Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning.

Background: There is a significant imbalance of mitochondrial activity and oxidative stress (OS) status in patients with atopic dermatitis (AD). This study aims to screen skin and peripheral mitochondria-related biomarkers, providing insights into the underlying mechanisms of mitochondrial dysfunction in AD. Methods: Public data were obtained from MitoCarta 3.0 and GEO database. We screened mitochondria-related differentially expressed genes (MitoDEGs) using R language and then performed GO and KEGG pathway analysis on MitoDEGs. PPI and machine learning algorithms were also used to select hub MitoDEGs. Meanwhile, the expression of hub MitoDEGs in clinical samples were verified. Using ROC curve analysis, the diagnostic performance of risk model constructed from these hub MitoDEGs was evaluated in the training and validation sets. Further computer-aided algorithm analyses included gene set enrichment analysis (GSEA), immune infiltration and mitochondrial metabolism, centered on these hub MitoDEGs. We also used real-time PCR and Spearman method to evaluate the relationship between plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels and disease severity in AD patients. Results: MitoDEGs in AD were significantly enriched in pathways involved in mitochondrial respiration, mitochondrial metabolism, and mitochondrial membrane transport. Four hub genes (BAX, IDH3A, MRPS6, and GPT2) were selected to take part in the creation of a novel mitochondrial-based risk model for AD prediction. The risk score demonstrated excellent diagnostic performance in both the training cohort (AUC = 1.000) and the validation cohort (AUC = 0.810). Four hub MitoDEGs were also clearly associated with the innate immune cells' infiltration and the molecular modifications of mitochondrial hypermetabolism in AD. We further discovered that AD patients had considerably greater plasma ccf-mtDNA levels than controls (U = 92.0, p< 0.001). Besides, there was a significant relationship between the up-regulation of plasma mtDNA and the severity of AD symptoms. Conclusions: The study highlights BAX, IDH3A, MRPS6 and GPT2 as crucial MitoDEGs and demonstrates their efficiency in identifying AD. Moderate to severe AD is associated with increased markers of mitochondrial damage and cellular stress (ccf=mtDNA). Our study provides data support for the variation in mitochondria-related functional characteristics of AD patients.

Validation of the Recap of Atopic Eczema (RECAP) Measurement Instrument for Eczema Control in Adult Patients in an Asian Clinical Setting.

Recap of atopic eczema (RECAP) is a self-reported 7-item questionnaire recommended by the Harmonising Outcome Measures in Eczema initiative to measure eczema control. As RECAP has not been validated in a real-world clinical population in Asia, RECAP was investigated as a measure of eczema control in Singapore. Patients with atopic eczema at the National Skin Centre from July 2019 to January 2020 were included for analysis. Both patient- and physician-reported outcome measures were available for correlation analyses. Correlation analysis was also performed to investigate construct validity, and floor or ceiling effects of RECAP. A total of 260 atopic eczema patients aged between 15 and 87 years were recruited. There were minimal floor and ceiling effects for RECAP scores. There were strong, significant correlations of RECAP with POEM (r = 0.84, p < 0.001) and DLQI (r = 0.81, p < 0.001). Correlation with SCORAD was moderate (r = 0.60, p < 0.001). Correlations remained similar after age, gender, and ethnicity adjustments. Discriminative validity was demonstrated by a significant linear trend of increasing RECAP scores with increasing eczema severity. RECAP demonstrates good discriminative and construct validity evidenced by strong correlations with symptoms and quality of life and moderate correlations with eczema signs. RECAP is useful to measure eczema control in Singapore.

Impact of Atopic Dermatitis on Adult Women's Lives: A Survey of 1,009 French Women.

