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Florian Anzengruber,1,2 Adhideb Ghosh,1–3 Julia-Tatjana Maul,1,2 Mathias Drach,1,2 Alexander A Navarini1–3 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; 2Faculty of Medicine, University of Zurich, Zurich, Switzerland; 3Competence Center Personalized Medicine University of Zurich/Swiss Federal Institute of Technology (ETH) Zurich, Switzerland Purpose: Several studies have suggested that an HLA-Cw6+ allele can predict an improved outcome of treatment in psoriasis patients. The aim of the study was to assess whether the published association between HLA-Cw6 allele carriers and response to ustekinumab has the potential to impact treatment decisions. Patients and methods: Differences in Psoriasis Activity and Severity Index 50, 75, and 90; Nail Psoriasis Severity Index; and Dermatology Life Quality Index at 16 weeks were evaluated between HLA-Cw6 allele carriers vs. non-carriers. Thirty patients with moderate-to-severe psoriasis under treatment with ustekinumab were included in our study. Results: There was no difference between the two groups with respect to Psoriasis Activity and Severity Index 50, 75, and 90 or in terms of change in Nail Psoriasis Severity Index or Dermatology Life Quality Index. Conclusion: In our retrospectively analyzed cohort, we could not detect the previously reported better response in HLA-Cw6+ vs. HLA-Cw6− patients. Keywords: human leukocyte antigen, Cw6, genetic variations, HLA-Cw6, ustekinumab

Psoriasis is a common, relapsing inflammatory skin disease characterized by erythematous scaly plaques. Histological manifestations of psoriasis include keratinocyte dysregulation and hyperproliferation, elongated rete ridges, and inflammatory infiltrates consisting of T cells, macrophages, dendritic cells, and neutrophils. Despite the availability of new effective drugs to treat psoriasis, the underlying mechanisms of pathogenesis are still poorly understood. Recent studies have shown that Aldara cream, used to treat benign skin abnormalities, triggers psoriasis-like disease in humans and mice and have implicated Th17 cells in disease initiation. Using this as a model, we found a predominant role for the Th17 signature cytokines IL-17A, IL-17F, and IL-22 in psoriasiform plaque formation in mice. Using gene-targeted mice, we observed that loss of Il17a, Il17f, or Il22 strongly reduced disease the severity of psoriasis. However, we found that Th17 cells were not the primary source of these pathogenic cytokines. Rather, IL-17A, IL-17F, and IL-22 were produced by a skin-invading population of γδ T cells and RORγt(+) innate lymphocytes. Furthermore, our findings establish that RORγt(+) innate lymphocytes and γδ T cells are necessary and sufficient for psoriatic plaque formation in an experimental disease model that closely resembles human psoriatic plaque formation. [ABSTRACT FROM AUTHOR]

Background: Due to similarities, the distinction between generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis (AGEP) has been a matter of debate for long time., Objective: Our aim was to define the molecular features of GPP and AGEP., Methods: We analyzed skin biopsy samples and clinical data from 125 patients with AGEP, GPP, palmoplantar pustulosis (PPP), plaque psoriasis (PSO), and non-pustular cutaneous adverse drug reactions (ADRs), as well as from healthy skin controls using RNA sequencing and blinded histopathological analyses., Results: The transcriptome and histopathologic features of AGEP and GPP samples exhibited significant overlap (177 differentially expressed genes (DEGs) in GPP and AGEP compared to healthy skin, only 2 DEGs comparing AGEP and GPP), yet displayed marked differences from those of PPP, PSO, and ADR samples, with a notable number of DEGs (131 DEGs comparing AGEP and PSO, 75 DEGs comparing AGEP and PPP and 52 DEGs comparing AGEP and ADR) and pathways. A transcriptome profile subgroup evaluation of more than 13,000 analyzed genes did not reveal any differentially expressed genes in drug-induced GPP and AGEP. Moreover, the immune response pattern and immune cell composition did not differ between drug-induced GPP and AGEP, whereas non-drug-induced GPP had higher expression of Th17-related genes and a higher neutrophil count than AGEP., Conclusion: We propose that AGEP is a drug-induced variant of GPP and therefore part of IL-36-related pustulosis. A key signature overarching this spectrum was identified, thereby opening the therapeutic approach of IL-36 inhibition to all subtypes of the disease., (Copyright © 2025. Published by Elsevier Inc.)

Pregnancy-associated changes in melanocytic nevi (MN), apart from size increase on the trunk, remain a topic of debate. We conducted the first prospective study to investigate dermoscopic changes in MN comparing pregnant with non-pregnant women on all body parts using a market-approved convolutional neural network (CNN). We included 25 pregnant and 25 non-pregnant women from Basel, Switzerland, who underwent standard skin cancer screenings and whose MN > 2 mm were digitally recorded and analysed by a CNN. Pregnant women were examined three times: in the first and third trimester and 8-12 weeks postpartum; non-pregnant women twice in an interval of 17-21 weeks. We analysed 2,799 MN. In pregnant women, diameter[p < 0.001], area[p < 0.001], number of colours [p = 0.009], shape asymmetry[p = 0.005] and border sharpness[p = 0.006] (inversely proportional value) increased while ellipseness [p < 0.001] decreased from first trimester to postpartum. Changes occurred mainly during the third trimester to postpartum. Compared to non-pregnant women (only first to third trimester) MN on the upper extremities of pregnant women increased in area[p = 0.011] and diameter[p = 0.025] and decreased in ellipseness[p = 0.037]. MN on the lower extremities increased in area[p = 0.044] and MN on the back increased in colour asymmetry[p = 0.022].

