NNT mediates redox-dependent pigmentation via a UVB- and MITF-independent mechanism.

Ultraviolet (UV) light and incompletely understood genetic and epigenetic variations determine skin color. Here we describe an UV- and microphthalmia-associated transcription factor (MITF)-independent mechanism of skin pigmentation. Targeting the mitochondrial redox-regulating enzyme nicotinamide nucleotide transhydrogenase (NNT) resulted in cellular redox changes that affect tyrosinase degradation. These changes regulate melanosome maturation and, consequently, eumelanin levels and pigmentation. Topical application of small-molecule inhibitors yielded skin darkening in human skin, and mice with decreased NNT function displayed increased pigmentation. Additionally, genetic modification of NNT in zebrafish alters melanocytic pigmentation. Analysis of four diverse human cohorts revealed significant associations of skin color, tanning, and sun protection use with various single-nucleotide polymorphisms within NNT. NNT levels were independent of UVB irradiation and redox modulation. Individuals with postinflammatory hyperpigmentation or lentigines displayed decreased skin NNT levels, suggesting an NNT-driven, redox-dependent pigmentation mechanism that can be targeted with NNT-modifying topical drugs for medical and cosmetic purposes.

Combined genome-wide association study of 136 quantitative ear morphology traits in multiple populations reveal 8 novel loci.

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology.

From decision to reflection: understanding the experiences and unmet care needs of patients treated with immunotherapy for melanoma in the adjuvant or metastatic setting.

BACKGROUND: Despite increased use of immune checkpoint inhibitors (ICIs) in patients with advanced melanoma, little is known about patient experiences during this treatment. This study aimed to gain an in-depth understanding of experiences and unmet care needs of patients treated in the adjuvant or metastatic setting for advanced melanoma regarding their ICI treatment trajectory. METHODS: Interviews and focus groups were conducted among 35 patients treated with ICIs in the adjuvant setting for completely resected stage III (n = 14), or in the metastatic setting for irresectable stage IV (n = 21) melanoma. A thorough thematic content analysis was conducted. RESULTS: Three main themes were identified. When (1) dealing with uncertainty in the decision-making process, adjuvant patients explored the pros and cons, whereas metastatic patients considered immunotherapy their only viable option. Both groups expressed the need for additional guidance. In (2) navigating the immunotherapy course, both perceived the trajectory as intense, experienced a major impact on their and their (close) relatives' lives, and felt the need to (re)gain control. When (3) looking back on the immunotherapy experience, metastatic patients generally felt relieved, while among adjuvant patients, feelings of doubt regarding their choice for ICIs were also reported. CONCLUSIONS: ICI treatment is perceived as intensive for both patient groups, facing both comparable and distinct challenges throughout the treatment trajectory, underscoring the need for stage-specific, individualised guidance. Options regarding flexible follow-ups, low-threshold contact and psychosocial support throughout the treatment trajectory should be explored.

Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis.

BACKGROUND: Actinic keratosis (AK) is a common dermatological condition, and among the most common dermatological diagnoses in older populations. Although the prevalence of AK depends on demographic and environmental factors, little is known about the global context of AK. OBJECTIVES: To provide a comprehensive and updated analysis of the global prevalence rate and incidence of AK in the general population through a systematic review and meta-analysis, and - through subgroup analyses - to identify high-risk phenotypes, demographic and lifestyle risk factors and regional variations in disease prevalence. METHODS: A systematic search of Embase, MEDLINE, Web of Science and Google Scholar was performed on 20 May 2022. Two reviewers independently screened and assessed the quality of each study using a validated critical appraisal checklist. Epidemiological measurements (e.g. prevalence) from individual studies performed in the general population were then pooled in a random-effects meta-analysis. Subgroup analyses (i.e. population age, geographical region, occupation, sex and study quality) were conducted. RESULTS: Of the 65 articles that made it through the full-text screening, 60 reported a point prevalence. A meta-analysis of these articles yielded an overall point prevalence of 14% [95% confidence interval (CI) 14-15]. In further analyses, the calculated prevalence rate varied depending on subgroup. The pooled incidence rate from the seven eligible studies analysed was 1928 per 100 000 person-years (PY; 95% CI -439 to 4294). CONCLUSIONS: This comprehensive meta-analysis provides an updated global prevalence rate of AK of 14%, indicating a significant worldwide disease burden. The incidence rate of AK was found to be 1928 per 100 000 PY, emphasizing a growing public health concern. However, high heterogeneity among studies suggests that various factors influence the AK prevalence rate, necessitating further research to understand the observed differences.