Atopic dermatitis (AD) is one of the most common inflammatory diseases, and has a higher prevalence among females in adulthood. The aim of this observational, cross-sectional, survey-based study was to evaluate the impact of AD on the daily lives of adult women patients. A scientific committee composed exclusively of women constructed a specific questionnaire in partnership with the French Eczema Association. Severity of AD was evaluated with the Patient-Oriented Eczema Measure (POEM). A sample of 1,009 adult women (mean age ± standard deviation: 41.8 ± 14.2 years) with AD was identified from a representative sample of the French population (82% response rate 1,230 women surveyed). According to the POEM, 50.64% (n = 511) of subjects were identified as having mild AD, 39.35% (n = 397) moderate AD, and 10.01% (n = 101) severe AD. Overall, 67.7% (n = 682) reported that their eczema involved a visible area (face, neck or hands), and 19.6% (n = 198) a sensual area (breasts/chest, genital area or buttocks). Of the 720 women with menstrual cycles, exacerbations of AD were reported to occur mostly before (50.6%) and during (48.3%) menstruation. A small proportion of women, 7.3% (n = 74), reported being afraid of  becoming pregnant because of their eczema. If AD involvement was in a visible area it had a greater impact on romantic relationships, sexual relationships and occupation. If AD involvement was in a sensual area it had a greater influence on romantic relationships and sexuality. Particular attention should be given to patients with localization of AD on the face, neck or hands, as they have a higher risk of social exclusion. Moreover, these results should encourage health professionals to ask patients with AD about the possible involvement of sensual areas.

Is Telemedicine Suitable for Patients with Chronic Inflammatory Skin Conditions? A Systematic Review.

Telemedicine, the provision of remote healthcare, has gained prominence, accelerated by the COVID-19 pandemic. It has the potential to replace routine in-person follow-up visits for patients with chronic inflammatory skin conditions. However, it remains unclear whether telemedicine can effectively substitute in-person consultations for this patient group. This systematic review assessed the effectiveness and safety of telemedicine compared with traditional in-person care for chronic inflammatory skin diseases. A comprehensive search in various databases identified 11 articles, including 5 randomized controlled trials (RCTs) and 1 clinical controlled trial (CCT). These studies evaluated telemedicine's impact on patients with psoriasis and atopic dermatitis, with varying methods like video consultations and digital platforms. The findings tentatively suggest that telemedicine does not seem to be inferior compared with in-person care, particularly in terms of condition severity and quality of life for patients with chronic inflammatory skin diseases. However, these results should be interpreted with caution due to the inherent uncertainties in the evidence. There are indications that telemedicine can offer benefits such as cost-effectiveness, time savings, and reduced travel distances, but it is important to recognize these findings as preliminary, necessitating further validation through more extensive research.

Lack of association of atopic dermatitis severity and morphology with asthma onset and control.

BACKGROUND: Asthma is one of the most well-recognized comorbidities of atopic dermatitis (AD). However, the relationship of AD severity and morphology with asthma characteristics in adults is not well defined. OBJECTIVES: To understand associations of AD severity and morphology with comorbid asthma age-of-onset and control in adults with AD. METHODS: A cross-sectional, dermatology practice-based study was performed in adults (≥ 18 years) with AD and history of asthma (N = 252). Self-administered electronic questionnaires were completed by patients, including demographics, patient-reported outcomes measures of AD severity, history of asthma, age-of-onset, and Asthma Control Test (ACT). Multivariable logistic regression models were constructed to examine relationships between AD severity and morphology with asthma age-of-onset and control. RESULTS: The mean ± standard deviation ACT score was 21.7 ± 4.3 (range 5-25), with 55 (21.8%) having ACT scores ≤ 19 indicating poorly controlled asthma. AD severity and morphology were not associated with adult-onset asthma or poor asthma control. CONCLUSIONS: AD severity and morphology were not consistently associated with comorbid asthma age-of-onset or control in adults with AD.

Treatment satisfaction in adults with atopic dermatitis: a cross-sectional, population-based study examining patient and physician perspectives in the US.

