Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

BACKGROUND: Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. OBJECTIVES: To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. METHODS: We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). RESULTS: Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. CONCLUSIONS: Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

Assessing field cancerization and actinic keratosis using ultraviolet-induced fluorescence dermatoscopy after the application of 5-aminolevulinic acid - An observational study.

BACKGROUND: Actinic keratoses (AK) are one of the most frequent reasons for consultations in dermatology. Ultraviolet-induced fluorescence dermatoscopy (UVFD) is a new method that allows the assessment of lesions in a spectrum of light that originates from the fluorochromes emitting UV-excited luminescence. The aim of this study was to assess the UVFD features of AKs before PDT and their intensity in field cancerization and single lesions. METHODS: This retrospective study was conducted from June to November 2023. Lesions were assessed with the Olsen scale clinically and dermatoscopically (DermLite DL5, 10x magnification) and photographed. UVFD fluorescence was categorized as 'none', 'weak', 'moderate', and 'intense'. A 1-mm thick layer of 10 % 5-ALA gel was applied to single lesions or cancerization field (depending on the patient) and covered with an occlusive dressing for 3 h. Prior the application of 10 % 5-ALA gel, the lesions were degreased with an alcoholic solution. The occlusion was removed, and the field was cleaned with a 0,9 % saline solution. Afterward, each lesion was photographed in polarized light and UVFD mode. RESULTS: A total of 194 dermatoscopic images were analyzed, 111 corresponded to field cancerization and 81 to single AKs. Overall, weak fluorescence was noticed in 22 of them (11,3 %), moderate in 107 (55,15 %), and intense in 65 (33,5 %). Amongst field cancerization (111 images), weak fluorescence was seen in 11 (9.9 %), moderate in 68 (61,26 %), and intense in 32 (28,82 %). In single lesions (81 images), weak fluorescence was detected in 11 (13,2 %), moderate in 39 (46,99 %), and intense in 33 (28.83 %) of the lesions. Slightly more intense fluorescence was noticed in higher Olsen grade (p = 0.04). CONCLUSIONS: UVFD can enhance our efficacy of pre-procedural examination and might arise as a useful device to predict the therapeutic effect of PDT.

Applications of Ultraviolet and Sub-ultraviolet Dermatoscopy in Neoplastic and Non-neoplastic Dermatoses: A Systematic Review.

Dermatoscopy is a non-invasive and cost-efficient imaging technique augmenting clinical examination in neoplastic and non-neoplastic dermatoses. Recently, novel dermatoscopic techniques based on principles of reflectance/absorption and excited fluorescence have been developed. However, comprehensive data on their applications are sparse, and terminology is inconsistent. In this systematic review, we addressed the principles of ultraviolet (UV) imaging and proposed categorization based on spectral characteristics and signal acquisition, as well as discussed documented and potential clinical applications, safety measures during examination, and limitations associated with reflectance and fluorescence dermatoscopy. A literature search was conducted in the PubMed medical database until 2 December 2023 according to PRISMA guidelines, and 28 papers fit the scope of this review, whereas additional relevant articles were included to provide broader context regarding the chosen terminology, chromophores described, safety of sub-UV/UV, and regulations for light-emitting devices. UV and sub-UV dermatoscopy, categorized into different methods on the basis of the emitted wavelength and signal acquisition process (reflectance versus fluorescence), augment conventional dermatoscopy by optimizing safety margins in melanoma, facilitating early detection of tumor recurrence, and enhancing visualization in non-neoplastic conditions, including pigmentation disorders, intertrigo, papulo-desquamative dermatoses, and beyond. The review highlights the limitations of these techniques, including difficulty in differentiating melanin from hemoglobin, challenges in evaluating uneven surfaces, and artifacts. Although UV dermatoscopy complements conventional dermatoscopy, clinicians should be aware of their peculiarities, artifacts, limitations, and safety concerns to optimize their diagnostic accuracy and ensure patient's safety.

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

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

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.

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI-assisted smartphone apps and web-based services for skin disease.

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

Lentigo maligna and lentigo maligna melanoma in patients younger than 50†years: a multicentre international clinical-dermoscopic study.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) is usually diagnosed in older patients, when lesions are larger. However, it is important to detect it at an earlier stage to minimize the area for surgical procedure. OBJECTIVES: To determine and define clinical, dermoscopic and reflectance confocal microscopy (RCM) features of LM/LMM in patients < 50 years old. METHODS: This was a multicentre study involving tertiary referral centres for skin cancer management. The study included cases of consecutively excised LM/LMM arising in patients < 50 years of age with a histopathological diagnosis of LM/LMM and a complete set of clinical and dermoscopic images; RCM images were considered when present. RESULTS: In total, 85 LM/LMM of the face from 85 patients < 50 years were included in the study. A regression model showed a direct association with the size of the lesion (R2 = 0.08; P = 0.01) and with the number of dermoscopic features at diagnosis (R2 = 0.12; P < 0.01). In a multivariable analysis, an increasing number of dermoscopic features correlated with increased patient age (P < 0.01), while the presence of grey colour was a predictor of younger age at diagnosis (P = 0.03). RCM revealed the presence of melanoma diagnostic features in all cases (pagetoid cells and atypical nesting). CONCLUSIONS: LM is not a disease limited to older people as previously thought. LM presenting in young adults tends to be smaller and with fewer dermoscopic features, making its diagnosis challenging. Careful evaluation of facial pigmented lesions prior to cosmetic procedures is imperative to avoid incorrectly treating early LM as a benign lesion.

