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Clinical & Translational Research
Safety and Efficacy of Ritlecitinib and Brepocitinib in Alopecia Areata: Results from the Crossover Open-Label Extension of the ALLEGRO Phase 2a Trial
The 24-week, double-blind period of the ALLEGRO phase 2a trial (NCT02974868) evaluated the safety and efficacy of ritlecitinib (Jak3/tyrosine kinase expressed in the hepatocellular carcinoma inhibitor) and brepocitinib (tyrosine kinase 2/Jak1 inhibitor) in patients with alopecia areata; patients could subsequently continue treatment in a 24-week single-blind extension, followed by a crossover open-label extension, described in this article. Patients who did not achieve ≥30% improvement from baseline in Severity of Alopecia Tool score at the end of the single-blind extension entered a 24-week crossover open-label extension: the ritlecitinib group switched to brepocitinib, and the brepocitinib group switched to ritlecitinib.Resolution of Eczema with Multivalent Peptides
The integrity of the skin is an important aspect of QOL. Whether caused by genetic deficiencies or environmental insults, disruption of the surface barrier allows irritants and allergens to penetrate the skin, which initiates inflammatory responses by immune cells that often lead to life-long allergies. In this study, eczema was induced on depilated mouse skin with topical lipopolysaccharide or a mixture of Staphylococcal enterotoxin B and an extract of house dust mites, which resulted in thickening of the epidermis, epidermal disruption, and abundant neutrophils in the dermis.A Scoping Review and Population Study Regarding Prevalence and Histopathology of Juvenile Vulvar Melanocytic Lesions. A Recommendation
Cases of vulvar melanocytic lesions in juveniles are rarely reported. We analyze the evidence regarding vulvar melanocytic lesions in juveniles with or without vulvar lichen sclerosus to help decision making by clinicians and pathologists. A scoping review on vulvar melanocytic lesions with or without vulvar lichen sclerosus, including malignant vulvar melanomas, in females up to age 18 years was performed. In addition, the histopathology records of the cohort of all such lesions in The Netherlands from 1991 through 2020 were investigated, and a structured analysis of tissue samples of the subset of cases with lichen sclerosus was performed.Restoring Prohealing/Remodeling-Associated M2a/c Macrophages Using ON101 Accelerates Diabetic Wound Healing
Diabetic wounds exhibit chronic inflammation and delayed tissue proliferation or remodeling, mainly owing to prolonged proinflammatory (M1) macrophage activity and defects in transition to prohealing/proremodeling (M2a/M2c; CD206+ and/or CD163+) macrophages. We found that topical treatment with ON101, a plant-based potential therapeutic for diabetic foot ulcers, increased M2c-like (CD163+ and CD206+) cells and suppressed M1-like cells, altering the inflammatory gene profile in a diabetic mouse model compared with that in the controls.Detecting Eczema Areas in Digital Images: An Impossible Task?
Assessing the severity of atopic dermatitis (AD, or eczema) traditionally relies on a face-to-face assessment by healthcare professionals and may suffer from inter- and intra-rater variability. With the expanding role of telemedicine, several machine learning algorithms have been proposed to automatically assess AD severity from digital images. Those algorithms usually detect and then delineate (segment) AD lesions before assessing lesional severity and are trained using the data of AD areas detected by healthcare professionals.Nasal Dysbiosis in Cutaneous T-Cell Lymphoma Is Characterized by Shifts in Relative Abundances of Non-Staphylococcus Bacteria
The nasal microbiome of patients with cutaneous T-cell lymphoma (CTCL) remains unexplored despite growing evidence connecting nasal bacteria to skin health and disease. Nasal swabs from 45 patients with CTCL (40 with mycosis fungoides, 5 with Sézary syndrome) and 20 healthy controls from the same geographical region (Chicago Metropolitan Area, Chicago, IL) were analyzed using sequencing of 16S ribosomal RNA and tuf2 gene amplicons. Nasal α-diversity did not differ between mycosis fungoides/Sézary syndrome and healthy controls (Shannon index, genus level, P = 0.201), but distinct microbial communities were identified at the class (R2 = 0.104, P = 0.023) and order (R2 = 0.0904, P = 0.038) levels.Expression of Staphylococcus aureus Virulence Factors in Atopic Dermatitis
Atopic dermatitis (AD) is a skin inflammatory disease in which the opportunistic pathogen Staphylococcus aureus is prevalent and abundant. S. aureus harbors several secreted virulence factors that have well-studied functions in infection models, but it is unclear whether these extracellular microbial factors are relevant in the context of AD. To address this question, we designed a culture-independent method to detect and quantify S. aureus virulence factors expressed at the skin sites. We utilized RNase-H‒dependent multiplex PCR for preamplification of reverse-transcribed RNA extracted from tape strips of patients with AD sampled at skin sites with differing severity and assessed the expression of a panel of S. aureus virulence factors using qPCR.How Do Experts Treat Patients with Bullous Pemphigoid around the World? An International Survey
