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Slatina Christov, Frenz Ohm, Matthias Augustin, Jan Nicolai Wagner Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, GermanyCorrespondence: Jan Nicolai Wagner, Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), 20246 Hamburg, Germany, Tel +49 (0) 40 74 10 52398, Fax +49 (0) 40 7410 55348, Email ja.wagner@uke.deAbstract: Linear psoriasis (LP) represents a rare variant of psoriasis. The clinical presentation includes erythematous plaques distributed along the Blaschko lines, reflecting the presence of embryological mosaicism. The clinical and histopathological features of this condition show many similarities with inflammatory linear verrucous epidermal nevus (ILVEN), which presents a challenge in differential diagnosis. Currently there is no disease-specific treatment guidelines causing a challenge in the therapeutic management. In this case report we describe a 28-year-old patient with LP. Clinically characterized by persistent, psoriasiform lesions that proved refractory to treatment with topical corticosteroids, vitamin D analogs, and systemic dimethyl fumarate. The histopathological findings showed psoriasiform epidermal hyperplasia with alternating ortho- and parakeratosis, subepidermal capillary dilatation, and perivascular lymphocytic infiltrates, confirming the diagnosis. Ixekizumab, a IL-17A antagonist, was administered leading to a rapid and significant reduction in disease severity within the first 16 weeks. The Psoriasis Area and Severity Index (PASI) decreased from 12.5 to 1.0 and as well as the Dermatology Life Quality Index (DLQI) improved to 1. Both scores prove significant improvement in quality of life and clinical severity. This case report shows the importance of histological confirmation in differentiating LP from clinically similar appearing diseases like ILVEN and highlights the potential therapeutic benefit of IL-17 blockade in LP. In addition, the findings emphasize the need for systematic studies to develop evidence-based treatment strategies for this rare psoriasis phenotype.Keywords: psoriasis, linear psoriasis, biologics, genodermatosis, ILVEN, IL-17A-antagonist, ixekizumab

