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Background: The 31st European Academy of Dermatology and Venereology (EADV) Congress took place between 7th and 10th of September 2022 in Milan, Italy. Objectives: We report presented clinical data on the efficacy/effectiveness, safety and tolerability of tirbanibulin 1% ointment that has recently been licensed for actinic keratosis (AK) of the face or scalp in adults. Methods: Summary of presentations given at the EADV Congress. Results: Prof. Pellacani presented two post hoc analyses from two phase‐III trials with AK patients (NCT03285477 [N = 351] and NCT03285490 [N = 351]): A descriptive analysis of medical history, concomitant medications, and safety results confirming a favourable profile for tirbanibulin showing that number of baseline AK lesions was not correlated to severity of local skin reactions. The latter analysis showed that cases of tirbanibulin application site pain or pruritus were few, and most were found to be mild. Prof. Kunstfeld reported six real‐life clinical cases in Austria showing good tirbanibulin effectiveness, safety and tolerability for the treatment of new or recurring AK lesions. Results demonstrated that after 2‐ to 4‐month follow‐up, tirbanibulin was well tolerated and effective in AK patients. Presentations by Dr. Patel confirmed good outcomes and tolerability of tirbanibulin in Olsen grade 1–2 AK (N = 12) and porokeratosis patients (N = 4) treated once daily for 5 consecutive days in the United Kingdom. Furthermore, real‐world experience in solid organ transplant recipients (N = 2) demonstrated effectiveness of tirbanibulin in skin field cancerization treatment. A symposium sponsored by Almirall was conducted during the congress in which Dr. Hadshiew and Dr. Lear brought together their clinical experience in Germany and the United Kingdom respectively. Interesting clinical cases of 5 consecutive days of tirbanibulin treatment compared to other treatments were discussed with attendees, as well as current treatment needs of AK patients. Conclusions: This article provides an overview of presentations and symposium discussions, summarizing key phase‐III results and real‐life clinical experience with tirbanibulin shared by dermatologists across Europe. [ABSTRACT FROM AUTHOR]

Andreas Pinter,1 Bernd Bonnekoh,2 Ina Marion Hadshiew,3 Sebastian Zimmer41Department of Dermatology, Venereology, and Allergology, University Hospital Frankfurt am Main, Frankfurt am Main, Germany; 2Clinic for Dermatology, Otto-von-Guericke-University Hospital, Magdeburg, Germany; 3Derma Köln am Heilig-Geist-Krankenhaus, Köln, Germany; 4MediCorium, Oberursel, GermanyAbstract: Brodalumab, a recombinant fully human monoclonal immunoglobulin IgG2 antibody with high affinity to human interleukin (IL)-17RA, is approved for the treatment of moderate-to-severe plaque psoriasis. In controlled clinical trials, brodalumab 210 mg administered by subcutaneous injection at weeks 0, 1, and 2, then 210 mg every 2 weeks, produced a rapid onset and sustained clinical response. Consistently, >80% of patients achieved PASI-75 and efficacy was maintained for >2 years. The benefits are apparent soon after the start of therapy and are maintained in the long term. Such results, from the reviewed literature, support the findings from 4 ’real world’ cases in mainstream clinical practice which are reported here. Psoriatic plaques, including on the scalp, nails, soles and palms, were largely resolved, and quality of life improved markedly. Therapeutic success was achieved in patients naïve to biologics (2 cases) and in those responding inadequately to other biologics (2 cases). The high affinity of brodalumab to human IL-17RA blocks the biological activities of the pro-inflammatory cytokines IL-17A, IL-17C, IL-17E, IL-17F, and IL-17A/F heterodimer, resulting in inhibition of the inflammation and clinical symptoms associated with psoriasis. This mechanism of blocking multiple IL-17 family cytokines differs from that of other available biologics which selectively target some parts of the Th-17 axis and may account for the effectiveness of brodalumab in patients poorly responsive to other biologics, a feature which has also been shown where subgroup analysis has been undertaken in clinical trials. The drug is well tolerated during the normal 12-week induction phase and with prolonged treatment (52 to 120 weeks), as it was in the current case series.Keywords: brodalumab, psoriasis, psoriatic arthritis, interleukin 17 axis, IL-17

