A quantitative assay for the assessment of cutaneous human papillomaviruses and polyomaviruses over time: A proof-of-concept in two patients with atopic dermatitis and psoriasis.

The human skin virome, unlike commensal bacteria, is an under investigated component of the human skin microbiome. We developed a sensitive, quantitative assay to detect cutaneous human resident papillomaviruses (HPV) and polyomaviruses (HPyV) and we first used it to describe these viral populations at the skin surface of two patients with atopic dermatitis (AD) and psoriasis (PSO). We performed skin swabs on lesional and non-lesional skin in one AD and one PSO patient at M0, M1 and M3. After extraction, DNA was amplified using an original multiplex PCR technique before high throughput sequencing (HTS) of the amplicons (named AmpliSeq-HTS). Quantitative results were ultimately compared with monoplex quantitative PCRs (qPCRs) for previously detected viruses and were significantly correlated (R2 = 0.95, ρ = 0.75). Fifteen and 13 HPV types (mainly gamma and beta-HPVs) or HPyV species (mainly Merkel Cell Polyomavirus (MCPyV)) were detected on the skin of the AD and PSO patients, respectively. In both patients, the composition of the viral flora was variable across body sites but remained stable over time in non-lesional skin samples, mostly colonized with gamma-papillomaviruses. In lesional skin samples, beta-papillomaviruses and MCPyV were the major components of a viral flora more prone to vary over time especially with treatment and subsequent clinical improvement. We believe this method might be further used in extensive studies to further enhance the concept of an individual cutaneous viral fingerprint and the putative role of its alterations through various skin diseases and their treatments.

The causal relationship between atopic dermatitis and brain cancer: A bidirectional Mendelian randomization study.

BACKGROUND: Atopic dermatitis ranks among the prevalent skin disorders. Research has indicated a potential association with brain cancer. Yet, establishing a direct causal relationship between atopic dermatitis and brain cancer continues to be challenging. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) significantly associated with atopic dermatitis (sample size = 382 254) at a genome-wide level from a large Finnish Genome-Wide Association Study (GWAS) dataset (n cases = 15 208, n controls = 367 046). Summary data for 372 622 cases of brain cancer (n cases = 606, n controls = 372 016) were obtained via the IEU Open GWAS database. We employed the Inverse Variance Weighted (IVW) method as our primary analytical approach for Mendelian Randomization (MR) analysis. Additionally, heterogeneity was measured using Cochran's Q value, and horizontal pleiotropy was evaluated using MR-Egger 、Mendelian Randomization Pleiotropy RESidual Sum and Outlier and leave-one-out analyses. RESULTS: The risk of brain cancer increases with the presence of atopic dermatitis, as evidenced by the odds ratios (ORs) and 95% confidence intervals (CIs),(OR = 1.0005; 95% CI = 1.0001, 1.0009; p = 0.0096). However, when conducting the analysis in reverse, no significant link was observed. CONCLUSION: The findings from our study indicate a causative link between atopic dermatitis and brain cancer, highlighting the importance of conducting broader clinical investigations into their potential association going forward.

Does Molluscum Contagiosum Need to be Managed Differently in Atopic Children?

The association between molluscum contagiosum and concomitant atopic dermatitis and its impact on clinical features and treatment outcomes remains unclear. This retrospective study, conducted in the paediatric dermatology clinic of a tertiary medical centre, aimed to compare molluscum patients with and without atopic dermatitis. A total of 615 children with molluscum were included, 13.17% of whom had atopic dermatitis. While the latter group exhibited higher lesion count and itchiness (p=0.026 and p=0.044, respectively), no significant differences were observed in average lesion diameter, ulceration, purulence, and erythema (p=0.239, p=0.730, p=0.682, and p=0.296, respectively). Both groups showed comparable responses to molluscum-specific and supportive treatments, with no distinct difference in outcomes or recurrence of visits. It was concluded that atopic dermatitis does not exacerbate molluscum morbidity, inflammation markers, treatment outcomes or recurrence rates.

Eugenol-Loaded Transethosomal Gel for Improved Skin Delivery and Treatment of Atopic Dermatitis.

