CONGRESS REPORTS
EADV 2021
European Association of Dermatology Venereology
Report written by
Dr Adrian ALEGRE SANCHEZ a
Dermatologist, Spain
Fillers I, Basics
The world of fillers
Prof. Daisy Kopera, Austria
In the basic session about fillers, Dr. Daisy Kopera talked abour the different types of fillers. Harmless fillers are those that can be decomposed by our body, such as collagen, hyaluronic acid (HA) and calcium hydroxyl apatit (CaHa). Collagen has been mostly displaced for hyaluronic acid, which is the most widely used. CaHa has demonstrated to be more active in remodelling the extracellular matrix. However, the main advantage of HA is that it can be used to produce volume but also to hydrate. It is no longer obtained from animal source but created by biofermentation. Main indications of fillers are cheeks, chin, lip augmentation and nasolabial folds. It is always recommended to respect patient desires but also to educate patient in realistic expectation and potential complications.
The most common Caucasian indications: Cheeks, nasolabial folds and lips
Dr. Hugues Cartier, France
Dr. Hugues Cartier reviewed the main indications in Caucasian patients which are cheeks, nasiolabial and marionette folds and lip augmentation. For cheeks he recommended to inject in supraperiosteal plane to fix cheeks and subcutaneously to blump cheeks, depending on patient age and choice. Regarding the nasolabial folds, the sandwich technique was recommended, with a firmer gel deeply and a lighter one more superficially. He recommended to use cannula for this area. In the case of
perioral a lip area, he also recommended canula for volume and subdermis and needle for precision injection.
On Hyaluronidase
Prof. Berthold Rzany, Germany
An interesting talk about Hyaluronidase was conducted by Berthold Rzany. Hyaluronidase is a must have products for all cosmetic dermatologists working with HA. It can be used as an emergency drug and to correct overuse or reactions of HA. In case of hyaluronic acid vascular occlusion, 1ml of 1:150 or 1:300 hyaluronidase units (Hylase Dessau) should be used in the area of arterial branching. For
the adverse reactions, such as hard nodules, sometimes hyaluronidase has to be injected in combination with corticosteroids or even oral doxyxicline or steroids. Luckily, more common than reactions are the overcorrections of filler.
Fillers II, Advanced
Tips and tricks for the advanced injector
Dr. Hugues Cartier, France
In the advance sessions about dermal fillers, Dr. Hugues Cartier gave us his tips and tricks in this topic. Regarding botulinum toxin, he advised us to take into consideration the possibility of a paradoxical effect if we do not take into consideration the asymmetries of the patient. In the case of masseter injection, it is recommended to use ultrasound during the injection so that we can go deep enough. The masseter injection can even correct a chin deviation and avoid a mandibular bone overgrowth. Masseter injection also has the effect of reducing the temporal fossa, with an increase in volume in up to 2 cc paradoxically. He also recommended the use of Poli-lactic acid with different dilutions for body tightening. Ultrasound-based injection is always recommended when injecting in deeper planes such as periosteum. A new way of visualizing the arteries of the face is a magnetic resonance angiography projected to the face of the patient with a smartphone. Probably in the future
we will have even smart syringe that detect the presence inside a vessel.
Diagnosis and management of delayed inflammatory reactions
Prof. Dr. Ines Verner Rashkovsky, Israel
Also in this session, the management of delayed reaction by filler was discussed by Dr. Ines Verner Rashkovsky. Soft tissue fillers are now considered the second most frequent non-invasive aesthetic treatment. We can consider a reaction as delayed after > 1 year (late reactions between 14 days and 1 year). Actually, late and delayed reactions are very similar pathologically. Typical histology is the formation of foreign body granulomas. Sometimes these granulomas are due to host`s immune system and other times biofilms of different bacteria are responsible. The problem with these biofilms is that they evade the immune system and antibiotics rarely get into them. The incidence of these delayed inflammatory reactions is between 1-5% probably. Some fillers might have a higher incidence due to their low molecular weights, due to the higher inflammatory state that they create after degrading. There are some triggers to these types of reactions, and they include any type of immune system activators such as viral infections, dental or surgical procedures, etc. Regarding treatment, oral antibiotics can be considered as first-line specially wit tetracyclines. Second line therapy would be steroid intralesional injection. Other therapies can be 5-FU injection, extraction with surgery or needle, PRP, etc. If the nodule is fluctuant, it would be recommended to drain the mass and send it to culture. Talking about prevention, it is not clear if cleansing the skin with chlorhexidine is better than with
alcohol. It is important to schedule dental appointments > 2 weeks before or after the filler injection.
Scars and wound healing
Treatment of scars: An overview
Dr. Maurice A. Adatto, Switzerland
The scar session started with an overview by Dr. Maurice Adatto. He reminded us that, although we tend to differentiate between keloids and hypertrophic scars, the truth is that in many cases these scars are similar and part of the same fibroproliferative process. Some risk factors are genetic, hormonal changes or local inflammation or trauma. The prevention during surgery is basic with good technique and suture along tension lines. Among topical products, only silicone has demonstrated some efficacy. When a hypertrophic scar or keloid is present, management combining intralesional drugs, compression and/or lasers is the best options. Is important to act as quickly as possible.
Lasers for scars
Prof. Keyvan Nouri, United States
The talk about lasers in scars was conducted by Prof. Keyvan Nouri. Different lasers have been used with the objective of preventing and treating scars. Pulsed-dye laser has demonstrated to improve the cosmetic appearance but also to reduce symptoms. Results are better if treated just after suture removal. Short pulses at low energies are the best settings. Non-ablative and ablative fractional lasers used early has also demonstrated to improve scar appearance.
Scars and Pico-laser
Prof. Leonardo Marini, Italy
Prof. Leonardo Marini presented the evidence of a new type of lasers: the use of picosecond fractional lasers to remodel the scars. The advantage of this laser is that you eliminate the phototermal effect and use a photoacoustic effect.
Management of acne scars: Holistic approach
Prof. Dr. Ashraf Badawi, Canada
Prof. Ashraf Badawi talked about the management of acne scars with a holistic approach. He explained that in most cases we can expect no more than 40-60% of improvement. Many times, we have changes deeper than the dermis, affecting to subcutaneous tissue. He proposed to treat these scars with a complete approach, including also procedures for skin tightening such as radiofrequency, IR light and lasers, HIFU, threads or even surgery. The non-ablative Nd:YAG laser with sub millisecond pulses is a great option for this objective.
Transepidermal drug delivery in scar treatment
Prof. Merete Haedersdal, Denmark
Especially relevant was the talk of Prof. Merete Haedersdal about the laser assisted drug delivery for scars. He reminded us that nowadays there are more than 100 publications available for this technique. The most common drugs delivered by lasers are triamcinolone and/or 5-fluorouracil, which typically is combined with triamcinolone in concentrations 9:1 or 3:1 (5-FU and TAC). For atrophic scars Poly-L-lactic has been used demonstrating an improvement in volume. Another option for drug delivery is the use of pneumatic injection (needle-free), achieving a penetration of up to 6 mm.
Has botulinum toxin a place in scar treatments?
Dr. Hugues Cartier, France
The topic of botulinum toxin use in scars was discussed by Dr. Hughes Cartier. Although there is increasing evidence, its use with this indication is still to be more defined. Probably the best indication is in preventing hypertrophic scars in tension areas, using 2,5-5 UI per cm2 and injecting deeply.
Rosacea
Recommendations for rosacea management: consensus 2019 panel
Prof. Dr. Martin Schaller, Germany
In the session of acne and rosacea, Dr. Martin Schaller presented the 2019 Rosco Consensus for Rosacea Management. It has been determined that almost 90% of patients with rosacea has a worsened life quality. In the new classification, classical types of rosacea are not considered to occur separatedly but in a combined phenotype (i.e. mix of papulopustular and phymatous rosacea). Therefore, we should talk more of rosacea phenotypes and not rosacea grades or types. Treatment duration should be of at least 12 weeks if we use for example topical ivermectin. The totally clear (IGA 0) status seems to be important to achieve, since the maximum improvement of quality of life is at that level. It also can extend time to relapse. In the consensus there is a treatment algorit. It includes alfaadrenergics and lasers/intense pulsed light for erythema and telangiectasias and drugs such as azelaic acid, ivermectin, metronidazole, isotretin and doxycycline for inflammatory lesiones. Transient erythema can be treated with beta-blockers.
Conventional and novel treatment modalities in rosacea
Prof. Dr. Burhan Engin, Turkey
Dr. Burhan Engin presented some novel treatment modalities for rosacea. Brimonidine tartrate 0.5% gel produces a vasoconstriction and might have anti-inflammatory effect. However, some patient can have a rebound effect after 12-24 hours. Ozymetazoline is another alpha-adrenergic receptor agonist approved with this indication. Intradermal botulinum toxin type A injection is a promising modality of
treatment for resistant cases and can provide a significant reduction of erythema. In the case of vascular lasers, both lasers such as pulsed-dye laser (PDL) or IPL can be used, and subpurpuric settings are more recommended but with the need of more sessions. Nd:YAG is an useful tool when telangiectasis are present.
