COVID-19-Related Risk Factors for Developing Occupational Contact Dermatitis Along With Its Incidence, Prevention, and Management: A Systematic Review.

Occupational contact dermatitis (OCD) is an eczematous local inflammatory skin irritation caused by repeated use of hand sanitizer and other chemical substances. Occupational irritant contact dermatitis (OICD) and occupational allergic contact dermatitis (OACD) are the two variants of CD that cannot be identified clinically. Hand dermatitis (HD) is typically assessed as a clinical consequence because it affects the hands most frequently at work as per epidemiological studies on OCD. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards were followed when conducting this umbrella review. We used the search terms "Occupational Contact Dermatitis AND COVID-19" to search for the most pertinent papers in full text on the databases PubMed/MedLine, ScienceDirect, and PubMed Central (PMC). Additionally, the reference section of the papers was used to find more articles. A total of 11,646 results were found, and eight papers remained after applying the inclusion criteria (full-text papers, English language, studies published in the previous 10 years, involving humans, and only systematic reviews). After completing the title and abstract screening, we obtained five papers. Next, the full-text screening and AMSTAR quality check were completed, yielding the same five papers. After searching ScienceDirect, five papers that met the inclusion criteria were included, and six papers were selected from the references, yielding a total of 11 papers. The causes of occupational dermatitis from protective face masks are discussed in this review. We anticipate an increase in the incidence of occupational dermatitis linked to face mask use given that a large segment of healthcare workers (HCWs) wear protective face masks. To understand the prevalence and available therapies for mask-related occupational dermatitis, further well-designed research is required.

The antimicrobial protein RNase 7 directly restricts herpes simplex virus infection of human keratinocytes.

Approximately 22% of moderately to severely affected atopic dermatitis (AD) patients have a history of eczema herpeticum, a disseminated rash primarily caused by herpes simplex virus type 1 (HSV-1). Reduced activity of antimicrobial peptides may contribute to the increased susceptibility of AD patients to HSV-1. We previously demonstrated that the antimicrobial protein RNase 7 limits HSV-1 infection of human keratinocytes by promoting self-DNA sensing. Here, we addressed whether RNase 7 has any effect on HSV-1 infection when infecting keratinocytes without exogenously added costimulatory DNA, and which step(s) of the infection cycle RNase 7 interferes with. We quantified viral gene expression by RT-qPCR and flow cytometry, viral genome replication by qPCR, virucidal effects by plaque titration, and plaque formation and the subcellular localization of incoming HSV-1 particles by microscopy. Recombinant RNase 7 restricted HSV-1 gene expression, genome replication, and plaque formation in human keratinocytes. It decreased HSV-1 immediate-early transcripts independently of the induction of interferon-stimulated genes. Its main effect was on intracellular infection processes and not on extracellular virions or virus binding to cells. RNase 7 reduced the amount of cell-associated capsids and the HSV-1 envelope glycoprotein D at 3 but not at 0.5 h postinfection. Our data show that RNase 7 directly restricts HSV-1 infection of human keratinocytes, possibly by promoting the degradation of incoming HSV-1 particles. This suggests that RNase 7 may limit HSV-1 spread in the skin and that mechanisms that reduce its activity in the lesional skin of AD patients may increase their susceptibility to eczema herpeticum.

A Case Series of Refractory Pediatric Atopic Dermatitis Effectively Treated With Dupilumab in Combination With Abrocitinib.

Children with severe atopic dermatitis (AD), refractory to conventional systemic treatment as well as single-agent biologic and Janus kinase inhibitor (JAKi) such as abrocitinib, currently face a lack of treatment options. In response to this clinical conundrum, we present three cases of severe and refractory pediatric AD successfully managed with combined dupilumab and abrocitinib. These children had exhausted all conventional treatments and had undergone treatment with both dupilumab and abrocitinib individually, as well as dupilumab in conjunction with methotrexate. It was only when the combination of dupilumab and abrocitinib was introduced that they finally achieved noticeable and sustained improvements in disease control.

