The use of biologics for immune modulation in allergic disease. van de Veen Willem,Akdis Mübeccel The Journal of clinical investigation The rising prevalence of allergies represents an increasing socioeconomic burden. A detailed understanding of the immunological mechanisms that underlie the development of allergic disease, as well as the processes that drive immune tolerance to allergens, will be instrumental in designing therapeutic strategies to treat and prevent allergic disease. Improved characterization of individual patients through the use of specific biomarkers and improved definitions of disease endotypes are paving the way for the use of targeted therapeutic approaches for personalized treatment. Allergen-specific immunotherapy and biologic therapies that target key molecules driving the Th2 response are already used in the clinic, and a wave of novel drug candidates are under development. In-depth analysis of the cells and tissues of patients treated with such targeted interventions provides a wealth of information on the mechanisms that drive allergies and tolerance to allergens. Here, we aim to deliver an overview of the current state of specific inhibitors used in the treatment of allergy, with a particular focus on asthma and atopic dermatitis, and provide insights into the roles of these molecules in immunological mechanisms of allergic disease. 10.1172/JCI124607
    Efficacy of biologics in atopic dermatitis. Wu Jianni,Guttman-Yassky Emma Expert opinion on biological therapy : Atopic dermatitis (AD) is a heterogeneous disease. Recent advancements in understanding AD pathogenesis resulted in the exponential expansion of its therapeutic pipeline, particularly following the success and FDA-approval of dupilumab. Different phenotypes of AD by age and ethnicity have also recently been described and clinical studies of emerging treatments will further clarify the role of each cytokine pathway in AD.: We review the impressive repertoire of biologics for treatment of moderate-to-severe AD, including those targeting Th2, Th22, Th17/IL-23 and IgE. We highlight the scientific rationale behind each approach and provide a discussion of the most recent clinical efficacy and safety data.: AD is a complex disease and recent research has identified numerous endotypes, reinforcing the rationale for developing targeted therapeutics to antagonize these factors. Dupilumab has revolutionized AD treatment and its mechanistic studies also offer crucial insight into AD pathogenesis. Nevertheless, this biologic does not work for everyone, highlighting the need for a more precise approach to address the unique immune fingerprints of each AD subset. Ultimately targeted therapeutics will complement our understanding of the AD molecular map and help push AD management into an era of personalized medicine. 10.1080/14712598.2020.1722998
    Advances in atopic dermatitis in 2017. Kennedy Katie,Heimall Jennifer,Spergel Jonathan M The Journal of allergy and clinical immunology This review encompasses relevant scientific and clinical advances in atopic dermatitis (AD) published in 2017. These include articles from the Journal of Allergy and Clinical Immunology, as well as other prominent publications that have contributed to the emerging field, on the microenvironment of the skin and molecular patterns guiding biologic treatment strategies. The most commonly questioned and explored themes of the year included the effect of the microbiome on AD development, as well as cell signaling and symptom severity. Topics also included the description of patient-specific molecular endotypes within the larger population with AD. All of these factors will create potential opportunities to guide personalized therapy with the broadening array of topical and systemic interventions currently available, as well as providing new insights to guide the development of novel molecularly targeted therapeutics. With recent US Food and Drug Administration approval of the first wave of new targeted therapies for AD, additional information exploring the safety profiles and long-term effects of these medications was also at the forefront in 2017. 10.1016/j.jaci.2018.10.012
    Adult atopic dermatitis: new and emerging therapies. Napolitano Maddalena,Marasca Claudio,Fabbrocini Gabriella,Patruno Cataldo Expert review of clinical pharmacology INTRODUCTION:Adult atopic dermatitis (AD) is very difficult to manage. Indeed, AD in adults is frequently refractory to topical treatment, especially with regards to the persistent form. Therefore, long-term treatment with oral immunosuppressive therapy is often required to control the burden of the disease, prevent flare-ups and achieve better patient quality of life outcomes. Areas covered: In the last decade the better understanding of AD pathogenesis has been used to improve treatment strategies with many emerging therapeutics options. Epidermal barrier impairment often plays the initial role in the initiation of the disease. Moreover, T helper 2 cytokines interleukin (IL)-4 and IL-13 and their downstream effects are prominent in AD, with pleiotropic effects on the innate and adaptive immune system. Targeting these cells, their products or receptors appears to be a reasonable therapeutic strategy. Expert commentary: In the next years, many therapeutic options for adult AD will be available. Clinical trials showed that JAK inhibitors, PDE-4 inhibitors and monoclonal antibodies against some IL (IL-4, IL 13, IL-17, IL-22, IL-31) seem to be the most promising drugs, but dermatologists will have to evaluate their effectiveness and safety in clinical practice. 10.1080/17512433.2018.1507734
    The Microbiome and Atopic Dermatitis: A Review. Pothmann Anna,Illing Tanja,Wiegand Cornelia,Hartmann Albert A,Elsner Peter American journal of clinical dermatology The microbiome is defined as the sum of microbes, their genomes, and interactions in a given ecological niche. Atopic dermatitis is a multifactorial chronic inflammatory skin disease leading to dryness and itchiness of the skin. It is often associated with comorbidities such as allergic rhinoconjunctivitis and asthma. Today, culture-free techniques have been established to define microbes and their genomes that may be both detrimental and beneficial for their host. There are signs that microbes, both on skin and in the gut, may influence the course of atopic dermatitis. Antiseptic treatment has been used for decades, however now, with the help of traditional culture-based methods and modern metagenomics, we are beginning to understand that targeted treatment of dysbiosis may possibly become part of an integrated therapy plan in the future. 10.1007/s40257-019-00467-1
    Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Furue Masutaka,Chiba Takahito,Tsuji Gaku,Ulzii Dugarmaa,Kido-Nakahara Makiko,Nakahara Takeshi,Kadono Takafumi Allergology international : official journal of the Japanese Society of Allergology Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder mostly associated with IgE elevation and skin barrier dysfunction due to decreased filaggrin expression. The lesional skin of AD exhibits Th2- and Th22-deviated immune reactions that are progressive during disease chronicity. Th2 and Th22 cytokines further deteriorate the skin barrier by inhibiting filaggrin expression. Some IgEs are reactive to self-antigens. The IgE autoreactivity may precipitate the chronicity of AD. Upon activation of the ORAI1 calcium channel, atopic epidermis releases large amounts of thymic stromal lymphopoietin (TSLP), which initiates the Th2 and Th22 immune response. Th2-derived interleukin-31 and TSLP induce an itch sensation. Taken together, TSLP/Th2/Th22 pathway is a promising target for developing new therapeutics for AD. Enhancing filaggrin expression using ligands for the aryl hydrocarbon receptor may also be an adjunctive measure to restore the disrupted barrier function specifically for AD. 10.1016/j.alit.2016.12.002
    Trends in nanoformulations for atopic dermatitis treatment. Ramos Campos Estefânia Vangelie,Proença Patrícia Luiza De Freitas,Doretto-Silva Lorena,Andrade-Oliveira Vinicius,Fraceto Leonardo Fernandes,de Araujo Daniele Ribeiro Expert opinion on drug delivery INTRODUCTION:Immunological skin dysfunctions trigger the synthesis and release of inflammatory cytokines, which induce recurrent skin inflammation associated with chronic itching, inefficient barrier behavior, and reduced skin hydration. These features characterize a multifactorial chronic inflammatory disease atopic dermatitis (AD). AD therapy includes anti-inflammatory drugs and immunosuppressors as well as non-pharmacological alternatives such as emollients, moisturizers, and lipids (ceramides, phospholipids) for modulating the skin hydration and the barrier repair. However, these treatments are inconvenient with low drug skin penetration and insufficient maintenance on the application site. AREAS COVERED:Nanotechnology-based therapies can be a great strategy to overcome these limitations. Considering the particular skin morphological organization, SC lipid matrix composition, and immunological functions/features related to nanocarriers, this review focuses on recent developments of nanoparticulate systems (polymeric, lipid-based, inorganic) as parent or hybrid systems including their chemical composition, physico-chemical and biopharmaceutical properties, and differential characteristics that evaluate them as new effective drug-delivery systems for AD treatment. EXPERT OPINION:Despite the several innovative formulations, research in nanotechnology-based carriers should address specific aspects such as the use of moisturizers associated to pharmacological therapies, toxicity studies, scale-up production processes and the nanocarrier influence on immunological response. These approaches will help researchers choose the most appropriate nanocarrier system and widen nanomedicine applications and commercialization. 10.1080/17425247.2020.1813107
    Leveraging Multilayered "Omics" Data for Atopic Dermatitis: A Road Map to Precision Medicine. Ghosh Debajyoti,Bernstein Jonathan A,Khurana Hershey Gurjit K,Rothenberg Marc E,Mersha Tesfaye B Frontiers in immunology Atopic dermatitis (AD) is a complex multifactorial inflammatory skin disease that affects ~280 million people worldwide. About 85% of AD cases begin in childhood, a significant portion of which can persist into adulthood. Moreover, a typical progression of children with AD to food allergy, asthma or allergic rhinitis has been reported ("allergic march" or "atopic march"). AD comprises highly heterogeneous sub-phenotypes/endotypes resulting from complex interplay between intrinsic and extrinsic factors, such as environmental stimuli, and genetic factors regulating cutaneous functions (impaired barrier function, epidermal lipid, and protease abnormalities), immune functions and the microbiome. Though the roles of high-throughput "omics" integrations in defining endotypes are recognized, current analyses are primarily based on individual omics data and using binary clinical outcomes. Although individual omics analysis, such as genome-wide association studies (GWAS), can effectively map variants correlated with AD, the majority of the heritability and the functional relevance of discovered variants are not explained or known by the identified variants. The limited success of singular approaches underscores the need for holistic and integrated approaches to investigate complex phenotypes using trans-omics data integration strategies. Integrating omics layers (e.g., genome, epigenome, transcriptome, proteome, metabolome, lipidome, exposome, microbiome), which often have complementary and synergistic effects, might provide the opportunity to capture the flow of information underlying AD disease manifestation. Overlapping genes/candidates derived from multiple omics types include , and in AD pathogenesis. Overlapping pathways include macrophage, endothelial cell and fibroblast activation pathways, in addition to well-known Th1/Th2 and NFkB activation pathways. Interestingly, there was more multi-omics overlap at the pathway level than gene level. Further analysis of multi-omics overlap at the tissue level showed that among 30 tissue types from the GTEx database, skin and esophagus were significantly enriched, indicating the biological interconnection between AD and food allergy. The present work explores multi-omics integration and provides new biological insights to better define the biological basis of AD etiology and confirm previously reported AD genes/pathways. In this context, we also discuss opportunities and challenges introduced by "big omics data" and their integration. 10.3389/fimmu.2018.02727
    Evolving Concepts in Atopic Dermatitis. Sidbury Robert,Khorsand Kate Current allergy and asthma reports PURPOSE OF REVIEW:Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management. RECENT FINDINGS:The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD. AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab. 10.1007/s11882-017-0710-5
    Novel systemic drugs in treatment of atopic dermatitis: results from phase II and phase III studies published in 2017/2018. Werfel Thomas Current opinion in allergy and clinical immunology PURPOSE OF REVIEW:The present review will give an update of recently published clinical studies on novel systemic treatment approaches in atopic dermatitis. RECENT FINDINGS:Until 2017 immunosuppressive drugs such as cyclosporine had to be used in atopic dermatitis when the disease could not sufficiently be treated with topical drugs. Several new substances specifically targeting inflammation in atopic dermatitis are currently studied. In 2017, dupilumab was approved in the United States and in Europe for first-line biologic treatment of moderate to severe atopic dermatitis in adults. The antibody blocks a subunit of the interleukin (IL)-4 and IL-13 receptor, thus inhibiting effects of two key cytokines in type 2 polarized inflammation. In addition to the studies on dupilumab recent clinical investigations on the effects on anti-IL-13 (lebrikizumab, tralokinumab), anti-IL-31 receptor (nemolizumab), anti-IL-22 (fezakinumab), and on small molecules targeting the histamine-4-receptor (ZPL389) and the Janus kinase inhibitor baricitinib have been published as full papers in the last 2 years. SUMMARY:A couple of promising novel therapeutical targets have recently been investigated and published in clinical trials on atopic dermatitis. 10.1097/ACI.0000000000000477