Energy-based devices: advanced session and complication management
Post-inflammatory hyperpigmentation - scientific background, risk stratification, and its management
Prof. Thierry Passeron, France
In the advanced session of energy-based devices, Prof. Thierry Passeron discussed the nature and management of post-inflammatory hyperpigmentation. As we know, it can occur at any age and any sex. It is more frequent in Asian and Hispanic and African American with darker photo types. In Caucasian population the incidence is of up to 6%. It can occur very frequently due to lasers such as q-switched ones. Its pathophysiology remains largely unknown, prostaglandins and leukotrienes are
known to be involved in melanocytes activation. The higher risk after a procedure is in the first two weeks and it can last up to two or even more years. Photoprotection is vital to prevent it after laser treatment with wide-protection filters (longwave UVA and visibile light and not only UVB). For the prevention sunscreen is recommended for at least 15 days prior. Hydroquinone 4% can also be used as prevention. For the treatment Hydroquinone with potent topical steroid up to 4 months is the best
option for recent PIH. If the PIH is resistant or very old, q-switched picosecond or nanosecond lasers can be used with a testing in some areas.
Common and rare side effects of light-based long term hair reduction
Dr. Hans-Joachim Laubach, Switzerland
The side effects related to light-based long term hair reduction devices was discussed by Dr. Hans-Joachim Laubach. Typical side effect is a superficial epidermal injury with pigmentation which is transient. Full epidermal injury appears with bullous reaction. In this case, active cooling is recommended and the use of clobetasol and Vaseline with occlusion. In this case it can heals with hypopigmentation that can repigment with the next sun exposure. Paradoxically hypertrichosis is another potential complication, especially when low energies are used in areas such as the face. To avoid it is better to recommend hair snipping instead of hair shaving and use cold packs outside treatment areas. In the axilla, hyperhidrosis or bromhidrosis can be found due to stimulation of eccrine glands. Lately, the doctor recommended to avoid treatment on tattoed areas.
Potential unwanted side effects of boy sculpting devices and their management - what’s the truth
Dr. Mathew Avram, United States
Unwanted effects of body contouring treatments were presented by Dr. Matthew Avram. He reminded as that are non-invasive devices for fat reduction are far more frequent than liposuction now. The main appeal of this treatments is that, although the efficacy is not high, these treatments are mainly safe and painless. Cryiolipolyisis is one of the most common type of treatments. It produces a selective crystallization of lipids inside fat cells at temperatures below freezing with fat reduction over 2-4 months. Some of its side effects include hernia, neuropathy, paradoxical fat appearance or blisters/rash. Paradoxically adipose hyperplasia appears delayed, 2-3 months post-treatment. Incidence rate is probably low (less than 1 per 4000 treatments). However, it should be included in the consent inform form. Controlled mechanical subcision is a treatment used for cellulite that typically produces hematomas, laceration of the skin and nodules. Chemical subcision (with collagenase
clostridum histolyticum) can be used for cellulite irregularities. Sometimes very dramatic bruising can appear in this case, which can last for 2-4 weeks. Hematomas can be treated with vascular lasers in lighter phototypes.
Acne
Insulin resistance and acne
Dr. Dipankar De, India
The topic of insulin resistance and its relation with acne was discussed by Dr. Dipankar De. Insulin resistance represents a reduced sensitivity of metabolic pathway of insulin action after binding its receptor. This leads to an impaired glucose transportation, glycogen synthesis and augmented glucose oxidation, increasing even more the synthesis of new insulin. The role of IGF-1 has been also highlighted in acne, since this factor is capable of stimulating 5a-reductase, sebocyte proliferation,
lipogenesis, adrenal and gonadal androgen synthesis. Insulin resistance is difficult to measure. There are different tests being one of the most common the HOMA test (Homeostasis model assessment – insulin resistance). In a recent study published in the Journal of American Academy of Dermatology, an increase of insulin resistance was related with more severe cases of acne. Two hormones also important are adiponectin and leptin, since they act as antidiabetogenic. In patients with acne these
hormones seem to be reduced. Regarding the management of this situation, if a severe insulin resistance is present, metformin can be a drug very useful. Also, low glycemic diet should be recommended. It has been determined that metformin effectively reduces the size of follicular comedones, without altering IGF-1 and other hormones or mRNA expression. These changes are translated into clinical improvement of acne and of the hormonal profile.
Acne fulminans: What is new?
Dr. Clio Dessinioti, Greece
Dr. Clio Dessinioti presented the news on the topic of acne fulminans. It is a severe form of acne with systemic symptoms (however, in new classifcations, acne fulminas without systemic symptoms is also included). It is more tipical in adolescent males, with ulceronecrotic lesions, crusts, scarring and laboratory alterations. It should be differentiated from acne conglobate, being the later slower, with more cysts and nodules and without systemic symptoms. In most cases of acne fulminans there is no
family history. Sometimes it can be related with the use of isotretinoine and no differences in Cutibacterium acnes phylotypes has been determined. There are only 5 large series of patients with more than 20 patients. Joint involvement is typical, and radiography is recommended to detect it. Acne fulminasns can be prevented with the use of prednisolone simultaneously to the start of isotretinoin, starting the steroid 2 weeks prior. If an induction by isotretinoin is suspected, it should be discontinued and start with prednisone. After crusts and erosions are resolved isotretinoin can be
started at low doses. Other treatments such as biologicals have been tested: anakinra, ustekinumab and adalimumab with some results.
Atrophic acne scars: How to prevent and treat
MD Vincenzo Bettoli, Italy
Regarding the prevention of atrophic acne scars, Vincenzo Bettoli reminded that early and maintained treatment is mandatory in inflammatory acne. When scars are stablished, he recommended to treat deeper scars individually with CROSS techniq or surgical techniques (excision, punch…) and shallow scars all together wih lasers, peelings or needling.
Ageing
Can sunscreens prevent photoaging?
Prof. Henry W. Lim, United States
In the session about ageing, Dr. Henry W. Lim tried to answer a very interesting question: can sunscreen prevent photoaging? We all know that UV radiation produces erythema, tanning, freckles production and wrinkles. People with darker skins are well known to have less photoaging. UVB produces matrix metalloproteinases that affect the extracellular matrix. UVA produce a direct effect on
dermal fibroblast with mutation on mitochondrial DNA and increase in reactive oxygen species. Also, visible light has some effect on aging, since it increases collagen degradation through different ways. Air pollution, smoking, tobacco smoke has not been demonstrated to produce photoaging. Regarding the use of sunscreen there is a study with more than 900 patients with a follow-up of 4 years, in which patients with daily use of sunscreen avoided increase in photoaging, while non-uses had 24% more aging. The ideal sunscreen should have SPF 30, broad spectrum to protect against UVA, it should be coloured to protect form visible light and with antioxidants to protect from infrared radiation.
Ageing
Dr. Susana Puig, Spain
Another interesting question was assessed by Dr. Susana Puig: can we distinguish between skin tumours and ageing skin? She presented that most important carcinogens and factors of ageing are sun exposure and tobacco. Melanoma and squamous cell carcinoma are the tumours with more rate of mutation, being the most frequent ones, the ones related with UV exposure. This mutation can be found not only on the tumor cells but also in skin surrounding. The most practical and useful tool to diagnosis tumours within aged skin is dermoscopy. Other imaging techniques such as confocal microscopy are useful and with increasing specificity.
Home-use devices (HUD) for acne: The Evidence - acne and beyond
LED devices for acne and more
Dr. Christine Dierickx, Luxembourg
The evidence behind LED devices was presented by Dr. Christine Dierickx. LED devices has photobiological effects. This light is going to produce different effect: activation of opsins receptors, circadian clock regulation trough CRY, nitric oxide formation. The cryptochromes and the opsins are the typical receptors. However, despite the progressing translation of photobiomodulation to commercial application, its clinical effect is still far from satisfactory. The parameters and settings are still to be more precisely determined. Blue light therapy has demonstrated to be effective in some inflammatory diseases such as acne. In acne, the 415 nm wavelength is the most frequent one, due to a special affinity by Cutibacterium acnes for this blue light. The potential damage to eyes is luckily very minimal in reality, however, there have been devices banned due to this potential effect. Another interesting question is if this type of devices can worsen melasma or pigmentation. The answer is not clear, but the potential effect has only been demonstrated in vitro and not in vivo (at a 20 cm distance, a maximized use of high intensity computer screen for 8 hours per day 5 days a week does not worsen melasma).
