Role of genetic aspect in pathogenesis of atopic dermatitis

2013 ◽  
Vol 9 ◽  
pp. 1-8
Author(s):  
Martyna Wesserlking
Keyword(s):  
Atopic Dermatitis ◽  
Genetic Background ◽  
Clinical Presentation ◽  
Skin Barrier ◽  
Future Research ◽  
Barrier Dysfunction ◽  
Additional Risk ◽  
Cornified Envelope ◽  
Complicated Process

The pathogenesis of atopic dermatitis (AD) is a very complicated process that involves an intricate array of molecules. Nowadays it is generally accepted that cytokines play an important role in the progression of the clinical presentation of atopic dermatitis. However, emerging data point to the possible involvement of cornified envelope proteins in the development of skin barrier dysfunction and illness. Unfortunately, our knowledge on relation of particular genotype to progression of AD is very limited. Therefore, intensive studies are needed to increase our understanding of genetic background of atopic dermatitis. Hopefully the future research will identify new factors that help us to determine the additional risk for certain patients with atopic dermatitis.

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 Characterisation of the immune cells and cytokines involved in a model of atopic dermatitis

2021 ◽  
Author(s):  
◽  
Karmella Naidoo
Keyword(s):  
Atopic Dermatitis ◽  
Wide Spectrum ◽  
Management Strategies ◽  
Substantial Reduction ◽  
Skin Barrier ◽  
Barrier Dysfunction ◽  
Effector Cells ◽  
Treatment And Prevention ◽  
Inflammatory Parameters

<p>Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It is a chronic and relapsing inflammatory skin disease which often poses a life-long burden for the affected individuals. AD has been a difficult disease to treat as it manifests with a wide spectrum of clinical phenotypes and the current clinical management strategies are non-specific. Therefore, it is imperative to identify specific immunological pathways that could be targeted to treat this disease. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch and immune dysregulation that are responsible for AD progression. However, the precise role of effector cells and cytokines have not been fully elucidated. To address this, I established a clinically relevant model of AD, using the vitamin D analogue, MC903. This MC903 model closely resembles the AD phenotype in patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, providing a novel platform to evaluate targets for the treatment and prevention of AD. Furthermore, this model exposed the cells and cytokines that are critically associated with disease severity, including eosinophils, mast cells, TSLP, IL-4 and IL-9, but not CD4+ T cells. The instrumental role of these effector cells and cytokines was established by their stepwise depletion or blockade. Indeed, functional eosinophil depletion via the use of inducible eosinophil (iPHIL) mice significantly ameliorated AD pathology, most notably itch. Similar results were obtained after blockade of the IL-4/IL-13 axis by genetic deletion of STAT6. The clinically more relevant use of soluble inhibitors targeting IL-9 and CRTh2 (in a prophylactic and therapeutic setting, respectively), both resulted in a substantial reduction in AD phenotype. In summary, this body of work led to the identification of key disease-initiating and effector cells and molecules that represent attractive targets for the treatment of AD.</p>

scholarly journals Expression Profiles of Genes Encoding Cornified Envelope Proteins in Atopic Dermatitis and Cutaneous T-Cell Lymphomas

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 862
Author(s):  
Magdalena Trzeciak ◽  
Berenika Olszewska ◽  
Monika Sakowicz-Burkiewicz ◽  
Małgorzata Sokołowska-Wojdyło ◽  
Jerzy Jankau ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
T Cell ◽  
Expression Profiles ◽  
Skin Barrier ◽  
Control Group ◽  
Mrna Levels ◽  
Barrier Dysfunction ◽  
Cornified Envelope ◽  
Protein Levels ◽  
T Cell Lymphomas

The skin barrier defect in cutaneous T-cell lymphomas (CTCL) was recently confirmed to be similar to the one observed in atopic dermatitis (AD). We have examined the expression level of cornified envelope (CE) proteins in CTCL, AD and healthy skin, to search for the differences and their relation to the courses of both diseases. The levels of FLG, FLG2, RPTN, HRNR, SPRR1A, SPRR1B, SPRR3 and LELP-1 mRNA were determined by qRT-PCR, while protein levels were examined using the ELISA method in skin samples. We have found that mRNA levels of FLG, FLG2, LOR, CRNN and SPRR3v1 were decreased (p ≤ 0.04), whereas mRNA levels of RPTN, HRNR and SPRR1Av1 were increased in lesional and nonlesional AD skin compared to the healthy control group (p ≤ 0.04). The levels of FLG, FLG2, CRNN, SPRR3v1 mRNA increased (p ≤ 0.02) and RPTN, HRNR and SPRR1Av1 mRNA decreased (p ≤ 0.005) in CTCL skin compared to the lesional AD skin. There was a strong correlation between the stage of CTCL and increased SPRR1Av1 gene expression at both mRNA (R = 0.89; p ≤ 0.05) and protein levels (R = 0.94; p ≤ 0.05). FLG, FLG2, RPTN, HRNR and SPRR1A seem to play a key role in skin barrier dysfunction in CTCL and could be considered a biomarker for differential diagnosis of AD and CTCL. SPRR1Av1 transcript levels seem to be a possible marker of CTCL stage, however, further studies on a larger study group are needed to confirm our findings.

