EADV Congress 2024 Highlights
Welcome to the opening day of the EADV Congress 2024! Set against the historic and picturesque backdrop of Amsterdam, the Netherlands, this year’s meeting promises valuable insights across all major fields of dermatology, delivered by the most esteemed figures in the field.
Catch a glimpse of each day’s activity in this bite-sized round-up of scientific highlights.
Wednesday
25 Sept 2024
Today's hot topics
Plenary session
Guiding dermatology towards a sustainable future
We were honoured to be joined by Dr Bertrand Piccard for today’s Plenary Lecture, where he delivered a thought-provoking presentation on “Renewable Energy and Clean Technologies: The New Medication for Our World.”
Dr Piccard is a modern-day pioneer renowned for his groundbreaking achievements in aviation, including his record-setting around-the-world balloon flight in 1999 and his circumnavigation of the globe in a solar-powered aeroplane in 2016. In his lecture, Dr Piccard drew powerful parallels between the spirit of exploration needed to achieve remarkable feats and the type of transformative leadership required to confront today’s climate challenges.
He urged industries, including dermatology, to embrace renewable energy and clean technologies as essential tools in combating climate change.
Dr Piccard called on attendees to rethink their roles as leaders and innovators, presenting them with an ongoing challenge to actively contribute to a more sustainable future, both within the field of dermatology and beyond. His inspiring message emphasised that sustainability is not just a responsibility, but also an opportunity to leave a legacy and lead the way forward.
New and emerging drugs
Novel treatments for hidradenitis suppurativa, alopecia and other skin conditions
Hidradenitis suppurativa
Dr James G. Krueger (New York, NY, United States) introduced this session by sharing his perspectives on hidradenitis suppurativa (HS). In contrast to other inflammatory diseases, comprising one immunological feature to guide drug development, HS is a complex, progressive condition involving innate and adaptive immune mechanisms, skin-based cytokines and bacterial dysbiosis, with different pathogenic elements –– there is no single cause.
Currently, approved drugs and in phase 2–3 development for HS represent diverse immune mechanisms, based on a translational medicine approach. Approvals based on HiSCR scores indicate TNF and IL-17 involvement although other inflammatory factors may be involved, with biomarkers suggesting that two main epithelial structures are altered: superficial psoriasiform epidermal hyperplasia and deep dermis epithelialised tunnels/fistulae. IL-17A, IL-17C, and IL-17F have been shown to be upregulated in HS skin regions with IL-17 signalling in tunnels. Cytokine targets for neutrophilic HS inflammation include those involved in innate and a Th17 cell response (e.g eltrekibart). IL-17A and IL-17F antagonists are in development (e.g. secukinumab and bimekizumab approved by the FDA and EMA, respectively). In addition, new nanobody-derived therapies (e.g. sonelokimab) reduce draining tunnels, which may be an important target in HS.
Gram-negative anaerobes also elicit a robust keratinocyte immune response and likely contribute to HS disease progression and IL-17 inflammation, supporting antibiotic therapy. Other targets may include C5a antagonism to improve tunnel drainage. While some psoriasis pathways (e.g. IL-23) may not apply in HS, B/plasma cells appear to be more abundant, with two early studies supporting the role of B cells in active HS inflammation.
Skin inflammation may be the tip of the iceberg
Atopic dermatitis
Prof. Thomas Bieber (Bonn, Germany) gave insights into advances for atopic dermatitis (AD) noting that currently more than 100 drugs are in development. Most treatments include steroids, topical calcineurin inhibitors (TCIs), small molecules and biologics; however, many are not available in Europe because of market access issues.
Drug therapy for AD is based largely on two mechanisms: skin barrier dysfunction and immune response. Improved insights into pathophysiology have transformed the potential for drug development of AD (and other pathological conditions), shifting from ‘on-therapy’ for treating flares to ‘off-therapy’ for long-term control.
Prof. Bieber illustrated potential targets for AD by simplifying the ‘immunological march’ approach, first looking at the classical downstream approach including the microbiome and Th2 cytokines (e.g. lebrikizumab and nemolizumab), targeting antigen-presentation costimulatory molecules with next-generation therapies: anti-OX-40 or OX40-L (e.g. rocatinlimab and amlitelimab); targeting ‘upstream’ innate signals, including IL-13 and anti-TSLP therapies; and amplifying T regulatory response, which represent a new hope, also for psoriasis (e.g. rezpegadesleukin targets the IL-2R has potential to restore immune balance and stop therapy).
Alopecia areata and vitiligo
In his presentation, Prof. Julien Seneschal (Bordeaux, France) highlighted that alopecia areata (AA) and vitiligo are distinct autoimmune disorders with different clinical characteristics (loss of hair or pigmentation). However, these conditions may be linked, as demonstrated by sharing of common genes, and with an interaction between epithelial cells and of CD8+T cells in both.
JAK inhibitors represent the most effective therapies to date, eliciting a type 1 immune response. Current therapies for AA include baricitinib and ritlecitinib, which have shown positive results on Severity of ALopecia Tool (SALT) scores. The factors for showing a good response include appropriate dose and duration of therapy, earlier response in patients with patients with severe AA and the need to maintain therapy.
For vitiligo, Prof. Seneschal explained that the aim is to halt pigmentation, induce regimentation and reduce relapses and stop disease spread. Topical ruxolitinib is currently approved for vitiligo and induces repigmentation over time, highlighting the importance of maintenance therapy.