Level of evidence for HMD
Prof. Dr. Peter Bjerring, Denmark
Dr. Peter Bjerring reviewed the evidence behind Home-Use devices. Typical LED devices emit blue light or red light (or both of them). Regarding blue light therapy, its evidence is actually low or very low if we review the literature. In one recent study they provide a B grade of recommendation in LEDs in general for acne. Level B of recommendation suggest clinician to recommend them but individualizing. We must take into consideration that there are only three double-blinded controlled studies with home-use LED for acne. These studies are small, uncontrolled and industry sponsored. This could suggest that these devices may have only modest results. As gpme-use devices deliver less energy per session than professional equipment, it is important that consumers are given realistic expectation of treatment outocmes.
Cosmeceuticals
Cosmetic in acne and rosacea
Prof. Elena Araviiskaia, Russian Federation
In the session about cosmeceuticals, Prof. Elena Araviiskaia reviewed the cosmetics in acne and rosacea. These two conditions have barrier disfunction and microbiota alteration. In both of them we can found elevated sebium production and barrier disruption. A deficiency of linoleic acid can be found. The use of face mask due to the COVID has demonstrated to increase acne and rosacea due to a prolonged occlusion and local pressure of the skin. The occlusion produces maceration and irritation of the skin. Recent studies have given importance to the activation of innate immunity in acne and rosacea due to a suppression of normal S. aureus colonies. Pathogenic S. aureus and S. epidermidis increase the production in substance P which is a pro-inflammatory signal. Aggressive cleansers can alter transepidermal water loss and produce aggravation of ance and rosacea. Therefore, the speaker recommended syndet cleansers instead of typical soaps. There is no consensus regarding the frequent of washing, but it is clear that moisturizing after washing is important. Moisturizes can even change the profile of gene transcription in the epidermis.
Dermocosmetics in acne and rosacea have three main objectives: management of side effects of medication (i.e., mositurizers), synergistic effect (i.e., salycilic acid) and prevention and maintenance (i.e. retinoids). These effects have been demomnstrated in different studies to be significant enough so as to recommend specific cosmetics.
Evolution of the use of antioxidants in anti-ageing cosmetics
Assoc. Prof. Jelena Stojkovic-Filipovic, Serbia
Another interesting topic was the evolution of antioxidants in antiageing cosmetics. This topic was discussed by Jelena Stojkovic-Filipovic. She reviewed that there are three different types of antioxidants: enzymatic antioxidants, non-enzymatic-low-molecular weight antioxidants (vimatin E, Vitamn C, glutathione…) and other antioxidants (coensim Q, ascorbate or carotenoids). The most frequent ones are vitamins (A, C, D, E), ubiquinone Q10 and carotenoids. However, their use in
cosmetics is still controversial if we focus on their real effect due to the lack of significant studies. Vitamin E is the most frequent one in topical products, being the tocopherol derivates more frequent than tocopherol itself. It is lipophilic so the penetration through the skin is easier. Most of vitamin Ebased products are actually used for moisturizing and not for anti-ageing. Vitamin C is another very common ingredient. Only a small portion of ingested vitamin C is actually present on the skin, so topical application can be of interest. Different forms of vitamin C are used in order to make it lipophilic (normally it would be hydrophilic). In this case, vitamin C is mostly use in anti-ageing products. What is already clear is that the combination of different antioxidant is superior to the use of only one of them.
Report written by Dr Hester COLBOC
Dermatologist, France
Autoinflammatory diseases
Pathophysiology of autoinflammatory syndromes
Prof. Dr. Amir Yazdi, Germany
Prof. Amir Yazdi begins this presentation by explaining that the concept of autoinflammation is a recent one, and has provided an explanation for pathologies that were previously poorly understood. The range of diseases associated with autoinflammation is broad, and their dermatological presentation varies from pustules to hives to pyoderma gangrenosum.
Autoinflammation results from a disorder of the innate immune system that can have multiple origins. It involves many different cells and proteins, including inflammasomes, intracellular protein complexes that play a major role in innate immunity. Inflammasome activation leads to the release of interleukins (ILs), including the IL-1 family, which plays a central role in the development of autoinflammatory diseases.
These pathologies have shared clinical characteristics. They generally affect young patients and are associated with fever and asthenia. Besides the dermatological signs cited above, other clinical signs may be more or less present, including arthritis, abdominal pain and oedema of the lower limbs.
While our knowledge of autoinflammatory diseases has greatly improved in recent years, many questions remain regarding their physiogenesis, clinical expression and treatment options. Other perspectives are also being explored, like the association of autoinflammatory diseases and immune system dysfunction, and a precise description of the interferonopathies.
IL-1-driven periodic syndromes
Dr. Antonio Torrelo, Spain
Antonio Torrelo continues the discussion with a more specific look at autoinflammatory diseases linked to the IL-1 family. Three ILs from this group are especially involved in the physiogenesis of these pathologies: IL-1 beta, IL-18 and IL-36. These ILs are the cause of multiple autoinflammatory pathologies. The involvement of one and the same IL can cause a highly varied range of clinical
expression; it is suspected that this clinical variability is the result of variation in the quantitative involvement of the ILs.
Anakinra, an interleukin-1 receptor antagonist, has revolutionised the treatment of these pathologies, justifying the importance of a fast diagnosis to enable early treatment. Several examples of this treatment are then presented, like a congenital deficit in the IL-1 receptor antagonist that causes severe infantile pustulosis and osteomyelitis.
Other treatments based on inhibition of the various ILs involved in these pathologies are currently being developed, and will certainly be part of the therapeutic arsenal for these pathologies in years to come.
Type I Interferon-mediated diseases and cutaneous signs
Prof. Michel Gilliet, Switzerland
Next, Michel Gilliet talks about pathologies associated with type I interferon (IFN-I), a family of cytokines that are involved in antiviral response, among other things. Accumulation of these IFNs is the cause of pathologies grouped together under the category of “type I interferonopathies”, such as Aicardi–Goutières syndrome, characterized by microcephaly, recurring fever and chilblain lesions.
Treatment of these pathologies is based on the use of corticosteroid therapy and
immunosuppressors, but also more targeted therapies like JAK/STAT pathway inhibitors and IFNAR (IFN-I receptor) blocking antibodies.
The discussion then turns to the involvement of IFN-I in the course of SARS-CoV2 infection. While many of the details are still unclear, its involvement now appears to be well established; massive early activation at the start of the infection is believed to be associated with mild forms of the infection, while delayed and prolonged activation seems to be associated with severe forms. IFN I could also be involved in the appearance of skin lesions observed in the course of SARS-CoV2 infections. More
advanced physiopathological studies of the skin, as well as other organs affected by the virus, are currently under way.
Treating pathological scars
Hyaluronic acid filler injections to soften and flatten keloid scars
Dr. Peter Velthuis, Netherlands
The session begins with Peter Velthuis, who reviews the different tools used for treating pathological scars: drug-based and laser-based approaches, as well as mechanical approaches like the use of compression garments. Intra-scar corticosteroid injections are still the most commonly used treatment at present, and the one most generally suggested for first-line treatment. While corticosteroids are still the most frequently used, Velthuis reminds us that other intralesional therapies exist, such as bleomycin, 5-FU, hyaluronic acid and hyaluronidase. The latter two show only mixed results at present, however, and the literature mainly emphasises their potential for reducing pruritus.
The speaker notes that it is often difficult to inject the treatments into the scars in the first few sessions, due to their mechanical resistance to injection. This resistance tends to diminish over time, due in particular to the progressive action of the local treatments, requiring doctors to provide multiple follow-up consultations for these patients.
Peter Velthuis concludes his presentation by emphasising the value of combining different approaches, e.g. by combining different intralesional treatments (such as 5-FU and corticosteroids) or combining laser and intralesional treatments.
Transepidermal drug delivery in scar treatment
Prof. Merete Haedersdal, Denmark
The session continues with Merete Haedersdal, who discusses the concept of transepidermal passage of drug treatments through keloid scars. As previously explained, the structure of these scars often makes it particularly difficult for treatments to penetrate into the dermis. Ordinary needles are thus of limited use, and new techniques have therefore been developed. One of these techniques is based on a combination of lasers (YAG or CO2) and drug treatments, most commonly 5-FU and corticosteroids. The laser is first used to create abrasions that promote penetration of the drug treatments, which are then simply applied to the scar. The laser’s action can be adjusted to adapt it perfectly to the size of the scar. This method has also been used with atrophic scars; in this case, a combination of CO2 laser and polylactic acid is used.
Merete Haedersdal describes another method to promote transepidermal penetration of drug treatments in scars: pneumatic injection. Performed without a needle, this technique allows for intrascar administration of drug treatments (corticosteroids, 5-FU, or a combination of both) at high energy (projection at 150 meters/second) and with penetration of up to 6 mm.
