Elena Araviiskaia: Treating Acne and Rosacea During Pregnancy

OCTOBER 31, 2020

EADV presenter Elena Araviiskaia, MD, PhD, discusses the challenges of and best treatments for managing acne and rosacea in pregnant patients.

Highlights from Saturday, October 31

AGING

Pathogenesis of aging—Prof. Dr. Jean Krutmann

Prof. Dr. Jean Krutmann began his presentation with a proposed definition of the skin aging exposome: “external and internal factors and their interactions, affecting a human from conception to death, as well as the response of the body to these factors, that lead to biological and clinical signs of aging.” Additionally, he categorized environmental factors found in the skin aging exposome into seven categories: sun radiation, pollution, tobacco, temperature changes, lack of sleep, stress, and nutrition. He discussed epidemiological research which established an association between chronic exposure to traffic-related air pollution and increased facial lentigines. He also emphasized the interaction of these seven environmental factors and the effect this interaction has on aging, pointing to the interaction of pollution and sun radiation as an example. In addition to the skin aging exposome, Dr. Krutmann discussed the genome as the second contributing factor that influences extrinsic skin aging phenotypes.

 

Evidence-based anti-aging cosmeceuticals—Dr. Robert Artur Dahmen

Dr. Robert Artur Dahmen opened his presentation by generally defining skin aging and its pathogenesis, marked by collagen fragmentation and collagen degradation with a decreased rate of collagen synthesis. He discussed 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. He also discussed how alpha-hydroxy acids can be effective anti-aging ingredients by promoting the production of ceramides, hyaluronic acid, and collagen and elastin. Dr. Dahmen then reviewed the anti-aging benefits of topical ascorbic acid and noted extreme instability as a disadvantage of the ingredient, but pointed to the more modern ethyl ascorbic acid, a stable, water-soluble derivative of ascorbic acid, as an effective alternative. He also discussed studies on peptides, including copper peptides and acetyl hexapeptide-8, that have demonstrated its anti-wrinkle abilities, and niacinamide. Dr. Dahmen finished his talk by structuring these ingredients into day and night regimens for a patient seeking an effective anti-aging routine.

COSMECEUTICALS

How to Protect the Skin from Pollution—Dr. Hok Bing Thio

Dr. Hok Bing Thio, of Erasmus University Medical Center in the Netherlands, began his presentation by emphasizing that aryl hydrocarbon receptors in the skin are the target of environmental pollution. He reviewed how pollution induces microbiota modulation, activates aryl hydrocarbon receptors, generates reactive oxygen species, and stimulates inflammation in the skin. He also discussed how environmental pollution can worsen acne and how N-acetyl cysteine, an antioxidant, has been shown to block this pollution and reduce particulate matter-induced skin inflammation. Further, he explained how we can protect the skin from pollution using emollients, phenolic compounds (e.g., phenolic acids, flavonoids, stilbenoids, ellagitannins, phlorotannins) from natural products (e.g., cocoa, green tea, grape, pomegranate, marine algae) and possibly probiotics, mainly Staphylococcus epidermidis. He also briefly mentioned the benefits of a healthy diet rich in vitamin C and other antioxidants.

 

Cosmeceuticals: What’s Real, What’s Not—Dr. Elisabeth Roider

Dr. Elisabeth Roider, attending physician at the Department of Dermatology at the University Hospital of Basel in Switzerland, began with an overview of the history and definitions of cosmeceuticals, defined generally as topical preparations that are sold as cosmetics, but have performance characteristics that suggest pharmaceutical action. She also reviewed the wide array of compounds that fall under the umbrella of cosmeceuticals and the regulatory standards for cosmeceuticals that vary between countries, noting that Korea and Japan are the only countries that distinguish between cosmetic products, functional cosmetics, and drugs, while all other countries currently have no legal requirements for proving cosmeceutical product efficacy. After briefly comparing the specifics of European versus American regulation of cosmetics and pharmaceuticals, Dr. Roider moved on to discussing the current size of the cosmeceutical market, which she noted is over double the size of the cosmetic and dermatology product markets.

