The European Academy of Dermatology and Venereology (EADV) held its Virtual Congress 2020 event online as a replacement for one of its regular in-person meetings that was cancelled due to COVID-19. The online experience gave researchers, physicians, and members of the industry the opportunity to share and learn about the latest research related to dermatology. The event included high-quality presentations on various clinical topics, as well as e-posters presenting cutting-edge research, such as the results from recent clinical trials assessing treatment options as well as information on comorbidities associated with dermatological diseases. In this article, we summarize selected sessions and e-posters that focused on the treatment of psoriasis, acne, atopic dermatitis, rosacea, and aesthetic dermatology.
Dr. Luís Puig, of the Department of Dermatology at the Hospital de la Santa Creu I Sant Pau in Barcelona, Spain, presented on new therapeutic targets based on psoriasis pathophysiology. Dr. Puig reviewed current concepts regarding the pathogenesis of psoriasis, which included discussion of the recent focus on keratinocytes as key drivers of inflammation in psoriasis through the production of several cytokines, including interleukin (IL)-36. According to Dr. Puig, patients with severe autoinflammatory types of generalized pustular psoriasis are thought to have mutations of the antagonist of the receptor of IL-36. Dr. Puig also discussed specific genes implicated in the pathogenesis of pustular psoriasis and reviewed the IL-1 cytokines superfamily, of which IL-36 is a part. Dr. Puig then discussed IL-36 receptor binding kinetics, in connection to psoriasis, which leads to the production of IL-17A by CD4+ T cells in generalized pustular psoriasis and other conditions characterized by pustulosis. Dr. Puig then reviewed therapies in development that block the activation of the IL-36 receptor, including spesolimab and imsidolimab.
Prof. Paolo Gisondi of the University of Verona and Borgo Trento Hospital discussed the frequent association between moderate-to-severe psoriasis and metabolic and inflammatory comorbidities, including possible reasons for this association, and the expression of psoriasis-related inflammation that manifests beyond the skin. Prof. Gisondi discussed the common genetic links between psoriasis and related comorbidities, such as obesity, diabetes, and myocardial infarction.The professor also noted how inflammatory mediators released from psoriatic lesions can have systemic effects on the liver, adipose tissue, and skeletal muscle, which contribute to endothelial dysfunction and atherosclerosis. Prof. Gisondi also discussed the similar metabolic and immunologic pathways shared by psoriasis and obesity, closing his talk by questioning whether systemic treatment of psoriasis could prevent the development of comorbidities and identifying this as an area for future investigation.
Prof. Dimitrios Ioannides from the Hospital for Skin and Venereal Diseases and the Medical School of Thessaloniki, Greece, presented a talk on the psychological burden of psoriasis. Prof. Ioannides began by acknowledging the significant socioeconomic burden psoriasis places on patients, characterized by functional impairment, loss of professional opportunities, and costs of psoriasis treatment. Prof. Ioannides also discussed a 2016 report from the World Health Organization (WHO) that emphasized the immense impact psoriasis can have on the lives of patients, including difficulties with its unpredictable disease course and its association with significant comorbidities, such as cardiovascular disease (CVD), metabolic syndrome (MetS), inflammatory bowel disease (IBD), and depression. According to Prof. Ioannides, the WHO report also indicated that many patients with psoriasis receive incorrect or delayed diagnoses, emphasizing the need for improvement in psoriasis diagnosis and treatment. Prof. Ioannides also reviewed recent research that investigated specific social and emotional obstacles faced by patients with psoriasis, as well as discussed mechanisms involved in the link between psoriasis and depression, citing the impact of systemic inflammation and overlapping cytokines present in depression and psoriasis. Prof. Ioannides concluded his talk by outlining the ultimate goal in psoriasis treatment—timely, sustained control of the multiple manifestations of the disease while also addressing other dimensions of patients’ lives through collaboration with psychologists.