Introduction: Skin cancer, a prevalent cancer type among fair-skinned patients globally, poses a relevant public health concern due to rising incidence rates. Ultraviolet (UV) radiation poses a major risk factor for skin cancer. However, intentional tanning associated with sunburns remains a common practice, notably among female adults. Appropriate prevention campaigns targeting children and adolescents are needed to improve sun protection behavior particularly in these age groups. The aim of our study was to investigate if an AI-based simulation of facial skin aging can enhance sun protection behavior in female adults., Methods: In this single-center, prospective, observational pilot study at Department of Dermatology at the University Hospital of Basel, we took photographs of healthy young females' faces with a VISIA-CR camera (Version 8.2; Canfield Scientific Inc., Parsippany, NJ, USA) between February and March 2021. Digital images were performed in three angles (straight, left 45°, and right 45°). All participants received an AI-based simulation of their facial skin with continuous aging to 80 years. A newly created anonymous questionnaire capturing participants' sociodemographic data and also tanning and sun protection behavior was completed in pre- and post-aging simulation. To observe long-term effects, a 2-year follow-up was conducted between March and April 2023., Results: The 60 participants (mean age 23.6 ± 2.5 years) evaluated the importance of sun protection significantly higher after skin aging simulation with VISIA-CR camera (p < 0.0001; 95% CI: 8.2-8.8). Post-intervention, 91.7% (55/60) of the females were motivated to reduce UV exposure and to intensify UV protection in the future since the individual UV-dependent risk was perceived significantly higher (p < 0.001; 95% CI: 5.9-6.7). At 2-year follow-up, 96% (24/25) indicated persistent effort reducing UV exposure. The preference for SPF 50+ sunscreen increased to 46.7% (28/65) directly after the skin aging simulation and continued to rise up to 60.0% (15/25) after 2 years., Conclusions: Our data emphasize the potential of AI-assisted photoaging interventions to enhance motivation for UV protection in the short and the long term. We encourage that different age and gender groups are addressed in a personalized, generation-specific manner with the appropriate media and by considering the Hawthorne effect. Campaigns with visual AI support can improve the intent of cancer-preventative behavior., Introduction: Skin cancer, a prevalent cancer type among fair-skinned patients globally, poses a relevant public health concern due to rising incidence rates. Ultraviolet (UV) radiation poses a major risk factor for skin cancer. However, intentional tanning associated with sunburns remains a common practice, notably among female adults. Appropriate prevention campaigns targeting children and adolescents are needed to improve sun protection behavior particularly in these age groups. The aim of our study was to investigate if an AI-based simulation of facial skin aging can enhance sun protection behavior in female adults., Methods: In this single-center, prospective, observational pilot study at Department of Dermatology at the University Hospital of Basel, we took photographs of healthy young females' faces with a VISIA-CR camera (Version 8.2; Canfield Scientific Inc., Parsippany, NJ, USA) between February and March 2021. Digital images were performed in three angles (straight, left 45°, and right 45°). All participants received an AI-based simulation of their facial skin with continuous aging to 80 years. A newly created anonymous questionnaire capturing participants' sociodemographic data and also tanning and sun protection behavior was completed in pre- and post-aging simulation. To observe long-term effects, a 2-year follow-up was conducted between March and April 2023., Results: The 60 participants (mean age 23.6 ± 2.5 years) evaluated the importance of sun protection significantly higher after skin aging simulation with VISIA-CR camera (p < 0.0001; 95% CI: 8.2-8.8). Post-intervention, 91.7% (55/60) of the females were motivated to reduce UV exposure and to intensify UV protection in the future since the individual UV-dependent risk was perceived significantly higher (p < 0.001; 95% CI: 5.9-6.7). At 2-year follow-up, 96% (24/25) indicated persistent effort reducing UV exposure. The preference for SPF 50+ sunscreen increased to 46.7% (28/65) directly after the skin aging simulation and continued to rise up to 60.0% (15/25) after 2 years., Conclusions: Our data emphasize the potential of AI-assisted photoaging interventions to enhance motivation for UV protection in the short and the long term. We encourage that different age and gender groups are addressed in a personalized, generation-specific manner with the appropriate media and by considering the Hawthorne effect. Campaigns with visual AI support can improve the intent of cancer-preventative behavior., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin condition associated with significant impairment of quality of life and potential risk of malignant transformation. However, diagnosis of VLS is often delayed due to its variable clinical presentation and shame-related late consultation. Machine learning (ML)-trained image recognition software could potentially facilitate early diagnosis of VLS., Objective: To develop a ML-trained image-based model for the detection of VLS., Methods: Images of both VLS and non-VLS anogenital skin were collected, anonymized, and selected. In the VLS images, 10 typical skin signs (whitening, hyperkeratosis, purpura/ecchymosis, erosion/ulcers/excoriation, erythema, labial fusion, narrowing of the introitus, labia minora resorption, posterior commissure (fourchette) band formation and atrophic shiny skin) were manually labelled. A deep convolutional neural network was built using the training set as input data and then evaluated using the test set, where the developed algorithm was run three times and the results were then averaged., Results: A total of 684 VLS images and 403 non-VLS images (70% healthy vulva and 30% with other vulvar diseases) were included after the selection process. A deep learning algorithm was developed by training on 775 images (469 VLS and 306 non-VLS) and testing on 312 images (215 VLS and 97 non-VLS). This algorithm performed accurately in discriminating between VLS and non-VLS cases (including healthy individuals and non-VLS dermatoses), with mean values of 0.94, 0.99 and 0.95 for recall, precision and accuracy, respectively., Conclusions: This pilot project demonstrated that our image-based deep learning model can effectively discriminate between VLS and non-VLS skin, representing a promising tool for future use by clinicians and possibly patients. However, prospective studies are needed to validate the applicability and accuracy of our model in a real-world setting., (© 2024 European Academy of Dermatology and Venereology.)

Real-world data on the effectiveness and safety of tildrakizumab, an interleukin 23p19 inhibitor, in Switzerland is limited. The objectives of this analysis were to assess the effectiveness and safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis in Switzerland. Twenty-eight adults from the Swiss Dermatology Network for Targeted Therapies registry (SDNTT), who were on tildrakizumab treatment and had at least 3 months' follow-up, were enrolled in this prospective, multicentre study. No missing data imputation was performed. The median Psoriasis Area and Severity Index (PASI) decreased from 9.5 at baseline to 2.1 and 0.3 (both p < 0.001) after 3 and 18 months, respectively, of tildrakizumab treatment. After 3 months, 76.9%/30.8% patients reached an absolute PASI <  3/ < 1. These rates increased to 85.7%/57.1% after 18 months of treatment. The proportions of patients achieving PASI 90/100 responses were 47.8%/30.4% at month 6 and 42.9%/14.3% at month 18. A significant improvement in quality of life up to 18 months of follow-up was observed as measured by the Dermatology Life Quality Index. There were no treatment discontinuations due to adverse events. This real-world registry provides robust evidence supporting the long-term effectiveness and favourable safety profile of tildrakizumab in treating patients with moderate-to-severe psoriasis.