scholarly journals Atopic dermatitis: experimentalmodels for study of pathogenesis and development of new methods of treatment

2011 ◽  
Vol 8 (6) ◽  
pp. 3-11
Author(s):  
N N Shershakova ◽  
A A Babakhin ◽  
O G Elisyutina ◽  
M R Khaitov ◽  
N N Shershakova ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Barrier ◽  
Skin Inflammation ◽  
Barrier Dysfunction ◽  
Skin Injury ◽  
Allergic Skin ◽  
Promising Area ◽  
Functional Peptides ◽  
Methods Of Treatment

Atopic dermatitis (AD) is characterized by allergic skin inflammation. A hallmark of AD is dry itchy skin due, at least in part, to defects in skin genes that are important for maintaining barrier function. The pathogenesis of AD remains incompletely understood. A number of mouse models of AD have been developed. This review discusses these models and emphasizes the role of mechanical skin injury and skin barrier dysfunction in eliciting allergic skin inflammation. Also, we describe various approaches to the treatment of atopic dermatitis, the latest of which is the introduction of siRN A. Development of drugs based on siRN A using functional peptides is a promising area of research in allergology.

scholarly journals Management of Patients with Atopic Dermatitis: The Role of Emollient Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
M. Catherine Mack Correa ◽  
Judith Nebus
Keyword(s):  
Atopic Dermatitis ◽  
Young Children ◽  
Stratum Corneum ◽  
Skin Disorder ◽  
Calcineurin Inhibitors ◽  
Skin Barrier ◽  
Barrier Dysfunction ◽  
Inflammatory Skin Disorder ◽  
Infants And Young Children

Atopic dermatitis is a common inflammatory skin disorder that afflicts a growing number of young children. Genetic, immune, and environmental factors interact in a complex fashion to contribute to disease expression. The compromised stratum corneum found in atopic dermatitis leads to skin barrier dysfunction, which results in aggravation of symptoms by aeroallergens, microbes, and other insults. Infants—whose immune system and epidermal barrier are still developing—display a higher frequency of atopic dermatitis. Management of patients with atopic dermatitis includes maintaining optimal skin care, avoiding allergic triggers, and routinely using emollients to maintain a hydrated stratum corneum and to improve barrier function. Flares of atopic dermatitis are often managed with courses of topical corticosteroids or calcineurin inhibitors. This paper discusses the role of emollients in the management of atopic dermatitis, with particular emphasis on infants and young children.

scholarly journals Characterisation of the immune cells and cytokines involved in a model of atopic dermatitis

2021 ◽  
Author(s):  
◽  
Karmella Naidoo
Keyword(s):  
Atopic Dermatitis ◽  
Wide Spectrum ◽  
Management Strategies ◽  
Substantial Reduction ◽  
Skin Barrier ◽  
Barrier Dysfunction ◽  
Effector Cells ◽  
Treatment And Prevention ◽  
Inflammatory Parameters

<p>Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It is a chronic and relapsing inflammatory skin disease which often poses a life-long burden for the affected individuals. AD has been a difficult disease to treat as it manifests with a wide spectrum of clinical phenotypes and the current clinical management strategies are non-specific. Therefore, it is imperative to identify specific immunological pathways that could be targeted to treat this disease. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch and immune dysregulation that are responsible for AD progression. However, the precise role of effector cells and cytokines have not been fully elucidated. To address this, I established a clinically relevant model of AD, using the vitamin D analogue, MC903. This MC903 model closely resembles the AD phenotype in patients, including inflammatory parameters, barrier dysfunction, itch, and histopathological characteristics, providing a novel platform to evaluate targets for the treatment and prevention of AD. Furthermore, this model exposed the cells and cytokines that are critically associated with disease severity, including eosinophils, mast cells, TSLP, IL-4 and IL-9, but not CD4+ T cells. The instrumental role of these effector cells and cytokines was established by their stepwise depletion or blockade. Indeed, functional eosinophil depletion via the use of inducible eosinophil (iPHIL) mice significantly ameliorated AD pathology, most notably itch. Similar results were obtained after blockade of the IL-4/IL-13 axis by genetic deletion of STAT6. The clinically more relevant use of soluble inhibitors targeting IL-9 and CRTh2 (in a prophylactic and therapeutic setting, respectively), both resulted in a substantial reduction in AD phenotype. In summary, this body of work led to the identification of key disease-initiating and effector cells and molecules that represent attractive targets for the treatment of AD.</p>

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 The Implications of Pruritogens in the Pathogenesis of Atopic Dermatitis

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee
Keyword(s):  
Atopic Dermatitis ◽  
Environmental Factors ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Disease ◽  
Targeted Therapies ◽  
Skin Barrier ◽  
Skin Barrier Function ◽  
Inflammatory Molecules

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.

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
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