Newer treatments in development represent other aspects of pathogenesis pathways and include memory T cells, ultraviolet light and regeneration of melanocytes.
Psoriasis
In the last presentation of this insightful session, Prof. Antonio Costanzo (Milan, Italy) provided the audience with a detailed view of the current treatment landscape for psoriasis.
Psoriasis is a single disease with many different clinical presentations, caused by the sequential actions of the immune system. By putting the clinical features together, such as chronic, acute and pustular plaque, it is possible to gain a better understand of what is new.
Despite the wide armamentarium of therapies available, Prof. Costanzo explained that most pharmacological research still focuses on the disease itself. He highlighted that newer biologics are being developed to specifically target the key cytokines involved in the pathophysiology of this condition.
With the advent of newer therapies, there is also a transition from injectable to innovative oral therapies, with personalised treatment for psoriasis a possibility in the future.
Key takeaway
- Better understanding of disease pathogenesis will help identify appropriate targets with the potential for disease-modifying therapies
JAK INHIBITORS
What’s new with JAK inhibitors?
The expanding landscape of JAK indications
Prof. Curdin Conrad (Lausanne, Switzerland) set the scene for the session with a discussion on the expanding role of JAK inhibitors in treating dermatological and autoimmune conditions. He highlighted how these inhibitors target multiple cytokine pathways, offering broader efficacy by modulating both innate and adaptive immune responses. While ongoing Phase III trials are exploring the full potential of JAK inhibitors, there remain some dermatological conditions where JAK inhibition has been tried but with less consistent and encouraging results. Prof. Conrad also noted the potential for combining JAK inhibitors with anti-PD-1 immunotherapy to enhance cancer treatment response, particularly in Hodgkin lymphoma and non-small cell lung cancer.
Is JAK inhibitor selectivity relevant in the real-world?
Dr Maryanne Makredes Senna (Winchester, United States) examined the relevance of JAK inhibitor selectivity in treating autoimmune conditions like alopecia areata. She highlighted that while selective JAK inhibitors, such as ritlecitinib, are designed to target specific pathways with fewer off-target effects, clinical outcomes between selective and non-selective inhibitors, such as baricitinib, don’t differ significantly in efficacy. She emphasised that factors like dosing, patient-specific characteristics, and comorbidities may play a larger role in treatment response than selectivity alone. Dr Senna concluded that treatment should be individualised, as both selective and non-selective JAK inhibitors can be effective options depending on the patient’s needs.
Upcoming topical and systemic JAKs
Dr Kamran Ghoreschi (Berlin, Germany) presented an enlightening presentation on the future of topical and systemic JAK inhibitors in dermatology, emphasising their advantages over glucocorticoids. Upcoming topical JAK inhibitors include delgocitinib, approved in Japan for atopic dermatitis and under investigation in Europe for chronic hand eczema, and ruxolitinib, the only approved topical JAK inhibitor in Europe. Delgocitinib has also shown promise in EGFR inhibitor-induced rash. Systemic JAK inhibitors, including brepocitinib, povorcitinib, deuruxolitinib, and rovadicitinib, are advancing in trials for hidradenitis suppurativa, alopecia areata, cGvHD, and prurigo nodularis, with significant disease control and tolerable safety. Rovadicitinib, a dual JAK1/2 and ROCK1/2 inhibitor, has shown notable efficacy in cGvHD, while gusacitinib, a dual pan-JAK and Syk inhibitor, demonstrated efficacy in chronic hand eczema, making them promising options for broader dermatological conditions.
Predicting the risk of JAK inhibitors
Dr Andreas Wollenberg (Augsburg, Germany) raised the question: Would you give this class of drugs to your children or your grandmother? This was followed by an in-depth overview of the safety and monitoring guidelines for JAK inhibitors, with a particular focus on risks such MACE, thrombosis, and cancer. He emphasised that while JAK inhibitors are a rapidly effective and versatile class of drugs, significant safety concerns persist. He reassured that these concerns should be saved for those patients with particular risk factors, such as atherosclerotic cardiovascular disease, malignancies, or those aged over 65. For these patients, JAK inhibitors should only be prescribed if no suitable alternatives are available. Dr Wollenberg also addressed the variations in safety profiles across different JAK inhibitors, stressing the importance of careful patient selection and individualised risk assessments when prescribing these therapies.
Key takeaways
- JAK inhibitors offer broad efficacy in treating dermatological and autoimmune conditions, but their safety remains a concern for high-risk patients.
- Personalised treatment plans and careful patient selection are crucial, with ongoing research needed to refine their optimal use.
Thursday
26 Sept 2024
Today's hot topics
HAIR DISORDERS
Advances in Diagnostics, Treatments, and Emerging Therapies for Hair Disorders
Hair follicle microenvironment
Dr Ralf Paus (Miami, United States) provided an insightful overview of the dynamic and complex microenvironment of hair follicles (HFs). He described how skin nerves around the HFs are loaded with neuromediators that are continuously communicating, giving HFs the power to not only regulate themselves, but also influence the entire skin’s immune system.
Dr Paus likened the HF to a kidney, noting its ingenious ability to “suck up” blood-borne molecules and remove toxins by embedding them into the hair shaft for excretion through shedding. The intricate communication taking place between HFs and their environment underscores the potential for novel alopecia treatments through immunological hair cycle manipulation.