Development and External Validation of a Prediction Model for Patients with Varicose Veins Suitable for Isolated Ambulatory Phlebectomy.

OBJECTIVE: Isolated ambulatory phlebectomy is a potential treatment option for patients with an incompetent great saphenous vein (GSV) or anterior accessory saphenous vein and one or more incompetent tributaries. Being able to determine which patients will most likely benefit from isolated phlebectomy is important. This study aimed to identify predictors for avoidance of secondary axial ablation after isolated phlebectomy and to develop and externally validate a multivariable model for predicting this outcome. METHODS: For model development, data from patients included in the SAPTAP trial were used. The investigated outcome was avoidance of ablation of the saphenous trunk one year after isolated ambulatory phlebectomy. Pre-defined candidate predictors were analysed with multivariable logistic regression. Predictors were selected using Akaike information criterion backward selection. Discriminative ability was assessed by the concordance index. Bootstrapping was used to correct regression coefficients, and the C index for overfitting. The model was externally validated using a population of 94 patients with an incompetent GSV and one or more incompetent tributaries who underwent isolated phlebectomy. RESULTS: For model development, 225 patients were used, of whom 167 (74.2%) did not undergo additional ablation of the saphenous trunk one year after isolated phlebectomy. The final model consisted of three predictors for avoidance of axial ablation: tributary length (< 15 cm vs. > 30 cm: odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02 - 0.40; 15 - 30 cm vs. > 30 cm: OR 0.18, 95% CI 0.09 - 0.38); saphenofemoral junction (SFJ) reflux (absent vs. present: OR 2.53, 95% CI 0.81 - 7.87); and diameter of the saphenous trunk (per millimetre change: OR 0.63, 95% CI 0.41 - 0.96). The discriminative ability of the model was moderate (0.72 at internal validation; 0.73 at external validation). CONCLUSION: A model was developed for predicting avoidance of secondary ablation of the saphenous trunk one year after isolated ambulatory phlebectomy, which can be helpful in daily practice to determine the suitable treatment strategy in patients with an incompetent saphenous trunk and one or more incompetent tributaries. Patients having a longer tributary, smaller diameter saphenous trunk, and absence of terminal valve reflux in the SFJ are more likely to benefit from isolated phlebectomy.

Cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas stratified for patients with organ transplantation and hematologic malignancies: A nationwide cohort study.

BACKGROUND: There is lack of nationwide data on the cumulative incidence and timing of subsequent cutaneous squamous cell carcinomas (cSCCs) among patients with a first cSCC. OBJECTIVE: To investigate the cumulative incidence and timing of subsequent cSCCs. METHODS: Patients with a first cSCC in 2007/2008 from the Netherlands Cancer Registry were linked to the Netherlands Pathology Registry for subsequent cSCCs and the Netherlands Organ Transplant Registry. Cumulative incidence function curves were calculated for subsequent cSCCs and stratified for immune status. RESULTS: Among the 12,345 patients, second to sixth cSCC occurred in 4325, 2010, 1138, 739, and 501 patients, with median time intervals of 1.4, 1.2, 0.9, 0.6, and 0.5 years after the previous cSCC, respectively. The cumulative incidence of a subsequent cSCC at 5 years increased from 28% to 67% for the second to sixth cSCC. For solid organ transplant recipients, the cumulative incidences increased from 74% to 92% and from 41% to 64% for patients with hematologic malignancy. LIMITATIONS: Only histopathologically confirmed cSCCs were included. CONCLUSION: The risk of a subsequent cSCC steeply rises with the number of prior cSCCs and immune status, while the time interval decreases. This can support more informed decisions about follow-up management.

The epidemiology of acne vulgaris in a multiethnic adolescent population from Rotterdam, the Netherlands: A cross-sectional study.