Alitretinoin versus phototherapy as the first-line treatment in adults with severe chronic hand eczema: the ALPHA RCT.

Background: Hand eczema is common and a cause of morbidity and occupational disability. When education, irritant/contact allergen avoidance, moisturisation and topical corticosteroids are insufficient to control chronic hand eczema, ultraviolet therapy or systemic immune-modifying drugs are used. There is no treatment pathway generally accepted by UK dermatologists. Primary objective: Compare alitretinoin and ultraviolet therapy as first-line therapy in terms of disease activity at 12 weeks post planned start of treatment. Design: Prospective, multicentre, open-label, two-arm parallel group, adaptive randomised controlled trial with one planned interim analysis, and an economic evaluation. Setting: UK secondary care dermatology outpatient clinics. Participants: Patients with severe chronic hand eczema unresponsive to at least 4 weeks of treatment with potent topical corticosteroids. Primary end point: Natural logarithm of the Hand Eczema Severity Index + 1, 12 weeks post planned start of treatment. Randomisation: Participants randomised 1 : 1 by minimisation to alitretinoin or ultraviolet therapy for 12 to 24 weeks. Blinding: Blinded primary end-point assessor. Results: Intention-to-treat population: 441 (100.0%) participants; 220 (49.9%) alitretinoin and 221 (50.1%) ultraviolet therapy. At least one dose was received by 212 (96.4%) alitretinoin and 196 (88.7%) ultraviolet therapy participants. Primary outcome: The unadjusted median (interquartile range) relative change in hand eczema severity index at 12 weeks was 30% (10-70%) of that at baseline for alitretinoin compared with 50% (20-100%) for ultraviolet therapy. There was a statistically significant benefit of alitretinoin compared with ultraviolet therapy at 12 weeks, with an estimated fold change or relative difference (95% confidence interval) = 0.66 (0.52 to 0.82), p = 0.0003 at 12 weeks. There was no evidence of a difference at 24 or 52 weeks, with the estimated fold change (95% confidence interval) equal to 0.92 (0.798 to 1.08) and 1.27 (0.97 to 1.67), respectively. Primary analysis results were consistent for secondary end points: Fifty-nine per cent allocated to alitretinoin and 61% allocated to ultraviolet therapy achieved a clear/almost clear assessment during the trial period. Differential treatment compliance observed: 145 (65.9%) alitretinoin and 53 (24.0%) ultraviolet therapy participants confirmed compliance (≥ 80% received, no treatment breaks > 7 days during first 12 weeks). High levels of missing data were observed. Safety: One hundred and thirty-five reportable adverse events across 79 participants, 55 (25.0%) alitretinoin and 24 (10.9%) ultraviolet therapy. Four serious adverse events (two alitretinoin, two ultraviolet therapy). Four pregnancies reported (three alitretinoin, one ultraviolet therapy). No new safety signals were detected. Conclusion: As a first-line therapy, alitretinoin showed more rapid improvement and superiority to ultraviolet therapy at week 12. This difference was not observed at later time points. Alitretinoin is cost-effective at weeks 12 and 52. Ultraviolet therapy is cost-effective after 10 years, with a high degree of uncertainty. Hand eczema severity index may be a useful primary outcome measure for hand eczema trials; ALPHA results will inform future trials. Limitations: Treatment compliance was poor for ultraviolet therapy. Regular twice weekly treatment was not received by most patients. Assessment of long-term effects of randomised treatments was complicated by use of second-line treatments post treatment phase. Further work: Further analysis of substudies and pilot data will provide valuable information for future studies. A clear need for better therapeutic approaches for severe chronic hand eczema remains. Future studies will need to further address long-term benefits of treatments given. Trial registration: This trial is registered as ISRCTN80206075. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/186/01) and is published in full in Health Technology Assessment; Vol. 28, No. 59. See the NIHR Funding and Awards website for further award information.

