scholarly journals Skin barrier status during dupilumab treatment in patients with severe atopic dermatitis

2021 ◽  
Vol 12 ◽  
pp. 204062232110583
Author(s):  
Silvia Ferrucci ◽  
Maurizio Romagnuolo ◽  
Carlo Alberto Maronese ◽  
Francesca Germiniasi ◽  
Simona Tavecchio ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Response To Therapy ◽  
Interleukin 4 ◽  
Severe Atopic Dermatitis ◽  
Barrier Dysfunction ◽  
Relative Variation ◽  
Good Tool ◽  
The Status

Background: Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease hallmarked by epidermal barrier dysfunction, increased transepidermal water loss (TEWL) and decreased skin hydration. Recent findings on the T helper 2 (Th2)-driven pathogenesis of AD have led to the development of dupilumab, a monoclonal antibody directed against interleukin-4 and interleukin-13 that has been demonstrated to be effective in the treatment of moderate-to-severe AD. The effect of dupilumab on skin barrier dysfunction, however, has not yet been adequately investigated. Objectives: The primary endpoint of this study was to assess the status of the skin barrier in nonlesional skin of patients with severe AD treated with dupilumab, by evaluating the association between the relative variation of TEWL and the achievement of a 75% reduction of EASI (EASI75) over time. Methods: TEWL was measured below the antecubital fossae by means of the Vapometer® at baseline, at week 4 (T4), at week 16 (T16) and at week 32 after dupilumab starting. EASI and NRS-itch were measured at the same time points. Results: Seventy-eight patients with severe AD treated with dupilumab were enrolled. Median TEWL relative variation respect to baseline was significantly higher in patients who achieved EASI75 as compared with those who did not achieve EASI75 at T16 and at T32, but not at T4. Conclusion: During dupilumab treatment, TEWL on nonlesional skin tends to significantly improve 4 months after treatment initiation and could be a good tool for monitoring response to therapy.

scholarly journals Echinochrome A Treatment Alleviates Atopic Dermatitis-like Skin Lesions in NC/Nga Mice via IL-4 and IL-13 Suppression

Marine Drugs ◽  
2021 ◽  
Vol 19 (11) ◽  
pp. 622
Author(s):  
Hyeong Rok Yun ◽  
Sang Woo Ahn ◽  
Bomin Seol ◽  
Elena A. Vasileva ◽  
Natalia P. Mishchenko ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Clinical Symptoms ◽  
Sea Urchins ◽  
Skin Barrier ◽  
Skin Lesions ◽  
Transepidermal Water Loss ◽  
Interleukin 4 ◽  
Barrier Dysfunction ◽  
Echinochrome A ◽  
Anti Inflammatory

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which skin barrier dysfunction leads to dryness, pruritus, and erythematous lesions. AD is triggered by immune imbalance and oxidative stress. Echinochrome A (Ech A), a natural pigment isolated from sea urchins, exerts antioxidant and beneficial effects in various inflammatory disease models. In the present study, we tested whether Ech A treatment alleviated AD-like skin lesions. We examined the anti-inflammatory effect of Ech A on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesions in an NC/Nga mouse model. AD-like skin symptoms were induced by treatment with 1% DNCB for 1 week and 0.4% DNCB for 5 weeks in NC/Nga mice. The results showed that Ech A alleviated AD clinical symptoms, such as edema, erythema, and dryness. Treatment with Ech A induced the recovery of epidermis skin lesions as observed histologically. Tewameter® and Corneometer® measurements indicated that Ech A treatment reduced transepidermal water loss and improved stratum corneum hydration, respectively. Ech A treatment also inhibited inflammatory-response-induced mast cell infiltration in AD-like skin lesions and suppressed the expression of proinflammatory cytokines, such as interferon-γ, interleukin-4, and interleukin-13. Collectively, these results suggest that Ech A may be beneficial for treating AD owing to its anti-inflammatory effects.

