Bacterial Skin Dysbiosis in Darier Disease.

INTRODUCTION: Darier disease is a rare inherited disease with dominant skin manifestations including keratotic papules and plaques on sebaceous and flexural areas. Secondary infection of skin lesions is common, and Staphylococcus aureus commonly colonizes these lesions. The aim of the study was to characterize the bacterial microbiome of cutaneous Darier lesions compared to normal-looking skin and disease severity. METHODS: All patients with a history of Darier followed up at Emek Medical Center were invited to participate in the study. Patients that did not use antibiotics in the past month and signed informed consent had four skin sites sampled with swabs: scalp, chest, axilla, and palm. All samples were analyzed for bacterial microbiome using 16S rDNA sequencing. RESULTS: Two hundred and eighty microbiome samples obtained from lesional and non-lesional skin of the scalp, chest, axilla, and palm of 42 Darier patients were included in the analysis. The most abundant bacterial genera across all skin sites were Propionibacterium, Corynebacterium, Paracoccus, Micrococcus, and Anaerococcus. Scalp and chest lesions featured a distinct microbiome configuration that was mainly driven by an overabundance of Staphylococci species. Patients with more severe disease exhibited microbiome alterations in the chest, axilla, and palm compared with patients with only mild disease, driven by Peptoniphilus and Moryella genera in scalp and palmar lesions, respectively. CONCLUSION: Staphylococci were significantly associated with Darier lesions and drove Darier-associated dysbiosis. Severity of the disease was associated with two other bacterial genera. Whether these associations also hold a causative role and may serve as a therapeutic target remains to be determined and requires further investigation.

[COMPREHENSIVE GUIDELINES AND INDICATIONS FOR DIGITAL MONITORING OF PATIENTS AT HIGH-RISK FOR MELANOMA: A POSITION PAPER BY THE ISRAELI ASSOCIATION FOR DERMATOLOGY].

INTRODUCTION: Early detection may lead to reduced morbidity and mortality from melanoma. This study aims to establish guidelines for selecting patients suitable for digital monitoring of skin lesions. METHODS: A literature review was conducted, followed by consensus among experts appointed by the Israeli Dermatology Association. RESULTS: Two effective methods for early melanoma diagnosis were identified: Total-body photography (TBP) and digital dermoscopy. TBP involves capturing clinical images of the entire skin area for long-term monitoring (6-12 months). Digital dermoscopy focuses on close-up images of distinct lesions for short-term monitoring (3-4 months). Various risk factors for melanoma were identified, including genetic and familial factors, as well as demographic and phenotypic characteristics. Based on these risk factors and feasibility of clinical follow-up, a comprehensive list of indications for TBP was developed, categorized into three groups based on the expected level of benefit. Digital dermoscopy surveillance is recommended for patients with flat or slightly raised skin lesions showing dermoscopic features that do not definitively indicate melanoma. DISCUSSION: TBP significantly improves early melanoma detection, enhancing sensitivity and specificity while reducing unnecessary biopsies. However, due to its high cost and limited coverage by the Israeli public health care system, prioritizing patients who would benefit most from TBP is crucial. The compiled list of indications aligns with international recommendations and provides further details within the article.

Suggested methodology for longitudinal evaluation of nevi based on clinical images.

BACKGROUND: Melanoma screening includes the assessment of changes in melanocytic lesions using images. However, previous studies of normal nevus temporal changes showed variable results and the optimal method for evaluating these changes remains unclear. Our aim was to evaluate the reproducibility of (a) nevus count done at a single time point (method I) versus two time points (method II); and (b) manual and automated nevus diameter measurements. MATERIALS AND METHODS: In a first experiment, participants used either a single time point or a two time point annotation method to evaluate the total number and size of nevi on the back of an atypical mole syndrome patient. A Monte Carlo simulation was used to calculate the variance observed. In a second experiment, manual measurements of nevi on 2D images were compared to an automated measurement on 3D images. Percent difference in the paired manual and automated measurements was calculated. RESULTS: Mean nevus count was 137 in method I and 115.5 in method II. The standard deviation was greater in method I (38.80) than in method II (4.65) (p = 0.0025). Manual diameter measurements had intraclass correlation coefficient of 0.88. The observed mean percent difference between manual and automated diameter measurements was 1.5%. Lightly pigmented and laterally located nevi had a higher percent difference. CONCLUSIONS: Comparison of nevi from two different time points is more consistent than nevus count performed separately at each time point. In addition, except for selected cases, automated measurements of nevus diameter on 3D images can be used as a time-saving reproducible substitute for manual measurement on 2D images.

