Atopic dermatitis (AD), a common chronic pruritic inflammatory skin disease, impacts the quality of life of patients and caregivers and has become a global health problem. It is increasingly ...recognized as a disease not only of children but also of adults who may have a persistent or relapsing course from childhood or who develop new-onset adult disease. Besides well-established atopic comorbidities, associations with a number of nonatopic comorbidities have been reported. AD is characterized by both immune dysregulation and epidermal barrier dysfunction. The findings that nonlesional skin in AD has both terminal keratinocyte differentiation defects and immune abnormalities as well as multiple markers of immune and inflammatory activation in the circulation point to the systemic nature of the disease and have important translational implications. Although AD is predominantly associated with type 2 immune responses, activation of other cytokine pathways including T
1, T
22, and T
17/IL-23 has been reported, suggesting potential therapeutic targets and provide a rationale for treatment with novel biologics. Dupilumab, a fully human mAb targeting the IL-4 Rα subunit, blocks signaling of both IL-4 and IL-13 and is the first biologic to be approved for the treatment of moderate-to-severe AD in adult patients. Other biologics in current trials for AD are targeting the IL-31 receptor, IL-13, and the common p40 subunit of IL-12/IL-23.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that is complicated by an increased risk for skin and systemic infections. Preventive therapy for AD is based on skin barrier improvement ...and anti-inflammatory treatments, whereas overt skin and systemic infections require antibiotics or antiviral treatments. This review updates the pathophysiology, diagnosis, management, controversy of antibiotic use, and potential treatments of infectious complications of AD.
Published literature obtained through PubMed database searches and clinical pictures.
Studies relevant to the mechanisms, diagnosis, management, and potential therapy of infectious complications of AD.
Skin barrier defects, type 2 inflammation, Staphylococcusaureus colonization, and cutaneous dysbiosis are the major predisposing factors for the increased infections in AD. Although overt infections require antibiotics, the use of antibiotics in AD exacerbation remains controversial.
Infectious complications are a comorbidity of AD. Although not common, systemic bacterial infections and eczema herpeticum can be life-threatening. Preventive therapy of infections in AD emphasizes skin barrier improvement and anti-inflammatory therapy. The use of antibiotics in AD exacerbation requires further studies.
Atopic dermatitis (AD) is a chronic pruritic inflammatory disease that commonly presents in the pediatric population. Although definitions and diagnosis of AD have largely been agreed upon, ...allergists and dermatologists have similar and divergent approaches to the management of AD. This review facilitated integration of the American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Joint Task Force 2012 AD Practice Parameter and the 2014 American Academy of Dermatology guidelines to highlight the basic principles of AD management and discuss therapies and management of AD from the distinct perspectives of the allergist and dermatologist.
Background Additional topical treatments for atopic dermatitis (AD) are needed that provide relief while minimizing risks. Objective We sought to assess the efficacy and safety of crisaborole ...ointment, a phosphodiesterase 4 inhibitor, in two phase III AD studies (AD-301: NCT02118766 ; AD-302: NCT02118792 ). Methods Two identically designed, vehicle-controlled, double-blind studies enrolled and randomly assigned (2:1, crisaborole:vehicle) patients aged 2 years or older with an Investigator's Static Global Assessment (ISGA) score of mild or moderate for twice-daily application for 28 days. The primary end point was ISGA score at day 29 of clear (0)/almost clear (1) with 2-grade or greater improvement from baseline. Additional analyses included time to success in ISGA score, percentage of patients achieving clear/almost clear, reduction in severity of AD signs, and time to improvement in pruritus. Results More crisaborole- than vehicle-treated patients achieved ISGA score success (clear/almost clear with ≥2-grade improvement; AD-301: 32.8% vs 25.4%, P = .038; AD-302: 31.4% vs 18.0%, P < .001), with a greater percentage with clear/almost clear (51.7% vs 40.6%, P = .005; 48.5% vs 29.7%, P < .001). Crisaborole-treated patients achieved success in ISGA score and improvement in pruritus earlier than those treated with vehicle (both P ≤ .001). Treatment-related adverse events were infrequent and mild to moderate in severity. Limitations Short study duration was a limitation. Conclusions Crisaborole demonstrated a favorable safety profile and improvement in all measures of efficacy, including overall disease severity, pruritus, and other signs of AD.
