"I Was Almost in Disbelief" - Qualitative Analysis of Experiences and Expectations Among Psoriasis Patients Undergoing Biologic Treatment with Secukinumab.

Purpose: Psoriasis is a highly debilitating chronic inflammatory disease. Increased understanding of its pathophysiology has enabled development of targeted treatments such as biologics. Several medical treatments have been shown to be influenced by patients' experiences and expectations. However, only little is known about patients' experiences with and expectations towards biologics. Our objectives were to identify patients' treatment experiences and treatment expectations and assess their trajectories over the course of treatment with the IL-17A inhibitor secukinumab. Moreover, we aimed to document effects of psoriasis, factors that influence symptomatology, and prior treatment experiences. Patients and Methods: We conducted semi-structured interviews with n = 24 patients with moderate-to-severe plaque psoriasis and employed a qualitative content analysis to derive thematic and evaluative codes. Findings were validated via peer debriefings with experienced dermatologists. Results: Patients reported burdensome physical and psychological psoriasis symptoms and identified factors that can improve or worsen symptomatology, including stress and self-efficacy. Prior treatment experiences were mostly negative. Past barriers to effective treatment included time constraints or limited access. Concerning secukinumab, patients initially expected complete to partial remission of symptoms and occurrence or absence of side effects. Closer inspection of expectations and experiences revealed three trajectories. For most patients, initial expectations were met and future expectations remained unchanged. For the other patients, however, the experience did not match their initial expectation. One group then adapted their future expectations according to their experience, while the other group did not. Conclusion: To our knowledge, this is the first qualitative study to assess expectations towards treatment effectiveness and side effects, their trajectories, and interplay with experiences among psoriasis patients. Our findings highlight the value of further research on the subject in order to optimize care for psoriasis patients and to learn more about the trajectories and influence of treatment expectations in general.

Patients' expectations towards a certain treatment can influence how well it will work and whether side effects occur or not. Such effects have been shown for a wide range of conditions, including dermatological ones. For patients suffering from psoriasis, a chronic inflammatory skin disease, modern biologics offer promising treatment options. Therefore, modern biologics are likely associated with high expectations by patients. Yet, the roles of treatment expectations and the experiences of patients undergoing biologic treatment have only received little attention to date. With this qualitative study, we aimed to understand patients' perspectives on these treatments, the symptoms they suffer from, expectations towards treatment effectiveness and side effects as well as treatment experiences in the past and over the course of treatment with a modern biologic. To this end, we conducted and transcribed interviews with 24 patients after several months of biologic treatment. We then analyzed interview transcripts to determine underlying categories and summarized these in a common framework. We found that patients' debilitating physical and psychological symptoms were often not well controlled in past treatments. Still, patients had positive expectations with regard to biologic treatment. For a large group of patients, their actual experiences met their expectations, leaving them with unchanged expectations for the future. Another important finding was the good understanding of factors influencing their symptomatology that patients had, like stress and self-efficacy. The reported findings may aid doctors in their clinical work, to further improve care for psoriasis patients.

Antibody responses after sequential vaccination with PCV13 and PPSV23 in patients with moderate to severe plaque psoriasis under immunosuppressive therapy.

A crucial step in lowering the risk of invasive pneumococcal illness in high-risk populations, such as individuals with plaque psoriasis, is pneumococcal vaccination. The serologic response to the sequential vaccination with Prevenar 13 (PCV13) and Pneumovax 23 (PPSV23) in psoriasis patients under immunosuppressive therapy is still poorly characterized despite national recommendations suggesting vaccination for immunocompromised patients. In this prospective study, we investigated the serological response in 57 patients under active systemic treatment for moderate to severe plaque psoriasis who underwent sequential vaccination with PCV13 followed by PPSV23. Our analysis focused on global and serotype-specific anti-pneumococcal antibody responses over a 7-month period post-vaccination. Our findings reveal a robust serological response in patients with plaque psoriasis under systemic therapy. When comparing our results with a cohort of kidney transplant recipients who completed a similar sequential vaccination protocol, psoriasis patients showed higher antibody concentrations. In psoriasis patients, the mean levels of all global antibody classes tested (IgG, IgG2, IgA, IgM) increased more than 4-fold (P < 0.0001) and serotype-specific antibodies more than 1.9-fold (P < 0.01). In addition to providing strong evidence of the safety and effectiveness of sequential pneumococcal vaccination in individuals with plaque psoriasis, our work sheds light on the complex interactions that exist between immunosuppressive treatment, vaccination schedule, and antibody responses in various risk groups. IMPORTANCE: To protect against severe courses of infection with Streptococcus pneumoniae, the national guidelines recommend sequential vaccination for these patients. However, there are only studies on the efficacy of a single administration of these vaccines in this particular risk group. The immunological responses to the vaccine were correlated with clinical patient data. In summary, our study shows for the first time that sequential vaccination is immunogenic in patients with moderate to severe plaque psoriasis.