BACKGROUND: Although acne is a prevalent multifactorial inflammatory skin condition, few studies were performed in multiethnic populations. OBJECTIVES: To study the prevalence and determinants of acne in a multiethnic study at the start of puberty. METHODS: This cross-sectional study is embedded in Generation R, a population-based prospective study from Rotterdam, the Netherlands. Three-dimensional facial photos at the center visit in 2016-2019 (of ∼13-year-olds) were used to grade acne severity using the Global Evaluation of the Acne Severity (GEA). Analyses were stratified by biological sex and explored through chi-square tests and multivariable ordinal logistic regression. RESULTS: A total of 4561 children (51% girls) with a median age of 13.5 (IQR 13.3-13.6) were included. The visible acne prevalence (GEA 2-5) for girls vs boys was 62% vs 45% and moderate-to-severe acne (GEA 3-5) 14% vs 9%. Higher puberty stages (adjusted odds ratios: 1.38 [1.20-1.59] and 2.16 [1.86-2.51] for girls and boys, respectively) and darker skin colors V and VI (adjusted odds ratios: 1.90 [1.17-3.08] and 2.43 [1.67-3.56]) were associated with more severe acne in both sexes, and being overweight in boys (adjusted odds ratio: 1.58 [1.15-2.17]). LIMITATIONS: Cross-sectional design. CONCLUSIONS: Acne prevalence was high at the age of 13 years and was associated with advanced puberty, darker skin color, and weight status.

Lifetime prevalence and associated factors of itch with skin conditions: Atopic dermatitis, psoriasis and dry skin in individuals aged over 50.

BACKGROUND: Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited. OBJECTIVES: This cross-sectional study aimed to determine the lifetime prevalence of itch with skin conditions and identify its associated factors in middle-aged and elderly individuals. METHODS: Participants from the Rotterdam Study, a population-based cohort, were interviewed to assess whether they had ever had an itchy skin condition, defining lifetime itch with skin conditions. Over 20 demographic, lifestyle, dermatological, and non-dermatological factors were collected. Multivariable logistic regression analysis explored associations between these factors and itch with skin conditions, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 5,246 eligible participants (age range: 51-100, median age: 67, female: 56.0%) revealed a lifetime prevalence of 33.7% for itch with skin conditions. Female sex (OR (95% CI): 1.26 (1.11-1.43)), body mass index (1.02 (1.01-1.03)), self-reported and presence of atopic dermatitis (4.29 (3.74-4.92), and 1.97 (1.60-2.43)), self-reported and presence of psoriasis (2.31 (1.77-3.01), and 2.11 (1.55-2.87)), self-reported dry skin (1.95 (1.73-2.29)), self-reported asthma (1.40 (1.08-1.83)), renal impairment (1.45 (1.17-1.79)), and clinically relevant depressive and anxiety symptoms (1.85 (1.52-2.25), and 1.36 (1.11-1.66)) were significantly associated with it. CONCLUSIONS: This study reveals a substantial one-third lifetime prevalence of itch with skin conditions in individuals aged over 50. Significant associations with diverse lifestyle, demographic, dermatological and, intriguingly, non-dermatological factors including renal impairment, imply additional contributors to itch induction or persistence in individuals with skin conditions.

Upadacitinib treatment in a real-world difficult-to-treat atopic dermatitis patient cohort.

BACKGROUND: Upadacitinib was the first JAK-1 selective inhibitor registered for the treatment of moderate-to-severe atopic dermatitis (AD). Although efficacy and safety have been shown in clinical trials, real-world data on the use of upadacitinib in patients that have been treated with other immunosuppressants and targeted therapies is limited. OBJECTIVES: To provide real-world evidence on the use of upadacitinib treatment in moderate-to-severe atopic dermatitis. METHODS: In this prospective observational single-centre study, all AD patients treated with upadacitinib treatment in the context of standard care were included between August 2021 and September 2022. Clinical outcome measures and adverse events (AEs) were analysed. RESULTS: Forty-eight patients were included. The majority (n = 39; 81%) had failed (ineffectiveness) on other targeted therapies, including other JAK inhibitors and biologics. Thirty-four (71%) patients were still using upadacitinib treatment at last follow up (median duration 46.5 weeks). Fourteen (29%) patients discontinued treatment due to ineffectiveness or AE. Upadacitinib treatment led to a significant decrease of disease severity during a median follow up of 37.5 weeks. Median IGA at baseline decreased from 3 (IQR 2-3) to 1.5 (IQR 1-2) at last review (p < 0.001). Median NRS itch decreased from 7 (IQR 5-8) at baseline to 2.25 (IQR 0.25-6.5) at last review (p < 0.001). Three patients discontinued treatment due to AE. Forty-eight AEs were reported, including acne-like eruptions (25%), nausea (13%) and respiratory tract infections (10%). CONCLUSIONS: In this real-world cohort, we confirmed that upadacitinib is an effective treatment in a subset of AD patients that have failed several previous systemic immunosuppressive and biologic treatments. Overall, AE were mostly well tolerated and not a reason to discontinue treatment for most patients.