Many treatments are currently proposed for treating patients with bullous pemphigoid (BP). We assessed treatment modalities of BP depending on the different countries, BP extent, and patients’ comorbidities. We surveyed worldwide experts about how they treat patients with BP. A total of 61 experts from 27 countries completed the survey. Severe and moderate BP were treated with oral prednisone (61.4 and 53.7%, respectively) or superpotent topical corticosteroids (CSs) (38.6 and 46.3%, respectively).Topical Calcipotriol Plus 5-Fluorouracil Immunotherapy for Actinic Keratosis Treatment
Actinic keratosis (AK) is a precursor to cutaneous squamous cell carcinoma. Lengthy treatment duration and severe side effects have limited the therapeutic efficacy of the Food and Drug Administration–approved topical AK treatments (Cornejo et al., 2020). In addition, the efficacy of these treatments against hypertrophic AK is unclear. We previously showed the high efficacy of topical calcipotriol (a low-calcemic vitamin D3 analog) in combination with 5-fluorouracil (5-FU, an established topical AK treatment) for the elimination of AK in patients with multiple AKs at baseline in a randomized, double-blind clinical trial (Cunningham et al., 2017).Presence of Uterine Leiomyomas Has No Significant Impact on Gene Expression Profile in the Scalp of Patients with Central Centrifugal Cicatricial Alopecia
Central centrifugal cicatricial alopecia (CCCA) is associated with increased expression of genes implicated in fibroproliferative disorders and a higher prevalence of uterine leiomyomas (ULs) among affected individuals. We sought to examine the effect of UL status on the gene expression profile of the lesional scalp in patients with CCCA. Scalp biopsy was obtained from 16 patients with a confirmed diagnosis of CCCA between 2017 and 2020. Microarray analysis was used to identify differential gene expression between patients with CCCA with a history of UL and those without the history.Evidence-Based Consensus Recommendations for the Evolving Treatment of Patients with High-Risk and Advanced Cutaneous Squamous Cell Carcinoma
Cutaneous squamous cell carcinoma is the second most common skin cancer in the United States. Currently, there is no standardized management approach for patients with cutaneous squamous cell carcinoma who develop metastatic or locally advanced disease and are not candidates for curative surgery or curative radiation. To address this issue, the Expert Cutaneous Squamous Cell Carcinoma Leadership program convened an expert steering committee to develop evidence-based consensus recommendations on the basis of a large, structured literature review.Assessing Disease Outcome Measures in Bullous Pemphigoid on Standard-Of-Care Therapies
Bullous pemphigoid (BP) is an autoimmune blistering disease resulting in pruritus and cutaneous blistering. Longitudinal studies characterizing the disease course of patients with BP on conventional therapy are lacking. We sought to characterize the changes in disease activity and pruritus of patients with BP on standard-of-care treatments. We conducted a retrospective cohort study on patients with BP on standard-of-care therapy. Generalized Estimating Equations were used to estimate the mean and standard errors for Bullous Pemphigoid Disease Activity Index (BPDAI) total activity score, BPDAI pruritus component score, and anti-BP180 autoantibody levels (BP180) over time.Understanding the Gut Microbiota in Pediatric Patients with Alopecia Areata and their Siblings: A Pilot Study
A cross-sectional study of 41 children aged 4–17 years with alopecia areata and 41 of their siblings without alopecia areata was conducted. A total of 51% had the Severity of Alopecia Tool scores in the range of 0–25%, 12% had scores between 26% and 49%, and 36% had scores between 75% and 100%. The fecal microbiome was characterized using shotgun metagenomic sequencing. A comparison of alpha and beta diversity yielded a small but statistically significant difference on the basis of Jaccard distance, which measures species presence and absence between samples.Using a Machine Learning Approach to Identify Low-Frequency and Rare FLG Alleles Associated with Remission of Atopic Dermatitis
Atopic dermatitis (AD) is a common relapsing inflammatory skin disease. FLG is the gene most consistently associated with AD. Loss-of-function variants in FLG have been previously associated with AD. Low-frequency and rare alleles (minor allele frequency < 5%) in this gene have been given less attention than loss-of-function variants. We fine sequenced the FLG gene in a cohort of individuals with AD. We developed a machine learning‒based algorithm to associate low-frequency and rare alleles with the disease.Use of Indoor Tanning Diagnosis Codes in Claims Data
The International Classification of Diseases: 10th Revision (effective from October 2015) included indoor tanning diagnosis codes for the first time. The majority of data on indoor tanning is self-reported. We used a large claims dataset to investigate the patients and settings in which indoor tanning International Classification of Diseases: 10th Revision codes are being used. We included encounters with the International Classification of Diseases: 10th Revision indoor tanning codes in Truven Health MarketScan data 2016–2018, which contain deidentified commercial insurance claims data for approximately 43 million patients.Patient Satisfaction of General Dermatology Providers: A Quantitative and Qualitative Analysis of 38,008 Online Reviews