    Abrocitinib: a potential treatment for moderate-to-severe atopic dermatitis. Nezamololama Novin,Crowley Erika L,Gooderham Melinda J,Papp Kim Expert opinion on investigational drugs INTRODUCTION:Atopic dermatitis (AD) is a common and debilitating dermatosis that often impacts the physical and psychological quality of life in children and adults. A limited number of treatment options are available for AD, and often these treatments result in an insufficient response or may be contraindicated for some patients. This treatment gap creates an increasing demand for alternative AD therapies. The Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway is known to play a critical role in the dysregulation of immune responses in AD. Inhibition of the JAK enzymes in the JAK-STAT pathway has shown potential for the treatment of this chronic skin condition. AREAS COVERED:We review the evolving efficacy and safety profile of abrocitinib, an oral JAK1 inhibitor, in the treatment of AD based on the data available from phase I, II, and III clinical trials. EXPERT OPINION:Evidence supports clinical efficacy, improved pruritus and an acceptable safety profile, making abrocitinib a viable alternative to conventional AD therapies. Pivotal phase III trials included subjects aged 12 years and above, providing a new mechanism of action for future treatment of adolescent and adult AD. Further investigations are required to have a thorough understanding of abrocitinib in the treatment of AD. 10.1080/13543784.2020.1804854
    Atopic Dermatitis: Pathophysiology. David Boothe W,Tarbox James A,Tarbox Michelle B Advances in experimental medicine and biology The pathophysiology of atopic dermatitis is complex and multifactorial, involving elements of barrier dysfunction, alterations in cell mediated immune responses, IgE mediated hypersensitivity, and environmental factors. Loss of function mutations in filaggrin have been implicated in severe atopic dermatitis due to a potential increase in trans-epidermal water loss, pH alterations, and dehydration. Other genetic changes have also been identified which may alter the skin's barrier function, resulting in an atopic dermatitis phenotype. The imbalance of Th2 to Th1 cytokines observed in atopic dermatitis can create alterations in the cell mediated immune responses and can promote IgE mediated hypersensitivity, both of which appear to play a role in the development of atopic dermatitis. One must additionally take into consideration the role of the environment on the causation of atopic dermatitis and the impact of chemicals such as airborne formaldehyde, harsh detergents, fragrances, and preservatives. Use of harsh alkaline detergents in skin care products may also unfavorably alter the skin's pH causing downstream changes in enzyme activity and triggering inflammation. Environmental pollutants can trigger responses from both the innate and adaptive immune pathways. This chapter will discuss the multifaceted etiology of atopic dermatitis which will help us to elucidate potential therapeutic targets. We will also review existing treatment options and their interaction with the complex inflammatory and molecular triggers of atopic dermatitis. 10.1007/978-3-319-64804-0_3
    Mediators of Chronic Pruritus in Atopic Dermatitis: Getting the Itch Out? Mollanazar Nicholas K,Smith Peter K,Yosipovitch Gil Clinical reviews in allergy & immunology For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options. 10.1007/s12016-015-8488-5
    Dust mite avoidance for the primary prevention of atopic dermatitis: A systematic review and meta-analysis. Bremmer Samuel F,Simpson Eric L Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology BACKGROUND:Dust mite sensitization plays a controversial role in the development of atopic dermatitis. Despite a lack of evidence for its efficacy, dust mite avoidance is commonly recommended for the prevention and treatment of atopic dermatitis. We aimed to evaluate whether dust mite avoidance strategies reduce the risk of developing atopic dermatitis in high-risk infants compared to randomized controls. METHODS:Studies were obtained by searching MEDLINE, PubMed, Scopus, The Cochrane Library, and The Global Resource of Eczema Trials databases. We included randomized, controlled trials of high-risk infants treated with a dust mite avoidance intervention and assessed for atopic dermatitis. Data were extracted independently by two reviewers using predefined criteria. RESULTS:Seven randomized controlled trials met our inclusion criteria (total n = 3040). Studies were largely unblinded but otherwise of reasonable quality. Three trials utilizing a dust mite avoidance approach but not additional interventions were combined in a meta-analysis. Dust mite avoidance provided no benefit in the prevention of atopic dermatitis (relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.78-1.49, I(2) = 73%). CONCLUSIONS:Dust mite avoidance strategies alone or in combination with additional allergen avoidance modalities do not decrease the risk of developing atopic dermatitis and, given the current state of the evidence, should not be recommended for this purpose. The utility of dust mite avoidance for the treatment of atopic dermatitis or for the prevention and treatment of asthma or seasonal rhinoconjunctivitis are outside the scope of this review. 10.1111/pai.12452
    Immunoadsorption for treatment of severe atopic dermatitis. Wegner Joanna,Weinmann-Menke Julia,von Stebut Esther Atherosclerosis. Supplements Atopic dermatitis (AD) is a common disease affecting up to 10-20% of the population with the largest disease burden in childhood. Treatment options include basic emollient treatment, topical as well as systemic immunosuppressants. The pathogenesis is complex and among various triggers, genetic predisposition and immunological alterations contribute to development of disease. Atopy is common in patients with AD and many patients have high levels of Immunoglobulin E (IgE), some of which recognizes exogenous or auto/self-allergens. Treatment options targeting IgE such as specific immunotherapy against e.g. house dust mites or using anti-IgE antibodies (omalizumab) showed variable results that were not convincing. We now review recent data on the application of unspecific and IgE-selective immunoadsorption (IA) in AD. All in all, 53 patients have been treated with non-specific pan Ig IA and 28 patients with IgE-selective IA. Side effects were rarely seen. The efficacy of IgE depletion was generally high (<∼80%) for each IA cycle, but transient and lasted only a few days/weeks. Of note, disease activity appeared to improve in almost all cases and lasted for several weeks. Although the evidence is still weak, these case studies suggest that IgE depletion in AD is effective and helped control the disease. The mechanism of action is not understood yet. Future controlled trials are needed to validate this observation. 10.1016/j.atherosclerosissup.2017.05.043
    Molecular aspects of allergens in atopic dermatitis. Campana Raffaela,Dzoro Sheron,Mittermann Irene,Fedenko Elena,Elisyutina Olga,Khaitov Musa,Karaulov Alexander,Valenta Rudolf Current opinion in allergy and clinical immunology PURPOSE OF REVIEW:Molecular allergology uses pure, mainly recombinant and structurally defined allergen molecules and allergen-derived epitopes to study mechanisms of IgE-associated allergy, to diagnose, and even predict the development of allergic manifestations and to treat and prevent IgE-associated allergies. Atopic dermatitis, a chronic inflammatory skin disease is almost always associated with IgE sensitization to allergens. However, also non-IgE-mediated pathomechanisms seem to be operative in atopic dermatitis and it is often difficult to identify the disease-causing allergens. Here we review recent work showing the usefulness of molecular allergology to study mechanisms of atopic dermatitis, for diagnosis and eventually for treatment and prevention of atopic dermatitis. RECENT FINDINGS:IgE sensitization to airborne, food-derived, microbial allergens, and autoallergens has been found to be associated with atopic dermatitis. Using defined allergen molecules and non-IgE-reactive allergen derivatives, evidence could be provided for the existence of IgE- and non-IgE-mediated mechanisms of inflammation in atopic dermatitis. Furthermore, effects of epicutaneous allergen administration on systemic allergen-specific immune responses have been studied. Multi-allergen tests containing micro-arrayed allergen molecules have been shown to be useful for the identification of culprit allergens in atopic dermatitis and may improve the management of atopic dermatitis by allergen-specific immunotherapy, allergen avoidance, and IgE-targeting therapies in a personalized medicine approach. SUMMARY:Molecular allergology allows for dissection of the pathomechanisms of atopic dermatitis, provides new forms of allergy diagnosis for identification of disease-causing allergens, and opens the door to new forms of management by allergen-specific and T cells-targeting or IgE-targeting interventions in a personalized medicine approach. 10.1097/ACI.0000000000000378
    The Role of Probiotics in the Prevention and Treatment of Atopic Dermatitis in Children: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials. Jiang Wen,Ni Bin,Liu Zhiyu,Liu Xuan,Xie Wanqin,Wu Irene X Y,Li Xingli Paediatric drugs BACKGROUND:Atopic dermatitis (AD) is a chronic inflammatory skin disease common among infants and children. It is associated with a high risk of allergies, asthma, and mental health problems. Attempts have been made to use probiotics in clinical interventions for AD. OBJECTIVE:Our objective was to perform an updated meta-analysis of recently published studies to evaluate the effect of probiotics in the prevention and treatment of AD in children and to further understand the role of probiotics in AD interventions in the clinic. METHOD:We searched the PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases with prespecified selection criteria from inception of each database to 11 January 2020. No language restrictions were applied. RESULTS:A total of 25 studies were included in our meta-analysis. Of these, 14 were prevention studies (with 3049 children enrolled) and 11 were treatment studies (with 816 children enrolled). One treatment study was excluded after the sensitivity analysis. From the 14 prevention studies included, the pooled relative risk ratio of AD in those treated with probiotics versus placebo was 0.70 [95% confidence interval (CI) 0.57-0.84; P = 0.0002]. Subgroup analyses showed that only mixed strains of probiotics had a significant effect on lowering the incidence of AD. Probiotics administered solely to infants did not prevent the development of AD, but effects were significant when probiotics were administered to both pregnant mothers and their infants or solely to pregnant mothers. In studies with treatment durations > 6 months, the incidence of AD decreased significantly; a similar effect was achieved when the treatment duration was < 6 months. Meta-analysis of the ten treatment studies showed a significant decrease in the weighted mean difference (WMD) in Scoring Atopic Dermatitis (SCORAD) index values in the probiotics group compared with the control group (WMD, - 7.23; 95% CI - 10.59 to - 3.88; P < 0.0001). Subgroup analyses showed that both single-strain and mixed-strain probiotics had a significant effect on improving SCORAD values. Studies with participants aged < 1 year (P = 0.07) reported no significant results. In studies with treatment periods > 8 weeks, SCORAD values seemed to decrease more than in studies with treatment periods < 8 weeks. However, the subgroup difference was only statistically significant when the analysis was performed according to participant age in prevention studies. CONCLUSION:Our updated meta-analysis demonstrates that interventions with probiotics potentially lower the incidence of AD and relieve AD symptoms in children, particularly when treating infants and children aged ≥ 1 year with AD. Interventions with mixed-strain probiotics tended to have better preventive and curative effects. Probiotics administered solely to infants appeared to produce negative preventive effects. Different intervention durations might also affect clinical outcomes. However, given the insignificant subgroup differences, except for treatment by participant age, and the moderate heterogeneity among the studies, these conclusions should be interpreted with caution, and more powerful randomized controlled trials using standardized measurements should be conducted to assess the long-term effects of probiotics. 10.1007/s40272-020-00410-6
    Atopic dermatitis phenotypes and the need for personalized medicine. Cabanillas Beatriz,Brehler Ann-Christin,Novak Natalija Current opinion in allergy and clinical immunology PURPOSE OF REVIEW:To describe recent developments in therapies which target the molecular mechanisms in atopic dermatitis. RECENT FINDINGS:Current advances in the understanding of the molecular basis of atopic dermatitis are leading to the stratification of different atopic dermatitis phenotypes. New therapies offer the option to target-specific molecules involved in the pathophysiology of atopic dermatitis. Current new therapies under investigation aim to modulate specific inflammatory pathways associated with distinctive atopic dermatitis phenotypes, which would potentially translate into the development of personalized, targeted-specific treatments of atopic dermatitis. SUMMARY:Despite the unmet need for well tolerated, effective, and personalized treatment of atopic dermatitis, the current standard treatments of atopic dermatitis do not focus on the individual pathogenesis of the disease. The development of targeted, phenotype-specific therapies has the potential to open a new promising era of individualized treatment of atopic dermatitis. 10.1097/ACI.0000000000000376
