Stevens-Johnson/terapia , Vasculite/induzido quimicamente , Vasculite/tratamento farmacológico , Vitiligo/induzido quimicamente , Vitiligo/terapiaRESUMO
IMPORTANCE: Systemic sclerosis (SSc) is a severe, chronic, and incurable autoimmune fibrotic skin disease with significant extracutaneous involvement. Low concordance rate in twin studies and unequal geographic distribution of SSc argues for importance of environment in disease initiation and progression. OBJECTIVE: In this manuscript we provide a summary of all investigated potential external risk factors for SSc. DATA SOURCES: A literature search in PubMed and EMBASE database was performed for studies published until January 1, 2020 by 2 reviewers (EN and LO) independently. FINDINGS: Occupational and/or environmental exposures to silica and organic solvents are associated with increased incidence and severity of SSc. Exposure to epoxy resins, asbestos, and particulate air pollution favors increased risk of SSc, but data are based on limited number of observational studies. There is insufficient evidence to conclude an association between SSc development and other occupational (eg, welding fumes) or personal exposures (eg, smoking, vitamin D deficiency). Association of SSc with silicone breast implants has been disproven. Infectious pathogens (eg, Helicobacter pylori and angiotropic viruses) and dysbiosis seem to play a role in SSc development and severity, but their role remains to be clarified. CONCLUSIONS AND RELEVANCE: It may be prudent to counsel our patients with SSc (or those at risk of SSc) to avoid occupations with exposure to silica, organic solvents, asbestos and epoxy resins; restraint from smoking, using cocaine or drugs with pro-fibrotic potential. While the association between low vitamin D and SSc remains to be confirmed, we believe that SSc patients should be encouraged to maintain healthy vitamin D levels as benefits outweigh the risks.
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Exposição Ambiental/efeitos adversos , Escleroderma Sistêmico/etiologia , Humanos , Fatores de Risco , Escleroderma Sistêmico/epidemiologiaRESUMO
Dupilumab, a monoclonal antibody against the common receptor of interleukin (IL)-4 and IL-13, was the first biologic therapy approved in Canada for treatment of moderate-to-severe atopic dermatitis (AD). While it is considered safe and effective, dupilumab is not universally effective and 8%-38% of patients develop conjunctivitis, while some patients develop head and neck dermatitis. Thus, new therapeutic options are warranted. While both IL-4 and IL-13 play important roles in the pathogenesis of AD, it has been recently demonstrated that IL-13 is the primary upregulated cytokine in AD skin biopsy samples. A placebo-controlled phase 2b clinical trial evaluating the efficacy and safety of lebrikizumab, an IL-13 inhibitor, in AD demonstrated that, at 16 weeks, Eczema Area and Severity Index (EASI) 75 and Investigator's Global Assessment (IGA) 0/1 were achieved by 60.6% and 44.6% of patients taking lebrikizumab at its highest dose (vs 24.3% and 15.3% of patients taking placebo, respectively). Moreover, treatment with lebrikizumab was associated with rapid improvement of pruritus and low rates of conjunctivitis (1.4%-3.8%). Another IL-13 monoclonal antibody, tralokinumab, was evaluated for safety and efficacy in moderate-to-severe AD. By week 12, among adults receiving 300 mg tralokinumab, 42.5% achieved EASI-75 and 26.7% achieved IGA 0/1 score (vs 15.5% and 11.8% in the placebo group, respectively). Both lebrikizumab and tralokinumab demonstrated acceptable safety profiles in AD (and non-AD) trials with adverse events often being comparable between treatment and control groups. Thus, IL-13 inhibitors may provide a safe and effective treatment alternative for patients with moderate-to-severe AD.
