Reference: May 2025 | Issue 5 | Vol 11 | Page 3
Highlights from the European Academy of Dermatology and Venereology Congress, which took place in Amsterdam, The Netherlands, and online from 25-28 September, 2024
Pioneering Irish study shows semaglutide improves outcomes for obese patients with hidradenitis suppurativa
Findings from the first study to explore the use of semaglutide in treating hidradenitis suppurativa (HS) were presented at the European Academy of Dermatology and Venereology Congress 2024. Dr Daniel Lyons, lead researcher from the Department of Dermatology, St Vincent’s University Hospital, Dublin, told the conference that results of the study “suggest that semaglutide, even at modest doses, can offer substantial benefits in managing HS”.
“While the drug’s role in promoting weight loss is well-established, what’s particularly exciting is its potential to also reduce the frequency of HS flare-ups, contributing to the notable improvements observed in patients’ quality of life.”
HS – a long-term condition characterised by painful abscesses and scarring – is estimated to affect approximately one in 100 people, and can severely impact patients’ quality of life. Obesity is a significant risk factor for developing the disorder. Despite advancements in managing HS, effective treatments remain limited and are often associated with adverse, and sometimes serious, side effects, highlighting a need for alternative and better tolerated treatment options. The research demonstrated that the addition of semaglutide to standard care for patients with obesity resulted in a notable reduction in exacerbations of HS and improvements in quality of life.
The study had a sample population of 30 patients with obesity, which was predominantly female (27 females, three males) with an average age of 42 years. Investigators examined data from June 2020 to March 2023 and assessed several health outcomes for varying stages of HS. Patients received the glucagon-like peptide (GLP)-1 RA semaglutide at a mean dose of 0.8mg once-weekly for an average of 8.2 months.
Researchers monitored changes in body mass index (BMI), weight, exacerbation frequency, Dermatology Life Quality Index (DLQI) value, and pain levels before and after starting the GLP-1 RA drug, as well as biochemical markers, including C-reactive protein (CRP), glucose, and haemoglobin A1c (HbA1c) levels.
The results showed marked improvements in outcomes across several key measures, including fewer HS flare-ups, with the frequency of exacerbations reducing from an average of once every 8.5 weeks to once every 12 weeks. Quality of life also improved significantly, reflected in a reduction of the DLQI score from an average of 13/30 to 9/30. Notably, one-third of patients achieved a DLQI score reduction of four points or more, which signifies a clinically significant improvement for this index.
The average BMI of patients decreased from 43.1 to 41.5 and their mean weight dropped significantly from 117.7kg to 111.6kg, with one-third of patients losing 10kg or more during the treatment period. Further positive changes were observed in the biochemical markers. HbA1c levels decreased from 39.3 to 36.6, indicating better glycaemic control, while average CRP levels fell from 7.8 to 6.9, indicating reduced levels of inflammation.
Dr Lyons added: “The results are highly encouraging and could represent a major breakthrough in HS treatment. To build on this progress, larger randomised controlled trials are necessary to validate these findings. Additionally, future research should explore the impact of higher doses of semaglutide and its effects, independently of concomitant medications, to fully understand its potential.
“Ultimately, we hope our preliminary data will encourage dermatologists to consider weight loss medication as an adjunct to existing HS treatments and inspire further research in this area aimed at improving outcomes for people living with this challenging condition.”
New research confirms link between perceived stress and psoriasis relapse
Perceived stress can directly trigger the relapse of psoriatic skin lesions, Prof Amos Gilhar, lead researcher from the Skin Research Laboratory, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel, told the European Academy of Dermatology and Venereology (EADV) Congress 2024. While it has long been suspected that stress plays a key role in exacerbating psoriasis, Prof Gilhar and his team are the first researchers to scientifically validate this connection in vivo.
With over three decades of experience in immunodermatology, Prof Gilhar’s lab has developed several internationally recognised humanised mouse models that are now widely used in preclinical drug trials. In 2006, he received the EM Farber Research Award for Excellence in Research from the Society for Investigative Dermatology, and his recent work includes creating models for autoimmune skin diseases like psoriasis and alopecia areata.
In the study, Prof Gilhar and his team induced psoriatic lesions in healthy human skin xenografts on severe combined immunodeficiency (SCID)/beige mice (n=25) through the injection of autologous, in vitro IL-2-preactivated peripheral blood mononuclear cells. After achieving lesion remission with topical dexamethasone, the mice were then exposed to either sonic or sham stress for 24 hours. The recurrence of psoriatic lesions was then tracked over the following 14 days.