Atopic dermatitis is a skin condition characterized by lichenification (thickening and increased skin marking), eczematous lesions, dry skin, itching, and pruritus. Eugenol is an aromatic polyphenolic compound that has attracted the attention of researchers due to its anti-inflammatory, anti-oxidant, and anti-cancer properties. The primary goal of the present study was to develop and evaluate eugenol-loaded transethosomes for the treatment of AD. Eugenol-loaded transethosomes were formulated using the ethanol injection method and subsequently subjected to particle size analysis, zeta potential, entrapment efficiency, deformability index, and HRTEM analysis. Transethosomal gel was prepared by direct-dispersion method by using Carbopol 940®. Results showed transethosomes to be lipid bilayer structures with acceptable size, and high entrapment efficiency. Transethosomal formulation showed shear-thinning behavior. Eugenol-loaded transethosomal gel was significantly able to enhance the retention of the drug in the skin. Transethosomal gel was significantly able to reduce Ear thickness, DLC, TLC, and IL-6 levels in mice model of AD. These results indicate that the eugenol-loaded transethosomal gel could be a promising carrier for the topical administration of eugenol for the treatment of AD.

Atopic Dermatitis Associated Retinal Detachment and Retinal Vasculitis: A Case Report.

Atopic dermatitis is usually associated with various ocular complications. We report a 21-year-old Chinese male who presented to our ophthalmology clinic with bilateral retinal detachment and cataracts. The patient had a clear medical history of atopic dermatitis, which had been diagnosed eight years earlier and had been treated with loratadine and pimecrolimus. Cataract surgery was performed for both eyes, combined with scleral buckling for the right eye and pars plana vitrectomy for the left eye. During postoperative follow-up, fundus fluorescein angiography showed retinal vasculitis in both eyes and macular edema in the left eye, which coincided with an exacerbation of atopic dermatitis. Macular edema improved after four months of regular dupilumab treatment in the dermatology department. The ocular condition remained stable three years postoperatively.

Pregabalin-induced delayed cutaneous hypersensitivity reaction occurring after 40 days of use: a case report.

Pregabalin is the first-line treatment for neuropathic pain. Cases of cutaneous hypersensitivity reactions caused by pregabalin generally occur within 2 weeks of initiating medication. We report a rare case of a delayed cutaneous hypersensitivity reaction caused by pregabalin, which was confirmed by a drug provocation test. A 72-year-old man with severe herpes zoster neuralgia developed maculopapular drug eruption covering 80% to 90% of his total body surface area after 40 days of combined multidrug analgesia. A drug provocation test for pregabalin was positive. The time interval between initiating medication and the onset of the patient's rash was the longest and he also had the largest area of skin affected compared with patients with a similar condition in previous related reports. Remaining vigilant for possible adverse cutaneous hypersensitivity reactions during treatment is important because of the long-term course of pregabalin treatment for neuropathic pain.

Assisted reproductive techniques and subsequent risk of asthma and allergic rhinitis in offspring: a nationwide birth cohort study in South Korea.

OBJECTIVE: The relationship between assisted reproductive techniques (ART) and the risk of asthma and allergic rhinitis (AR) is controversial. Thus, we aimed to investigate the relationship between ART and the risk of asthma and AR in a nationwide, large-scale birth cohort. PATIENTS AND METHODS: This study utilized the National Health Insurance Service data in South Korea to conduct a nationwide, large-scale, population-based birth cohort. We included all infants born between 2017 and 2018. AR, asthma, food allergies, and atopic dermatitis were defined using the International Classification of Diseases tenth edition codes. Asthma was classified as allergic or non-allergic based on accompanying allergic diseases (AR, food allergy, or atopic dermatitis). Using 1:10 propensity score matching, we compared infants conceived through ART with those conceived naturally (non-ART). After matching, logistic regression was used to compare the hazard ratio for asthma and AR between the two groups. RESULTS: We included 543,178 infants [male infants, 280,194 (51.38%)]. After matching, 8,925 and 74,229 infants were selected for the ART and non-ART groups, respectively. The ART group showed a decreased risk of asthma in the offspring [adjusted hazard ratio (aHR), 0.45; 95% confidence interval (CI), 0.41-0.48]. Similarly, for AR, being conceived by ART was associated with a decreased risk of AR (aHR, 0.25; 95% CI, 0.12-0.37). ART offspring showed a decreased risk of asthma and AR in offspring compared to that observed in non-ART offspring. CONCLUSIONS: Our study offers important insights for clinicians, researchers, and parents regarding the health outcomes of ART-conceived infants and enhances our understanding of ART's impact on respiratory health.

A Review of Dupilumab in the Treatment of Atopic Dermatitis in Infants and Children.