Scars and Pico-laser
Prof. Leonardo Marini, Italy
Next, Leonardo Marini presents the promising effects of picolasers in the treatment of pathological scars. This technique uses a laser whose beam is fractionated very rapidly, with the “pico” prefix referring to picoseconds. This ensures a minimal thermal effect while maximising the photoacoustic effect which generates the therapeutic action. This laser can also be very finely adjusted to act only intradermally, without causing any epidermal abrasion. Finally, studies are currently under way to evaluate its potential with transepidermal penetration of drug treatments into scars.
Has botulinum toxin a place in scar treatments?
Dr. Hugues Cartier, France
Hugues Cartier closes out the session with a discussion of botulinum toxin in the treatment of pathological scars. Numerous studies have been published on this subject in recent years, demonstrating the toxin’s benefits in this context. The toxin must be injected at the edge of the scar, where it then causes temporary paralysis of the muscles around the scar, thereby reducing the tension around it and improving its appearance. The toxin also reduces gene expression and cell renewal of fibroblasts, the main cells involved in the growth of pathological scars. Dr Cartier notes that
the toxin must be administered at a particular moment: it should not be injected too early, as opposed to corticosteroids, which are sometimes administered intraoperatively. Injecting botulinum toxin too early can cause delays in wound healing. Finally, Dr Cartier points out that the cost of botulinum toxin is still very high, and therefore represents one of the biggest constraints on its widespread use.
Basal cell carcinoma (BCC)
New guidelines for cutaneous BCC
Prof. Nicole Basset-Seguin, France
Prof. Nicole Basset-Seguin reminds the audience that BCC has a broad clinical spectrum, with the difficulty of treatment varying according to the region, the localisation, the type of BCC, and both the size and number of the carcinomas. These different variables require the deployment of variable treatment options, ranging from curative surgery to palliative approaches.
There are currently a number of non-surgical options, including curative options, for the treatment of BCCs. Examples include imiquimod, 5-FU and cryotherapy for the treatment of superficial BCCs. The speaker reminds us that laser is not one of the therapeutic options in this context.
Prof. Basset-Seguin then turns the discussion to Hedgehog pathway inhibitors, of which there are currently two: vismodegib and sonidegib. They can be used in a wide variety of situations: locally advanced BCC, metastatic BCC, patients who do not qualify for general anaesthetic, BCC with complex localisation, failure of surgical treatment, etc. While their efficacy is comparable, the literature reports 10% fewer undesirable side effects with sonidegib.
Finally, the use of these treatments as neoadjuvants is also addressed: by allowing for tumour reduction, they can reduce initially inoperable tumours to an operable size, and can thus be integrated into a curative surgical approach.
Management of multiple BCC
Dr. John Lear, United Kingdom
John Lear continues the presentation with a look at the complexities of treating multiple BCCs, as in the case of Gorlin syndrome. He reminds the audience that there is currently no formal algorithm for the treatment of patients with multiple BCCs.
He distinguishes two broad categories of patients with multiple BCCs:
- those in whom the number of concomitant BCCs is limited, thus allowing for surgical treatment targeting one of them at a time, and
- those with multiple concomitant BCCs which continue to develop between each consultation, and for whom a systematic approach based on curative surgery often quickly reaches its limits because it is too debilitating. For these patients, local treatments like cryotherapy, imiquimod and 5-FU, as well as Hedgehog pathway inhibitors, show strong potential. The focus in these cases is on controlling the
tumours, not on a curative approach.
The speaker presents other treatment options for which initial studies have shown promising results, such as cryosurgery, SUBA (Super-BioAvailable) itraconazole, topical rapamycin, or intratumoural injections of interferon gamma.
Finally, John Lear reports on the benefits of nicotinamide (vitamin PP) in preventing BCC. A study of 19 patients showed that this treatment, at a dosage of 500 mg twice daily, led to a 23% reduction in the risk of developing skin cancer. Larger studies should be conducted to explore this promising direction with patients presenting multiple BCCs.
Best strategies using smooth inhibitors or immunotherapy in advanced BCC
Dr. Ulrike Leiter, Germany
To conclude the presentation, Ulrike Leiter returns to the topic of Hedgehog pathway inhibitors and their undesirable side effects. The main ones are cramps and weight loss associated with dysgeusia. The consequences of these side effects can be very significant in patients for whom a change in overall health may have been the reason for initiating treatment with Hedgehog pathway inhibitors in the first place.
Two treatments have proven effective for cramps: L-carnitine and calcium channel blockers (amlodipine in particular). Dysgeusia can be ameliorated with zinc gluconate. In addition, discontinuous dosing regimens can be used in certain situations with these treatments, helping to improve patients’ tolerance while maintaining a certain level of efficacy.
Finally, the speaker describes a study published in The Lancet Oncology in May 2021. The study reports on the efficacy of cemiplimab, an anti-PD1 monoclonal antibody, in the treatment of 84 patients; a response was observed in 31% of patients and stability in 49%. This treatment is now approved in Germany and the United States, and should be brought to the market soon in other countries as well.
Report written by Dr Nicolas KLUGER
Dermatologist, Finland
Posters
What is the worldwide prevalence of scars?
P0827 Amici JM et al.
It may seem surprising, but this question has never been studied before.
This was an international study conducted in five countries (Brazil, China, United States, France, Russia). It involved nearly 11,000 people selected according to the quota method from a database of millions of people having agreed to take part in surveys.
Overall, almost one in two (48.5%) people reported having at least one scar: Russia (61%), United States (53%), France (51%), Brazil (46%) and China (36%). For one in five respondents (22%), the scar was less than one-year old. The total average number of scars (around four) was comparable between men and women. In women, the scar was most often located on the stomach (20.4%), followed by the face (15.9%), whereas in men, the scar tended to be on the face (18.7%) and then on
the stomach (13%).
The most frequent causes were
1. AN ACCIDENT OR DISEASE: 46-69.4%
2. GENERAL OR ORTHOPAEDIC SURGERY: 20.6-40.4%
Cosmetic procedures were seldom reported: 0.8-4.2%
Benefits of oral contraception for patients with hidradenitis suppurativa
P0003 Montero-Vichel T et al.
A Spanish prospective study evaluated the impact of oral contraception (OC) on the outcome of hidradenitis suppurativa (HS) after 12 weeks.
One hundred female patients between the ages of 15 and 49 were included: 50 received OC and 50 did not. The groups were comparable in terms of age, disease duration, BMI, severity (Hurley score), etc.
The proportion of patients with a decrease in the number of inflammatory nodules and abscesses was significantly higher in the OC group (53.9% versus 38.4%). However, the result was at the limit of significance (p=0.049). Disease duration and the occurrence of flare-ups during menstruation were associated with a decrease in inflammatory nodules.
Patients receiving non-combined OC were older, were more likely to smoke, had a longer disease duration, and had a disease that was more severe.
To conclude, OC may be beneficial for HS patients, especially if there is aggravation during menstruation. However, the poster was not very clear in terms of the statistical analyses or the type of OC used.
Aquagenic keratoderma during COVID
P0490 Burgos Blasco P, et al.
Since the start of the pandemic, cases of aquagenic keratoderma (AK) have been described; however, these cases have been attributed to excessive hand-washing, not to COVID-19.
Blasco et al. reported a small series of eight patients (collected between March 2020 and March 2021, between the ages of five and 34) who developed AK. AK bilaterally affected both palms of the hands but spared the soles of the feet. Five patients had a SARS-CoV-2 PCR test and two others showed signs compatible with infection. Resolution was complete for seven of the eight patients and was partial for the final patient.
The physiopathogenesis of AK is not clear. AK is generally associated with various situations including cystic fibrosis, atopic dermatitis, hyperhidrosis and the use of non-steroidal anti-inflammatory drugs. SARS-CoV-2 infection had never been mentioned before. Viral tropism for eccrine glands or dysfunction of angiotensin-converting enzyme 2 may explain the onset of its transient symptoms.
Prevalence of inflammatory bowel disease during hidradenitis suppurativa
P0044 Ohm F et al.
A multi-centre, non-interventional German study involving 342 patients with HS found that 1.2% had ulcerative colitis, 2.9% Crohn’s disease, and 7.9% functional digestive disorders (irritable bowel syndrome).
It is important to pay attention to digestive symptoms (bloody diarrhoea, abdominal pain, weight loss).
New contact allergies
Prof. Margarida Gonçalo, Portugal
I. Acrylates
Acrylates are a common cause of allergy in oral healthcare personnel and in beauticians (hand/nail treatments). Methacrylates are part of the European standard battery. However, a new acrylate, isobornyl acrylate (IBOA), has been involved in contact allergies to glucose sensors and insulin pumps.