SKIN BARRIER AND MICROBIOME

Targeting the Gut-skin Axis: Probiotics for Skin Disorder Management—Mariusz Sikora, MD, PhD

Mariusz Sikora, MD, PhD, 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 multi-factorial interplay between the microbiome, immune system, intestinal integrity, and environmental factors, such as 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 and inflammatory bowel disease). 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 probiotics used to improve psoriasis, pointing to a study that reported 30 out of 45 of its participants (66.7%) who took a probiotic pill for 12 weeks achieved PASI-75, while only 18 out of 43 participants (41.9%) in the placebo group achieved the same. Next, he discussed the gut-skin axis in atopic dermatitis (AD), explaining that people with AD display a lack of commensal gut bacteria, including Bifidobacteria and Lactobacillus, and anti-inflammatory metabolites, such as short-chain fatty acids. Dr. Sikora highlighted a study that observed a decrease in SCORAD, an increase in the anti-inflammatory IL-10, 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 general recommendations on the dose and duration of probiotic administration cannot yet be made based on the available evidence.

 

Role of the Microbiome in Rosacea—Prof. Elena Araviiskaia

Prof. Elena Araviiskaia, MD, PhD, began her presentation by explaining the role of microbes in rosacea, pointing to symbiotic microbiota, such as Demodex folliculorum and Staphylococcus epidermidis, and potentially pathogenic agents, such as Bacillus oleronius, Chlamydia pneumoniae, and Helicobacter pylori. She discussed a few studies that have investigated the differences in skin microbiota composition in people with normal skin versus those with rosacea, but noted the specific types of bacteria potentially involved in rosacea must be studied further to be determined. Dr. Araviiskaia also explained the effects of age and skin temperature on the skin bacteria composition and activity in ways that are thought to influence rosacea. She also pointed out interesting research that found that the topical antibiotic metronidazole, an effective treatment for rosacea, does not alter the skin microbiota composition.

Highlights from Friday, October 30

INFLAMMATORY DISEASES: ATOPIC DERMATITIS

Update on Pathophysiology of Atopic Dermatitis—Prof. Dr. Tilo Biedermann

Tilo Biedermann, MD, of the Department of Dermatology and Allergy at the Technical University of Munich, began his presentation emphasizing the exponentially growing rate of scholarly publication on atopic dermatitis within the last five years. He described the general pathophysiology of AD as an interdependence between epidermal barrier dysfunction and immune responses present in patients with the condition. Dr. Biedermann explained that genetic susceptibility to barrier defects encourages skin dysbiosis in people with AD. He also reviewed how type 2 immune responses are the entry point for the development of AD, as it leads to the downregulation of barrier function. Further, he explained how barrier dysfunction and cutaneous dysbiosis also act as entry points for AD, as both induce type 2 inflammation. He highlighted research indicating that at baseline, the skin microbiome of people with AD contains 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, explained Dr. Biedermann. He pointed to research in which investigators tested interventions to remedy this dysbiosis by placing bacterial signals onto the skin and observed significant reductions in SCORAD after one month. Dr. Biedermann also discussed modern therapeutics, such as dupilumab, that reverse the drivers of AD.

 

Complications and Comorbidities—Assoc. Prof. Patrick Brunner

Patrick M. Brunner, MD, MSc, discussed complications and comorbidities of AD. Dr. Brunner discussed the increased risk of coronary artery disease in severe AD as a result of systemic inflammation that affects the vascular system. One possible explanation for this, explained Dr. Brunner, is the presence of circulating inflammatory mediators in the blood of people with AD, which activate endothelial cells, contributing to cardiovascular disease. He mentioned research showing that these inflammatory mediators can be reduced with treatment with cyclosporine, which, while not a long-term treatment, shows promise that these mediators are modifiable. Dr. Brunner also referred to research that showed an increased risk of bone fractures in people with AD but did not establish whether this is due to the disease itself or corticosteroid treatment. He also discussed infectious complications of AD, including impetigo, eczema herpeticum, eczema coxsakium, and molluscum contagiosum, and pointed to the dearth of antimicrobial peptides on AD-affected skin that might contribute to these infections. Dr. Brunner briefly mentioned weaker associations between AD and lymphoma, basal cell carcinoma, and squamous cell carcinoma before discussing clearer associations between AD and neuropsychiatric disorders, such as depression, anxiety, attention deficit 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.