Background and Objectives: Data on the population-based epidemiology of hyperhidrosis (HH) are scarce. This study investigated the epidemiology and healthcare of HH in Germany., Design and Setting: Claims data of adult persons insured by a German statutory health insurance (DAK-Gesundheit) between 2016 and 2020 were analysed. Included were persons aged 18 years and older with a diagnosis of HH (confirmed inpatient or outpatient diagnosis in the observation year) who were continuously insured. Following outcomes were measured: prevalence and incidence rates, severity of hyperhidrosis and inpatient and outpatient care by a group of specialists., Results: In 2020, 0.70% of insured adults were confirmed to have HH (mean age 59.5 years, SD 18.9, 61.6% female), with 9.24% having a 'localised' form, 8.65% a 'generalised' form and 84.80% an 'unspecified' form. 0.04% of the total population had a severe form. The incidence was 0.35%. Localised HH was more common in younger age groups (18 to <30 years), while older age groups (70 to <80 years) were significantly more likely to suffer from generalised HH. Systemic anticholinergics were used in 4.55%, and botulinum toxin injection therapy in 0.81%. General practitioners were most frequently involved in care. Inpatient stays due to HH were very rare, with 0.14% in 2019 and 0.04% in 2020., Conclusion: Multisource data analysis connecting primary and secondary data will be needed for a complete picture of the healthcare and epidemiology of HH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Topical agents are an essential component of psoriasis therapy., Objectives: To develop a new version of the patient-reported Patient Benefit Index assessing the importance and achievement of treatment goals in topical psoriasis therapy in adult patients (PBI-TOP)., Methods: Through semi-structured interviews, focus groups and free-text questionnaires, patients reported their needs in topical treatment. Based on qualitative content analysis, items were developed by a consensus group and were refined in cognitive debriefing interviews. A pilot validation assessed the PBI-TOP and convergent criteria [Dermatology Life Quality Index (DLQI); Psoriasis Area and Severity Index (PASI); affected Body Surface Area (BSA)]., Results: Thirty patients (26-72 years, mean 47; 60% male) reported various treatment goals relating to the themes 'effectiveness' and 'characteristics of the preparation'. Twenty patients took part in cognitive debriefings (22-84 years, mean 50.6, 50% male). There were 154 patients who participated in the pilot validation (18-85 years, mean 46.9, 63.6% male). An importance-weighted total score on overall effectiveness and three subscales based on exploratory factor analysis were defined: effectiveness on symptoms, effectiveness on quality of life (QoL), and characteristics of the preparation. All scores showed excellent internal consistency (α > 0.9). The global effectiveness score correlated significantly with DLQI (r = -0.41), PASI (r = -0.32) and BSA (r = -0.22). The effectiveness subscales (symptoms; QoL) correlated significantly with DLQI (r = -0.41; -0.32) and PASI (r = -0.27; -0.33). The score on characteristics of the preparation correlated significantly with the DLQI (r = -0.34)., Conclusions: The PBI-TOP showed good feasibility and favourable psychometric characteristics in this pilot validation., Competing Interests: Conflicts of interest C.B. has received speaker honoraria, research grants and/or awards from Amgen/Celgene, AstraZeneca, Bauerfeind, Hartmann, Helios Klinik Leisnig, Janssen-Cilag, Kreussler, Lilly, Mapi Group, medi, Pfizer, Stiefel Laboratories, The EuroQol Group and Urgo. M.A. has served as a consultant, or has been a paid speaker, or has received institutional grants for studies sponsored by companies that manufacture drugs used for the treatment of psoriasis, including Abbvie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer and UCB Pharma; he is license holder of the Patient Benefit index., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Innate immunity not only shapes the way epithelial barriers interpret environmental cues but also drives adaptive responses. Therefore, modulators of innate immune responses are expected to have high therapeutic potential across immune-mediated inflammatory diseases. IRAK4 is a kinase that integrates signaling downstream of receptors acting at the interface between innate and adaptive immune responses, such as Toll-like receptors (TLRs), interleukin-1R (IL-1R), and IL-18R. Because effects of IRAK4 inhibition are stimulus, cell type, and species dependent, the evaluation of the therapeutic potential of IRAK4 inhibitors requires a highly translational approach. Here, we profiled a selective IRAK4 inhibitor, GLPG2534, in an extensive panel of models of inflammatory skin diseases, translationally expanding evidence from in vitro to in vivo and from mouse to human. In vitro, IRAK4 inhibition resulted in substantial inhibition of TLR and IL-1 responses in dendritic cells, keratinocytes, granulocytes, and T cells but only weakly affected dermal fibroblast responses. Furthermore, disease activity in murine models of skin inflammation (IL-23-, IL-33-, imiquimod-, and MC903-induced) was markedly dampened by IRAK4 inhibition. Last, inhibiting IRAK4 reversed pathogenic molecular signatures in human lesional psoriasis and atopic dermatitis biopsies. Over the variety of models used, IRAK4 inhibition consistently affected central mediators of psoriasis (IL-17A) and atopic dermatitis (IL-4 and IL-13). Overall, our data highlight IRAK4 as a central player in skin inflammatory processes and demonstrate the potential of IRAK4 inhibition as a therapeutic strategy in chronic inflammatory skin diseases.

Since 2021, adalimumab biosimilar ABP 501 can be used alternatively to adalimumab originator (ADAO) in the treatment of hidradenitis suppurativa (HS). Effectiveness and safety data remain scarce. We investigated the impact of switching from ADAO to ABP 501 on disease severity and the occurrence of adverse events (AEs) in patients with HS. We analyzed clinical data on patients enrolled in the German HSBest registry. Evaluation outcomes were assessed at three time points (baseline of originator (t0), prior to switching to biosimilar (t1) and 12 to 14 weeks after switching (t2)) and included patient-reported AEs and disease severity using the International Hidradenitis Suppurativa Severity Score System (IHS4) score. In total, 94 patients were switched from ADAO to ABP 501. Overall, 33.3% ( n = 31/94) of the patients developed AEs and/or loss of response (LoR) within 12 to 14 weeks after switching. Of these, 61.3% ( n = 19/31) experienced LoR but no AEs, 22.6% ( n = 7/31) LoR combined with AEs and 16.1% ( n = 5/31) AEs only. Our study showed that switching HS patients from ADAO to ABP 501 does significantly affect treatment effectiveness. Switching patients who are on remission maintenance therapy should be viewed critically.