A randomized clinical trial of isolated ambulatory phlebectomy versus saphenous thermal ablation with concomitant phlebectomy (SAPTAP Trial).

BACKGROUND: Current treatment of patients with saphenous trunk and tributary incompetence consists of truncal ablation with concomitant, delayed or no treatment of the tributary. However, reflux of the saphenous trunk may be reversible after treatment of the incompetent tributary. The aim of this study was to determine whether single ambulatory phlebectomy with or without delayed endovenous truncal ablation (SAP) is non-inferior to thermal endovenous ablation with concomitant phlebectomy (TAP), and whether SAP is a cost-effective alternative to TAP. METHODS: A multicentre, non-inferiority RCT was conducted in patients with an incompetent great saphenous vein or anterior accessory saphenous vein with one or more incompetent tributaries. Participants were randomized to receive SAP or TAP. After 9 months, additional truncal treatment was considered for SAP patients with remaining symptoms. The primary outcome was VEnous INsufficiency Epidemiological and Economic Study Quality of Life/Symptoms (VEINES-QOL/Sym score) after 12 months. Secondary outcomes were, among others, cost-effectiveness, perceived improvement of symptoms, and anatomical success. RESULTS: Some 464 patients received the allocated treatment (SAP 227, TAP 237). VEINES-QOL scores were 52.7 (95 per cent c.i. 51.9 to 53.9) for SAP and 53.8 (53.3 to 55.1) for TAP; VEINES-Sym scores were 53.5 (52.6 to 54.4) and 54.2 (54.0 to 55.6) respectively. Fifty-eight patients (25.6 per cent) in the SAP group received additional truncal ablation. Treatment with SAP was less costly than treatment with TAP. CONCLUSION: One year after treatment, participants who underwent SAP had non-inferior health-related quality of life compared with those who had TAP. Treatment with SAP was a cost-effective alternative to TAP at 12 months. REGISTRATION NUMBER: NTR 4821 (www.trialregister.nl).

Oncological healthcare providers' perspectives on appropriate melanoma survivorship care: a qualitative focus group study.

BACKGROUND: The increasing group of melanoma survivors reports multiple unmet needs regarding survivorship care (SSC). To optimise melanoma SSC, it is crucial to take into account the perspectives of oncological healthcare providers (HCPs) in addition to those of patients. The aim of this study is to gain an in-depth understanding of HCPs' perspectives on appropriate melanoma SSC. METHODS: Four online focus groups were conducted with mixed samples of oncological HCPs (dermatologists, surgeons, oncologists, oncological nurse practitioners, support counsellors and general practitioners) (total n = 23). A topic guide was used to structure the discussions, focusing on perspectives on both SSC and survivorship care plans (SCPs). All focus groups were recorded, transcribed verbatim, and subjected to an elaborate thematic content analysis. RESULTS: Regarding SSC, HCPs considered the current offer minimal and stressed the need for broader personalised SSC from diagnosis onwards. Although hardly anyone was familiar with SCPs, they perceived various potential benefits of SCPs, such as an increase in the patients' self-management and providing HCPs with an up-to-date overview of the patient's situation. Perceived preconditions for successful implementation included adequate personalisation, integration in the electronic health record and ensuring adequate funding to activate and provide timely updates. CONCLUSIONS: According to HCPs there is considerable room for improvement in terms of melanoma SSC. SCPs can assist in offering personalised and broader i.e., including psychosocial SSC. Aside from personalisation, efforts should be focused on SCPs' integration in clinical practice, and their long-term maintenance.