The main question was which treatment was better at easing symptoms of severe hand eczema after 12 weeks. The two treatments compared were ones used most often by UK dermatologists. The first is a tablet called alitretinoin, which is taken once a day. The second is called ultraviolet therapy, where hands are soaked in a special liquid and placed under ultraviolet light twice a week at a hospital. We treated 220 patients with alitretinoin and 221 patients with ultraviolet therapy. Patients received treatment for 12 to 24 weeks depending on how well their hand eczema responded. Patients could have different treatments afterwards, and we collected information on their hand eczema symptoms for up to 1 year. After 12 weeks, severe hand eczema symptoms improved for both groups of patients but improved most for patients who took alitretinoin. However, 1 year after joining the trial, there was no evidence of a difference between alitretinoin and ultraviolet therapy as a first-line treatment. More patients stopped ultraviolet therapy early compared with patients who received alitretinoin. Different treatments may have been prescribed after the first treatment. Alitretinoin provides a convenient, instant relief or a 'quick fix' for patients with severe hand eczema. Alitretinoin is more convenient for lots of people, but it is important to have other options available for people who would prefer not to, or are unable to, take alitretinoin. For example, people who take alitretinoin can experience unwanted side effects, and people who are able to become pregnant must also use contraception. Long-term control of severe hand eczema is important. Individual discussions on the pros and cons of each treatment for hand eczema symptoms is needed. Providing flexible options to attend ultraviolet therapy appointments could be helpful (e.g. weekend/evenings).

Skin diseases among adults in Tasiilaq, East Greenland.

Cold climate and unique genetic and environmental factors may influence the prevalence of skin diseases in Greenland. However, there is a lack of epidemiological studies on skin diseases in the adult Greenlandic population. To address this unmet need a cross-sectional study, run by dermatologists from Denmark, the UK, and Switzerland estimated the prevalence and clinical manifestations of skin diseases among adults in East Greenland in May 2022. All adults ≥18 years in the town of Tasiilaq were invited, and 295 individuals aged 18-78 years participated (22.5% of the overall adult population in Tasiilaq). Two-hundred and three participants (69%) had visible signs of current skin disease, and among these, 242 cases of dermatoses were identified. The most common skin diseases were hand eczema (22.4%), lichen simplex (9.5%), discoid eczema (7.1%), psoriasis, atopic dermatitis and acne vulgaris (5.8% each). Scabies was the most frequent infectious skin disease (4.4%). No cases of skin cancer were identified. Atopic dermatitis and psoriasis presented with disease that was of limited extent and different from the classical presentations. Skin diseases showed a high prevalence among adults in East Greenland, and some of them were severe. This indicates a noteworthy public health problem that warrants better access to dermatologist support.

Skin Lipid Barrier: Structure, Function and Metabolism.

Lipids are important skin components that provide, together with proteins, barrier function of the skin. Keratinocyte terminal differentiation launches unique metabolic changes to lipid metabolism that result in the predominance of ceramides within lipids of the stratum corneum (SC)-the very top portion of the skin. Differentiating keratinocytes form unique ceramides that can be found only in the skin, and generate specialized extracellular structures known as lamellae. Lamellae establish tight hydrophobic layers between dying keratinocytes to protect the body from water loss and also from penetration of allergens and bacteria. Genetic and immunological factors may lead to the failure of keratinocyte terminal differentiation and significantly alter the proportion between SC components. The consequence of such changes is loss or deterioration of skin barrier function that can lead to pathological changes in the skin. This review summarizes our current understanding of the role of lipids in skin barrier function. It also draws attention to the utility of testing SC for lipid and protein biomarkers to predict future onset of allergic skin diseases.

Treatment of chronic hand eczema with topical anti-inflammatory drugs other than topical corticosteroids.