Remarkably, sonic stress led to a relapse of psoriatic lesions in all human skin xenografts within 14 days. This was accompanied by significant changes in psoriasis-related skin phenomena, including increased epidermal thickness, K16 expression, keratinocyte proliferation, anti-microbial peptide expression, and immune activation of intraepidermal cells.
Further analysis showed that sonic stress significantly increased immune cell presence in the skin and elevated pro-inflammatory mediators. Additionally, neurogenic inflammation biomarkers, such as nerve growth factor (NGF) and substance P (SP), were upregulated. Sonic stress also led to elevated levels of tryptase, indicating mast cell activation, and increased expression of NK-1R, the receptor for SP.
“Psycho-emotional stress triggers the release of pro-inflammatory neuropeptides like SP, leading to neurogenic skin inflammation by activating immune cells, particularly through mast cell degranulation,” said Prof Gilhar. “This is further amplified by corticotropin-releasing hormone and NGF, which heighten inflammation and promote keratinocyte hyperproliferation, thereby triggering and worsening psoriatic lesions in susceptible individuals,” Prof Gilhar said.
Tumour-specific antibodies able to detect melanoma in its earliest stages
Promising results using tumour-specific profiling to detect antibodies unique to stage I and II melanoma were presented at the European Academy of Dermatology and Venereology Congress 2024. The method could significantly enhance diagnosis and prognosis by identifying the disease at its earliest, most treatable stages.
Melanoma produces immunogenic markers that trigger an immune response, resulting in the production of antibodies against cancer-testis antigens (CTAgs). These CTAgs lead to the production of specific antibodies that can act as early diagnostic and prognostic markers for melanoma.
In this study, a cancer array was used to analyse and compare blood samples from 199 patients with stage I and II melanoma. A total of 38 healthy donors were recruited through Lifeblood (the national blood, milk, and microbiota donation and manufacturing service for Australia). Blood samples were collected at initial diagnosis and within 30 days of curative-intent surgery.
Specific Immunoglobulin (Ig)G antibodies against three tumour antigens were identified as promising diagnostic biomarkers for early-stage melanomas, with area under the curve (AUC) values ranging from 0.857 to 0.981 in the discovery cohort and from 0.824 to 0.985 in the internal validation cohort.
Of the three identified markers, one showed an AUC value of 0.9805 in the discovery cohort, with 98 per cent sensitivity and 76 per cent specificity, and 0.9846 in the validation cohort, with 99 per cent sensitivity and 82 per cent specificity.
“These results indicate that 99 per cent of melanoma patients in the validation cohort were positive for this marker, while 82 per cent of healthy individuals were correctly identified as negative using the recommended threshold,” explained Dr Cristina Vico-Alonso, lead researcher from the Victorian Melanoma Service, Melbourne, Australia.
“While 18 per cent of healthy individuals were incorrectly identified as positive for this marker, combining it with the other two markers into a multiparameter signature does, however, help improve accuracy.”
Based on the validation data in the study, only 1 per cent of melanoma patients would have a negative test for this top marker, suggesting that a negative result is highly precise and indicative of the absence of melanoma. “It is important to note, though, that this cohort included healthy individuals with no prior or current cancers and excluded individuals at high risk of developing melanoma,” Dr Vico-Alonso emphasised.
“Further testing in a real-world cohort is necessary to determine if these findings hold true when confounding factors, such as comorbidities, are considered…. One significant advantage of this cancer array is its tumour-agnostic nature…. CTAgs are expressed in many solid tumours, making the diagnostic signature identified here applicable beyond melanoma. However, the specific cognate antigen combination remains unique to melanoma compared to other solid tumours.
“We are currently using the cancer array to identify candidates for a pan-cancer diagnostic test, initially focusing on melanoma, lung, bowel, and pancreatic cancers…. In previous research, we identified a unique signature of antigens in advanced melanoma patients associated with more aggressive disease or metastases. Recently, we also identified another distinct antigen signature that differentiates between stage III melanoma patients who experienced recurrence and those who did not.”
