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

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.

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 ◽  
...  

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.


2019 ◽  
Vol 4 (3) ◽  
pp. 01-08
Author(s):  
Nora Harfouch ◽  
Fouz Hassan

Background:Atopic dermatitis (AD) is a common chronic inflammatory skin disorder that induces several symptoms including pruritus and dryness, and is often associated with secondary cutaneous infections. AD is considered to be one of the most prevalent and studied skin diseases yet poorly understood, and its pathophysiology remains obscure. Even though other skin diseases (such as psoriasis) share the same pathologic factor -skin barrier defect - with atopic dermatitis, patients diagnosed with those diseases don't suffer infectious exacerbations like atopic patients do. Aim: Although many international researches have already discussed the relationship between staphylococcus aureus and AD, no studies about this subject in the Arabic region was documented. The aim of our study is to compare staphylococcus aureus colonization rates and densities between atopic dermatitis patients and non-atopic subjects, and to relate the colonization to the severity and duration of the disease. Materials and methods: This observational analytic study included 200 participants (99 diagnosed with atopic dermatitis and 101 control subjects without atopic dermatitis); nasal and skin swabs (lesional and non-lesional) were collected from patients, while nasal and only normal skin swabs were collected from controls. Positive swabs were assessed to determine the density of colonization. Results: 57.6% of patients had nasal colonization, 56.6% had lesional colonization and 30.3% had normal skin colonization. Nasal colonization rates and densities were higher in the patients group. We detected a correlation between colonization and severity of eczema, but no correlation between colonization and duration of the disease was detected. Conclusion: The high rates and densities of staphylococcus aureus colonization in lesional skin of atopic dermatitis patients point out the role of these organisms in the pathophysiology of the disease, put antibiotics on the treatment list of atopic dermatitis and explain infectious features in AD exacerbations.


2021 ◽  
Vol 22 (16) ◽  
pp. 8403
Author(s):  
Leszek Blicharz ◽  
Lidia Rudnicka ◽  
Joanna Czuwara ◽  
Anna Waśkiel-Burnat ◽  
Mohamad Goldust ◽  
...  

Atopic dermatitis (AD) is a common inflammatory dermatosis affecting up to 30% of children and 10% of adults worldwide. AD is primarily driven by an epidermal barrier defect which triggers immune dysregulation within the skin. According to recent research such phenomena are closely related to the microbial dysbiosis of the skin. There is growing evidence that cutaneous microbiota and bacterial biofilms negatively affect skin barrier function, contributing to the onset and exacerbation of AD. This review summarizes the latest data on the mechanisms leading to microbiome dysbiosis and biofilm formation in AD, and the influence of these phenomena on skin barrier function.


2016 ◽  
Vol 136 (9) ◽  
pp. S182
Author(s):  
S. Danby ◽  
H. Wan ◽  
J. Chittock ◽  
K. Brown ◽  
A. Wigley ◽  
...  

1993 ◽  
Vol 5 (2) ◽  
pp. 92-96 ◽  
Author(s):  
Takashi Yoshiike ◽  
Yosuke Aikawa ◽  
Jirot Sindhvananda ◽  
Hajime Suto ◽  
Kumiko Nishimura ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hongxiu Ji ◽  
Xiao-Kang Li

Atopic dermatitis (AD) is a chronic pruritic skin disorder affecting many people especially young children. It is a disease caused by the combination of genetic predisposition, immune dysregulation, and skin barrier defect. In recent years, emerging evidence suggests oxidative stress may play an important role in many skin diseases and skin aging, possibly including AD. In this review, we give an update on scientific progress linking oxidative stress to AD and discuss future treatment strategies for better disease control and improved quality of life for AD patients.


