Marni C. Wiseman

Risk of Second Primary Cancer and Death Following a Diagnosis of Nonmelanoma Skin Cancer

Cancer-free patients diagnosed with a first primary nonmelanoma skin cancer (NMSC) offer an opportunity for studying the risk of a second primary cancer without the confounding effect of systemic treatment. The objective of the study was to estimate the risk of second primary cancer in people with a history of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) and the risk of dying in cancer patients with a NMSC history. BCC and SCC cases diagnosed between 1956 and 2000 in Manitoba, Canada were followed-up for second primaries (other than NMSC). Standardized incidence and mortality ratios (SIR and SMR) were calculated. Men [SIR, 1.06; 95% confidence interval (95% CI), 1.02-1.10] and women (SIR, 1.07; 95% CI, 1.02-1.12) with a BCC history as well as men (SIR, 1.15; 95% CI, 1.08-1.22) with a SCC history were at greater risk of a second primary cancer. Overall, the increased risk was observed only in the first 4 years following a NMSC, although it remained increased for specific cancer sites. The risk remained higher in all age groups up to 75 years of age. People with a history of BCC (males: SMR, 1.09; 95% CI, 1.04-1.14; females: SMR, 1.24; 95% CI, 1.16-1.32) or SCC (males: SMR, 1.18; 95% CI, 1.09-1.27; females: SMR, 1.55; 95% CI, 1.35-1.79) had a greater risk of death following their second primaries. Even if NMSC patients are at greater risk of a second cancer, it is not recommended to follow them up beyond the generally accepted periodic examination of the skin.

Incidence and anatomic presentation of cutaneous malignant melanoma in central Canada during a 50-year period: 1956 to 2005

BACKGROUND Incidence rates of cutaneous malignant melanoma (CMM) have increased worldwide. Long-term studies examining rates and anatomic site-specific incidence on a population-based level are infrequent. OBJECTIVE We sought to examine the historical changes in the incidence and anatomic site presentation of CMM during a 50-year period in Manitoba, Canada. METHODS Using population-based data, all first diagnoses of CMM reported between 1956 and 2005 were identified. Age-specific rates, age-standardized incidence rates, and anatomic sites were recorded. RESULTS Incidence rates of CMM slowed for each sex beginning in 1981 for female patients and 1992 for male patients. Annual percent change revealed decreasing rates among male patients younger than 40 years (1992-2005: -5.3% [P = .03]) and female patients younger than 40 years (1987-2005: -1.8% [P = .15]). Similarly, middle-aged individuals (age 40-59 years) also had diminished annual percent change (men 1992-2005: 0.6% [P = .65]; women 1983-2005: -0.3% [P = .68]). The annual percent change for older men and women (60-79 and > or =80 years) continued to increase. Anatomic site-specific analyses revealed that the trunk was the most frequent site of CMM for young male patients (<60 years) whereas the lower extremities were the most common among young female patients (<60 years). Incidence rates for each site, however, are slowing. Among those aged 60 years and older, the rates for each anatomic site increased. LIMITATIONS Determining changes in tumor thickness would have been useful in determining whether the nature of tumors have changed over time; however, this is not recorded in our registry. CONCLUSION The rates of CMM are slowing; however, this change is confined to younger individuals. Anatomic site-specific CMMs are changing; rates among older individuals continue to increase for both sexes.

Topical 5% imiquimod in the treatment of lentigo maligna.

Background: Standard treatment for lentigo maligna (LM) is surgical excision with 5 to 10 mm margins. This can be cosmetically disfiguring. Imiquimod locally induces Toll-like receptors to release cytokines that destroy neoplastic melanocytes. Objective: The off-label use of topical 5% imiquimod cream may provide an alternative to surgery. This study reviews the use of imiquimod to treat LM. Methods: A 5-year retrospective and prospective chart analysis was conducted. Pretreatment biopsies confirmed the diagnosis. Treatment was individualized for each patient. Posttreatment biopsies and dermoscopy determined clearance of LM. Results: Twenty-seven patients were reviewed. There were 20 responders (74.1%) and 7 failures. The mean tumor size (area of an ellipse) was 6.69 cm2, and the mean treatment duration was 17.68 weeks. Neither the size of the tumor (p = .86) nor treatment duration (p = .18) was related to resolution of the lesion. Conclusion: Imiquimod is an effective treatment for LM that provides patients with a cosmetically favorable outcome when standard surgery is not an option.

Bullous cellulitis caused by Serratia marcescens.