Dermoscopic features of basal cell carcinoma and its subtypes: A systematic review.

BACKGROUND: Multiple studies have reported on dermoscopic structures in basal cell carcinoma (BCC) and its subtypes, with varying results. OBJECTIVE: To systematically review the prevalence of dermoscopic structures in BCC and its subtypes. METHODS: Databases and reference lists were searched for relevant trials according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were assessed for the relative proportion of BCC dermoscopic features. Random-effects models were used to estimate summary effect sizes. RESULTS: Included were 31 studies consisting of 5950 BCCs. The most common dermoscopic features seen in BCC were arborizing vessels (59%), shiny white structures (49%), and large blue-grey ovoid nests (34%). Arborizing vessels, ulceration, and blue-grey ovoid nests and globules were most common in nodular BCC; short-fine telangiectasia, multiple small erosions, and leaf-like, spoke wheel and concentric structures in superficial BCC; porcelain white areas and arborizing vessels in morpheaform BCC; and arborizing vessels and ulceration in infiltrative BCC. LIMITATIONS: Studies had significant heterogeneity. Studies reporting BCC histopathologic subtypes did not provide clinical data on pigmentation of lesions. CONCLUSION: In addition to arborizing vessels, shiny white structures are a common feature of BCC. A constellation of dermoscopic features may aid in differentiating between BCC histopathologic subtypes.

The diagnostic accuracy of dermoscopy for basal cell carcinoma: A systematic review and meta-analysis.

BACKGROUND: Dermoscopy is a noninvasive technique for the diagnosis of skin lesions. Its accuracy for basal cell carcinoma (BCC) has not been systematically studied. OBJECTIVE: We sought to systematically investigate the accuracy of dermoscopy for the diagnosis of BCC compared with examination with the naked eye. METHODS: A systematic review of studies reporting the accuracy of naked eye examination and dermoscopy for the diagnosis of BCC was conducted. A meta-analysis for sensitivity and specificity was performed using a bivariate mixed-effects logistic regression modeling framework. RESULTS: Seventeen studies were identified. The pooled sensitivity and specificity of dermoscopy for the diagnosis of BCC were 91.2% and 95%, respectively. In studies comparing test performance, adding dermoscopy to naked eye examination improved sensitivity from 66.9% to 85% (P = .0001) and specificity from 97.2% to 98.2% (P = .006). The sensitivity and specificity of dermoscopy were higher for pigmented than nonpigmented BCC. Sensitivity increased when dermoscopy was performed by experts and when the diagnosis was based on in-person dermoscopy as opposed to dermoscopic photographs. LIMITATIONS: Significant heterogeneity among studies with a medium-to-high risk of bias. CONCLUSION: Dermoscopy is a sensitive and specific add-on tool for the diagnosis of BCC. It is especially valuable for pigmented BCC.

Association of bullous pemphigoid with malignancy: A systematic review and meta-analysis.

BACKGROUND: Studies evaluating whether malignancy rate is increased in patients with bullous pemphigoid (BP) have reached conflicting results. OBJECTIVE: We sought to determine whether BP is associated with malignancy. METHOD: Medline, EMBASE, the Cochrane library, and reference lists of included studies were searched for comparative studies that evaluated the relationship between BP and malignancy. Data were analyzed on the basis of study design: cross-sectional, case control, and cohort. A meta-analysis was performed by using a random effects model to estimate pooled odds ratio. RESULTS: The review included 8 studies. No association between BP and overall cancer was found for any of the study designs. Although a single cohort study reported an association with lymphoid leukemia and kidney and larynx cancer, a pooled analysis of case-control studies did not. A pooled analysis of cross-sectional studies found a significant association between BP and hematologic malignancies. LIMITATIONS: The paucity of well-designed studies hindered the possibility of proving or disproving the BP-cancer association. CONCLUSION: We did not find an association of BP with overall malignancy, but a possible association with hematologic malignancy was observed.

Picosecond lasers for tattoo removal: a systematic review.