Perifollicular linear projections: A dermatoscopic criterion for the diagnosis of lentigo maligna on the face.

BACKGROUND: Lentigo maligna (LM) can mimic benign, flat, pigmented lesions and can be challenging to diagnose. OBJECTIVE: To describe a new dermatoscopic feature termed "perifollicular linear projections (PLP)" as a diagnostic criterion for LM on the face. METHODS: Retrospective study on reflectance confocal microscopy and dermatoscopy images of flat facial pigmented lesions originating from 2 databases. PLP were defined as short, linear, pigmented projections emanating from hair follicles. Dermatoscopy readers were blinded to the final histopathologic diagnosis. RESULTS: From 83 consecutive LMs, 21/83 (25.3%) displayed "bulging of hair follicles" on reflectance confocal microscopy and 18 of these 21 (85.7%), displayed PLP on dermatoscopy. From a database of 2873 consecutively imaged and biopsied lesions, 252 flat-pigmented facial lesions were included. PLP was seen in 47/76 melanomas (61.8%), compared with 7/176 lesions (3.9%) with other diagnosis (P < .001). The sensitivity was 61.8% (95% CI, 49.9%-72.7%), specificity 96.0% (95% CI, 92.9%-98.4%). PLP was independently associated with LM diagnosis on multivariate analysis (OR 26.1 [95% CI, 9.6%-71.0]). LIMITATIONS: Retrospective study. CONCLUSION: PLP is a newly described dermatoscopic criterion that may add specificity and sensitivity to the early diagnosis of LM located on the face. We postulate that PLP constitutes an intermediary step in the LM progression model.

Porokeratoses-A Comprehensive Review on the Genetics and Metabolomics, Imaging Methods and Management of Common Clinical Variants.

Porokeratosis is a heterogeneous group of keratinising disorders characterised by the presence of particular microscopic structural changes, namely the presence of the cornoid lamella. This structure develops as a consequence of a defective isoprenoid pathway, critical for cholesterol synthesis. Commonly recognised variants include disseminated superficial actinic porokeratosis, disseminated superficial porokeratosis, porokeratosis of Mibelli, palmoplantar porokeratosis (including porokeratosis palmaris et plantaris disseminata and punctate porokeratosis), linear porokeratosis, verrucous porokeratosis (also known as genitogluteal porokeratosis), follicular porokeratosis and porokeratoma. Apart from the clinical presentation and epidemiology of each variant listed, this review aims at providing up-to-date information on the precise genetic background, introduces imaging methods facilitating the diagnosis (conventional and ultraviolet-induced fluorescence dermatoscopy, reflectance confocal microscopy and pathology), discusses their oncogenic potential and reviews the literature data on the efficacy of the treatment used, including the drugs directly targeting the isoprenoid-mevalonate pathway.

Management of periocular keratinocyte carcinomas with Mohs micrographic surgery and predictors of complex reconstruction: a retrospective study.

BACKGROUND: Skin cancer is the most frequent cancer worldwide and the most frequent periocular tumor. Keratinocyte Carcinomas (KC) located in periorificial areas, such as periocular tumors, are considered high-risk tumors. Mohs Micrographic Surgery (MMS) is considered the first line for the treatment of high-risk KC, providing a lower recurrence rate than conventional wide excision. OBJECTIVE: To describe the clinical-pathological features of periocular KC treated with MMS in a tertiary university center in Chile. METHODS: A single-center, retrospective study of patients with KC located on the periocular area, that underwent MMS between 2017‒2022. MMS details were recorded. RESULTS: One hundred thirteen patients with periocular carcinomas were included. The mean age was 59 ± 13 years; 52% were women. The most frequent location was the medial canthus (53%), followed by the lower eyelid (30.1%). The most frequent BCC histology was the nodular variant (59.3%). Regarding MMS, the average number of stages was 1.5 ± 0.7, and 54% of the cases required only 1 stage to achieve clear margins. To date, no recurrence has been reported. Tumors larger than 8.5 mm in largest diameter or 43.5 mm2 were more likely to require complex reconstruction. STUDY LIMITATIONS: Retrospective design and a relatively low number of patients in the SCC group. Possible selection bias, as larger or more complex cases, may have been referred to oculoplastic surgeons directly. CONCLUSION: The present study confirms the role of MMS for the treatment of periocular KCs. Periocular KCs larger than 8.5 mm might require complex reconstruction. These results can be used to counsel patients during pre-surgical visits.

