Top Ten Research Priorities for Psoriasis, Atopic Dermatitis and Hidradenitis Suppurativa: The SkIN Canada Priority Setting Initiative.

BACKGROUND: The Skin Investigation Network of Canada (SkIN Canada) is a new national skin research network. To shape the research landscape and ensure its value to patient care, research priorities that are important to patients, caregivers, and health care providers must be identified. OBJECTIVES: To identify the Top Ten research priorities for 9 key skin conditions. METHODS: We first surveyed health care providers and researchers to select the top skin conditions for future research within the categories of inflammatory skin disease, skin cancers (other than melanoma), and wound healing. For those selected skin conditions, we conducted scoping reviews to identify previous priority setting exercises. We combined the results of those scoping reviews with a survey of patients, health care providers, and researchers to generate lists of knowledge gaps for each condition. We then surveyed patients and health care providers to create preliminary rankings to prioritize those knowledge gaps. Finally, we conducted workshops of patients and health care providers to create the final Top Ten lists of research priorities for each condition. RESULTS: Overall, 538 patients, health care providers, and researchers participated in at least one survey or workshop. Psoriasis, atopic dermatitis and hidradenitis suppurativa (inflammatory skin disease); chronic wounds, burns and scars (wound healing); and basal cell, squamous cell and Merkel cell carcinoma (skin cancer) were selected as priority skin conditions. Top Ten lists of knowledge gaps for inflammatory skin conditions encompassed a range of issues relevant to patient care, including questions on pathogenesis, prevention, non-pharmacologic and pharmacologic management. CONCLUSIONS: Research priorities derived from patients and health care providers should be used to guide multidisciplinary research networks, funders, and policymakers in Canada and internationally.

Efficacy of Allogeneic Hematopoietic Cell Transplantation for Autoimmune Diseases.

Allogeneic hematopoietic cell transplantation (HCT) may be efficacious for autoimmune diseases (AIDs), but its efficacy for individual AIDs is unknown. Factors influencing the likelihood of relapse for each AID are also unknown. This study aimed to determine the likelihood of relapse for each common AID and to generate hypotheses about factors influencing the likelihood of relapse. We reviewed charts of adult patients with nonhematologic AIDs who had undergone HCT in Alberta (n = 21) and patients described in the literature (n = 67). We used stringent inclusion criteria to minimize the inclusion of patients whose AID may have been cured before transplantation. We also used stringent definitions of AID relapse and remission. AID relapsed in 2 of 9 patients (22%) with lupus, in 4 of 12 (33%) with rheumatoid arthritis (RA), in 0 of 4 (0%) with systemic sclerosis (SSc), in 3 of 16 (19%) with psoriasis, in 1 of 12 (8%) with Behçet's disease (BD), in 1 of 15 (7%) with Crohn's disease (CD), in 0 of 5 (0%) with ulcerative colitis (UC), in 4 of 8 (50%) with multiple sclerosis (MS), and in 3 of 3 (100%) with type 1 diabetes mellitus (T1DM). Among highly informative patients (followed for >1 year after discontinuation of immunosuppressive therapy if no relapse, or donor AID status known if relapse), relapse occurred in 0 of 3 patients with lupus, in 2 of 7 with RA, in 0 of 2 with SSc, in 3 of 6 with psoriasis, in 0 of 3 with BD, in 0 of 10 with CD, in 0 of 3 with UC, in 2 of 3 with MS, and in 2 of 2 with T1DM. There appeared to be no associations between AID relapse and low intensity of pretransplantation chemoradiotherapy, multiple lines of AID therapy (surrogate for AID refractoriness) except perhaps for lupus, absence of serotherapy for graft-versus-host disease (GVHD) prophylaxis, lack of GVHD except perhaps for lupus, or incomplete donor chimerism. Even though remission commonly occurs after HCT in lupus, RA, SSc, psoriasis, BD, CD, and UC, HCT is efficacious for only a subset of patients. The efficacy appears to be unrelated to pretransplantation therapy, GVHD, or chimerism. Large studies are needed to determine the characteristics of patients likely to benefit from HCT for each AID.

Dermatologic Training and Practice in Canada: An In-Depth Review [Formula: see text].

As part of an in-depth review of the specialty for the Royal College of Physicians and Surgeons of Canada (RCPSC), the Dermatology Working Group (DWG) was tasked with leading a comprehensive and objective analysis of the current state of Dermatology practice and training patterns in Canada. Preliminary research for the report was conducted in 3 areas: a jurisdictional analysis, a literature review, and a landscape overview. The results of this research were published in the spring 2019 edition of the Journal of Cutaneous Medicine and Surgery. Various factors impacting the discipline were explored, including trends in the workforce, population needs, accessibility, and wait times, as well as issues in undergraduate and postgraduate medical education. The DWG, supported by the RCPSC's Office of Specialty Education, used information gained from the reviews, a national survey, and stakeholder perspectives to develop recommendations that address the current challenges and build upon opportunities for advancement in the specialty.

