Cutaneous Melanoma Mortality-to-Incidence Ratio and Its Association With Socioeconomic and Healthcare Factors in Canada: A National Ecological Study.

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.

Anti-inflammatory effect of biologic therapy in patients with psoriatic disease: A prospective cohort FDG PET study.

AIM: The aim of the study was to evaluate the changes in central vascular inflammation measured by FDG PET and myocardial blood flow reserve (MFR) determined by 82Rb PET following therapy with biologic agents for 6 months in patients with psoriatic arthritis (PsA) and/or cutaneous psoriasis (PsO) (group 1) and compare with PsO subjects receiving non-biologic therapy (group 2) and controls (group 3). METHODS AND RESULTS: Target-to-background ratio (TBR) by FDG PET in the most diseased segment of the ascending aorta (TBRmax) was measured to assess vascular inflammation. 82Rb PET studies were used to assess changes in left ventricular MFR. A total of 34 participants were enrolled in the study (11 in group 1, 13 in group 2, and 10 controls). A significant drop in the thoracic aorta uptake was observed in the biologic-treated group (ΔTBRmax: - .46 ± .55) compared to the PsO group treated with non-biologic therapy (ΔTBRmax: .23 ± .67). Those showing response to biologic agents maintained MFR compared to who showed no response. CONCLUSION: In a cohort of psoriasis patients treated with biologics, FDG uptake in the thoracic aorta decreased over the study period. Patients who demonstrated a significant anti-inflammatory response on FDG PET imaging maintained their MFR compared to non-responders.

Identification of significant geographic clustering of polycythemia vera cases in Montreal, Canada.

BACKGROUND: Polycythemia vera (PV) is a chronic myeloproliferative neoplasm associated at times with debilitating symptoms and a significant mortality rate. Understanding the demographics, epidemiology, and geography of this disease may provide further insight into important risk factors associated with its development. The objective of this study was to analyze patient demographics, incidence, and mortality rates, as well as the geographic distribution of PV patients in Canada between 1992 and 2010. METHODS: This study was achieved by analyzing the Canadian Cancer Registry, Le Registre Québécois du Cancer, and the Canadian Vital Statistics patient databases. RESULTS: A total of 4645 patients were diagnosed with PV between 1992 and 2010. While the annual incidence rate of this cancer fluctuated in Canada, mortality rate analysis indicated a decreasing trend. Geographically, PV incidence rates were notably elevated in the province of Quebec compared with the Canadian average. Further analysis of high-incidence forward sortation areas indicated a striking clustering of cases in the H4W region encompassing the Côte-Saint-Luc borough of Montreal, with an incidence of 102.97 (95% confidence interval, 75.11-137.79) cases per million per year, which is >13 times the national average. CONCLUSION: The residential area of Côte-Saint-Luc is an important PV cluster in Canada, with high concentration of retirement homes and geriatric hospices. Also, Jewish residents comprise >60% of the population in this neighborhood. These findings suggest that an older age and, potentially, an inherent genetic predisposition may be implicated in the pathogenesis of this malignancy. This study provides a comprehensive overview of PV burden/geographic distribution of cases in Canada.

Analysis of acute myeloid leukemia incidence and geographic distribution in Canada from 1992 to 2010 reveals disease clusters in Sarnia and other industrial US border cities in Ontario.

BACKGROUND: Several risk factors have been implicated in acute myeloid leukemia (AML) leukemogenesis. However, the epidemiologic distribution and precise triggers for AML in Canada remain poorly understood. METHODS: In this study, demographic data for AML patients in Canada from 1992 to 2010 were analyzed using 3 independent population-based cancer registries. The AML incidence and mortality rates were examined at the levels of province/territory, city, and forward sortation area (FSA) postal code. RESULTS: In total, 18,085 patients were identified. AML incidence was documented to be 30.61 cases per million individuals per year (95% confidence interval [CI], 30.17-31.06) from 1992 to 2010. Five industrial cities in Ontario were identified where incidence rates were significantly higher than the national average: Sarnia, Sault Ste. Marie, Thunder Bay, St. Catharines, and Hamilton. Analysis at the FSA postal code level identified significant patient clusters of AML in these cities. Specifically, FSA N7V in Sarnia, Ontario had an incidence of 106.81 (95% CI, 70.96-161.86) cases per million individuals per year, which is >3 times higher than the national average. The pollution from local oil refineries and chemical plants in Sarnia may be implicated as a risk factor for AML in that city. Analysis of mortality rates at the province and city levels corroborated the findings from the incidence data. CONCLUSION: These results provide a comprehensive analysis of AML burden in Canada and reveal striking geographic case clustering in industrial Ontario cities and potentially implicate exposure to materials/pollution from these plants as an important risk factor for developing AML in Canada.