Studies examining the real-world treatment satisfaction in adults with atopic dermatitis (AD) and the physicians who treat adults with AD are scarce. We sought to characterize treatment satisfaction of adults with AD and physicians' perceived patient satisfaction with AD treatment. We performed a cross-sectional study of adults > = 18 years of age (modified AD UK Working Party Criteria, age onset < = 18 [N = 767]) with AD and a parallel-physician survey among allergists/immunologists [N = 148], dermatologists [N = 149] and primary care medicine [N = 104]. Logistic regression models were used to examine factors associated with patient treatment satisfaction (PTS) or physician-perceived patient treatment satisfaction (pPTS). Factors associated with increased PTS included female, older age, and receiving a written eczema action plan (EAP). Severe AD, itch, pain, and insomnia, greater impact on partner relationships, feeling not adequately informed about AD causes, and being separated, never married, or living with a partner was associated with less PTS. From the physician's perspective, mild AD and development of EAP was associated with increase pPTS, whereas being in practice longer was associated with less pPTS. Limitations include the potential for misclassification of AD and the inability to match AD patients to individual physicians. Recognizing which factors are associated with treatment satisfaction can help inform counseling and decision-making strategies, including the use of an eczema action plan, and support patient-physician outcomes alignment.

American Academy of Dermatology Guidelines for Managing Atopic Dermatitis.

The American Academy of Dermatology first published a series of guidelines for diagnosing and managing atopic dermatitis in 2014. Twelve clinicians were selected to review, grade, and offer clinical insight on available data regarding the clinical features, symptomology, pathophysiology, education, treatment, and emerging clinical studies on atopic dermatitis (AD). Based on these findings, the AAD released a guideline to streamline information on atopic dermatitis for physicians, recommending using clinical evidence to diagnose and first treating with nonpharmacologic therapies to restore the natural skin barrier. Topical pharmacologic therapies were recommended for improving pruritus and inflammation and newer systemic agents for clinically relevant moderate-to-severe cases. Evidence-based practices were emphasized in comparison to those that lacked therapeutic data. To highlight the emerging evidence and pharmacologic breakthroughs in atopic dermatitis, the AAD produced an updated set of guidelines educating physicians on new agents and their role in treatment. This chapter reviews the AAD guidelines as a tool for managing atopic dermatitis and staying up to date on disease advancements.

Defining and Measuring the Scope of Atopic Dermatitis.

Atopic dermatitis (AD) has no definitive diagnostic test and has a large range of phenotypes, making it a difficult disease to assess and define. However, an agreed-upon definition of AD is important for clinical trials, population-based studies, and clinical practice. Several diagnostic criteria systems have been proposed to fill these needs, with none considered the gold standard. To further aid in standardized assessment of AD patients, numerous disease severity and quality-of-life measurement tools have been proposed. There is similarly no gold standard and efforts are ongoing to develop a single consensus scale. Finally, assessment of AD-associated comorbidities, including allergic/immunologic conditions, psychiatric disorders, and metabolic/cardiac conditions, is important when evaluating this patient population.

PDE4D and miR-203 are promising biomarkers for canine atopic dermatitis.

BACKGROUND: Canine atopic dermatitis (CAD) is a common genetically predisposed, inflammatory, and pruritic skin disorder that affects dogs globally. To date, there are no specific biomarkers available to diagnose CAD, and the current diagnosis is based on a combination of criteria including patient history, clinical signs, and exclusion of other relevant differential diagnoses. METHODS AND RESULTS: We examined the gene expression of phosphodiesterase 4D (PDE4D) in peripheral blood mononuclear cells (PBMCs), as well as miR-203 and miR-483 in plasma, in three groups: healthy dogs, CAD dogs, and other inflammatory pruritic skin diseases (OIPSD) such as pemphigus foliaceus, scabies, cutaneous lymphoma, and dermatophytosis. Our results showed that PDE4D gene expression in the CAD group is statistically higher compared to those in the healthy and OIPSD groups, suggesting PDE4D may be a specific marker for CAD. Nevertheless, no correlation was found between PDE4D gene expression levels and the lesion severity gauged by CAD severity index-4 (CADESI-4). We also showed that miR-203 is a generic marker for clinical dermatitis and differentiates both CAD and OIPSD inflammatory conditions from healthy controls. CONCLUSIONS: We show that PDE4D is a potential marker to differentiate CAD from non-atopic healthy and OIPSD while miR-203 may be a potential marker for general dermatologic inflammation. Future study of PDE4D and miR-203 on a larger scale is warranted.