    Spotlight on dupilumab in the treatment of atopic dermatitis: design, development, and potential place in therapy. D'Erme Angelo Massimiliano,Romanelli Marco,Chiricozzi Andrea Drug design, development and therapy Atopic dermatitis (AD) is among the most common inflammatory skin diseases in children and adults in industrialized countries. Up to one-third of adults (probably a smaller proportion in childhood) suffer from moderate-to-severe AD, whose recommended treatment is usually based on systemic therapies. The currently available therapeutics are limited, and AD management becomes challenging in most cases. Over the last few years, new advances in the understanding of AD pathogenic mechanisms and inflammatory pathways have led to the identification of specific therapeutic targets and new molecules have been tested. Dupilumab is a fully human monoclonal antibody directed against the IL-4 receptor α subunit that is able to block the signaling of both IL-4 and IL-13 and achieve rapid and significant improvements in adults with moderate-to-severe AD. Dupilumab is ready to inaugurate a long and promising biological target treatment option for Th2 cell-mediated atopic immune response that characterizes AD. 10.2147/DDDT.S113192
    Real-world experience of dupilumab treatment for atopic dermatitis in adults: a retrospective analysis of patients' records. Wang Candice,Kraus Christina N,Patel Krupa G,Ganesan Anand K,Grando Sergei A International journal of dermatology BACKGROUND:Clinical trial data for dupilumab, a monoclonal antibody against the interleukin-4 receptor (IL-4Rα), have shown that it is safe and effective for the treatment of moderate to severe atopic dermatitis in patients whose disease is resistant to other therapies. However, little real-world experience with dupilumab use has been reported thus far. The aim of this retrospective study was to assess overall outcomes in adult patients with atopic dermatitis (AD) treated with dupilumab. METHODS:A retrospective review of electronic medical records was conducted for patients treated with dupilumab in the Department of Dermatology at the University of California, Irvine. RESULTS:We analyzed the medical records of 77 AD patients who received dupilumab according to standard dosing and had at least one documented follow-up visit. In 66 patients (86%), dupilumab improved clinical disease severity, with 23 patients (30%) experiencing complete clearance on dupilumab. Dupilumab was generally well-tolerated and caused no serious adverse events. The most common side effects included dry eyes, conjunctivitis, and keratitis. The most common reason for discontinuation of treatment was lack of substantial clinical improvement or progression of disease severity, followed by ophthalmologic side effects. CONCLUSIONS:Overall, dupilumab was well-tolerated and resulted in clinical improvement in our patient population. These results provide additional important information on the safety and utility of dupilumab treatment for moderate to severe atopic dermatitis in the real-world clinical setting. 10.1111/ijd.14573
    Dupilumab after the 2017 approval for the treatment of atopic dermatitis: what's new and what's next? van der Schaft Jorien,Thijs Judith L,de Bruin-Weller Marjolein S,Balak Deepak M W Current opinion in allergy and clinical immunology PURPOSE OF REVIEW:The IL-4/13 antagonist dupilumab was approved in 2017 as the first biologic for atopic dermatitis. Here, we comprehensively review compelling new data regarding dupilumab published following the approval. RECENT FINDINGS:Daily clinical practice reports of dupilumab in atopic dermatitis are favorable and in line with the registration trials. Dupilumab does not appear to negatively affect pharmacokinetics of CYP450-metabolized drugs nor vaccination responses. Type 2 inflammation biomarkers in skin and serum are reduced following dupilumab treatment. Dupilumab increases the risk for conjunctivitis, especially with higher baseline atopic dermatitis severity and a history of conjunctivitis, but the underlying mechanisms are unknown. Favorable effects of dupilumab have been reported in treatment-recalcitrant hand eczema and prurigo nodularis cases; for allergic contact dermatitis and alopecia areata, there are conflicting responses to dupilumab, possible stemming from pathophysiological heterogeneity. SUMMARY:Daily practice data support the continued use of dupilumab for atopic dermatitis. The only safety signal is an increased risk for conjunctivitis; mechanistic studies into dupilumab-associated conjunctivitis should lead to risk mitigation strategies. Prospective, controlled evaluations are needed for dupilumab in hand eczema and prurigo nodularis. A precision medicine-driven drug-development approach is essential to assess dupilumab for diseases with heterogeneous pathophysiologies, such as alopecia areata and allergic contact dermatitis. 10.1097/ACI.0000000000000551
    Atopic Dermatitis: New Developments. Kusari Ayan,Han Allison M,Schairer David,Eichenfield Lawrence F Dermatologic clinics Herein we review recent developments in our understanding and treatment of atopic dermatitis. Key insights from the recent literature are summarized, from findings on the pathogenesis of this multifactorial disease to a new and more nuanced understanding of its natural history. Therapeutic advances and new data on comorbidities are also discussed. 10.1016/j.det.2018.07.003
    Dupilumab for treatment of atopic dermatitis. Seegräber Marlene,Srour Jerome,Walter Alexandra,Knop Macarena,Wollenberg Andreas Expert review of clinical pharmacology INTRODUCTION:Dupilumab is a new treatment option for patients with moderate-to-severe atopic dermatitis. It blocks IL-4/IL13-signaling and thereby inhibits receptor signaling downstream the JAK-STAT-pathway. Three of the main disease mechanisms of atopic dermatitis are affected by blocking this pathway; the decrease of skin barrier function, the class switch to IgE and the TH2-differentiation. Areas Covered: Dupilumab showed promising results in clinical trials of phase I-III. Clinical outcome parameters such as SCORAD, EASI, IGA and BSA improved with dupilumab. A positive effect on patient-reported outcomes like DLQI or pruritus-rating-scales was also demonstrated. The safety profile of dupilumab is superior to conventional immunosuppressive drugs, such as cyclosporine or methotrexate. Injection-site reactions and conjunctivitis were the most relevant side-effects. Skin infections were less frequently observed compared to placebo. Data on the use of dupilumab during pregnancy or in children are not published to date. Expert Commentary: Dupilumab was approved by the FDA in April 2017 for the treatment of adult patients with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. 10.1080/17512433.2018.1449642
    Dupilumab: A review of its use in the treatment of atopic dermatitis. Gooderham Melinda J,Hong H Chih-Ho,Eshtiaghi Panteha,Papp Kim A Journal of the American Academy of Dermatology Atopic dermatitis (AD) is a chronic, pruritic immune-mediated inflammatory dermatosis characterized by a T helper 2 (Th2) immune response phenotype and may be associated with systemic inflammation. Dupilumab is an interleukin 4 (IL-4) receptor α-antagonist that inhibits IL-4 and IL-13 signaling through blockade of the shared IL-4α subunit. Blockade of IL-4/13 is effective in reducing Th2 response. Dupilumab has recently been approved in the United States and Europe for the treatment of adult patients with moderate-to-severe AD. Clinical trials have shown that adults with moderate-to-severe AD who receive weekly or biweekly dupilumab injections have significantly improved clinical and patient-reported outcomes, including Eczema Area Severity Index, SCORing Atopic Dermatitis, Dermatology Life Quality Index, and itch Numeric Rating Scale scores. Concomitant use of topical corticosteroids along with dupilumab results in a greater improvement in signs and symptoms of AD than with use of dupilumab alone. Biomarker analyses show that dupilumab modulates the AD molecular signature and other Th2-associated biomarkers. Common adverse events reported in the clinical trials were nasopharyngitis, upper respiratory tract infection, injection site reactions, skin infections, and conjunctivitis. These were mild-to-moderate in nature, and overall rates of adverse events occurred with similar frequency between the treatment and placebo groups. There were no significant serious safety concerns identified in phase III clinical trials. Dupilumab, as monotherapy or with concomitant use of topical corticosteroids, can significantly improve clinical outcomes and quality of life in patients suffering from moderate-to-severe AD. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use. 10.1016/j.jaad.2017.12.022
    Phytomedicines are Efficient Complementary Therapies for the Treatment of Atopic Dermatitis: A Review of Mechanistic Insight and Recent Updates. Tumpang Mohamad Aidil,Ramli Nor Amlizan,Hussain Zahid Current drug targets BACKGROUND:Phytomedicines have been well-accepted alternative complementary therapies for the treatment of a wide range of acute and chronic skin inflammatory diseases including chronic herpes, prurigo, psoriasis, and atopic dermatitis (AD). A plethora of in vitro and in vivo studies have evidenced the therapeutic viability of phytomedicines, polyherbal formulations, plant-based materials and their decoctions for the treatment of mild-to-severe AD. OBJECTIVE:This review was aimed to summarize and critically discuss the convincing evidence for the therapeutic effectiveness of phytomedicines for the treatment of AD and explore their anti-AD efficacy. RESULTS:The critical analysis of a wide algorithm of herbal medicines revealed that their remarkable anti-AD efficacy is attributed to their potential of reducing erythema intensity, oedema, inflammation, transepidermal water loss (TEWL) and a remarkable suppression of mRNA expression of ADassociated inflammatory biomarkers including histamine, immunoglobulin (Ig)-E, prostaglandins, mast cells infiltration and production of cytokines and chemokines in the serum and skin biopsies. CONCLUSION:In conclusion, herbal medicines hold great promise as complementary and alternative therapies for the treatment of mild-to-moderate AD when used as monotherapy and for the treatment of moderate-to-severe AD when used in conjunction with other pharmacological agents. 10.2174/1389450118666170913162147
    Atopic dermatitis. Langan Sinéad M,Irvine Alan D,Weidinger Stephan Lancet (London, England) Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research. 10.1016/S0140-6736(20)31286-1
    Current insights into the role of human β-defensins in atopic dermatitis. Chieosilapatham P,Ogawa H,Niyonsaba F Clinical and experimental immunology Anti-microbial peptides or host defence peptides are small molecules that display both anti-microbial activities and complex immunomodulatory functions to protect against various diseases. Among these peptides, the human β-defensins (hBDs) are localized primarily in epithelial surfaces, including those of the skin, where they contribute to protective barriers. In atopic dermatitis skin lesions, altered skin barrier and immune dysregulation are believed to be responsible for reduced hBD synthesis. Impaired hBD expression in the skin is reportedly the leading cause of increased susceptibility to bacterial and viral infection in patients with atopic dermatitis. Although hBDs have considerable beneficial effects as anti-microbial agents and immunomodulators and may ameliorate atopic dermatitis clinically, recent evidence has also suggested the negative effects of hBDs in atopic dermatitis development. In the current review, we provide an overview of the regulation of hBDs and their role in the pathogenesis of atopic dermatitis. The efforts to utilize these molecules in clinical applications are also described. 10.1111/cei.13013
    Relative efficacy of systemic treatments for atopic dermatitis. Seger Edward W,Wechter Todd,Strowd Lindsay,Feldman Steven R Journal of the American Academy of Dermatology BACKGROUND:Systemic medications are often required for severe atopic dermatitis (AD) refractory to topical therapies. Biologic medications are a recent advancement in the field and a comparison with standard systemic approaches would be beneficial. OBJECTIVE:To compare efficacies of systemic therapies for the treatment of AD. METHODS:A systematic literature review was performed using Medline, Ovid, and Embase. Randomized controlled trials looking at the efficacy of systemic treatments for AD in adults and children were included. RESULTS:A total of 41 studies met criteria and were included in our final analysis. Consistent improvements in Eczema Area and Severity Index and Scoring Atopic Dermatitis were reported with dupilumab and cyclosporine. Phase 2 clinical trials for lebrikizumab and tralokinumab were effective and would benefit from phase 3 trials. No study reported efficacy of biologic medications in pediatric patients; however, cyclosporine improved clinical severity by the greatest amount in this group. LIMITATIONS:A lack of well controlled comparison studies make direct comparisons between the treatments difficult. CONCLUSION:For treatment of severe AD, the strongest evidence currently exists for dupilumab and cyclosporine at improving clinical disease severity. Further research is required to determine long-term safety and efficacy of biologic medications. 10.1016/j.jaad.2018.09.053
    Epithelial barrier dysfunctions in atopic dermatitis: a skin-gut-lung model linking microbiome alteration and immune dysregulation. Zhu T H,Zhu T R,Tran K A,Sivamani R K,Shi V Y The British journal of dermatology BACKGROUND:Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. OBJECTIVES:This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. METHODS:A literature search was conducted using the PubMed database for relevant articles with the keywords 'atopic dermatitis', 'epithelial barrier', 'skin', 'gut', 'lung', 'microbiome' and 'immune dysregulation'. RESULTS:Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin-mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. CONCLUSIONS:As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long-term outcomes and reduce allergen sensitization in the airway and gut. 10.1111/bjd.16734