Comparison of visual diagnostic accuracy of dermatologists practicing in Germany in patients with light skin and skin of color.

Visual clinical diagnosis of dermatoses in people of color (PoC) is a considerable challenge in daily clinical practice and a potential cause of misdiagnosis in this patient cohort. The study aimed to determine the difference in visual diagnostic skills of dermatologists practicing in Germany in patients with light skin (Ls) and patients with skin of color (SoC) to identify a potential need for further education. From April to June 2023, German dermatologists were invited to complete an online survey with 24 patient photographs depicting 12 skin diseases on both Ls and SoC. The study's primary outcomes were the number of correctly rated photographs and the participants' self-assessed certainty about the suspected visual diagnosis in Ls compared to SoC. The final analysis included surveys from a total of 129 dermatologists (47.8% female, mean age: 39.5 years). Participants were significantly more likely to correctly identify skin diseases by visual diagnostics in patients with Ls than in patients with SoC (72.1% vs. 52.8%, p ≤ 0.001, OR 2.28). Additionally, they expressed higher confidence in their diagnoses for Ls than for SoC (73.9 vs. 61.7, p ≤ 0.001). Therefore, further specialized training seems necessary to improve clinical care of dermatologic patients with SoC.

Psoriasis as a Systemic Disease.

BACKGROUND: Psoriasis was long regarded as an inflammatory disease limited to the skin. Data from dermatologic, rheumatologic and cardiologic research now show it to be a systemic disease, for which the term psoriatic disease is used. METHODS: This paper is based on a selective literature search with special attention to the findings of clinical trials and other current publications, as well as the recommendations of international guidelines. RESULTS: Immunologically mediated inflammation of the skin, arteries, bones, and joints is a central feature of psoriatic disease. Other diseases that are known to be associated with psoriatic disease include hypertension, metabolic syndrome, and depression. The main risk factor for the development of psoriatic disease is obesity, which also increases the likelihood of psoriatic arthritis. The main known trigger factors are stress, infection, and, less commonly, medication. Psoriatic disease is characterized by complex genetics and by a characteristic pattern of inflammation that involves elements of both innate and acquired immunity and, in particular, the cytokines interleukin 17 and 23. The inflammatory processes underlying psoriatic disease can now be targeted with modern biologic and other therapies. CONCLUSION: In view of the complexity of psoriatic disease, structured management is now recommended so that physicians and patients can work together to determine the optimal treatment strategy.

Discontinuation of Fumaric Acid Esters is Affected by Depressive Symptomatology: A Retrospective Analysis.

Fumaric acid esters (FAEs) remain a widespread therapy option for moderate-to-severe psoriasis. However, drug survival of FAEs is limited by adverse events (AEs) or inadequate treatment response. Depressive disturbances are highly prevalent in psoriasis patients and are hypothesized to be associated with the reporting of AEs and therapy discontinuation. This study's aim was to analyze whether psoriasis patients with comorbid depressive symptomatology are more likely to discontinue treatment with FAEs due to AEs and/or inadequate treatment response. Data were retrospectively extracted from the records of patients starting therapy with FAEs in the Department of Dermatology, University Hospital Essen, Germany between 2017 and 2022, covering the first 52 weeks of treatment. Psoriasis severity and depressive symptomatology, as well as AEs and therapy discontinuation, were analyzed. Psoriasis patients (N = 95, 47.37% female) with depressive symptomatology (42.11%) were more likely to discontinue therapy due to patient-reported AEs, while the total number of reported AEs was not associated with depression. The results support the hypothesis that among psoriasis patients with depressive symptoms, the associated introspection and somatization may result in increased sensitivity for AEs and thus in quicker therapy discontinuation. In these patients, the occurrence of nocebo effects should be minimized, e.g. by special communication techniques.