Chronic hand eczema is a fluctuating, inflammatory, pruritic disease of the hands and wrists that is commonly treated with topical corticosteroids and emollients. In a recent report in The Lancet, Bissonnette et al. demonstrated that delgocitinib cream showed superior efficacy versus a cream vehicle and was well tolerated over 16 weeks in adults with moderate to severe chronic hand eczema.

Primary nipple melanoma in a patient with breast cancer: A diagnosis to consider.

Melanoma in situ of the nipple is an uncommon diagnosis, with only a few reports in the literature. Due to the variety of pathologies that can affect the nipple-areola complex, the diagnosis can be challenging. In this case report we describe a patient with cosmetic bilateral breast implants who presented with eczema of the left nipple-areola complex and suspicious microcalcifications in the lower inner quadrant of the ipsilateral breast on mammography, subsequently diagnosed with nipple melanoma and concomitant ductal carcinoma in situ.

Current and Emerging Biologics for Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic pruritic inflammatory skin disease that affects all ages and is recognized as a global health problem. Pathophysiology is complex with skin barrier abnormalities, immune dysregulation, and microbial dysbiosis all implicated. Markers of immune and inflammatory activation in the circulation provide a rationale for systemic therapy. Type 2 immune polarization is central, though other cytokine pathways including Th22 and Th17/IL-23 have been described, suggesting additional therapeutic targets in a subset of patients. Dupilumab and tralokinumab are monoclonal antibodies currently approved for moderate-to-severe AD with lebrikizumab and nemolizumab in late stages of development.

Analysis of heritability and environmental factors in preschool children with eczema: a case-control study.

Eczema is common in children, and its onset is affected by both genetic and environmental factors. We investigated the effects of genetic and environmental factors on the incidence of eczema in preschool children. 515 preschool children with eczema and 515 children participating in the physical examination were enrolled. The study included the incidence of childhood eczema, the child's birth and feeding conditions, the history of eczema in the parents, and relevant environmental risk factors, and to comprehensively analyze the genetic and environmental factors influencing childhood eczema. Among 1030 children, 173 parents (8.4%) had eczema, with a heritability of 73.59% for boys' parents and 58.59% for girls' parents. Multivariate logistic regression results showed that premature infants, low birth weight, children who had used antibiotics before the age of 1 year the living environment between the first year of mother pregnancy and the first year of the child is humid, a father with a history of eczema, a mother with a history of eczema are risk factors for eczema in children. Actively preventing environmental factors related to eczema may be an effective means to reduce the risk of eczema in children.

Mental health among parents and their children with eczema in Hong Kong.

INTRODUCTION: This cross-sectional survey research investigated mental health symptoms and quality of life among Chinese parents and their children with eczema at a paediatric dermatology clinic in Hong Kong from November 2018 to October 2020. METHODS: Health-related quality of life, eczema severity, and mental health among children with eczema, as well as their parents' mental health, were studied using the Children's Dermatology Life Quality Index (CDLQI), Infants' Dermatitis Quality of Life Index (IDQOL), Nottingham Eczema Severity Score (NESS), Patient-Oriented Eczema Measure (POEM), and the Chinese version of the 21-item Depression, Anxiety, and Stress Scales (DASS-21). RESULTS: In total, 432 children and 380 parents were recruited. Eczema severity (NESS and POEM) and health-related quality of life (CDLQI) were significantly positively associated with parental and child depression, anxiety, and stress levels according to the DASS-21, regardless of sex (children: r=0.28- 0.72, P<0.001 to 0.007; parents: r=0.20-0.52, P<0.001 to 0.034). Maternal depression was marginally positively associated with increased anxiety in boys with eczema (r=0.311; P=0.045). Younger parents had higher risk of developing more anxiety and stress compared with the older parents (adjusted odds ratio [aOR]=-0.342, P=0.014 and aOR=-0.395, P=0.019, respectively). Depression level of parents with primary to secondary education was 58% higher than their counterparts with post-secondary education or above (aOR=-1.579; P=0.007). CONCLUSION: Depression, anxiety, and stress among children with eczema and their parents were associated with eczema severity and impaired quality of life in those children. These findings regarding impaired mental health in children with eczema and their parents highlight the need to include mental well-being and psychosocial outcomes in future studies and clinical practice.