Given that the pigment particles in tattoos have a relaxation time of <10 ns, picosecond lasers would be expected to be more effective than nanosecond lasers in tattoo removal. To systematically review the evidence regarding the effectiveness and safety of picosecond lasers for tattoo removal, Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and reference lists were searched for relevant trials. The primary outcome was >70 % clearance of tattoo pigment. Secondary outcomes were 90-100 % clearance of tattoo pigment, number of laser sessions required, and adverse effects. Eight trials were included, six with human participants (160 participants) and 2 with animal models. Seven of the eight trials explored the usage of either 755, 758, 795, 1064, or 1064/532-nm picosecond lasers for black and blue ink tattoos. In the human trials, 69-100 % of tattoos showed over 70 % clearance of pigment after 1-10 laser treatments. Reported side effects included pain, hyperpigmentation and hypopigmentation, blister formation and transient erythema, edema, and pinpoint bleeding. Included articles varied in type of laser investigated, mostly non-comparative studies and with a medium to high risk of bias. There is sparse evidence that picosecond lasers are more effective than their nanosecond counterparts for mainly black and blue ink tattoo removal, with minor side effects.

Importance of Both Clinical and Dermoscopic Findings in Predicting High-Risk Histopathological Subtype in Facial Basal Cell Carcinomas.

INTRODUCTION: Being able to recognize high-risk facial basal cell carcinoma (BCC) may lead to fewer incomplete excisions and inappropriate treatments. OBJECTIVES: We sought to investigate clinical and dermoscopic criteria for predicting facial BCC subtypes, analyze the interobserver agreement between readers, and develop a diagnostic algorithm to predict high-risk histopathological subtype. METHODS: In this single-center, retrospective investigation, 6 independent readers evaluated predefined clinical and dermoscopic criteria in images of histopathologically verified primary facial BCCs including: topography, border demarcation, vessels, ulceration, white porcelain areas, shiny white blotches and strands, and pigmented structures and vessels within ulceration. RESULTS: Overall, 297 clinical and dermoscopic image pairs were analyzed. The strongest associations with high-risk subtype were: "bumpy" topography (OR 3.8, 95% CI, 3.1-4.7), ill-defined borders (OR 3.4, 95% CI 3.1-4.7), white porcelain area (OR 3.5, 95% CI 2.8-4.5), and vessels within ulceration (OR 3.1, 95% CI 2.4-4.1). Predominantly focused vessels were a positive diagnostic criterium for either nodular (OR 1.7, 95% CI 1.3-2.2) or high-risk (OR 2.0, 95% CI 1.6-2.5) subtypes and a strong negative diagnostic criterium for superficial BCC (OR 14.0, 95% CI 9.6-20.8). Interobserver agreement ranged from fair to substantial (κ=0.36 to 0.72). A diagnostic algorithm based on these findings demonstrated a sensitivity of 81.4% (95% CI, 78.9-83.7%) and a specificity of 53.3% (95% CI, 49.7-56.9%) for predicting high-risk BCC subtype. CONCLUSIONS: Integration of both clinical and dermoscopic features (including novel features such as topography and vessels within ulceration) are essential to improve subtype prediction of facial BCCs and management decisions.

BCN20000: Dermoscopic Lesions in the Wild.

Advancements in dermatological artificial intelligence research require high-quality and comprehensive datasets that mirror real-world clinical scenarios. We introduce a collection of 18,946 dermoscopic images spanning from 2010 to 2016, collated at the Hospital Clínic in Barcelona, Spain. The BCN20000 dataset aims to address the problem of unconstrained classification of dermoscopic images of skin cancer, including lesions in hard-to-diagnose locations such as those found in nails and mucosa, large lesions which do not fit in the aperture of the dermoscopy device, and hypo-pigmented lesions. Our dataset covers eight key diagnostic categories in dermoscopy, providing a diverse range of lesions for artificial intelligence model training. Furthermore, a ninth out-of-distribution (OOD) class is also present on the test set, comprised of lesions which could not be distinctively classified as any of the others. By providing a comprehensive collection of varied images, BCN20000 helps bridge the gap between the training data for machine learning models and the day-to-day practice of medical practitioners. Additionally, we present a set of baseline classifiers based on state-of-the-art neural networks, which can be extended by other researchers for further experimentation.

Facial demodicosis in the immunosuppressed state: a retrospective case series from a tertiary referral center.

