Prevalence of hypersensitivity reactions in various forms of mastocytosis: A pilot study of 2485 adult patients with mastocytosis collected in the ECNM registry.

BACKGROUND: Hypersensitivity reactions (HR) are common in mastocytosis. However, little is known about triggers and risk factors. The registry of the European Competence Network on Mastocytosis (ECNM) enables reliable studies in a larger cohort of mastocytosis patients. We assessed prevalence, triggers and risk factors of HR in adults with mastocytosis in the ECNM registry. METHODS: Data were collected in 27 ECNM centers. We analyzed potential triggers (Hymenoptera venoms, food, drug, inhalant and others) and risk factors at diagnosis and during follow-up. The study group consisted of 2485 adults with mastocytosis, 1379 women (55.5%) and 1106 men (44.5%). Median age was 48.2 years (range 18-91 years). RESULTS: Nine hundred and forty eight patients (38.1%) reported one or more HR`. Most common triggers were Hymenoptera venoms in cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), whereas in advanced SM (advSM), most common elicitors were drugs, including nonsteroidal anti-inflammatory agents and penicillin. In multivariate analyses, tryptase level < 90 ng/mL, <15% infiltration by mast cells in bone marrow biopsy-sections, and diagnosis of ISM were identified as independent risk factors for HR. For drug-induced HR, prominent risk factors were advSM and high tryptase levels. New reactions were observed in 4.8% of all patients during 4 years follow-up. CONCLUSIONS: HR are mainly triggered by Hymenoptera venoms in patients with CM and ISM and by drugs in patients with advSM. Tryptase levels <90 ng/mL, mast cell bone marrow infiltration <15%, and WHO category ISM are predictors of HR. New HR occur in 4.8% of all patients within 4 years.

Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomized controlled trial.

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. OBJECTIVES: To assess the clinical efficacy of IA in addition to best medical treatment (BMT). METHODS: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods. RESULTS: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). CONCLUSIONS: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoantibody-driven blistering diseases, which present with erosions or blisters on skin and/or mucous membranes. Treatment is based on long-term immunosuppressive agents. Immunoadsorption (IA) is a procedure that removes autoantibodies from the blood and has emerged as a fast-acting treatment option for pemphigus.We conducted a trial comparing best medical treatment (BMT) (prednisolone 1.0 mg kg per day plus azathioprine or mycophenolate) with best medical treatment plus IA (BMT + IA). A total of 26 centres from Germany and Austria recruited 72 patients with active pemphigus (34 women and 38 men, aged 42­72 years) who were randomly allocated in a ratio of 1 : 1 to the treatment groups.Following inclusion of 72 patients in the BMT + IA (n = 34) or BMT (n = 38) groups, the study ended prematurely owing to safety concerns. The main outcome, time to complete remission (relief of all symptoms) while still receiving therapy, was not significantly different for the two groups. In contrast, the cumulative dose of prednisolone was significantly lower in the BMT + IA compared with BMT alone. In an additional analysis, patients with more extensive pemphigus showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group. While more adverse events were observed in the BMT group (29 vs. 25), severe adverse events were more frequent in the BMT + IA group (17 vs. 11). In this study, IA did not show a shorter time to clinical remission, but a prednisolone-sparing effect was observed. In patients with extensive pemphigus, adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Unmet Needs in Darier's Disease from a Patient's Perspective: Lessons Learnt from the German Registry.

The MDHHgermany registry was initiated to characterize the "real-life" situation of affected individuals with Darier's disease (DD; Morbus Darier, MD) and Hailey-Hailey disease (HH), including their treatment and healthcare. To gain deeper insights into medical care of patients with DD, various aspects such as demographics, subjective symptoms, patient satisfaction with medical care, past and current therapies were explored. Patients with diagnosed DD were included. Subjective symptoms such as itch, pain and burning sensation were assessed. Individual therapy goals were recorded and patients assessed previous/current therapies along with satisfaction of medical care and treatment. A total of 55 patients were recruited; 47 patients were eligible for the analysis. Pruritus was rated the most bothersome symptom. Some 42.6% had not received systemic treatment so far or systemic therapies were rated ineffective (32.6%). Most commonly oral retinoids were prescribed, followed by corticosteroids. Patient satisfaction with medical care and treatment proved to be mediocre. This "real-life" data show an alarming unmet need regarding patients' satisfaction with medical care and treatment, evidenced by the reported lack of disease control. Further studies and interventions are needed to improve the spectrum of available therapies. MDHHgermany provides a foundational platform for future clinical trials, epidemiological studies, and pathophysiological analyses.

