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Stratum corneum barrier and epidermal barrier.

Stratum corneum barrier and epidermal barrier.

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Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion, which is frequently encountered in clinical practice. Skin barrier dysfunction leads to enhanced skin irritability to non-specific stimuli and epicutaneous sensitization. In the lesion site, a further inflammation-related reduction in skin barri...

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... stratum corneum forms a barrier contributing to the prevention of leakage of body fluids, retention of internal water within the cell layers, and contributes to biological defense ( Fig. 1, 2). If the barrier function of the horny cell layer is dysfunctional, skin irritability to non-specific stimuli is enhanced, and allergen sensitization and inflammation are likely to occur. 4 Intercellular lipids of the stratum corneum are mainly composed of ceramide, cholesterol, and free fatty acids, and in the case of AD, the function ...

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Background: Atopic dermatitis (AD), a chronic, recurrent inflammatory skin condition primarily affects children. Topical treatment, systemic treatment, and phototherapy are mainstays of treatment. Topical corticosteroids (TCS) are first-line therapy for AD but are associated with various adverse effects. Topical calcineurin inhibitors (TCI) can be...

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... TCIs can be used as a maintenance treatment to minimize the use of TCSs in patients whose disease has stabilized. The application of tTAC 2-3 times a week for up to 1 year increases the number of days without acute AD lesions and lengthens the time of AD exacerbation [48,49]. Recent data also suggest that TCIs may have a positive impact on the altered skin microbiome, as they reduce S. aureus colonization and increase microbial diversity in lesional areas of the skin [50]. ...
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Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.
... Atopic dermatitis (AD) is a common chronic inflammatory skin disease, which is characterized by pruritic, eczematous lesions with the fluctuation of remission and relapse (1). It is often associated with high levels of serum immunoglobulin E (IgE) and a personal/ family history of atopic diseases (1). ...
... Atopic dermatitis (AD) is a common chronic inflammatory skin disease, which is characterized by pruritic, eczematous lesions with the fluctuation of remission and relapse (1). It is often associated with high levels of serum immunoglobulin E (IgE) and a personal/ family history of atopic diseases (1). The underlying pathogenesis of AD involves complex interactions among immune dysregulation, pruritus, and skin barrier dysfunction (2). ...
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Background Sweat aggravates atopic dermatitis (AD). In patients with AD, type-I hypersensitivity to sweat may be shown by histamine release from patients’ basophils in response to the semi-purified sweat antigen (QR), and the presence of specific immunoglobulin E (IgE) binding to MGL_1304, the component of QR. However, there has been no information on the immunological changes of type-I hypersensitivity to the sweat antigen in patients with well-controlled AD using topical corticosteroids (TCSs) and/or biologics as treatments. Method Histamine-releasing tests using patients’ basophils and QR and the detection of serum IgE against MGL_1304 and mite allergen Der f 1 were performed in patients with AD who were well controlled by topical TCS with/without dupilumab for 53–96 weeks. Results In total, 14 patients were enrolled. Seven patients received TCS therapy alone (TCS group), and seven patients received TCS with dupilumab therapy (dupilumab group). In all participants, the level of specific IgE against MGL_1304 decreased after treatments, but histamine release from basophils in response to QR did not show a statistically significant reduction; rather, it increased. In the dupilumab group, all changes in histamine release induced by QR (increase), the IgE level against MGL_1304 (decrease), and that against Der f 1 (decrease) were statistically significant, whereas the TCS group showed no significant change in any of them. Conclusion The well-controlled condition for 53–96 weeks resulted in no reduction of the hyperreactivity of basophils against in patients with AD, even with the treatment with dupilumab. This study suggests persistent basophil hyperreactivity to sweat antigen over a year or longer.
... Current treatment guidelines in Japan, Europe, and the USA recommend a combination approach consisting of topical antiinflammatory treatment (topical corticosteroids [TCS], topical calcineurin inhibitors, or a topical Janus Kinase [JAK] inhibitor), skin care, and elimination of exacerbating factors for the treatment of AD, with varying strengths of TCS used depending on disease severity [5][6][7][8][9]. Several new systemic therapies have recently been approved in Japan, but the use of traditional systemic therapy has been limited. ...