Atopic dermatitis (AD) is an important chronic or relapsing inflammatory skin disease that often precedes asthma and allergic disorders. New insights into the genetics and pathophysiology of AD point ...to an important role of structural abnormalities in the epidermis as well as immune dysregulation not only for this skin disease but also for the development of asthma and allergies. Patients with AD have a unique predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus. Measures directed at healing and protecting the skin barrier and addressing the immune dysregulation are essential in the treatment of patients with AD, and early intervention may improve outcomes for both the skin disease as well as other target organs.
An update to the atopic dermatitis (AD) practice parameter was published in 2013 using an established grading system for determining category of evidence and strength of recommendation. Since the ...previous update in 2004, a number of seminal observations regarding skin barrier and immune dysregulation in AD have been made with important therapeutic implications. A key addition to the treatment algorithm based on our understanding that normal-appearing skin in patients with AD is not normal is proactive therapy. Studies with both topical steroids and a topical calcineurin inhibitor have shown that in patients with relapsing AD, if they are able to clear or almost clear their eczema, then twice-weekly proactive treatment of normal-appearing skin that tends to flare leads to better disease control. For difficult-to-manage patients, the value of wet wrap therapy is reaffirmed in the practice parameter update. In addition, allergen immunotherapy is now a consideration in select patients with AD and aeroallergen sensitivity. Beyond the practice parameter, novel approaches to filaggrin deficiency are being evaluated. With respect to immune dysregulation, dupilumab, a fully human monoclonal antibody directed at the IL-4 receptor alpha subunit was recently shown to be effective in treating adults with moderate-to-severe AD.
Atopic dermatitis: A practice parameter update 2012 Schneider, Lynda, MD; Tilles, Stephen, MD; Lio, Peter, MD ...
Journal of allergy and clinical immunology,
02/2013, Letnik:
131, Številka:
2
Journal Article
Recenzirano
This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & ...Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Atopic dermatitis: a practice parameter update 2012.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. Published practice parameters of the Joint Task Force on Practice Parameters for Allergy & Immunology are available online at http://www.jcaai.org.
Population-based estimates on the prevalence of atopic dermatitis in adults vary widely. The objectives of this study were to determine the prevalence of atopic dermatitis in the population of the ...United States, the distribution of disease severity, and its impact on health-related quality of life. Among 1,278 participating adults, the prevalence (95% confidence interval) of atopic dermatitis was 7.3% (5.9–8.8). Overall, 60.1% (56.1–64.1) of participants were classified as having mild, 28.9% (25.3–32.7) as having moderate, and 11% as having severe (8.6–13.7) disease. Patients with atopic dermatitis and those with more severe disease had higher scores in the dermatology life quality index (mean standard deviation for AD patients = 4.71 6.44 vs. control individuals = 0.97 2.12) (P < 0.001) and the hospital anxiety (mean standard deviation for AD patients = 7.03 4.80 vs. control individuals = 4.73 4.8) and depression (mean, standard deviation for AD patients = 5.83 4.54 vs. control individuals = 3.62 3.61) scales, indicating a worse impact on quality of life and an increased likelihood of anxiety or depression. Based on our prevalence estimates, 16.5 million adults would have a diagnosis of atopic dermatitis, with 6.6 million meeting criteria for moderate to severe disease. Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.
Background Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene ...encoding filaggrin in a subset of patients with AD. Objective We investigated whether reduced filaggrin expression was found in patients with AD who were not carriers of known filaggrin mutations and whether filaggrin expression was modulated by the atopic inflammatory response. Methods Filaggrin expression was measured in skin biopsies and cultured keratinocytes using real-time RT-PCR and immunohistochemistry. Filaggrin loss-of-function mutations were screened in a total of 69 subjects. Results Compared with normal skin, filaggrin expression was significantly reduced ( P < .05) in acute AD skin, with further reduction seen in acute lesions from 3 European American subjects with AD who were heterozygous for the 2282del4 mutation. This was confirmed by using immunohistochemistry. AD skin is characterized by the overexpression of IL-4 and IL-13. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression (0.04 ± 0.01 ng filaggrin/ng glyceraldehyde 3-phosphate dehydrogenase; P < .05) compared with media alone (0.16 ± 0.03). Conclusion Patients with AD have an acquired defect in filaggrin expression that can be modulated by the atopic inflammatory response. Clinical implications The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity.
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