Bullous cellulitis is a distinctive form of cellulitis most often caused by beta hemolytic streptococci. This report describes a case of bullous cellulitis caused by Serratia marcescens in an elderly diabetic woman with peripheral vascular disease. A discussion of this ubiquitous, nosocomial pathogen follows.

2016 Addendum to the Canadian Guidelines for the Management of Plaque Psoriasis 2009

Disclaimer: As in the original guidelines, physicians should use their best clinical judgment when determining whether and how to apply treatment recommendations in the individualized care of patients. This document is not intended to replace the guidance found in the relevant Canadian product monographs or other official information available for the therapeutics discussed. Every reasonable effort has been made to ensure the accuracy of this document. Any errors made here will be corrected in the next edition of the guidelines. Drug names: As in the original guidelines document, generic names have been used throughout this document. Any new trade name or generic name used in the addendum has been has listed in Appendix I at the end of this document. Directions for readers: This addendum should be used in conjunction with the original 2009 Canadian Guidelines for the Management of Plaque Psoriasis as a tool to guide physicians in clinical decision making. All changes to the content of the 2009 guidelines are presented by chapter, which correspond to the chapters in the original document. All new information is cross-referenced by page number and section/subsection to the original guidelines where the addendum applies. A table listing only new recommendations or modifications to existing recommendations follows each chapter. Legend XXXX X = If only additional references are added to existing text in the original guidelines, these are indicated in bold. All original text from the 2009 Guidelines is underlined. All new recommendations or modifications to existing recommendations are indicated in bold.

The Skin Microbiome in Atopic Dermatitis and Its Relationship to Emollients

Background: Human-associated bacterial communities on the skin, skin microbiome, likely play a central role in development of immunity and protection from pathogens. In atopic patients, the skin bacterial diversity is smaller than in healthy subjects. Objective: To review treatment strategies for atopic dermatitis in Canada, taking the skin microbiome concept into account. Methods: An expert panel of 8 Canadian dermatologists explored the role of skin microbiome in clinical dermatology, specifically looking at atopic dermatitis. Results: The panel reached consensus on the following: (1) In atopic patients, the skin microbiome of lesional atopic skin is different from nonlesional skin in adjacent areas. (2) Worsening atopic dermatitis and smaller bacterial diversity are strongly associated. (3) Application of emollients containing antioxidant and antibacterial components may increase microbiome diversity in atopic skin. Conclusion: The skin microbiome may be the next frontier in preventive health and may impact the approach to atopic dermatitis treatment.

A Consensus on Acne Management Focused on Specific Patient Features

Background: Most treatment guidelines for acne are based on clinical severity. Our objective was to expand that approach to one that also comprised individualized patient features: a case-based approach. Methods: An expert panel of Canadian dermatologists was established to develop demographic and clinical features considered to be particularly important in acne treatment selection. A nominal group consensus process was used for inclusion of features and corresponding appropriate treatments. Results: Consensus was achieved on the following statements: follicular epithelial dysfunction contributes to acne pathogenesis; inflammation from underlying disease(s) or prior treatment may impact further patient management; management focusing on specific patient features and on addressing psychosocial factors, including impact on quality of life, may improve treatment adherence and outcomes; and case-based scenarios are a practical approach to illustrate the effect of these factors. To address the latter, eight case profiles were developed. Conclusions: Management of acne should be based on multifactorial considerations beyond clinically determined acne severity and should include patient-reported impact, gender, skin sensitivity (including preexisting dermatoses), and phototype.

Case Report of Patient With Erythropoietic Protoporphyria and Basal Cell Carcinoma Diagnoses.

Background: Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer. There is a clear association between BCC development and ultraviolet (UV) radiation. Erythropoietic protoporphyria (EPP) is an inherited porphyria disorder that is a result of protoporphyrin accumulation, typically manifesting with phototoxicity. Case Summary: We report a case of a 24 year-old man with both EPP and BCC diagnoses. At the age of 4 years, the patient was diagnosed with EPP. The patient presented with a BCC on his nose at age 24 years, despite sun avoidance as the primary treatment for his EPP diagnosis. Conclusion: Consider the diagnosis of BCC in a patient with EPP, despite sun avoidance.

