Exploring the Complexities of Atopic Dermatitis: Pathophysiological Mechanisms and Therapeutic Approaches (original) (raw)
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Pharmaceuticals
Atopic dermatitis (AD) is a pathological skin condition with complex aetiological mechanisms that are difficult to fully understand. Scientific evidence suggests that of all the causes, the impairment of the skin barrier and cutaneous dysbiosis together with immunological dysfunction can be considered as the two main factors involved in this pathological skin condition. The loss of the skin barrier function is often linked to dysbiosis and immunological dysfunction, with an imbalance in the ratio between the pathogen Staphylococcus aureus and/or other microorganisms residing in the skin. The bibliographic research was conducted on PubMed, using the following keywords: ‘atopic dermatitis’, ‘bacterial therapy’, ‘drug delivery system’ and ‘alternative therapy’. The main studies concerning microbial therapy, such as the use of bacteria and/or part thereof with microbiota transplantation, and drug delivery systems to recover skin barrier function have been summarized. The studies examine...
Insights Into Atopic Dermatitis – From Pathogenesis to Therapy
Acta Medica Bulgarica
Atopic dermatitis (AD), or eczema, is a common skin disease that is often associated with other atopic disorders, such as allergic rhinitis and asthma. The disease can develop both in infancy and adulthood, and characterizes with recurrent episodes impairing the quality of life. The review аnalyzes the genetical, immunological, and environmental factors in the pathogenesis of AD. The role of the skin barrier function is also considered in regard of the main hypotheses for AD development. Further elucidation of the mechanisms involved in the pathogenesis of AD could give interesting and useful clues for therapeutic protocols and prophylactic approaches.
Atopic Dermatitis: Recent Trends in Pathogenesis and Therapy
Journal of Investigative Dermatology, 1994
Emerging concepts in the areas related to the pathogenesis and treatment of atopic dermatitis are reviewed. In particular, recent findin gs have revealed several key steps in the maintenance of a vicious circle of spongiotic dermatitis associated with elevated T-lymphocyte activation, hyperstimulatory Langerhans cells, defective cell-mediated immunity, and B-cell IgE overproduction. The discovery of specific IgEbinding structures on Langerhans cells provides a mechanism for Langerhans cells to capture and present IgE-targeted allergens to allergen-specific T cells. Furthermore, certain microbial allergens that tend to preferentially elicit IgE-type responses also elicit a T-cell response dominated by the IgEinducing lymphokine interleukin 4. Repeated stimulation by activated Langerhans cells appears to induce just such a response. Abnormal biochemical responsiveness and mediator release by AD monocytes, mast cells, and eosinophils also participate in the sustainment or initiation of such a vicious circle, and contribute directly to the dermatitis as well. Developments in the areas of neuropeptides, genetics, microbial superantigens, and cytokine networks in the skin also appear to have promise in providing a rational link between immune defects and the inflammatory events in AD. R ecent a~vances in the pathog, eneSiS of atopic dermatitis are leadmg to novel forms of therapies for this disease, which can have enormous impact, not only on the life of the patient, but also on his or her family. An understanding of these developments and the underlying biology is critical to successful physician utilization of our cllrrently available agen ts and newer agents that are currently under develop
Biomedicines
Atopic dermatitis (AD) is a common chronic inflammatory and immune-mediated skin disease with a complex pathophysiology and still represents a therapeutic challenge, owing to limited responses to available treatments. However, recent advances in the understanding of AD pathophysiology have led to the discovery of several new potential therapeutic targets, and research in the field of new molecules with therapeutic perspectives is boiling, with more than 70 new promising drugs in development. The aim of this systematic review is to provide the state of the art on the current knowledge concerning the pathophysiology of the disease and on novel agents currently being investigated for AD, and to highlight which type of evolution is going to take place in therapeutic approaches of atopic dermatitis in the coming years.
Immunological and molecular targets of atopic dermatitis treatment
British Journal of Dermatology, 2014
Atopic dermatitis (AD) is a common, chronic inflammatory skin disease with a highly variable clinical phenotype and heterogeneous pathophysiology. Its pathogenesis is associated with alterations to both the skin barrier and the immune system, which may in turn be influenced by genetic mutations and the patient's environment. Basic and translational research, as well as clinical trials, have helped broaden our knowledge of the molecular mechanisms underlying the development of AD and to identify potential treatment targets and approaches. These include new ways of reducing transepidermal water loss and the shedding of corneocytes, new ways of interacting with established molecular targets (such as histamine receptors and interleukins and other T-cell cytokines), and the identification of new molecular targets (such as toll-like receptors and tight junction proteins). Well-established treatment options such as emollients, corticosteroids and topical calcineurin inhibitors will clearly continue to have a role in treating AD. Among the new agents that could be joining them in the near future are sphinganin (a precursor of ceramides 1 and 3), cannabinoids, highly targeted monoclonal antibodies and subcutaneous immunotherapy.
Atopic Dermatitis—Beyond the Skin
Diagnostics
Atopic dermatitis is a chronic inflammatory disease that can arise during the first months of life or at maturity and have a significant negative impact on the quality of life. The main pathogenic mechanism is the breakdown of cutaneous barrier integrity, which is associated with systemic inflammatory immunologic disorders. Atopic dermatitis involves numerous immunologic, allergic, respiratory, and ophthalmologic comorbidities that develop through similar intricate pathogenic phenomena. The atopic march represents the evolution in time of various allergic diseases, of which food allergies often cause the first manifestations of atopy, even from a very young age. Chronic inflammation translated through specific markers, next to increased immunoglobulin E (IgE) serum levels and heterogenous clinical manifestations, argue for the inclusion of atopic dermatitis in the systemic disease category.
Scratching the Surface: Towards Understanding the Pathogenesis of Atopic Dermatitis
Critical Reviews™ in Immunology, 2008
Atopic dermatitis (AD) is a chronic inflammatory skin disease with a steadily increasing prevalence affecting 10%-20% of infants and 1%-3% of adults globally. It is often the first clinical manifestation of atopic disease preceding asthma and allergic rhinitis. At least half of the children with AD develop some other form of atopic disease later in life. The pathogenesis of AD involves a complex interplay of factors, including genetic predisposition due to altered immune or skin barrier function, interactions with the environment, and infectious triggers of inflammation. In this review, we summarize the recent advances in understanding the contribution of different factors in the pathophysiology of AD in human and animal model systems. These insights provide new therapeutic potential for the treatment of human AD.
International Journal of Molecular Sciences
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encount...