Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study.

BACKGROUND: Scarce data related to the drug survival of biologic agents in psoriasis patients aged ≥65 years is available. OBJECTIVES: To evaluate the drug survival of interleukin (IL)-23 or the IL-17 inhibitors approved for the treatment of moderate-to-severe psoriasis in elderly patients (aged ≥65 years), compared with younger adult patients (aged <65 years), and to identify clinical predictors that can influence the drug survival. METHODS: This retrospective multicentric cohort study included adult patients with moderate-to-severe psoriasis, dissecting two-patient subcohorts based on age: elderly versus younger adults. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: We included 4178 patients and 4866 treatment courses; 934 were elderly (1072 treatment courses), and 3244 were younger patients (3794 treatment courses). Drug survival, considering all causes of interruption, was higher in patients aged <65 years than in elderly patients overall (log-rank p < 0.006). This difference was significant for treatment courses involving IL-23 inhibitors (p < 0.001) but not for those with IL-17 inhibitors (p = 0.2). According to both uni- and multi-variable models, elder age was associated with an increased risk of treatment discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062-1.422; p < 0.006; multivariable analysis: HR: 1.199, 95% CI 1.010-1.422; p = 0.0377). Anti-IL-23 agents were associated with a reduced likelihood of treatment discontinuation after adjusting for other variables (HR: 0.520, 95% CI 0.368-0.735; p < 0.001). Being previously treated with IL-17 inhibitors increased the probability of discontinuation. CONCLUSION: Elderly patients with psoriasis have an increased risk of biologic treatment discontinuation compared with younger adult patients, particularly, if being treated with IL-23 inhibitors. However, in stratified analyses conducted in elderly patients, IL-23 inhibitors showed higher drug survival rates than IL-17 inhibitors.

Actinic keratosis: Current challenges and unanswered questions.

Actinic keratoses (AK) are common skin lesions associated with chronic exposure to sun. They are believed to be precursors of malignancy as they potentially may progress to invasive squamous cell carcinomas. The goal of current therapies is to reduce the number of AK and to prevent future cancer development. This review aims at providing an overview of the hallmarks of AK and skin field cancerization. We discuss epidemiology trends, risk factors and the state of the art and evidence of the current treatments. We review key figures of AK prevalence from different countries with regard to skin cancer risk and the associated economic burden of AK. We discuss the mutational status in AK lesions and the difficulties encountered by clinicians in evaluating AK visible and invisible lesions, referring to the concept of field cancerization. Based on a systematic literature review, we further evaluate the available treatment options. The presence of subclinical skin alterations in the periphery of visible AK lesions has gained a particular attention as those non-visible lesions are known to contain the same genetic changes as those found in the AK lesions themselves, prompting the concept of 'field cancerization'. Therefore, AK treatment guidelines now recognize the importance of treating the field in patients with AK. A recent systematic literature review and network meta-analysis showed that 5-FU interventions were associated with the best efficacy and a satisfactory acceptability profile compared with other field-directed therapies used in the treatment of AK. Although AK are considered quite common, they lack an accurate descriptive definition and conclusive epidemiologic data. Limited public awareness is a barrier to early and effective treatment, including prevention strategies. While different treatment options are available, there is still a limited understanding of long-term outcomes of treatment as measured by recurrence of cancer prevention.

Photodynamic Therapy for the Treatment of Basal Cell Carcinoma: A Comprehensive Review of Randomized Controlled Trials.

INTRODUCTION: Basal cell carcinoma (BCC) is the most common skin cancer worldwide and has been reported to have a rising incidence in the last years. Multiple therapeutic modalities are approved for the treatment of BCC, making it difficult for physicians to choose the most suitable option for every patient. Photodynamic therapy (PDT) using either 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) as photosensitizing agents is an established treatment option for low-risk BCC. OBJECTIVES: This review aims to summarize the available evidence from randomized clinical trials (RCTs) that utilize either ALA or MAL PDT and compare it with other treatment modalities. The main outcomes related to the effectiveness, adverse events, cosmetic outcomes and pain sensation, along with data from long-term follow-ups will be presented and discussed. METHODS: Thorough literature searches were conducted through the electronic databases ClinicalTrials. gov and Pubmed/MEDLINE from inception up to 28 March 2023. Only studies in English were included. All relevant data were extracted accordingly from the eligible studies. RESULTS: Eight RCTs included superficial BCC (sBCC) alone, 7 included nodular BCC (nBCC), 2 included both sBCC and nBCC and 1 included BCC of unspecified subtype. Follow-up duration ranged from 3 months to 5 years. Both ALA-PDT and MAL-PDT demonstrated acceptable efficacy, adverse events, cosmetic outcomes and pain sensation while no major differences were observed between them. PDT was less effective than surgery but with better reported cosmetic outcomes. CONCLUSIONS: PDT is a safe and efficacious treatment option for sBCC and to a lesser extent nBCC.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Neuroticism and inflammatory skin diseases: a bidirectional Mendelian randomization study.