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Introduction: Treatment satisfaction in patients with atopic dermatitis (AD) has been investigated in several studies, but the desire for alternative treatment options is unclear and has not been previously evaluated. We conducted a cross-sectional, web-based survey aimed at evaluating the desire for alternative treatment options in adults with AD from a patient registry in Japan. Methods: Main eligibility criteria were adults aged ≥ 18 years with AD who were receiving treatment with topical corticosteroids (TCS) and not systemic therapy. Questionnaires included the Patient Oriented Eczema Measure (POEM) and pruritus Numeral Rating Scale. The proportion of patients with a desire for an alternative treatment option was assessed, overall (Overall Desire) and by specific type of alternative treatment option (Specific Desire), including change in medication, hospital transfer, and complementary and alternative medicine (CAM) use. Patient background factors associated with desire were evaluated using multivariate logistic regression. Results: Of the 1500 patients included in the analysis, 91.5% (n = 1372) had an Overall Desire, with the most common Specific Desire being a change in medication (n = 1213, 80.9%), followed by CAM (n = 593, 39.5%) and hospital transfer (n = 429, 28.6%). Dissatisfaction with current treatment was significantly (p < 0.05) associated with Overall Desire and Specific Desire (p < 0.001 each). Severe disease according to POEM was significantly associated with Overall Desire and a change in medication (p < 0.001 each). Conclusions: A high proportion of Japanese patients with AD being treated with TCS had a desire for alternative treatment options. The desire was greatly affected by patients' satisfaction with their current treatment and perception of disease severity. These findings highlight the importance of assessing patients' satisfaction or perception of disease severity, and facilitating early discussions between patient and doctor on their available treatment options, including new treatment options.
... Amidst the longstanding debate (7, 54-56), a number of scientific organizations have recently withdrawn or downgraded their recommendation for pHF in allergy prevention guidelines (57)(58)(59)(60)(61)(62). The switch in recommendation was mainly based on the findings of recent systematic reviews and meta-analyses which pointed out inadequate scientific evidence supporting the preventive role of pHF and raised concerns for bias on several levels in most previous studies (including selection, assessment, attrition and conflict of interest) (13,14). ...
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Background The role of partially hydrolyzed formulas (pHF) as part of nutritional interventions to prevent the development of allergic manifestations (AM) is questioned, and efficacy of each specific pHF should be substantiated. Objective To investigate the risk-reduction effect of a whey-based pHF on the development of cow's milk protein allergy (CMPA) and atopic dermatitis (AD) in infants at high-risk for allergy within the first 6 months of life. Materials and Methods In a multicenter double-blinded randomized controlled setting, healthy non-exclusively breastfed full-term infants, received either a specific whey-based pHF or a standard cow's milk-based formula (SF) and were clinically assessed for AM at 2, 4, and 6 months of age, supported by the objective scoring tools SCORAD and CoMiSS. CMPA was confirmed by open food challenge. Intention-to-Treat (ITT) and Per-Protocol (PP) analyses were performed. Results Of 331 randomized subjects (ITT analysis set), 160 received the pHF and 171 the SF. Six (3.8%) infants in the pHF and 12 (7%) in the SF group developed CMPA ( p = 0.186). AD incidence was significantly lower in those receiving pHF as compared to SF (10.6% vs. 18.7%, p = 0.024) with a relative risk (RR, 95% CI) of 0.54 (0.32, 0.92), in particular when adjusting for family history of AD [6.5% vs. 27.3%, RR 0.24 (0.07, 0.78), p = 0.018] representing a risk reduction of 76%. The PP analysis showed similar results. Conclusion This specific whey-based pHF reduced the risk of AD development, particularly in those with a family history of AD, and tended to reduce the development of CMPA in non-exclusively breastfed infants at high-risk for allergy. The A.R.T. study suggests that this particular pHF may contribute to measures aimed at prevention of allergic manifestations. However, further studies are needed to confirm this risk-reduction effect.