Multiple myeloma epidemiology and patient geographic distribution in Canada: A population study.

BACKGROUND: Multiple myeloma (MM) is a malignancy of mature plasma cells. Environmental risk factors identified for this malignancy, among others, include farming and exposure to pesticides. METHODS: Using 3 independent population-based databases (the Canadian Cancer Registry, le Registre Québécois du Cancer, and Canadian Vital Statistics), this study analyzed patients' clinical characteristics and the incidence, mortality, and geographic distribution of MM cases in Canada during 1992-2015. RESULTS: In total, ~32,065 patients were identified, and 53.7% were male. The mean age at the time of diagnosis was 70 ± 12.1 years. The average incidence rate in Canada was 54.29 cases per million individuals per year, and linear regression modeling showed a steady rise in the annual rate of 0.96 cases per million individuals per year. At the provincial level, Quebec and Ontario had significantly higher incidence rates than the rest of Canada. An analysis of individual municipalities and postal codes showed lower incidence rates in large metropolitan areas and in high-latitude regions of the country, whereas high incidence rates were observed in smaller municipalities and rural areas. Land use analysis demonstrated increased density of crop farms and agricultural industries in high-incidence areas. A comparison with the available data from 2011-2015 showed several consistent trends at provincial, municipal, and regional levels. CONCLUSIONS: These results provide a comprehensive analysis of the MM burden in Canada. Large metropolitan cities as well as high-latitude regions were associated with lower MM incidence. Higher incidence rates were noted in smaller cities and rural areas and were associated with increased density of agricultural facilities.

Cutaneous malignant melanoma incidence and mortality trends in Canada: A comprehensive population-based study.

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) is on the rise in many parts of the world. However, there is limited knowledge on the epidemiology of CMM in Canada. OBJECTIVE: To conduct a comprehensive population-based study of CMM in Canada. METHODS: We examined patient clinical and pathologic characteristics as well as the incidence and mortality trends of CMM in Canada using 3 independent population-based registries. RESULTS: In total, 72,565 Canadian patients were given CMM diagnoses during 1992-2010; 47.5% were women. Average age at the time of diagnosis was 56.5 years for women and 60.4 years for men. We report a steady increase in CMM incidence and mortality rates in both sexes. The overall incidence rate of CMM in Canada was 12.29 cases/100,000 person-years. We also report important differences in the incidence and mortality rates between Canadian provinces and territories; the highest incidence of this cancer was documented in Nova Scotia and Prince Edward Island. LIMITATIONS: Data on race, clinical disease stage, and Breslow depth of CMM was not available. CONCLUSION: This study, for the first time, defines the disease burden of CMM in Canada and highlights important longitudinal, geographic, and spatial differences in the distribution of CMM in this country.

Incidence, Mortality, and Spatiotemporal Distribution of Cutaneous Malignant Melanoma Cases Across Canada.