Federated Learning for Decentralized Artificial Intelligence in Melanoma Diagnostics.

Importance: The development of artificial intelligence (AI)-based melanoma classifiers typically calls for large, centralized datasets, requiring hospitals to give away their patient data, which raises serious privacy concerns. To address this concern, decentralized federated learning has been proposed, where classifier development is distributed across hospitals. Objective: To investigate whether a more privacy-preserving federated learning approach can achieve comparable diagnostic performance to a classical centralized (ie, single-model) and ensemble learning approach for AI-based melanoma diagnostics. Design, Setting, and Participants: This multicentric, single-arm diagnostic study developed a federated model for melanoma-nevus classification using histopathological whole-slide images prospectively acquired at 6 German university hospitals between April 2021 and February 2023 and benchmarked it using both a holdout and an external test dataset. Data analysis was performed from February to April 2023. Exposures: All whole-slide images were retrospectively analyzed by an AI-based classifier without influencing routine clinical care. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) served as the primary end point for evaluating the diagnostic performance. Secondary end points included balanced accuracy, sensitivity, and specificity. Results: The study included 1025 whole-slide images of clinically melanoma-suspicious skin lesions from 923 patients, consisting of 388 histopathologically confirmed invasive melanomas and 637 nevi. The median (range) age at diagnosis was 58 (18-95) years for the training set, 57 (18-93) years for the holdout test dataset, and 61 (18-95) years for the external test dataset; the median (range) Breslow thickness was 0.70 (0.10-34.00) mm, 0.70 (0.20-14.40) mm, and 0.80 (0.30-20.00) mm, respectively. The federated approach (0.8579; 95% CI, 0.7693-0.9299) performed significantly worse than the classical centralized approach (0.9024; 95% CI, 0.8379-0.9565) in terms of AUROC on a holdout test dataset (pairwise Wilcoxon signed-rank, P < .001) but performed significantly better (0.9126; 95% CI, 0.8810-0.9412) than the classical centralized approach (0.9045; 95% CI, 0.8701-0.9331) on an external test dataset (pairwise Wilcoxon signed-rank, P < .001). Notably, the federated approach performed significantly worse than the ensemble approach on both the holdout (0.8867; 95% CI, 0.8103-0.9481) and external test dataset (0.9227; 95% CI, 0.8941-0.9479). Conclusions and Relevance: The findings of this diagnostic study suggest that federated learning is a viable approach for the binary classification of invasive melanomas and nevi on a clinically representative distributed dataset. Federated learning can improve privacy protection in AI-based melanoma diagnostics while simultaneously promoting collaboration across institutions and countries. Moreover, it may have the potential to be extended to other image classification tasks in digital cancer histopathology and beyond.

Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma.

Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists' decisions has not yet been evaluated. Building upon previous research, we introduce an XAI system that provides precise and domain-specific explanations alongside its differential diagnoses of melanomas and nevi. Through a three-phase study, we assess its impact on dermatologists' diagnostic accuracy, diagnostic confidence, and trust in the XAI-support. Our results show strong alignment between XAI and dermatologist explanations. We also show that dermatologists' confidence in their diagnoses, and their trust in the support system significantly increase with XAI compared to conventional AI. This study highlights dermatologists' willingness to adopt such XAI systems, promoting future use in the clinic.

[Inpatient care for psoriasis: quo vadis?-A retrospective study at the University Hospitals of Aachen, Bonn, and Essen from 2010 to 2019]. / Stationäre Psoriasistherapie: Quo vadis? ­ Eine retrospektive Studie an den Universitätskliniken Aachen, Bonn und Essen im Zeitraum von 2010 bis 2019.