BACKGROUND: Data on Demodex in the immunosuppressed state is limited, focusing mainly on patients with human immunodeficiency virus and hematological malignancies. The aim of this study was to describe the manifestations of facial demodicosis in diverse immunosuppressive states. METHODS: The medical records of all patients followed at a Demodex outpatient clinic of a tertiary medical center from January 2008 to November 2020 were retrospectively reviewed. Data on patients who were immunosuppressed while with demodicosis were retrieved. RESULTS: The cohort included 28 patients (17 women and 11 men; median age, 58 years). Types of immunosuppression included treatments with hydroxyurea for polycythemia vera/essential thrombocytosis, mycophenolic acid, tacrolimus, and prednisone for liver and/or kidney transplantation, prednisone with cyclosporine/methotrexate/azathioprine/rituximab mainly for autoimmune diseases, mercaptopurine with/without anti-tumor necrosis factor alpha (TNF-α) for Crohn's disease, chemotherapy for neoplasms, anti-TNF-α for psoriasis, and Cushing's syndrome. The clinical types of demodicosis included: papulopustular, erythematotelangiectatic and fulminant rosacea, hyperpigmented, pityriasis folliculorum, pustular folliculitis, and dermatitis. The diverse clinical presentations led to various differential diagnoses. Topical treatment with ivermectin (monotherapy/combination with other treatments) was effective. CONCLUSION: Clinicians treating immunosuppressed patients should be familiar with the different forms of demodicosis and include them in the differential diagnosis of facial eruptions.

Using blend wavelengths in order to improve the safety and efficacy of laser hair removal.

BACKGROUND: As the pursuit for a safe and effective device for laser hair removal continues, the use of simultaneous multiple wavelengths in a single device requires further exploration. AIM: To evaluate the safety and efficacy of a novel multi-wavelength laser device for hair removal. PATIENTS AND METHODS: This retrospective cohort study included adult participants of both sexes with Fitzpatrick skin types of III and IV. Hairy sites were treated by a multiple wavelength (810nm, 940nm, and 1064nm) laser device (Primelase, Coccoon medical, Barcelona, Spain). Laser parameters included: fluence of 14-20 J/cm2 , pulse duration of 7-30 ms, and spot size of 20*9 mm2 . Participants underwent up to 7 treatments at 6-8 weeks intervals and were followed for 6 months after the last treatment session. "Before" and "after" clinical photographs were acquired and were used to evaluate efficacy by 2 independent dermatologists. They employed the Global Aesthetic Improvement Scale (GAIS; scale of 0 [no improvement] to 4 [excellent improvement; Over 75% hair reduction]). Participants' satisfaction was rated on a scale of 1 (not satisfied) to 5 (very satisfied). Pain perception and adverse events were recorded as well. RESULTS: Eighteen participants (6 men, 12 women) were included with a total of 49 treatment sites. Mean hair reduction was 3.6 out of 4 in the GAIS. Participants' satisfaction rate was high (mean 4.5). Beside mild transient discomfort during the procedure, no adverse events were recorded. CONCLUSION: The use of a multiple wavelengths' laser device is safe and effective for hair removal.

Clinical and dermoscopic features of Fibroepithelioma of Pinkus: case series with an emphasis on hypopigmented to pink lines intersecting at acute angles.

Fibroepithelioma of Pinkus (FEP) is a subtype of basal cell carcinoma (BCC) that can clinically resemble intradermal nevi (IDN) and fibromas. We performed a retrospective review of consecutively biopsied lesions confirmed to be FEP on histopathology diagnosed from January 1, 2008 to April 8, 2019. Clinical (n = 48), contact non-polarized dermoscopy (NPD) (n = 44), and contact polarized dermoscopy (PD) (n = 22) images from 36 patients were reviewed. Mean age was 64.5 years (SD 15.1 years, range 24-86 years) at diagnosis of first FEP lesion. Most lesions were located on the torso (n = 28, 58.3%), followed by the lower extremity (n = 9, 18.8%). The most common differential diagnoses at the time of biopsy included BCC (n = 40) and nevus (other than IDN, n = 5). Clinically, FEP were pink (95.8%), scaly (66.7%) papules (77.1%) displaying disrupted skin markings (62.5%) and absence of hair follicles (87.5%). NPD revealed serpentine (97.7%), dotted (81.8%), or polymorphous vessels (86.4%), and hypopigmented to pink lines intersecting at acute angles (HPLA) (52.3%). PD demonstrated serpentine (95.5%), dotted (86.4%), or polymorphous vessels (81.8%), shiny white lines (50.0%), and HPLA (59.1%). Classic features of BCC such as arborizing vessels (n = 2), ulceration (n = 1), shiny white blotches and strands (n = 1), blue-gray ovoid nest (n = 1), and leaf-like areas (n = 1) were uncommon. FEP often presents as scaly, erythematous papules with disrupted skin markings and absence of hair follicles. Dermoscopy reveals polymorphous vessels with shiny white lines and HPLA.

A patient-centric dataset of images and metadata for identifying melanomas using clinical context.