BACKGROUND: We recently reported a steady increase in the incidence and mortality of cutaneous malignant melanoma (CMM) in Canada during 1992-2010. OBJECTIVES: The objective of this article is to examine the distribution of Canadian CMM patients at the level of provinces, cities, and forward sortation area (FSA) postal codes. METHODS: Using 3 Canadian population-based registries, we conducted an in-depth examination of the incidence and mortality trends for 72 565 Canadian CMM patients over the period 1992-2010. RESULTS: We found that among 20- to 39-year-olds, the incidence of CMM in women (7.17 per 100 000 individuals) was significantly higher than in men (4.60 per 100 000 individuals per year). Women age 80 years and older had an incidence of CMM (58.46 cases per 100 000 women per year) more than 4 times greater than the national average (12.29 cases per 100 000 population per year) and a corresponding high mortality rate (20.18 deaths per 100 000 women per year), when compared with the Canadian melanoma mortality of 2.4 deaths per 100 000 per year. In other age groups men had higher incidence and corresponding melanoma mortality rates. We also studied CMM incidence by province, city, and FSA postal codes and identified several high-incidence communities that were located near the coast/waterfronts. In addition, plotting latitude measures for cities and FSAs vs CMM incidence rate confirmed the inverse relationship between geographical latitude and incidence of melanoma in Canada (slope = -0.22 ± 0.05). CONCLUSIONS: This research may help develop sex-, age- and geographic region-specific recommendations to decrease the future burden of CMM in Canada.

Drug-induced phototoxicity: A systematic review.

BACKGROUND: Phototoxicity has been attributed to numerous oral drugs over the past 60 years. OBJECTIVE: Determine the quality of evidence supporting suspected phototoxicity from oral drugs. METHODS: The MEDLINE and EMBASE databases were searched for all studies that contain original data for drug-induced phototoxicity and were published between May 1959 and December 2016. Study quality was assessed by using a modified Grading of Recommendations, Assessment, Development and Evaluation scale. RESULTS: The review included 240 eligible studies with a total of 2466 subjects. There were 1134 cases of suspected phototoxicity associated with 129 drugs. Most associations were supported by either very low-quality or low-quality evidence (89.1% of the studies). Medications supported by stronger evidence were vemurafenib, nonsteroidal anti-inflammatory drugs, and antibiotics, specifically, fluoroquinolones and tetracyclines. The most frequently reported drugs were vemurafenib, voriconazole, doxycycline, hydrochlorothiazide, amiodarone, and chlorpromazine. Photobiologic evaluation was performed in only 56 studies (23.3%), whereas challenge-rechallenge was done in 10% of cases. LIMITATIONS: Only English-language publications were reviewed. Cases of phototoxicity that had been incorrectly categorized as photoallergy would not have been included. CONCLUSIONS: Most purported associations between oral drugs and phototoxicity are not supported by high-quality evidence. Despite the variable quality of data, clinicians should be aware of the possible consequences of long-term use of culprit drugs.

Cutaneous candidiasis mimicking acute generalized exanthematous pustulosis: A case report.

Disseminated cutaneous candidiasis is a rare manifestation of candidiasis that arises most commonly from Candida albicans. It is described as a widespread erythematous papulopustular skin infection that typically affects premature newborns or immunocompromised patients. While candidal infections usually respond well to antifungal therapy, the clinical presentation of disseminated cutaneous candidiasis can often mimic a variety of other dermatologic conditions, that can lead to delayed diagnosis and treatment. We present a 67-year-old comorbid male patient with widespread erythema and superficial pustules resembling acute generalized exanthematous pustulosis (AGEP) that was actually an unexpected manifestation of disseminated cutaneous candidiasis. Prompt initiation of a topical and oral antifungal regimen contributed to marked improvement. Given the high frequency of drug eruptions in comorbid patients receiving multiple medications, alternate diagnoses like infections should be included in the differential diagnosis.

Imiquimod-induced bullous pemphigoid: A case report.

A 72-year-old man treated with 3.5% imiquimod cream for scalp actinic keratoses developed the usual crusted and erosive reaction but developed bullae on the scalp, as well as the limbs and torso after several weeks into treatment. Biopsy confirmed bullous pemphigoid. He was treated with clobetasol ointment, prednisone and methotrexate, with eventual disease control. He had a severe disease course. Bullous pemphigoid is usually idiopathic, but can be induced by skin trauma, as well as by several medications; this is the first report of imiquimod as a trigger. Imiquimod is a toll-like receptor 7 agonist that induces cellular apoptosis and recruits pro-inflammatory cytokines including tumour necrosis factor-alpha and interferon-alpha, which have been implicated in autoimmunity. This case highlights an unusual but severe adverse effect from topical imiquimod.

