Gordon E. Searles

Hidradenitis Suppurativa in 64 Female Patients: Retrospective Study Comparing Oral Antibiotics and Antiandrogen Therapy

Background: Hidradenitis suppurativa (HS) is a recurrent disease confined to apocrine gland-bearing areas causing painful, deep-seated lesions and draining sinus tracts. Uniformly effective therapy is lacking. Improvements in current medical management strategies are needed. Objective: We sought to determine the success rate for a variety of treatments in our female HS patients and whether androgen-related tests can predict a response to antiandrogen therapy. As HS has been linked to a hyperandrogen state, we sought to determine if it is also associated with polycystic ovary syndrome (PCOS). Methods: A retrospective chart review was performed examining hormonal profiles and the response to a variety of treatments in female patients with HS. Results: Sixty-four female HS patients were identified (mean age 33 years). Antiandrogen therapy was superior to oral antibiotic therapy (55% vs 26%) based on a two-sample, two-sided, t-test statistic (p < .04). The prevalence of PCOS among our study patients in whom androgen markers were available was 8 of 21 (38.1%), and even if taken over all study patients, not necessarily investigated for PCOS, the prevalence was 8 of 64 (12.5%). This reflects a greater than expected prevalence among all women (10%). Conclusion: As a proof-of-concept study, despite limitations inherent in a retrospective chart review, there is sufficient signal to suggest that a hormonal manipulation approach to therapy should be considered in all women presenting with HS. Female patients presenting with HS should prompt investigations for underlying PCOS and insulin resistance.

THE EPIDERMAL MELANIN UNIT IN THE PATHOPHYSIOLOGY OF MALIGNANT MELANOMA

The epidermal melanin unit (EMU) denotes the symbiotic relationship between a melanocyte and a pool of associated keratinocytes. We propose to show that alterations in the biology of the EMU are the main determinant of the different patterns of intraepidermal growth of melanocytes in lentigo maligna melanoma (LMM) and superficial spreading melanoma (SSM). They also appear to affect the biosynthesis of melanin and melanosomes during malignant transformation. Findings in histochemical studies with monoclonal antibodies generated against melanosomal proteins to produce different stains of melanocytes of normal skin, dysplastic melanocytic nevi (DMN), common melanocytic nevi (CMN), LMM, and SSM have led to the suggestion that the altered melanosome synthesis is a main phenotype in the pathophysiology in neoplastic transformation of melanocytes. Altered melanin synthesis may also affect the carcinogenesis in malignant melanoma: pheomelanin is increased in malignant melanoma and DMN, but not in normal skin and CMN. Pheomelanin and its precursors could aid the malignant transformation of melanocytes through the generation of mutagenic ultraviolet photoproducts in familial DMN syndrome.

The Amazing Vanishing Canadian Dermatologist: Results from the 2006 Canadian Dermatology Association Member Survey

Background: The 2006 Canadian Dermatology Association (CDA) member survey tracked the Canadian dermatology workforce. Information on use of nondermatologist extenders, impact of financial burden on practice style, and wait times was collected in the survey. Objective: To survey Canadian dermatologists for specialty-specific physician resource information including demographics, workload, and future career plans and compare it to results from the 2001 survey. In addition, to explore three other areas not covered in the previous survey: patient access to dermatologic care through wait times, the use of nondermatologist extenders, and potential impact of educational financial debt on practice styles. Methods: CDA members in 2006 were surveyed by mail. Follow-up mailings were done for nonresponders. Survey results were compared to those of the 2001 survey. Results: Thirty-six percent (216 of 602) of Canadian dermatologists responded (70% in 2001). The national distribution was identical between surveys. The median age increased to 55 years; two-thirds of dermatologists are male. The median retirement age remained at 65 years. There was a shift from rural to urban practice locations; 78% practice in private offices. Three-fifths of dermatologists do mainly medical dermatology, a decrease between surveys. Pediatric dermatology decreased 10%, whereas surgical dermatology increased 52% between surveys. Fewer practitioners perform noninsured services, and half as many perform research or hospital consultations or teach medical students. Financial debt burden had no impact on selection of practice style. Median wait times for nonurgent consultations doubled from 5 to 10 weeks; follow-up visits increased from 4 to 5 weeks; noninsured consultations increased from 4 to 5 weeks. The national median wait time for a third available consultation appointment was 42 days (range 7–161 days). Seventeen percent of dermatologists reported using nondermatologist extenders. Training programs produce only 60% of new practitioners needed to replace retirees over the next 5 years. Existing training programs are at full capacity, and only the creation of new programs can expand training capacity. Conclusions: Although the face of Canadian dermatology shows a productive specialty committed to patient care, teaching, and research, the demographics of the Canadian baby boom generation will have a major negative impact on the effectiveness of Canadian dermatology in the service of the Canadian population. The attrition rate predicted in the 2001 survey and validated by the 2006 survey spotlights the critical imperative for the specialty to adapt to the future of a shrinking workforce in the face of expanding demand for its services.