Trends in incidence, treatment and survival of Merkel cell carcinoma in England 2004-2018: a cohort study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumour with neuroendocrine differentiation and high associated mortality. Studies that describe the epidemiology of MCC are often limited by small sample size, short duration of follow-up, absence of nationwide data and paucity of data on different risk factors. OBJECTIVES: To determine the incidence, demographics and survival for MCC in England between 2004 and 2018. METHODS: This national retrospective cohort study identified all cases of MCC in England from 2004 to 2018 using national population-based data from the National Disease Registration Service. Crude counts, European age-standardized incidence rates (EASRs) and joinpoint analysis were conducted. Patient demographics and treatments received were described. Multivariable Cox regression analysis was used to study risk factors for MCC-specific mortality, by including a priori defined demographic factors, tumour characteristics and immunosuppression. Treatment data were not included in the Cox regression analysis. RESULTS: A total of 3775 MCC tumours were registered. The median age at diagnosis was 81 years (interquartile range 74-87). Overall, 96·6% of patients identified as White ethnicity, and 8·3% of patients were immunosuppressed. The most common site was the face (27·4%). Patients most often presented with stage one disease (22·8%); however, stage was unknown in 31·0%. In total, 80·7% of patients underwent surgical excision, 43·5% radiotherapy and 9·2% systemic therapy. The EASR increased from 0·43 per 100 000 person-years (PYs) to 0·65 per 100 000 person-years between 2004 and 2018, representing a significant annual percentage change of 3·9%. The EASR was greater in men than in women for all years, with an overall male-to-female ratio of 1·41 : 1. The highest EASR was in South West England. Five-year disease-specific survival was 65·6% [95% confidence interval (CI) 63·8-67·4], with a median follow-up of 767 days. MCC-specific mortality increased with age [hazard ratio (HR) 1·02, 95% CI 1·02-1·03], deprivation (HR 1·43, 95% CI 1·16-1·76), immunosuppression (HR 2·80, 95% CI 2·34-3·34) and stage at diagnosis (HR 8·24, 95% CI 5·84-11·6). CONCLUSIONS: This study presents the largest national MCC dataset in Europe, and the most complete reporting of MCC incidence and survival ever published. With the EASR of MCC increasing and high associated mortality, this study encourages further research into the pathology, diagnosis and therapeutic options for MCC to support management guidelines.

Younger facial looks are associate with a lower likelihood of several age-related morbidities in the middle-aged to elderly.

BACKGROUND: Looking older for one's chronological age is associated with a higher mortality rate. Yet it remains unclear how perceived facial age relates to morbidity and the degree to which facial ageing reflects systemic ageing of the human body. OBJECTIVES: To investigate the association between ΔPA and age-related morbidities of different organ systems, where ΔPA represents the difference between perceived age (PA) and chronological age. METHODS: We performed a cross-sectional analysis on data from the Rotterdam Study, a population-based cohort study in the Netherlands. High-resolution facial photographs of 2679 men and women aged 51.5-87.8 years of European descent were used to assess PA. PA was estimated and scored in 5-year categories using these photographs by a panel of men and women who were blinded for chronological age and medical history. A linear mixed model was used to generate the mean PAs. The difference between the mean PA and chronological age was calculated (ΔPA), where a higher (positive) ΔPA means that the person looks younger for their age and a lower (negative) ΔPA that the person looks older. ΔPA was tested as a continuous variable for association with ageing-related morbidities including cardiovascular, pulmonary, ophthalmological, neurocognitive, renal, skeletal and auditory morbidities in separate regression analyses, adjusted for age and sex (model 1) and additionally for body mass index, smoking and sun exposure (model 2). RESULTS: We observed 5-year higher ΔPA (i.e. looking younger by 5 years for one's age) to be associated with less osteoporosis [odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62-0.93], less chronic obstructive pulmonary disease (OR 0.85, 95% CI 0.77-0.95), less age-related hearing loss (model 2; B = -0.76, 95% CI -1.35 to -0.17) and fewer cataracts (OR 0.84, 95% CI 0.73-0.97), but with better global cognitive functioning (g-factor; model 2; B = 0.07, 95% CI 0.04-0.10). CONCLUSIONS: PA is associated with multiple morbidities and better cognitive function, suggesting that systemic ageing and cognitive ageing are, to an extent, externally visible in the human face.

Tralokinumab treatment for patients with moderate-to-severe atopic dermatitis in daily practice.