Psoriasis, a chronic inflammatory skin disease, affects millions of people worldwide. It imposes a significant burden on patients' quality of life and healthcare systems, creating an urgent need for optimized diagnosis, treatment, and management. In recent years, image-based artificial intelligence (AI) applications have emerged as promising tools to assist physicians by offering improved accuracy and efficiency. In this review, we provide an overview of the current landscape of image-based AI applications in psoriasis. Emphasis is placed on machine learning (ML) algorithms, a key subset of AI, which enable automated pattern recognition for various tasks. Key AI applications in psoriasis include lesion detection and segmentation, differentiation from other skin conditions, subtype identification, automated area involvement, and severity scoring, as well as personalized treatment selection and response prediction. Furthermore, we discuss two commercially available systems that utilize standardized photo documentation, automated segmentation, and semi-automated Psoriasis Area and Severity Index (PASI) calculation for patient assessment and follow-up. Despite the promise of AI in this field, many challenges remain. These include the validation of current models, integration into clinical workflows, the current lack of diversity in training-set data, and the need for standardized imaging protocols. Addressing these issues is crucial for the successful implementation of AI technologies in clinical practice. Overall, we underscore the potential of AI to revolutionize psoriasis management, highlighting both the advancements and the hurdles that need to be overcome. As technology continues to evolve, AI is expected to significantly improve the accuracy, efficiency, and personalization of psoriasis treatment., (© 2024. The Author(s).)

Chronic pruritus is a highly prevalent disease associated with high psychosocial and economic burdens. In addition to pharmacological treatments, device-based physical therapies also offer antipruritic effects. Phototherapy, laser, electrical neurostimulation technologies, acupuncture, cryotherapy, and cold atmospheric plasma are, in part, still experimental but emerging treatment options that augment our repertoire to treat patients with chronic pruritus. In this narrative review, we provided an overview of these physical modalities and their role in itch management., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Even though past research suggests that visual learning may benefit from conceptual knowledge, current interventions for medical image evaluation often focus on procedural knowledge, mainly by teaching classification algorithms. We compared the efficacy of pure procedural knowledge (three-point checklist for evaluating skin lesions) versus combined procedural plus conceptual knowledge (histological explanations for each of the three points). All students then trained their classification skills with a visual learning resource that included images of two types of pigmented skin lesions: benign nevi and malignant melanomas. Both treatments produced significant and long-lasting effects on diagnostic accuracy in transfer tasks. However, only students in the combined procedural plus conceptual knowledge condition significantly improved their diagnostic performance in classifying lesions they had seen before in the pre- and post-tests. Findings suggest that the provision of additional conceptual knowledge supported error correction mechanisms., (© 2023. The Author(s).)

With rising melanoma incidence and mortality, early detection and surgical removal of primary lesions is essential. Multispectral imaging is a new, non-invasive technique that can facilitate skin cancer detection by measuring the reflectance spectra of biological tissues. Currently, incident illumination allows little light to be reflected from deeper skin layers due to high surface reflectance. A pilot study was conducted at the University Hospital Basel to evaluate, whether multispectral imaging with direct light coupling could extract more information from deeper skin layers for more accurate dignity classification of melanocytic lesions. 27 suspicious pigmented lesions from 23 patients were included (6 melanomas, 6 dysplastic nevi, 12 melanocytic nevi, 3 other). Lesions were imaged before excision using a prototype snapshot mosaic multispectral camera with incident and direct illumination with subsequent dignity classification by a pre-trained multispectral image analysis model. Using incident light, a sensitivity of 83.3% and a specificity of 58.8% were achieved compared to dignity as determined by histopathological examination. Direct light coupling resulted in a superior sensitivity of 100% and specificity of 82.4%. Convolutional neural network classification of corresponding red, green, and blue lesion images resulted in 16.7% lower sensitivity (83.3%, 5/6 malignant lesions detected) and 20.9% lower specificity (61.5%) compared to direct light coupling with multispectral image classification. Our results show that incorporating direct light multispectral imaging into the melanoma detection process could potentially increase the accuracy of dignity classification. This newly evaluated illumination method could improve multispectral applications in skin cancer detection. Further larger studies are needed to validate the camera prototype., (© 2024. The Author(s).)

AI image classification algorithms have shown promising results when applied to skin cancer detection. Most public skin cancer image datasets are comprised of dermoscopic photos and are limited by selection bias, lack of standardization, and lend themselves to development of algorithms that can only be used by skilled clinicians. The SLICE-3D ("Skin Lesion Image Crops Extracted from 3D TBP") dataset described here addresses those concerns and contains images of over 400,000 distinct skin lesions from seven dermatologic centers from around the world. De-identified images were systematically extracted from sensitive 3D Total Body Photographs and are comparable in optical resolution to smartphone images. Algorithms trained on lower quality images could improve clinical workflows and detect skin cancers earlier if deployed in primary care or non-clinical settings, where photos are captured by non-expert physicians or patients. Such a tool could prompt individuals to visit a specialized dermatologist. This dataset circumvents many inherent limitations of prior datasets and may be used to build upon previous applications of skin imaging for cancer detection., (© 2024. The Author(s).)

Background: Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms., Objectives: This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape., Methods: Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion., Results: Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05)., Conclusions: Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons., Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method., Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion., Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques.", Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