Trichoscopy and imaging techniques
Dr Marta Sar-Pomian (Warsaw, Poland) presented compelling evidence for the need to bridge the gap between trichoscopy and histopathology in hair disorder diagnosis and management. Using images from a variety of hair disorders, she demonstrated that while trichoscopy provides a non-invasive, detailed view of the scalp surface, it lacks the cellular precision of Reflectance Confocal Microscopy (RCM) and Line-field Confocal Optical Coherence Tomography (LC-OCT). LC-OCT, for example, provides both vertical and horizontal images of the scalp and a dermoscopy camera for a real-time, 3D view of the examination area.
The future integration of AI in LC-OCT image analysis may significantly improve the diagnosis and monitoring of hair and scalp disorders.
The challenge lies in creating a microenvironment that maintains the HF in anagen longer, maximising therapeutic opportunities that current hair treatments might not fully exploit.
Female androgenetic alopecia
Prof. Bianca Maria Piraccini (Bologna, Italy) discussed Female Androgenetic Alopecia (FAGA), which peaks during the reproductive years and post-menopause.
She discussed the efficacy of a range of branded, generic, combination, and off-label treatment options, the most evidence-based promoting dermal papilla cell proliferation and upregulating keratin-associated proteins. However, she cautioned that some off-label treatments require necessary considerations for contraception and exclusion of postmenopausal women with hormone-dependent breast cancer history.
Prof. Piraccini concluded by emphasing that quality of life considerations must not be forgotten during treatment decision-making.
Male androgenetic alopecia
Prof. Dimitrios Ioannides (Thessaloniki, Greece) discussed the pathogenesis, diagnosis, and treatment of Male Androgenetic Alopecia (AGA), highlighting the potential for mesotherapy and microneedling to enhance the results of traditional treatments.
Prof. Ioannides also discussed some exciting emerging therapies, including one that leverages nanoparticles to bind to messenger RNA and inhibit protein synthesis, reducing androgen receptor activity in dermal papilla cells without side effects. This downregulation effectively addresses hair loss at a molecular level, surpassing traditional treatments.
Prof. Ioannides stressed the importance of personalised treatment plans, suggesting that combining topical and oral treatments with innovative nanotechnology and exosomes could significantly improve therapeutic outcomes.
Key takeaways
- Hair follicles are complex, presenting numerous challenges and opportunities for treatment.
- Advancements in imaging techniques are paving the way for more precise diagnostics and personalised treatments.
Atopic dermatitis
Different AD phenotypes, microbiome modulation and novel treatments
Adult-onset AD: What is it?
Prof. Emma Guttman-Yassky (New York, NY, United States) started the session by sharing the key characteristics of adult-onset AD (AOAD) and how this differs from paediatric-onset AD (POAD).
Atopic dermatitis (AD) is the most common inflammatory skin disease, which can affect daily activities. AOAD appears for the first time in adulthood, while most POAD cases are in children aged 5 years or younger.
AOAD is characterised by unique epidemiological and clinical features, distinct from POAD, that persist into adulthood and can include a non-typical clinical presentation with face/neck, scalp, hand/feet, or peri-ocular involvement, or present as diffuse eczema. AOAD is associated with vesicle/nodule involvement with loss of the outer third of the eyebrow. Exposome exposure, including the environment, lifestyle and stress, can impact on AD trajectory.
Prof. Guttman-Yassky explained that while both conditions share some inflammatory features (significant Th2 and Th22 immune and barrier dysregulation), there are also important differences. Clinical studies have shown greater Th1/IFN-gamma skewing in AOAD, compared with greater Th2/Th22/Th17 skewing and epidermal parallel barrier defects in POAD skin. In serum, inflammatory and cardiovascular risk proteins are also increased in AOAD. The age of onset in AOAD patients delineates two different AD endo-phenotypes, with potential therapeutic implications.
“Spitz nevus believes he is melanoma. He behaves and dresses like melanoma. But, he is not melanoma. He can’t kill. Once he realises this, his life becomes meaningless, and he kills himself; he disappears.”
Microbiome modulation: Prevention or treatment of AD?
In his engaging session, Prof. Tilo Biedermann (Munich, Germany) discussed the feasibility of modulating the microbiome in AD, by supplementing the skin with commensals.
Studies have shown that the diversity of microbiome (i.e. staphylococci) breaks down in AD patients with flare; however, simply reducing Staphylococcus. aureus (S. aureus) outgrowth by different means may not be sufficient to treat AD effectively. Blocking type 2 inflammation in moderate-to-severe AD can reduce S. aureus and restore barrier function, thus, treating the underlying disease can help to restore the microbiome.
Prof. Biedermann discussed three concepts for intervention: barrier restoration/strengthening (emollient use), reducing cutaneous inflammation (topical or systemic treatment) and dysbiosis to modulate microbial composition (introducing balancing microbes and nutrients). He explained that readjustment of treatment goals is needed and a focus on the effect size of ‘good microbes’, not only anti-inflammatory topical or systemic drugs. He introduced a new concept of reducing inflammation in combination with microbiome modulation and how stabilisation of microbial composition may prevent relapses. However, clinical trials to assess the preventive effects in AD are necessary but are cumbersome to perform.
Nurturing a ‘good microbiome’ may represent a novel goal in AD and lead to microbiota-friendly emollients, Prof. Biedermann concluded.
Hard to identify and treat AD
Prof. Phyllis I. Spuls (Amstelveen, Netherlands) highlighted the current gaps and unmet needs in AD diagnosis and treatment. Currently, there are variations in AD prevalence between countries and age groups. AD presents a spectrum of dermatological manifestations, and there is a need for consensus on validated diagnostic criteria to diagnose AD and consensus is needed on AD clinical phenotypes. The HOME core outcome set for trials should be implemented to improve research.