Atopic dermatitis (AD), a common pruritic and chronic inflammatory skin disease, has a major impact on a patient's quality of life. It is characterized by dry, itchy, and eczema-like rashes. AD is more prevalent in young children and has been linked to a variety of other allergy disorders. Traditional drug therapy has certain limitations for treating young children with AD. However, biologics have good clinical application prospects in the medical treatment of young patients. Dupilumab, a fully human monoclonal antibody, specifically binds to the IL-4 Rα subunit, inhibiting IL-4 and IL-13 signaling and blocking the occurrence of type 2 inflammatory response. It has a good effect on treating infants and children with moderate-to-severe AD. This review explores the safety and efficacy of dupilumab in the treatment of AD in infants and children and the impact of early intervention on AD progression, with the aim of informing clinical practice in the use of dupilumab for the treatment of young patients with AD.

Analysis of Reddit Reveals JAK Inhibitor Questions Among Atopic Dermatitis Patients.

Reddit is a popular social media website that is increasingly being used as a source of health information and discussion, especially among the younger population. We analyzed the subreddit "eczeJAKs" (a group whose "about" statement is: "Janus Kinase Inhibitors for Th2 Dermatitis"), and found many gaps in patient knowledge, showing areas for future improvement.  J Drugs Dermatol. 2024;23(4):7787.     doi:10.36849/JDD.7787R2.

Use of a topical Janus kinase inhibitor in immune checkpoint inhibitor-induced eczematous reaction: a case report.

In this report, we describe the case of a 28-year-old female with bilateral breast cancer in the setting of a BRCA1 mutation, who presented to dermatology with an eczematous reaction, ultimately diagnosed as a cutaneous immune-related adverse event (cirAE) secondary to an immune checkpoint inhibitor (ICI), pembrolizumab. Our case report highlights a novel therapeutic option for an eczematous cirAE: the topical JAK 1/2 inhibitor, ruxolitinib. CirAEs can occur in up to 55% of patients on ICIs, a class of medications seeing rapidly increasing use in cancer therapy, and prior research has demonstrated that ICI-induced dermatitis may involve different pathways than traditionally observed in their spontaneous counterparts. Specifically, marked Th1 skewing is noted in ICI-induced dermatitis, as opposed to a predominant Th2 response which typically characterizes spontaneous atopic dermatitis. To our knowledge, this is the first case report in the literature discussing use of a topical JAK inhibitor, ruxolitinib, in the treatment of topical steroid-refractory cirAEs. Furthermore, as topical JAK inhibitors are thought to not carry the risks of systemic JAK inhibitors, including malignancy, ruxolitinib cream is a promising therapeutic option for this challenging patient population.

Dupilumab-associated head and neck dermatitis shows a pronounced type 22 immune signature mediated by oligoclonally expanded T cells.

Dupilumab, an IL4R-blocking antibody, has shown clinical efficacy for atopic dermatitis (AD) treatment. In addition to conjunctivitis/blepharitis, the de novo appearance of head/neck dermatitis is now recognized as a distinct side effect, occurring in up to 10% of patients. Histopathological features distinct from AD suggest a drug effect, but exact underlying mechanisms remain unknown. We profiled punch biopsies from dupilumab-associated head and neck dermatitis (DAHND) by using single-cell RNA sequencing and compared data with untreated AD and healthy control skin. We show that dupilumab treatment was accompanied by normalization of IL-4/IL-13 downstream activity markers such as CCL13, CCL17, CCL18 and CCL26. By contrast, we found strong increases in type 22-associated markers (IL22, AHR) especially in oligoclonally expanded T cells, accompanied by enhanced keratinocyte activation and IL-22 receptor upregulation. Taken together, we demonstrate that dupilumab effectively dampens conventional type 2 inflammation in DAHND lesions, with concomitant hyperactivation of IL22-associated responses.

A systematic review investigating the proportion of clinical images shared in prospective randomized controlled trials involving patients with atopic dermatitis and systemic pharmacotherapy.

For individuals with atopic dermatitis (AD), interpreting scientific papers that present clinical outcomes including the Eczema Area and Severity Index (EASI) and Investigators Global Assessment may be difficult. When compared to tabulated data and graphs, images from before and after treatment are often far more meaningful to these patients that ultimately will be candidates for the treatment. This systematic review focused on determining the frequency of clinical image sharing in AD research.Conducted in accordance with PRISMA guidelines, the review concentrated on randomized controlled trials that investigated predefined and available systemic treatments for AD. The search was performed in the MEDLINE database for studies published from the inception until 21 December 2023.The review included 60 studies, encompassing 17,799 randomized patients. Across these studies, 16 images representing 6 patients were shared in the manuscripts, leading to a sharing rate of 0.3‰.The almost missing inclusion of patient images in clinical trial publications hinders patient understanding. Adding images to scientific manuscripts could significantly improve patients' comprehension of potential treatment outcomes. This review highlights the need for authors, the pharmaceutical industry, study sponsors, and publishers to enhance and promote patient information through increased use of visual data.