The early detection of melanoma remains a pressing challenge in oncology, with this research representing a significant step forward, offering hope for more effective, non-invasive diagnostic tools. Critically, early detection can lead to earlier surgical and therapeutic interventions, reducing the number of patients presenting with advanced disease and improving outcomes.
“This method of early detection could be integrated into current melanoma screening practices to provide additional information, especially in uncertain cases, potentially avoiding unnecessary procedures,” Dr Vico-Alonso concluded.
New targets identified for improved wound healing
Novel research has identified key molecular targets that could significantly enhance the healing of both acute and chronic wounds. The findings, which were presented at the European Academy of Dermatology and Venereology Congress 2024, represent a major advancement in wound care, and may pave the way for more effective treatment options and improved patient outcomes.
Globally, acute and chronic wounds affect nearly one billion people. An acute wound, defined as a recent wound of any aetiology that is expected to progress through the normal sequential phases of wound healing, is generally easily managed in the clinical setting.
Chronic wounds – those that do not heal or reduce in size by more than 40 to 50 per cent within a month – are often problematic. They may have different aetiologies and are commonly classified in the categories of diabetic foot ulcers, wounds related to peripheral arterial disease, venous leg ulcers, pressure injuries, and atypical hard-to-heal wounds. Chronic wounds pose a substantial economic burden on healthcare systems and severely impact the quality of life for those affected.
Despite this burden, current treatment strategies are often limited, highlighting an urgent need for improved understanding of the mechanisms underlying impaired wound healing. To address this, researchers conducted a study using healthy, full-thickness, human skin punches, creating central, partial wounds. These samples were then cultured under either physiological or pathological conditions, including hyperglycaemia, oxidative stress, and hypoxia, to mimic acute and chronic wounds, respectively.
The team monitored gene expression changes over a five-day period using advanced comparative transcriptomic profiling with bulk RNA sequencing. The results revealed several critical differences in gene activity between acute and chronic wounds.
Key wound repair-associated genes (such as KRT6A-C, PTX3, KRT1, KRT10, COL1A1), along with pathways including Wnt signalling and actin cytoskeleton organisation, were differentially regulated between acute and chronic wounds. Additionally, overall gene expression was downregulated in chronic wounds compared to acute wounds, suggesting that essential genes required for effective wound healing are inadequately transcribed in these conditions. Notably, FGF7, a key promoter of epithelial cell proliferation and tissue repair, was significantly downregulated in chronic wounds by day five.
In contrast, MMP10, a tissue-degrading enzyme, was elevated throughout the study period in chronic wounds. To counteract these imbalances, the researchers tested the effects of recombinant FGF7 protein and an MMP10-neutralising antibody (α-MMP10) on acute and chronic wounds in the ex vivo wound models. Topical administration of α-MMP10 led to a significant increase in wound tongue length, indicating improved healing in acute wounds. In contrast, FGF7 did not show a significant effect on its own. The combined application of FGF7 and α-MMP10, however, significantly enhanced re-epithelisation in both types of wounds.
“While we must be cautious when discussing synergistic effects, our preliminary data reveal that combinatorial therapy may be a valid option for treating chronic wounds,” said Dr Marta Bertolini, lead author of the study. Dr Bertolini, PhD, is the Managing Director of QIMA Monasterium GmbH, Münster, Germany, belonging to the QIMA Life Sciences group. She graduated in Pharmaceutical Biotechnologies in Italy, and obtained her PhD in Germany, with a thesis on hair follicle immunology. Her scientific contribution focuses on skin and hair translational research.
“We believe that administering excessive FGF7 promotes epidermal keratinocyte proliferation and mobilisation, which are crucial for wound healing. At the same time, neutralising MMP10 removes a barrier to keratinocyte movement, potentially accelerating re-epithelisation,” Dr Bertolini added.
The study also identified osteopontin (SPP1) as a gene that is significantly upregulated on days three and five in acute wounds, compared to chronic wounds. To leverage this finding, the researchers administered FOL005, an osteopontin-derived peptide, to experimentally induce wounds ex vivo. Treatment with FOL005 significantly enhanced skin re-epithelisation under both physiological and pathological conditions.
“We believe these findings mark a significant step forward in understanding the complex biology of wound healing,” concluded Dr Bertolini. “Our transcriptomic data will soon be accessible and we hope this will inspire other researchers and industry to identify additional promising targets that could offer much-needed relief to patients affected by these challenging and often debilitating wounds.”