Next generation mycological diagnosis: Artificial intelligence-based classifier of the presence of Malassezia yeasts in tape strip samples.

BACKGROUND: Malassezia yeasts are almost universally present on human skin worldwide. While they can cause diseases such as pityriasis versicolor, their implication in skin homeostasis and pathophysiology of other dermatoses is still unclear. Their analysis using native microscopy of skin tape strips is operator dependent and requires skill, training and significant amounts of hands-on time. OBJECTIVES AND METHODS: To standardise and improve the speed and quality of diagnosis of Malassezia in skin tape strip samples, we sought to create an artificial intelligence-based algorithm for this image classification task. Three algorithms, each using different internal architectures, were trained and validated on a manually annotated dataset of 1113 images from 22 samples. RESULTS: The Vision Transformer-based algorithm performed the best with a validation accuracy of 94%, sensitivity of 94.0% and specificity of 93.5%. Visualisations providing insight into the reasoning of the algorithm were presented and discussed. CONCLUSION: Our image classifier achieved very good performance in the diagnosis of the presence of Malassezia yeasts in tape strip samples of human skin and can therefore improve the speed and quality of, and access to this diagnostic test. By expanding data sources and explainability, the algorithm could also provide teaching points for more novice operators in future.

Implementing well-being in the management of psoriasis: An expert recommendation.

Psoriasis causes detriment in a person's physical, mental and social health which impairs their quality of life (QoL). However, the current psoriasis management may not adequately address all relevant health domains. Since the goal of healthcare is to restore or maintain health, health outcomes should include all areas of the patient's overall health. Life satisfaction, QoL and patient well-being are essential to a comprehensive approach to the disease. With the inclusion of more people-centred policies, care of patients with psoriasis should evolve towards a holistic and integrated assessment of the disease impact, including subjective measures of well-being in order to encompass all aspects of health. The main objective of this expert review is to give the concept of well-being a place as an entity within the holistic therapeutic approach for patients with psoriasis. Identifying and defining common goals beyond the skin with the patient and testing them throughout the course of treatment will benefit and enhance treatment success. We propose a series of recommendations for application in clinical practice, providing tangible clinical guidance for implementing well-being in the management of psoriasis. Among the recommendations are the need to initially listen to the patient, to know their level of empowerment or what they want to achieve, their preferences in decision making, the evaluation of not only the physical but also the emotional impact of the disease (well-being), the definition of the aspects that can generate a cumulative deterioration of the disease throughout life, and a continuous assessment of the patient's preferences with the opinion of the expert clinician and the integration of the knowledge of external clinical evidence.

Burden of atopic dermatitis in Europe: A population-centred approach leveraging web search data in 21 European countries.

BACKGROUND: The complexity, high prevalence, and substantial personal and socioeconomic burden collectively render atopic dermatitis (AD) a major public health concern. Using crowdsourced Internet data has the potential to provide unique insights into this concern, as demonstrated by several previous studies. However, a comprehensive comparison across European countries remains lacking. OBJECTIVES: The study aimed to investigate AD-related web searches across Europe to assess spatiotemporal variations and associations between disease-related and external factors. METHODS: AD-related web search data were extracted for 21 European countries between February 2019 and January 2023. Descriptive analysis and autocorrelation functions were performed to examine spatiotemporal patterns. Correlations (r) were used to evaluate the associations between web searches and disease-related, socioeconomic and meteorological data. RESULTS: Over 241 million AD-related web searches were identified, with search volume varying substantially among European countries (p < 0.001) and correlating with AD prevalence and disease burden (both r = 0.51, p = 0.019). Search volume increased between 2019 and 2023 in all countries and seasonally peaked in January and March. Negative correlations with median population age (r = -0.46, p = 0.039), number of general practitioners (r = -0.29, p = 0.226) and specialists (r = -0.27, p = 0.270) were observed. Moderate to strong correlations were found between search volume and cold, humid and windy weather with fewer sunshine hours, while higher online interest typically occurred 1-3 months after such weather conditions. CONCLUSION: The study highlights the great potential of online crowdsourced data analysis, for example, to investigate the impact of climate change or to identify unmet needs at a population level. Furthermore, the growing online interest in AD and the corresponding seasonal peaks emphasize the necessity of adapting treatment plans, intensifying public health campaigns, and disseminating reliable online information by governments and healthcare providers, especially during these periods.

