scholarly journals Biologic Therapy of Moderate and Severe Forms of Atopic Dermatitis in Children

2020 ◽  
Vol 19 (6) ◽  
pp. 432-443
Author(s):  
Nikolay N. Murashkin ◽  
Leyla S. Namazova-Baranova ◽  
Leonid A. Opryatin ◽  
Roman V. Epishev ◽  
Alexander I. Materikin ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Chronic Inflammation ◽  
Biologic Therapy ◽  
Pediatric Population ◽  
Normal Skin ◽  
Skin Barrier ◽  
Skin Microbiome ◽  
Barrier Dysfunction ◽  
Microbial Dysbiosis ◽  
Unaffected Skin

Atopic dermatitis (AD) is the disease with chronic inflammation, epidermal barrier dysfunction and microbial dysbiosis. AD is widespread, including pediatric population. The article discusses the disease’s pathogenesis: skin barrier deficiency, immunological causes of chronic inflammation, characteristics of normal skin microbiome and its disorders on both affected and unaffected skin of children with AD. Main principles of systemic treatment for moderate and severe forms of disease are considered. Features of targeted therapy with dupilumab (IL 4/IL 13 inhibitor) in children with moderate and severe forms of AD are discussed. The overview of the research results on the dupilumab efficacy and safety is presented.

scholarly journals JAK-STAT Inhibitors in Atopic Dermatitis from Pathogenesis to Clinical Trials Results

2020 ◽  
Vol 8 (11) ◽  
pp. 1743 ◽  
Author(s):  
Krzysztof Szalus ◽  
Magdalena Trzeciak ◽  
Roman J. Nowicki
Keyword(s):  
Atopic Dermatitis ◽  
Sleep Disturbances ◽  
Pediatric Population ◽  
Adult Population ◽  
Skin Barrier ◽  
Immunosuppressive Drugs ◽  
Common Disease ◽  
Microbial Dysbiosis ◽  
Barrier Defect ◽  
Inflammatory Skin Disorder

A common disease worldwide is known as atopic dermatitis (AD), named also as atopic eczema, which is a chronic recurrent complex inflammatory skin disorder. It affects 2–10% of the adult population and up to 20% of the pediatric population. The clinical AD picture appears in typically localized eczema and dry skin, and is dominated by a persistent pruritus followed by sleep disturbances. AD strongly impacts on the quality of life of AD patients and their families as well as on social and economic aspects. The pathogenesis of the disease is complex and consists of multiple interactions between immunological disturbances, skin barrier defect, and microbial dysbiosis with environmental influences. The treatment of AD reflects the pathogenetic disorders, starting from basic emollient therapy, and goes to topical anti-inflammatory regimens followed by phototherapy, systemic immunosuppressive drugs, and new biologic immunomodulators. This paper will thus summarize the novel collection of biological treatment JAK-STAT inhibitors dedicated to AD.

scholarly journals Quorum sensing between bacterial species on the skin protects against epidermal injury in atopic dermatitis

2019 ◽  
Vol 11 (490) ◽  
pp. eaat8329 ◽  
Author(s):  
Michael R. Williams ◽  
Stephen K. Costa ◽  
Livia S. Zaramela ◽  
Shadi Khalil ◽  
Daniel A. Todd ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Quorum Sensing ◽  
Normal Skin ◽  
Bacterial Species ◽  
Skin Barrier ◽  
Toxin Production ◽  
Skin Microbiome ◽  
Coagulase Negative Staphylococci ◽  
Normal Human Skin ◽  
Autoinducing Peptides

Colonization of the skin by Staphylococcus aureus is associated with exacerbation of atopic dermatitis (AD), but any direct mechanism through which dysbiosis of the skin microbiome may influence the development of AD is unknown. Here, we show that proteases and phenol-soluble modulin α (PSMα) secreted by S. aureus lead to endogenous epidermal proteolysis and skin barrier damage that promoted inflammation in mice. We further show that clinical isolates of different coagulase-negative staphylococci (CoNS) species residing on normal skin produced autoinducing peptides that inhibited the S. aureus agr system, in turn decreasing PSMα expression. These autoinducing peptides from skin microbiome CoNS species potently suppressed PSMα expression in S. aureus isolates from subjects with AD without inhibiting S. aureus growth. Metagenomic analysis of the AD skin microbiome revealed that the increase in the relative abundance of S. aureus in patients with active AD correlated with a lower CoNS autoinducing peptides to S. aureus ratio, thus overcoming the peptides’ capacity to inhibit the S. aureus agr system. Characterization of a S. hominis clinical isolate identified an autoinducing peptide (SYNVCGGYF) as a highly potent inhibitor of S. aureus agr activity, capable of preventing S. aureus–mediated epithelial damage and inflammation on murine skin. Together, these findings show how members of the normal human skin microbiome can contribute to epithelial barrier homeostasis by using quorum sensing to inhibit S. aureus toxin production.