A case of classic adult pityriasis rubra pilaris successfully treated with a combination of acitretin and ustekinumab: A case report.

Classic adult pityriasis rubra pilaris is a severe papulosquamous disease that tends to resolve in 3-5 years but can have a devastating impact on patients while active. It shares features with psoriasis, but treatment remains largely empiric, based on case reports and series. The condition is often refractory to treatment, especially initially, with topical corticosteroids and oral acitretin the more commonly employed agents. Relatively high doses of acitretin are needed for adequate response, and adverse events often limit adherence. Given the similarity to psoriasis, biologic agents approved for psoriasis have been used with good effect in classic adult pityriasis rubra pilaris and show better tolerance than other agents. In this report, we describe the successful use of a combination of acitretin and ustekinumab in a case of classic adult pityriasis rubra pilaris.

Hypergammaglobulinemic purpura of Waldenström-Unusual and impressive case in a patient with myeloma: A case report.

Background: Hypergammaglobulinemic purpura of Waldenström is an uncommon disease, which presents mostly in women on the lower extremities. It is sometimes associated with underlying immune dysregulation. Sjögren syndrome is the most common association; however, rare occurrences of the self-resolving syndrome with lymphoma or myeloma have been reported. Case Summary: We describe an unusual and impressive presentation of hypergammaglobulinemic purpura of Waldenström in an elderly female patient with myeloma. Notably, the patient did not have any concurrent connective tissue diseases. Despite her florid presentation, her hypergammaglobulinemic purpura of Waldenström spontaneously resolved within a few days. Conclusion: Hypergammaglobulinemic purpura of Waldenström is a self-resolving but recurrent syndrome, which may be associated with autoimmune disorders or rarely myeloma. Early diagnosis of the syndrome may avoid unnecessary treatment interventions and should prompt screening for underlying diseases.

A rare case of granuloma faciale presenting with ulceration: A case report.

Granuloma faciale is an uncommon inflammatory dermatosis characterized by persistent dermal plaques, typically on the face, that mimic granulomatous disorders like sarcoidosis. Ulceration of granuloma faciale has very rarely been reported, and the plaques are usually asymptomatic and of cosmetic impact. We present a case of an 83-year-old male with recurrent granuloma faciale with spontaneous ulceration and monoclonal gammopathy of undetermined significance. Intralesional triamcinolone, 10 mg/mL monthly for 5 months, with pimecrolimus cream twice daily resolved the ulceration and the lesion continues to flatten and lighten. Ulceration is rare and atypical in granuloma faciale lesions which can be treated.

Vitiligo, reactive oxygen species and T-cells.

The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo.

Environmental and Other Extrinsic Risk Factors Contributing to the Pathogenesis of Cutaneous T Cell Lymphoma (CTCL).

The applications of disease cluster investigations in medicine have developed rather rapidly in recent decades. Analyzing the epidemiology of non-random aggregation of patients with a particular disease fostered identification of environmental and external exposures as disease triggers and promoters. Observation of patient clusters and their association with nearby exposures, such as Dr. John Snow's astute mapping analysis in the mid-1800's, which revealed proximity of cholera patients in London to a contaminated water pump infected with Vibrio cholerae, have paved the way for the field of epidemiology. This approach enabled the identification of triggers for many human diseases including infections and cancers. Cutaneous T-cell lymphomas (CTCL) represent a group of non-Hodgkin lymphomas that primarily affect the skin. The detailed pathogenesis by which CTCL develops remains largely unknown. Notably, non-random clustering of CTCL patients was reported in several areas worldwide and this rare malignancy was also described to affect multiple members of the same family. These observations indicate that external factors are possibly implicated in promoting CTCL lymphomagenesis. Here, we review the epidemiology of CTCL worldwide and the clinical characteristics of CTCL patients, as revealed by global epidemiological data. Further, we review the known risk factors including sex, age, race as well as environmental, infectious, iatrogenic and other exposures, that are implicated in CTCL lymphomagenesis and discuss conceivable mechanisms by which these factors may trigger this malignancy.