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1.
J Cutan Med Surg ; 28(5): 439-446, 2024.
Article in English | MEDLINE | ID: mdl-39075667

ABSTRACT

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.


Subject(s)
Melanoma , Skin Neoplasms , Socioeconomic Factors , Humans , Melanoma/mortality , Melanoma/epidemiology , Skin Neoplasms/mortality , Skin Neoplasms/epidemiology , Incidence , Canada/epidemiology , Melanoma, Cutaneous Malignant , Female , Healthcare Disparities , Male
2.
J Eur Acad Dermatol Venereol ; 37(4): 680-688, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36606565

ABSTRACT

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.


Subject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , Skin Neoplasms , Humans , Prospective Studies , Mycosis Fungoides/pathology , Lymphoma, T-Cell, Cutaneous/pathology , Skin Neoplasms/pathology , Biopsy
3.
J Cutan Med Surg ; 27(1): 20-27, 2023.
Article in English | MEDLINE | ID: mdl-36408849

ABSTRACT

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.


Subject(s)
Biomedical Research , Humans , Canada , Surveys and Questionnaires , Educational Status
4.
J Cutan Med Surg ; 27(4): NP1-NP36, 2023.
Article in English | MEDLINE | ID: mdl-37401812

ABSTRACT

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.


Subject(s)
Dermatology , Transgender Persons , Infant, Newborn , Humans , Male , Female , Gender Identity , Transgender Persons/psychology , Risk Factors
5.
Int J Mol Sci ; 24(5)2023 Mar 05.
Article in English | MEDLINE | ID: mdl-36902419

ABSTRACT

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.


Subject(s)
Keratosis, Actinic , Photochemotherapy , Humans , Keratosis, Actinic/pathology , Aminolevulinic Acid , Diclofenac , Imiquimod/therapeutic use , Photochemotherapy/adverse effects , Fluorouracil/therapeutic use , Photosensitizing Agents/therapeutic use , Treatment Outcome
6.
Dermatology ; 238(6): 1006-1017, 2022.
Article in English | MEDLINE | ID: mdl-35679838

ABSTRACT

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.


Subject(s)
Melanoma , Skin Neoplasms , Humans , Melanoma/epidemiology , Melanoma/etiology , Melanoma/prevention & control , Skin Neoplasms/epidemiology , Skin Neoplasms/etiology , Skin Neoplasms/prevention & control , Incidence , Ultraviolet Rays/adverse effects , Canada/epidemiology , Melanoma, Cutaneous Malignant
7.
J Cutan Med Surg ; 26(6): 600-603, 2022.
Article in English | MEDLINE | ID: mdl-36214337

ABSTRACT

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.


Subject(s)
Arthritis, Psoriatic , Psoriasis , Humans , Arthritis, Psoriatic/diagnosis , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/epidemiology , Prospective Studies , Psoriasis/complications , Psoriasis/drug therapy , Psoriasis/epidemiology , Referral and Consultation , Risk Assessment
8.
J Cutan Med Surg ; 26(1): 33-49, 2022.
Article in English | MEDLINE | ID: mdl-34261335

ABSTRACT

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.


Subject(s)
Immunity, Innate , Immunotherapy/methods , Skin Diseases/immunology , Skin Diseases/therapy , Wound Healing/immunology , Cytokines/immunology , Humans , Th2 Cells/immunology
9.
Skin Therapy Lett ; 27(6): 1-5, 2022 11.
Article in English | MEDLINE | ID: mdl-36469536

ABSTRACT

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.


Subject(s)
Janus Kinase Inhibitors , Psoriasis , Humans , TYK2 Kinase/therapeutic use , Psoriasis/drug therapy , Psoriasis/pathology , Thalidomide/adverse effects , Janus Kinase Inhibitors/adverse effects , Treatment Outcome , Severity of Illness Index
10.
Skin Therapy Lett ; 27(2): 1-5, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35385630

ABSTRACT

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.


Subject(s)
Agammaglobulinemia , Heterocyclic Compounds , Neutropenia , Papillomavirus Infections , Warts , Agammaglobulinemia/drug therapy , Benzylamines , Cyclams , Fantasy , Hematopoietic Stem Cell Mobilization , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/therapeutic use , Humans , Neutropenia/drug therapy , Primary Immunodeficiency Diseases , Receptors, CXCR4/therapeutic use , Syndrome , Warts/drug therapy , Warts/pathology
11.
Skin Therapy Lett ; 27(5): 1-6, 2022 09.
Article in English | MEDLINE | ID: mdl-36469458

ABSTRACT

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.


Subject(s)
Dermatology , Graft vs Host Disease , Lymphoma, T-Cell, Cutaneous , Photopheresis , Scleroderma, Systemic , Skin Neoplasms , Humans , Photopheresis/methods , Graft vs Host Disease/drug therapy , Lymphoma, T-Cell, Cutaneous/drug therapy , Scleroderma, Systemic/therapy
12.
Int J Mol Sci ; 23(20)2022 Oct 20.
Article in English | MEDLINE | ID: mdl-36293471

ABSTRACT

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.


Subject(s)
Carcinoma, Basal Cell , Carcinoma, Squamous Cell , Skin Neoplasms , Humans , Skin Neoplasms/drug therapy , Skin Neoplasms/prevention & control , Skin Neoplasms/pathology , Retinoids/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/prevention & control , Vitamin A/therapeutic use , Carcinoma, Basal Cell/drug therapy , Carcinoma, Basal Cell/prevention & control
13.
Dermatology ; 237(6): 1007-1015, 2021.
Article in English | MEDLINE | ID: mdl-33361697

ABSTRACT

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.