An Open Letter to Health Canada

Regulators are mandated to provide structured guidance on drug development. They approve drugs based upon their scientific and medical merits. They negotiate a disclosure of a drug’s profile—the label. And they provide ongoing monitoring of manufacturing, use, and safety once the drug is marketed. Posting of guidance documents notwithstanding, the foregoing are conducted behind closed doors and subject to coveted decision processes. The warnings and directions provided in the drug label are for the most part warranted. On occasion, the warnings and requirements are restrictive and unwarranted. The recent US Food and Drug Administration (FDA) approval and release of the brodalumab label bears witness. Brodalumab (Siliq), an IL-17R antagonist, was evaluated for the treatment of Crohn disease, psoriasis, and psoriatic arthritis (NCT02024646, NCT02029495). Six completed suicides occurred across all development programs, 4 within the psoriasis studies. One of the suicides reported in the psoriasis program was adjudicated as an accidental overdose of illicit drugs. With more than 4000 patients and nearly 10 000 patient years of exposure, the approximate suicide event rate of 30 per 100 000 patient years is marginally greater than the range of rates reported in the adult US population: 12 to 24 per 100,000. Depression is a known comorbidity of psoriasis. We know that depression is the major risk factor for suicide ideation, suicide attempts, and completion. Interestingly, depression scores improve in psoriasis populations receiving effective therapy, as do patients treated with brodalumab. The US Siliq label contains a boxed warning that advises physicians to be aware of the potential for depression and take action should a patient be at risk of suicide. Warnings of this sort deserve attention for all populations at risk. The label clearly states that no causal association with suicide ideation or completed suicide and brodalumab was found. Absence of implied and mechanistic causality, the cornerstones of Hill’s hypothesis, argues for statistical fluctuation within the sample population. Still, the monograph imposes an onerous burden on prescribers. The boxed warning and registration requirements appear orthogonal to a balanced and scientifically derived statement of facts. Motivation for inclusion of the boxed warning is obscure and unjustified. The Canadian health care system is undermanned and our patients underserviced. Imposing burdensome risk mitigation programs will do little more than impair access and limit therapeutic options available to our patients. As concerned clinicians, we respectfully request Health Canada provide scientifically and clinically sound guidance for brodalumab and not mime the United States.

Management of Moderate to Severe Plaque Psoriasis: The Emerging Role of IL-17 Inhibition

Over the past 15 years, we have witnessed great advances in the management of moderate to severe psoriasis. Exploration of pathways of tumour necrosis factor (TNF)–α and interleukins (ILs)—IL-12, IL-22, and IL-23—have evolved our understanding of the pathogenesis of psoriasis. These advances have allowed us to develop biologic therapies that significantly improved skin-related outcomes and overall well-being for patients with moderate to severe psoriasis. We developed a more in-depth understanding of how psoriasis affects different aspects of patients’ daily lives and its correlation with other common physical and psychological comorbidities. The availability of disease-specific tools and outcome measures has enabled us to assess the efficacy of available therapies and consider patient perspectives and satisfaction with treatments. With a better understanding of what patients expect from therapy, our ability to tailor the therapeutic approach toward individual characteristics and particular needs has significantly improved. This supplement focuses on interleukin IL-17–targeted therapies, the latest addition to the psoriasis treatment armamentarium. The IL-17 pathway was first identified in 1993; however, it was not until the past couple of years that its key role in chronic inflammatory conditions such as psoriasis was elucidated. This new understanding has come to fruition in agents that target IL-17A (secukinumab and ixekizumab) and the IL-17 receptor A (brodalumab). These novel agents hold the promise to overcome some of the current unmet needs in the treatment of moderate to severe psoriasis, including the achievement of complete skin clearance in a significant number of patients. In addition to providing an overview of the efficacy of IL-17–targeted therapies compared to other biologics, as demonstrated in phase II and III trials, we also discuss the impact of complete skin clearance on patient satisfaction with the treatment, which, until now, has been a significant unmet need and challenge faced by dermatologists. The latest evidence points to our being on the cusp of achieving 90% to 100% improvement on the Psoriasis Area and Severity Index (PASI) in a majority of our patients with psoriasis. The complete (PASI 100) or almost complete (PASI 90) skin clearance was previously possible in the minority of patients. That being said, one should keep in mind that the older agents such as TNF-α inhibitors and ustekinumab will continue to play a significant role in psoriasis management. Some of these agents have been used for over a decade and have established both short and long efficacy and safety profiles. The availability of novel agents with different mechanisms of action and their ability to clear the most ‘stubborn’ and bothersome disease should be welcome additions to psoriasis treatment armamentarium. Some patients, whether skin, joints, or bowel, respond better to older agents than the newer agents. There are patients who lose response even on the newer agents and may be required to revert to older therapies. In addition to the high efficacy and improved outcomes, these molecules have also been shown to have excellent safety profiles. As with any novel therapy, however, there is Original Article 722552 CMSXXX10.1177/1203475417722552Journal of Cutaneous Medicine and SurgeryLynde et al research-article2017