Th1 and Th2 cytokine expression in hyperkeratotic chronic hand eczema and the role of Tofacitinib a oral JAK inhibitor.

Tissue cytokines in chronic hand eczema (CHE) can predict targeted therapy with novel drugs including JAK inhibitors. Our primary objective was to assess the tissue expression of cytokines of Th1 and Th2 cell lines in CHE patients and to study the efficacy of oral tofacitinib. We recruited patients presenting with recalcitrant CHE. Lesional and non-lesional tissue samples were assessed for Th1(IFN-γ, TNF-α) and Th2 related cytokines (IL-4, IL-13, IL-2,) using real time PCR. Tofacitinib 5 mg twice daily was initiated with 4 weekly assessment and we also noted relapses post therapy.Of 21 refractory hyperkeratotic CHE patients, cytokine analysis was performed in 11 patients which showed upregulation of IL-4 [n = 5/11, 1.87-fold increase], TNF-α (n = 5/11, 5.13-fold) and IFN-γ (n = 6/11, 1.98-fold) as compared to uninvolved skin. All patients (100%) had used topical corticosteroids (TCS) and 4/21 (19%) had failed methotrexate and 2/21 (9.5%) had failed acitretin. Tofacitinib 5 mg twice daily was given in 15/21 patients. The mean time to achieve hand eczema severity index 90 (HECSI 90) was 4 weeks (mean duration of treatment:5.8 months, n = 12). Side effects were observed in 4/12 (33.3%) patients and relapse was noted in 3/12 (25%) patients after a mean duration of 7 months after discontinuation of tofacitinib. Tofacitinib (pan-JAK inhibitor) showed an excellent response in refractory CHE patients with predominant tissue Th1/Th2 cells related cytokine expression.

Five-year real-world drug survival of dupilumab in severe atopic dermatitis and associate predictors.

BACKGROUND: Atopic dermatitis (AD) profoundly impacts patients' lives, necessitating long-term systemic treatments. METHODS: This retrospective study involved 709 severe AD patients receiving dupilumab. Drug survival (DS) was analyzed using Kaplan-Meier curves, evaluating reasons for discontinuation. The log-rank test and Cox regression analysis were applied to assess differences in drug survival across baseline clinical characteristic groups. RESULTS: Dupilumab showcased remarkable overall drug survival, reaching 74.1% at 65 months. Survival rates remained robust even when considering discontinuation solely due to primary or secondary inefficacy (86.4% at 65 months). For overall DS, the log-rank test did not reveal a statistically significant difference among the groups. Cox regression analysis showed that patients with nummular eczema-like as a phenotype have an increased risk of discontinuing dupilumab due to the development of psoriasis (p < .001, hazard ratio = 26.15, confidence interval [CI] 6.903-99.016). The multivariate logistic regression analysis confirmed these results (p < .001, OD = 18.956, CI 4.205-85.458), even when considering other clinical and epidemiological characteristics. CONCLUSION: This investigation establishes dupilumab's enduring efficacy and safety in severe AD, emphasizing its potential as a sustained therapeutic option over 5+ years. Baseline characteristics did not seem to influence DS, with the exception of the nummular eczema-like phenotype, which emerged as a significant predictor of psoriasis occurrence.

Evaluation of validity, reliability and ability to detect change for the Hand Eczema Severity Index (HECSI) and evaluation of HECSI-75 and HECSI-90 as within-patient responder definitions.