Non-melanoma Skin Cancer in Canada Chapter 3: Management of Actinic Keratoses:

Background Actinic keratosis (AK) and cheilitis (AC) are lesions that develop on photodamaged skin and may progress to form invasive squamous cell carcinomas (SCCs). Objective To provide guidance to Canadian health care practitioners regarding management of AKs and ACs. Methods Literature searches and development of graded recommendations were carried out as discussed in the accompanying introduction (chapter 1 of the NMSC guidelines). Results Treatment of AKs allows for secondary prevention of skin cancer in sun-damaged skin. Because it is impossible to predict whether a given AK will regress, persist, or progress, AKs should ideally be treated. This chapter discusses options for the management of AKs and ACs. Conclusions Treatment options include surgical removal, topical treatment, and photodynamic therapy. Combined modalities may be used in case of inadequate response. AKs are particularly common following the longterm immunosuppression in organ transplant patients, who should be monitored frequently to identify emerging lesions that require surgery.

Think beyond the Skin: 2014 Canadian Expert Opinion Paper on Treating to Target in Plaque Psoriasis

Objective: Explore the feasibility of Treat to Target in the area of psoriasis as seen in other therapeutic areas such as hypertension, hyperlipidemia, diabetes and rheumatoid arthritis. Methods: Review validated, measurable targets for psoriasis, including physician global assessment (PGA), psoriasis area and severity index (PASI) and dermatology life quality index (DLQI). Examine principles brought forth in the published European consensus on psoriasis and develop a Canadian consensus on Treat to Target in psoriasis. Results: As PASI and DLQI are not routinely used in the community setting, we are recommending target at a PGA of zero (clear). Conclusion: Recommend that the target is a PGA of zero (clear) as it provides a simple and measurable result that the patient and physician can clearly understand.

Update on alefacept safety.

Background: Alefacept has been demonstrated in clinical trials to be an effective, safe, and well-tolerated treatment strategy when used alone or in combination with other antipsoriatic therapies in patients with chronic plaque psoriasis. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, Canadian phase IV registry evaluating the efficacy and safety of alefacept, alone or in combination with other antipsoriatic therapies, in patients with psoriasis. Methods: Patients with chronic plaque psoriasis were treated with at least one course of alefacept followed by an off-treatment period, typically lasting 12 or more weeks. Prospective follow-up was at least 60 weeks, depending on when patients presented for retreatment. Safety data collected throughout the study included the incidence of serious adverse events (SAEs), dosing suspensions, and withdrawals owing to adverse events. Results: Twelve SAEs were reported in psoriasis patients treated with at least one course of alefacept, with only one considered to be possibly related to the study drug. Approximately one-quarter of patients missed at least one dose of alefacept during the course of the study. A total of 291 doses of alefacept were missed, representing almost 4% of the total doses administered in this group of patients. Low CD4+ count was the most frequent reason for missed doses; however, no patient had persistently low CD4+ counts requiring permanent discontinuation of alefacept treatment. Seven patients in the AWARE registry discontinued treatment with alefacept, with the most common reason being patient request. Conclusion: The AWARE study supports the safety of alefacept used alone or in combination with other antipsoriatic therapies, in a broad population of real-world chronic plaque psoriasis patients in Canada.

Patterns of Combination Therapy with Alefacept for the Treatment of Psoriasis in Canada in the AWARE Study

Background: Evidence from clinical trials supports the use of alefacept for the treatment of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept. Methods: Patients with chronic plaque psoriasis were treated with at least one course of alefacept treatment followed by a period of at least 12 weeks off-treatment. The use of combination therapy with alefacept in a real-world population of psoriasis patients is presented here, including the types of psoriasis therapies received by patients at the time of enrolment, reasons for initiating alefacept, and discontinuation or dosage reduction of concomitant therapy. Results: The majority of patients were receiving other antipsoriatic therapies at the time of enrolment into the AWARE study, most commonly topical therapy, systemic agents, or phototherapy. Most patients were receiving monotherapy prior to the initiation of alefacept. There was little change in the use of topical therapies with alefacept at 24 weeks, whereas a substantial proportion of patients were able to reduce or discontinue concomitant systemic therapies and/or phototherapy. The use of combination therapy regimens was relatively consistent across the country and by age groups, although younger patients were prescribed systemic agents more often than older patients. Conclusion: Alefacept is commonly added to other antipsoriatic therapies in a broad population of real-world chronic plaque psoriasis patients in Canada and may allow for dosage reduction or discontinuation of concomitant systemic agents or phototherapy.