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Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Interleucina-13/antagonistas & inibidores , HumanosRESUMO
BACKGROUND: Gallbladder and biliary tract cancers are rare malignancies that carry a poor prognosis. Research on their epidemiologic trends is scarce. METHODS: We performed a retrospective analysis of the data in Canada using population-based cancer registries from 1992 to 2010. The incidence and mortality of gallbladder and extrahepatic bile duct cancers were examined at the levels of provinces/territories, cities, and Forward Sortation Area (FSA) postal codes. RESULTS: The incidence and mortality rates decreased over the study period. The average national incidence rate of gallbladder and biliary tract cancers was 30.92 cases per million individuals per year. Higher than average incidence rates were observed in Manitoba, Saskatchewan and Québec; there were contiguous regions with high incidence in Saskatchewan and Manitoba that suggest an area of putative case clustering. Higher incidence of gallbladder cancer was observed in women, whereas higher incidence of extrahepatic bile duct cancers was noted in men. Lower socioeconomic status and Hispanic race were found to be risk factors for gallbladder and biliary tract cancers. CONCLUSION: This is the first study to analyze the burden of gallbladder and biliary tract cancers in Canada. The geographic clustering trends present new avenues for research on environmental triggers.
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Ductos Biliares Extra-Hepáticos , Neoplasias do Sistema Biliar , Neoplasias da Vesícula Biliar , Neoplasias do Sistema Biliar/diagnóstico , Neoplasias do Sistema Biliar/epidemiologia , Canadá/epidemiologia , Feminino , Vesícula Biliar , Neoplasias da Vesícula Biliar/epidemiologia , Humanos , Incidência , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Cutaneous melanoma (CM) incidence has been increasing around the world. The goal of this study is to describe geographic trends in incidence and mortality of CM in Russia between 2001 and 2017. METHODS: To achieve this we used geo-informatic technique (mapping) and descriptive statistical analysis. Additionally, we studied the associations between ethnicity, geographic latitude/longitude, and CM incidence/mortality rates. We retrospectively analyzed the data from the Moscow Oncology Research Institute, Ministry of Health of the Russian Federation, for the period of the study. Routine methods of descriptive epidemiology were used to study incidence and mortality rates by age groups, years, and jurisdictions (i.e., Federal Districts and Federal Subjects of Russia). RESULTS: In total, 141,597 patients were diagnosed with melanoma in Russia over the period 2001-2017, of whom 62% were women. The overall age-standardized incidence and mortality rates were 4.27/100,000 and 1.62/100,000, respectively. Geographic mapping revealed north-to-south and east-to-west gradients. As the study was fully descriptive, retrospective, and based on official statistical reports, detailed characteristics of clinical forms, anatomic sites, Breslow depth, and treatments could not be analyzed. CONCLUSIONS: This study outlined the burden of melanoma in the Russian Federation, and the trends were similar to those observed in countries with similar latitudes and skin phenotype. The importance of the skin color gradient and recreational/cultural practices were some of the most important risk factors highlighted in this study for the development of melanoma in Russia.
Assuntos
Melanoma/epidemiologia , Neoplasias Cutâneas/epidemiologia , Feminino , Humanos , Incidência , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estudos Retrospectivos , Federação Russa/epidemiologia , Neoplasias Cutâneas/mortalidade , Melanoma Maligno CutâneoRESUMO
Human papillomavirus (HPV) remains the most common sexually transmitted infection with a lifetime incidence of over 75%. Based on US data from the Centers for Disease Control and Prevention (CDC), 64% of invasive HPV-associated cancers are attributable to HPV 16 or 18 (65% for females; 63% males) and may be prevented by vaccination with either the quadrivalent or nonavalent HPV vaccine. Public HPV vaccination programs are now the norm for women aged 9-45 years and men aged 9-26 years in Canada. Yet, only recently have guidelines begun to consider vaccination of men older than 26 years of age. There now exist compelling reasons to recommend vaccination against HPV amongst males >26 years of age. Recognizing that the risks posed by HPV infection persist beyond 26 years of age, that the vaccination of men aged 26-45 years with HPV vaccine confers immunogenicity at levels demonstrably efficacious against HPV-related diseases, and that the Food and Drug Administration recently expanded the HPV vaccination to include older men, it is argued that HPV vaccination in men older than 26 years of age should be routinely recommended.