European Task Force on Atopic Dermatitis: position on vaccination of adult patients with atopic dermatitis against COVID-19 (SARS-CoV-2) being treated with systemic medication and biologics.
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SUBMITTER: Thyssen JP
PROVIDER: S-EPMC8014632 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation and skin barrier dysfunction. We are currently experiencing a new era of understanding of the pathogenesis of AD and, as a consequence, a new era of innovation in therapeutics, including small molecules and biologic therapy. Recently, advances in translational research have challenged the traditional AD pathogenesis paradigm of AD being solely a Th2-dominant disease. Other immune pathways seem to play a role in the complex AD pathophysiology, although the clinical relevance of these additional immune pathway abnormalities is unclear. Type 1, type 22, and type 17 pathway activation (with related cytokines/chemokines) have been demonstrated in the skin and blood of AD patients. Type 2 (interleukin [IL]-4, IL-13), IL-31, and type 22 (IL-22) pathway cytokines are increased in AD acute lesions. IL-22 induces both an epidermal hyperplasia at the onset of acute AD and a marked increase in the terminal differentiation S100 genes. This understanding of pathogenesis corresponds to a historic increase in therapeutic development in AD. The extreme clinical heterogeneity and the chronic progression of AD establish the need for newer, safer, and more effective treatments, control the disease, and improve the quality of life of affected patients.
| S-EPMC7875213 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, inflammatory skin disease with an eczematous rash and itching. Due to undesired adverse effects of traditional systemic treatment, there is still an unmet need for safe and effective long-term therapy for refractory AD. As our understanding of the pathogenesis underlying AD grows, novel treatments targeting specific molecules have been developed. Here, we discuss the efficacy and safety profiles of these drugs in recent clinical trials. Among their adverse effects, of particular note is AD acceleration. Although there is still debate about whether certain adverse reactions can be said to be paradoxical adverse events (PAEs), a wide range of PAEs have been reported during biological treatment for chronic immune-mediated diseases. Close surveillance of novel biologics is crucial to detect new undescribed paradoxical reactions and to shed light on the convoluted pathogenesis of AD.
| S-EPMC8181104 | biostudies-literature
Project description:Atopic dermatitis (AD) is a prevalent inflammatory skin disorder affecting all age and ethnic groups. The age-dependent varying appearance and extent of pruritic lesions are accompanied by distinct individual suffering, highlighting the importance of effective treatment options. Over the past years systemic drugs have considerably extended therapeutic approaches of patients with moderate to severe AD, in particular new biologics, most notably dupilumab has appeared as major breakthrough. In addition to monoclonal blockade of IL-4 and IL-13 pathway, more cytokines have been found to play a substantial role in AD pathogenesis, presenting potential targets for new therapy options.
| S-EPMC8648434 | biostudies-literature
Project description:The era of biologics for the treatment of moderate-to-severe atopic dermatitis (AD) began in 2017 with the approval of dupilumab, a monoclonal antibody that binds to the α-subunit of the interleukin IL-4 receptor. Until then, only conventional immunosuppressants were available for systemic treatment, of which only cyclosporine is approved for the treatment of severe AD. In the meantime, the therapeutic landscape of AD has been changing rapidly, and additional biologics have been developed which target IL-13, the IL-31 receptor, OX40, and OX40L, among others. Many of these substances have already shown promising results in phase 1, 2, and in some cases also phase 3 trials. In June 2021, tralokinumab, an IL-13 antibody, has been approved in Europe for the treatment of moderate-to-severe AD in adults. In addition to antibody-based therapies, "small molecules" that, e.g., inhibit Janus kinases enrich the armamentarium of systemic AD therapies. With all these agents, not only will many more targeted therapies become available, but also will the complex and heterogeneous pathophysiological processes of this disease be better understood.
| S-EPMC8439107 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic, systemic, inflammatory disease that affects the skin and is characterized by persistent itch and marked redness. AD is associated with an increased risk of skin infections and a reduced quality of life. Most AD treatment options to date were not designed to selectively target disease-causing pathways that have been established for this indication. Topical therapies have limited efficacy in moderate-to-severe disease, and systemic agents such as corticosteroids and immunosuppressants present with tolerability issues. Advances in the understanding of AD pathobiology have made possible a new generation of more disease-specific AD therapies. AD is characterized by the inappropriate activation of type 2 T helper (Th2) cells and type 2 innate lymphoid (ILC2) cells, with a predominant increase in type 2 cytokines in the skin, including interleukin (IL)-13 and IL-4. Both cytokines are implicated in tissue inflammation and epidermal barrier dysfunction, and monoclonal antibodies targeting each of these interleukins or their receptors are in clinical development in AD. In March 2017, dupilumab, a human anti-IL-4R? antibody, became the first biologic to receive approval in the United States for the treatment of moderate-to-severe AD. The anti-IL-13 monoclonal antibodies lebrikizumab and tralokinumab, which bind different IL-13 epitopes with potentially different effects, are currently in advanced-stage trials. Here, we briefly review the underlying pathobiology of AD, the scientific basis for current AD targets, and summarize current clinical studies of these agents, including new research to develop both predictive and response biomarkers to further advance AD therapy in the era of precision medicine.