Prof. Spuls highlighted that patient education is crucial and can help to improve outcomes, and that information for patients should be harmonised among all healthcare workers involved. Healthcare professionals should take an active role in explaining that AD is multifactorial, detailing the underlying causes (aetiology and triggers), and providing guidance on bathing and emollient use, in addition to details on how and when to use active treatment.
There are well-conducted Cochrane reviews of topical, ultraviolet (UV) and systemic treatments (including living network meta-analyses). The calcineurin inhibitor tacrolimus is currently not available in the Netherlands, highlighting the need for more topical treatments for AD. Additionally, improved research is also warranted for topical/UV and systemic treatments, as well as for combination therapies. Randomised controlled trials are ongoing for UVB treatment in AD.
Prof. Spuls explained that newer trials should include long-term data, patient-reported outcomes, patient subgroups, and active comparators to move away from placebo-controlled comparisons. Observational and practice data, such as the TREAT Registry Taskforce, are also warranted.
New topical and systemic treatments
In the last presentation, Dr Robert Bissonnette (Montreal, Canada) outlined novel treatments for AD.
Currently, there are a limited number of topical treatments available in Europe and more treatment options are available in the United States (US). These include ruxolitinib (a JAK inhibitor), roflumilast (a phosphodiesterase-4 inhibitor), both approved in the US for AD, and tapinarof (an aryl hydrocarbon receptor agonist) approved for psoriasis in US and Japan. All treatments demonstrated efficacy in treating children and adults in AD in Phase 3 clinical trials; however, the trials were conducted in different patient populations and comparisons cannot be made. Dr. Bissonnette highlighted that a remittive effect was observed in psoriasis with tapinarof after 115 days, meaning that treatment can be stopped and started as needed and that data in AD are pending.
Novel systemic treatments approved in the last year or in late-phase experimental development include lebrikizumab and nemolizumab (anti-IL13 monoclonal antibodies [mAbs] approved/completed phase 3 trials for AD). Newer therapies that are currently in phase 3 trial stage target OX40, which is expressed on T cells and OX40L expressed on antigen-presenting cells. These therapies include two anti-OX40 mAbs (telarzorlimab and rocatinlimab) and an anti-OX40L mAb (amlitelimab) and both phase 2 clinical trials show positive results. Furthermore, a greater proportion of responders achieved study outcomes with rocatinlimab vs placebo in the recently published phase 3 trial.
Key takeaways
- Consensus on different AD patient phenotypes is needed to better target therapy.
- The use of ‘good microbes’ to modulate the microbiome modulation may prevent AD relapses and represent a new goal for AD.
- New topical and systemic therapies will soon be available for AD; however, UV therapy should not be forgotten.
Chronic urticaria
Chronic Urticaria Uncovered: Pathophysiology, Phenotypes, and Emerging Treatments
From pathophysiology to phenotypes
Dr Martin Metz (Berlin, Germany) provided a compelling case for leveraging pathophysiology and phenotypes to guide treatment decision-making in Chronic Spontaneous Urticaria (CSU). Comparing type I (autoallergy) and type IIb (classical autoimmunity) mechanisms in CSU, Dr Metz demonstrated how type IIb is more challenging to treat and responds differently to medications.
Dr Metz advised measuring total IgE, noting that patients with low total IgE and high IgG-anti-TPO are more likely to have type IIb autoimmunity. He also highlighted the need for more research into various CSU phenotypes, including those with or without angioedema, comorbid Chronic Inducible Urticaria, average duration of wheals, and treatment responses, to facilitate personalised care and improve patient outcomes.
Difficult to treat chronic urticaria
Dr Christian Vestergaard (Aarhus N, Denmark) shined a light on the complexities of managing difficult-to-treat urticaria, including CSU and angioedema. He outlined the standard treatment, which begins with second-generation H1-antihistamines that can be increased up to fourfold if necessary.
If symptoms remain uncontrolled, anti-IgE therapy can be introduced, with evidence suggesting efficacy of higher dosing, although potential side effects may occur. For severe cases, immunosuppressive or combination treatments may be required. He explained that in cases resistant to standard treatments, newer therapeutic options, such as anti-KIT monoclonal antibodies, are currently being explored in clinical trials.
Novel targeted treatments will provide new insights into the pathophysiology of urticaria, and better knowledge of biomarkers and phenotypes will enable us to give more targeted treatments.
New treatments in the pipeline
Dr Emek Kocatürk Göncü (Istanbul, Turkey) presented a promising future for the treatment of chronic urticaria (CU). She noted that CU is a mast cell-mediated disease, so eliminating mast cells could prevent its occurrence. A key target in CU treatment is Bruton’s Tyrosine Kinase (BTK), crucial for FcεRI receptor signalling and mast cell degranulation, while also playing a role in B-cell maturation.
Targeting the tyrosine kinase receptor KIT is another strategy, but current inhibitors lack selectivity, leading to off-target effects like cardiovascular issues. Dr Kocatürk Göncü also presented a new treatment that depletes mast cells and shows potential in conditions like cold urticaria, although its long-term effects remain unknown.