The socio-economic burden of H1-antihistamine-refractory chronic spontaneous urticaria in Germany.

BACKGROUND AND STUDY AIM: Data from the AWARE study (A Worldwide Antihistamine-Refractory chronic urticaria patient Evaluation) illustrate a substantial disease burden in German patients with H1-antihistamine (-H1-AH)-refractory chronic spontaneous urticaria (CSU). Detrimental effects on patients' quality of life, poor disease control and impairment in the ability to work and perform other daily activities are reported. Based on these findings, this study aims to quantify the epidemiological and socio-economic burden of H1-AH-refractory CSU in Germany. METHODS: To determine the epidemiological burden of H1-AH-refractory CSU, the age- and gender-specific prevalence of CSU and the proportion of H1-AH-refractory patients in Germany anonymized data from the InGef research database have been used. In a second step, the socio-economic burden in terms of lost numbers of hours in paid and unpaid work was calculated by extrapolating the age- and gender-specific work productivity and activity impairment (WPAI) observed in AWARE to the H1-AH-refractory CSU population in Germany. Finally, productivity losses in paid and unpaid work were monetized using the human capital and the friction cost approach respectively. Moreover, socio-economic burden was calculated depending on symptom control of the patients (measured by urticaria control test [UCT]). RESULTS: In Germany, over 203,000 patients (20 years or older) had H1-AH-refractory CSU in 2018. The avoided lost paid and unpaid work hours attributable to H1-AH-refractory CSU summed up to over 100 million. Overall, the socio-economic burden of H1-AH-refractory CSU in monetary terms was evaluated at € 2.2 billion and the majority of this was due to unpaid work loss. Patients with poor disease control, as indicated by UCT score < 12, were more likely to suffer from high impairment than patients with controlled disease, resulting in a higher socio-economic burden. CONCLUSION: The results of our analyses picture the substantial socio-economic burden of H1-AH-refractory CSU and therefore the tremendous impact it has on daily lives of individuals and society overall.

Modelling of patient journey in chronic spontaneous urticaria: Increasing awareness and education by shorten patients' disease journey in Germany.

BACKGROUND: Chronic spontaneous urticaria (CSU) is both physically and emotionally stressful, and guideline recommendations are often not optimally implemented in clinical practice. The objective of this study was to provide an overview on the patient journey in CSU and to develop a mathematical model based on solid data. METHODS: The journey of CSU patients in Germany was traced through literature review and expert meetings that included medical experts, pharmacists and representatives of patient organizations. The current situation's main challenges in the patient journey (education, collaboration and disease management) were discussed in depth. Then, a probabilistic model was developed in a co-creation approach to simulate the impact of three potential improvement strategies: (1) patient education campaign, (2) medical professional education programme and (3) implementation of a disease management programme (DMP). RESULTS: Chronic spontaneous urticaria patients are severely burdened by delays in diagnosis and optimal medical care. Our simulation indicates that in Germany, it takes on average of 3.8 years for patients to achieve disease control in Germany. Modelling all three optimization strategies resulted in a reduction to 2.5 years until CSU symptom control. On a population level, the proportion of CSU patients with disease control increased from 44.2% to 58.1%. CONCLUSION: In principle, effective CSU medications and a disease-specific guideline are available. However, implementation of recommendations is lagging in practice. The approach of quantitative modelling of the patient journey validates obstacles and shows a clear effect of multiple interventions on the patient journey. The data generated by our simulation can be used to identify strategies for improving patient care. Our approach might helping in understanding and improving the management of patients beyond CSU.

Digital Media Usage Behavior and Its Impact on the Physician-Patient Relationship: Cross-Sectional Study Among Individuals Affected by Psoriasis in Germany.