Previous observational studies have linked inflammatory skin diseases with mental health issues and neuroticism. However, the specific impact of neuroticism and its subclusters (i.e. worry, depressed affect, and sensitivity to environmental stress and adversity) on these conditions remains underexplored. In this work, we explored causal associations between common inflammatory skin diseases and neuroticism. We conducted a two-sample, bidirectional Mendelian randomization (MR) analysis using data from genome-wide association studies in psoriasis, atopic dermatitis, neuroticism and relevant genetic subclusters conducted on participants of European ancestry. Corrections for sample overlap were applied where necessary. We found that psoriasis was causally associated with increased levels of worry (odds ratio, 95% confidence intervals: 1.011, 1.006-1.016, P = 3.84 × 10-6) while none of the neuroticism subclusters showed significant association with psoriasis. Sensitivity analyses revealed considerable evidence of directional pleiotropy between psoriasis and neuroticism traits. Conversely, genetic liability to atopic dermatitis did not exhibit any significant association with neuroticism traits. Notably, genetically predicted worry was linked to an elevated risk of atopic dermatitis (odds ratio, 95% confidence intervals: 1.227, 1.067-1.41, P = 3.97 × 10-3). Correction for overlapping samples confirmed the robustness of these results. These findings suggest potential avenues for future interventions aimed at reducing stress and worry among patients with inflammatory skin conditions.

Bimekizumab in psoriasis: a monocentric study evaluating short- and mid-term effectiveness and safety profile in a real-world setting.

INTRODUCTION: Bimekizumab is a humanized monoclonal IgG1 antibody with a unique mechanism of action, as it inhibits both IL17A and IL17F molecules. This dual inhibition is thought to be responsible for its high efficacy in treating chronic plaque psoriasis with rapid onset of action in Randomized Controlled Trials (RCTs). Concerning safety, oral candidiasis was one of the most common drug-related adverse events, commonly mild-to-moderate in severity. Although data from RCTs supporting this efficacy and safety profile of bimekizumab is numerous, results from the real-world setting concerning short- and mid-term treatment effectiveness and safety profile are limited. MATERIALS AND METHODS: An observational, retrospective, monocentric study was conducted at the Psoriasis Outpatient Unit of "A. Sygros" Hospital for Skin and Venereal Diseases, in Athens, Greece, which included 61 adult patients with moderate-to-severe skin psoriasis, who received at least one dosage of bimekizumab. RESULTS: At week 4, 65.7% achieved PASI75, 45.7% PASI90, and 32.4% PASI100. After 16 weeks of treatment, 92.3/76.9/66.7% of the patients achieved PASI75/90/100, respectively. Increased BMI, previous treatment with another IL-17 inhibitor, or previous exposure to another biologic did not seem to influence the possibility of achieving PASI90 and PASI100 at week 16 of bimekizumab treatment in this cohort. Six (9.8%) cases of possibly drug-related AEs were reported, from which four incidences of oral candidiasis. CONCLUSION: Our results confirm that this IL17A/F inhibitor is highly effective, with a tolerability profile similar to the one expected from RCTs.

Current Diagnostic and Therapeutic Practices in Alopecia Areata in Two Mediterranean Countries: A Survey-Based Study.

INTRODUCTION: Alopecia areata (AA) affects approximately 2% of the general population and is associated with significant psychosocial morbidity and poor health-related quality of life. Despite the high incidence of the disease the available clinical practice guidelines to help clinicians and improve patients' care are very poor and of a low methodological quality, as compared to other high-burden dermatoses. The aim of this survey is to capture the current clinical practice in AA management, as performed by dermatologists, in two Mediterranean countries to identify potential disparities and gaps in diagnosis and treatment. METHODS: A 50-item questionnaire was created in the English language and then translated into Greek and Italian language and sent to the Greek and Italian dermatologists via email. RESULTS: A total of 490 dermatologists from Italy and 234 from Greece participated in the survey. The diagnosis of AA is usually based on history and clinical examination, supported by trichoscopy. The rate of use of severity scores and scales to evaluate impact on quality of life by dermatologists was low. Treatment of patchy AA, in both adult and pediatric populations, is based on use of topical steroids as first-line treatment. Results on special site involvement (eyebrows, beard, and ophiasis), chronic cases, and the pediatric population highlight extreme heterogeneity in treatment approach. CONCLUSIONS: Our results highlight that management of AA, in terms of diagnosis and treatment, is still challenging.

Diagnosis of invasive cutaneous squamous cell carcinoma, imaging and staging.