... Atopic dermatitis (AD) is a chronic and inflammatory skin disease that commonly affects young children. AD causes healthrelated burdens associated with pruritus and poor quality of life (1). A systematic review and meta-analysis showed that parental history of AD increased the risk of AD in the offspring [pooled odds ratio: 3.30, 95% confidence interval (CI): 2.45-4.42] ...
... According to a global epidemiological study conducted between 1994 and 1996, the prevalence of AD as reported by parents in a questionnaire was ∼7% among school-age children (3). The prevalence of AD as confirmed by a physician's examination in Japan is 12.8% in children aged 4 months old, 9.8% at 1.5 years old, and 13.2% at 3 years old (1,4). In a previous cohort study involving 1,157 children in Tokyo, Japan, 32.3% of children were diagnosed with AD by age nine, and four AD phenotypes were identified (5). ...
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Background Atopic dermatitis (AD) is a chronic and inflammatory skin disease that causes health-related burdens associated with pruritus and poor quality of life. Our previous study demonstrated that moisturizer (2e) application has a primary preventive effect on AD. However, this effect was not observed in recent randomized control trials. Thus, the ideal moisturizer type and application frequency for preventing AD development in infants remains unclear. We hypothesize that twice daily application of moisturizer is more effective than once daily application. We predict that applying sufficient amounts of high-quality moisturizer may be effective for preventing AD development in neonates and infants. Here, we describe a protocol for comparing the efficacy of twice daily and once daily application of Fam's Baby™ moisturizer and once daily application of 2e moisturizer for preventing AD in neonates. Methods This study is a single-center, three-parallel group, assessor-blind, superiority, individually randomized, controlled, phase II trial. Sixty newborns with at least one parent or sibling who has had AD is randomly assigned to application of Fam's Baby twice daily, Fam's Baby once daily, or 2e once daily in a 1:1:1 ratio until 32 weeks old. The primary outcome is the time to the first onset of AD during administration of the moisturizer. Discussion This is the first phase II randomized, controlled trial in Japan to estimate how effective the twice daily or once daily application of Fam's Baby moisturizer is in preventing AD compared to the once daily application of 2e moisturizer. In this study, we will use 2e once daily as a control to confirm the efficacy for primary prevention of AD as found in our previous trial. Based on the results of this study, we hope to conduct a phase III study to determine the optimal method for preventing AD via moisturizer application. Evaluation of application of moisturizers for preventing AD in this study is expected to contribute to a reduction in the prevalence of AD and a reduction in health care costs. Trial registration Japan Registry of Clinical Trials (jRCT); ID: jRCTs031200070.
... Many topical and systemic therapies have been evaluated for their ability to improve skin barrier function in patients with AD. Topical medications include topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), phosphodiesterase-4 (PDE-4) inhibitors, and Janus kinase J o u r n a l P r e -p r o o f inhibitors (JAKi) (Eichenfield et al., 2014;Katoh et al., 2020;Singh 2020;Wollenberg et al., 2018a). ...
... Conventional systemic immunosuppressive agents, such as corticosteroids, cyclosporine A, methotrexate, mycophenolate mofetil, and azathioprine, broadly target inflammation, but their use as treatments for AD is limited by safety concerns and the need to monitor for toxicities (Eichenfield et al., 2017;Katoh et al., 2020;Wollenberg et al., 2018b). To date, there is limited evidence that these treatments improve the skin barrier. ...
Article
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Skin barrier dysfunction, a defining feature of atopic dermatitis (AD), arises from multiple interacting systems. In AD, skin inflammation is caused by host–environment interactions involving keratinocytes, as well as tissue-resident immune cells such as type 2 innate lymphoid cells, basophils, mast cells, and T-helper type 2 cells, which produce type 2 cytokines including interleukin (IL)-4, IL-5, IL-13, and IL-31. Type 2 inflammation broadly impacts expression of genes relevant for barrier function, such as intracellular structural proteins, extracellular lipids, and junctional proteins, and enhances Staphylococcus aureus skin colonization. Systemic anti-type 2 inflammation therapies may improve dysfunctional skin barrier in AD.