INTRODUCTION: A number of new, highly effective biologic drugs for psoriasis have been approved over the past few decades, which raises the question whether psoriasis is still a disease that requires inpatient treatment. METHODS: We conducted a retrospective analysis of inpatient data between 2010 and 2019 (the last 10 years prior to the coronavirus disease 2019 [COVID-19] pandemic) from three German dermatology departments at university hospitals (Aachen, Bonn, and Essen). The data collected included age, gender, the primary admission diagnosis, length of stay (LOS), and number of all comorbidities recorded during hospitalization. RESULTS: A total of 59,500 patients were admitted to the three dermatological departments in the defined 10-year period. Of these patients, psoriasis (L40.-) was the main diagnosis for 4322 (7.3%). An almost continuous increase was observed in all inpatient dermatological cases, which was as high as 27% in 2016 compared to 2010. For psoriasis patients, the most substantial increase in the number of admissions was reached in 2016 compared to 2010 and was as high as 45%. While there was a statistically significant reduction of the mean LOS for all dermatological inpatient cases from 6.4 ± 6.6 days in 2010 to 5.1 ± 4.6 days in 2019 (p < 0.001), the decrease in 2019 compared to 2010 (from 12.2 ± 5.5 to 8.9 ± 3.3 days) was significantly greater for the inpatient psoriasis patients compared to the inpatient population overall (p < 0.001). CONCLUSIONS: Our data show a stable need for inpatient psoriasis facilities in Germany. Further analysis of hospital admissions after the end of the COVID-19 pandemic is needed to understand the ongoing influence of modern systemic treatment options on inpatient psoriasis care in Germany.

Interleukin 17 signaling supports clinical benefit of dual CTLA-4 and PD-1 checkpoint inhibition in melanoma.

Recent studies suggest that BRAFV600-mutated melanomas in particular respond to dual anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) immune checkpoint inhibition (ICI). Here we identified an over-representation of interleukin (IL)-17-type 17 helper T (TH17) gene expression signatures (GES) in BRAFV600-mutated tumors. Moreover, high baseline IL-17 GES consistently predicted clinical responses in dual-ICI-treated patient cohorts but not in mono anti-CTLA-4 or anti-PD-1 ICI cohorts. High IL-17 GES corresponded to tumor infiltration with T cells and neutrophils. Accordingly, high neutrophil infiltration correlated with clinical response specifically to dual ICI, and tumor-associated neutrophils also showed strong IL-17-TH17 pathway activity and T cell activation capacity. Both the blockade of IL-17A and the depletion of neutrophils impaired dual-ICI response and decreased T cell activation. Finally, high IL-17A levels in the blood of patients with melanoma indicated a higher global TH17 cytokine profile preceding clinical response to dual ICI but not to anti-PD-1 monotherapy, suggesting a future role as a biomarker for patient stratification.

How familiar are German dermatologists with placebo and nocebo effects and to what extent are these targeted in clinical practice: A survey within the dermatological community.

BACKGROUND: Every medical treatment inevitably comprises not only physiological, but also psychological components, reflected by placebo and nocebo effects, which significantly affect treatment outcome. However, the extent of knowledge on the mechanisms steering placebo and nocebo effects in the dermatological community in Germany is currently unclear. OBJECTIVES: To assess the state of knowledge about placebo and nocebo effects in the German dermatological community, to evaluate whether this knowledge is already being used in clinical practice, and to investigate whether German dermatologists are interested in learning more about the topic. METHODS: German Dermatologists, the majority working in their own practice, were asked to fill in an online survey addressing the knowledge about placebo and nocebo effects and the feasibility of special techniques to enhance placebo and minimize nocebo effects within the clinical routine. RESULTS: N = 154 complete (79%) or partial (21%) responses to the survey were recorded in the online database and included in the analysis. All participants reported to know what the placebo effect is and 59.7% (74/124) indicated that they already had experience with prescribing or recommending a treatment without active substances. In contrast, only 62.0% (80/129) stated to know what the nocebo effect is. Participants showed a rather superficial knowledge regarding placebo and nocebo mechanisms. The majority of participants (76.7%, 99/129) expressed their willingness to be further educated about the underlying mechanisms mediating placebo and nocebo effects and the possible application in clinical practice. CONCLUSIONS: The current survey offers a so far unique insight into the state of knowledge of German dermatologists on placebo and nocebo effects. The results indicate a need for education about this topic. Encouragingly, however, German dermatologists considered communication strategies to maximize placebo and reduce nocebo effects and expressed motivation to be trained to implement these strategies in everyday clinical practice.