Introduction: Dimethyl fumarate (DMF) is an oral compound to treat plaque psoriasis. Data on the treatment of patients with psoriasis affecting impactful areas are scarce. In this interim analysis of the prospective, noninterventional SKILL study, we summarized results of DMF treatment regarding effectiveness (overall and in impactful areas) and safety., Methods: Data from 676 patients suffering from moderate-to-severe plaque psoriasis were analyzed after 52 weeks of DMF treatment. Of these, 257 had data available after 52 weeks. The considered impactful areas were nails, palms, soles, and scalp. Data analysis included observed cases (OC) and last observation carried forward (LOCF)., Results: All effectiveness parameters improved after 52 weeks. The Psoriasis Area and Severity Index score was reduced by 79.5% (OC) and 65.7% (LOCF). Compared with baseline, improvements were shown for 70.2% of the patients in their nail psoriasis [nail-Physician Global Assessment (PGA)] and for 57.3% in palmoplantar disease (palmoplantar-PGA). The proportion of patients with scalp-PGA 0/1 (clear/almost clear) increased significantly to 79.8% (OC) and 69.3% (LOCF, both p < 0.001) (versus 37.5% and 36.6% at baseline, respectively). Significant reduction of pruritus (p < 0.001) was also observed. No unexpected adverse drug reactions were observed., Conclusion: Long-term treatment with DMF in routine practice showed good overall effectiveness and safety, and a positive effect on plaque-psoriasis-affected impactful areas., (© 2022. The Author(s).)

Background: Chronic cutaneous pain has a substantial negative impact on quality of life (QoL). Dermo-cosmetics can support therapies for treatment of chronic skin diseases, providing symptomatic relief from chronic cutaneous pain and improved QoL., Objectives: To assess the global tolerance and efficacy of a dermo-cosmetic spray containing Rhealba ® Oat Plantlet and Uncaria tomentosa extracts in reducing cutaneous pain when used as a monotherapy or in association with drug or dermo-cosmetic treatments in patients with an underlying skin pathology., Methods: Patients aged ≥1 month with a cutaneous pain level ≥3 and an underlying skin pathology were provided with the spray to use up to six times daily for 6-8 weeks. Immediate effect on cutaneous pain and patient satisfaction were assessed after the first application. Global efficacy and tolerance, reduction in symptoms, improvement in QoL, pain reduction and patient overall satisfaction were assessed after 6-8 weeks., Results: Immediately after the first application, significant reductions in cutaneous pain were observed across all age groups (P < 0.0001), with 94% of patients reporting a reduction in pain. After 6-8 weeks, global tolerance was rated 'very good' or 'good' for 97% of patients, and the spray was efficacious in 95% of patients. Patient satisfaction with the efficacy of the spray was 95%. QoL scores improved in 86% and 94% of patients aged ≥12 and <12 years, respectively. Findings were similar across underlying pathology and therapy types (monotherapy or in association with another therapy)., Conclusions: The spray was well-tolerated and efficacious in providing symptom relief in patients with mild-to-moderate cutaneous pain, irrespective of the underlying pathology or therapy type., (© 2022 European Academy of Dermatology and Venereology.)

Background: The 29th EADV Virtual Congress took place between the 29th-31st of October 2020. On October 29th, there was a Session on systemic treatment in which Professors Ulrich Mrowietz and Mar Llamas-Velasco presented the latest research on the efficacy of dimethyl fumarate (DMF) treatment for moderate-to-severe plaque psoriasis (BRIDGE and DIMESKIN 1 studies, respectively). The accepted DMF abstract from Professor Matthias Augustin, on the SKILL study, is also presented here. Results: Data from either prospective interventional (BRIDGE) or non-interventional (DIMESKIN 1, SKILL) studies among patients with moderate-to-severe psoriasis showed that DMF provides a positive efficacy profile in all four body regions included in the Psoriasis Area and Severity Index assessment (head and neck, trunk, upper and lower extremities) and a particularly interesting profile (strong efficacy) in the head and neck region. These findings may be of special interest to patients with scalp psoriasis who have been using topical therapies for a long time. Patient-reported outcomes (quality of life, pruritus) also improved during the 24 weeks of DMF treatment. The safety profile of DMF was similar to the previously described with fumaric acid esters. Conclusions: In summary, these results confirm the favorable efficacy and safety profile of DMF in long-term treatment.

Small DNA oligonucleotides homologous to the 3' overhang of human telomeres, called T-oligos, stimulate pigmentation in human epidermal melanocytes in vitro and in vivo. They induce UV-mimetic effects in the absence of DNA-damage, however, it is unknown how T-oligos affect human hair follicle keratinocyte and melanocyte functions in situ. Here, we present the first evidence that these oligonucleotides are powerful modulators of pigmentation and growth of microdissected, organ-cultured human scalp hair follicles. Hair follicles were incubated with T-oligo or vehicle control and were then assessed for changes in hair shaft length, follicle morphology, pigmentation, proliferation and apoptosis. After only 48 h, T-oligos induced a fourfold increase in pigmentation of human anagen VI hair bulbs, while hair matrix keratinocyte proliferation was reduced by 65%, without apparent changes in hair bulb cell apoptosis. This corresponded well with a significant inhibition of hair shaft elongation, which was not accompanied by premature catagen induction in anagen VI hair follicles. These diametrically opposed effects of T-oligos on human hair follicle melanocytes (stimulation of melanogenesis) versus human hair bulb keratinocytes (inhibition of proliferation) in situ illustrate that human hair follicle organ culture offers an excellent tool for T-oligo research. They suggest that T-oligos deserve to be further explored for the management of clinical hair growth and pigmentation disorders, and raise the possibility that this model may offer a unique "time lapse system" for studying skin and hair follicle biology and DNA repair strategies under physiologically relevant conditions.