2019 ◽  
pp. 156-167
Author(s):  
E. N. Saverskaya

Due to high prevalence in the pediatric population, chronic recurrent course and difficulties in choosing the local therapy, atopic dermatitis is an urgent problem for pediatricians, dermatologists and allergists. The review presents data on the prevalence and features of the clinical manifestations of atopic dermatitis in various age periods. The authors consider structural, functional and immunological features of the skin barrier are considered in detail under normal and under pathological conditions. They emphasize the problems of quality of life, compliance and steroidophobia of patients with atopic dermatitis. Particular attention is paid to the concept of sensitive skin, the definition of this concept and the localization of sensitive skin area on the surface of the body. The article describes approaches to the method of choosing external therapy according to the European guidelines for the treatment of atopic dermatitis in 2018. It presents a modern practical algorithm for prescribing local anti-inflammatory drugs (topical glucocorticosteroids, topical calcineurin inhibitors) taking into account the severity of the clinical manifestations of the disease and the areas of application (sensitive skin areas/other parts of the body). The authors provide evidence of the efficacy and safety of topical calcineurin inhibitors, in particular pimecrolimus, in the treatment of patients with mild to moderate severity of atopic dermatitis, especially in sensitive skin areas.


2019 ◽  
Vol 19 (7) ◽  
pp. 1083-1087 ◽  
Author(s):  
Paolo Romita ◽  
Caterina Foti ◽  
Luca Stingeni ◽  
Katharina Hansel ◽  
Thea Magrone ◽  
...  

Background: The relationship between atopic dermatitis and allergic contact dermatitis is frequently debated, particularly in children. The impaired skin barrier of atopic subjects can facilitate the penetration of exogenous agents and its mutations in the filaggrin gene might be implicated in an increased risk to develop contact dermatitis. Moreover, atopic children are protractedly exposed to chemical substances contained in skin care products from an early age. Patients And Methods: The aim of this retrospective study is to determine if atopic children are more prone to allergic contact dermatitis and which substances are more frequently related to this disease. From 2014 to 2016, a total of 268 children under 14 years with a history of eczematous dermatitis, of whom 141 (52.6%) were affected, and 127 (47.4%) were not affected by AD, underwent patch testing with the baseline S.I.D.A.P.A standard series. Results: Based on the results of our study, the prevalence of contact allergy in atopic children is comparable to that noted in non-atopic children. The most frequent causes of contact allergy in children are fragrances, and their prevalence is significantly higher in atopic children (19.9%) than in non-atopic ones, (11.8%; p < .05). Conclusion: Our study highlights the importance of patch testing in atopic children for continuously monitoring the trends and changes of contact allergies that are a common disease and is even significantly increasing for some allergens, as fragrances. We may speculate that the protracted use of skincare products, associated with the impaired skin barrier of atopic children, enhances the risk of sensitization to the ingredients of these products.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Nanna Fyhrquist ◽  
Gareth Muirhead ◽  
Stefanie Prast-Nielsen ◽  
Marine Jeanmougin ◽  
Peter Olah ◽  
...  

Abstract Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.


Author(s):  
Nicholas Stefanovic ◽  
Alan D. Irvine ◽  
Carsten Flohr

Abstract Purpose of review Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children and up to 5% of adults worldwide, contributing to significant disease-related morbidity in this patient cohort. Its aetiopathogenesis is underpinned by multiple factors, including genetic susceptibility, skin barrier defects, a skewed cutaneous immune response and microbiome perturbation in both the skin and the gut. In this review, we aim to examine the biological effects of key environmental exposures (the sum of which is termed the “exposome”) at the population, community and individual levels in order to describe their effect on AD pathogenesis. Recent findings It is now understood that as well as considering the type of environmental exposure with regard to its effect on AD pathogenesis, the dosage and timing of the exposure are both critical domains that may lead to either exacerbation or amelioration of disease. In this review, we consider the effects of population-wide exposures such as climate change, migration and urbanization; community-specific exposures such as air pollution, water hardness and allergic sensitisation; and individual factors such as diet, microbiome alteration, psychosocial stress and the impact of topical and systemic therapy. Summary This review summarises the interaction of the above environmental factors with the other domains of AD pathogenesis, namely, the inherent genetic defects, the skin barrier, the immune system and the cutaneous and gut microbiota. We specifically emphasise the timing and dosage of exposures and its effect on the cellular and molecular pathways implicated in AD.


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