Griffiths et al presented results from their integrated long-term safety analysis of ixekizumab, which included data from 16 clinical trials involving 6,645 patients with moderate-to-severe plaque psoriasis. The investigators evaluated five years of treatment-emergent adverse event data, adjusting incidence rates with a special focus on reported infections, serious infection, injection-site reactions, allergic reaction/hypersensitivity, depression, major adverse cerebro-cardiovascular event, malignancies, and inflammatory bowel syndrome (IBS). According to their analysis, 4,184 participants developed adverse events, with nasopharyngitis and upper respiratory tract infection being the most common, 963 experienced serious adverse events, 510 participants discontinued treatment at some point, and 35 deaths were noted. Allergic reactions and hypersensitivity occurred in 941 participants, and depression was reported in 218 participants. For patients with IBS, either ulcerative colitis or Crohn’s disease were reported. Given the available data, Griffiths et al concluded that incidence rates for adverse events declined over the course of the studies, and ixekizumab’s safety and tolerability were “consistent with the known safety profile in patients with psoriasis.”
According to presenters Seyger et al, past studies have shown ixekizumab’s effectiveness in achieving Psoriasis Area and Severity Index (PASI)-75 scores in pediatric patients with moderate-to-severe psoriasis in as early as 12 weeks. Seyger et al presented the results from their most recent clinical trial supporting these previous findings. Here, the investigators evaluated the effectiveness of ixekizumab following 12 weeks of treatment weeks in pediatric patients with moderate-to-severe psoriasis. Using the Psoriasis Area and Severity Index (PASI) scores, researchers compared clearance rates of pediatric patients who were administered 40mg, 80mg, or 160mg (dosage based on body weight) of ixekizumab to those who received either etanercept, a tumor necrosis factor (TNF) inhibitor, or placebo. Researchers reported that following 12 weeks of treatment, pediatric patients with moderate-to-severe plaque psoriasis who received ixekizumab achieved greater improvements in PASI scores than patients in the other treatment groups.
Blauvelt et al presented the results of their study that analyzed the long-term effectiveness of ixekizumab based on data from the UNCOVER-3 study, which included participants with psoriasis of the scalp, nails, palms, or soles who were randomized to rreceive either 80mg of ixekizumab every two or four weeks (after a starting dose of 160mg), 50mg of etanercept twice a week, or placebo. At Week 12, eligible patients entered the long-term extension (LTE) period receiving ixekizumab every four weeks, which could be increased to every two weeks after Week 60, if deemed necessary by investigators, for up to five years. The results presented by Blauvelt et al pertain to this group of LTE patients. Results were measured using Psoriasis Scalp Severity Index (PSSI), the Nail Psoriasis Severity Index (NAPSI), and/or the Palmoplantar Psoriasis Area and Severity Index (PPASI). In patients with baseline scalp (n=329), nail (n=219), and/or palmoplantar (n=91) psoriasis who received ixekizumab every two or four weeks, including those who dosages were increased in frequency from every four weeks to every two weeks, 82.6 percent, 73.3 percent, and 88.5 percent reported complete clearance by Week 264, respectively. The investigators concluded that ixekizumab was able to sustain a high degree of efficacy through five years in patients with psoriasis of the scalp, nail, and/or palmoplantar areas.
Dr. Mariusz Sikora of the Department of Dermatology Medical University of Warsaw, began his presentation with an overview of the gut–skin axis, which, according to Dr. Sikora, involves a complex and multifactorial interplay between the microbiome, immune system, intestinal integrity, and environmental factors (e.g., diet). Dr. Sikora discussed this concept in the context of psoriasis, which he noted is associated with several gastrointestinal symptoms and diseases (e.g., celiac disease, IBD). He also highlighted his own recent research, which demonstrated an association between psoriasis and an altered gut barrier and possible translocation of bacterial metabolites. Dr. Sikora moved on to discuss research on the use of probiotics in the treatment of psoriasis, highlighting results of a study that reported 30 out of 45 of its participants (66.7%) who took a probiotic pill for 12 weeks achieved PASI-75 compared to18 out of 43 participants (41.9%) in the placebo group. Next, he discussed the gut–skin axis in atopic dermatitis (AD), explaining that people with AD appear to lack commensal gut bacteria (e.g., Bifidobacteria, Lactobacillus) or anti-inflammatory metabolites (e.g., short-chain fatty acids). Dr. Sikora described the results of a study in which researchers reported a decrease in SCORing Atopic Dermatitis (SCORAD) scale scores, an increase in IL-10 levels, and positive changes in the intestinal microbiome of participants with AD after eight weeks of probiotic supplementation. Despite this promising research, Dr. Sikora explained that additional research is required before general recommendations on the dose and duration of probiotic administration can be made.