The flavonoid alpha-glucosylrutin (AGR) is a potent antioxidant with a high epidermal bioavailability. This makes this substance particularly suitable for various dermato-cosmetic applications. Flavonoids are phytamines with a common chemical structure and a broad range of activities, the most prominent being their radical scavenging ability. Reactive oxygen species (ROS) damage cells by different mechanisms. Direct cytotoxic effects include destruction of the cell membrane by causing radical chain reactions or induction of mutagenic changes in the nuclear and mitochondrial DNA. Indirect changes involve modification of intracellular signal transduction pathways that regulate inflammatory or proliferative activities. The excellent antioxidant efficacy of AGR has been shown in various experimental studies, both in vitro and in vivo. Subsequent clinical studies have demonstrated that AGR is also effective in the prevention of dermatologic diseases in which oxidative stress is of pathogenetic relevance, e.g. in polymorphous light eruption (PLE). Other promising dermato-cosmetic areas for AGR application are aging of the skin, especially photoaging. All in vivo evaluations indicate that AGR in the applied concentrations is a very well-tolerated ingredient for medical skin care preparations.

Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN), and their receptors, GDNF family receptor alpha-1 (GFRalpha-1) and GDNF family receptor alpha-2 (GFRalpha-2), are critically important for kidney and nervous system development. However, their role in skin biology, specifically in hair growth control, is as yet unknown. We have studied expression and function of GDNF, neurturin, GFRalpha-1, and GFRalpha-2 in murine skin during the cyclic transformation of the hair follicle (HF) from its resting state (telogen) to active growth (anagen) and then through regression (catagen) back to telogen. GDNF protein and GFRalpha-1 messenger RNA are prominently expressed in telogen skin, which lacks NTN and GFRalpha-2 transcripts. Early anagen development is accompanied by a significant decline in the skin content of GDNF protein and GFRalpha-1 transcripts. During the anagen-catagen transition, GDNF, GFRalpha-1, NTN, and GFRalpha-2 transcripts reach maximal levels. Compared with wild-type controls, GFRalpha-1 (+/-) and GFRalpha-2 (-/-) knockout mice show a significantly accelerated catagen development. Furthermore, GDNF or NTN administration significantly retards HF regression in organ-cultured mouse skin. This suggests important, previously unrecognized roles for GDNF/GFRalpha-1 and NTN/GFRalpha-2 signaling in skin biology, specifically in the control of apoptosis-driven HF involution, and raises the possibility that GFRalpha-1/GFRalpha-2 agonists/antagonists might become exploitable for the treatment of hair growth disorders that are related to abnormalities in catagen development.

Multiple pathways are involved in accurate synthesis and distribution of DNA during replication, repair and maintenance of genomic integrity. An increased error rate, abovethe spontaneous mutation baseline, has been implicated in carcinogenesis and aging. Moreover, cytogenetic abnormalities are increased in Down's, Edwards', Patau's, and Klinefelter's syndromes with increasing maternal age, and in Marfan's and Apert's syndromes with paternal age. In response to DNA damage, multiple overlapping systems of DNA repair have evolved, preferentially repairing the transcribed strand within transcriptionally-active regions of the genome. These include direct reversal of dimers and specific adducts and pathways for base excision, nucleotide excision, and mismatch repair. A consensus has emerged that some DNA repair capacities decline with organism age, contradictory reports notwithstanding. As is the case for inborn defects in humans, knockout mice lacking components of nucleotide excision repair or DNA-damage checkpoint arrest have increased frequencies of skin and internal cancers, whereas mice overexpressing DNA repair genes have fewer spontaneous cancers. Oxidative stress and resultant free radicals can damage genomic and mitochondrial DNA; damage increases with age but decreases with caloric restriction. We review recent studies of long-lived C. elegans mutants which appear to involve metabolic attenuation, the role of telomere shortening and telomerase in cellular senescence, and the genetic bases of progeroid syndromes in humans. Finally, we discuss roles of extrinsic and intrinsic factors in skin aging, and their association with DNA damage, emphasizing preventive and protective measures and prospects for intervention by modulating DNA repair pathways in the skin.