Beta3-Tubulin is Critical for Microtubule Dynamics, Cell Cycle Regulation, and Spontaneous Release of Microvesicles in Human Malignant Melanoma Cells (A375).

Microtubules (MTs), microfilaments, and intermediate filaments, the main constituents of the cytoskeleton, undergo continuous structural changes (metamorphosis), which are central to cellular growth, division, and release of microvesicles (MVs). Altered MTs dynamics, uncontrolled proliferation, and increased production of MVs are hallmarks of carcinogenesis. Class III beta-tubulin (ß3-tubulin), one of seven ß-tubulin isotypes, is a primary component of MT, which correlates with enhanced neoplastic cell survival, metastasis and resistance to chemotherapy. We studied the effects of ß3-tubulin gene silencing on MTs dynamics, cell cycle, and MVs release in human malignant melanoma cells (A375). The knockdown of ß3-tubulin induced G2/M cell cycle arrest, impaired MTs dynamics, and reduced spontaneous MVs release. Additional studies are therefore required to elucidate the pathophysiologic and therapeutic role of ß3-tubulin in melanoma.

Dermatologic Training and Practice in Canada: A Historical Overview.

The specialty of dermatology is constantly changing to meet the medical needs of our society. The discipline is in flux because of a variety of factors such as growing population needs, technological advancements, fiscal restraint, and demographic changes. As part of an in-depth review of the specialty, the Dermatology Working Group (DWG) for the Royal College of Physicians and Surgeons of Canada sought to determine whether the current training configuration is suitably preparing graduates to meet the societal health needs of dermatology patients. In this first of a 2-part series, the authors conducted comprehensive literature and historical reviews and a jurisdictional analysis to understand the current state of dermatology practice in Canada. Herein, they explore trends in the dermatology workforce, population needs, accessibility, and wait times, as well as issues in undergraduate and postgraduate medical education. In a subsequent publication, the DWG will utilize information gained from this historical analysis and jurisdictional review, stakeholder perspectives, and a national survey to shape the future of dermatology training in Canada.

Dermatologic uses of omalizumabtitle.

PURPOSE: Omalizumab is a recombinant humanized monoclonal antibody that inhibits the binding of immunoglobulin E (IgE) to the high-affinity IgE receptor (FceRI) on the surface of mast cells and basophils. Omalizumab has been approved for use in asthma, and new reports show promise in a variety of dermatologic diseases. Herein, we review the literature on omalizumab in dermatology and discuss the safety, efficacy and mechanisms of action for this emerging therapy. MATERIALS AND METHODS: PubMED, MEDLINE and Embase databases were searched for the period 1 January 1990 to 1 September 2016. Articles sourced were graded according to the Oxford Center for Evidence-Based Medicine Levels of Evidence Grades of Recommendation criteria. RESULTS: A total of 99 articles met our inclusion criteria. They included reports on the use of omalizumab in chronic spontaneous urticaria, atopic dermatitis, mastocytosis, hyper-IgE syndrome, bullous pemphigoid, Netherton syndrome, urticarial vasculitis, Churg-Strauss syndrome and toxic epidermal necrolysis. CONCLUSIONS: Omalizumab is effective in a variety of recalcitrant immune-mediated and autoimmune skin disorders. It is a safe and effective treatment for use in chronic idiopathic urticaria (Grade of recommendation: A). Randomized clinical trials with long-term follow-ups are warranted to firmly establish the role of omalizumab in the treatment of dermatologic disease.

Incidence of melanoma in organ transplant recipients in Alberta, Canada.

BACKGROUND: Many studies have documented the increased risk of non-melanoma skin cancers in organ transplant recipients (OTRs). However, the incidence of melanoma is less well defined. To date, there have been no studies on the incidence of melanoma in Canadian OTRs. Herein, we determine the incidence and clinical features of melanoma in a cohort of OTRs in Southern Alberta, Canada. METHODS: We used the Southern Alberta Transplant database to identify kidney and liver transplant recipients between the years 2000 and 2012. This population was cross-referenced with the Alberta Cancer Registry for a diagnosis of melanoma. The clinical features of all cases were obtained, and the standardized incidence rate was calculated. RESULTS: We identified 993 OTR patients, representing 5955 person-years. Only one patient developed a melanoma post-transplant, and this was a nodular melanoma. The age-standardized incidence rate was 11 per 100 000 (0.6 per 5955), compared to 13.4 per 100 000 in the general Alberta population (incidence rate ratio of 1.29, with 95% confidence interval of 0.17 to 9.82). CONCLUSIONS: This is the first Canadian study to investigate the association between organ transplantation and melanoma. Our study did not identify an increased risk of developing a de novo melanoma post-transplant.