Atopic Dermatitis in Children.

Atopic dermatitis (AD) is extremely common in the pediatric population, and most children with AD will first present to their primary care provider (PCP). The PCP can recognize AD by its clinical features, including itch, a chronic relapsing course, and the characteristic eruption. The cornerstone of AD therapy is dry skin care, typically a short daily bath/shower followed by an emollient applied to all skin. Most children with AD will also require topical medications, such as topical corticosteroids and/or topical nonsteroidal therapies. For children with more severe disease, systemic agents, including several novel therapies, may be required. In managing AD, the clinician must monitor for side effects of medications as well as complications of the AD itself, the most common of which is secondary infection. An understanding of the pathogenesis, treatments, and complications of AD is essential for the PCP, as untreated (or undertreated) AD has a significant impact on the quality of life of affected children and their caregivers. [Pediatr Ann. 2024;53(4):e121-e128.].

Associations of Eosinophilic Gastrointestinal Disorders with Other Gastrointestinal and Allergic Diseases.

Eosinophilic gastrointestinal disorders (EGIDs) are becoming more common causing significant suffering and reduced quality of life. These conditions can affect different parts of the digestive system, either individually or in combination. Recognition of their link to allergic disorders or other gastrointestinal (GI) diseases has raised questions about their shared underlying mechanisms, which has had implications for diagnosis and management. The authors critically examine the current understanding of the connection between EGIDs and allergic conditions (ie, atopic dermatitis, allergic rhinitis, asthma, and food allergy) and GI diseases (ie, inflammatory bowel disease, celiac disease, gastroesophageal reflux disease, and motility disorders).

Population-based cohort study to investigate the changes in prevalence, severity profile, and treatment modalities used in Korean atopic dermatitis patients.

In this retrospective study spanning from 2002 to 2019, we analyzed data from 355,277 Korean patients diagnosed with atopic dermatitis (AD) through the National Health Insurance System. Our objective was to comprehensively analyze the trends in prevalence, severity profiles, and treatment approaches for AD in Korea over this 18-year period. Initially, AD prevalence stood at 3.88% in 2002 but notably rose to 5.03% by 2019. During the same period, while AD prevalence decreased in the 0-1-year-old group (from 34.52% to 24.83%), it remained relatively stable in the 1-11-year-old group. Conversely, the 12-19-year-old and 20 years or older age groups witnessed substantial increases in AD prevalence, climbing from 2.55 to 6.02% and 1.44% to 3.53%, respectively. Moreover, the proportion of patients classified as having moderate to severe AD grew from 30.96 to 39.78%. Surprisingly, the prescription pattern, predominantly based on corticosteroid administration, exhibited minimal change despite the rising prevalence of moderate and severe AD cases. These findings underline a persistent reliance on corticosteroid-based treatments for AD, even as the condition's severity escalates among Korean adolescents and adults. Consequently, there is a pressing need to develop novel treatment guidelines emphasizing biologics that offer enhanced safety and efficacy.

Effectiveness of atopic dermatitis patient education programs - a systematic review and meta-analysis.

Patient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens. In addition to improving patient education, past investigations of educational interventions have demonstrated profound reductions in disease severity for patients living with AD. However, prior meta-analytical work has focused mostly on comparing in-person interventions, and thus the need to determine the effectiveness of virtual methodologies in the current post-COVID era remains. In this study, we conducted a systematic review of the literature to determine the effectiveness of online programming in AD education compared to in-person interventions. A comprehensive search was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 2019. Studies were retrieved based on articles published up to 04 April 2023. Adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement guided the reportage process for this systematic review and meta-analysis. The primary outcome of our meta-analysis was the effect of various educational modalities on atopic dermatitis severity as measured by multiple scales across the studies, the most common including SCORAD, Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), and Eczema Area and Severity Index (EASI). Most studies were randomized controlled trials, primarily from North America and Western Europe and focused on patient and/or caregiver education about disease management, self-care techniques, avoidance of triggers, and comprehensive understanding of the disease process. Our pooled analyses showed that targeted educational programs in understudied adult populations can be as impactful as those in pediatric groups. Moreover, virtual interventions can be employed as constructive tools for reducing barriers of access to patient education. Future research on educational interventions should utilize various methodologies to encourage individual learning preferences with a focus on adult cohorts.