Importance: Total body photography for skin cancer screening is a well-established tool allowing documentation and follow-up of the entire skin surface. Artificial intelligence-based systems are increasingly applied for automated lesion detection and diagnosis., Design and Patients: In this prospective observational international multicentre study experienced dermatologists performed skin cancer screenings and identified clinically relevant melanocytic lesions (CRML, requiring biopsy or observation). Additionally, patients received 2D automated total body mapping (ATBM) with automated lesion detection (ATBM master, Fotofinder Systems GmbH). Primary endpoint was the percentage of CRML detected by the bodyscan software. Secondary endpoints included the percentage of correctly identified "new" and "changed" lesions during follow-up examinations., Results: At baseline, dermatologists identified 1075 CRML in 236 patients and 999 CRML (92.9%) were also detected by the automated software. During follow-up examinations dermatologists identified 334 CRMLs in 55 patients, with 323 (96.7%) also being detected by ATBM with automated lesions detection. Moreover, all new (n = 13) or changed CRML (n = 24) during follow-up were detected by the software. Average time requirements per baseline examination was 14.1 min (95% CI [12.8-15.5]). Subgroup analysis of undetected lesions revealed either technical (e.g. covering by clothing, hair) or lesion-specific reasons (e.g. hypopigmentation, palmoplantar sites)., Conclusions: ATBM with lesion detection software correctly detected the vast majority of CRML and new or changed CRML during follow-up examinations in a favourable amount of time. Our prospective international study underlines that automated lesion detection in TBP images is feasible, which is of relevance for developing AI-based skin cancer screenings., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HA Haenssle received honoraria and/or travel expenses from companies involved in the development of devices for skin cancer screening: Scibase AB, FotoFinder Systems GmbH, Heine Optotechnik GmbH, Magnosco GmbH. JK Winkler received honoraria and/or travel expenses from BMS, Fotofinder Systems GmBH, LaRoche Posay, Almirall, Biotest, Amgen, BMS, Leo Pharma, MSD, Philochem and Roche. LV Maul has served as advisor and/or received speaking fees and/or travel expenses and/or participated in clinical trials sponsored by Almirall, Amgen, BMS, Celgene, Eli Lilly, Kyowa Kirin, Incyte, L’Oreal, MSD, Novartis, Pierre Fabre, Roche, and Sanofi. The other authors state no conflict of interest related to the study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Deep-learning convolutional neural networks (CNNs) have outperformed even experienced dermatologists in dermoscopic melanoma detection under controlled conditions. It remains unexplored how real-world dermoscopic image transformations affect CNN robustness., Objectives: To investigate the consistency of melanoma risk assessment by two commercially available CNNs to help formulate recommendations for current clinical use., Methods: A comparative cohort study was conducted from January to July 2022 at the Department of Dermatology, University Hospital Basel. Five dermoscopic images of 116 different lesions on the torso of 66 patients were captured consecutively by the same operator without deliberate rotation. Classification was performed by two CNNs (CNN-1/CNN-2). Lesions were divided into four subgroups based on their initial risk scoring and clinical dignity assessment. Reliability was assessed by variation and intraclass correlation coefficients. Excisions were performed for melanoma suspicion or two consecutively elevated CNN risk scores, and benign lesions were confirmed by expert consensus (n = 3)., Results: 117 repeated image series of 116 melanocytic lesions (2 melanomas, 16 dysplastic naevi, 29 naevi, 1 solar lentigo, 1 suspicious and 67 benign) were classified. CNN-1 demonstrated superior measurement repeatability for clinically benign lesions with an initial malignant risk score (mean variation coefficient (mvc): CNN-1: 49.5(±34.3)%; CNN-2: 71.4(±22.5)%; p = 0.03), while CNN-2 outperformed for clinically benign lesions with benign scoring (mvc: CNN-1: 49.7(±22.7)%; CNN-2: 23.8(±29.3)%; p = 0.002). Both systems exhibited lowest score consistency for lesions with an initial malignant risk score and benign assessment. In this context, averaging three initial risk scores achieved highest sensitivity of dignity assessment (CNN-1: 94%; CNN-2: 89%). Intraclass correlation coefficients indicated 'moderate'-to-'good' reliability for both systems (CNN-1: 0.80, 95% CI:0.71-0.87, p < 0.001; CNN-2: 0.67, 95% CI:0.55-0.77, p < 0.001)., Conclusions: Potential user-induced image changes can significantly influence CNN classification. For clinical application, we recommend using the average of three initial risk scores. Furthermore, we advocate for CNN robustness optimization by cross-validation with repeated image sets., Trial Registration: ClinicalTrials.gov (NCT04605822)., (© 2023 European Academy of Dermatology and Venereology.)

Background: Psoriatic arthritis (PsA) is a prevalent comorbidity among patients with psoriasis, heavily contributing to their burden of disease, usually diagnosed several years after the diagnosis of psoriasis., Objectives: To investigate the predictability of psoriatic arthritis in patients with psoriasis and to identify important predictors., Methods: Data from the Swiss Dermatology Network on Targeted Therapies (SDNTT) involving patients treated for psoriasis were utilized. A combination of gradient-boosted decision trees and mixed models was used to classify patients based on their diagnosis of PsA or its absence. The variables with the highest predictive power were identified. Time to PsA diagnosis was visualized with the Kaplan-Meier method and the relationship between severity of psoriasis and PsA was explored through quantile regression., Results: A diagnosis of psoriatic arthritis was registered at baseline of 407 (29.5%) treatment series. 516 patients had no registration of PsA, 257 patients had PsA at inclusion, and 91 patients were diagnosed with PsA after inclusion. The model's AUROCs was up to 73.7%, and variables with the highest discriminatory power were age, PASI, physical well-being, and severity of nail psoriasis. Among patients who developed PsA after inclusion, significantly more first treatment series were classified in the PsA-group, compared to those with no PsA registration. PASI was significantly correlated with the median burden/severity of PsA ( P = .01)., Conclusions: Distinguishing between patients with and without PsA based on clinical characteristics is feasible and even predicting future diagnoses of PsA is possible. Patients at higher risk can be identified using important predictors of PsA., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ms. Nielsen has nothing to declare Dr. Petersen has nothing to declare With no relation to the present manuscript Dr. LV Maul has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Eli Lilly, MSD, Novartis, Pierre Fabre, Roche, and Sanofi. Dr. Thomsen has been a speaker or advisor for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals, and received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals, outside the submitted work. With no relation to the present manuscript, Dr. Schlapbach has received honoraria as adviser for Abbvie, BMS, LEO Pharma, Lilly, Kiowa Kirin, Novartis, and Pfizer and has received research funding from PPM Services. Prof. Kündig has intermittent, project focused consulting and/or advisory relationships with Leo Pharma, Janssen-Cilag, Eli Lilly, Pierre Fabre, Sanofi Genzyme, Abbvie, Biomed AG, Novartis, Almirall, Bristol-Myers Squibb, Galderma, L’Oréal/LaRoche-Posay, Merck-Sharp & Dohme, Zur Rose AG, Allergy Therapeutics AG, Derma2go AG, Oncobit AG, EVAX AG, Saiba Biotechnology AG, Saiba Animal Health AG, AltiBio Corp, Encoded Corp, Mabylon AG, MannKind Corp, XBiotech Corp. With no relation to the present manuscript, Dr. Wu is or has been an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Codex Labs, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Incyte, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, and Zerigo Health. Dr. Cozzio is or has been involved in advisory activities for AbbVie, Eli Lilly, Sanofi, Janssen-Cilag, Leo, Amgen. Dr. Conrad is or has been Scientific adviser and/or clinical study investigator for AbbVie, Actelion, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli-Lilly, Galderma, Incyte, Janssen, LEO pharma, MSD, Novartis, Pfizer, Samsung, Sanofi, and UCB With no relation to the present manuscript, Prof. Navarini declares being a consultant and advisor and/or receiving speaking fees and/or grants and/or served as an investigator in clinical trials for AbbVie, Almirall, Amgen, Biomed, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre Pharma, Regeneron, Sandoz, Sanofi, and UCB. With no relation to the present manuscript Dr. Thyssen is a full time employee at LEO Pharma and is an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, a speaker for AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and received research grants from Pfizer, Regeneron, and Sanofi-Genzyme. Dr. Boehncke has received honoraria as a speaker and/or advisor from Abbvie, Almirall, Amgen, BMS, Leo, Lilly, Novartis, and UCB. With no relation to the present manuscript Dr. Kristensen reports speakers bureau: Pfizer, AbbVie, Amgen, UCB, Galapagos, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals & Consultancy for Pfizer, AbbVie, Amgen, UCB, Gilead, Biogen, BMS, MSD, Novartis, Eli Lilly, and Janssen pharmaceuticals. With no relation to the present manuscript Dr. Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, Boehringer Ingelheim, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and honoraria as consultant and/or speaker from AbbVie, Almirall, Leo Pharma, Zuellig Pharma Ltd., Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, McNeil Consumer Healthcare, Horizon Therapeutics, Boehringer Ingelheim, and Janssen Pharmaceuticals. With no relation to the present manuscript Dr. Maul has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB. With no relation to the present manuscript Dr. Yawalkar has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galderma, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi-Genzyme, UCB., (© The Author(s) 2023.)