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

scholarly journals Effects of mineral complex material treatment on 2,4- dinitrochlorobenzene-induced atopic dermatitis like-skin lesions in mice model

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Johny Bajgai ◽  
Jing Xingyu ◽  
Ailyn Fadriquela ◽  
Rahima Begum ◽  
Dong Heui Kim ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Water Loss ◽  
Immunoglobulin E ◽  
Skin Barrier ◽  
Skin Lesions ◽  
Total Serum ◽  
Skin Barrier Function ◽  
Barrier Dysfunction ◽  
Complex Material ◽  
Mineral Complex

Abstract Background Atopic dermatitis (AD) is a chronic allergic inflammatory skin disease characterized by complex pathogenesis including skin barrier dysfunction, immune-redox disturbances, and pruritus. Prolonged topical treatment with medications such as corticosteroids, calcineurin inhibitors, and T-cell inhibitors may have some potential side-effects. To this end, many researchers have explored numerous alternative therapies using natural products and mineral compounds with antioxidant or immunomodulatory effects to minimize toxicity and adverse-effects. In the current study, we investigated the effects of mineral complex material (MCM) treatment on 2, 4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in SKH-1 hairless mice. Methods Animals were divided into four groups; normal control (NC), negative control treated with DNCB only (DNCB only), positive control treated with DNCB and tacrolimus ointment (PC) and experimental group treated with DNCB and MCM patch (MCM). Skin inflammation and lesion severity were investigated through analyses of skin parameters (barrier score and strength, moisture and trans-epidermal water loss level), histopathology, immunoglobulin E, and cytokines. In addition, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT) levels were measured in both serum and skin lysate. Results Our results demonstrates that MCM patch improved the progression of AD-like skin lesions by significantly increasing skin barrier strength and decreasing trans-epidermal water loss. Additionally, dermal administration of MCM patch significantly reduced epidermal thickness, ROS, and NO levels in skin lysate. Furthermore, we found that MCM suppressed the levels of AD-involved (Th1 and Th2) cytokines such as IL-2, IFN-γ, and IL-4 in blood. In addition, the levels of other Th1, and Th2 and inflammatory cytokines such as IL-1β, TNF-α, IL-6, IL-12(p70) and IL-10 were found lowest in the MCM group than in the DNCB only and PC groups. Moreover, we found total serum IgE level significantly increased after DNCB treatment, but decreased in the PC and MCM groups. Conclusion Taken together, our findings suggest that MCM application may have beneficial effects either systemic or regional on DNCB-induced AD lesional skin via regulation of the skin barrier function and immune-redox response.

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.

TRPV1 mediates itch‐associated scratching and skin barrier dysfunction in DNFB‐induced atopic dermatitis mice

2021 ◽  
Author(s):  
Liu Tang ◽  
Jiefang Gao ◽  
Xiaoqin Cao ◽  
Lu Chen ◽  
Huiling Wang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Barrier Dysfunction

scholarly journals Efficacy of Phototherapy With 308-nm Excimer Light for Skin Microbiome Dysbiosis and Skin Barrier Dysfunction in Canine Atopic Dermatitis

2021 ◽  
Vol 8 ◽  
Author(s):  
Ju-Yong Park ◽  
Seon-Myeong Kim ◽  
Jung-Hyun Kim
Keyword(s):  
Atopic Dermatitis ◽  
Relative Abundance ◽  
Barrier Function ◽  
Therapeutic Option ◽  
Clinical Signs ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Skin Microbiome ◽  
Canine Atopic Dermatitis ◽  
Allergic Skin