Targeted Combined Endpoint Improvement in Patient and Disease Domains in Atopic Dermatitis: A Treat-to-Target Analysis of Adults with Moderate-to-Severe Atopic Dermatitis Treated with Upadacitinib.

A treat-to-target approach was recently developed to guide systemic treatment for adults with atopic dermatitis (AD). Recommendations outlined criteria for a 3-month initial acceptable treatment target and a 6-month optimal target, evaluated using global assessment of patient-reported disease severity, as well as Eczema Area and Severity Index, itch assessed on an 11-point numerical rating scale, Dermatology Life Quality Index, or Patient-Oriented Eczema Measure. Achievement of these targets with once-daily upadacitinib (15 mg and 30 mg) monotherapy was evaluated using integrated adult data from the Measure Up 1 and 2 phase 3 studies. Among the 852 patients treated with upadacitinib 15 mg or 30 mg, the 3-month initial acceptable target was achieved by >80%, >78%, and ≥87% of patients, and the 6-month optimal target was achieved by ≥53%, >61%, and >73% of patients at weeks 2, 16, and 52, respectively. Achievement of all 6 individual criteria for each of the target goals also increased over time. These findings suggest that upadacitinib 15 mg and 30 mg may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

Discovery of biomarkers in the psoriasis through machine learning and dynamic immune infiltration in three types of skin lesions.

Introduction: Psoriasis is a chronic skin disease characterized by unique scaling plaques. However, during the acute phase, psoriatic lesions exhibit eczematous changes, making them difficult to distinguish from atopic dermatitis, which poses challenges for the selection of biological agents. This study aimed to identify potential diagnostic genes in psoriatic lesions and investigate their clinical significance. Methods: GSE182740 datasets from the GEO database were analyzed for differential analysis; machine learning algorithms (SVM-RFE and LASSO regression models) are used to screen for diagnostic markers; CIBERSORTx is used to determine the dynamic changes of 22 different immune cell components in normal skin lesions, psoriatic non-lesional skin, and psoriatic lesional skin, as well as the expression of the diagnostic genes in 10 major immune cells, and real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry are used to validate results. Results: We obtained 580 differentially expressed genes (DEGs) in the skin lesion and non-lesion of psoriasis patients, 813 DEGs in mixed patients between non-lesions and lesions, and 96 DEGs in the skin lesion and non-lesion of atopic dermatitis, respectively. Then 144 specific DEGs in psoriasis via a Veen diagram were identified. Ultimately, UGGT1, CCNE1, MMP9 and ARHGEF28 are identified for potential diagnostic genes from these 144 specific DEGs. The value of the selected diagnostic genes was verified by receiver operating characteristic (ROC) curves with expanded samples. The the area under the ROC curve (AUC) exceeded 0.7 for the four diagnosis genes. RT-qPCR results showed that compared to normal human epidermis, the expression of UGGT1, CCNE1, and MMP9 was significantly increased in patients with psoriasis, while ARHGEF28 expression was significantly decreased. Notably, the results of CIBERSORTx showed that CCNE1 was highly expressed in CD4+ T cells and neutrophils, ARHGEF28 was also expressed in mast cells. Additionally, CCNE1 was strongly correlated with IL-17/CXCL8/9/10 and CCL20. Immunohistochemical results showed increased nuclear expression of CCNE1 in psoriatic epidermal cells relative to normal. Conclusion: Based on the performance of the four genes in ROC curves and their expression in immune cells from patients with psoriasis, we suggest that CCNE1 possess higher diagnostic value.

Patch test in Brazilian children with a clinical diagnosis of atopic dermatitis: a cross-sectional study using an extended patch test battery.