Background: Psoriasis is a disease that often requires prolonged systemic treatment. It is important to determine the safety of available therapies. There is currently little insight into sex-specific differences in the safety of systemic psoriasis therapies., Objectives: To examine the real-world, long-term safety of systemic psoriasis therapies with sex stratification in drug-related adverse events (ADRs)., Methods: Ten-year data from adults with moderate-to-severe psoriasis requiring systemic treatment (conventional systemic therapies [CST], biologics) were obtained from the Swiss psoriasis registry (SDNTT). ADRs were categorized according to the international terminology Medical Dictionary for Regulatory Activities (MedDRA). Safety was assessed by calculating event rates per 100 patient-years (PY). We used descriptive statistics for patient and disease characteristics, and binomial and t-tests to compare treatment groups and sex., Results: In total, 791 patients (290 females) were included with a mean age of 46 years. 358 (45%) received CSTs and 433 (55%) biologics; both groups had similar baseline characteristics except for more joint involvement in patients using biologics (26.86% vs. 14.8%, p < 0.0001). CSTs were associated with a 2.2-fold higher ADR rate (40.43/100 PY vs. 18.22/100 PY, p < 0.0001) and an 8.0-fold higher drug-related discontinuation rate than biologics (0.16/PY vs. 0.02/PY, p < 0.0001). Trends showed non-significant higher serious adverse event rates per 100 PY for biologics (8.19, CI 6.87-9.68) compared to CSTs (7.08, CI 5.39-9.13) (p = 0.3922). Sex stratification revealed a significantly higher overall ADR rate for all treatments in females (1.8-fold for CSTs [57.30/100 PY vs. 31.69/100 PY] and 2.0-fold for biologics [27.36/100 PY vs. 13.9/100 PY], p < 0.0001), and drug-related discontinuation rates for most CSTs in females., Conclusion: Females were associated with a significantly higher rate of ADRs and drug-related discontinuation rates. Sex stratification should be taken into consideration when designing studies in the patient-tailored management of psoriasis., (© 2023 European Academy of Dermatology and Venereology.)

Generalized pustular rashes have various etiologies and can be challenging to diagnose and manage at first presentation. The authors provide an in-depth analysis of common pustular skin eruptions including generalized pustular psoriasis (GPP) and acute generalized exanthematous pustulosis, focusing on their pathophysiology, triggers, clinical presentation, diagnostic challenges, and management strategies. The article also highlights recent advances in genetic research and biologic therapies for GPP and the future directions in personalized medicine and prevention strategies., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objective: Skin thermal diffusivity plays a crucial role in various applications, including laser therapy and cryogenic skin cooling.This study investigates the correlation between skin thermal diffusivity and two important skin parameters, melanin content and erythema, in a cohort of 102 participants., Methods: An in-house developed device based on transient temperature measurement was used to assess thermal diffusivity at different body locations. Melanin content and erythema were measured using a colorimeter. Statistical analysis was performed to examine potential correlations., Results: The results showed that the measured thermal diffusivity values were consistent with previous reports, with variations observed among subjects. No significant correlation was found between thermal diffusivity and melanin content or erythema. This suggests that other factors, such as skin hydration or epidermis thickness, may have a more dominant influence on skin thermal properties., Conlcusion: This research provides valuable insights into the complex interplay between skin thermal properties and physiological parameters, with potential implications for cosmetic and clinical dermatology applications., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Inflammatory bowel disease (IBD) occurring following allogeneic stem cell transplantation (aSCT) is a very rare condition. The underlying pathogenesis needs to be better defined. There is currently no systematic effort to exclude loss- or gain-of-function mutations in immune-related genes in stem cell donors. This is despite the fact that more than 100 inborn errors of immunity may cause or contribute to IBD. We have molecularly characterized a patient who developed fulminant inflammatory bowel disease following aSCT with stable 100% donor-derived hematopoiesis. A pathogenic c.A291G; p.I97M HAVCR2 mutation encoding the immune checkpoint protein TIM-3 was identified in the patient's blood-derived DNA, while being absent in DNA derived from the skin. TIM-3 expression was much decreased in the patient's serum, and in vitro-activated patient-derived T cells expressed reduced TIM-3 levels. In contrast, T cell-intrinsic CD25 expression and production of inflammatory cytokines were preserved. TIM-3 expression was barely detectable in the immune cells of the patient's intestinal mucosa, while being detected unambiguously in the inflamed and non-inflamed colon from unrelated individuals. In conclusion, we report the first case of acquired, "transplanted" insufficiency of the regulatory TIM-3 checkpoint linked to post-aSCT IBD., (© 2024. The Author(s).)