BACKGROUND: Evidence about tralokinumab treatment for moderate-to-severe atopic dermatitis (AD) in daily practice is limited. AIM: To report the first evidence, to our knowledge, from daily practice of treatment with tralokinumab in patients with AD. METHODS: In this observational prospective study, patients with AD who received tralokinumab treatment in the context of routine care at the Erasmus Medical Centre were included between November 2021 and February 2022. This included 28 patients who had previously been treated with dupilumab, and 14 patients who had been treated with a Janus kinase inhibitor (JAKi). The Investigator's Global Assessment (IGA; 0-4) and the numeric rating scale peak pruritus during the past 7 days (NRS itch 7d: 0-10), adverse events and reasons for discontinuation were analysed. A good clinical response was defined as any decrease in IGA and NRS itch 7d and if a patient was satisfied with the treatment and wished to continue with therapy. RESULTS: In total, 37 patients were treated with tralokinumab. Twenty-two (59%) patients showed a good response to tralokinumab treatment. Fifteen (41%) patients discontinued treatment because of inadequate AD control or adverse events. Treatment-related adverse events were mild in most patients. Half of the patients where treatment with dupilumab had failed had a good clinical response to tralokinumab. CONCLUSIONS: Tralokinumab was found to be effective in most patients in this cohort with difficult-to-treat, severe AD from daily practice. Interestingly, tralokinumab was also found to be effective in 50% of patients who had previously experienced insufficient response or adverse events with dupilumab treatment.

Quality of life and stigmatization in people with skin diseases in Europe: A large survey from the 'burden of skin diseases' EADV project.

BACKGROUND: Several large studies on the burden of skin diseases have been performed in patients recruited in hospitals or clinical centres, thus missing people with skin diseases who do not undergo a clinical consultation. OBJECTIVES: To evaluate the burden of the most common dermatological diseases in adult patients across Europe, in terms of quality of life, work life, and stigmatization. METHODS: Population-based survey on a representative sample of the European general population aged 18 years or older. Participants who declared to have had one or more skin problem or disease during the previous 12 months completed the Dermatology Life Quality Index questionnaire, and answered questions regarding the impact of their skin disease on daily and work life, anxiety/depression, and stigmatization. RESULTS: The study population included 19,915 individuals, 44.7% of whom were men. Quality of life was particularly impaired in people with hidradenitis suppurativa (HS), and sexually transmitted diseases. About a half of participants with acne, alopecia, or chronic urticaria, and about 40% of those with atopic dermatitis (AD), skin cancers, or psoriasis reported a modest to extremely large effect of the disease on their quality of life. Overall, 88.1% of participants considered their skin disease as embarrassing in personal life and 83% in work life. About half of the respondents reported sleeping difficulty, feeling tired, and impact of the disease on taking care of themselves. Concerning stigmatization, 14.5% felt to have been rejected by others because of the skin disease, and 19.2% to have been looked at with disgust. Anxiety and depression were frequently reported by patients with all the diseases. CONCLUSIONS: Skin diseases may heavily affect patients' daily and work life, and cause feelings of stigmatization. An early intervention is needed to avoid consequences on the patients' life course.

Public perception of dermatologists in Europe: Results from a population-based survey.

BACKGROUND: The public perception of dermatology has been poorly investigated in Europe. OBJECTIVE: To determine the general public's perception of dermatologists in Europe. METHODS: This multinational, cross-sectional study was conducted within the framework of the EADV population-based survey on the 'Burden of skin diseases in Europe'. Data were collected using a web-based online survey on a representative sample of the general populations aged 18 years or more of 27 European countries. Proportional quota sampling with replacement design was used for each country. RESULTS: A total of 44,689 adult participants responded to the questionnaire, of whom 18,004 visited a dermatologist in the preceding 3 years. The dermatologist was the second most often visited specialist among all medical specialties, with 69.7%, 72.1%, 42.1% and 78.1% of participants in Western Europe (WE), Eastern Europe (EE), Northern Europe (NE) and Southern Europe (SE), respectively, having consulted a dermatologist over the past 24 months. Most participants across all regions agreed that the dermatologist was the first healthcare provider for chronic skin diseases (61.9% in WE, 69.8% in EE, 45.7% in NE and 60.4% in SE) and for skin cancers (65.5% in WE, 67.6% in EE, 42.4% in NE and 63.0% in SE). The five most common reasons for visiting a dermatologist among all participants were: naevi check-up or skin cancer screening (20.2%), chronic skin diseases (16.5%), acute skin diseases (12.4%), cosmetic advice or procedure (10.2%), hyperpigmentation or congenital lesions (9.1%) and hair or nail disorder (7.7%). Most participants (84.6% in WE, 82.5% in EE, 78.3% in NE and 82.8% in SE) were very swatisfied/somewhat satisfied with the service provided. CONCLUSION: Our study findings underscore the central role of dermatologists in skin health and highlights them as valued and trusted care providers across Europe. Understanding the perceived position of the dermatologist is the first step in improving health policy development and implementation. Notably, access to a dermatologist was lowest in NE, probably reflecting differences in healthcare organizational structures or possibly cultural differences in healthcare seeking behaviour.