    Immune Dysregulation in the Pathogenesis of Atopic Dermatitis. Gavrilova Tatyana Dermatitis : contact, atopic, occupational, drug Atopic dermatitis is a multifactorial disease. Epidermal barrier impairment often plays the initial role in the initiation of the disease. Immune dysregulation of the innate and adaptive immunity plays a central role in the pathogenesis of atopic dermatitis. Alteration of the epidermal microbiome-host interaction serves a catalytic role in propagating this immune response. The understanding of this disease pathogenesis is important in generating treatment options, especially those such as biologic agents that can target a specific immune pathway. 10.1097/DER.0000000000000340
    Oral small molecules for the treatment of atopic dermatitis: a systematic review. Mobasher Pezhman,Heydari Seradj Mehran,Raffi Jodie,Juhasz Margit,Atanaskova Mesinkovska Natasha The Journal of dermatological treatment : Atopic dermatitis (AD) is a chronic, inflammatory skin disease. Conventional treatments include topical emollients, corticosteroids, calcineurin inhibitors, phototherapy, and systemic immunomodulatory agents, however, these medications have limitations in the treatment of moderate to severe AD. Current literature demonstrates that oral small molecules may be an effective modality to treat AD. Using PubMed/MEDLINE, Embase, Cochrane Skin databases and clinicaltrials.gov a search with terms 'atopic dermatitis or atopic eczema' and 'name of the oral small molecule' was conducted resulting in 1197 articles. Inclusion criteria were studies involving human subjects treated with oral small molecule medication for AD and written in English. Randomized clinical trials, open-label prospective trials, and case reports/series were reviewed. Seven articles, with a total of 250 patients, were included for review. Oral small molecules studied include: apremilast, baricitinib, JNJ-39758979, and tofacitinib. Small molecules demonstrate improvement in AD disease scores, patient-reported outcomes, and quality of life. Preliminary results demonstrate that oral small molecules are an effective treatment option in AD with minimal side effects. Additional randomized studies with larger sample sizes are needed to determine the efficacy and long-term side effects of these novel therapies. 10.1080/09546634.2018.1544412
    Clinical practice guidelines for the management of atopic dermatitis 2018. Katoh Norito,Ohya Yukihiro,Ikeda Masanori,Ebihara Tamotsu,Katayama Ichiro,Saeki Hidehisa,Shimojo Naoki,Tanaka Akio,Nakahara Takeshi,Nagao Mizuho,Hide Michihiro,Fujita Yuji,Fujisawa Takao,Futamura Masaki,Masuda Koji,Murota Hiroyuki,Yamamoto-Hanada Kiwako The Journal of dermatology Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. 10.1111/1346-8138.15090
    Towards personalized treatment in atopic dermatitis. van der Schaft Jorien,Thijs Judith L,Garritsen Floor M,Balak D,de Bruin-Weller Marjolein S Expert opinion on biological therapy INTRODUCTION:For many years, oral immunosuppressive drugs such as cyclosporine A, azathioprine, mycophenolic acid, and methotrexate were the only treatment options, in addition to topical treatment, in patients with severe atopic dermatitis (AD). Dupilumab, a monoclonal antibody targeting the IL-4 receptor alpha, is the first antibody-based treatment commercially available for the treatment of AD. In the near future, more antibody-based treatments and small molecules will become available in the treatment of severe AD. AREAS COVERED:This review gives an overview of current and future therapies for severe AD, outlines options to optimize treatment with oral immunosuppressive drugs and gives an insight into the future of personalized treatment in AD. EXPERT OPINION:Due to the heterogeneous character of AD, it is unlikely that all patients will respond equally to these newly tested drugs. We believe that biomarkers will lead to better identification of patients that will benefit from these highly specific, but expensive new treatments. In addition to a role for biomarkers in new treatments, the use of pharmacogenomic biomarkers can improve the efficacy of currently used oral immunosuppressive drugs in AD, which will still be needed for the treatment of moderate to severe AD in the coming years. 10.1080/14712598.2019.1583204
    The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: A retrospective chart review. Raffi Jodie,Suresh Raagini,Botto Nina,Murase Jenny E Journal of the American Academy of Dermatology BACKGROUND:It is unclear whether the type 2 T helper cell-specific immunosuppressive action of dupilumab interferes with patch testing. OBJECTIVES:We sought to evaluate the reliability of patch testing on dupilumab and the contribution of allergic contact dermatitis (ACD) to complex dermatitis in patients with residual dermatitis on dupilumab. METHODS:This is a retrospective chart review of 48 patients with atopic dermatitis (AD) who were treated with dupilumab. We compare the results of patch tests performed before and after the initiation of dupilumab and the prevalence of comorbid ACD in patch-tested individuals. RESULTS:A minority of patch test reactions were "lost" on dupilumab (13/125; 10.4%). Five of 13 lost reactions occurred in individuals with documented immunodeficiency. Thirty-two of 35 patch-tested patients (91.4%) had comorbid ACD; 92.3% of individuals patch tested on dupilumab experienced further clinical improvement with allergen avoidance. LIMITATIONS:This is a nonrandomized study in a small cohort of patients. The clearance of dupilumab was assessed by subjective patient reports. CONCLUSIONS:Dupilumab does not appear to exert a dampening effect on patch test results. AD with comorbid ACD was highly prevalent and allergen avoidance resulted in significant improvement in residual dermatitis that had not resolved without dupilumab therapy. 10.1016/j.jaad.2019.09.028
    Dupilumab in the treatment of moderate-to-severe atopic dermatitis. Kraft Magdalena,Worm Margitta Expert review of clinical immunology INTRODUCTION:Atopic dermatitis is a common inflammatory skin disease with an increasing prevalence. Treatment of patients suffering from mild or moderate disease includes the use of emollients and topical glucocorticoids or topical calcineurin inhibitors. Patients with chronic and severe atopic dermatitis where topical therapy is usually insufficient require the use of systemic immunosuppressive drugs, which is often limited due to toxicity and severe adverse effects. Areas covered: This review summarizes the literature on the mechanism of action, clinical efficacy and safety of dupilumab, a monoclonal antibody that targets the α-subunit of the interleukin-4 receptor (IL-4Rα) leading to the inhibition of both the IL-4 and IL-13 pathways. A literature search was performed on Pubmed and ClinicalTrials.gov using key words 'dupilumab', 'REGN668', 'IL-4'/'IL-13' and 'atopic dermatitis'. Expert commentary: Dupilumab offers an innovative therapeutic approach for moderate-to-severe atopic dermatitis. It is not approved for clinical use in any country yet; however, due to its excellent clinical efficacy and a favorable safety profile, dupilumab may revolutionize the treatment of moderate-to-severe atopic dermatitis in the next upcoming years. 10.1080/1744666X.2017.1292134
    Atopic dermatitis: the skin barrier and beyond. Tsakok T,Woolf R,Smith C H,Weidinger S,Flohr C The British journal of dermatology BACKGROUND:Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors. METHODS:This is a narrative review based on a systematic literature search. CONCLUSIONS:Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high-risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma. 10.1111/bjd.16934
    T-cell inhibitors for atopic dermatitis. Tidwell W James,Fowler Joseph F Journal of the American Academy of Dermatology The management of atopic dermatitis is changing with the development of novel biologic agents to target specific molecules in the inflammatory cascade. Following the ability of dupilumab has proved its ability to act on the interleukin 4 receptor in treating atopic dermatitis. Thymic stromal lymphopoietin monoclonal antibody (AMG157/MEDI9929) and OX40 blocking antibody (GBR 830) were developed by targeting the same pathway as dupilumab further upstream. The clinical data on the efficacy for these drugs are not yet known. There is some early evidence that AMG157/MEDI9929 attenuates most measures of allergen-induced asthmatic responses. However, there are no public data on its ability to treat atopic dermatitis. In a phase 2a study, GBR 830 showed at least a 50% reduction in the Eczema Area and Severity Index scores of 17 of 23 patients, but it was not sufficiently powered for identification of statistical differences between GBR 830 versus placebo. Although there is potential for these 2 drugs to greatly improve the management of severe atopic dermatitis, significant clinical trials have not yet been completed to prove efficacy, and there are not yet any available phase 3 clinical trials, which are needed to truly evaluate their efficacy in affecting T-cells. 10.1016/j.jaad.2017.12.020
    Bathing and Associated Treatments in Atopic Dermatitis. Gittler Julia K,Wang Jason F,Orlow Seth J American journal of clinical dermatology Atopic dermatitis is one of the most common complaints presenting to dermatologists, and patients typically inquire as to appropriate bathing recommendations. Although many dermatologists, allergists, and primary-care practitioners provide explicit bathing instructions, recommendations regarding frequency of bathing, duration of bathing, and timing related to emollient and medication application relative to bathing vary widely. Conflicting and vague guidelines stem from knowledge related to the disparate effects of water on skin, as well as a dearth of studies, especially randomized controlled trials, evaluating the effects of water and bathing on the skin of patients with atopic dermatitis. We critically review the literature related to bathing and associated atopic dermatitis treatments, such as wet wraps, bleach baths, bath additives, and balneotherapy. We aim to provide readers with a comprehensive understanding of the impact of water and related therapies on atopic dermatitis as well as recommendations based upon the published data. 10.1007/s40257-016-0240-2
    Japanese Guideline for Atopic Dermatitis 2014. Katayama Ichiro,Kohno Yoichi,Akiyama Kazuo,Aihara Michiko,Kondo Naomi,Saeki Hidehisa,Shoji Shunsuke,Yamada Hidekazu,Nakamura Koichiro, Allergology international : official journal of the Japanese Society of Allergology Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is a inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level. The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2012 (ADGL2012)" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2013" together with those for other allergic diseases. 10.2332/allergolint.14-RAI-0769
    European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period. Vestergaard C,Wollenberg A,Barbarot S,Christen-Zaech S,Deleuran M,Spuls P,Flohr C,Trzeciak M,von Kobyletzki L,Seneschal J,Paul C,Bieber T,Werfel T,Fölster-Holst R,Darsow U,Gieler U,Svensson Å,Cork M,Stalder J-F,De Raeve L,Kunz B,Simon D,Chernyshov P,Hijnen D,Gelmetti C,Ring J,Taieb A,de Bruin-Weller M,Thyssen J P Journal of the European Academy of Dermatology and Venereology : JEADV Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine. 10.1111/jdv.15709
    Clinical impact in the real life of guidelines recommendations for atopic dermatitis in a tropical population (TECCEMA cohort). Sánchez Jorge,Toro Yuliana,Cardona Ricardo Revista alergia Mexico (Tecamachalco, Puebla, Mexico : 1993) BACKGROUND:Real-life impact of guidelines for the management of atopic dermatitis has been poorly studied. OBJECTIVE:To assess atopic dermatitis clinical control in residents of a tropical area managed according to international consensuses. METHODS:Prospective study with a 24-month follow-up. Clinical response was assessed with SCORAD, DLQI and a subjective scale (SS) on severity perception by the patient. RESULTS:Two-hundred and thirty-three patients were stratified according to SCORAD: 53 had mild severity (22%), 116 moderate (49%) and 64 severe (27%). Baseline SCORAD mean was 33 (15-41), for DLQI, it was 14 (11-20), and for the subjective scale, 85% (67-99). At 6 months, there was significant reduction (p < 0.5): SCORAD 29 (14-41), DLQI 12 (8-16) and subjective scale 62% (45-80). At 2 years, SCORAD was 21 (9-34), DLQI 7 (4-10) and subjective scale 41% (27-56); only 33% achieved complete control (SCORAD < 15%, DLQI < 5, subjective scale < 20%). CONCLUSIONS:Following international guidelines' recommendations reduces eczema severity and improves quality of life, although only 33% achieved complete control after 2 years. 10.29262/ram.v64i3.244
    Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. Sidbury Robert,Davis Dawn M,Cohen David E,Cordoro Kelly M,Berger Timothy G,Bergman James N,Chamlin Sarah L,Cooper Kevin D,Feldman Steven R,Hanifin Jon M,Krol Alfons,Margolis David J,Paller Amy S,Schwarzenberger Kathryn,Silverman Robert A,Simpson Eric L,Tom Wynnis L,Williams Hywel C,Elmets Craig A,Block Julie,Harrod Christopher G,Begolka Wendy Smith,Eichenfield Lawrence F, Journal of the American Academy of Dermatology Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option. 10.1016/j.jaad.2014.03.030