SARS-CoV-2

SARS-CoV-2-associated Acro-syndromes and Cutaneous Vasculitis—Dr. Cristina Galván

Dr. Cristina Galván of the University Hospital Móstoles in Madrid, Spain discussed her research which attempted to clarify and classify various skin manifestations of SARS-CoV-2. She identified five clinical patterns which can classify these cutaneous manifestations, including pseudo-chilblain, vesicular, urticarial, maculo-papular, and livedo-necrotic patterns. Each of these patterns, she explained, appear to be associated with a specific age group, systemic severity, and SARS-CoV-2 clinical phase. Dr. Galván focused her talk on the two patterns at the far ends of the spectrum: the pseudo-chilblain pattern and acro-ischemia. She explained that the pseudo-chilblain pattern is associated with good clinical outcomes, younger ages, relevant inflammation, minimal vascular damage, robust interferon-I response, and absent or minimal viral load. Conversely, Dr. Galván explained that acro-ischemia is associated with more severe disease and higher mortality, older ages, major vascular damage, thrombosis, minimal inflammatory responses, complement deposits, endothelial extensive viral protein, and no interferon signaling.

 

How the SARS-CoV-2 Pandemic has Changed our Daily Practice—Dr. Luigi Naldi

In his presentation, Luigi Naldi, MD, discussed strategies of containment, cutaneous manifestations of COVID-19, SARS-CoV-2 and dermatological therapies, effects on the dermatology workforce and education, and questions for the future. Dr. Naldi began with an overview of the multi-dimensional impacts of the pandemic and the varying societal interventions that have been undertaken in order to contain the pandemic, which have impacted office-based dermatological practice and led to a boom in technological healthcare solutions. He then discussed the current knowledge of skin reactions associated with precautions aimed at preventing the spread of COVID-19, such as mask wearing and increased hand washing. Dr. Naldi also mentioned long-term cutaneous sequelae currently under investigation in connection to COVID-19, including telogen effluvium, and immune-related diseases, such as psoriasis, as a possible risk factor for COVID-19 related death. Further, Dr. Naldi discussed calls for trials on anti-tumor necrosis factor therapy for COVID-19 as well as the recruitment of dermatologists who were enrolled in COVID-19 hospital units during the acute phase of the pandemic.

 

Vaccination for SARS-CoV-2: Challenges and Outlook—Prof. Dr. Thomas M. Kündig

Dr. Kündig began with the question of whether robust immunity is present after a coronavirus infection and pointed to animal studies suggesting that immunity does appear to be present following infection, with occasional instances of reinfection and rare instances of death following reinfection. Dr. Kündig asserted that this is good news for the creation of a vaccine. He then turned his attention to the frontrunners in the race to an effective coronavirus vaccine. This included an mRNA-based vaccine which produced a notable amount of side effects but showed promise. Dr. Kündig explained that an effective COVID-19 vaccine must introduce neutralizing antibodies, and this particular vaccine candidate was shown to do this on a level similar to convalescent plasma, which received emergency authorization by the United States Food and Drug Administration to treat severe COVID-19. However, makers of this vaccine published further research that found a less robust response in older (aged 65–85) recipients. Dr. Kündig also pointed out the logistical disadvantages of RNA vaccines, which can be developed quickly but are difficult to produce on a large scale for many people. He also discussed data on Sputnik V, the vaccine already approved by the Russian government.

SPOTLIGHT SESSIONS

New Aesthetic Procedures—Prof. Dr. Ashraf Badawi

Ashraf Badawi, MD, PhD, presented updates on laser applications in dermatology. Dr. Badawi began by discussing laser procedures during pregnancy and referred to a review paper describing instances where laser procedures have been used safely in pregnant patients, including carbon dioxide and neodymium-doped YAG laser treatments for genital condylomata and holmium YAG and pulse-dye lasers for the treatment of urolithiasis. However, according to Dr. Badawi, he does not treat pregnant women with laser therapies to avoid being blamed for any pre-existing congenital anomalies. Dr. Badawi also addressed the question of cancer risk associated with laser tattoo removal brought about by reports of patients who developed melanoma after undergoing laser tattoo removal. He explained that these instances of melanoma aren’t an effect of the laser itself, but develop from preexisting nevi that are present before the procedure and are masked by the tattoos. Dr. Badawi said that for this reason, tattoo removal lasers need to be in the hands of certified dermatologists who will properly examine the tattooed skin for suspicious lesions before these procedures. He moved on to review challenges in treating pigmented lesions with lasers, including resistance, recurrence, complications, unrealistic patient expectations, and low profitability.