The journey of patients with skin diseases from the first consultation to the diagnosis in a representative sample of the European general population from the EADV burden of skin diseases study.

BACKGROUND: The journey of patients with skin diseases through healthcare has been scarcely investigated. OBJECTIVE: To analyse the journey of people with skin diseases in the different healthcare environment in Europe. METHODS: This multinational, cross-sectional, European study was conducted on a representative sample of the adult general population of 27 European countries. The prevalence of the most frequent skin diseases was determined. Information was collected on the patient journey from the first medical consultation to the diagnosis, and the reasons for not consulting a healthcare professional. RESULTS: On a total of 44,689 individuals, 30.3% reported to have consulted a dermatologist during the previous 2 years. Participants consulted mainly for mole control or skin cancer screening (22.3%), followed by chronic skin diseases (16.2%). The diagnoses of acne, atopic dermatitis, psoriasis and rosacea were made most frequently by a dermatologist, while fungal skin infections were diagnosed more often by a general practitioner (GP), and sexually transmitted diseases (STD) by other specialists. The diagnosis was not always definitive at the first consultation, in particular for STD. The percentage of people who did not consult a healthcare professional for their skin disease was particularly high for acne (36.4%), alopecia (44.7%) and fungal infection (30.0%). Moreover, 17.7% of respondents with psoriasis did not consult. A high percentage of participants with alopecia thought that the disease was not worrying, while patients with psoriasis often answered that they were able to manage the disease since they had already consulted a doctor. Many patients with acne (41.1%) and fungal infection (48.2%) thought that they were able to handle the disease by themselves. CONCLUSION: The analysis of the self-reported medical journey of patients with common skin diseases may allow to understand the unmet needs of patients, thus improving outcomes and reducing expenses.

Limited impact of COVID-19-related diagnostic delay on cutaneous melanoma and squamous cell carcinoma tumour characteristics: a nationwide pathology registry analysis.

BACKGROUND: The COVID-19 pandemic reduced the number of skin cancer diagnoses, potentially causing a progression to unfavourable tumour stages. OBJECTIVES: To identify the impact of delayed diagnostics on primary invasive melanoma and cutaneous squamous cell carcinoma (cSCC) by comparing tumour (pT) stage, Breslow thickness and invasion depth from before to after the first and second lockdown periods. METHODS: In this population-based cohort study, histopathology reports registered between 1 January 2018 and 22 July 2021 were obtained from the nationwide histopathology registry in the Netherlands. The Breslow thickness of melanomas, invasion depth of cSCCs, and pT stage for both tumour types were compared across five time periods: (i) pre-COVID, (ii) first lockdown, (iii) between first and second lockdowns, (iv) second lockdown and (v) after second lockdown. Breslow thickness was compared using an independent t-test. pT-stage groups were compared using a χ2 -test. Outcomes were corrected for multiple testing using the false discovery rate. RESULTS: In total, 20 434 primary invasive melanomas and 68 832 cSCCs were included in this study. The mean primary melanoma Breslow thickness of the prepandemic era (period i) and the following time periods (ii-v) showed no significant difference. A small shift was found towards unfavourable pT stages during the first lockdown compared with the pre-COVID period: pT1 52·3% vs. 58·6%, pT2 18·9% vs. 17·8%, pT3 13·2% vs. 11·0%, pT4 9·1% vs. 7·3% (P = 0·001). No relevant changes were seen in subsequent periods. No significant change in pT stage distribution was observed between the pre-COVID (i) and COVID-affected periods (ii-v) for cSCCs. CONCLUSIONS: To date, the diagnostic delay caused by COVID-19 has not resulted in relatively more unfavourable primary tumour characteristics of melanoma or cSCC. Follow-up studies in the coming years are needed to identify a potential impact on staging distribution and survival in the long term.