Subject(s)
Skin Neoplasms/epidemiology , Skin Neoplasms/pathology , Age Distribution , Aged , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Russia/epidemiology , Sex Distribution , Survival Rate
14.
J Cutan Med Surg ; 25(1): 59-76, 2021.
Article in English | MEDLINE | ID: mdl-32746624

ABSTRACT

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.


Subject(s)
Drug Eruptions/therapy , Immune Checkpoint Inhibitors/adverse effects , Lichenoid Eruptions/therapy , Neoplasms/drug therapy , Pemphigoid, Bullous/drug therapy , Psoriasis/therapy , Alopecia Areata/chemically induced , Alopecia Areata/drug therapy , Body Surface Area , Drug Eruptions/etiology , Humans , Lichenoid Eruptions/chemically induced , Pemphigoid, Bullous/chemically induced , Psoriasis/chemically induced , Severity of Illness Index , Stevens-Johnson Syndrome/etiology , Stevens-Johnson Syndrome/therapy , Vasculitis/chemically induced , Vasculitis/drug therapy , Vitiligo/chemically induced , Vitiligo/therapy
15.
J Cutan Med Surg ; 25(2): 188-204, 2021.
Article in English | MEDLINE | ID: mdl-32988228

ABSTRACT

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.


Subject(s)
Environmental Exposure/adverse effects , Scleroderma, Systemic/etiology , Humans , Risk Factors , Scleroderma, Systemic/epidemiology
16.
J Cutan Med Surg ; 25(3): 315-328, 2021.
Article in English | MEDLINE | ID: mdl-33350863

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Dermatitis, Atopic/drug therapy , Interleukin-13/antagonists & inhibitors , Humans
17.
HPB (Oxford) ; 23(10): 1541-1549, 2021 10.
Article in English | MEDLINE | ID: mdl-33863655

ABSTRACT

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.


Subject(s)
Bile Ducts, Extrahepatic , Biliary Tract Neoplasms , Gallbladder Neoplasms , Biliary Tract Neoplasms/diagnosis , Biliary Tract Neoplasms/epidemiology , Canada/epidemiology , Female , Gallbladder , Gallbladder Neoplasms/epidemiology , Humans , Incidence , Male , Retrospective Studies
18.
Dermatology ; 236(6): 500-507, 2020.
Article in English | MEDLINE | ID: mdl-32506063

ABSTRACT

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.


Subject(s)
Melanoma/epidemiology , Skin Neoplasms/epidemiology , Female , Humans , Incidence , Male , Melanoma/mortality , Middle Aged , Retrospective Studies , Russia/epidemiology , Skin Neoplasms/mortality , Melanoma, Cutaneous Malignant
19.
J Cutan Med Surg ; 24(3): 285-291, 2020.
Article in English | MEDLINE | ID: mdl-32154741

ABSTRACT

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.


Subject(s)
Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/administration & dosage , Adult , Age Factors , Canada/epidemiology , Guidelines as Topic , Humans , Incidence , Male , Middle Aged , Papillomavirus Infections/epidemiology , Prevalence
20.
J Cutan Med Surg ; 24(4): 340-349, 2020.
Article in English | MEDLINE | ID: mdl-32238063

ABSTRACT

BACKGROUND: Oral cavity cancers (OCCs) and oropharyngeal cancers (OPCs) continue to be a major source of morbidity and mortality worldwide requiring the shared effort of numerous specialists. Tobacco and alcohol consumption have long been identified as risk factors for both OCC and OPC. In addition, human papilloma virus (HPV) is gaining its position as the main causal agent for OPC. OBJECTIVE: The objective of this study is to analyze the epidemiology of OCC and OPC in Canada. METHODS: Data pertaining to the year of diagnosis, the patient's sex, age at the time of diagnosis, province/territory, city and postal code of oral cavity, and oropharyngeal malignancies diagnosed during 1992-2010 were extracted from the Canadian Cancer Registry and Le Registre Québécois du Cancer. RESULTS: In total, 21 685 OCC cases and 15 965 OPC cases were identified from 1992 to 2010. Of those, 84.97% were oral cavity squamous cell carcinomas (SCCs), 88.10% were oropharyngeal SCCs, and both had a significant male predominance. While oral cavity SCC incidence stabilized over the study period, oropharyngeal SCC continued to increase. Oral cavity SCC incidence increased with age, while oropharyngeal SCC incidence peaked in the 50- to 59-year age group. Detailed geographic distribution analysis of patients at the provincial/territorial, city, and postal code levels identified several patient clusters. CONCLUSIONS: This work highlights important epidemiological differences in trends between oral and oropharyngeal cancers, identifies high-incidence postal codes for each malignancy, and correlates incidence/mortality with known risk factors including alcohol/tobacco use and HPV infections, therefore providing a comprehensive understanding of epidemiology for these cancers in Canada.


Subject(s)
Mouth Neoplasms/epidemiology , Oropharyngeal Neoplasms/epidemiology , Squamous Cell Carcinoma of Head and Neck/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Alcohol Drinking/epidemiology , Canada/epidemiology , Child , Child, Preschool , Cities/epidemiology , Humans , Incidence , Infant , Infant, Newborn , Middle Aged , Mouth Neoplasms/mortality , Oropharyngeal Neoplasms/mortality , Papillomavirus Infections/epidemiology , Sex Factors , Squamous Cell Carcinoma of Head and Neck/mortality , Tobacco Use/epidemiology , Young Adult
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