Acne and Rosacea
Elena Araviiskaia, MD, PhD, of the Department of Dermatology and Venereal Diseases at the First Pavlov State Medical University in St. Petersburg, Russia, presented on the topic of acne and rosacea in pregnant women. Dr. Araviiskaia discussed mechanisms involved in the worsening of acne during certain periods of pregnancy, the scattered data concerning safety profiles of acne treatments, and the absence of high-quality clinical recommendations for managing acne in this patient population. She explained why acne might improve during the first trimester of pregnancy, citing the physiological increase of estrogens and the decrease of insulin-like growth factor (IGF)-1. However, Prof. Araviiskaia noted that an increase of androgens and progesterone during this period presents the risk of worsening acne during the first trimester. Prof. Araviiskaia also described commonly used acne treatments and their safety profiles for use in pregnant women, including azelaic acid, benzoyl peroxide, erythromycin, and clindamycin. She noted that topical dapsone should be stopped at least one month prior to infant delivery and that topical retinoids tretinoin and adapalene are not recommended for use during pregnancy. Prof. Araviiskaia discussed oral zinc as a safe and effective treatment for acne during pregnancy at doses below 75mg/day. In regard to rosacea treatment in pregant women, Dr. Araviiskaia cited azelaic acid and topical metronidazole and clindamycin as effective treatments for mild-to-moderate papulopustular rosacea in this patient population. She also provided guidance for treating rosacea fulminans during pregnancy, highlighting a topical treatment course comprising topical drying compounds and surgical drainage.
Prof. Araviiskaia also presented on another topic—the role of microbes in rosacea, including symbiotic microbiota (e.g., Demodex folliculorum, Staphylococcus epidermidis) and potential pathogens (e.g., Bacillus oleronius, Chlamydia pneumoniae, Helicobacter pylori). Prof. Araviiskaia reviewed studies that have compared skin microbiota composition in people with normal skin to those with rosacea, noting that the specific types of bacteria potentially involved in rosacea must be studied further to be determined. Prof. Araviiskaia also described the effects of aging and skin temperature on the skin bacteria composition and activity and how these effects might influence rosacea, highlghting research that demonstrated the topical antibiotic metronidazole, used in the treatment for rosacea, did not appear to alter the skin microbiota composition.
Tilo Biedermann, MD, of the Department of Dermatology and Allergy at the Technical University of Munich, began his presentation with discussion of the exponentially growing number of scholarly publications on AD within the last five years. The general pathophysiology of AD as an interdependence between epidermal barrier dysfunction and immune responses present in patients with the condition was described. Discussion regarding how genetic susceptibility to barrier defects encourages skin dysbiosis in people with AD was provided. Type 2 immune responses were described as being the entry point for the development of AD due to downregulation of barrier function, and barrier dysfunction and cutaneous dysbiosis were also described as entry points for AD, due to the resulting Type 2 inflammation. The presenter highlighted research that has shown that the skin microbiome of people with AD to contain a diverse variety of bacteria, but during a flare, skin microbiome diversity is lost and Staphylococcaceae becomes dominant, with the number of Staphylococcaceae increasing with the severity of the condition. However, this diversity has been shown to be recoverable post-flare. He highlighted research in which investigators tested interventions to remedy this dysbiosis by placing bacterial signals on the skin and observing significant reductions in SCORAD after one month. Dr. Biedermann also discussed how modern therapeutics, such as dupilumab, can reverse the drivers of AD.