Recognising different types of angioedema
Dr Thomas Buttgereit (Berlin, Germany) described the significant challenges in identifying the exact cause of angioedema due to variations in pathophysiology, including mast cell-mediated, bradykinin-mediated, vascular endothelial dysfunction, and drug-induced angioedema. He emphasised the need for a thorough diagnostic workup—considering family history, medications, and laboratory tests—to differentiate angioedema types and tailor treatment.
Dr Buttgereit concluded by advocating for the DANCE classification, which aims to standardise the classification of angioedema, aiding global research and clinical practice.
Key takeaways
- Understanding the different pathophysiological mechanisms and phenotypes underlying CU is crucial for guiding treatment.
- The future looks bright for the treatment of CU, with new targeted therapeutic options on the horizon.
Friday
27 Sept 2024
Today's Hot topics
Dermoscopy pigmented lesions
Mastering dermoscopy: Unlocking the secrets of pigmented lesions
Naevi
Prof. Monika Arenbergerova (Prague, Czech Republic) discussed the seven dermoscopic classifications of melanocytic nevi: globular, reticular, starburst, homogenous blue, site-related, nevi with special features, and unclassifiable. These melanocytic nevi, whether acquired or congenital, are further categorised into junctional, compound, or dermal types based on the location of melanocytes in the skin.
When evaluating nevi, Prof. Monika Arenbergerova stressed the importance of considering their pattern, colour, and pigmentation distribution, along with patient-related factors that influence their appearance, such as age, skin type, UV exposure, and pregnancy. However, she also noted the diagnostic challenge posed by recurrent nevi (“pseudomelanoma”) due to their similarity to melanoma.
Prof. Arenbergerova concluded that genetic examination has the potential to redefine the classification of melanocytic lesions—an advancement that is not just a future aspiration but is happening now.
Early melanoma
Prof Aimilios Lallas (Thessaloniki, Greece) opened with a quote from American dermotologist Bernard Ackerman: “No one should die of melanoma.” He pointed out that melanoma is often detectable long before it is recognisable or life-threatening, making early detection crucial.
Prof Lallas outlined key clinical and dermoscopic features for identifying early melanoma, including atypical networks, irregular globules, streaks, and regression structures. He also noted that detection varies by location, with some heavily pigmented lesions being less distinct under dermoscopy.
Prof Lallas stressed that the only way to miss early melanomas is by not using a dermoscope. Addressing concerns of overdiagnosis, he argued that these concerns should be directed towards preventing the alarming number of melanoma deaths that are still occurring in an era where early diagnosis is possible.
It is very important for clinicians and dermoscopists to cooperate with pathologists to study new diagnoses and correlations.
Challenges in dark lesions
Prof. Giovanni Pellacani (Rome, Italy) discussed the challenges in diagnosing black lesions, highlighting that while these are often considered potential melanomas due to their pigmentation, they can also represent nevi or other non-melanocytic lesions. He emphasised the importance of understanding the “black” in these lesions and examining them within their clinical context, explaining that different sources contribute to pigmentation and how colour variations seen in dermoscopy provide clues about the lesion’s depth and source of pigmentation.
Given that black lesions often obscure underlying patterns, Prof. Pellacani recommended a detailed examination that includes border assessment, tape-stripping to remove surface pigmentation, and advanced imaging technologies like confocal microscopy to reveal subsurface details.
Facial lesions
Prof Danica Tiodorovic (Nis, Serbia) delved into the complexities of diagnosing facial lesions, from common cases to rare and challenging ones. She introduced the “SPARK nevus,” a blend of Spitz nevus and Clark’s dysplastic nevus, highlighting its distinctive dermoscopic features. Demonstrating how two facial lesions can appear identical until examined with a dermoscope, Dr Tiodorovic underscored the tool’s crucial role in diagnosis.
Prof Tiodorovic emphasised the importance of recognising early signs of conditions like Bazex-Dupré-Christol syndrome, linked with early-onset basal cell carcinomas, hair abnormalities, and hand atrophoderma. She also raised awareness of the difficulty in distinguishing early melanoma in the head and neck area from junctional nevi, advocating for clinico-pathologic correlation to enhance diagnostic accuracy.
Prof Tiodorovic concluded her presentation by calling for a multidisciplinary approach to the diagnosis and management of facial lesions.
Key takeaways
- By providing detailed insights into lesion characteristics, dermoscopy aids in differentiating between benign and malignant lesions.
- With dermoscopy in their arsenal, there is no reason for dermatologists to miss early diagnoses.
Dermoscopy non-pigmented lesions
Dermoscopy unveiled: Mastering non-pigmented lesions for precise diagnosis
Actinic keratosis and squamous cell carcinoma
Prof. Bengu Nisa Akay (Ankara, Turkey) detailed key features of Actinic Keratosis (AK) and Squamous Cell Carcinoma (SCC), engaging the audience with clinical images and asking them to identify AK and SCC among various lesions.
Prof. Akay described white structureless areas, white circles, four-dot clods, keratin masses, and associated vascular patterns like radial vessels and blood spots for well-differentiated SCC. For poorly differentiated SCC, she emphasised tumoral infiltration, ulceration, lack of keratinization, and polymorphic vessels.
In AK, Prof. Akay pointed to the presence of white circles – indicating hyperkeratosis in the infundibular epidermis – as a unique dermoscopic clue.
Basal cell carcinoma
Prof. Susana Puig (Barcelona, Spain) provided a compelling case for the critical role of dermoscopy in diagnosing basal cell carcinoma (BCC). She cited a meta-analysis demonstrating that adding dermoscopy to naked eye examination increases diagnostic sensitivity from 66.9% to 85% and specificity from 97.2% to 98.2%.