The assessment of patients with a lesion raising the suspicion of an invasive cutaneous squamous cell carcinoma (cSCC) is a frequent clinical scenario. The management of patients with cSCC is a multistep approach, starting with the correct diagnosis. The two main diagnostic goals are to differentiate from other possible diagnoses and correctly recognize the lesion as cSCC, and then to determine the tumor spread (perform staging), that is if the patient has a common primary cSCC or a locally advanced cSCC, or a metastatic cSCC (with in-transit, regional lymph nodal, or rarely distant metastasis). The multistep diagnostic approach begins with the clinical characteristics of the primary cSCC, it is complemented with features with dermoscopy and, if available, reflectance confocal microscopy and is confirmed with histopathology. The tumor spread is assessed by physical examination and, in some cases, ultrasound and/or computed tomography or magnetic resonance imaging, mainly to investigate for regional lymph node metastasis or for local infiltration into deeper structures. In the last step, the clinical, histologic and radiologic findings are incorporated into staging systems.

European consensus-based interdisciplinary guideline for diagnosis, treatment and prevention of actinic keratoses, epithelial UV-induced dysplasia and field cancerization on behalf of European Association of Dermato-Oncology, European Dermatology Forum, European Academy of Dermatology and Venereology and Union of Medical Specialists (Union Européenne des Médecins Spécialistes).

A collaboration of multidisciplinary experts from the European Association of Dermato-Oncology, the European Dermatology Forum, the European Academy of Dermatology and Venereology, and the European Union of Medical Specialists was formed to develop European recommendations on AK diagnosis and treatment, based on current literature and expert consensus. This guideline addresses the epidemiology, diagnostics, risk stratification and treatments in immunocompetent as well as immunosuppressed patients. Actinic keratoses (AK) are potential precursors of cutaneous squamous cell carcinoma (cSCC) and display typical histopathologic and immunohistochemical features of this malignancy in an early stage. They can develop into cSSC in situ and become invasive in a low percentage of cases. AK is the most frequent neoplasia in white populations, frequently occurring within a cancerous field induced by ultraviolet radiation. Since it cannot be predicted, which lesion will progress to cSCC and when treatment is usually recommended. The diagnosis of AK and field cancerization is made by clinical examination. Dermatoscopy, confocal microscopy, optical coherence tomography or line-field confocal-OCT can help in the differential diagnosis of AK and other skin neoplasms. A biopsy is indicated in clinically and/or dermatoscopically suspicious and/or treatment-refractory lesions. The choice of treatment depends on patients' and lesion characteristics. For single non-hyperkeratotic lesions, the treatment can be started upon patient's request with destructive treatments or topical treatments. For multiple lesions, field cancerization treatment is advised with topical treatments and photodynamic therapy. Preventive measures such as sun protection, self-examination and repeated field cancerization treatments of previously affected skin areas in high-risk patients are advised.

Germline cancer susceptibility in individuals with melanoma.

BACKGROUND: Prior studies have estimated a small number of individuals with melanoma (2%-2.5%) have germline cancer predisposition, yet a recent twin study suggested melanoma has the highest hereditability among cancers. OBJECTIVE: To determine the incidence of hereditary melanoma and characterize the spectrum of cancer predisposition genes that may increase the risk of melanoma. METHODS: Four hundred individuals with melanoma and personal or family history of cancers underwent germline testing of >80 cancer predisposition genes. Comparative analysis of germline data was performed on 3 additional oncologic and dermatologic data sets. RESULTS: Germline pathogenic/likely pathogenic (P/LP) variants were identified in 15.3% (61) individuals with melanoma. Most variants (41, 67%) involved genes considered unrelated to melanoma (BLM, BRIP1, CHEK2, MLH1, MSH2, PMS2, RAD51C). A third (20, 33%) were in genes previously associated with familial melanoma (BAP1, BRCA2, CDKN2A, MITF, TP53). Nearly half (30, 46.9%) of P/LP variants were in homologous repair deficiency genes. Validation cohorts demonstrated P/LP rates of 10.6% from an unselected oncologic cohort, 15.8% from a selected commercial testing cohort, and 14.5% from a highly selected dermatologic study. LIMITATIONS: Cohorts with varying degrees of selection, some retrospective. CONCLUSION: Germline predisposition in individuals with melanoma is common, with clinically actionable findings diagnosed in 10.6% to 15.8%.

Factitious Disorder as a Skin Ulcer: A Case Report.