Patrick M. Brunner, MD, MSc, presented a talk on complications and comorbidities of AD. DIscussion included the increased risk of coronary artery disease in patients with severe AD due to systemic inflammation that affects the vascular system. One possible explanation for this is the presence of circulating inflammatory mediators in the blood of people with AD, which activate endothelial cells, contributing to CVD. Research that has shown that treatment with cyclosporine can reduce these inflammatory mediators was highlighted. While not a long-term treatment, this research indicates that these mediators are modifiable. Data demonstrating an increased risk of bone fracture in people with AD was reviewed, but whether this increased risk was due to the disease itself or corticosteroid treatment was unclear. Infectious complications of AD were discussed, including impetigo, eczema herpeticum, eczema coxsakium, and molluscum contagiosum, suggesting that the dearth of antimicrobial peptides on AD-affected skin might contribute to these infections. Weaker associations between AD and lymphoma, basal cell carcinoma, and squamous cell carcinoma were briefly discussed; more in-depth discussion was provided regarding the clearer associations between AD and neuropsychiatric disorders, such as depression, anxiety, attention deficit hyperactivity disorder, and autism spectrum disorders, pointing to chronic systemic inflammation, which has been shown to negatively impact brain function, as a possible cause of these comorbid conditions.
Ashraf Badawi, MD, PhD, presented updates on laser applications in aesthetic dermatology. Use of laser procedures during pregnancy was reviewed, with reference to an analysis that demonstrated the safety of laser treatments during pregnancy, including carbon dioxide and neodymium-doped yttrium-aluminum garnet [YAG]) laser treatments for genital condylomata and holmium YAG and pulse-dye laser treatments for urolithiasis. The question of whether laser tattoo removal increases risk of cancer, based on reports of patients who developed melanoma following this procedure, was addressed: melanoma is not an effect of the laser itself, but rather due to pre-existing nevi that are masked by the tattoos. For this reason, tattoo removal laser procedures should only be performed by certified dermatologists who will properly examine the tattooed skin for suspicious lesions prior to treatment. Challenges in treating pigmented lesions with lasers, including resistance, recurrence, complications, unrealistic patient expectations, and low profitability were also discussed.
Prof. Thierry Passeron gave a presentation on vitiligo treatment. The three objectives of vitiligo treatment were reviewed: halting melanocytic loss, inducing the differentiation and proliferation of melanocytes, and preventing relapses. Treatments used to halt depigmentation act by targeting the immune system were discussed, including recent research on Janus-kinase (JAK) inhibitors, such as oral tofacitinib and ruxolitinib (oral and topical), which have been shown to halt depigmentation and induce repigmentation in patients with vitiligo. Treatments inducing the differentiation of melanocyte stem cells were reviewed, including targeting the Wnt pathway to induce the differentiation and proliferation of melanocyte progenitors. Discussion regarding targeting IL-15 to deplete memory resident T cells. to prevent relapes was also provided.
Dr. Robert Artur Dahmen opened his presentation by generally defining skin aging and its pathogenesis, marked by collagen fragmentation, collagen degradation, and a decreased rate of collagen synthesis. Research on new retinoid formulations, including two new retinoids, retinyl retinoate and hydroxypinacolone retinoate, both of which have demonstrated efficacy similar to retinoic acid, but without as much irritation, was also discussed. Discussion also included the use of alpha-hydroxy acids as anti-aging ingredients due to their ability to promote the production of ceramides, hyaluronic acid, collagen, and elastin. Antiaging benefits of topical ascorbic acid were reviewed, and extreme instability as a disadvantage of the ingredient was noted. The more modern ethyl ascorbic acid, a stable, water-soluble derivative of ascorbic acid, was highlighted as an effective alternative. Studies on peptides, including copper peptides and acetyl hexapeptide-8, that have demonstrated anti-wrinkle properties, and niacinamide were reviewed. Discussion regarding structuring these ingredients into day and night regimens for patients seeking an effective anti-aging routine was also provided.