... [88][89][90][91][92][93][94][95][96][97] Atopic dermatitis • The itch in AD is mediated by several mediators other than histamine, such as substance P, IL-31, protease, and gastrin-releasing peptides. [98] Since histamine is not the sole mediator, the usefulness of antihistamines in AD is controversial and debated. The 2019 guidelines on the management of AD in India suggest that a subset of patients of AD with allergic rhinitis and bronchial asthma benefit maximum from antihistamines [99] • The sedating properties of first-generation antihistamines have been used by physicians to ameliorate nocturnal itch by inducing sedation. ...
... [7,103] As there is no difference in treatment efficacy between sedative and nonsedative antihistamines, it is recommended that a nonsedating antihistamines should be selected. [98] Cutaneous mastocytosis ...
... The major drawback of first-generation antihistamines is their sedative potential, however, in children, they are paradoxically known to cause excitation, irritability and can precipitate seizures, especially in known epileptics or cases of febrile convulsions. [98,121,126] It is hypothesized that first-generation antihistamines may reduce the seizure threshold by blocking the histamine activity in central nervous system. [127] Third-generation antihistamines Consensus group on new generation antihistamines (COGNA) [17] in support with British society of allergy and clinical immunology have made recommendations for a drug to classify as third-generation antihistamine, it should have the following properties: ...
Article
Antihistamines are widely used drugs in pediatric population. First-generation antihistamines have been in use since last many years, though adequate data on their efficacy and safety in pediatric population is scarce. In contrast, second-generation antihistamines have been studied extensively in children and have a better safety profile with more receptor selectivity and less adverse effects. Pruritus has a significant impact on the quality of life in children and its management is of paramount importance. This article reviews the first and second-generation antihistamines in the light of recent advances in the understanding of their pharmacological properties and safety profile in children. An extensive literature search was done; all clinical trials, randomized double-blinded or single-blinded controlled trials, open-label studies, retrospective studies, reviews, case series, and case reports focusing on the use of antihistamines in pediatric age groups were screened. The selected articles were retrieved; the final manuscript was prepared, analyzed, and presented in a narrative fashion.
... The pathological mechanism of AD comprises three aspects: skin barrier dysfunction, T helper 2 (Th2) immune skewing, and pruritus. In AD, skin barrier dysfunction increases irritability due to external stimuli, and the skin becomes more prone to allergen sensitization and inflammation [27]. Filaggrin is a major protein that fills the cytoplasm of corneocytes. ...
... Filaggrin is a major protein that fills the cytoplasm of corneocytes. It aggregates keratin fibers, and its degradation products serve as moisturizing factors, indicating that filaggrin plays an important role in maintaining skin barrier function, retaining moisture, and lowering pH [27]. Abnormal barrier function due to filaggrin gene mutations was confirmed in patients with AD or AA, and filaggrin gene mutations have been shown to increase the risk of developing early and severe AD, as well as AA in patients with AD [28]. ...
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The incidence of allergic diseases is increasing, and research on their epidemiology, pathophysiology, and the prevention of onset is urgently needed. The onset of allergic disease begins in infancy with atopic dermatitis and food allergy and develops into allergic asthma and allergic rhinitis in childhood; the process is defined as “atopic march”. Atopic march is caused by multiple immunological pathways, including allergen exposure, environmental pollutants, skin barrier dysfunction, type 2 inflammation, and oxidative stress, which promote the progression of atopic march. Using recent evidence, herein, we explain the involvement of allergic inflammatory conditions and oxidative stress in the process of atopic march, its epidemiology, and methods for prevention of onset.
... By contrast, pimecrolimus plus topical corticosteroid in active lesions or topical corticosteroids are recommended in children aged 3-12 months (18). A key recommendation is to appropriately examine the extent of inflammation to apply a sufficient degree of these agents (19). [14] Topical antihistamines Topical antihistamines evidenced little utility for pruritus but they generate AEs such as skin hypersensitivity and alteration of the skin microbiome which limit their risk/benefit use (8). ...