Dermatitis artefacta (factitious dermatitis) is a dermatological disease of different types; it could appear on various parts of the body. It is associated with severe difficulties, such as psychic distress and negative feelings aroused in healthcare personnel or borderline personality disorder, and the long-term possibility of patient self-harm to create more symptoms, resulting in unnecessary medical procedures. This is a case of a 17-year-old girl who was hospitalized with a skin ulcer on her right ankle that proved to be a factitious disorder. She was experiencing severe symptoms of anxiety, such as feeling nervous, having trouble sleeping and concentrating, and an inability to control worry due to her preparation for university studies. She refused to see a mental health professional since the onset of anxiety symptoms, i.e., the last four months. Patients who present with factitious disorder deliberately create clinical signs of a somatic disease because they need warmth and attention in a medical environment. Symptoms offer no significant benefit, and the pathophysiological mechanisms are mainly psychological. The primary treatment for factitious disorder is psychotherapy while the management of the ulcer requires dermatosurgical treatment.

Use of Dermoscopy among Greek Dermatologists in Everyday Clinical Practice: A National Questionnaire-Based Study.

Background: Dermatoscopy has been established as an important diagnostic tool for a wide range of skin diseases. This study aims to evaluate the use of dermatoscopy in clinical practice among Greek dermatologists. Methods: A nationwide questionnaire-based survey was conducted collecting data on the frequency of dermatoscopic examinations, the types of lesions examined, training and educational resources, as well as factors influencing the choice to incorporate dermatoscopy into daily clinical routines. Results: A total of 366 Greek dermatologists participated in the survey. Most of the respondents reported the daily use of dermatoscopy in their practice. Pigmented and non-pigmented lesions, inflammatory diseases, cutaneous infectious, hair disorders, and nail lesions were the most common indications for dermatoscopy. Factors influencing the utilization of dermatoscopy included increased diagnostic accuracy, enhanced patient care, better patient communication and general compliance, and improved satisfaction among dermatologists. Conclusions: This national questionnaire-based study demonstrates that dermatoscopy has become an integral part of daily dermatological practice in Greece. The findings highlight the significance of structured training and education to promote dermoscopy's effective and routine use. Incorporating dermatoscopy into clinical practice not only improves diagnostic precision but also enhances patient care, contributing to the overall quality of dermatological services in Greece.

A Retrospective Study of Diameter and Breslow Thickness in Invasive Melanomas.

INTRODUCTION: A diameter larger than 6 mm is included in the criteria used in public health messages to detect a cutaneous melanoma. We aimed to investigate the independent association of Breslow thickness with the melanoma diameter. METHODS: A retrospective study was performed in patients with invasive melanomas of the nodular melanoma (NM) or superficial spreading melanoma (SSM) subtype. The quartiles of the diameter (lower, median, upper) were studied in non-parametric quantile regression model. RESULTS: In total, 537 cases of invasive melanomas were included and 60% had Breslow thickness ≤1.0 mm. There were 429 SSM (79.9%) and 108 NM (20.1%). Although NMs were significantly thicker (median Breslow thickness: 2.7 mm vs. 0.7 mm, respectively, p < 0.0001), they were not associated with larger diameter compared to SSMs (p = 0.71). After adjustment for age and sex, melanoma location and subtype, having Breslow thickness ≤1.0 mm was not significantly associated with the lower quartile, median and upper quartile of the diameter (p values: 0.063, 0.083, and 0.791, respectively). CONCLUSION: In our study including melanomas of the NM or SSM subtype, Breslow thickness was not associated with the diameter, adding evidence to support the limitations of using diameter larger than 6 mm for the detection of invasive melanomas and indicating the potential of smaller melanomas to be thicker tumors.

Expert Agreement on the Presence and Spatial Localization of Melanocytic Features in Dermoscopy.

Dermoscopy aids in melanoma detection; however, agreement on dermoscopic features, including those of high clinical relevance, remains poor. In this study, we attempted to evaluate agreement among experts on exemplar images not only for the presence of melanocytic-specific features but also for spatial localization. This was a cross-sectional, multicenter, observational study. Dermoscopy images exhibiting at least 1 of 31 melanocytic-specific features were submitted by 25 world experts as exemplars. Using a web-based platform that allows for image markup of specific contrast-defined regions (superpixels), 20 expert readers annotated 248 dermoscopic images in collections of 62 images. Each collection was reviewed by five independent readers. A total of 4,507 feature observations were performed. Good-to-excellent agreement was found for 14 of 31 features (45.2%), with eight achieving excellent agreement (Gwet's AC >0.75) and seven of them being melanoma-specific features. These features were peppering/granularity (0.91), shiny white streaks (0.89), typical pigment network (0.83), blotch irregular (0.82), negative network (0.81), irregular globules (0.78), dotted vessels (0.77), and blue-whitish veil (0.76). By utilizing an exemplar dataset, a good-to-excellent agreement was found for 14 features that have previously been shown useful in discriminating nevi from melanoma. All images are public (www.isic-archive.com) and can be used for education, scientific communication, and machine learning experiments.