The AWARE Study: Methodology and Baseline Characteristics

Background: Alefacept was the first biologic therapy approved by Health Canada for the treatment of moderate to severe chronic plaque psoriasis and is used either alone or as part of combination therapy. Objective: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational phase IV Canadian study of psoriasis patients treated with alefacept. This studys main goals were to develop a shared, real-time, national clinical database to support best practice and optimize the care of patients receiving alefacept and to gain an understanding of how alefacept is used in Canadian clinical practice. Baseline patient demographic data are described herein. Methods: Patients with chronic plaque psoriasis were enrolled from 37 clinics across Canada. Subjects received at least one course of alefacept treatment followed by a period of at least 12 weeks off treatment and were prospectively followed for at least 60 weeks. Baseline assessments included patient demographics, relevant medical history, psoriasis and treatment history, reasons for initiating alefacept, enrolling physicians initial alefacept treatment plan and strategy, percent body surface area (BSA) involvement with psoriasis, and physicians baseline assessment of disease control. Subsequent assessments at each follow-up visit included the patients response and the physicians assessment. Results: A total of 426 adult patients with predominantly chronic plaque psoriasis, with or without other types of psoriasis, were enrolled into the AWARE registry. Patients generally had moderate to severe psoriasis, with more than half (55.8%) having little or no disease control at baseline as assessed by their clinician, and 77% had > 10% BSA involvement with psoriasis. All patients in the AWARE patient population were receiving one or more treatments for psoriasis prior to or at the time of enrolment, and the majority continued to receive concomitant treatments at the time of study enrolment. Conclusion: The AWARE registry enrolled a broad group of real-world patients with chronic plaque psoriasis treated with alefacept in clinical practices across Canada.

Non-melanoma Skin Cancer in Canada Chapter 1 Introduction to the Guidelines

Background Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma, represents the most common malignancy. Objective The aim of this document is to provide guidance to Canadian health care practitioners on NMSC management. Methods After conducting a literature review, the group developed recommendations for prevention, management, and treatment of basal cell carcinomas, squamous cell carcinomas, and actinic keratoses. These tumour types are considered separately in the accompanying articles. The Grading of Recommendations Assessment, Development and Evaluation system was used to assign strength to each recommendation. Results This introduction describes the scope and structure of the guidelines and the methods used to develop them. The epidemiology of NMSC is reviewed, as are the pathophysiologic changes occurring with damage to the skin, which lead to the formation of actinic keratoses and invasive squamous or basal cell carcinomas. Conclusions This introduction describes the need for primary prevention and offers an overview of treatment options that are discussed in later chapters of the guidelines.

Fatal toxic epidermal necrolysis associated with use of terconazole vaginal suppository.

Apreviously well, 25-year-old white woman presented to the University of Alberta Hospital Burn Unit with widespread cutaneous blistering. Five days previously, she had developed a pruritic vaginal discharge which a physician diagnosed as candidiasis, and a single terconazole vaginal suppository was administered. Twelve hours later, she developed the sudden onset of severe perineal pain, generalized skin redness, mouth tenderness, and bloody vaginal discharge. Examination at a local hospital showed the oral temperature of 38.5°C, confluent macular erythema involving approximately 25% of her body surface area (BSA), and edema of the oral mucosa, vaginal vault, and introitus. Within 12 hours, she had a positive Nikolsky sign, bullae appeared within erythematous areas which now involved approximately 70% BSA; the oropharynx was diffusely eroded, and bilateral blepharo-conjunctivitis was noted. Stevens-Johnsonsyndrome was diagnosed and she received two intravenous doses of prednisolone, but continued to developmore cutaneous bullae. Her white blood cell count was 0.9 X 109 per litre, and vaginal culture yielded nontypable alpha-hemolytic streptococcus. Viral, chlamydial, and mycoplasma cultures were negative. Upon transfer to the University of Alberta Hospital Burn Unit on day 5 of her illness, she was febrile (40.2°C), tachycardic, tachypneic, and hypotensive (blood pressure 100155 mm Hg). Mucosal surfaces of the mouth, eye, and vagina, and over 95% of her BSA had either bullae or showed marked redness and fragility. A white blood count was 1.1 X 109 per litre, with 35% bands; hemoglobin was 95 gIL, hematocrit 0.38, and platelet count 68 X 10 per