Prof. Puig outlined key dermoscopic features of BCC, including blue-gray globules, arborizing vessels, ulceration, and maple leaf-like areas, stressing the importance of leveraging dermoscopy to distinguish BCC subtypes.
Prof. Puig also highlighted “Multiple Aggregated Yellow/White (MAY) globules” as a significant diagnostic marker, with a study finding them in 21% of BCC cases versus just 0.8% of other lesions (OR: 32.0). Notably, MAY globules were absent in superficial BCC, underscoring their value in identifying other subtypes, particularly high-risk BCC.
We should use dermoscopy whenever we encounter a skin lesion. I hope you will use it all the time, even with the most subtle ones.
Pink tumours
Dr Roberta Giuffrida (Messina, Italy) opened her presentation by asking, “How do you feel when assessing a pink lesion without a dermatoscope?” This led to a discussion about the challenges of diagnosing pink tumours due to limited dermoscopic criteria, emphasising the importance of vascular morphology.
Dr Giuffrida outlined six common vascular types, including arborizing, dotted, and hairpin-like vessels, noting that polymorphous patterns raise suspicion for malignancy. She also pointed out that a negative pigment network can appear in hypopigmented melanocytic lesions, while a white network in elevated pink tumours suggests Spitz nevi or other benign lesions.
In concluding her presentation, Dr Giuffrida recommended vessel caliber and density to differentiate indolent from aggressive tumours, with branched vessels acting as a clue for non-pigmented BC and yellow plugs with an erythematous background being a diagnostic marker for primary cutaneous B-cell lymphoma.
Rare skin tumours
Prof. Giuseppe Argenziano (Naples, Italy) discussed the identification and management of three groups of rare skin tumours: Merkel cell carcinoma (MCC), sarcomas, and adnexal carcinomas. He noted MCC as being the most frequent among rare tumours, followed by atypical fibroxanthoma, dermatofibrosarcoma protuberans (DFSP), angiosarcoma, and dermal sarcoma.
The challenges of MCC were presented, particularly on the sun-damaged scalps of older patients, where he advised prioritising potentially invasive lesions. Prof. Argenziano also addressed the aggressiveness of sarcomas, such as DFSP and angiosarcoma, including those that may develop post-radiotherapy.
Concluding his presentation, Prof. Argenziano emphasised the need to also consider rarity in respect to common tumours – some of which have atypical presentations.
Squamous cell carcinoma
The role of HPV, prognostication, adjuvant radiotherapy, and high-risk patient staging and follow-up in SCC
The role of HPV in SCC
Prof. Thomas Meyer (Bochum, Germany) opened the session by giving overview of the human papilloma virus (HPV), small double-stranded DNA virus with over 200 types. Beta (β)-HPV, acquired in childhood, represents the most abundant viral species in the skin microbiome and the main HPV type in cutaneous squamous cell carcinoma (cSCC).
Prof. Meyer moved on to discuss the two controversial roles HPV in cSSC, and whether the virus is involved in tumour formation or offers a protective effect.
Studies have shown that HPV may prevent cSCC development by promoting local T cell immune responses against abnormal keratinocytes. However, loss of immunity and ultraviolet (UV) exposure may impair elimination of HPV- infected cells, permitting an increased expression of viral oncogenic factors. This process may block DNA repair, resulting in the accumulation of UV-induced DNA mutations, affecting p53 and pRB expression, enabling further tumour suppression and progression. The inability to eliminate pre-malignant and malignant cells results in uncontrolled cell proliferation and cSCC manifestation.
Regardless of the potential dual role of HPV, enhancing immune function against β-HPV or infected keratinocytes may represent a promising approach to prevent cSCC development.
New prognostic factors in SCC beyond staging
Prof. Ketty Peris (Rome, Italy) described the current challenges associated with cSCC staging. Currently, four staging systems available based on traditional clinico-pathological risk factors, which differ in terms of their recommendations included. Such variations may lead to sub-optimal classification of high-risk features such as perineural invasion (PNI), cell differentiation, and depth of invasion) caused by non-standardised reporting.
An ‘ideal’ staging system should include distinctiveness (outcome difference among different tumour staging classes), homogeneity (outcome similarity within the same class), and monotonicity (outcome worsening with increasing class). Studies using these three pillars have shown mixed results, suggesting that some guidelines may be more appropriate than others to identify patient subsets (i.e. Tb2/3 for high-risk patients, and T1 to eliminate further treatment).
Prof. Peris then discussed how combining clinico-pathological factors and protein biomarkers have been used to bridge the gap. Novel prognostic biomarkers using transcriptomics and proteomics are expected to improve risk stratification, to identify high-risk patients who may benefit from additional treatment, and to reduce over treatment in those at low risk
Adjuvant radiotherapy
After an insightful introduction, Prof. Javier Canueto (Salamanca, Spain) assessed the evidence for using adjuvant radiotherapy (ART) after surgery to reduce the risk of recurrence in cSCC.
Clinical studies have shown that ART leads to improved outcomes in different cSCC patient types, including an increased disease-free and overall survival (OS) in locoregional disease; a greater prognosis of extrapancreatic PNI with a PNI of gross calibre nerves (with ≥5 nerves having the greatest impact) and PNI ≥0.1 mm (but not <0.16 mm with clear margins and no other risk factors). In addition, ART may be useful in cSCC with minimal residual disease if surgery is not possible; however, administration to the tumour bed appears to no impact on nodal metastasis or OS. In addition, ART can be considered after clear margins in very high-risk cases (T3 with >6 cm and recurrent tumours) and in those with three or more risk factors.