Experiences of resuming life after immunotherapy and associated survivorship care needs: a qualitative study among patients with metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have significantly improved the overall survival of patients with metastatic melanoma. It is unclear how the growing group of metastatic melanoma survivors resume their lives after treatment, and which needs they have regarding survivorship care (SSC). OBJECTIVES: To gain an in-depth understanding of metastatic melanoma survivors' experiences of resuming life after ICIs and their associated SSC needs. METHODS: A qualitative study was conducted among 20 patients with metastatic melanoma in whom ICIs had been discontinued after ongoing tumour response. One focus group (n = 9) was held, which was complemented by 11 individual interviews. Purposive sampling was used to select a variable sample in terms of sex, age, time since discontinuation of ICIs, and perceived impact of the disease. A topic guide was used to structure the (group) interviews, which were transcribed verbatim and analysed in a thematic content analysis, using several phases of coding. RESULTS: In resuming life after ICIs, the prognosis switch often caused mixed feelings among patients, mainly because of the uncertainty about the future. Demands and expectations from self and others, persistent complaints and new problems in different life domains often make it challenging to proceed with life as it was prior to metastatic cancer. Patients indicated they needed to find a new balance, which included learning to cope with uncertainty and a changed perspective on life and close relationships. In terms of SSC needs, patients particularly stressed the need for more tailored patient information, available at one location. In addition, they emphasized the need to know who to turn to in case of questions and indicated the need for psychosocial support, also for their close relatives. CONCLUSIONS: Metastatic melanoma survivors face various challenges in resuming life after ICIs and are left with several unmet SSC needs. Efforts should be focused on offering psychosocial supportive care in addition to medical care, from diagnosis onwards, taking into account the patient's close relatives. A single point of contact and personalized survivorship care plan (SCP) could be of added value in guiding them through the patient journey, which is, given its multidisciplinary nature, particularly important in melanoma care. What is already known about this topic? Since the introduction of immune checkpoint inhibitors (ICIs) the overall survival of patients with metastatic melanoma has improved significantly, leading to a growing group of melanoma survivors. Melanoma survivors may face various problems and challenges in resuming life after treatment, which may be associated with unmet survivorship care (SSC) needs. An in-depth understanding of their experiences with resuming life and the associated SSC needs is currently lacking. What does this study add? Metastatic melanoma survivors experience various challenges after immunotherapy, from the uncertain prognosis switch to the struggle of finding a new balance in life. Besides negative aspects, such as complaints in different life domains, the patient journey is often accompanied by positive outcomes, for example a changed perspective on life. They stress the need for tailored patient information and broader supportive care, also for their close relatives. What are the clinical implications of this work? In addition to medical care, efforts should be focused on offering psychosocial supportive care, including return-to-work issues, from diagnosis onwards, ideally taking into account the patient's close relatives. To guide them through the patient journey, a single point of contact and a personalized survivorship care plan (SCP) could be of added value. The latter is particularly important in melanoma care, given its multidisciplinary nature.

Validation of four cutaneous squamous cell carcinoma staging systems using nationwide data.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer worldwide with relatively low metastatic potential (2-5%). Developments in therapeutic options have highlighted the need to better identify high-risk patients who could benefit from closer surveillance, adjuvant therapies and baseline/follow-up imaging, while at the same time safely omitting low-risk patients from further follow-up. Controversy remains regarding the predictive performance of current cSCC staging systems and which methodology to adopt. OBJECTIVES: To validate the performance of four cSCC staging systems [American Joint Committee on Cancer 8th edition (AJCC8), Brigham and Women's Hospital (BWH), Tübingen and Salamanca T3 refinement] in predicting metastasis using a nationwide cohort. METHODS: A nested case-control study using data from the National Disease Registration Service, England, 2013-2015 was conducted. Metastatic cSCC cases were identified using an algorithm to identify all potential cases for manual review. These were 1 : 1 matched on follow-up time to nonmetastatic controls randomly selected from 2013. Staging systems were analysed for distinctiveness, homogeneity, monotonicity, specificity, positive predictive value (PPV), negative predictive value (NPV) and c-index. RESULTS: We included 887 metastatic cSCC cases and 887 nonmetastatic cSCC controls. The BWH system showed the highest specificity [92.8%, 95% confidence interval (CI) 90.8-94.3%, PPV (13.2%, 95% CI 10.6-16.2) and c-index (0.84, 95% CI 0.82-0.86). The AJCC8 showed superior NPV (99.2%, 95% CI 99.2-99.3), homogeneity and monotonicity compared with the BWH and Tübingen diameter and thickness classifications (P < 0.001). Salamanca refinement did not show any improvement in AJCC8 T3 cSCC staging. CONCLUSIONS: We validated four cSCC staging systems using the largest nationwide dataset of metastatic cSCC so far. Although the BWH system showed the highest overall discriminative ability, PPV was low for all staging systems, which shows the need for further improvement and refining of current cSCC staging systems.