Since then, new IBOA-free pumps and sensors have been released, but new allergens have been found such as N,N-Dimethylacrylamide and 2,2'-Methylenebis(6-tert-butyl-4-methylphenol) monoacrylate. Acrylates are contained in a number of medical devices such as ECG electrodes, tapes, medical dressings, and glues used for the treatment of varicose veins (butyl-cyanoacrylate).
II. Acetophenone azine
Acetophenone azine (CAS 729-47-1) is a new allergen that has been found responsible for contact dermatitis in relation to shin guards. This same allergen has been identified in other sporting equipment: sports shoes (trainers, flip-flops, ski shoes), protective equipment (swimming goggles, bike seats, etc.) and even facial protection during COVID-19.
III. Isothazolinones
MCI/MI allergy has been on the decline since the entry into force of the European directive. For example, positive reactions with patch tests for methylisothiazolinone dropped from 7.9% in 2014 to 3.1% in 2019. However, MCI and MI are still present in household products and paints. Reactions have been observed with other isothiazolinones: benzisothiazolinone (BIT) and octylisothiazolinone
(OIT).
Benzisothiazolinone is found in:
- Paints
- Household detergents (washing-up soap, fabric softeners)
- Polyvinyl gloves
Moreover, isothiazolinones can persist after washing clothes.
Octylisothiazolinone is found in leather:
- Shoes
- Belts
- Watch straps
- Sofas (arm chairs, car seats)
IV. COVID-19
The large majority of the reactions to face masks that have been observed during the pandemic have not been allergic: they have been either the famous macne, or else rosacea, seborrhoeic dermatitis, vitiligo or non-allergic contact dermatitis of the hands, caused by intensive washing and the use of hand sanitiser. However, some cases of true allergic reactions to face masks have been described, associated in particular with nickel, formaldehyde or isocyanate.
Rituximab in bullous skin diseases
Prof. Michael Hertl, Germany
Current and future targeted treatments for pemphigus
> Anti-B-cell antibodies
- Anti-CD20 antibodies: ofatumumab, veltuzumab, obinutuzumab
- BAFF inhibitors: belimumab
- BTK inhibitors
- APRIL inhibitors: atacicept
- Anti-CD19 antibodies: inebilizumab
> Anti-T-cell antibodies
- Anti-IL4 antibodies (dupilumab)
> Anti-IgG antibodies
The first European guidelines on pemphigus were published in 2015. They recommended first-line systemic corticosteroid therapy (1-1.5 mg/kg/day) followed by a second-line steroid-sparing immunosuppressant and then third-line rituximab, intravenous immunoglobulins, immunoadsorption and cyclophosphamide. In 2020, rituximab was officially approved as a first-line treatment for moderate to severe pemphigus.
Rituximab induces B-cell depletion with stoppage of antibody protection; however, rituximab also has an impact on self-reactive CD4 T-cells.
Recent studies investigating rituximab have shown that complete remission is possible when rituximab is used as first-line therapy and that early treatment induces long-term remission, more so than when it is used as second- or third-line therapy.
Rituximab in combination with oral corticosteroid therapy is more effective than oral corticosteroid therapy alone. Another study published this year in the New England Journal of Medicine, comparing rituximab with mycophenolate mofetil (MMF), showed that the steroid-sparing effect was greater with rituximab than with MMF. There were fewer flare-ups with rituximab and there was a higher percentage of patients in remission than with MMF.
For other bullous auto-immune diseases such as pemphigoid, rituximab is less effective in terms of disease control and partial and complete remission than for pemphigus.
Aphthosis and other cutaneous and mucosal disorders during Behçet’s disease
Prof. Erkan Alpsoy, Turkey
Behçet’s disease (BD) is a systemic inflammatory disease affecting the skin and mucous membranes (oral, genital and/or anal), as well as the eyes, joints and central nervous system, among other things. BD develops between the ages of 20 and 40 years and affects both men and women. The disease is prevalent in Asia, from Japan to Turkey, along the famous Silk Road. The prevalence is 4 14- 2/100,000 inhab. The prevalence is highest in Turkey (1/250 in Istanbul, 20-420/100,000 inhabitants in Turkey). In the rest of Europe, the prevalence rate is lower, ranging from 0.3 to 7.5 per 100,000 inhabitants with a clear south-to-north gradient (5.6-7.5/100,000 in Spain, 1.2/100,000 in Sweden).
The mucocutaneous symptoms are important to be able to recognise the disease.
- Mouth sores/ulcers: there is major aphthosis with involvement of several sites (lips, soft palate, tongue).
- Genital sores: the most specific to BD, the lesions are similar to those of the mouth, but with a lower frequency of recurrence. They leave a scar. In women, they affect the labia majora and minora and in men, the scrotum.
- Sterile cutaneous papules-pustules are usually associated with a positive pathergy test and arthritis.
- Erythema nodosum improves within 2-3 weeks without any ulceration, but it can leave residual hyperpigmentation (depending on the patient’s ethnic origin).
- Superficial thrombophlebitis is often associated with a vascular form of the disease.
- Various other cutaneous abnormalities can be observed: cutaneous ulceration, leg ulcers, pyoderma gangrenosum, Sweet’s syndrome, erythema multiforme-like lesions, neutrophilic dermatosis (Sweet’s syndrome) or palpable purpura.
- The pathergy test is a non-specific test. The ventral forearm is pricked with a needle at an angle of 45 degrees to a depth of 5 mm. The test is positive if a papule or pustule develops within 48 hours.
Positive pathergy testing varies depending on the geographic region and is stronger among men.
Treating aphthosis in Behçet’s disease
Colchicine is used as first-line treatment, sometimes combined with second-line benzathine penicillin.
Apremilast can be proposed as third-line therapy. The other treatments include azathioprine, cyclosporine and anti-TNF alpha, followed by miscellaneous therapies (thalidomide, zinc, dapsone, etc.).
Overview of some new therapies for atopic dermatitis
Prof. Richard Langley, Canada
This was an overview of some pivotal studies and recent data submitted to AAD.
A. Cytokine inhibitors
I. Dupilumab
Phase-3 studies on moderate to severe atopic dermatitis (AD): SOLO-1 and SOLO-2, CHRONOS, CAFE
The EASI75 score at week 16 of treatment ranged from 48 to 69% and EASI90 from 33 to 46%
The EASI75 score at week 52 was 65% and EASI90 was 51%
Dupilumab was far superior to the placebo. A major side effect: conjunctivitis
The Liberty AD PEO-OLE study was a study on dupilumab and topical corticosteroid treatments in adolescents with moderate to severe AD. In adolescents aged 12 to 17, 77 to 86% achieved EASI75 at 52 weeks. Similar results were observed with children aged six to 11 years, with 79% achieving EASI75 at 52 weeks.
In the end, the safety results for dupilumab were reassuring in terms of tolerance, except for cases of conjunctivitis.
II. Tralokinumab
ECZTRA 1-3 phase-3 studies on moderate to severe AD Tralokinumab was administered at the dose of 300 mg every two weeks
The EASI75 score was achieved for 60% of patients if concomitant use of topical corticosteroids.
The safety profile was reassuring with fewer cases of conjunctivitis, compared with dupilumab.
There have been several ECZTRA studies – 1, 2, 3... up to 8 – depending on the objectives and the treatments being compared.
The ECZTEND study was an open-label extension that included patients from various studies (ECZTRA 1, 2, 3 and 5). At week 56 of this study, 90% of subjects achieved EASI50, 83% EASI75, and 61% EASI90.
B. JAK inhibitors
These small molecules are administered orally. By nature, JAK inhibitors are not specific to a single target, but they tend to have an affinity for certain JAKs.
I. Baricitinib
BREEZE study: Baricitinib 2 mg in combination with topical corticosteroids. 49-51% achieved EASI75 at week 16.
II. Abrocitinib
JADE-MONO1, JADE-MONO2 studies: At the dose of 100 mg abrocitinib, 40-45% of subjects achieved EASI75; 61-63% achieved EASI75 at the dose of 200 mg.
JADE TEEN study: EASI75 responses occurred in 68% (100 mg) and 72% (200 mg) of subjects at week 12.
It should be noted, however, that there were some safety issues with nausea, vomiting, dizziness and dose-dependent acne flare-ups.
III. Upadacitinib
UP1, UP2, AD UP studies
A new HEADS UP comparative head-to-head study directly compared upadacitinib and dupilumab at the dose of 300 mg every two weeks. At week 16, upadacitinib was more effective with EASI75, 90 and 100 scores of 71%, 61% and 28% respectively versus 61%, 39% and 8% for dupilumab. The most frequent side effects were acne for the JAK inhibitor and conjunctivitis for dupilumab.
Overall, the studies on new AD therapies show encouraging results, with acceptable safety profiles.