Prior skin image datasets have not addressed patient-level information obtained from multiple skin lesions from the same patient. Though artificial intelligence classification algorithms have achieved expert-level performance in controlled studies examining single images, in practice dermatologists base their judgment holistically from multiple lesions on the same patient. The 2020 SIIM-ISIC Melanoma Classification challenge dataset described herein was constructed to address this discrepancy between prior challenges and clinical practice, providing for each image in the dataset an identifier allowing lesions from the same patient to be mapped to one another. This patient-level contextual information is frequently used by clinicians to diagnose melanoma and is especially useful in ruling out false positives in patients with many atypical nevi. The dataset represents 2,056 patients (20.8% with at least one melanoma, 79.2% with zero melanomas) from three continents with an average of 16 lesions per patient, consisting of 33,126 dermoscopic images and 584 (1.8%) histopathologically confirmed melanomas compared with benign melanoma mimickers.

Retinoic acid receptor agonist as monotherapy for early-stage mycosis fungoides: does it work?

BACKGROUND: Retinoids exert their biologic effects by binding to intracellular retinoic-acid receptors (RARs) and/or retinoid X receptors (RXRs). Early-stage mycosis fungoides (MF) has been effectively treated with bexarotene, an RXR-agonist, with overall response (OR) rates 54-67% and complete response (CR) rates 7-27%. Data on RAR-agonist monotherapy are limited. OBJECTIVE: To analyze the effectiveness of RAR-agonist monotherapy for early-stage MF. METHODS: Data on patients with early-stage MF treated with acitretin/isotretinoin monotherapy at a tertiary cutaneous lymphoma clinic in 2010-2017 were collected retrospectively from the medical files. RESULTS: Thirty-five patients (26 males) of median age 50 years (range 8-83) with early-stage MF (IA 9, IB 26) underwent 37 treatment events: 25 acitretin and 12 isotretinoin at a median dosages of 0.3 mg/kg (range 0.2-0.9) and 0.2 mg/kg (range 0.1-0.7), respectively. Median time to maximal response was 6 months for both (range 1-10 for acitretin, 3-16 for isotretinoin); median treatment duration was 10 months (range 3-46) for acitretin, and 9 months (range 3-55) for isotretinoin. OR was 64% for acitretin and 80% for isotretinoin, and CR, 4% and 8%, respectively. Side-effect profiles were as previously reported for retinoids. CONCLUSIONS: Early-stage MF patients may benefit from low dose RAR-agonist monotherapy, although the CR rate is low.

Are Biologics Efficacious in Atopic Dermatitis? A Systematic Review and Meta-Analysis.

BACKGROUND: Current systemic treatments for atopic dermatitis (AD) offer limited efficacy and are often restricted by safety concerns. Biologics may address the unmet need for improved AD therapeutics. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of biologic agents in AD. METHODS: A systematic review and meta-analysis of studies evaluating AD patients treated with biologics was performed. The primary outcome was the Eczema Area and Severity Index (EASI)-75 response, while secondary outcomes were SCOring Atopic Dermatitis (SCORAD)-75, EASI-50, SCORAD-50, Investigator Global Assessment 0/1 responses, change in responses from baseline, and adverse events. RESULTS: We included 13 randomized controlled trials (RCTs) and 10 observational studies evaluating nine biologics. High-quality evidence was available for dupilumab, nemolizumab and ustekinumab. Pooling five studies, at weeks 12-16 dupilumab 300 mg every week to every 2 weeks achieved EASI-75 responses of 55%, superior to placebo [relative risk (RR) 3.3, 95% confidence interval (CI) 2.9-3.6]. Nemolizumab had similar EASI-75 responses as placebo, but significantly improved pruritus. In online reports, lebrikizumab demonstrated superior EASI-50 responses versus placebo (RR 1.3, 95% CI 1.04-1.7), while tralokinumab had superior SCORAD-50 responses versus placebo, with borderline significance (RR 1.7, 95% CI 0.97-3.1). In two RCTs each, omalizumab and ustekinumab were comparable with placebo, while antithymic stromal lymphopoietin receptor, infliximab, and rituximab lacked adequate evidence of efficacy. All medications had a comparable safety profile to placebo. LIMITATIONS: Lack of RCTs and the use of variable outcome measures limited conclusions. CONCLUSION: Dupilumab is currently the only biologic with robust evidence of efficacy in AD. Nemolizumab, lebrikizumab, and tralokinumab show promise but further data are needed. Longer follow-up and larger studies will establish their safety profile.