scholarly journals Update on Atopic Dermatitis

2019 ◽  
Vol 32 (9) ◽  
pp. 606 ◽  
Author(s):  
Tiago Torres ◽  
Eduarda Osório Ferreira ◽  
Margarida Gonçalo ◽  
Pedro Mendes-Bastos ◽  
Manuela Selores ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Disease Severity ◽  
Clinical Manifestations ◽  
Skin Barrier ◽  
Future Research ◽  
Severe Atopic Dermatitis ◽  
Inadequate Response ◽  
Barrier Dysfunction ◽  
Therapeutic Goals ◽  
Global Health Issue

With an increasing prevalence during the past decades, atopic dermatitis has become a global health issue. A literature search following a targeted approach was undertaken to perform this non-systematic review, which intends to provide an overview of the epidemiology, pathophysiology, clinical features, comorbidities, and current therapies for the treatment of atopic dermatitis. In sum, this is a heterogeneous skin disorder associated with variable morphology, distribution, and disease course. Although not completely understood, its pathogenesis is complex and seems to result from a combination of genetic and environmental factors that induce skin barrier dysfunction, cutaneous and systemic immune dysregulation, skin microbiota dysbiosis, and a strong genetic influence. Diagnosis is based on specific criteria that consider patient and family history and clinical manifestations. Overall disease severity must be determined by evaluating both objective signs and subjective symptoms. Therapeutic goals require a multistep approach, focusing on reducing pruritus and establishing disease control. Patients should be advised on basic skin care and avoidance of triggers. Topical anti-inflammatory agents should be considered in disease flares or chronic/recurrent lesions. In case of inadequate response, phototherapy, systemic immunosuppressants and, more recently, dupilumab, should be added. Nevertheless, the treatment of moderate-to-severe atopic dermatitis remains challenging and novel, efficacious, safe and targeted treatments are urgently needed. In conclusion, although the last few years have seen important improvement in the understanding of the disease, future research in atopic dermatitis will continue exploring gene-environment interactions and how it affects pathophysiology, disease severity, and treatment outcomes.

scholarly journals Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis

2020 ◽  
Vol 9 (11) ◽  
pp. 3741
Author(s):  
Masutaka Furue
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Coal Tar ◽  
Calcineurin Inhibitors ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Interleukin 4 ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Therapeutic Implications

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, the type 2 cytokines IL-4 and especially IL-13 have been indicated to have pathogenic significance in AD. Accumulating evidence has shown that the skin barrier function is regulated via competition between the aryl hydrocarbon receptor (AHR) axis (up-regulation of barrier) and the IL-13/IL-4‒JAK‒STAT6/STAT3 axis (down-regulation of barrier). This latter axis also induces oxidative stress, which exacerbates inflammation. Conventional and recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, and JAK inhibitors inhibit the IL-13/IL-4‒JAK‒STAT6/STAT3 axis, while older remedies such as coal tar and glyteer are antioxidative AHR agonists. In this article, I summarize the pathogenic and therapeutic implications of the IL-13/IL-4‒JAK‒STAT6/STAT3 axis and the AHR axis in AD.

scholarly journals The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype

2019 ◽  
Vol 11 (480) ◽  
pp. eaav2685 ◽  
Author(s):  
Donald Y. M. Leung ◽  
Agustin Calatroni ◽  
Livia S. Zaramela ◽  
Petra K. LeBeau ◽  
Nathan Dyjack ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Food Allergy ◽  
Sampling Method ◽  
Skin Barrier ◽  
Skin Surface ◽  
Transepidermal Water Loss ◽  
Barrier Dysfunction ◽  
Ceramide Content ◽  
Immune Pathways

Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD FA+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD FA−) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD FA+. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD FA+ were substantially lower than in AD FA− and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD FA+ had increased abundance of Staphylococcus aureus compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD FA+. The skin transcriptome of AD FA+ had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD FA+, whereas filaggrin breakdown products were negatively correlated with AD FA+. These data suggest that the most superficial compartment of nonlesional skin in AD FA+ has unique properties associated with an immature skin barrier and type 2 immune activation.