    Emerging small-molecule compounds for treatment of atopic dermatitis: a review. Vávrová Kateřina Expert opinion on therapeutic patents INTRODUCTION:Atopic dermatitis is a chronic, relapsing, pruritic inflammatory skin disease. Both skin barrier defects and abnormal immune reactions contribute to this complex disease. Current therapeutic guidelines recommend the use of moisturizers, good skin care and allergen avoidance as the first-line approach. In patients who do not respond well to these measures, topical corticosteroids, calcineurin inhibitors, and, in severe cases, systemic immunosuppressive agents are mostly used. AREAS COVERED:This review summarizes the patent applications for small-molecule compounds for the treatment of atopic dermatitis from 2009 to date. These substances include compounds targeting the skin barrier (filaggrin production promoters, filaggrin breakdown products and compounds improving stratum corneum lipid barrier including pseudoceramides), anti-inflammatory compounds (PDE4/7 inhibitors, CRTH2 inhibitors, chemokine receptor antagonists, inhibitors of chymase and other) and compounds specifically targeting itch (TRP agonists, opioid ligands, serotonin 7 and histamine 4 antagonists). EXPERT OPINION:Recent advances in understanding the pathogenic mechanisms of atopic dermatitis have created a strong rationale for the design of targeted therapeutics. Most emerging compounds target inflammation and/or pruritus, probably because of the broader therapeutic utility of such compounds. Specific skin barrier-corrective therapies are much fewer but bear strong potential to actually prevent inflammation. 10.1517/13543776.2016.1101451
    Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. Eichenfield Lawrence F,Tom Wynnis L,Chamlin Sarah L,Feldman Steven R,Hanifin Jon M,Simpson Eric L,Berger Timothy G,Bergman James N,Cohen David E,Cooper Kevin D,Cordoro Kelly M,Davis Dawn M,Krol Alfons,Margolis David J,Paller Amy S,Schwarzenberger Kathryn,Silverman Robert A,Williams Hywel C,Elmets Craig A,Block Julie,Harrod Christopher G,Smith Begolka Wendy,Sidbury Robert Journal of the American Academy of Dermatology Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed. 10.1016/j.jaad.2013.10.010
    Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. Eichenfield Lawrence F,Tom Wynnis L,Berger Timothy G,Krol Alfons,Paller Amy S,Schwarzenberger Kathryn,Bergman James N,Chamlin Sarah L,Cohen David E,Cooper Kevin D,Cordoro Kelly M,Davis Dawn M,Feldman Steven R,Hanifin Jon M,Margolis David J,Silverman Robert A,Simpson Eric L,Williams Hywel C,Elmets Craig A,Block Julie,Harrod Christopher G,Smith Begolka Wendy,Sidbury Robert Journal of the American Academy of Dermatology Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence. 10.1016/j.jaad.2014.03.023
    EAACI Biologicals Guidelines-dupilumab for children and adults with moderate-to-severe atopic dermatitis. Agache Ioana,Akdis Cezmi A,Akdis Mubeccel,Brockow Knut,Chivato Tomas,Del Giacco Stefano,Eiwegger Thomas,Eyerich Kilian,Giménez-Arnau Ana,Gutermuth Jan,Guttman-Yassky Emma,Maurer Marcus,Ogg Graham,Ong Peck Y,O'Mahony Liam,Schwarze Jürgen,Warner Amena,Werfel Thomas,Palomares Oscar,Jutel Marek Allergy Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed. 10.1111/all.14690
    Japanese guidelines for atopic dermatitis 2020. Katoh Norito,Ohya Yukihiro,Ikeda Masanori,Ebihara Tamotsu,Katayama Ichiro,Saeki Hidehisa,Shimojo Naoki,Tanaka Akio,Nakahara Takeshi,Nagao Mizuho,Hide Michihiro,Fujita Yuji,Fujisawa Takao,Futamura Masaki,Masuda Koji,Murota Hiroyuki,Yamamoto-Hanada Kiwako, Allergology international : official journal of the Japanese Society of Allergology 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 barrier function, enhanced irritability and scratching-related stimuli deteriorate eczema, leading to vicious cycle of inflammation. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. 10.1016/j.alit.2020.02.006
    Guideline-based medicine grading on the basis of the guidelines of care for ambulatory atopic dermatitis treatment in the United States. Fleischer Alan B Journal of the American Academy of Dermatology PURPOSE:This study was designed to assess the adherence to evidence-based guidelines of care for atopic dermatitis (AD). METHODS:To characterize AD treatment in the United States, ambulatory visits from the 2006-2015 National Ambulatory Medical Care Survey were analyzed. For each medication prescribed, a grade was assigned on the basis of the American Academy of Dermatology treatment guidelines for topical and systemic medications. Considering all visit prescriptions, I calculated a composite grade, analogous to the US academic grading system (scores A-F). RESULTS:I noted prescribing differences across specialty groups. Systemic corticosteroids were more likely to be prescribed by family and general physicians and less likely by pediatricians. Dermatologists were more likely than other specialties to prescribe nonsedating antihistamines, which lack a guideline base supporting their use. Depending upon modeling of care assumptions, all physician specialty visits earned mean guideline-based grades of B or C in their care of AD patients. LIMITATIONS:The clinical, social, and demographic factors influencing prescribing behavior cannot be completely assessed by using extant data. CONCLUSIONS:This preliminary study demonstrates that physicians might benefit from reviewing guidelines of care; there might be an educational gap in the implementation of these guidelines. 10.1016/j.jaad.2018.09.026
    When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. Simpson Eric L,Bruin-Weller Marjolein,Flohr Carsten,Ardern-Jones Michael R,Barbarot Sebastien,Deleuran Mette,Bieber Thomas,Vestergaard Christian,Brown Sara J,Cork Michael J,Drucker Aaron M,Eichenfield Lawrence F,Foelster-Holst Regina,Guttman-Yassky Emma,Nosbaum Audrey,Reynolds Nick J,Silverberg Jonathan I,Schmitt Jochen,Seyger Marieke M B,Spuls Phyllis I,Stalder Jean-Francois,Su John C,Takaoka Roberto,Traidl-Hoffmann Claudia,Thyssen Jacob P,van der Schaft Jorien,Wollenberg Andreas,Irvine Alan D,Paller Amy S Journal of the American Academy of Dermatology BACKGROUND:Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking. OBJECTIVE:To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient. METHODS:A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion. RESULTS:We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy. LIMITATIONS:Our work is a consensus statement, not a systematic review. CONCLUSION:The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies. 10.1016/j.jaad.2017.06.042
    Current guidelines for the evaluation and management of atopic dermatitis: A comparison of the Joint Task Force Practice Parameter and American Academy of Dermatology guidelines. Eichenfield Lawrence F,Ahluwalia Jusleen,Waldman Andrea,Borok Jenna,Udkoff Jeremy,Boguniewicz Mark The Journal of allergy and clinical immunology 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. 10.1016/j.jaci.2017.01.009
    Clinical Management of Atopic Dermatitis in Adults: Mapping of Expert Opinion in 4 Nordic Countries using a Modified Delphi Process. Thyssen Jacob P,Berents Teresa,Bradley Maria,Deleuran Mette,Grimstad Øystein,Korhonen Laura,Langeland Tor,Särnhult Tore,Thomsen Simon Francis,Thune Turid,Wahlgren Carl-Fredrik,Vestergaard Christian,Kobyletzki Laura B,Remitz Anita Acta dermato-venereologica Similarities and differences in the everyday clinical management of moderate-to-severe atopic dermatitis in Nordic countries are unknown. Using a modified Delphi approach, 15 dermatologists from Denmark, Finland, Norway and Sweden completed face-to-face and online questionnaires and participated in summary discussions to map expert opinion on the clinical management of moderate-to-severe atopic dermatitis in these Nordic countries. Through discussions, 6 adult patient profiles, reflecting common disease presentations of atopic dermatitis, were identified. Using these case profiles, diagnostic work-up, treatment goals, patient education and treatment approaches were discussed. Patient education was identified as essential for effective management. A treatment sequence of moderate-to-potent topical glucocorticosteroids and emollients, followed by systemic treatment, was recommended, allowing 3 months to ascertain systemic treatment response before switching, if necessary. Consensus was not reached on systemic treatment choice, reflecting differences in clinical practice and reimbursement between countries. Practical, case-based clinical recommendations were developed for optimal patient care. 10.2340/00015555-3369
    [TRADITIONAL CHINESE MEDICINE IN TREATMENT OF ATOPIC DERMATITIS]. Schachter Orit,Perla David,Greenberger Shoshana,Barzilai Aviv,Baum Sharon Harefuah BACKGROUND:Atopic dermatitis is a common chronic inflammatory skin disease, affecting up to 15-30% of children in industrialized countries. As there is no definitive cure for atopic dermatitis, patients often seek other complementary therapeutic options, such as traditional Chinese medicine (TCM). TCM comprises numerous treatment modalities for the management of atopic dermatitis including acupuncture and herbal medicine. We report a case of a two and a half year old child with atopic dermatitis exacerbation treated successfully with TCM. During the treatment, we observed gradual decreases in symptoms with complete disappearance of dermatological complaints following 4 months of treatment. CONCLUSIONS:There is considerable evidence suggesting a benefit in the use of TCM for the treatment of atopic dermatitis. As the current state of evidence of TCM treatment for atopic dermatitis remains unknown, further studies should be conducted before definite guidelines can be published. DISCUSSION:The use of TCM has become increasingly popular among children with atopic dermatitis, as clinical evidence report efficacy in improving quality of life and symptoms severity, along with reduction of topical corticosteroid use. Yet, this data is inconclusive, as studies are not randomized double blind controlled.
    An update on the topical and oral therapy options for treating pediatric atopic dermatitis. Glines Katelyn R,Stiff Katherine M,Freeze Megan,Cline Abigail,Strowd Lindsay C,Feldman Steven R Expert opinion on pharmacotherapy INTRODUCTION:Atopic dermatitis (AD) is one of the most common childhood skin disorders. Multiple mechanisms contribute to the pathology of AD and treatment approaches are directed at these processes. AREAS COVERED:The purpose of this review is to discuss the chemical treatment options for pediatric atopic dermatitis, including immunomodulators and small molecule inhibitors. A systematic literature search was conducted, and publications were reviewed for applicable treatment guidelines. EXPERT OPINION:Topical therapy is first-line for pediatric atopic dermatitis. Providers should work closely with patients and caregivers to promote the success of topical treatments. In disease refractory to topical treatments, systemic agents may be considered. Clinical trials are ongoing for the use of biologics in the treatment of pediatric AD. When choosing the most appropriate treatment, physicians should consider the drug efficacy, potential adverse effects, patient adherence, and quality of life for both patients and caregivers. Additional studies are required to determine the safest and most effective doses for systemic therapy in childhood AD. 10.1080/14656566.2018.1561868
    A comparison of international management guidelines for atopic dermatitis. LePoidevin Lindsey M,Lee Dylan E,Shi Vivian Y Pediatric dermatology BACKGROUND/OBJECTIVES:Atopic dermatitis (AD) is a chronic condition that is predominantly found in pediatric patients and commonly presents therapeutic challenges. The management of AD encompasses a variety of factors, and the pillars of optimal management revolve around skin barrier repair and antiinflammatory, antimicrobial, and antipruritic treatment. AD management guidelines exist in various geographic regions globally. The purpose of this review was to compare international guidelines to highlight the similarities and variances among populations and skin types. Comparisons were made for recommendations regarding moisturization, bathing, wet wrap therapy, topical corticosteroids, topical calcineurin inhibitors, antihistamines, antipruritics, antibiotics, systemic immunosuppressants, and biologics. METHODS:A literature search of the PubMed, EMBASE, and MEDLINE databases was performed for published guidelines in each geographic region. Inclusion criteria included publications available in English that were established by a dermatological association or group including dermatologists, pertained to the treatment of AD in humans, were the most recent guidelines available that were published between 2007 and 2018, and included comprehensive treatment recommendations. RESULTS:Publications from Europe, North America, Asia, the Asia-Pacific region, Australia, and Africa were reviewed, encompassing 14 guidelines. Notable diversity exists across these guidelines regarding recommendations for moisturization and bathing, as well as topical and systemic therapies for AD. CONCLUSIONS:Due to the heterogeneity of the disease and regional treatment accessibility, complete standardization of AD management guidelines may be difficult. Nevertheless, more consensus on management guidelines is needed, and recommendations should be updated as new treatment modalities become available. 10.1111/pde.13678
    Atopic dermatitis guidelines: Diagnosis, systemic therapy, and adjunctive care. Sidbury Robert,Kodama Samantha Clinics in dermatology Atopic dermatitis is an important and chronic skin condition that has recently been the subject of enormous volumes of basic science, clinical, and epidemiologic research. This field is undergoing rapid expansion, making it vitally important to integrate the emerging data with our current body of knowledge. In 2014, the American Academy of Dermatology published Guidelines of Care for the Management of Atopic Dermatitis, composed of four parts, reflecting the work of 17 experts from North America and the United Kingdom. It uses a patient-oriented system, SORT (Strength of Recommendation Taxonomy), to provide evidence-based guidance in the management of this common, vexing dermatitis. These guidelines join a series of similar efforts published recently across the world, reflecting universal interest in distilling the tremendous volume of basic scientific and clinical data previously generated. With new therapies rapidly emerging, clinicians require a current understanding of the field to be able to incorporate new treatments in their practice. 10.1016/j.clindermatol.2018.05.008