[Randomized clinical trial of compression therapy of the lower legs in patients with psoriasis]. / Randomisierte klinische Studie zur Kompressionstherapie der Unterschenkel bei Patienten mit Psoriasis.

BACKGROUND: Psoriatic plaques at the distal lower extremities are notoriously treatment resistant. Medical compression therapy could potentially be a useful supplementary therapeutic measure at this site. However, there is concern that the Koebner phenomenon may cause a worsening of the skin condition. Therefore, the purpose of this study was to investigate the effects of compression therapy on psoriatic plaques in the presence of coexisting edema of the lower legs. PATIENTS AND METHODS: Compression therapy was performed in addition to standard of care on one lower leg for 4 weeks (half-side test) in patients with psoriatic plaques and edema on both lower legs. The primary endpoint of the study was clinical response of the psoriatic plaques on the lower legs measured with the lesion severity score (LSS) and the locally affected body surface area in a side-by-side comparison at week 4 compared with baseline. Secondary endpoints were related to patient-reported outcomes. RESULTS: Data from 30 patients were included in the analysis. In the descriptive analysis, the mean LSS results and the subjective pain reported by the patients showed a slightly greater improvement on the compressed lower leg compared with the non-compressed lower leg. None of the patients showed evidence of the Koebner phenomenon induced by compression therapy. CONCLUSION: This is the first clinical study that systematically investigated the impact of compression therapy on psoriatic plaques. During the study period of 4 weeks, there was no significant improvement in psoriatic plaques; however, there was also no evidence of worsening of the skin condition. Thus, anti-edematous compression therapy can be performed in psoriasis patients without causing complications if basic contraindications are considered.

COVID-19 vaccination in psoriasis patients receiving systemic treatment: A prospective single-center study.

Background: The rate of seroconversion after COVID-19 vaccination in patients with moderate to severe psoriasis requiring systemic treatment is poorly understood. Objectives: The aim of this prospective single-center cohort study performed between May 2020 and October 2021 was to determine the rate of seroconversion after COVID-19 vaccination in patients under active systemic treatment for moderate to severe psoriasis. Methods: Inclusion criteria were systemic treatment for moderate to severe psoriasis, known COVID-19 vaccination status, and repetitive anti-SARS-CoV-2-S IgG serum quantification. The primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination. Results: 77 patients with a median age of 55.9 years undergoing systemic treatment for moderate to severe psoriasis were included. The majority of patients received interleukin- (n=50, 64.9%) or tumor necrosis factor (TNF)-α inhibitors (n=16, 20.8%) as systemic treatment for psoriasis; nine patients (11.7%) were treated with methotrexate (MTX) monotherapy, and one patient each received dimethyl fumarate (1.3%), respectively apremilast (1.3%). All included patients completed COVID-19 vaccination with two doses over the course of the study. Serum testing revealed that 74 patients (96.1%) showed an anti-SARS-CoV-2-S IgG seroconversion. While all patients on IL-17A, -12 or -12/23 inhibitors (n=50) achieved seroconversion, three of 16 patients (18.8%) receiving MTX and/or a TNF-α inhibitor as main anti-psoriatic treatment did not. At follow-up, none of the patients had developed symptomatic COVID-19 or died from COVID-19. Conclusions: Anti-SARS-CoV-2-S IgG seroconversion rates following COVID-19 vaccination in psoriasis patients under systemic treatment were high. An impaired serological response, however, was observed in patients receiving MTX and/or TNF-α inhibitors, in particular infliximab.