BACKGROUND: Psoriasis is a chronic skin disorder with a high burden of disease. People affected with psoriasis increasingly use the internet for health-related reasons, especially those with younger age, higher education, and higher disease severity. Despite advantages such as enhancing the individuals' knowledge with the use of digital media for health-related issues, disadvantages were also present such as quality control, and variability in the individuals' health information literacy. While patients with psoriasis within medical settings generally trust physicians over digital media, they commonly withhold their web-based research findings from health care providers. OBJECTIVE: The study aims to (1) identify further factors associated with regular psoriasis-related internet use, (2) rank specific digital media platforms used, and (3) examine digital media within the physician-patient relationship among individuals with and without dermatological treatment. METHODS: A cross-sectional, questionnaire-based study was conducted among individuals with self-reported psoriasis in Germany between September 2021 and February 2022. Participants were recruited via digital media platforms and in person at a University Hospital Department of Dermatology in southern Germany. The questionnaire asked about demographic and medical information, individual psoriasis-related digital media use, and the impact of digital media on the physician-patient relationship. Data were analyzed descriptively, and logistic regression models were performed to assess the factors associated with regular psoriasis-related internet use. RESULTS: Among 321 individuals with a median age of 53 (IQR 41-61) years (nonnormally distributed; females: 195/321), female sex, shorter disease duration, moderate mental burden of disease, and good self-assessed psoriasis-related knowledge were associated with regular psoriasis-related internet use. Of the 188 participants with a mean age of 51.2 (SD 13.9) years (normally distributed) who used digital media 106 (56.4%) usually searched for information on psoriasis-based websites and 98 (52.1%) on search engines, primarily for obtaining information about the disease and therapy options, while social media were less frequently used (49/188, 26.1%). Nearly two-thirds of internet users (125/188) claimed that their physicians did not recommend digital media platforms. About 44% (82/188) of the individuals reported to seek for additional information due to the insufficient information provided by their physician. CONCLUSIONS: This study revealed the importance of digital media in the context of psoriasis, especially among women, individuals with shorter disease duration, and moderate mental disease severity. The lack of physicians' digital media recommendations despite their patients' desire to receive such and being more involved in health-related decisions seems to be a shortcoming within the physician-patient relationships. Physicians should guide their patients on digital media by recommending platforms with evidence-based information, thereby potentially creating an adequate framework for shared decision-making. Future research should focus on strategies to prevent the spread of false information on digital media and address the needs of patients and physicians to enhance health-related digital media offerings.

Attitudes Toward and Use of eHealth Technologies Among German Dermatologists: Repeated Cross-Sectional Survey in 2019 and 2021.

BACKGROUND: In recent years, legal and infrastructural conditions have been set to improve the adoption of digital applications in health care in Germany. The impact of these actions was amplified by the COVID-19 pandemic. So far, no studies have confirmed this progress in dermatology. OBJECTIVE: The aim of this study was to measure changes in knowledge, interest, expectation, and use of digital applications in health care among dermatologists in Germany in 2019 and 2021. METHODS: We administered a repeated cross-sectional survey among dermatologists in medical practices and clinics in Germany at 2 time points: t1 (2019; before the COVID-19 pandemic) and t2 (2021; during the COVID-19 pandemic). We used a standardized questionnaire, including items on respondents' knowledge, interest, expectation, and use of digital applications, as well as their demographics. The survey was distributed by post and email. The data were analyzed descriptively as well as with multiple logistic regressions. RESULTS: At t1, 585 (272/571, 47.6% female; mean age 52.4, SD 8.9 years) dermatologists and at t2, 792 (360/736, 48.9% female; mean age 54.3, SD 8.6 years) dermatologists participated in this survey. Interest in digital medicine was higher at t1 than at t2 (381/585, 65.1% vs 458/792, 57.8%; P≤.001). Nevertheless, 38.6% (306/792) had used digital applications more often since the beginning of the pandemic. For example, real-time telemedicine with patients (12/585, 2.1% vs 160/792, 7.6%; P≤.001) and other specialists did increase (33/385, 5.7% vs 181/792, 22.8%; P≤.001). Almost one-third expressed great concerns about digitalization (272/792, 34.3% vs 294/792, 37.1%; P=.21). Spatial analysis revealed higher interest in, more positive expectations toward, and higher use of digital applications in urban areas in comparison to rural areas. For instance, dermatologists from urban areas assessed future applications as having less risk (adjusted odds ratio [aOR] 0.51, 95% CI 0.35-0.76) than did dermatologists from rural areas. The situation was similar with the age groups, as, for example, dermatologists aged <50 years also expected lower risks (aOR 0.51, 95% CI 0.34-0.77) than those aged ≥50 years. There were no differences between sexes in use, but there were differences in knowledge and expectation; for example, male participants assessed their confidence in using digital applications as higher (aOR 1.44, 95% CI 1.01-2.04) than did female participants. CONCLUSIONS: During the pandemic, the use of digital applications in dermatology increased but still remained at a moderate level. The regional and age-related disparities identified indicate the need for further action to ensure equal access to digital care.