BACKGROUND: The Hand Eczema Severity Index (HECSI) is a Clinician-Reported Outcome measure of the severity of hand eczema (HE). OBJECTIVES: This study aimed to evaluate the validity, reliability and ability to detect change of the HECSI, and the HECSI-75 and HECSI-90 as responder definitions. METHODS: Analyses were performed using data from a sample of n = 258 patients with Chronic Hand Eczema (CHE) from a Phase 2b, randomised, double-blind, vehicle-controlled trial of delgocitinib cream, pooled across treatment groups. The measurement properties of the HECSI were assessed and the adequacy of the HECSI-75 and HECSI-90 as responder definitions was explored through cross-tabulation. RESULTS: Inter-item correlations provided support for the scoring, whereby items are grouped by areas of the hand. HECSI demonstrated good test-retest reliability with intra-class correlations >0.70. Construct validity was supported by a logical pattern of correlations with concurrent measures and significant differences in HECSI scores across severity groups (p < 0.001). HECSI was responsive with statistically significant improvements over time and with significant differences (p < 0.001) between improved and stable groups. Data provided support for both HECSI-75 and HECSI-90 as within-patient responder definitions. CONCLUSIONS: HECSI has strong validity, reliability and ability to detect change as a measure of CHE severity. HECSI-75 and HECSI-90 are appropriate responder definitions.

Preclinical Models of Atopic Dermatitis Suitable for Mechanistic and Therapeutic Investigations.

Atopic dermatitis (AD) is a complex immune-mediated abnormality of the skin characterized by impaired barrier function, eczematous dermatitis, chronic pruritus and itch. The immunological response in AD is mediated by a Th2-dominated immune response in the early acute phase followed by a Th1/ Th2 mixed immune response in the chronic phase. AD is the first step of the "atopic march" that progresses into food allergy, allergic rhinitis, and asthma. Different models are indispensable for studying AD pathogenesis and for designing pre-clinical studies for therapeutic discovery. They reflect the characteristic morphological features of typical human AD with regard to epidermal thickening, hyperkeratosis, acanthosis, and spongiosis and help understand the immunopathogenesis of the disease with respect to IgE levels and cellular infiltration of eosinophils, mast cells, and lymphocytes. Although it is difficult to replicate all human AD clinical features in a model, several AD in vivo models comprising spontaneous, induced, transgenic, and humanized and in vitro models, including 2D, co-culture, and 3D, have been described previously. However, several questions remain regarding whether these models satisfactorily reflect the complexity of human AD. Therefore, this review comprehensively highlights the diversity of currently available models and provides insights into the selection of suitable models based on research questions. It also summarizes the diverse mechanisms associated with each model, which may be valuable for better study design to test new therapeutic options.

Risk factors and associations with atopic diseases in the pediatric population in Qatar.

Introduction: Asthma is a common noncommunicable disease with public health implications due to the rising number of cases among the pediatric population in Qatar. Aim: The objective of the current study is to explore possible risk factors and associations in relation to pediatric asthma, allergic rhinitis, and eczema cases in Qatar. Methods: Using the Global Asthma Network questionnaires, this study sampled 2646 children, of which 1210 were aged 6-7 years and 1436 were aged 13-14 years in addition to 3831 adult parents or guardians. The STROBE guidelines were used to ensure the reporting of this cross-sectional study. Univariate and multivariate logistic regression were used to produce the odds ratio for the various risk factors and associated factors, respectively. Multiple associations and risk factors for each of the three diseases were reported. Results: Based on the outcome of a multivariate logistic regression, being born in Qatar was the only risk factor present across all three diseases. Being male, wheezing ever, wheezing after exercise, and having eczema were other risk factors reported for asthma. Being in the older age group, wheezing ever, and having hay fever were other risk factors reported for allergic rhinitis. Conclusion: The study concluded that further evaluation into associated and risk factors for asthma, allergic rhinitis, and eczema is warranted in the future.