These findings open the door for chemoradiation (chemo-ART), with improved local control observed in initial studies. Findings from phase 3 studies (C-POST and KEYNOTE-630) in high-risk cSCC are much anticipated. However, data with targeted therapies are scarce and adjuvant immunotherapy is being evaluated. In the future, gene expression profiling may help to define patients likely to most benefit from ART.
Staging and follow-up of high-risk SCC
In the final presentation of this session, Dr Emily Ruiz (Boston, United States) provided compelling evidence for the stratification and appropriate use of staging and follow-up in patients with high-risk cSCC.
Dr Ruiz explained that, ideally, staging should include prognostic features beyond the staging system, with physicians considering individual patient risk. Although tumours at the same stage may pose a similar risk, the same treatment may not be appropriate. Several important features outside of the classic staging systems, such as lymphovascular invasion and metastasis, could help to improve prognostic ability.
Furthermore, newer prognostic models may help to identify high-risk cSCC and which patients should receive radiological staging and surveillance. Imaging allows for early identification and treatment, while also identifying nodal metastases, which are associated with better outcomes. Defining the patient population is important but challenging. Ultrasound can be used for detection, and this may also detect other cancers.
Dr Ruiz concluded that validation of prognostic models and other ancillary tests are needed to determine how best to risk stratify cSCCs. The availability of more tools (i.e. riSCC) will help to individualise risk assessment with patient comorbidities; however, improved guidelines for cSCC are much needed.
Key takeaways:
- Improved guidelines are needed for cSCC to identify staging and identify patient subsets (Tb2/3 for high risk and T1 for risk).
- The use of clinico-pathological factors together with protein biomarkers may improve risk stratification.
- While ART improve outcomes in specific cSCC subgroups, chemoradiation and gene expression profiling may further refine treatment and define patients most likely benefit in the future.
Saturday
28 Sept 2024
Today's Hot topics
Acne
New guidance, spironolactone use, and recommendations treating and preventing scarring and hyperpigmentation in acne
New guidelines in acne
Prof. Alison Layton (York, United Kingdom) opened the session with an informative presentation, focusing on two new guidelines for managing acne to advise of new updates, differences, with new developments and questions to inform research.
Both the 2021 UK National Institute for Health and Care Excellence (NICE) and 2024 American Association of Dermatology (AAD) guidelines used a standardised review protocol to select the most relevant information, with similar recommendations for topical first-line treatment and maintenance therapies based on current evidence.
Currently, there is a paucity of information on skin care/dietary advice and scarring, with little evidence for hormonal or light-based therapy in NICE. A significant difference is that recommendations for hormonal therapy (oral contraceptives) and good practice statements are included in the AAD guideline (not included in NICE). New updates in AAD include monitoring in those with risk factors for hyperkalaemia (e.g. older patients or with medical comorbidities).
Unmet needs for future research include isotretinoin use and dosing studies, laser and light-based procedures, dietary changes and alternative therapies.
One of the problems with guidelines… they are only as robust as the clinical trials that have been done.
Spironolactone: a place in the algorithm of adult female acne
Prof. Brigitte Dréno (Nantes, France) gave a compelling overview of the rationale for spironolactone, a potassium-sparing diuretic, as a treatment option for adult female acne.
Spironolactone, a synthetic 17-lactone steroid that binds to the androgen receptor in the skin demonstrated efficacy in early studies, where positive predictors of response were inflammatory lesions and previous isotretinoin treatment (not contraceptive use). The best candidates appeared to be adult females with mandibular acne, hypermenorrhoea, inflammatory lesions, with peripheral hyperandrogenism, acne of the trunk, isotretinoin failures, or depression. Adverse events were typically low and dose-related, and routine potassium monitoring may only be required in older patients. Retrospective studies confirmed that spironolactone is not associated with venous thromboembolism, increased risk of breast/gynaecological malignancies, or hypertension.
More recently, the first double-blind, randomised controlled clinical trial (FASCE) demonstrated the superiority of low-dose spironolactone 150 mg/day vs doxycycline 100 mg (both with placebo), with good clinical tolerance with no hyperkalaemia.
Prof. Dréno highlighted that despite this positive evidence, spironolactone is still awaiting marketing authorisation for treating female acne, even in the United States, where it has been prescribed off-label for over 30 years. This is essential at a time when cyproterone acetate (at ≥2 mg) has lost its indication in acne and alternatives to isotretinoin are necessary for treatment failures or contraindications.
Acne scars: prevention and treatment
In an engaging presentation, Prof. Sewon Kang (Baltimore, United States) guided the audience through the process of acne scarring to elucidate appropriate treatment and prevention.
After showing a clinical case, Prof. Kang noted that acne is dominated by inflammatory lesions. While research into the progresses leading to atrophic scarring in acne pathogenesis is lacking, it is known that three types generally predominate: rolling, boxed, or icepick scars
Prof. Kang then shared two lines of evidence to help stratify treatment and prevention, by evaluating the natural history of acne lesions and scarring. In the first, a pulsed dye laser was used in a split-face design to evaluate lesions over time. Computer-assisted alignment of superimposed images identified that in most atrophic scars, >70% were of the icepick type. The contribution of inflamed papules, pustules and comedones play a role, and scars can form quickly (<3 months)
Molecular profiling in biopsies of involved (lesions) and non-involved skin confirm the upregulation of inflammatory cytokines, elevated matrix metalloproteinases (typically around the sebaceous follicle) with dermal collagen destruction, and this is likely the process of scar development.