The neglected twin: Nummular eczema is a variant of atopic dermatitis with codominant TH2/TH17 immune response.

BACKGROUND: Nummular eczema (NE) is a common chronic inflammatory skin disease characterized by multiple, pruritic, discoid-shaped lesions. Since the underlying immune mechanisms are not fully understood, it is unclear whether NE should be regarded as variant of atopic dermatitis (AD) or a distinct disease. OBJECTIVE: We compared the clinical, histopathologic, and molecular signatures of NE with that of type 2 and type 3 skin diseases. METHODS: We performed bulk RNA sequencing as well as histologic and clinical studies in lesional and nonlesional skin biopsy specimens from NE (n = 50), AD (n = 47), and psoriasis (n = 90) patients. RESULTS: NE displayed typical hallmarks of AD, such as an impaired epidermal barrier, microbial colonization, spongiosis, and eosinophil infiltration, but also aspects of psoriasis, including increased epidermal thickness, number of Ki-67+ cells, and neutrophilic infiltration. At the gene expression level, neutrophil-attracting cytokines (IL19, CXCL8, CXCL5) were upregulated, whereas TH2-related cytokines (IL13, CCL17, CCL18, CCL26, CCL27) were similarly expressed in NE compared to AD. Principal component analysis of transcriptome data from lesional skin showed that AD and NE cluster together distinct of psoriasis. In line with this, an established molecular classifier identified NE as AD rather than psoriasis. Finally, we demonstrated clinical and molecular efficacy of dupilumab treatment in NE. CONCLUSION: NE shows overlapping type 2 and type 3 immune signatures, while type 2 immunity predominates and should be the primary target of specific therapeutic interventions. This supports the view of NE as a variant of AD.

Patient journey and disease-related digital media usage: A cross-sectional study among dermatology patients across Germany.

BACKGROUND AND OBJECTIVES: This study aimed to fill the gap of evidence-based data by examining the impact of health-related digital media use's impact on the patient-physician relationship and patient journey, with the goal of driving positive changes in office-based dermatological practice. PATIENTS AND METHODS: German individuals with skin conditions completed a questionnaire assessing health-related digital media use, eHealth literacy, impact of digital media use on the patient-physician relationship and patient journey, and sociodemographic and health characteristics from June to November 2022, followed by descriptive analysis and linear regressions. RESULTS: Overall, 919 participants were analyzed (median age: 47.00, interquartile range [28.00; 61.00] years, female: 53.6%, health-related digital media users: 56.8%). Google and online encyclopedias were commonly used before and after dermatological consultations. Online self-help groups were used by 75% of non-treated participants. Digital media use had no impact on the patient-physician relationship and a positive impact on the patient journey. Positive impacts were associated with higher eHealth literacy, satisfaction with digital media quality, importance of digital media, rural residence, high education, and trust in dermatologists. CONCLUSIONS: The potential of health-related digital media in office-based dermatological care necessitates the drive of an evidence-based digital health platform to improve eHealth literacy and satisfaction with the quality of digital media among affected individuals.

Vitiligo - a disease: A position paper on stigmatization, life quality impairment and psychosocial comorbidity.

Vitiligo is a common disorder characterized by the visible loss of skin pigmentation. Non-segmental vitiligo (NSV) is the major subtype. The disease is caused by autoimmune-mediated destruction of melanocytes. Vitiligo leads to stigmatization and a significant reduction in quality of life. Disregarding the psychosocial burden, vitiligo is sometimes viewed solely as a cosmetic problem and, according to a global survey, is diagnosed on average only after 2.4 years. This delay contributes to a considerable burden of disease, including suicidal ideation. Stigmatization promotes the development of psychological comorbidities such as anxiety and depressive disorders, with prevalence rates varying by country and study (0.1%-67.9%). Data for Germany are heterogeneous and largely based on estimates. Due to psychosocial factors, the inflammatory component, and a higher incidence of somatic comorbidities, NSV may be regarded as an inflammatory systemic disease. We recommend optimizing care by incorporating the assessment of quality of life as a standard in routine care, in addition to monitoring disease activity. Moreover, early screening for psychological comorbidities is crucial to initiate appropriate treatment before the condition becomes chronic and cumulative (irreversible) impairments occur. The goal is a personalized and patient-centered integrated care approach that sustainably improves the health status of those affected.

Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism.

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line-derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.

Biomarkers associated with the development of comorbidities in patients with atopic dermatitis: A systematic review.

Biomarkers associated with the development of comorbidities in atopic dermatitis (AD) patients have been reported, but have not yet been systematically reviewed. Seven electronic databases were searched, from database inception to September 2021. English language randomized controlled trials, prospective and retrospective cohort, and case-control studies that investigated the association between a biomarker and the development of comorbidities in AD patients were included. Two authors independently screened the records for eligibility, one extracted all data, and critically appraised the quality of studies and risk of bias. Fifty six articles met the inclusion criteria, evaluating 146 candidate biomarkers. The most frequently reported biomarkers were filaggrin mutations and allergen specific-IgE. Promising biomarkers include specific-IgE and/or skin prick tests predicting the development of asthma, and genetic polymorphisms predicting the occurrence of eczema herpeticum. The identified studies and biomarkers were highly heterogeneous, and associated with predominately moderate-to-high risk of bias across multiple domains. Overall, findings were inconsistent. High-quality studies assessing biomarkers associated with the development of comorbidities in people with AD are lacking. Harmonized datasets and independent validation studies are urgently needed.

Limited Reimbursement and Underuse of Digital Healthcare Concepts Are Major Barriers to Clinical Allergological Care in Germany.

INTRODUCTION: Allergic diseases represent a broad spectrum of high-prevalence, chronic conditions that remain underdiagnosed and undertreated. The aims of this interdisciplinary, questionnaire-based, non-interventional study were to identify and analyze potential barriers to clinical allergological care in Germany. METHODS: All hospitals listed in the German hospital register involved in the treatment of allergological patients (n = 899) were invited to participate. The study yielded a response rate of 52.1% (n = 468). RESULTS: Overall, 88.5% of clinics agreed that allergological care in Germany needs improvement, especially in terms of reimbursement for diagnostics and therapy. More than 80% of participating clinics reported that the decreased availability of test substances and the time-intensity of allergological testing represent relevant barriers. For dermatology and pulmonology, the former is the strongest barrier, while for pediatric and ENT clinics, time-intensity is regarded as the strongest barrier. The availability of good therapy and appropriate guidelines present no barriers to allergological care. Regarding the use of digital healthcare concepts, a very large majority of clinics (n = 352; 91.4%) do not offer video consultations or the use of health applications in patient care. CONCLUSION: In conclusion, we have identified several structural barriers to allergological care in Germany. Reimbursement and the use of digital healthcare concepts in German clinics providing allergological care need improvement. Based on the results of this study, there is an urgent need for researchers and policymakers to further investigate and support allergology departments in their clinical work and in their implementation of digital healthcare concepts.

The Potential of Instagram to Reduce Stigmatization of People with Psoriasis: A Randomized Controlled Pilot Study.

Psoriasis is a stigmatized skin disease. This randomized controlled trial aimed to evaluate an Instagram based stigma-reduction intervention targeting daily Instagram users aged 18 to 49 years without psoriasis. After stratification for baseline characteristics (t0), stigmatization of psoriasis was assessed using a questionnaire and a photo-rating task immediately before (t1) and after (t2) the intervention and two weeks post-intervention (t3). Data from 54 participants, recruited in a university setting and via Instagram, were analysed. For 10 min between t1 and t2, the intervention group (n = 26) and the control group (n = 28) scrolled through two different Instagram accounts. Psoriasis-sensitizing content was displayed to the intervention group while beauty-glorifying posts were shown to the control group. Results indicated significantly less Disease-related Misconceptions in the intervention group in comparison to the control group at t2 (U = 145.50, Z = -3.79, p < 0.001) and at t3 (U = 177.00, Z = -3.25, p = 0.003). Moreover, the intervention group showed a significant reduction over time in Stereotype Endorsement (F(2, 50) = 13.40, p < 0.001, partial η² = 0.35) and Disease-related Misconceptions (χ2(2) = 12.64, p = 0.002). These findings suggest that addressing psoriasis on Instagram has the potential to effectively reduce the related stigmatization. Further studies are necessary to assess the impact of social media on stigmatization concerning psoriasis in more depth.