scholarly journals Effect of Topically Applied Wikstroemia dolichantha Diels on the Development of Atopic Dermatitis-Like Skin Symptoms in Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 914 ◽  
Author(s):  
Jonghwan Jegal ◽  
No-June Park ◽  
Tae-Young Kim ◽  
Sangho Choi ◽  
Sang Woo Lee ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Barrier Function ◽  
Immunoglobulin E ◽  
Skin Barrier ◽  
Skin Lesions ◽  
Transepidermal Water Loss ◽  
Skin Hydration ◽  
Interleukin 4 ◽  
Skin Barrier Function ◽  
Skin Symptoms

Plants of the genus Wikstroemia are traditionally used to treat inflammatory diseases like bronchitis and rheumatoid arthritis. In the present study, the anti-atopic effects of an EtOH extract of Wikstroemia dolichantha (WDE) on oxazolone- and DNCB (2,4-dinitrochlorobenzene)-induced dermatitis in mice were investigated. Both ears of BALB/c mice were exposed to oxazolone, and dorsal skins of SKH-1 hairless mice were sensitized with DNCB to induce acute eczematous atopic skin lesions. 1% WDE was applied daily to oxazolone- and DNCB-induced AD mice for two or three weeks, respectively. Total IL-4 and IgE concentrations in serum, transepidermal water loss (TEWL) and skin hydration were assessed. High-performance liquid chromatography/mass spectrometry (HPLC/MS) was used to determine the composition of WDE. Dermal application of 1% WDE grossly and histopathologically improved oxazolone- and DNCB-induced AD skin symptoms. Epidermal thickness and mast cell infiltration were significantly lower in animals treated with WDE than in vehicle controls. Furthermore, in addition to reducing DNCB-induced increases in serum IL-4 (interleukin 4) and IgE (immunoglobulin E) levels, WDE also decreased TEWL and increased skin hydration (indicative of improved skin barrier function). The four flavonoids taxifolin, aromadendrin, padmatin and chamaejasmine were tentatively identified in WDE by HPLC-DAD/QTOF-MS. The above results show WDE protected against oxazolone- and DNCB-induced AD in mice by down-regulating the TH2-associated cytokine IL-4 and improving skin barrier function and suggest WDE might be useful for the management of atopic dermatitis.

scholarly journals THE FUNCTIONAL STATUS OF THE SKIN BARRIER IN CHILDREN WITH ATOPIC DERMATITIS

2013 ◽  
Vol 10 (1) ◽  
pp. 52-57
Author(s):  
E T Kindeeva ◽  
E E Varlamov ◽  
A N Pampura
Keyword(s):  
Staphylococcus Aureus ◽  
Atopic Dermatitis ◽  
Topical Therapy ◽  
Skin Barrier ◽  
Specific Ige ◽  
Transepidermal Water Loss ◽  
Severe Atopic Dermatitis ◽  
Skin Ph ◽  
Skin Colonization

Introduction. One of the factors in the pathogenesis of atopic dermatitis is a dysfunction of the skin barrier. Background. To reveal the features of the barrier function of the skin in children with atopic dermatitis by measuring transepidermal water loss (TEWL) and the pH of the skin. Methods. The study included 98 children with atopic dermatitis. All patients measurement was performed by TEWL (Tewameter TM 300, Multi Probe Adapter MPA 5/9, Courage + Khazaka) and the pH of the skin (Skin-pHMeter, Multi Probe Adapter MPA 5/9, Courage + Khazaka). Results. TEWL value was significantly higher in children with severe atopic dermatitis (p=0,00001), in children up to 3 years (p=0,002), in patients with skin colonization of Staphylococcus aureus (p=0,006) and with specific IgE to staphylococcal enterotoxins. Skin pH was significantly higher in children with severe atopic dermatitis (p=0,0001), and in children under the age of 3 years (p=0,04). Conclusion. The determination of the level of TEWL and skin pH to assess the degree of inflammation activity in atopic dermatitis and to justify use of topical therapy, aimed to restoring the epidermal barrier of the skin at children with atopic dermatitis, is substantiated.