Treatment approaches include those used for photo-aged skin (retinoic acid, adapalene 0.3% gel) which can help build up the dermal matrix and prevent scarring. The key is to start early, and treat aggressively, over time.
Acne-associated hyperpigmentation: dos and don’ts
In the last presentation of the session, Prof. Dr. Jose Luis Lopez-Estebaranz (Madrid, Spain) provided the audience with invaluable recommendations for treating postinflammatory hyper pigmentation (PIH).
Most PIH is focused on the epidermis and can be difficult to distinguish in patients with skin of colour. To date, evidence is lacking on effective treatments. Prof. Lopez-Estebaranz recommended to treat the underlying inflammation early and effectively, without causing damage to the skin barrier, using appropriate sun protection, including daily application of a broad-spectrum sunscreen, particularly in skin of colour (tinted products are particularly useful).
Regarding topical treatments for PIH, retinoids can be used first-line, but it there is a risk of dermatitis with higher concentrations and some excipients. Topical hydroquinone (2–4%) may lead to lightening over 3–6 months if the increase in pigmentation is limited to the epidermis. Triple combinations (e.g. fluocinolone acetonide/hydroquinone/tretinoin) are more effective but should only be applied to the affected area to avoid hypopigmentation. Other potential therapeutic options include azelaic acid, α-hydroxy, L-ascorbic, tranexamic acid, kojic acids, cysteamine, arbutin, liquorice extracts, mequinol, niacinamide, N-acetyl glucosamine, and soy.
Prof. Lopez-Estebaranz concluded by cautioning against the use of ablative laser or invasive procedures. Superficial chemical peels can be used as adjuvant therapy, starting with a low dose and increasing as needed. He also acknowledged a role for lasers with long wavelength, long pulses and low fluences as second line therapy in refractory lesions.
Key takeaways
- Updated guidelines may indicate areas for future research in acne.
- In the advent of cyproterone acetate losing its indication in acne and the need for alternatives to isotretinoin, the approval of spironolactone is necessary.
- Retinoic acid treatment and other therapies may pave the way to effective treatment of scarring and PIH.
Hyperpigmentation
Beyond the surface: Exploring the pathogenesis and management of melasma
Pathogenesis of melasma
Prof. Mauro Picardo delivered an insightful presentation on the complex pathogenesis of melasma, outlining key contributors such as genetic predisposition, sun exposure, hormonal changes, and medications. He also delved into histopathological features, including epidermal hyperpigmentation, solar elastosis, increased vascularization, and mast cell activity.
Prof. Picardo emphasised the vital role of fibroblasts and sebaceous glands in melasma. Fibroblasts not only release growth factors that drive melanogenesis but also secrete cytokines, fuelling inflammation and pigmentation. Sebaceous glands engage in a complex cycle where sebocytes influence fibroblast activity, which in turn affects melanocyte function, further amplifying melanin production.
The complex interplay between melanocytes, fibroblasts, sebocytes, and inflammation underscores the need for a comprehensive treatment approach.
Prevention and treatment of melasma
Dr Robert Artur Dahmen presented evidence on the prevention and treatment of melasma, which he highlighted as being a frustrating and embarrassing condition for patients.
Dr Dahmen stressed the importance of a multi-step approach to managing melasma, including tinted sunscreen, skin lighteners, lasers, peels, oral or topical agents, and cosmetics to control melanin production, limit melanosome transfer, and clear excess melanin.
Dr Dahmen emphasised that melasma treatment is not just about lasers and peels. While both can be effective, they are not a cure and may result in recurrence and post-inflammatory hyperpigmentation.
Post- inflammatory hyperpigmentation
Dr Marta Sar-Pomian discussed the two types of post-inflammatory hyperpigmentation (PIH), which primarily affects individuals with darker skin tones: epidermal (melanin accumulation in the epidermis) and dermal (melanin deposition in the dermis). She outlined the key causes of PIH, including inflammatory skin disorders such as acne, atopic dermatitis, contact dermatitis, skin injuries, and even procedures like chemical peels.
Dr Sar-Pomian described PIH’s pathogenesis as involving inflammatory responses that trigger cytokine and growth factor release, leading to melanocyte proliferation and increased melanin production. As such, she stressed that effective treatments must address both inflammation and pigmentation.
Acquired pigmentary disorders
Dr Susanne Grether-Beck (Düsseldorf, Germany) shed light on how environmental factors drive pigmentary disorders and skin aging. She emphasised that hyperpigmentation is triggered not just by UVB/UVA, but also by high-energy visible light (HEVL), especially in individuals with darker skin. She further highlighted the role of air pollution in oxidative stress-induced tanning.
Sharing data from the CASAI cohort study in India, Dr Grether-Beck linked rising ambient temperatures to signs of skin aging, such as facial lentigines and wrinkles. As a potential mitigation strategy for temperature-induced pigmentation, she recommended using topical antioxidants.
Dr Grether-Beck concluded with an emphasis on how the interplay between the exposome (environmental factors), genome, and phenome collectively shapes skin health and aging.
Key takeaways:
- Environmental factors – both preventable and unpreventable – play a significant role in hyperpigmentation and ageing.
- The complex pathogenesis underlying hyperpigmentation and melasma necessitates a multi-step treatment and management approach.