... They must be exclusively used in active infections (14). In case of fungal infection by Malassezia located in the head and neck, topical antifungals such as ketoconazole and cyclopyroxolamine can be used (1,2) but lack evidence in large-scale studies (19). ...
... Reported serious AEs of cyclosporine A include nephrotoxicity, infection, hypertension, electrolyte problems, tremor, hypertrichosis, headache, gingival hyperplasia, and nonmelanoma skin cancer and only nephrotoxicity was irreversible (11). Cyclosporin A therapy should be quickly switched to conventional topical treatment after the relief of symptoms (19). A systematic review concluded that serum levels of cyclosporine should be recommended in specific pediatric groups (children receiving multiple medications), in patients with liver or kidney failure, and in non-responders (21). ...
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Atopic dermatitis is a major chronic, pruritic, and inflammatory dermatological disease with a deep psychosocial and physical burden. Despite the numerous treatment options available, discrepancies exist between international guidelines. This work aims to make a review and expert recommendations by consensus statement of the pharmacological options available for atopic dermatitis in adults and children. The experts developed 15 consensus statements of the pharmacological management of atopic dermatitis. Additionally, treatment options were classified into topical and systemic options. However, a comprehensive management also includes adjuvant pharmacological options for infections and itching control. The doses, routes of administration, and precautions of all the recommended pharmacological options for atopic dermatitis in children and adults have been compiled in a single document. Br J Bio Med Res Copyright©2021 Benjamin Hidalgo-Matlock et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for any purpose, even commercially, provided the original work is properly cited and states its license.
... Atopic dermatitis (AD) is a common, chronic inflammatory skin disease associated with intense pruritus, pain, sleep disturbance, and diminished quality of life [1][2][3][4]. Patients with moderate-to-severe disease who do not respond adequately to topical therapies have few effective approved treatment options [1,5,6]. ...
Article
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Background Pivotal phase III studies demonstrated that abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is effective treatment for moderate-to-severe atopic dermatitis (AD) as monotherapy and in combination with topical therapy.Objective The aim of this study was to evaluate the long-term safety of abrocitinib 200 mg and 100 mg in an integrated analysis of a phase IIb study, four phase III studies, and one long-term extension study.Methods Two cohorts were analyzed: a placebo-controlled cohort from 12- to 16-week studies and an all-abrocitinib cohort including patients who received one or more abrocitinib doses. Adverse events (AEs) of interest and laboratory data are reported.ResultsTotal exposure in the all-abrocitinib cohort (n = 2856) was 1614 patient-years (PY); exposure was ≥ 24 weeks in 1248 patients and ≥ 48 weeks in 606 (maximum 108 weeks). In the placebo-controlled cohort (n = 1540), dose-related AEs (200 mg, 100 mg, placebo) were nausea (14.6%, 6.1%, 2.0%), headache (7.8%, 5.9%, 3.5%), and acne (4.7%, 1.6%, 0%). Platelet count was reduced transiently in a dose-dependent manner; 2/2718 patients (200-mg group) had confirmed platelet counts of < 50 × 103/mm3 at week 4. Incidence rates (IRs) were 2.33/100PY and 2.65/100 PY for serious infection, 4.34/100PY and 2.04/100PY for herpes zoster, and 11.83/100PY and 8.73/100PY for herpes simplex in the 200-mg and 100-mg groups, respectively. IRs for nonmelanoma skin cancer, other malignancies, and major adverse cardiovascular events were < 0.5/100PY for both doses. Five venous thromboembolism events occurred (IR 0.30/100PY), all in the 200-mg group. There were three deaths due to gastric carcinoma (diagnosed at day 43), sudden death, and COVID-19.Conclusion Abrocitinib, with proper patient and dose selection, has a manageable tolerability and longer-term safety profile appropriate for long-term use in patients with moderate-to-severe AD.Trial RegistriesClinicalTrials.gov: NCT02780167, NCT03349060, NCT03575871, NCT03720470, NCT03627767, NCT03422822.