Are you familiar with cutavirus?
Dr. Söderlund-Venermo, Finland
Parvoviridae are small, non-enveloped viruses with single-stranded DNA that have numerous hosts (vertebrates and invertebrates). The clinical symptoms in humans range from asymptomatic/subclinical to fatal infection.
Two representatives are parvovirus B19 and bocavirus. The former is well known to dermatologists as it causes fifth disease (epidemic megalerythema) as well as anaemia, arthritis and foetal infections.
Bocavirus is responsible for respiratory infections.
Other protoparvoviruses have been described since 2012:
- bufavirus (Burkina Faso, digestive infection)
- tusavirus (Tunisia, digestive infection)
- cutavirus (CuV, found in faecal samples and in lesions of cutaneous T-cell lymphomas such as mycosis fungoides)
The seroprevalence of CuV in the population is around 1 to 6%.
In a Finnish study from 2019, 16% (4/25) of cutaneous T-cell lymphoma skin samples were positive for CuV, versus 2.9% (4/137) of patients having received organ transplants (healthy skin or tumour skin) and, especially, 0% of 93 healthy control subjects. No patients showed infection with bufavirus or tusavirus.
The host cells of CuV include keratinocytes, T cells and macrophages.
The symptoms of a possible acute CuV infection are currently unknown.
There seems to be a significant association between CuV and cutaneous T-cell lymphomas. However, the role of this virus remains unknown: is the virus oncogenic? oncotropic? or oncolytic?
Artificial intelligence in skin cancer
Prof. Dr. Holger Haenssle, Germany
AI outperforms clinicians in diagnosing malignant lesions
Brinker et al. reviewed 19 studies published between 2017 and 2021 comparing the performance of AI with that of clinicians. Of these 19 studies, 11 focused on dermatoscopy, nine on clinical images and two on histological slides. All found AI to be superior or equivalent to clinicians.
The robustness of AI is still called into question
There is the ability to rotate, enlarge (zoom into), or expose images. Current studies show that rotating or enlarging images can impact their interpretation with AI. Similarly, the rule of dermatoscopy can also disrupt AI.
Contextualisation is essential
A number of other factors come into play in anatomical-clinical reasoning, but AI only takes the given image into account. For example, a Spitz lesion will be considered a Spitz naevus in a young child and melanoma in an adult for clinicians. However, AI will consider the lesion as malignant in both cases. It will therefore be important in the future to incorporate various other factors, such as age, gender and the distribution of lesions, into algorithms. One study showed that including these parameters increased accuracy by 5%. This figure remains modest but provides an idea of the potential and importance of contextualisation.
Figure 1. Contextual factors to be taken into account in AI. (*the factors currently taken into account in studies on AI).
The proper use of systemic glucocorticoids in dermatology
MD Cornelus Sanders, Netherlands
Reminder of the effects of glucocorticoids (GCs)
Cardiovascular:
After one year of treatment, the risk of cardiovascular disease is doubled for low doses and multiplied by six if using > 25mg/day of prednisolone. Traditional risk factors (obesity, smoking, high blood pressure) must be taken into account.
Infection:
Updating of vaccines
Take reactivation tuberculosis into account
Prophylaxis against Pneumocystis jirovecii
Prevention of strongyloidiasis if patient from an endemic region
Therapeutic principles:
Use the minimum effective dose, over a minimum period sufficient to treat the disease and avoid adverse effects
Take into account:
The patient’s activity
Comorbidities
Combination treatments
Relapses
Prolonged treatment
Before starting treatment:
Weight, height, BMI, blood pressure
Glucose, HbA1c, lipid profile, 25-OH-vitamin D, calcium, creatinine
FRAX calculation of bone fracture risk (age > 70, > 7.5 mg/day for > 3 months, bone density T-score <- 2.5, history of fragility fracture)
Risk of adrenal insufficiency:
Patients taking 5 mg/day of prednisolone for more than four weeks are at risk of adrenal insufficiency.
It is important to inform them of this risk in the event of stress or a surgical procedure.
However, this presentation did not address some important points such as when to start a bisphosphonate, how to stop/taper off corticosteroid therapy, etc.
What’s new in cutaneous vasculitis?
Prof. Erkan Alpsoy, Turkey
1. Drug-induced vasculitis
Medications can be a cause of cutaneous vasculitis (CV) in 10 to 20% of cases. Correia et al. (P0071) reported a case of CV with rivaroxaban four months after its introduction. There was necrotic purpura on the lower limbs. Twenty-six CV cases have been described in the literature. However, the poster’s authors did not have a review of the literature and the classic time to onset was not described.
Moreover, the authors did not carry out reintroduction tests.
The other cutaneous complications of rivaroxaban include generalised pruritus, haematoma and ecchymosis.
2. Cutaneous vasculitis and COVID-19
Several cases of CV have been reported either during SARS-CoV-2 infection or after vaccination.
In the first case, Frioui et al. (P0291) observed IgA vasculitis with segmental necrotising glomerulonephritis four days after the start of infection, while Bay et al. (P0444) reported a case of CV occurring 15 days later. Macrophage activation syndrome was diagnosed following a case of cutaneous vasculitis associated with COVID-19 (Tahiri et al., P0459).
Cases of post-vaccine CV have also been reported. They occurred fairly rapidly after vaccination, i.e. three (Idrissi et al., P0092) to 21-25 days (Jabbour et al., P0488) later.
3. Decision-making algorithm when faced with a case of cutaneous vasculitis
a. Clinical presentation
Symmetrical palpable purpura on the lower limbs is highly suggestive of CV.
The other clinical signs suggesting CV:
Urticarial papules
Pustules
Vesicles/bullae
Necrosis
Livedo
Target lesions
Leg ulceration/ulcers, papules
b. Histology
Two biopsies (standard and direct immunofluorescence)
Recent lesion in past 24-48h
With a circular blade (punch biopsy) or scalpel depending on the type of lesion
c. Causes
Idiopathic in nearly one in two cases
Infection (15-20%)
Inflammatory (15-20%)
Drug-induced (10-20%)
Cancer 5%
d. Work-up
Minimum work-up: CBC, kidney and liver function, urinalysis, chest x-ray
If other clinical symptoms: antistreptolysin, throat sample, CRP, protein electrophoresis, viral hepatitis/HIV, ANA, anti-DNA, anti-ENA, ANCA, RF, anti-CCP, complement, cryoglobulin
Migrant health dermatology
Dr. Valeska Padovese, Malta
Prof. Dr. Jan Gutermuth, Belgium
Current immigration flows:
- Syria 6,300,000
- Afghanistan 2,600,000
- South Sudan 2,400,000
- Somalia, Sudan, Democratic Republic of the Congo, etc.
Immigration factors:
- Armed conflicts
- Climate change/climate disasters
- Searching for a work permit
- Family gatherings
- Education
Dr Valeska Padovese shared her experience in Malta. Malta is the southernmost country in Europe, located between Sicily and North Africa, on the Central Mediterranean immigration route.
The prevalence of skin diseases among migrants arriving in Malta ranges from 19% to 96% depending on the population and the geographic region of origin.
Scabies is the no. 1 transmissible disease in migrants. Specific dermatological features include burns from salt abrasion on boats due to seawater and the sun. Chickenpox outbreaks have been observed in refugee camps. Tropical diseases such as filariasis, leishmaniasis and deep fungal infections should not be overlooked. In refugee camps, for example in Jordan, the prevalence of cutaneous inflammatory disorders, especially eczema, is around 72%, with skin infections accounting for 21%
(primarily fungal and viral infections).
In the Kutupalong refugee camp (Bangladesh), the prevalence of skin diseases is 30% (for 800,000 people). Once again, the majority of cases involve fungal infections.
STIs in Malta (mainly young male population, aged 19-34)
1. C. Trachomatis
2. Candida and ringworm
3. HIV 5.5%
It is important to stress the fact that migrants have high-risk behaviours once they arrive in Europe.
1. Sexuality
- no use of condoms
- sex with multiple partners
- lack of knowledge on how to access healthcare services
2. Social inequalities
- related to sex trafficking
- due to HIV-related discrimination
- related to changes in sexual behaviour after migration
3. Sexual abuse/sex workers
As a result, 37% of newly diagnosed HIV infections are diagnosed following migration.
Efficacy of topical ruxolitinib in non-segmental vitiligo
Dr. David Rosmarin, United States
The physio-pathogenesis of vitiligo is largely related to interferon-gamma via the JAK signalling pathway. Ruxolitinib (RUX) is a JAK1/JAK2 inhibitor whose 1.5% cream form applied twice daily is currently being tested for vitiligo. RUX was found to be effective in a 52-week phase-2 study. Here, the results of the Topical Ruxolitinib Evaluation Vitiligo 1 and 2 (TRuE-V) phase-3 studies were presented. These were two similar double-blind multi-centre studies comparing RUX with a vehicle (placebo). The studies included a total of 674 adolescents (12 years and over) and adults with nonsegmental vitiligo in a 24-week trial comparing RUX with a vehicle.