 

Emerging Therapies for Vitiligo—Prof. Thierry Passeron

Prof. Thierry Passeron began his presentation by reviewing the three objectives of vitiligo treatment: halting melanocytic loss, inducing the differentiation and proliferation of melanocytes, and preventing relapses. Dr. Passeron reviewed how most treatments used to halt depigmentation act by targeting the immune system and reviewed recent research on Janus-kinase (JAK) inhibitors, such as oral tofacitinib and ruxolitinib (oral and topical), used to halt depigmentation and induce repigmentation in patients with vitiligo. Moving on to inducing the differentiation of melanocyte stem cells, Dr. Passeron discussed targeting the WNT pathway to induce the differentiation and proliferation of melanocyte progenitors. To prevent relapses, Dr. Passeron discussed targeting IL-15 to deplete memory resident T cells.

Highlights from Thursday, October 29

INFLAMMATORY DISEASES: PSORIASIS

New Therapeutic Targets Based on Pathophysiology—Prof. Dr. Luís Puig

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 provided a review of the current concept of the pathogenesis of psoriasis and acknowledged a more recent focus on keratinocytes as key drivers of inflammation in psoriasis through the production of several cytokines, including interleukin (IL)-36, which Dr. Puig payed special attention to during his talk. Patients with severe autoinflammatory types of generalized pustular psoriasis, says Dr. Puig, 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 discussed therapies in development that block the activation of the IL-36 receptor, including spesolimab and imsidolimab.

 

Psoriasis: A Systemic Disease—Prof. Paolo Gisondi

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, possible reasons for this association, and the expression of psoriasis-related inflammation that manifests beyond the skin. Prof. Gisondi discussed the common genetic background linking psoriasis and its comorbidities and reviewed specific overlapping genes between psoriasis and these comorbidities, including obesity, diabetes, and myocardial infarction. He also noted how inflammatory mediators released from psoriatic lesions can have systemic effects, including effects on the liver, adipose tissue, and skeletal muscle that contribute to endothelial dysfunction and atherosclerosis. Prof. Gisondi also discussed the similar metabolic and immunologic pathways shared between psoriasis and obesity. Prof. Gisondi closed his talk by questioning whether systemic treatment of psoriasis could prevent the development of comorbidities and identified this as an area for future investigation.

 

Psychological Burden of Psoriasis—Prof. Dimitrios Ioannides

Prof. Dimitrios Ioannides of the Hospital for Skin and Venereal Diseases and the Medical School of Thessaloniki, Greece, presented on the psychological burden of psoriasis. Prof. Ioannides began by acknowledging the significant socioeconomic burden on people with psoriasis, 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 on the lives of patients with psoriasis, citing such difficulties as the unpredictable disease course and association with significant comorbidities, such as cardiovascular disease, metabolic syndrome, inflammatory bowel disease, and depression. According to Prof. Ioannides, the WHO report also indicated that many patients with psoriasis experience incorrect or delayed diagnoses, emphasizing the opportunity for improvement in psoriasis treatment. Prof. Ioannides also discussed research that investigated specific social and emotional obstacles faced by patients with psoriasis. In addition, he discussed the mechanistic explanation of the association between psoriasis and depression, citing the impact of systemic inflammation and the overlapping cytokines indicated in the pathogenesis of both 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.

SPOTLIGHT SESSIONS

Sunscreens: Where are we going?—Prof. Dr. Jean Krutmann

Jean Krutmann, MD, provided a lecture on the future of sunscreens. Sunscreen application is a well-documented method of preventing skin cancer and photoaging, and Dr. Krutmann began his presentation with an overview of the supporting evidence behind these concepts. Dr. Krutmann then discussed special requirements sunscreens must fulfill to effectively prevent skin aging, emphasizing the necessity of sunscreens to protect against not only ultraviolet (UV)A and UVB radiation, but also against infrared radiation and visible light. Dr. Krutmann discussed research comparing the effectiveness of SPF30 versus SPF30 plus an antioxidant mixture in protecting the skin against infrared radiation and found that, after analyzing biomarkers indicating wrinkle formation, the SPF30 with added antioxidants was more effective. Next, Dr. Krutmann discussed visible light, which has been shown to contribute to skin aging by inducing hyperpigmentation in people with darker skin tones, and pointed to research indicating that sunscreens containing iron oxides can be effective in partially absorbing visible light and preventing melasma relapses. Dr. Krutmann ended his presentation with a discussion of a recent paper published by himself and his colleagues, in which they discussed controversial current issues in the area of sunscreens. These issues included standardizing the efficacy of sunscreens, questions around human toxicity and ecological safety, possible consequences of galenic formulations, and the potential of oral photoprotective measures.