Measuring patient satisfaction of general dermatology providers is an important goal because it can lead to improved clinical outcomes. Online reviews are emerging as the newest forum for evaluating physicians in real time and provide a valuable tool for measuring patient satisfaction. We analyzed both quantitative and qualitative online reviews of general dermatology providers at 121 Accreditation Council for Graduate Medical Education‒accredited dermatology programs across the country to determine which elements are most discussed in online ratings using the online platforms Vitals, US News, WebMD, Google Reviews, and Healthgrades.A Literature Review of Real-World Effectiveness and Safety of Dupilumab for Atopic Dermatitis
Atopic dermatitis (AD) is a chronic inflammatory skin disease with pruritus, characterized by recurrent eczema with exacerbations and remissions. AD impairs patients’ QOL and places a heavy burden on patients. Recently, dupilumab, an anti–IL-4Rα antibody, was approved for the treatment of patients with moderate-to-severe AD who are refractory to topical agents and/or conventional systemic therapy. Clinical trials of dupilumab for AD demonstrated high efficacy and tolerable safety profiles. Furthermore, real-world evidence of dupilumab for AD is accumulating.A Sensitization-Free Dimethyl Fumarate Prodrug, Isosorbide Di-(Methyl Fumarate), Provides a Topical Treatment Candidate for Psoriasis
Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide DMF (IDMF), which was designed to have antipsoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is nonirritating and nonsensitizing in animal models (rat, rabbit, guinea pig).Optimal Biomechanical Parameters for Measuring Sclerotic Chronic Graft-Versus-Host Disease
Skin biomechanical parameters (dynamic stiffness, frequency, relaxation time, creep, and decrement) measured using a myotonometer (MyotonPRO) could inform the management of sclerotic disease. To determine which biomechanical parameter(s) can accurately differentiate patients with sclerotic chronic graft-versus-host disease from post–hematopoietic cell transplant controls, 15 patients with sclerotic chronic graft-versus-host disease and 11 post–hematopoietic cell transplant controls were measured with the myotonometer on 18 anatomic sites.Irritated Skin Is Not Sensitive Skin
I was especially interested in the paper from Harding et al. (2021) on a genomic test on tissue-engineered skin equivalents for the determination of chemical irritation potential. The authors concluded that the expression of a seven-gene panel in human skin equivalents, based on immortalized keratinocytes, in combination with multivariate statistical approaches showed enhanced confidence in the discrimination of skin irritants from nonirritants. Such models are very interesting in the context of European Union directives prohibiting the use of animal testing for cosmetics or other ethic rules worldwide, which exclude the formerly used tests on animals.Diffuse Reflectance Spectroscopy with Infrared Thermography for Accurate Prediction of Cellulitis
Cellulitis is frequently misdiagnosed owing to its clinical mimickers, collectively known as pseudocellulitis. This study investigated diffuse reflectance spectroscopy (DRS) alone and in combination with infrared thermography (IRT) for the differentiation of cellulitis from pseudocellulitis. A prospective cohort study at an urban academic hospital was conducted from March 2017 to March 2018. Patients presenting to the emergency department with presumed cellulitis were screened for eligibility, and 30 adult patients were enrolled.Bath Psoralen Plus UVA Therapy Suppresses Keratinocyte-Derived Chemokines in Pathogenetically Relevant Cells
Psoriasis is a chronic inflammatory proliferative skin disease involving various types of chemokines regulating immune cell migration, localization, and activation. Bath psoralen plus UVA (PUVA) treatment is an established phototherapy for psoriasis, but its effects on chemokine levels remain unknown. We investigated the levels of 22 serum chemokines in 20 patients with psoriasis first treated with bath PUVA therapy between 2007 and 2011 in a single center and analyzed the associations between the chemokines and disease severity (PASI) before and after therapy to investigate the mechanisms of action of bath PUVA therapy.Safety and Efficacy of FIT039 for Verruca Vulgaris: A Placebo-Controlled, Phase I/II Randomized Controlled Trial
Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris.SB206, a Nitric Oxide–Releasing Topical Medication, Induces the Beginning of the End Sign and Molluscum Clearance
The beginning of the end (BOTE) sign has been proposed to describe well-recognized clinical signs of inflammation (including erythema, induration, and scale) that predict imminent resolution of molluscum contagiosum (MC). This phenomenon has never been prospectively studied. An integrated analysis of two prospective, 12-week, randomized, double-blind clinical trials of topical nitric oxide–releasing SB206 gel evaluated an association between BOTE sign and MC lesion reduction. Of 707 randomized patients, ~80% exhibited BOTE signs regardless of treatment assignment.Psoriasis Severity, Comorbidities, and Treatment Response Differ among Geographic Regions in the United States
Little is known about how psoriatic disease characteristics and treatment outcomes differ geographically in the United States. Our aim was to explore real-world, geographic variations in the use of biologic classes and outcomes within the Corrona Psoriasis Registry. Patient demographics and disease characteristics were assessed at biologic initiation and at 6 months. Logistic regressions were conducted to evaluate the odds of achieving targeted outcomes for seven United States geographic regions.
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