COVID-19 vaccination in advanced skin cancer patients receiving systemic anticancer treatment: A prospective singlecenter study investigating seroconversion rates.

Background: COVID-19 vaccination reduces risk of SARS-CoV-2 infection, COVID-19 severity and death. However, the rate of seroconversion after COVID-19 vaccination in cancer patients requiring systemic anticancer treatment is poorly investigated. The aim of the present study was to determine the rate of seroconversion after COVID-19 vaccination in advanced skin cancer patients under active systemic anticancer treatment. Methods: This prospective single-center study of a consecutive sample of advanced skin cancer patients was performed from May 2020 until October 2021. Inclusion criteria were systemic treatment for advanced skin cancer, known COVID-19 vaccination status, repetitive anti-SARS-CoV-2-S IgG serum quantification and first and second COVID-19 vaccination. Primary outcome was the rate of anti-SARS-CoV-2-S IgG seroconversion after complete COVID-19 vaccination. Results: Of 60 patients with advanced skin cancers, 52 patients (86.7%) received immune checkpoint inhibition (ICI), seven (11.7%) targeted agents (TT), one (1.7%) chemotherapy. Median follow-up time was 12.7 months. During study progress ten patients had died from skin cancer prior to vaccination completion, six patients were lost to follow-up and three patients had refused vaccination. 41 patients completed COVID-19 vaccination with two doses and known serological status. Of those, serum testing revealed n=3 patients (7.3%) as anti-SARS-CoV-2-S IgG positive prior to vaccination, n=32 patients (78.0%) showed a seroconversion, n=6 patients (14.6%) did not achieve a seroconversion. Patients failing serological response were immunocompromised due to concomitant hematological malignancy, previous chemotherapy or autoimmune disease requiring immunosuppressive comedications. Immunosuppressive comedication due to severe adverse events of ICI therapy did not impair seroconversion following COVID-19 vaccination. Of 41 completely vaccinated patients, 35 (85.4%) were under treatment with ICI, five (12.2%) with TT, and one (2.4%) with chemotherapy. 27 patients (65.9%) were treated non adjuvantly. Of these patients, 13 patients had achieved objective response (complete/partial response) as best tumor response (48.2%). Conclusion and relevance: Rate of anti-SARS-CoV-2-S IgG seroconversion in advanced skin cancer patients under systemic anticancer treatment after complete COVID-19 vaccination is comparable to other cancer entities. An impaired serological response was observed in patients who were immunocompromised due to concomitant diseases or previous chemotherapies. Immunosuppressive comedication due to severe adverse events of ICI did not impair the serological response to COVID-19 vaccination.

Model soups improve performance of dermoscopic skin cancer classifiers.

BACKGROUND: Image-based cancer classifiers suffer from a variety of problems which negatively affect their performance. For example, variation in image brightness or different cameras can already suffice to diminish performance. Ensemble solutions, where multiple model predictions are combined into one, can improve these problems. However, ensembles are computationally intensive and less transparent to practitioners than single model solutions. Constructing model soups, by averaging the weights of multiple models into a single model, could circumvent these limitations while still improving performance. OBJECTIVE: To investigate the performance of model soups for a dermoscopic melanoma-nevus skin cancer classification task with respect to (1) generalisation to images from other clinics, (2) robustness against small image changes and (3) calibration such that the confidences correspond closely to the actual predictive uncertainties. METHODS: We construct model soups by fine-tuning pre-trained models on seven different image resolutions and subsequently averaging their weights. Performance is evaluated on a multi-source dataset including holdout and external components. RESULTS: We find that model soups improve generalisation and calibration on the external component while maintaining performance on the holdout component. For robustness, we observe performance improvements for pertubated test images, while the performance on corrupted test images remains on par. CONCLUSIONS: Overall, souping for skin cancer classifiers has a positive effect on generalisation, robustness and calibration. It is easy for practitioners to implement and by combining multiple models into a single model, complexity is reduced. This could be an important factor in achieving clinical applicability, as less complexity generally means more transparency.