ARTIFICIAL INTELLIGENCE AND BIG DATA

Consequences of Deep Learning for the Healthcare System—Jacques Biot

Jacques Biot, past president of the Ecole Polytechnique in France, provided a presentation on artificial intelligence (AI) and healthcare. According to Biot, the utilization of deep learning in healthcare, including dermatology, have flourished in the area of diagnosis, but are less common in therapeutic applications. Biot also discussed the application of AI in care provision organization, but points to deficiencies in these deep learning systems that can create biases when used to manage patients. However, Biot emphasized the role of AI in clinical research, which can be used to select and stratify patients. He also discussed the assessment methodology used by the United States Food and Drug Administration (FDA) to evaluate artificial intelligence used for healthcare purposes, noting that the FDA has approved between 50 and 64 algorithms so far. Biot also covered methodological and technical challenges to overcome in the future of AI and clinical research. In regard to societal concerns regarding the use of AI in healthcare, specifically the concerns associated with preserving the physician-patient relationship, Biot proposes that advances in the use of AI in healthcare will allow for more time for physicians to focus on the patient-physician relationship, thus strengthening this area of healthcare.

 

Diagnosis of Pigmented Lesions—Dr. Josep Malvehy

Dr. Josep Malvehy discussed the diagnosis of pigmented lesions using artificial intelligence. He reviewed different applications of machine learning in skin cancer, including tumor classification using clinical, dermoscopy, and dermatopathology images, skin tumor assessment using mobile application and personal monitoring devices, machine learning facilitation of large-scale epidemiological research, and precision medicine. He discussed algorithms currently in development that can potentially refine the evaluation of risk of metastasis and death in patients with melanoma based on the inclusion of parameters not present in current staging systems. Additionally, Dr. Malvehy also discussed the potential of AI to remedy the unmet needs in dermatology resulting from the differences in density of available dermatologists between countries and urban or rural areas, which, according to research cited by Dr. Malvehy, is correlated with higher melanoma mortality. Dr. Malvehy pointed out limitations in using machine learning to diagnose melanoma, suggesting a future where a hybrid system of human physicians and artificial intelligence is used to provide efficient and optimal care.

PREGNANCY AND SKIN DISEASES

How to Manage Primary Melanoma During Pregnancy—Marek Pásek, MD

Marek Pasek, MD, spoke about managing primary melanoma during pregnancy. Dr. Pasek began by reviewing changes of pigmented nevi during pregnancy, including peripheral rings of globules and accentuation of reticular patterns. He moved on to review the epidemiology and prognosis of melanoma during pregnancy, citing reports indicating no difference in survival between pregnant and non-pregnant women with melanoma. Dr. Pasek also emphasized that melanoma during pregnancy does not appear to be influenced by pregnancy-related hormones, but thickness of the tumor and ulceration status appear to be significant predictors of survival in pregnant women with melanoma. Next, Dr. Pasek discussed staging procedures that can be safely performed during pregnancy, citing ultrasound and magnetic resonance imaging as safe options. Other topics discussed included management of surgery in patients with melanoma during pregnancy and sentinel lymph node biopsies and dissection of regional lymph nodes during pregnancy.

 

Acne and Rosacea—Prof. Elena Araviiskaia, MD, PhD

Prof. Elena Araviiskaia, MD, PhD, of the Department of Dermatology and Venereal Diseases at the First Pavlov State Medical University in St. Petersburg, Russia, spoke about acne and rosacea during pregnancy. Dr. Araviiskaia covered reasons for the worsening of acne during certain periods of pregnancy, the scattered data concerning the safety profile of drugs, and the absence of high-quality clinical recommendations for managing acne during pregnancy. 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, she notes, an increase of androgens and progesterone during this period presents the risk of worsening acne during the first trimester. Dr. Araviiskaia also discussed commonly used acne treatments and their safety profile for use in pregnant women, including azelaic acid, benzoyl peroxide, erythromycin, and clindamycin. She also discussed topical dapsone, which she recommends be stopped at least one month before delivery, and the topical retinoids tretinoin and adapalene, which are not recommended for use during pregnancy. Dr. Araviiskaia also pointed to oral zinc, which she says has been shown to be safe and effective in the treatment of acne in pregnant women; at doses below 75mg/day, she continues, elemental zinc does not appear to harm a growing fetus. Moving on to rosacea, Dr. Araviiskaia cited azelaic acid and topical metronidazole and clindamycin as effective treatments for mild-to-moderate papulopustular rosacea during pregnancy. She also provided guidance for treating rosacea fulminans during pregnancy, emphasizing a topical treatment course comprising topical drying compounds and surgical drainage.

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