INTRODUCTION: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease mainly affecting children. Similarly, Allergic contact dermatitis (ACD) is an inflammatory skin disease, but unlike AD it results from direct exposure to an external agent. Theoretically, the impaired skin barrier facilitates the penetration of potential allergens. Therefore, AD patients are at risk for an associated ACD, exacerbating their skin condition. Because eczema is similar, performing a patch test (PT) for the differential diagnosis is essential. METHODS: In this cross-sectional transversal study, we performed a PT with 30 sensitizers in 26 children with AD, selected according to established criteria for suspected ACD, and treated at an AD center of a pediatric university hospital in Rio de Janeiro. Clinical presentation, patient profile, main sensitizers, and frequency of ACD caused by therapeutic skincare products were evaluated. RESULTS: In all, 23 (88.5%) patients reacted to at least one allergen, 21 (80.7%) had a relevant positive patch test, and 15 (57.7%) were polysensitized. The main positive sensitizers were nickel (38.5%), blue disperse (30.8%), fragrance mix (30.8%), and neomycin (23.1%). Nineteen (73%) patients reacted to substances present in therapeutic or skincare products. CONCLUSION: Our data underscore the importance of performing a PT in AD children whose eczema has atypical distribution. The expressive percentage of positive tests, especially of allergens in skincare products, indicates the constant need to review the proposed treatments. Therefore, we recommend a specific and expanded PT battery for pediatric AD patients, including a negative control, to increase sensitivity for diagnosing ACD.

Clinical Presentation of Atopic Dermatitis.

Atopic dermatitis, commonly known as eczema, is a chronic inflammatory dermatosis that can affect individuals from infancy to adulthood. Also referred to as "the itch that rashes," atopic dermatitis is classically associated with significant pruritus that is accompanied by characteristic cutaneous and other clinical findings. The diagnosis of atopic dermatitis can be challenging due to the wide range of clinical presentations based on patient factors such as age, skin type, ethnicity, and other comorbid conditions. This chapter reviews the classical findings as well as the less common manifestations of atopic dermatitis.

Application of multiple validated algorithms for identifying incident breast cancer among individuals with atopic dermatitis.

PURPOSE: Validated algorithms (VAs) in insurance claims databases are often used to estimate the prevalence and incidence of comorbidities and evaluate safety signals. However, although they are then used in different data sources or subpopulations from those in which they were developed the replicability of these VAs are rarely tested, making their application and performance in these settings potentially unknown. This paper describes testing multiple VAs used to identify incident breast cancer cases in a general population and in an indication-specific population, patients with atopic dermatitis (AD). METHODS: Two algorithms were tested in multiple insurance claims databases and four cohorts were created. Modifications were made to account for the US insurance setting. The resulting incidence rates (IRs) were then compared across algorithms and against surveillance, epidemiology, and end results (SEER) estimates to assess reliability. RESULTS: Algorithm 1 produced low IRs compared to Algorithm 2. Algorithm 2 provided similar estimates to those of SEER. Individuals in the AD cohorts experienced lower incident breast cancer cases than those in the general population cohorts. CONCLUSION: Regardless of an algorithm's reported accuracy, the original study setting and targeted population for the VAs may matter when attempting to replicate the algorithm in an indication-specific subpopulation or varying data sources. Investigators should use caution and conduct sensitivity analyses or use multiple algorithms when attempting to calculate incidence or prevalence estimates using VAs.

Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts. / Atopische Keratokonjunktivitis: Pathophysiologie, Klinik und potenzielle neue Therapiekonzepte.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Biomarkers for phenotype-endotype relationship in atopic dermatitis: a critical review.

Atopic dermatitis (AD) is the most common form of chronic skin inflammation with diverse clinical variants. Historically, various AD phenotypes have been grouped together without considering their heterogeneity. This approach has resulted in a lack of phenotype- and endotype-adapted therapeutic strategies. Comprehensive insights into AD pathogenesis have enabled precise medicinal approach for AD. These efforts aimed to redefine the endophenotype of AD and develop various biomarkers for diverse purposes. Among these endeavours, efforts are underway to elucidate the mechanisms (and related biomarkers) that lead to the emergence and progression of atopic diseases originating from AD (e.g., atopic march). This review focuses on diverse AD phenotypes and calls for a definition of endophenotypes. While awaiting scientific validation, these biomarkers ensure predicting disease onset and trajectory and tailoring therapeutic strategies for the future.