scholarly journals Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predates and predicts atopic dermatitis at 1 year

2015 ◽  
Vol 135 (4) ◽  
pp. 930-935.e1 ◽  
Author(s):  
Maeve Kelleher ◽  
Audrey Dunn-Galvin ◽  
Jonathan O'B. Hourihane ◽  
Deirdre Murray ◽  
Linda E. Campbell ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Water Loss ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Barrier Dysfunction

scholarly journals ‘Barrier dysfunction in Atopic newBorns studY’ (BABY): protocol of a Danish prospective birth cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. e033801
Author(s):  
Trine Gerner ◽  
Anne-Sofie Halling ◽  
Maria Rasmussen Rinnov ◽  
Nina Haarup Ravn ◽  
Mette Hjorslev Knudgaard ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Cohort Study ◽  
Birth Cohort ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Birth Cohort Study ◽  
Tape Stripping ◽  
Barrier Dysfunction ◽  
Prospective Birth Cohort ◽  
Prospective Birth Cohort Study

IntroductionSkin barrier development and dysfunction in premature and mature newborns is important for the risk of atopic dermatitis (AD).Methods and analysisThe Barrier dysfunction in Atopic newBorns studY (BABY) Cohort is a prospective birth cohort study of 150 preterm children (gestational age (GA) below 37+0) and 300 term children (GA 37+0 to 41+6). Skin barrier is assessed through transepidermal water loss, tape stripping, Raman-spectroscopy and microbiome sampling. Clinical examinations are done and DNA from buccal swabs is collected for genetic analyses. Thymus size is assessed by ultrasound examination. Information on pregnancy, delivery, parental exposures and diseases are collected, and structured telephone interviews are conducted at 18 and 24 months to assess exogenous exposures in the child and onset of AD. Hanifin and Rajka criteria as well as The UK Working Party's Diagnostic Criteria for Atopic Dermatitis are used to diagnose AD. Severity of AD is assessed using the Eczema Area and Severity Index (EASI) and Patient Oriented Eczema Measure (POEM).Ethics and disseminationThe study is approved by the scientific Ethical Committee of the Capital Region (H-16042289 and H-16042294).Outcomes will be presented at national and international conferences and in peer-reviewed publications.

scholarly journals Role of skin microbiome in epidermal barrier dysfunction and development of atopic dermatitis in high risk infants

2019 ◽  
Vol 16 (1) ◽  
pp. 59-64
Author(s):  
N B Migacheva
Keyword(s):  
At Risk ◽  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Transepidermal Water Loss ◽  
Skin Microbiome ◽  
Children At Risk ◽  
Barrier Dysfunction ◽  
Epidermal Barrier ◽  
Microbiome Composition

Background. Colonization of skin with S. aureus in atopic dermatitis (AD) patients is a widespread phenomenon and a factor complicating the course of the disease. At present, it is not quite clear the role of S. aureus in the development of AD in children at risk. The aim of our study was to discribe the skin microbiome composition in young children at risk, as well as to investigate the role of S. aureus in skin barrier dysfunction and the development of AD. Material and methods. 12months follow-up study of 37 infants at risk has been performed. It included a general clinical examination, a microbiological investigation of skin microbiome (at 1 and 6 months), and investigation of epidermal barrier function by determining the transepidermal water loss (TEWL) at 1, 3, 6 and 12 months. Realization of AD during the observation period was considered as main outcome. Results. The prevalence of S. aureus colonization of infants aged 1 month was 45.9%, at the age of 6 months - 29.7%. Correlation analysis revealed an association between the skin colonization with S. aureus and a decrease of TEWL (p = 0.004), as well as the cumulative incidence of AD (p

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