    New science and treatment paradigms for atopic dermatitis. Dinulos James G,Trickett Alyssa,Crudele Caroline Current opinion in pediatrics PURPOSE OF THE REVIEW:The prevalence of atopic dermatitis is increasing in industrialized countries for unclear reasons. One theory centers on reduced exposure to microbes during infancy and childhood. Alterations in the epidermal permeability barrier, place certain patients at risk for the immunological dysfunction seen in atopic dermatitis. This review examines current research pertaining to the epidermal permeability barrier, the cutaneous microbiome, and the immunology of atopic dermatitis. New collaborative research has led to evidence-based management guidelines. RECENT FINDINGS:Increased skin barrier permeability and dysfunction of innate and adaptive immunity cause atopic dermatitis. Genetic and environmental factors leading to decreased filaggrin underlie many cases of atopic dermatitis. Defective epidermal barrier function allows for an increased density of Staphylococcus aureus and a subsequent shift in adaptive immunity to a type 2 immune response. Multiple evaluation and management guidelines have been published based on current available evidence. These guidelines highlight state of the art management of seven main areas: inflammation, infection, irritation, itch, ichthyosis (dry skin), immunological influences, and impeding (comorbid) conditions. SUMMARY:Pediatricians are central to the successful diagnosis and management of atopic dermatitis. Increased basic and clinical research and well published clinical guidelines will lead to improved outcomes for the patients and families affected by this chronic relapsing disorder. 10.1097/MOP.0000000000000560
    Quality assessment of atopic dermatitis clinical practice guidelines in ≤ 18 years. de María Díaz Granados Luz,Quijano María Adelaida,Ramírez Paola Andrea,Aguirre Natalia,Sanclemente Gloria Archives of dermatological research Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects the patients' quality of life greatly often from a very young age. Its worldwide incidence in children and adults varies, but it is usually among the first ten causes of dermatological consultation worldwide. There is a wide variety of treatment options for this condition including topical and systemic regimes. The decision to choose a treatment option in dermatological diseases is greatly influenced by the personal experience of each specialist, which increases variability in the selection of available therapies. Clinical practice guidelines (CPGs) not only offer recommendations supported on the available scientific evidence, but also are intended to assist in making appropriate decisions in clinical scenarios. To standardize the way in which CPGs should be developed, an instrument called AGREE II (Appraisal of Guidelines for Research and Evaluation) is used. In this study, ten clinical practice guidelines in ≤ 18 years were evaluated. Six domains (scope and purpose, stakeholder involvement, rigor of development, clarity and presentation, applicability, and editorial independence) were assessed for each guideline, by three reviewers. Most of the domains obtained high scores except in the applicability domain. It is suggested that future atopic dermatitis CPGs should emphasize in the facilitating factors and barriers that may influence the application of guideline recommendations. 10.1007/s00403-017-1791-7
    What's the story? An analysis of children's books about atopic dermatitis. Tappel Anna C,Cresce Nicole,Zlotoff Barrett Pediatric dermatology BACKGROUND/OBJECTIVES:Atopic dermatitis is an inflammatory skin condition with significant disease burden. Bibliotherapy, the use of storybooks to understand an illness, has been proven effective in several pediatric disorders but has not been studied in dermatologic disease. The purpose of this study was to assess the availability of storybooks about atopic dermatitis and analyze them based on adherence to American Academy of Dermatology guidelines for the treatment of atopic dermatitis, readability, author qualifications, cost, and availability. METHODS:Selection criteria included that the books were primarily about atopic dermatitis, were illustrated, cost less than $25, and were written in English. Storybooks were identified using an Internet search of the Google, Amazon, and Barnes & Noble websites. Flesch-Kincaid Grade Level was used to calculate reading level. RESULTS:Twenty-three storybooks were identified. The mean cost of the storybooks was $8.2 ± 7.0. Authors included mothers, professional authors, and medical professionals. Mean reading grade level was 4.1 ± 1.5. Of American Academy of Dermatology-recommended treatments, most storybooks mentioned moisturizers or bathing. Fewer than half discussed moisturizing after bathing, topical corticosteroids, wet wrap therapy, oral antihistamines, antimicrobials, systemic agents, or phototherapy. None mentioned topical calcineurin inhibitors or bleach baths. CONCLUSION:Storybooks about atopic dermatitis are available. Of those reviewed, none covered all the American Academy of Dermatology treatment guidelines. Studies have shown that bibliotherapy can be useful for education and behavioral modification for pediatric diseases, and future studies are needed to examine whether comprehensive, accurate storybooks about atopic dermatitis improve clinical outcomes or improve the quality of life of individuals with atopic dermatitis and their caregivers. 10.1111/pde.13590
    Contact Dermatitis in Atopic Dermatitis Children-Past, Present, and Future. Borok Jenna,Matiz Catalina,Goldenberg Alina,Jacob Sharon E Clinical reviews in allergy & immunology Allergic contact dermatitis (ACD) used to be considered a rarity in children, but recently has been estimated to effect 4.4 million children in the USA alone, with a notable rise in investigative research in the field of pediatric ACD. Researchers have shown that patch testing is safe and effective in afflicted children and that those with atopic dermatitis (AD) have similar sensitization rates, although they have a higher sensitization to certain allergens, thought to be related to the inflammatory (IL-4) milieu. Patch testing assessment guidelines in children include five key considerations: if a patient's dermatitis worsens, changes distribution, fails to improve with topical therapy, or immediately rebounds after removal of topical treatments; if a patient has a particular distribution of dermatitis; if a working patient has hand eczema that fails to improve with therapy; if the patient has AD that started in adolescence or adulthood with definitely no history of childhood eczema; and importantly, if a patient has severe or widespread atopic dermatitis that will require immunosuppressive systemic medication. 10.1007/s12016-018-8711-2
    Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial. Skjerven Håvard Ove,Rehbinder Eva Maria,Vettukattil Riyas,LeBlanc Marissa,Granum Berit,Haugen Guttorm,Hedlin Gunilla,Landrø Linn,Marsland Benjamin J,Rudi Knut,Sjøborg Kathrine Dønvold,Söderhäll Cilla,Staff Anne Cathrine,Carlsen Kai-Håkon,Asarnoj Anna,Bains Karen Eline Stensby,Carlsen Oda C Lødrup,Endre Kim M Advocaat,Granlund Peder Annæus,Hermansen Johanne Uthus,Gudmundsdóttir Hrefna Katrín,Hilde Katarina,Håland Geir,Kreyberg Ina,Olsen Inge Christoffer,Mägi Caroline-Aleksi Olsson,Nordhagen Live Solveig,Saunders Carina Madelen,Skrindo Ingebjørg,Tedner Sandra G,Værnesbranden Magdalena R,Wiik Johanna,Jonassen Christine Monceyron,Nordlund Björn,Carlsen Karin C Lødrup Lancet (London, England) BACKGROUND:Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. METHODS:This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. FINDINGS:2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI -0·3 to 6·5) for skin intervention and 1·0% (-2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. INTERPRETATION:Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. FUNDING:The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council-the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare-FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust. 10.1016/S0140-6736(19)32983-6
    Clinical Practice Guidelines for the Management of Atopic Dermatitis 2016. Saeki Hidehisa,Nakahara Takeshi,Tanaka Akio,Kabashima Kenji,Sugaya Makoto,Murota Hiroyuki,Ebihara Tamotsu,Kataoka Yoko,Aihara Michiko,Etoh Takafumi,Katoh Norito, The Journal of dermatology Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. Most patients have an atopic predisposition. The definitive diagnosis of AD requires the presence of all three features: (i) pruritus; (ii) typical morphology and distribution of the eczema; and (iii) chronic and chronically relapsing course. The current strategies to treat AD in Japan from the perspective of evidence-based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity-related patient outcomes with respect to several important points requiring decision-making in clinical practice. 10.1111/1346-8138.13392
    Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. Wollenberg A,Barbarot S,Bieber T,Christen-Zaech S,Deleuran M,Fink-Wagner A,Gieler U,Girolomoni G,Lau S,Muraro A,Czarnecka-Operacz M,Schäfer T,Schmid-Grendelmeier P,Simon D,Szalai Z,Szepietowski J C,Taïeb A,Torrelo A,Werfel T,Ring J, Journal of the European Academy of Dermatology and Venereology : JEADV This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline. 10.1111/jdv.14888
    Japanese guidelines for atopic dermatitis 2017. Katayama Ichiro,Aihara Michiko,Ohya Yukihiro,Saeki Hidehisa,Shimojo Naoki,Shoji Shunsuke,Taniguchi Masami,Yamada Hidekazu, Allergology international : official journal of the Japanese Society of Allergology Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is an inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level. The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2015 (ADGL2015)" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2016" together with those for other allergic diseases. 10.1016/j.alit.2016.12.003
    Italian guidelines for therapy of atopic dermatitis-Adapted from consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis). Damiani Giovanni,Calzavara-Pinton Piergiacomo,Stingeni Luca,Hansel Katharina,Cusano Francesco, , , ,Pigatto Paolo D M Dermatologic therapy Atopic dermatitis (AD) therapeutic approach calls for a long-term treatment. Treatment options for AD have recently undergone a revolutionary change by the introduction of the first biologic drug. Availability in daily practice of the last version of international AD guidelines, taking peculiarities of the country into account, can contribute to good clinical practice in Italy. To adapt European Dermatology Forum (EDF) guidelines for AD to the Italian medical-legal context, the EDF guidelines were assessed independently by two independent Italian renowned experts in the field and further integrated with articles published and systematically reviewed before May 2019. The first draft was collegially corrected and updated by the members of the SIDEMAST, ADOI, and SIDAPA. Recommendation levels (A; B; C; D) were graded based on the evidence levels (1-4). The adapted guidelines presented here focus on topical and systemic therapies in AD patients, both children and adults. As opposed to previous Italian guidelines, they include indications about biologics. New relevant evidence available from very recent literature and peculiarities of the Italian medical and legal context have been integrated in the revision process. If compared to general guidelines for AD not adapted to a specific national and cultural context, a revision for specific Italian needs is now available: It comprises the option of implementing the new biologic treatments and is likely to provide an important contribution to the improvement of clinical practice in Italy. Cooperation between patients, dermatologists, allergologists, and pediatricians remains mandatory in AD management. The authors of the present revision recommend an update of the Italian guidelines to be performed at least every second year. 10.1111/dth.13121
    Efficacy and Safety of Crisaborole Ointment, 2%, for the Treatment of Mild-to-Moderate Atopic Dermatitis Across Racial and Ethnic Groups. Callender Valerie D,Alexis Andrew F,Stein Gold Linda F,Lebwohl Mark G,Paller Amy S,Desai Seemal R,Tan Huaming,Ports William C,Zielinski Michael A,Tallman Anna M American journal of clinical dermatology BACKGROUND:Atopic dermatitis is highly prevalent in black/African American, Asian, and Hispanic patients, making assessment of these populations in clinical trials important. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. In two pivotal phase III clinical trials in patients aged ≥ 2 years, crisaborole was superior to vehicle in reducing global disease severity. The most common treatment-related adverse event was application site pain. OBJECTIVE:The objective of this study was to investigate the efficacy and safety of crisaborole according to patient race and ethnicity. METHODS:A pooled post hoc analysis by race and ethnicity of the two pivotal trials and a safety extension trial was performed. Race included white or nonwhite (encompassing Asian/native Hawaiian/other Pacific Islander, black/African American, and other/American Indian/Alaskan native); ethnicity included Hispanic/Latino or not Hispanic/Latino. RESULTS:In white, nonwhite, Hispanic/Latino, and not Hispanic/Latino groups at day 29, more crisaborole- than vehicle-treated patients achieved improvements in global disease severity [Investigator's Static Global Assessment of clear/almost clear with a ≥ 2-grade improvement (white: 33.5% vs. 22.3%, nominal p < 0.001; nonwhite: 30.0% vs. 21.3%, nominal p < 0.05; Hispanic/Latino: 35.4% vs. 18.2%, nominal p < 0.01; not Hispanic/Latino: 31.3% vs. 22.8%, nominal p < 0.01)]. Crisaborole treatment also improved atopic dermatitis signs/symptoms and quality of life. Frequency of crisaborole-related adverse events was 7.1-8.5% in the pivotal trials. CONCLUSION:Across races and ethnicities, crisaborole demonstrated efficacy for the treatment of mild-to-moderate atopic dermatitis, with a low frequency of treatment-related adverse events. 10.1007/s40257-019-00450-w