The sex hormone estradiol has recently gained attention in human decision-making research. Animal studies have already shown that estradiol promotes dopaminergic transmission and thus supports reward-seeking behavior and aspects of addiction. In humans, natural variations of estradiol across the menstrual cycle modulate the ability to learn from direct performance feedback ("model-free" learning). However, it remains unclear whether estradiol also influences more complex "model-based" contributions to reinforcement learning. Here, 41 women were tested twice - in the low and high estradiol state of the follicular phase of their menstrual cycle - with a Two-Step decision task designed to separate model-free from model-based learning. The results showed that in the high estradiol state women relied more heavily on model-free learning, and accomplished reduced performance gains, particularly during the more volatile periods of the task that demanded increased learning effort. In contrast, model-based control remained unaltered by the influence of hormonal state across the group. Yet, when accounting for individual differences in the genetic proxy of the COMT-Val158Met polymorphism (rs4680), we observed that only the participants homozygote for the methionine allele ( n = 12; with putatively higher prefrontal dopamine) experienced a decline in model-based control when facing volatile reward probabilities. This group also showed the increase in suboptimal model-free control, while the carriers of the valine allele remained unaffected by the rise in endogenous estradiol. Taken together, these preliminary findings suggest that endogenous estradiol may affect the balance between model-based and model-free control, and particularly so in women with a high prefrontal baseline dopamine capacity and in situations of increased environmental volatility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Diekhof, Geana, Ohm, Doll and Frank.)

In a recent work, an algorithm to compare chemical patterns, written for example in SMARTS, was presented. This algorithm, called SMARTScompare, is able to assess the identity, subset relation, and similarity of a pair of patterns. Here we used an implementation of SMARTScompare to analyze SMARTS filter sets that were published in the context of, for example, high-throughput screening. We found that the difference in intentions with which the filter sets were designed is mirrored in the similarity values we calculated. The analysis revealed which patterns from one filter set are covered by filters from another set. In one case it became obvious that a filter set is more or less completely covered by another. Furthermore, we analyzed pattern hierarchies for consistency, and we propose a method to remove redundant patterns. SMARTScompare together with SMARTScompareView equips users with powerful methods to visualize, compare, and focus their filter sets.

Molecular patterns are widely used for compound filtering in molecular design endeavors. They describe structural properties that are connected with unwanted physical or chemical properties like reactivity or toxicity. With filter sets comprising hundreds of structural filters, an analytic approach to compare those patterns is needed. Here we present a novel approach to solve the generic pattern comparison problem. We introduce chemically inspired fingerprints for pattern nodes and edges to derive an easy-to-compare pattern representation. On two annotated pattern graphs we apply a maximum common subgraph algorithm enabling the calculation of pattern inclusion and similarity. The resulting algorithm can be used in many different ways. We can automatically derive pattern hierarchies or search in large pattern collections for more general or more specific patterns. To the best of our knowledge, the presented algorithm is the first of its kind enabling these types of chemical pattern analytics. Our new tool named SMARTScompare is an implementation of the approach for the SMARTS language, which is the quasi-standard for structural filters. We demonstrate the capabilities of SMARTScompare on a large collection of SMARTS patterns from real applications.

Background: History taking and empathetic communication are two important aspects in successful physician-patient interaction. Gathering important information from the patient's medical history is needed for effective clinical decision making while empathy is relevant for patient satisfaction. We wanted to investigate whether medical students near graduation are able to combine both skills as required in daily medical practice., Methods: Thirty near graduates from Hamburg Medical School participated in an assessment for clinical competences including a consultation hour with five standardized patients. Each patient interview was videotaped and standardized patients rated participants with the CARE questionnaire for consultation and relational empathy. All videotaped interviews were rated with a checklist based on the number of important medical aspects for each case. Data were analysed with the linear mixed model to correct for random effects. Regression analysis was performed to look for correlations between the number of questions asked by a participant and their respective empathy rating., Results: Of the 123 aspects that could have been gathered in total, students only requested 56.4% (95% CI 53.5-59.3). While no difference between male and female participants was found, a significant difference (p<.001) was observed between the two parts of the checklist with 61.1% (95% CI 57.9-64.3) of aspects asked for in part 1 (patient's symptoms) versus 52.0 (95 47.4-56.7) in part 2 (further history). All female standardized patients combined rated female participants (mean score 14.2, 95% CI 12.3-16.3) to be significantly (p<.01) more empathetic than male participants (mean score 19.2, 95% CI 16.3-22.6). Regression analysis revealed no correlation between the number of medical aspects gathered by a participant and his or her respective empathy score given by the standardized patient in the CARE questionnaire., Conclusion: Gathering sufficient medical data from a patient's history and empathetic communication are two completely separate sides of the coin of history taking. While both skills have to be acquired during medical school training with particular focus on their respective learning objectives, medical students need to be provided with additional learning and feedback opportunities where they can be observed exercising both skills combined as required in physicians' daily practice.