To be included, the patients had to have depigmentation covering > 0.5% of the total surface area of the face and > 3% of the total surface area of the body (excluding the face).
The study was then extended over a period of 28 weeks where all patients received the treatment.
The primary objective here was to evaluate the proportion of patients achieving F-VASI75 at week 24.
At week 24:
TRuE-V1
TRuE-V2
The results were comparable between the two studies and ruxolitinib outperformed the vehicle in terms of repigmentation. There was also efficacy on the body with 20.6% to 26.1% of patients achieving T-VASI75 versus with the vehicle (4.9% to 11.3%) at week 24.
The major side effects were acne flare-ups and pruritus in 5% of patients.
Ruxolitinib is a topical treatment that appears to be effective at treating vitiligo, compared with a placebo. The side effects are limited. We are now waiting for studies comparing this drug with standard treatments such as topical corticosteroids and calcineurin inhibitors.
Is abrocitinib more effective than dupilumab for atopic dermatitis?
Prof. Dr. Kristian Reich, Germany
Kristian Reich presented a phase-3 Jade Dare study (B7451050) that compared abrocitinib 200 g/day (JAK1 inhibitor) with dupilumab 300 mg every two weeks (IL-4 inhibitor) for the treatment of moderate to severe atopic dermatitis in adults not responsive to topical treatments or requiring systemic treatment.
The duration of the study was 26 weeks and it included over 700 patients (abrocitinib n=362, dupilumab n=365). The study was completed by at least 90% of patients.
At week 2, PP-NRS4 (pruritus) was 48% for abrocitinib versus 25% (p<0.001). However, over time, the two curves met and at week 12, there were no major differences, subject to the statistical analysis, which was not mentioned in the communication (PP-NRS4 of 61% for dupilumab versus 66% for abrocitinib), with results of 63% versus 68% at week 26.
The side effects in the abrocitinib group included nausea (19%), headaches (13%) and acne flare-ups (13%). In the dupilumab group, 10% of patients developed conjunctivitis.
In the end, abrocitinib in this study, at the dose of 200 mg/day, was more effective and acted faster against pruritus than dupilumab. It was still effective at week 16. Its safety profile was acceptable. This type of head-to-head study is essential to be able to administer personalised treatments to patients based on their history and clinical symptoms.
Report written by Prof Anna ZALEWSKA JANOWSKA
Dermatologist, Poland
Plenary Lecture A
Microbiome
Senescence
Introduction
Prof. Brigitte Dréno, France
Plenary session was chaired by Professor Brigitte Dréno from Nantes in France who is currently the EADV Scientific Programming Committee Chair.
Emerging priorities for microbiome research
Prof. Richard L. Gallo, United States
Professor Richard Gallo from San Diego in the USA delivered a lecture on emerging priorities in microbiome research. Microbiome is defined as all microorganisms in a particular environment (bacteria, bacteriophage, fungi, protozoa and viruses). Often research is focused on the genetic material of the organisms, also often on bacteria, furthermore, also focused on gut (namely fecal bacteria) and finally often focused on the potentially beneficial microbes. Prof. Gallo stressed that the first principle for understanding microbiome science is to remember that microbes can be good, bad
or irrelevant. Skin interactomes comprise microbe to microbe and microbe to host interactions and they can demonstrate either pathogen-pathogen, pathogen-commensal, pathogen-host or commensal-host interactions. The total microbiome-host-skin interactome is complex, a special axis gut-brain-skin is formed. Of note, microbe activity at one organ many affect a distinct organ.
Interactions between organs are bidirectional. Understanding the microbiome seems to be useful in treating skin diseases such as atopic dermatitis. Evidence that favours the microbiome theory in AD is the following: S. aureus colonization is correlated with human disease severity, microbial dysbiosis precedes diseases development in children, preclinical models show that S. aureus colonization drives inflammation and effective therapy of immune defect results in improved microbiome. Research data demonstrated that host and microbiome defence failures enable S. aureus to survive in AD.
Some trials were undertaken to characterize ideal biotherapy by microbes – they should be beneficial to the host, can produce multiple active molecules, should survive in the human environment, does not disrupt the normal microbiome and does not cause infection. Professor Gallo group undertook parallel screening and deep sequencing from human skin microbiome to discover biotherapeutics. S. hominis A9 was nominated to be a biotherapeutic candidate. This microbe promoted early clinical
response in subgroup with S. aureus killing (Nakatsuji, Gall et al, Nature Medicine 2021). In conclusion, biotherapy with S. hominis A9 was well tolerated and inhibited S. aureus. S. hominis A9 decreased skin inflammation and improved the microbiome. These preliminary results are very promising and seem to open new era of treatment of many skin diseases, but extensive and in-depth microbiome research is needed.
The role of senescence in health and disease
Prof. Manuel Serrano, Spain
Professor Manuel Serrano from Barcelona in Spain presented a topic on senescence in health and disease. Senescence is a non-apoptotic cellular response to damage. Senescent cells markers (usually combination of markers) are the following: highly secretory (IL-6, IL-1β, TGF- β, PAI-1), CDK inhibitors (p16, p21) and hyperactivation of retinoblastoma and expanded lysosomal compartment (β-galactosidase activity). In young organisms there are less than 1% of senescent cells whereas in old ones (>75 years Homo sapiens) is percentage equals to about 5%. Ageing associated degenerative diseases demonstrates about 50% of senescent cells. Primary senescence depends on environmental factors, ageing, genetic predisposition, persistent allergens or autoimmunity and leads to senescence-associated secretory phenotype (SASP) development (IL6, IL-1β, TGF- β, PAI-1), then senescent fibroblasts and myofibroblasts change and matrix deposition. develops Therapeutic
strategies targeting senescence are either senomorphic (reduced pro-fibrotic and pro-inflammatory secretome) or senolytic (apoptosis that may be followed by repair). Senolytics are currently applied in idiopathic pulmonary fibrosis as a first-in-human, open-label pilot study. On the web ClinicalTrials.gov current studies in the subject could be observed. They are definitely quite promising also for dermatology.
The Neuroscience of Unconscious Bias & Implications in Medicine
Michele Nevarez, United States
Ms Michele Nevarez from Williamstown in the USA focused on neuroscience of unconscious bias and implications in medicine. Unconscious bias are social stereotypes about certain groups of people that individuals form outside their own conscious awareness. Implicit an explicit bias contributes to lowerquality health care. Compared with white patients, black patients were 40 percent less likely to receive
medication to ease acute pan and Hispanic patients 25% less likely, in USA. Neuroscience of perception demonstrates that our brain is constantly predicting and simulating its experience based on its past experiences and expectations. We assign meaning to our perceptions and emotions based on what we have learned and has been modelled to us over our lives and draw upon our social influences, lineage of sense making and beliefs. Our brain treats pain in a person from outside our group as being of less intensity, and thus less/no empathy is raised than pain experienced by a
member of our group. So, we should practice in ourselves conscious awareness, conscious sensemaking and or ability to connect with others. Those features are of extreme importance specially in medical professions.
Plenary Lecture B
Atopic dermatitis
Autoimmunity
Autoinflammation
Biologics
Psychodermatology
Introduction
Prof. Alexander Stratigos, Greece
Professor Alexander Stratigos, from Athens in Greece, the current president of EADV presented the distinguished speakers of plenary lectures pointing out at their breaking through achievements.
Atopic dermatitis and biologics after 5 years: Where are we?
Prof. Thomas Bieber, Germany
Professor Thomas Bieber from Bonn in Germany delivered a lecture on atopic dermatitis and biologic treatment of this disease available already for the last 5 years. The lecturer stressed that first new biologic treatment for atopic dermatitis was introduced 25 years after systemic cyclosporine. As for dupilumab, this first biologic treatment for atopic dermatitis, based on personal experience of the speaker – 25-30% of patients show good response to monotherapy whereas 10-15% of patients are no-responders. As for the rest i.e., 55-75% of atopic dermatitis patients, we can call them partial responders. The latter require additional local treatment with either corticosteroids or calcineurin inhibitors in different regimens (once daily to 1-2 times per week). Currently targeted therapy against an underestimated cytokine IL-13 emerged. Possible consequences of IL-13 in atopic dermatitis are the following: skin barrier defects, skin infections, inflammation, itch and skin thickening. Drugs
interfering with IL-13 pathways are the following: lebrikizumab and anrukizumab, tralokinumab and RPC4046, ASLAN0004. Tralokinumab (Adtralza) was approved in EU for moderate to severe atopic dermatitis patients on 17.06.2021. Lebrikizumab demonstrates EASI90 response in about 40% of patients after 16 weeks of treatment. Namolizumab (anti IL-31) is extremely effective in prurigo nodularis, is a powerful approach against itching in atopic dermatitis but good clinical response is observed only in a subgroup of patients. Professor Bieber also highlighted complex interactions
between genetics and exposome in AD demonstrating evidence for an “immunologic march” with innate and adaptive immune responses involved (Bieber T, Nature Review Drug Discovery 2021). AD due to its complex pathophysiology has the potential of being treated by many different biologics. Precision medicine is “knocking at the door”.