    The use of methotrexate for treating childhood atopic dermatitis: a multicenter retrospective study. Taieb Yossi,Baum Sharon,Ben Amitai Dan,Barzilai Aviv,Greenberger Shoshana The Journal of dermatological treatment BACKGROUND:Atopic dermatitis is a chronic inflammatory skin disease. Methotrexate is an off-label systemic agent for treating uncontrolled atopic dermatitis. OBJECTIVE:This study assessed the safety and efficacy of methotrexate in pediatric patients with atopic dermatitis. METHODS:This multicenter, retrospective study assessed pediatric patients with atopic dermatitis who were treated with methotrexate. RESULTS:Medical records of 26 pediatric patients with atopic dermatitis were reviewed. All the patients had Investigator Global Assessment (IGA) scores of 3-4 and had received systemic therapy before receiving methotrexate. In all, 53.85% patients showed clinical improvement at 3 and 6 months after methotrexate initiation. The IGA scores of the patients decreased significantly at 3 months after methotrexate initiation compared with those at baseline; moreover, the IGA scores of the patients at 6 months after methotrexate initiation were lower than those at 3 months after methotrexate initiation. In all, 54% study patients are still undergoing methotrexate treatment. Median satisfaction rate with methotrexate was 7.5/10. However, 10.35% patients developed adverse events, of which only one patient discontinued the treatment. CONCLUSIONS:Our results indicate that methotrexate is a tolerable and effective agent for treating refractory childhood atopic dermatitis. 10.1080/09546634.2018.1508816
    Current treatments for atopic dermatitis in Japan. Miyano Kyohei,Tsunemi Yuichiro The Journal of dermatology The goal of a treatment regimen for atopic dermatitis is to reach and maintain a state where the patient exhibits mild symptoms or an absence of symptoms, and the patient should not experience disturbance during daily activities. The basis of a treatment regimen for atopic dermatitis is topical therapy, and currently there exist topical corticosteroids, tacrolimus and delgocitinib. Using these, proactive therapy is performed as maintenance therapy after remission induction therapy. However, in cases of moderate to severe atopic dermatitis, topical drugs alone cannot induce remission and systemic therapies such as cyclosporin, ultraviolet therapy, and dupilumab should be used in combination. In particular, dupilumab has many advantages such as high efficacy, relatively few adverse reactions, and ease of use in elderly patients with severe atopic dermatitis. In this review, we present a treatment algorithm for atopic dermatitis that emphasizes the importance of maintaining remission after induction of remission, and summarizes the characteristics of current medication therapy for atopic dermatitis in Japan. 10.1111/1346-8138.15730
    Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus. Kabashima Kenji,Matsumura Takayo,Komazaki Hiroshi,Kawashima Makoto, The New England journal of medicine BACKGROUND:Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis. METHODS:In a 16-week, double-blind, phase 3 trial, we randomly assigned Japanese patients with atopic dermatitis and moderate-to-severe pruritus and an inadequate response to topical agents in a 2:1 ratio to receive subcutaneous nemolizumab (60 mg) or placebo every 4 weeks until week 16, with concomitant topical agents. The primary end point was the mean percent change in the visual-analogue scale (VAS) score for pruritus (range, 0 to 100, with higher scores indicating worse pruritus) from baseline to week 16. Secondary end points included the time course of change in the VAS score for pruritus up to week 4, the change in the Eczema Area and Severity Index (EASI) score (range, 0 to 72, with higher scores indicating greater severity), a score of 4 or less on the Dermatology Life Quality Index (DLQI; range, 0 to 30, with higher scores indicating a greater effect on daily life), a score of 7 or less on the Insomnia Severity Index (ISI; range, 0 to 28, with higher scores indicating greater severity), and safety. RESULTS:A total of 143 patients were randomly assigned to receive nemolizumab and 72 to receive placebo. The median VAS score for pruritus at baseline was 75. At week 16, the mean percent change in the VAS score was -42.8% in the nemolizumab group and -21.4% in the placebo group (difference, -21.5 percentage points; 95% confidence interval, -30.2 to -12.7; P<0.001). The mean percent change in the EASI score was -45.9% with nemolizumab and -33.2% with placebo. The percentage of patients with a DLQI score of 4 or less was 40% in the nemolizumab group and 22% in the placebo group; the percentage of patients with an ISI score of 7 or less was 55% and 21%, respectively. The incidence of injection-related reactions was 8% with nemolizumab and 3% with placebo. CONCLUSIONS:In this 16-week trial, the use of subcutaneous nemolizumab in addition to topical agents for atopic dermatitis resulted in a greater reduction in pruritus than placebo plus topical agents. The incidence of injection-site reactions was greater with nemolizumab than with placebo. Longer and larger trials are necessary to determine whether nemolizumab has a durable effect and is safe for atopic dermatitis. (Funded by Maruho; JapicCTI number, 173740.). 10.1056/NEJMoa1917006
    Clinically Meaningful Responses to Dupilumab in Adolescents with Uncontrolled Moderate-to-Severe Atopic Dermatitis: Post-hoc Analyses from a Randomized Clinical Trial. Paller Amy S,Bansal Ashish,Simpson Eric L,Boguniewicz Mark,Blauvelt Andrew,Siegfried Elaine C,Guttman-Yassky Emma,Hultsch Thomas,Chen Zhen,Mina-Osorio Paola,Lu Yufang,Rossi Ana B,He Xinyi,Kamal Mohamed,Graham Neil M H,Pirozzi Gianluca,Ruddy Marcella,Eckert Laurent,Gadkari Abhijit American journal of clinical dermatology BACKGROUND:Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator's Global Assessment 0/1 at week 16. OBJECTIVE:The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. METHODS:R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator's Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children's Dermatology Life Quality Index from baseline. RESULTS:Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5-69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9-53.3]; both p < 0.0001). Results were similar in adolescents with Investigator's Global Assessment > 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5-66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7-48.1]; both p < 0.0001). CONCLUSIONS:Dupilumab provided clinically meaningful improvements in signs, symptoms, and quality of life in adolescents with moderate-to-severe atopic dermatitis among patients with Investigator's Global Assessment > 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. TRIAL REGISTRATION:ClinicalTrials.gov; NCT03054428. Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4  212916 kb). 10.1007/s40257-019-00478-y
    Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis. Ivert Lina U,Wahlgren Carl-Fredrik,Ivert Lena,Lundqvist Maria,Bradley Maria Acta dermato-venereologica Dupilumab, the first biologic approved for treatment of atopic dermatitis, has demonstrated significant clinical effect and quality of life-enhancing capacity in clinical trials. In these, dupilumab-associated conjunctivitis where reported in a minority of patients. The present case series describe 10 patients treated with dupilumab where eye complications were very common. We have described patient characteristics, including FLG mutations, atopic history and clinical effect of dupilumab. Nine of 10 developed eye-complications, most commonly conjunctivitis (in 7/10). Other adverse events were herpes simplex virus uveitis and varicella-zoster virus meningitis. Although our case series is small, we conclude that dupilumab is an effective treatment option in severe atopic dermatitis, but that the risk of adverse events from the eyes and recurrence of herpes virus infections should be kept in mind. Close collaboration with an ophthalmologist is recommended, especially among patients with severe, long-lasting atopic dermatitis and/or previous eye disease. 10.2340/00015555-3121
    A lamellar body mimetic system for the treatment of oxazolone-induced atopic dermatitis in hairless mice. Moner Verónica,Fernández Estibalitz,Calpena Ana Cristina,Garcia-Herrera Adriana,Cócera Mercedes,López Olga Journal of dermatological science BACKGROUND:Atopic dermatitis is a common skin disease characterized by a Th2 cell-dominant inflammatory infiltrate, elevated serum IgE levels and impaired epidermal barrier function. It is associated to abnormal epidermal lamellar body secretion, producing alteration in lipid composition and extracellular lamellar membrane organization. OBJECTIVES:The oxazolone-induced atopic dermatitis in hairless mice was used to evaluate in vivo the effect of the application of a lipid system that mimics the morphology, structure and composition of epidermal lamellar bodies. METHODS:The skin barrier function was evaluated measuring TEWL and skin hydration in vivo. Inflammation was assessed by analysis of serum IgE levels and histological analysis. The microstructure of the intercellular lipid region was also evaluated before and after treatment. RESULTS:The skin condition was improved after 10 days of treatment indicated by decreased TEWL, decreased serum IgE levels, reduced epidermal thickness and reduced lymphocyte-dominated infiltrate. However, the treatment did no improve skin hydration. CONCLUSIONS:The treatment with this lipid system seems to improve the skin condition by reinforcing the barrier function and reducing the skin inflammation. Therefore, the present study provides evidence that this lipid system combining appropriate lipid composition and morphology could be of interest for the development of future treatments for atopic dermatitis. 10.1016/j.jdermsci.2018.01.010
    Monoclonal antibodies for the treatment of atopic dermatitis. Renert-Yuval Yael,Guttman-Yassky Emma Current opinion in allergy and clinical immunology PURPOSE OF REVIEW:To evaluate the treatment revolution atopic dermatitis, the most common inflammatory skin disease, has been going through in recent years, thanks to breakthroughs in disease understanding, delineating the immune fingerprint of atopic dermatitis. RECENT FINDINGS:The treatment for moderate-to-severe atopic dermatitis patients has been largely unchanged for decades and relied on broad-acting immunosuppressants. A huge unmet need existed for effective, well tolerated and narrow-targeted therapeutics. Multiple therapies, targeting various aspects of the complex immune activation of atopic dermatitis, are now assessed in clinical trials, and hold promise for a new era in the treatment of atopic dermatitis, comparable with the treatment shift seen for psoriasis in the last decade. The first effective monoclonal antibody licensed for the treatment of atopic dermatitis, dupilumab, not only offers a much-needed systemic agent for moderate-to-severe patients but also provides strong evidence for the potential role of other monoclonal antibodies in disease management. SUMMARY:In this rapidly changing field, new atopic dermatitis-targeted monoclonal antibodies will be reviewed in light of the recently discovered pathomechanisms of the disease. 10.1097/ACI.0000000000000455
    Topical ozone therapy restores microbiome diversity in atopic dermatitis. Zeng Jinrong,Dou Jianhua,Gao Lihua,Xiang Yaping,Huang Jinhua,Ding Shu,Chen Jing,Zeng Qinghai,Luo Zhen,Tan Wenbin,Lu Jianyun International immunopharmacology BACKGROUND:Staphylococcus aureus (S. aureus) accounts for 90% of the microbiome in atopic dermatitis (AD) lesions and plays a role in disease flare-ups and worsens disease outcome. Ozone treatment can improve AD conditions by its bactericidal effect on S. aureus. OBJECTIVE:To study the effects of topical ozone therapy on microbiome diversity in AD lesions and explore potential probiotic pathogens correlated with AD progression. METHODS:Patients with moderate to severe bilateral skin lesions in AD were recruited. Randomized split sides were performed. One side was treated with ozone hydrotherapy followed by ozonated oil; while the contralateral side with tap water and basal oil. Patients' SCORAD scores and modified EASI were recorded before and after treatments. The microbiological compositions in targeting sites were determined using 16S rDNA sequencing. RESULTS:After three-day ozone therapy, patients showed a significant decrease in SCORAD scores and inflammatory cell infiltration in AD lesions. The micro-ecological diversity was higher in the non-lesional as compared with lesional areas (p < 0.05), which was also negatively correlated with the severity of AD (r = -0.499, p < 0.05). The proportion of S. aureus in AD lesions was positively correlated with the severity of AD (r = 0.564, p = 0.010), which was decreased after ozone treatment (p = 0.07). Ozone therapy showed an increase in microbiological diversity with a significant increase in the proportion of Acinetobacter (p < 0.05). CONCLUSION:Topical ozone therapy is highly effective for treatment for AD. It can change the proportional ratio of Staphylococcus and Acinetobacter, thereby restoring the microbiological diversity in AD lesions. 10.1016/j.intimp.2020.106191