| S-EPMC6850480 | biostudies-literature
Project description:BACKGROUND:Atopic dermatitis (AD) is a common inflammatory skin disease with a global prevalence ranging from 3% to 20%. Patients with AD have an increased risk for complications after viral infection (eg, herpes simplex virus), and vaccination of patients with AD with live vaccinia virus is contraindicated because of a heightened risk of eczema vaccinatum, a rare but potentially lethal complication associated with smallpox vaccination. OBJECTIVE:We sought to develop a better understanding of immunity to cutaneous viral infection in patients with AD. METHODS:In a double-blind randomized study we investigated the safety and immunogenicity of live attenuated yellow fever virus (YFV) vaccination of nonatopic subjects and patients with AD after standard subcutaneous inoculation or transcutaneous vaccination administered with a bifurcated needle. Viremia, neutralizing antibody, and antiviral T-cell responses were analyzed for up to 30 days after vaccination. RESULTS:YFV vaccination administered through either route was well tolerated. Subcutaneous vaccination resulted in higher seroconversion rates than transcutaneous vaccination but elicited similar antiviral antibody levels and T-cell responses in both the nonatopic and AD groups. After transcutaneous vaccination, both groups mounted similar neutralizing antibody responses, but patients with AD demonstrated lower antiviral T-cell responses by 30 days after vaccination. Among transcutaneously vaccinated subjects, a significant inverse correlation between baseline IgE levels and the magnitude of antiviral antibody and CD4(+) T-cell responses was observed. CONCLUSIONS:YFV vaccination of patients with AD through the transcutaneous route revealed that high baseline IgE levels provide a potential biomarker for predicting reduced virus-specific immune memory after transcutaneous infection with a live virus.
| S-EPMC3960337 | biostudies-literature
Project description:BACKGROUND:The first International Society of Atopic Dermatitis (ISAD) global meeting dedicated to atopic dermatitis (AD) in Sub-Saharan Africa (SSA) was held in Geneva, Switzerland in April 2019. A total of 30 participants were present at the meeting, including those from 17 SSA countries, representatives of the World Health Organization (WHO), the International Foundation for Dermatology (IFD) (a committee of the International League of Dermatological Societies, ILDS www.ilds.org), the Fondation pour la Dermatite Atopique, as well as specialists in telemedicine, artificial intelligence and therapeutic patient education (TPE). RESULTS:AD is one of the most prevalent chronic inflammatory skin diseases in SSA. Besides neglected tropical diseases (NTDs) with a dermatological presentation, AD requires closer attention from the WHO and national Departments of Health. CONCLUSIONS:A roadmap has been defined with top priorities such as access to essential medicines and devices for AD care, in particular emollients, better education of primary healthcare workers for adequate triage (e.g. better educational materials for skin diseases in pigmented skin generally and AD in particular, especially targeted to Africa), involvement of traditional healers and to a certain extent also patient education, bearing in mind the barriers to effective healthcare faced in SSA countries such as travel distances to health facilities, limited resources and the lack of dermatological expertise. In addition, several initiatives concerning AD research in SSA were discussed and should be implemented in close collaboration with the WHO and assessed at follow-up meetings, in particular, at the next ISAD meeting in Seoul, South Korea and African Society of Dermatology and Venereology (ASDV) meeting in Nairobi, Kenya, both in 2020.
| S-EPMC6899619 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic and relapsing disease affecting an increasing number of patients. Usually starting in early childhood, AD can be the initial step of the so-called atopic march, i.e. followed by allergic rhinitis and allergic asthma. AD is a paradigmatic genetically complex disease involving gene-gene and gene-environment interactions. Genetic linkage analysis as well as association studies have identified several candidate genes linked to either the epidermal barrier function or to the immune system. Stress, bacterial or viral infections, the exposure to aero- or food-allergens as well as hygienic factors are discussed to aggravate symptoms of AD. Athough generalized Th2-deviated immune response is closely linked to the condition of AD, the skin disease itself is a biphasic inflammation with an initial Th2 phase and while chronic lesions harbour Th0/Th1 cells. Regulatory T cells have been shown to be altered in AD as well as the innate immune system in the skin. The main treatment-goals include the elimination of inflammation and infection, preserving and restoring the barrier function and controlling exacerbating factors. The overall future strategy in AD will be aimed to control skin inflammation by a more proactive management in order to potentially prevent the emergence of sensitization as well as to design customized management based on genetic and pathophysiologic information.
| S-EPMC2883413 | biostudies-literature
Project description:A clinical trial assessed the cutaneous immune response and short-term efficacy, safety, and tolerability in adults with mild to moderate AD who applied SB414 2% and 6% BID for 2 weeks.
2020-11-23 | GSE141571 | GEO
Project description:Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in AD pathogenesis, but the alterations in the proteome that occur in the entire epidermis have not been defined. Employing a pressure-cycling technology-data-independent acquisition (PCT-DIA) approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and non-lesional skin of AD patients. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry or by immunofluorescence staining. The identified proteins reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the epidermis. These results provide insight into the molecular alterations in the epidermis of AD patients and identify novel targets for pharmaceutical intervention.
2022-10-04 | PXD025431 | Pride