Professor Bieber elegantly pointed at future challenges and opportunities for all stakeholders in management of atopic dermatitis using biologics. Unravelling the complexity of AD, establishing treatment algorithms, biomarker discovery for future stratification for precision medicine are challenges for academia and researchers. To adopt systemic therapy, understand and translate the rapidly evolving therapeutic landscape to the patients are challenges for prescribes. Whereas challenges for the patients seem to be the following -to understand the disease and improve literacy
for participative decisions. Pharmaceutic companies will have to accept the complexity and adapt their CDP towards precision medicine, including marker access aspects. Challenges for Health Technology Assessment Agencies and third-party payers should adopt positive attitude towards innovative therapies, translate precision medicine as an option for cost-effectiveness modelling. Above just a few challenges, more to be revealed in the nearest future.
The power of touch
Prof. Dr. Michael Musalek, Austria
Professor Michael Musalek psychiatrist, neurologist and psychotherapist from Vienna in Austria delivered a “touching” lecture on the power of touch. Skin has numerous functions including being a barrier, respiratory, absorption, immune and sensory organ as well as communication one. Homo sapiens is a social creature from the very beginning of her/his life. The word “social” has both philosophical and empirical-scientific approach. Both in Berlin and Vienna, Institute for Social Aesthetics and Mental Health operates. Such institute requires multidisciplinary team and works on
social aesthetics issue i.e., science and art of how to live together in general and how to establish beautiful encounter and relationship in particular. Touching itself could be divided into physical (e.g., hand-hand, head-to-head, embracing, kissing), mental (emotional response to touching, emotions, situations etc) and spiritual (e.g.by transcendental fantasies and ideas) touching. All 3 form of touching are interconnected. Experiences quality of touching is influenced by magnitude (intensity,
area), time, context (location, situation, atmosphere), standards (society, culture). Touching could reduce stress but also could produce stress. We should be aware of both. For positives touching provides possibilities for encounter/relations, intensify confidence in self another, opens up door for mutual experience of beauty, augments and reinforces power/vitality, enables for lived togetherness/solidarity. The lecturer underlined that touch is not just touch, it requires to be at the right place, at the right time and at the right situation.
Pruritus
New treatments for chronic pruritus and prurigo
Prof. Dr. Sonja Ständer, Germany
Professor Sonja Stander from Munich in Germany chaired the session and also delivered a very promising lecture on new treatments for chronic pruritus and prurigo. Based on extensive review by Lay M and Dong X (Annu Rev Neurosci 2020; 43:187-205) prof. Stander pointed out to numerous targets in itch processing and subsequently potential therapies for itch. The targets for therapy include: immunomediator receptors (such as IL-4, IL-13, IL-31 receptors), JAK/STAT pathway,
pruritogen-receptor (histamine, neuropeptides, Mas-related G protein-coupled receptors), Ion channels (TRPV1, TRPA1) or spinal pruriceptors (GRPR, KOR). Of note, equilibrium between neuroand immunological pathways seems to play an important role in pathophysiology of itch. Crucial role of IL-31 was underlined in pruritus, but also in neuronal growth, inflammation, tissue remodelling and barrier dysfunction. Numerous data demonstrated that in chronic nodular prurigo itch intensity correlated with the number of IL-31, IL-31RA and OSM-expressing cells. Professor Stander presented clinical trials in chronic nodular prurigo. The ongoing ones are the following: dupilumab (phase III, IL4Ralfa antagonist), nemolizumab (phase III, IL-31RA antagonist), nalbuphine (phase II/III, KOR agonist/MOR antagonist), vixarelimab (phase II, OMRbeta inhibitor). Results of those trials seem to be very promising. Treatment ladder in prurigo was presented. Of note – emollients should be used in every step, interdisciplinary approach and individualization of therapy is expected. Topical corticosteroids, topical calcineurin inhibitors and H1-antihstamines are used in step 1. Step 2 comprises topical capsaicin, intralesional corticosteroids and UV phototherapy. In step 3 gabapentin, pregabalin, antidepressants, cyclosporine A and methotrexate are placed. NK1R antagonist, μ-opioid receptor antagonists, dupilumab and nemolizumab can be found. Of interest European guidelines on chronic pruritus were published in Acta Derm Venereol 2019, 99, 469-506. Professor Stander underlined that novel therapy in pruritus and prurigo should address neuroimmune or central neuronal communication issues and earliest approval in expected in 2022/2023 on the market.
Approach to the patient with chronic pruritus
Prof. Franz Legat, Austria
Professor Franz Legat from Graz in Austria acquainted the audience with thorough approach to the patient with chronic pruritus (itch), which is very common in general population (8-9%) with life-time prevalence of 22%. The lecturer pointed out that during the first visit the patients want to tell their story, to know the reason, to get an effective treatment and finally to be cured, whereas physicians should have an open ear, a big heart, a lot of time and a strategy to approach the patient. Of note, key
to aetiology of chronic pruritus are patient extensive medical history, physical examination and lab tests. Patients with chronic pruritus should be classified into 3 groups: with primary skin lesions (including psoriasis, atopic dermatitis or other eczema, urticaria, bullous pemphigoid, lichen planus, myosis fungoides/Sezary syndrome, without skin lesions (systemic diseases – kidney, liver, hematologic, endocrinologic, metabolic, infectious and with secondary skin lesions; neurologic;
psychiatric/psychosomatic; drug-induced; pregnancy-associated). The groups 1st and 2nd lead to 3rd group development i.e., with secondary skin lesions. Basic laboratory tests include CRP, complete blood count a differential, liver and renal parameters, glucose, LDH, electrolytes, TSH, ferritin n urine. Definitely, taking care of the patient with chronic pruritus required a lot of time and empathy, not
mention knowledge and experience.
The burden of pruritus in dermatology
Assoc. Prof. Joanna Wallengren, Sweden
Professor Joanna Wallengren from Lund in Sweden presented an overview on burden of pruritis in different dermatological diseases such as atopic dermatitis, psoriasis, urticaria, chronic prurigo, bullous pemphigoid, pemphigus, ichthyosis epidermolysis bullosa. Prevalence of pruritus in many dermatological diseases is very high and account to 70-90%. Pruritus is rated as the most or second troublesome symptom of skin disease. Quality of life of affected patients is impaired in the following areas: stigmatization, sleeping problems or sexual dysfunction. Burden of pruritus is higher in affected children, women and black patients. Depression and anxiety are common co-morbidities in patients suffering from pruritus. Pruritus also impacts quality of life of the families of affected patients and financial burden of pruritus on families and society is high, so effective and affordable anti-pruritic
therapies are strongly needed.
The unifying concept of chronic prurigo
Prof. Kenji Kabashima, Japan
Furthermore, the unifying concept of chronic prurigo was delivered by Professor Kenji Kabashima from Kyoto in Japan. Professor Kabashima roughly presented guidelines of Japanese Dermatology Association for the diagnosis and treatment of prurigo published in the Journal of Dermatology this year. He also gave a very extensive overview of knowledge on prurigo that can be found in Rook Textbook of Dermatology i.e., “dermatological bible”. He then focused on chronic prurigo as a reactive
skin disease characterized by isolated papules or nodules induced by itch. Chronic prurigo includes prurigo nodularis and can be induced by dermatological/ systemic/ neuropathic or psychogenic diseases. Prurigo is characterized by neuroanatomical changes such as thickened peripheral nerves, increased substance P, CGRP, IL-31, mast cells, basophiles and eosinophiles. Of importance anti-IL-4R/IL-31Ra antibodies are effective in prurigo treatment and Th2-ILC2- and basophil-derived type 2
inflammatory cytokines (IL-4,13 and 31) seem to be involved in the pathogenesis of chronic prurigo via JAK/STAT pathway. The lecturer also pointed out at the areas and questions that are still unanswered such as what is the most appropriate definition of prurigo; is prurigo an independent disease; what is the inducer of prurigo, IL-4/13/31 or others; are there any endotypes of prurigo; what is the relationship between skin diseases such as atopic dermatitis and prurigo nodularis; how prurigo nodularis is induced by other conditions such as HIV, DM or liver diseases; what is the relationship with psychosocial problems (result or cause). The topic is fascinating and still requires a lot of research.