    Nemolizumab in moderate to severe atopic dermatitis: An exploratory analysis of work productivity and activity impairment in a randomized phase II study. Mihara Ryosuke,Kabashima Kenji,Furue Masutaka,Nakano Miwa,Ruzicka Thomas The Journal of dermatology Atopic dermatitis negatively impacts work productivity. This study investigated the impact of nemolizumab on work productivity and activity impairment in adults with moderate to severe atopic dermatitis inadequately controlled by topical treatments in a two-part, phase II, randomized control trial. The Work Productivity and Activity Impairment - Atopic Dermatitis questionnaire was an exploratory end-point. Part A was a 12-week, placebo-controlled study in which patients received s.c. nemolizumab 0.1, 0.5 or 2.0 mg/kg every 4 weeks or 2.0 mg/kg every 8 weeks. Part B was a 52-week extension in which all patients received active treatment. A total of 138 patients had Work Productivity and Activity Impairment - Atopic Dermatitis data; 104 were employed at baseline. At week 12, patients receiving nemolizumab every 4 weeks showed greater mean (standard error) Work Productivity and Activity Impairment - Atopic Dermatitis improvement (score reduction) from baseline versus placebo: Percent Work Time Missed (0.1, 0.5 or 2.0 mg/kg vs placebo): -4.0% (3.9%), -1.7% (4.2%) and -1.6% (4.2%) versus 4.9% (4.5%); Percent Impairment While Working, -15.8% (6.0%), -24.1% (6.5%) and -34.3% (6.4%) versus -16.5% (7.1%); Percent Overall Work Impairment, -16.3% (6.0%), -23.1% (6.5%) and -34.5% (6.3%) versus -16.6% (7.1%); and Percent Activity Impairment, -13.4% (5.3%), -23.5% (5.3%) and -41.9% (5.5%) versus -10.9% (5.7%). Improvements were sustained through week 64. Nemolizumab-treated patients with moderate to severe atopic dermatitis reported improvements in Work Productivity and Activity Impairment through week 64. 10.1111/1346-8138.14934
    Advances in phototherapy for psoriasis and atopic dermatitis. Kemény Lajos,Varga Emese,Novak Zoltan Expert review of clinical immunology : Phototherapy has long been used for the treatment of inflammatory skin diseases, such as psoriasis and atopic dermatitis. The most frequent treatment approach utilizes ultraviolet (UV) light, however, recently, different lasers and low-level light therapies (LLLT) emitting wavelengths in the spectrum of the visible light have also been tried for the treatment of inflammatory skin diseases with variable success.: This review provides an update on the different forms of phototherapy used for the treatment of psoriasis and atopic dermatitis. The proposed mechanism of action of the different phototherapeutical approaches are covered, including the immunosuppressive effect of UV light, the anti-inflammatory effect of vascular lasers and the LLLT induced photobiomodulation. The clinical efficacy of the different treatment options is also discussed.: Based on the efficacy and safety, NB-UVB represents the gold standard for treating psoriasis and atopic dermatitis. The UVB excimer laser and excimer lamp might be the best option for clearing localized therapy-resistant lesions. Home UV phototherapy systems might promote treatment adherence and better compliance of the patients. Vascular lasers, IPLs and LLLT, however, can not currently be recommended for the treatment of inflammatory skin diseases because of the lack of well-controlled studies. 10.1080/1744666X.2020.1672537
    Clinical Efficacy of Oligofructans from Ophiopogon japonicus in Reducing Atopic Dermatitis Flare-ups in Caucasian Patients. Mainzer Carine,Le Guillou Maud,Vyumvuhore Raoul,Chadoutaud Bernard,Bordes Sylvie,Closs Brigitte Acta dermato-venereologica Atopic dermatitis is a chronic relapsing inflammatory skin disease affecting 15-20% children and 2-10% adults worldwide. Topical treatments include corticosteroids and calcineurin inhibitors, despite frequently observed adverse events such as skin atrophy, itching and burning sensations. Good alternatives that can prolong disease relief in between flare-ups are therefore needed. We conducted a randomized, single-blind, placebo-controlled, multicenter clinical trial in a Caucasian cohort of 90 children and 144 adults with mild-to-moderate atopic dermatitis that applied tested products twice daily for 60 days. A natural active from Ophiopogon japonicus, that improves atopic dermatitis symptoms in vivo, was successful in reducing the SCORing of Atopic Dermatitis (SCORAD), including erythema, pruritus and body surface area in both cohorts. The active also improved patient's quality of life and significantly reduced the number of patients relapsing compared to placebo. We conclude that this treatment could be an effective solution to help control the disease in between flare-ups. 10.2340/00015555-3224
    Evaluation of chamomile oil and nanoemulgels as a promising treatment option for atopic dermatitis induced in rats. El-Salamouni Noha S,Ali Mai M,Abdelhady Sherien A,Kandil Lamia S,Elbatouti Gihan A,Farid Ragwa M Expert opinion on drug delivery : Atopic dermatitis is a chronic inflammatory skin disease that remarkably affects the quality-of-life of patients. Chamomile oil is used to treat skin inflammations. We evaluated the efficacy of chamomile oil and nanoemulgel formulations as a natural alternative therapeutic option for atopic dermatitis.: Formulations were developed comprising chamomile oil: olive oil (1:1), Tween 20/80 or Gelucire 44/14 as surfactant-cosurfactant mixtures, propylene glycol (10%w/w), water and hydroxypropyl methylcellulose (3%w/w). In-vitro physicochemical characterization, stability testing and in-vivo assessment of inflammatory biomarkers and histopathological examination of skin lesions were conducted in rats induced with atopic dermatitis.: Nanoemulgels G and X which displayed the smallest particle size of 137.5 ± 2.04 and 207.1 ± 5.44 nm, good homogeneity and high zeta-potential values of -26.4 and -32.7 mV were selected as the optimized emulgel. Nanoemulgels were nonirritating of pH value 5.56, readily spreadable, and were physically stable following 10 heating-cooling cycles. Treatment with nanoemulgels showed a two-fold decrease in duration of skin healing and no spongiosis compared to chamomile oil. Levels of biomarkers were reduced after topical application of both nanoemulgels and chamomile oil.: Nanoemulgels are a potential cost effective, safe topical carrier system for chamomile in treating atopic dermatitis. 10.1080/17425247.2020.1699054
    Artesunate attenuates 2, 4-dinitrochlorobenzene-induced atopic dermatitis by down-regulating Th17 cell responses in BALB/c mice. Bai Xin-Yu,Liu Ping,Chai Yee-Wen,Wang Yan,Ren Shuang-Hua,Li Ying-Ying,Zhou Hong European journal of pharmacology Steroidal agent is a standard clinical treatment of atopic dermatitis; however, have serious side effects. Artesunate is reported to exhibit anti-inflammatory properties although its effect on atopic eczema remains unknown. We investigated the therapeutic effects and possible mechanism of systemic artesunate on DNCB-induced atopic dermatitis in a BALB/c mouse model. To ascertain artesunate (5 and 10 mg/kg) efficacy, skin dermatitis severity and ear, spleen, and lymph node weight were evaluated. Skin tissue mRNA and protein expression and serum cytokine levels were examined. Artesunate significantly improved atopic dermatitis symptoms, decreasing the dermatitis score, ear weight difference, spleen weight, and lymph node weight compared with those following DNCB treatment. Artesunate reduced ear and skin epidermal thickness and mast cell infiltration, as determined using hematoxylin-eosin and toluidine blue staining, respectively. The basal level of IgE (287.67 ± 70.41 ng/ml) and TNF-α (19.94 ± 3.98 pg/ml) were Significantly elevated by DNCB (IgE: 1273.23 ± 176.53 ng/ml; TNF-α: 57.53 ± 3.87 pg/ml), while markedly been suppressed in the treatment group (AS-L: IgE: 1100.25 ± 135.32 ng/ml; TNF-α: 38.47 ± 3.26 pg/ml; AS-H: IgE: 459.46 ± 74.75 ng/ml; TNF-α: 24.38 ± 3.85 pg/ml). Among Th17 cell-related factors, DNCB treatment increased mRNA expression of IL-6, IL-17, IL-23, STAT3, and ROR-γt, but reduced TGF-β and SOCS 3; While artesunate reverse these changes. Compared with the model group, artesunate promoted SOCS3 protein and significantly inhibited ROR-γt protein and STAT3 phosphorylation. Thus, artesunate attenuates DNCB-induced atopic dermatitis by inhibiting the release of inflammatory cytokines and downregulating Th17 cell responses in atopic dermatitis mice. 10.1016/j.ejphar.2020.173020
    3,3'-Diindolylmethane alleviates acute atopic dermatitis by regulating T cell differentiation in a mouse model. Wu Xianxian,Liu Jinxuan,Chen Chaoqin,Huang Zhen,Zang Yuhui,Chen Jiangning,Dong Lei,Zhang Junfeng,Ding Zhi Molecular immunology Atopic dermatitis is a severe, chronic relapsing inflammatory disease of the skin with family clustering. It is characterized into acute phase, which is dominated by T helper 2-type immune responses, and chronic phase, which is dominated by T helper 1-type immune responses. Studies have shown that 3,3'-diindolylmethane not only has antitumor effects but also can relieve symptoms of inflammatory diseases by inhibiting the nuclear factor-κB signaling pathway and regulating T cell differentiation. To study the effect of 3,3'-diindolylmethane on atopic dermatitis and the underlying mechanism, a mouse model of acute atopic dermatitis was established using 2,4-dinitrofluorobenzene. After intraperitoneal injection of 3,3'-diindolylmethane, skin erythema and edema in mice were significantly alleviated. Furthermore, 3,3'-diindolylmethane reduced immune activation, probably by inhibiting the secretion of thymic stromal lymphopoietin by keratinocytes. 3,3'-Diindolylmethane also promoted the differentiation of regulatory T cells and inhibited the activation of T helper 2 and T helper 17 cells to reduce atopic dermatitis-related immune responses. However, it showed no significant effect on the differentiation of T helper 1 cells. These results indicate that 3,3'-diindolylmethane has a significant inhibitory effect on T helper 2 cells in the acute phase of atopic dermatitis. Our findings may provide not only more insights into the pathological mechanism of AD, but also a new candidate medicine for it. 10.1016/j.molimm.2020.11.013
    Pseudoephedrine alleviates atopic dermatitis-like inflammatory responses in vivo and in vitro. Chen Xiaolei,Lin Jiacheng,Liang Qingsong,Chen Xiaoyin,Wu Zhongping Life sciences AIMS:Atopic dermatitis is a chronic inflammatory disease characterized by eczematous lesions and has become a serious health problem worldwide. Pseudoephedrine (PSE) is a nasal decongestant to treat the common cold. PSE has been reported that is beneficial to allergic diseases. However, whether PSE has the potential in atopic dermatitis remains to be elucidated. MAIN METHODS:Male BALB/c mice were challenged with 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like lesion and orally administrated with PSE for two weeks. The skin hydration and the scratching behavior were detected. The skin lesions and histopathological changes were evaluated and inflammatory factors levels were detected. Human Keratinocytes (HaCaT cells) were stimulated by TNF-α/IFN-γ after PSE-pretreatment. The transcriptions of inflammatory factors were detected. KEY FINDINGS:PSE decreased skin lesion area and skin thickness in atopic dermatitis mice. PSE improved skin hydration and scratching. Histologically, PSE reduced mast cell and CD4+ cell infiltration. PSE suppressed serum TNF-α and IgE levels, reducing cytokines (IL-1β, IL-4, IL-6, IL-13, IL-33, TSLP, and IL-23) and neutrophil migration factors (CCL2 and MMP-9) in skin tissues. In addition, PSE inhibited TNF-α/IFN-γ-induced release of inflammatory factors (TNF-α, IL-1β, and IL-23) in HaCaT cells. Furthermore, PSE suppressed the activation of MAPKs and NF-κB signaling pathways in vivo and in vitro. SIGNIFICANCE:These results demonstrate that PSE could inhibit inflammatory responses in atopic dermatitis models. PSE may serve as a viable alternatives drug for the treatment of atopic dermatitis. 10.1016/j.lfs.2020.118139
    Atopic dermatitis endotypes and implications for targeted therapeutics. Czarnowicki Tali,He Helen,Krueger James G,Guttman-Yassky Emma The Journal of allergy and clinical immunology Recent research advancements indicate that atopic dermatitis (AD) is a complex disease characterized by different subtypes/phenotypes based on age, disease chronicity, ethnicity, filaggrin and IgE status, and underlying molecular mechanisms/endotypes. This heterogeneity advocates against the traditional "one-size-fits-all" therapeutic approaches still used to manage AD. Precision medicine approaches, striving for targeted, tailored, endotype-driven disease prevention and treatment, rely on detailed definitions of the disease's variability across different phenotypes. Studies have shown that AD harbors different endotypes across different age groups and ethnicities and according to IgE levels and filaggrin mutation status. These include European American versus Asian patients, children versus adults, intrinsic versus extrinsic (IgE status) disease, and patients with and without filaggrin mutations. Therapies targeting different cytokine axes and other mechanisms involved in disease pathogenesis, which are currently being tested for patients with AD across the disease spectrum, will expand our ability to dissect the relative contribution of each of these pathways to disease perpetuation. 10.1016/j.jaci.2018.10.032
    Monoclonal Antibodies for Atopic Dermatitis: Progress and Potential. Vakharia Paras P,Silverberg Jonathan I BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy Atopic dermatitis (AD) is a complex and heterogeneous inflammatory skin disorder with a profound symptom and lesional burden. Moderate-to-severe AD is particularly challenging to manage, as topical treatments are often inadequate and the systemic immunosuppressants are limited by concerns of toxicity and tolerability. Recent AD research has elucidated the mechanisms and immunologic factors involved in AD pathogenesis. These breakthroughs have led to the development of multiple therapeutic monoclonal antibodies that are directed against specific immunologic targets. This review provides an overview on the pathogenesis of AD as well as the rationale for the targets of various monoclonal antibodies. Additionally, this review explores the efficacy and safety of use for various monoclonal antibodies in the management of AD, as well as the potential role of these agents in the treatment of AD. 10.1007/s40259-017-0241-6