Toll-like receptors: role in dermatological disease.

Toll-like receptors (TLRs) are a class of conserved receptors that recognize pathogen-associated molecular patterns (PAMPs) present in microbes. In humans, at least ten TLRs have been identified, and their recognition targets range from bacterial endotoxins to lipopeptides, DNA, dsRNA, ssRNA, fungal products, and several host factors. Of dermatological interest, these receptors are expressed on several skin cells including keratinocytes, melanocytes, and Langerhans cells. TLRs are essential in identifying microbial products and are known to link the innate and adaptive immune systems. Over the years, there have been significant advances in our understanding of TLRs in skin inflammation, cutaneous malignancies, and defence mechanisms. In this paper, we will describe the association between TLRs and various skin pathologies and discuss proposed TLR therapeutics.

Prevalence of non-organ-specific autoantibodies in patients with pemphigus vulgaris.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening, organ-specific, autoimmune, blistering disease of the skin and mucous membranes. Although several reports suggest an association between pemphigus and other autoimmune connective tissue disorders, studies that measure non-organ-specific autoantibodies are lacking. OBJECTIVE: To evaluate the prevalence of antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) antibodies, and antibodies against extractable nuclear antigens (ENAs) in PV patients. METHODS: Serum samples were obtained from 59 PV patients and 50 healthy controls. Indirect immunofluorescence assays containing human epithelial cell substrates (HEp-2) and Crithidia luciliae were used to detect ANA and anti-dsDNA antibodies, respectively. A multiplexed addressable laser bead immunoassay was employed to measure autoantibodies to: Smith (Sm), ribonucleoprotein (RNP), Sjögren syndrome B (SSB/La), Sjögren syndrome A (SSA/Ro), histidyl transfer ribonucleic acid synthetase (Jo-1), topoisomerase I (Scl-70), and ribosome-P (Ribo-P) antigens. RESULTS: Positive ANAs were obtained in 22 of 59 (37.3%) PV patients compared with 4 of 50 (8.0%) healthy controls (p

Effect of intravenous immunoglobulin on prednisone dose in patients with pemphigus vulgaris.

BACKGROUND: Current therapeutic options for the treatment of pemphigus vulgaris (PV) are prednisone and immunosuppressants. Patients unresponsive to high-dose systemic corticosteroids and conventional immunosuppressants may respond to intravenous immunoglobulin (IVIG). OBJECTIVE: The primary outcome was the change in prednisone dose at 6 months and 1 year post-IVIG administration. METHODS: A retrospective chart review of PV patients treated at Sunnybrook and Women's College Health Sciences Centre between January 1999 and October 2004 was conducted. Demographic information, corticosteroid and IVIG use, dosage, and the timing of administration for all patients were obtained. RESULTS: Eight PV patients, mean age of 50 years (+/- 14.7 years), were reviewed. There was a significant decrease in mean prednisone dose at 6 months (45%) and 12 months (71%) compared with the mean dose at the start of treatment (p < .05). LIMITATIONS: Concomitant medication use may influence results. CONCLUSION: This study demonstrates that IVIG can lower prednisone doses in PV patients.

Canadian consensus statement on the use of intravenous immunoglobulin therapy in dermatology.

BACKGROUND: As a safe, well-tolerated, and potentially beneficial therapy, intravenous immunoglobulin (IVIG) has been increasingly used by dermatologists to treat immune-mediated skin disease. However, practical and comprehensive guidelines for the use of IVIG have yet to be established. OBJECTIVE: To develop the first Canadian consensus statement on the use of IVIG therapy in skin disease. METHODS: A group of Canadian dermatologists convened to discuss current issues in IVIG therapy. The participants reviewed and evaluated the literature and shared clinical experience. Using a modified Delphi process, a consensus statement was developed. RESULTS: Herein we provide a brief overview of pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Recommendations for the management of these diseases are detailed, and therapeutic algorithms for the treatment of various autoimmune mucocutaneous blistering diseases are presented. The appropriate use of IVIG therapy is placed in context for each disease. CONCLUSION: Although preliminary data suggest that IVIG is a safe and effective therapy for many skin disorders, uncontrolled clinical trials, case series, and anecdotal case reports dominate the literature. Collaborative randomized controlled trials are required to firmly establish the role of IVIG in dermatology.