Methodological quality of systematic reviews on atopic dermatitis treatments: a cross-sectional study.

BACKGROUND: Systematic reviews (SRs) could offer the best evidence supporting interventions, but methodological flaws limit their trustworthiness in decision-making. This cross-sectional study appraised the methodological quality of SRs on atopic dermatitis (AD) treatments. METHODS: We searched MEDLINE, EMBASE, PsycINFO, and Cochrane Database for SRs on AD treatments published in 2019-2022. We extracted SRs' bibliographical data and appraised SRs' methodological quality with AMSTAR (A MeaSurement Tool to Assess systematic Reviews) 2. We explored associations between methodological quality and bibliographical characteristics. RESULTS: Among the 52 appraised SRs, only one (1.9%) had high methodological quality, while 45 (86.5%) critically low. For critical domains, only five (9.6%) employed comprehensive search strategy, seven (13.5%) provided list of excluded studies, 17 (32.7%) considered risk of bias in primary studies, 21 (40.4%) contained registered protocol, and 24 (46.2%) investigated publication bias. Cochrane reviews, SR updates, SRs with European corresponding authors, and SRs funded by European institutions had better overall quality. Impact factor and author number positively associated with overall quality. CONCLUSIONS: Methodological quality of SRs on AD treatments is unsatisfactory. Future reviewers should improve the above critical methodological aspects. Resources should be devolved into upscaling evidence synthesis infrastructure and improving critical appraisal skills of evidence users.

Therapeutic textiles: A promising approach for human skin dysbiosis?

The close interaction between skin and clothing has become an attractive cornerstone for the development of therapeutic textiles able to alleviate skin disorders, namely those correlated to microbiota dysregulation. Skin microbiota imbalance is known in several skin diseases, including atopic dermatitis (AD), psoriasis, seborrheic dermatitis, rosacea, acne and hidradenitis suppurative (HS). Such microbiota dysregulation is usually correlated with inflammation, discomfort and pruritus. Although conventional treatments, that is, the administration of steroids and antibiotics, have shown some efficacy in treating and alleviating these symptoms, there are still disadvantages that need to be overcome. These include their long-term usage with side effects negatively impacting resident microbiota members, antibiotic resistance and the elevated rate of recurrence. Remarkably, therapeutic textiles as a non-pharmacological measure have emerged as a promising strategy to treat, alleviate the symptoms and control the severity of many skin diseases. This systematic review showcases for the first time the effects of therapeutic textiles on patients with skin dysbiosis, focusing on efficacy, safety, adverse effects and antimicrobial, antioxidant and anti-inflammatory properties. The main inclusion criteria were clinical trials performed in patients with skin dysbiosis who received treatment involving the use of therapeutic textiles. Although there are promising outcomes regarding clinical parameters, safety and adverse effects, there is still a lack of information about the impact of therapeutic textiles on the skin microbiota of such patients. Intensive investigation and corroboration with clinical trials are needed to strengthen, define and drive the real benefit and the ideal biomedical application of therapeutic textiles.

The role of thymic stromal lymphopoietin in cutaneous disorders.

Thymic Stromal Lymphopoietin (TSLP) is an important cytokine that invokes early immune responses. TSLP, an IL-7-like cytokine encoded by the TSLP gene, activates JAK1 and JAK2 signaling pathways, stimulating dendritic cells to induce inflammatory Th2 cells. This cytokine is associated with pruritus in various cutaneous disorders, particularly atopic dermatitis. Varying levels of the cytokine TSLP have been demonstrated in studies of different cutaneous disorders. Pharmacological treatment targeting TSLP has been explored recently, particularly in the realm of atopic dermatitis.This review explores the relation of TSLP to cutaneous diseases, highlighting its potential as a biomarker for monitoring disease progression in discoid lupus erythematosus (DLE). The pharmacological therapy involving TSLP is discussed, along with the potential role of TSLP promotion in the treatment of alopecia areata. This overview examines the background, structure, and functions of TSLP, with a focus on its association with cutaneous disorders and a special focus on the impact of the atopic march.

An OX-Tra'Ordinary Tale: The Role of OX40 and OX40L in Atopic Dermatitis.

The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management.