Out-of-Pocket Costs in Alopecia Areata: A Cross-Sectional Study in German-speaking Countries.

Alopecia areata is a common skin disease which is associated with psychosocial and financial burden. No curative therapy exists and, hence, affected persons resort to self-financed cosmetic solutions. However, studies on the economic impact of alopecia areata on individuals are limited. To estimate annual individual out-of-pocket costs in persons with alopecia areata, a cross-sectional study using a standardized online questionnaire was performed in Germany, Austria and Switzerland. A total of 346 individuals (95.1% women, mean age: 38.5 ± 11.6 years) with alopecia areata participated between April and August 2020. Mean additional spending on everyday necessities was 1,248€ per person per year, which was significantly influenced by the duration of the illness, the treatment provider, and disease severity. Hair replacement products and cosmetics accounted for the highest monthly costs, followed by costs for physician visits, hospital treatments, and medication. Most participants (n = 255, 73.7%) were currently not undergoing treatment, due to lack of efficacy, side-effects, costs and acceptance of the disease. Sex differences in expenses were observed, with women having higher expenditures. Alopecia areata-related out-of-pocket costs place a considerable financial burden on affected individuals, are higher compared with those of other chronic diseases, and should be considered in economic assessments of the impact of this disease.

Happiness Behind the Scenes: Associations between Heuristic Happiness and Related Dimensions in Skin Diseases.

Positive health approaches, such as happiness, are largely unexplored in medicine, including dermatology. Taking into consideration the various happiness measures, the aims of this cross-sectional study were to assess this concept using a 1-item heuristic happiness question and its related dimensions (Satisfaction with Life, Positive and Negative Affect, Quality of Life, and Compound Psychological Capital) in outpatients with different skin diseases between December 2019 and June 2020, and to examine the link between these dimensions. Overall, 414 dermatological patients were included: 67 with psoriasis, 84 atopic eczema, 10 mastocytosis, 19 nummular eczema, 84 malignant melanoma and 150 keratinocyte carcinoma. Comparing the skin diseases, differences were observed for heuristic happiness, Positive Affect, and some domains of Quality of Life and Compound Psychological Capital. Analysing the relationship between heuristic happiness and other happiness measures, the data revealed moderate to strong correlations (r = 0.30-0.46, p< 0.001) and variations in the understanding of happiness between the skin diseases. Overall, the most important facet of happiness was Hope as a domain of Compound Psychological Capital. This study emphasizes the individual definition of heuristic happiness in patients with skin diseases. A 1-item heuristic approach may be a simple and practical method to assess the complexity and individuality of happiness.

Itching in Atopic Dermatitis: Patient- and Physician-reported Outcomes in the German Atopic Dermatitis Registry TREATgermany.

TREATgermany is an investigator-initiated prospective disease registry. It investigates physician- and patient-reported disease severity (Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator Global Assessment, Patient-Oriented Eczema Measure (POEM), Patient Global Assessment (PGA)), patient-reported symptoms (itch, sleep loss, depressive symptoms), therapy courses and dermatological quality of life (DLQI) in moderate-to-severe atopic dermatitis with SCORAD > 20. 1,134 atopic dermatitis patients (mean age 41.0 ± 14.7 years, 42.5% females) were enrolled by 40 German recruiting sites (dermatological clinics and practices) between June 2016 and April 2021. The current analysis focuses on itch scores obtained with a numerical rating scale (NRS)) documented for the previous 3 days prior to baseline visit. The results show that 97.2% (1,090 of 1,121) patients experienced itch. Itch severity correlated moderately with severity of atopic dermatitis oSCORAD (rho = 0.44 (0.39-0.48)) and EASI score (rho = 0.41 (0.36-0.46)). A strong correlation was found with self-reported disease severity as PGA (rho = 0.68 (0.65-0.71)), POEM sum score (rho = 0.66 (0.63-0.69)) and dermatological quality of life impairment DLQI (rho = 0.61 (0.57-0.65)). Itch as a subjective complaint is more closely correlated with patient-reported outcomes than with objective assessments by the physician.