Importance: The COVID-19 pandemic resulted in delayed access to medical care. Restrictions to health care specialists, staff shortages, and fear of SARS-CoV-2 infection led to interruptions in routine care, such as early melanoma detection; however, premature mortality and economic burden associated with this postponement have not been studied yet., Objective: To determine the premature mortality and economic costs associated with suspended melanoma screenings during COVID-19 pandemic lockdowns by estimating the total burden of delayed melanoma diagnoses for Europe., Design, Setting, and Participants: This multicenter economic evaluation used population-based data from patients aged at least 18 years with invasive primary cutaneous melanomas stages I to IV according to the American Joint Committee on Cancer (AJCC) seventh and eighth editions, including melanomas of unknown primary (T0). Data were collected from January 2017 to December 2021 in Switzerland and from January 2019 to December 2021 in Hungary. Data were used to develop an estimation of melanoma upstaging rates in AJCC stages, which was verified with peripandemic data. Years of life lost (YLL) were calculated and were, together with cost data, used for financial estimations. The total financial burden was assessed through direct and indirect treatment costs. Models were building using data from 50 072 patients aged 18 years and older with invasive primary cutaneous melanomas stages I to IV according to the AJCC seventh and eighth edition, including melanomas of unknown primary (T0) from 2 European tertiary centers. Data from European cancer registries included patient-based direct and indirect cost data, country-level economic indicators, melanoma incidence, and population rates per country. Data were analyzed from July 2021 to September 2022., Exposure: COVID-19 lockdown-related delay of melanoma detection and consecutive public health and economic burden. As lockdown restrictions varied by country, lockdown scenario was defined as elimination of routine medical examinations and severely restricted access to follow-up examinations for at least 4 weeks., Main Outcomes and Measures: Primary outcomes were the total burden of a delay in melanoma diagnosis during COVID-19 lockdown periods, measured using the direct (in US$) and indirect (calculated as YLL plus years lost due to disability [YLD] and disability-adjusted life-years [DALYs]) costs for Europe. Secondary outcomes included estimation of upstaging rate, estimated YLD, YLL, and DALY for each European country, absolute direct and indirect treatment costs per European country, proportion of the relative direct and indirect treatment costs for the countries, and European health expenditure., Results: There were an estimated 111 464 (range, 52 454-295 051) YLL due to pandemic-associated delay in melanoma diagnosis in Europe, and estimated total additional costs were $7.65 (range, $3.60 to $20.25) billion. Indirect treatment costs were the main cost driver, accounting for 94.5% of total costs. Estimates for YLD in Europe resulted in 15 360 years for the 17% upstaging model, ranging from 7228 years (8% upstaging model) to 40 660 years (45% upstaging model). Together, YLL and YLD constitute the overall disease burden, ranging from 59 682 DALYs (8% upstaging model) to 335 711 DALYs (45% upstaging model), with 126 824 DALYs for the real-world 17% scenario., Conclusions and Relevance: This economic analysis emphasizes the importance of continuing secondary skin cancer prevention measures during pandemics. Beyond the personal outcomes of a delayed melanoma diagnosis, the additional economic and public health consequences are underscored, emphasizing the need to include indirect economic costs in future decision-making processes. These estimates on DALYs and the associated financial losses complement previous studies highlighting the cost-effectiveness of screening for melanoma.

Background: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer., Objective: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI-assisted smartphone applications (apps) and web-based services for skin diseases with emphasis on skin cancer detection., Methods: An initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance., Results: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non-medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web-based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users., Conclusions: The utilisation of AI-assisted smartphone apps and web-based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

It is important but challenging for prospective health professionals to learn the visual distinction between potentially harmful and harmless skin lesions, such as malignant melanomas and benign nevi. Knowledge about factors related to diagnostic performance is sparse but a prerequisite for designing and evaluating evidence-based educational interventions. Hence, this study explored how the characteristics of 240 skin lesions, the number of classified lesions and the response times of 137 laypeople were related to performance in diagnosing pigmented skin cancer. Our results showed large differences between the lesions, as some were classified correctly by more than 90% and others by less than 10% of the participants. A t-test showed that for melanomas, the correct diagnosis was provided significantly more often than for nevi. Furthermore, we found a significant Pearson correlation between the number of solved tasks and performance in the first 50 diagnostic tasks. Finally, t-tests for investigating the response times revealed that compared to true decisions, participants spent longer on false-negative but not on false-positive decisions. These results provide novel knowledge about performance-related factors that can be useful when designing diagnostic tests and learning interventions for melanoma detection., (© 2023. The Author(s).)

Objectives: The study aimed to improve the safety and accuracy of laser osteotomy (bone surgery) by integrating optical feedback systems with an Er:YAG laser. Optical feedback consists of a real-time visual feedback system that monitors and controls the depth of laser-induced cuts and a tissue sensor differentiating tissue types based on their chemical composition. The developed multimodal feedback systems demonstrated the potential to enhance the safety and accuracy of laser surgery., Materials and Methods: The proposed method utilizes a laser-induced breakdown spectroscopy (LIBS) system and long-range Bessel-like beam optical coherence tomography (OCT) for tissue-specific laser surgery. The LIBS system detects tissue types by analyzing the plasma generated on the tissue by a nanosecond Nd:YAG laser, while OCT provides real-time monitoring and control of the laser-induced cut depth. The OCT system operates at a wavelength of 1288 ± 30 nm and has an A-scan rate of 104.17 kHz, enabling accurate depth control. Optical shutters are used to facilitate the integration of these multimodal feedback systems., Results: The proposed system was tested on five specimens of pig femur bone to evaluate its functionality. Tissue differentiation and visual depth feedback were used to achieve high precision both on the surface and in-depth. The results showed successful real-time tissue differentiation and visualization without any visible thermal damage or carbonization. The accuracy of the tissue differentiation was evaluated, with a mean absolute error of 330.4 μm and a standard deviation of ±248.9 μm, indicating that bone ablation was typically stopped before reaching the bone marrow. The depth control of the laser cut had a mean accuracy of 65.9 μm with a standard deviation of ±45 μm, demonstrating the system's ability to achieve the pre-planned cutting depth., Conclusion: The integrated approach of combining an ablative laser, visual feedback (OCT), and tissue sensor (LIBS) has significant potential for enhancing minimally invasive surgery and warrants further investigation and development., (© 2023 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.)