The management of canine atopic dermatitis, an allergic skin disorder, is challenging. To investigate the effect of phototherapy using a 308-nm excimer light as a topical treatment for canine atopic dermatitis, 10 dogs with canine atopic dermatitis and 10 with non-allergic skin were enrolled in this study. Phototherapy was applied every 7 days for a total of 2 months. The skin microbiome, skin barrier function, and clinical outcomes were evaluated after phototherapy. Phototherapy significantly changed the composition of the skin microbiome of dogs with atopic dermatitis and significantly increased the relative abundance of the phyla Actinobacteria and Cyanobacteria. It significantly alleviated the clinical signs of canine atopic dermatitis without serious adverse effects. Transepidermal water loss, as a measure of skin barrier function, significantly decreased after phototherapy. In addition, phototherapy increased microbial diversity and decreased the relative abundance of Staphylococcus pseudintermedius associated with the severity of canine atopic dermatitis. These results suggest that the excimer light therapy is a suitable and safe therapeutic option for canine atopic dermatitis, which is also a spontaneous animal model of atopic dermatitis.

An untargeted investigation into the skin surface lipidome in the West Highland white terrier dog, with and without atopic dermatitis

2020 ◽  
Author(s):  
Helen Louise Orbell ◽  
Nick J Cave ◽  
Katharina Parry ◽  
Craig E Griffin
Keyword(s):  
Atopic Dermatitis ◽  
Lipid Analysis ◽  
Critical Role ◽  
Skin Barrier ◽  
Disease Status ◽  
Skin Surface ◽  
Surface Lipids ◽  
Skin Surface Lipids ◽  
Secondary Hypothesis ◽  
Unaffected Skin

Abstract Background – The skin barrier is important in the pathogenesis of atopic dermatitis and stratum corneum lipids have a critical role. Skin surface lipids have been largely overlooked but also contribute to barrier function. An untargeted approach was used to compare the skin surface lipids from atopic and non-atopic West Highland White terrier dogs. The primary hypothesis was that a difference in the lipidome of atopic and non-atopic dogs would be found and the secondary hypothesis was that affected and unaffected skin would differ in lipid profile.Results – Thirty-nine dogs were classified into one of four disease status groups based on strict criteria. Samples for lipid analysis were collected from affected and unaffected skin, and liquid chromatography/mass spectrometry found 421 lipid soluble features. Ten lipids were positively identified. Statistical analysis could not distinguish between non-atopic and atopic dogs. Partial least squares-discriminant analysis revealed a difference in the lipid profiles from affected and non-affected skin irrespective of disease status. Conclusions – An untargeted approach found a large array of unidentified lipids from the skin surface. There was a difference in the lipidome between affected and unaffected skin that was not related to disease status. Investigation into the lipidome of the skin surface in health and disease is an emerging area of research which could have clinical and therapeutic applications.

scholarly journals Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis

2020 ◽  
Vol 21 (8) ◽  
pp. 2867 ◽  
Author(s):  
Gabsik Yang ◽  
Jin Kyung Seok ◽  
Han Chang Kang ◽  
Yong-Yeon Cho ◽  
Hye Suk Lee ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Systemic Disease ◽  
Skin Barrier ◽  
Immune Dysregulation ◽  
Food Allergies ◽  
Atopic Diseases ◽  
Barrier Dysfunction ◽  
Underlying Mechanisms ◽  
Chronic Pruritus ◽  
And Function

Atopic dermatitis (AD) is a common and relapsing skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. While AD was previously thought to occur primarily in children, increasing evidence suggests that AD is more common in adults than previously assumed. Accumulating evidence from experimental, genetic, and clinical studies indicates that AD expression is a precondition for the later development of other atopic diseases, such as asthma, food allergies, and allergic rhinitis. Although the exact mechanisms of the disease pathogenesis remain unclear, it is evident that both cutaneous barrier dysfunction and immune dysregulation are critical etiologies of AD pathology. This review explores recent findings on AD and the possible underlying mechanisms involved in its pathogenesis, which is characterized by dysregulation of immunological and skin barrier integrity and function, supporting the idea that AD is a systemic disease. These findings provide further insights for therapeutic developments aiming to repair the skin barrier and decrease inflammation.

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