Patterns of Recurrence of Cutaneous Melanoma: A Literature Review.

The incidence of melanoma has been dramatically increasing over the last decades. Melanoma is considered to have a high metastatic potential and it can progress via lymphatic vessels or through hematogenous metastasis. Different patterns of recurrence have been described, namely, local, satellite, and in transit metastasis (LCIT), lymphatic metastasis, and systemic metastasis. With a more advanced melanoma stage at diagnosis, there is a higher risk for systemic metastasis in comparison to LCIT; in contrast, early-stage melanoma tends to recur more frequently as LCIT and less commonly as systematic metastasis. The aim of this review was to summarize the patterns of recurrence of cuta-neous melanoma, giving the clinician a practical summary for diagnosis, prognosis, and surveillance. There is a knowledge gap of the common patterns of recurrence that needs to be addressed to better identify patients at high risk of disease recurrence and personalize surveillance strategies as well as patient counseling.

Generation of a Melanoma and Nevus Data Set From Unstandardized Clinical Photographs on the Internet.

Importance: Artificial intelligence (AI) training for diagnosing dermatologic images requires large amounts of clean data. Dermatologic images have different compositions, and many are inaccessible due to privacy concerns, which hinder the development of AI. Objective: To build a training data set for discriminative and generative AI from unstandardized internet images of melanoma and nevus. Design, Setting, and Participants: In this diagnostic study, a total of 5619 (CAN5600 data set) and 2006 (CAN2000 data set; a manually revised subset of CAN5600) cropped lesion images of either melanoma or nevus were semiautomatically annotated from approximately 500 000 photographs on the internet using convolutional neural networks (CNNs), region-based CNNs, and large mask inpainting. For unsupervised pretraining, 132 673 possible lesions (LESION130k data set) were also created with diversity by collecting images from 18 482 websites in approximately 80 countries. A total of 5000 synthetic images (GAN5000 data set) were generated using the generative adversarial network (StyleGAN2-ADA; training, CAN2000 data set; pretraining, LESION130k data set). Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) for determining malignant neoplasms was analyzed. In each test, 1 of the 7 preexisting public data sets (total of 2312 images; including Edinburgh, an SNU subset, Asan test, Waterloo, 7-point criteria evaluation, PAD-UFES-20, and MED-NODE) was used as the test data set. Subsequently, a comparative study was conducted between the performance of the EfficientNet Lite0 CNN on the proposed data set and that trained on the remaining 6 preexisting data sets. Results: The EfficientNet Lite0 CNN trained on the annotated or synthetic images achieved higher or equivalent mean (SD) AUROCs to the EfficientNet Lite0 trained using the pathologically confirmed public data sets, including CAN5600 (0.874 [0.042]; P = .02), CAN2000 (0.848 [0.027]; P = .08), and GAN5000 (0.838 [0.040]; P = .31 [Wilcoxon signed rank test]) and the preexisting data sets combined (0.809 [0.063]) by the benefits of increased size of the training data set. Conclusions and Relevance: The synthetic data set in this diagnostic study was created using various AI technologies from internet images. A neural network trained on the created data set (CAN5600) performed better than the same network trained on preexisting data sets combined. Both the annotated (CAN5600 and LESION130k) and synthetic (GAN5000) data sets could be shared for AI training and consensus between physicians.

Pityriasis Versicolor-A Narrative Review on the Diagnosis and Management.

This narrative review presents a comprehensive overview of the diagnosis and management of pityriasis versicolor (PV), a common superficial fungal infection caused by the yeast Malassezia. PV is characterised by scaly hypopigmented or hyperpigmented patches, primarily affecting the upper trunk, neck, and upper arms. Regarding commensal interactions, Malassezia utilises nutrient sources without affecting the human host. In cases of pathogenicity, Malassezia can directly harm the host via virulence factors or toxins, or indirectly by triggering damaging host responses. The diagnosis typically relies on recognising characteristic clinical features. Due to the wide variability in its clinical presentation, recognising the differential diagnosis is critical. In this paper, we discuss the clinical differentials, with their dermatoscopic presentation, but also describe a range of helpful diagnostic techniques (microscopy, conventional and ultraviolet-induced fluorescence dermatoscopy, and confocal microscopy). Topical therapies are the primary treatment for PV, encompassing non-specific antifungal agents like sulphur with salicylic acid, selenium sulphide 2.5%, and zinc pyrithione. Additionally, specific topical antifungal medications with either fungicidal or fungistatic properties may also be incorporated into the topical treatment regimen, such as imidazoles, allylamines, and ciclopirox olamine. Systemic therapies might occasionally be used. Patient education and the promotion of good personal hygiene are pivotal to reduce the risk of recurrence. In recurrent cases, particularly during warmer and more humid periods, prolonged prophylaxis with topical agents should be considered.