Mutations in CD46 predispose to atypical hemolytic uremic syndrome (aHUS) with low penetrance. Factors driving immune-dysregulatory disease in individual mutation carriers have remained ill-understood. In addition to its role as a negative regulator of the complement system, CD46 modifies T cell-intrinsic metabolic adaptation and cytokine production. Comparative immunologic analysis of diseased vs. healthy CD46 mutation carriers has not been performed in detail yet. In this study, we comprehensively analyzed clinical, molecular, immune-phenotypic, cytokine secretion, immune-metabolic, and genetic profiles in healthy vs. diseased individuals carrying a rare, heterozygous CD46 mutation identified within a large single family. Five out of six studied individuals carried a CD46 gene splice-site mutation causing an in-frame deletion of 21 base pairs. One child suffered from aHUS and his paternal uncle manifested with adult-onset systemic lupus erythematosus (SLE). Three mutation carriers had no clinical evidence of CD46-related disease to date. CD4 + T cell-intrinsic CD46 expression was uniformly 50%-reduced but was comparable in diseased vs. healthy mutation carriers. Reconstitution experiments defined the 21-base pair-deleted CD46 variant as intracellularly-but not surface-expressed and haploinsufficient. Both healthy and diseased mutation carriers displayed reduced CD46-dependent T cell mitochondrial adaptation. Diseased mutation carriers had lower peripheral regulatory T cell (Treg) frequencies and carried potentially epistatic, private rare variants in other inborn errors of immunity (IEI)-associated proinflammatory genes, not found in healthy mutation carriers. In conclusion, low Treg and rare non-CD46 immune-gene variants may contribute to clinically manifest CD46 haploinsufficiency-associated immune-dysregulation., (© 2023. The Author(s).)

Introduction: We evaluated the anti-interleukin-36 receptor antibody spesolimab in patients with moderate-to-severe palmoplantar pustulosis (PPP)., Methods: This phase IIb trial comprised a loading dose period to week (W) 4, then maintenance dosing to W52. Patients were randomised 2:1:1:1:2 to subcutaneous spesolimab 3000 mg to W4 then 600 mg every 4 weeks (q4w), spesolimab 3000 mg to W4 then 300 mg q4w, spesolimab 1500 mg to W4 then 600 mg q4w, spesolimab 1500 mg to W4, 300 mg q4w to W16 then 300 mg every 8 weeks (q8w), or placebo switching to spesolimab 600 mg q4w at W16. The primary efficacy endpoint was percentage change from baseline in Palmoplantar Pustular Area and Severity Index (PPP ASI) at W16. Secondary endpoints included a Palmoplantar Pustular Physician's Global Assessment (PPP PGA) score of 0/1. Safety (including adverse events [AEs], local tolerability) was assessed., Results: 152 patients were treated. The primary endpoint was not met; mean differences for spesolimab versus placebo ranged from - 14.6% (95% confidence interval [CI]: - 31.5%, 2.2%) to - 5.3% (95% CI: - 19.1%, 8.6%); none reached significance. At W16, 23 (21.1%) and two (4.7%) patients in the combined spesolimab and placebo groups, respectively, achieved PPP PGA 0/1 (mean difference 16.4%; 95% CI: 3.8%, 25.7%), increasing to 59 (54.1%; combined spesolimab) and 12 (27.9%; placebo switch to spesolimab) patients at W52. Non-Asian patients had significant improvements in the primary endpoint (mean difference - 17.7%; nominal P = 0.0394) and PPP PGA 0/1 at W16 with spesolimab versus placebo. Rates of AEs and AE-related discontinuations were similar for spesolimab and placebo. Local tolerability events and injection-site reactions were more frequent with spesolimab than placebo., Conclusion: The primary objective to demonstrate a non-flat dose-response relationship and proof-of-concept was not achieved; improvements with spesolimab occurred in secondary endpoints and in non-Asian patients, indicating potential modest benefits. Spesolimab was generally well tolerated (ClinicalTrials.gov NCT04015518)., (© 2023. The Author(s).)

Thermal effects during bone surgery pose a common challenge, whether using mechanical tools or lasers. An irrigation system is a standard solution to cool the tissue and reduce collateral thermal damage. In bone surgery using Er:YAG laser, insufficient irrigation raises the risk of thermal damage, while excessive water lowers ablation efficiency. This study investigated the potential of optical coherence tomography to provide feedback by relating the temperature rise with the photo-thermal expansion of the tissue. A phase-sensitive optical coherence tomography system (central wavelength of λ=1.288 μm, a bandwidth of 60.9 nm and a sweep rate of 104.17 kHz) was integrated with an Er:YAG laser using a custom-made dichromatic mirror. Phase calibration was performed by monitoring the temperature changes (thermal camera) and corresponding cumulative phase changes using the phase-sensitive optical coherence tomography system during laser ablation. In this experiment, we used an Er:YAG laser with 230 mJ per pulse at 10 Hz for ablation. Calibration coefficients were determined by fitting the temperature values to phase later and used to predict the temperature rise for subsequent laser ablations. Following the phase calibration step, we used the acquired values to predict the temperature rise of three different laser-induced cuts with the same parameters of the ablative laser. The average root-mean-square error for the three experiments was measured to be around 4 °C. In addition to single-point prediction, we evaluated this method's performance to predict the tissue's two-dimensional temperature rise during laser osteotomy. The findings suggest that the proposed principle could be used in the future to provide temperature feedback for minimally invasive laser osteotomy., (© 2023. The Author(s).)

Background: Convolutional neural networks (CNNs) have outperformed dermatologists in classifying pigmented skin lesions under artificial conditions. We investigated, for the first time, the performance of three-dimensional (3D) and two-dimensional (2D) CNNs and dermatologists in the early detection of melanoma in a real-world setting., Methods: In this prospective study, 1690 melanocytic lesions in 143 patients with high-risk criteria for melanoma were evaluated by dermatologists, 2D-FotoFinder-ATBM and 3D-Vectra WB360 total body photography (TBP). Excision was based on the dermatologists' dichotomous decision, an elevated CNN risk score (study-specific malignancy cut-off: FotoFinder >0.5, Vectra >5.0) and/or the second dermatologist's assessment with CNN support. The diagnostic accuracy of the 2D and 3D CNN classification was compared with that of the dermatologists and the augmented intelligence based on histopathology and dermatologists' assessment. Secondary end-points included reproducibility of risk scores and naevus counts per patient by medical staff (gold standard) compared to automated 3D and 2D TBP CNN counts., Results: The sensitivity, specificity, and receiver operating characteristics area under the curve (ROC-AUC) for risk-score-assessments compared to histopathology of 3D-CNN with 95% confidence intervals (CI) were 90.0%, 64.6% and 0.92 (CI 0.85-1.00), respectively. While dermatologists and augmented intelligence achieved the same sensitivity (90%) and comparable classification ROC-AUC (0.91 [CI 0.80-1.00], 0.88 [CI 0.77-1.00]) with 3D-CNN, their specificity was superior (92.3% and 86.2%, respectively). The 2D-CNN (sensitivity: 70%, specificity: 40%, ROC-AUC: 0.68 [CI 0.46-0.90]) was outperformed by 3D CNN and dermatologists. The 3D-CNN showed a higher correlation coefficient for repeated measurements of 246 lesions (R = 0.89) than the 2D-CNN (R = 0.79). The mean naevus count per patient varied significantly (gold standard: 210 lesions; 3D-CNN: 469; 2D-CNN: 1324; p < 0.0001)., Conclusions: Our study emphasises the importance of validating the classification of CNNs in real life. The novel 3D-CNN device outperformed the 2D-CNN and achieved comparable sensitivity with dermatologists. The low specificity of CNNs and the lack of automated counting of TBP nevi currently limit the use of augmented intelligence in clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SEC has no conflict of interest. PC has no conflict of interest. LK has received speaking fees for a presentation sponsored by Boehringer Ingelheim. SH has no conflict of interest. MK has received speaking fees from Almirall and Sanofi outside of the current work. J-TM has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, BMS, Celgene, Eli Lilly, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, UCB. JSB has no conflict of interest. CFD has no conflict of interest. AG has no conflict of interest. CJ has no conflict of interest. LMS has no conflict of interest. JKP has no conflict of interest. ML has received research funding unrelated to the manuscript from Roche, Novartis, Molecular Partners, and Oncobit. AAN declares being a consultant and advisor and/or receiving speaking fees and/or grants and/or served as an investigator in clinical trials for AbbVie, Almirall, Amgen, Biomed, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, GSK, LEO Pharma, Janssen-Cilag, MSD, Novartis, Pfizer, Pierre Fabre Pharma, Regeneron, Sandoz, Sanofi, and UCB. LVM has served as advisor and/or received speaking fees and/or participated in clinical trials sponsored by Almirall, Amgen, Eli Lilly, MSD, Novartis, Pierre Fabre, Roche, and Sanofi outside of the current work., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Teledermatology is currently finding its place in modern health care worldwide as a rapidly evolving field., Objective: The aim of this study was to investigate the acceptance of teledermatology compared to in-person consultation from the perspective of patients and professionals., Methods: This multicenter, cross-sectional pilot study was performed at secondary and tertiary referral centers of dermatology in Switzerland from August 2019 to January 2020. A customized questionnaire addressing demographics and educational data, experience with telemedicine, and presumed willingness to replace in-patient consultations with teledermatology was completed by dermatological patients, dermatologists, and health care workers in dermatology., Results: Among a total of 664 participants, the ones with previous telemedicine experience (171/664, 25.8%) indicated a high level of overall experience with it (patients: 73/106, 68.9%, dermatologists: 6/8, 75.0%, and health care workers: 27/34, 79.4%). Patients, dermatologists, and health care workers were most likely willing to replace in-person consultations with teledermatology for minor health issues (353/512, 68.9%; 37/45, 82.2%; and 89/107, 83.2%, respectively). We observed a higher preference for telemedicine among individuals who have already used telemedicine (patients: P<.001, dermatologists: P=.03, and health care workers, P=.005), as well as among patients with higher educational levels (P=.003)., Conclusions: This study indicates that the preference for teledermatology has a high potential to increase over time since previous experience with telemedicine and a higher level of education were associated with a higher willingness to replace in-patient consultations with telemedicine. We assume that minor skin problems are the most promising issue in teledermatology. Our findings emphasize the need for dermatologists to be actively involved in the transition to teledermatology., Trial Registration: ClinicalTrials.gov NCT04495036; https://classic.clinicaltrials.gov/ct2/show/NCT04495036., (©Lara Valeska Maul, Anna Sophie Jahn, Gustavo S P Pamplona, Markus Streit, Lorena Gantenbein, Simon Müller, Mia-Louise Nielsen, Christian Greis, Alexander A Navarini, Julia-Tatjana Maul. Originally published in JMIR Dermatology (http://derma.jmir.org), 11.08.2023.)

Background: Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step., Objectives: This study explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance., Methods: Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T-cell-intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type versus mutant LIG4 were performed in LIG4 knockout Jurkat T cells, and DNA damage tolerance was subsequently assessed., Results: A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia, and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naive CD4 + T cells and low TCR-Vα7.2 + T cells, while T-/B-cell receptor repertoires showed only mild alterations. Cohort screening identified 2 other nonrelated patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T-cell-intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient., Conclusions: This study provides evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest The full list is provided in Appendix S1 (see Supporting Information).

Acute generalized exanthematous pustulosis (AGEP) is a rare, acute, severe cutaneous adverse reaction mainly attributed to drugs, although other triggers, including infections, vaccinations, ingestion of various substances, and spider bites, have also been described. AGEP is characterized by the development of edema and erythema followed by the eruption of multiple punctate, non-follicular, sterile pustules and subsequent desquamation. AGEP typically has a rapid onset and prompt resolution within a few weeks. The differential diagnoses for AGEP are broad and include infectious, inflammatory, and drug-induced etiologies. Diagnosis of AGEP depends on both clinical and histologic criteria, as cases of overlap with other disease processes have been reported. Management includes removal of the offending drug or treatment of the underlying cause, if necessary, and supportive care, as AGEP is a self-limited disease. This review aims to provide an overview and update on the epidemiology, pathogenesis, reported precipitating factors, differentials, diagnosis, and management of AGEP., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Pruritus is a common symptom of cutaneous graft-versus-host disease (GVHD) following haematopoietic stem cell transplantation (HSCT). However, little is known about its prevalence, pathophysiology, perceptual characteristics, impact on quality of life and response to antipruritic therapies. The aim of this review was to determine the current knowledge on pruritus in cutaneous GVHD. The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. Of the 338 studies screened, 13 were included. The prevalence of pruritus in cutaneous GVHD was reported in three studies, ranging from 37.0% to 63.8%. Only four trials used pruritus assessment tools. There was little or no information on the intensity of pruritus, its qualitative perception, the location of pruritus and the impact of pruritus on quality of life. Antipruritic treatments for GVHD-associated pruritus were mentioned in five studies (38.5%), including topical ointments (steroids, tacrolimus and calcipotriene), broadband UVB, systemic antihistamines and oral ursodeoxycholic acid. In conclusion, pruritus in cutaneous GVHD appears to be common, but very little is known about the pathophysiology, impact on quality of life and effective treatment options. Basic research and controlled clinical trials are warranted to improve knowledge and management of this important issue., (© 2023 European Academy of Dermatology and Venereology.)