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The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients., (© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Pruritus is a hallmark of atopic dermatitis (AD), which affects disease severity and patient quality of life. In AD uncontrolled with first-line topical therapies or in moderate to severe AD, systemic therapies are used; however, there is a paucity of head-to-head trials comparing the effectiveness of these therapies. The aim of this study was to compare the effectiveness of systemic therapies in relieving pruritus in moderate to severe AD in adults, using a meta-analysis. The PubMed, EMBASE, Medline and CINAHL databases were searched from inception up to 31 May 2020 for randomized, placebo-controlled trials investigating the effectiveness of systemic therapies on pruritus with moderate to severe AD in patients aged ≥ 16 years. In total, 26 studies (n = 5190 participants) were identified. Compared with placebo, there was a large and statistically significant (P < 0.001 for all) reduction in pruritus [standard mean difference (SMD); 95% CI] with dupilumab every 2 weeks (-0.88; -1.13 to -0.63), dupilumab every 2 weeks plus topical corticosteroids (-0.77; -0.91 to -0.62), dupilumab once weekly (-0.99; -1.29 to -0.68), dupilumab once weekly plus topical corticosteroids (-0.70; -0.81 to -0.59). There was also a large and statistically significant reduction with ciclosporin (-1.30; -2.34 to -0.26; P = 0.01) and a large, although not statistically significant reduction with azathioprine (-0.85; -2.07 to 0.35). There was a small reduction with both mepolizumab (-0.27; -0.89 to 0.35) and interferon-γ (-0.31; -0.75 to 0.12). Of the investigational drugs, nemolizumab 2.0 mg/kg was the most effective (-8.13; -9.31 to -6.94). The majority of systemic therapies were superior to placebo in reducing pruritus. In particular, the dupilumab studies consistently showed large improvements in pruritus, while nemolizumab showed the strongest antipruritic effects. However, future head-to-head trials are required for conclusive evidence., (© 2021 British Association of Dermatologists.)

Purpose of Review: To describe new and emerging therapies for pediatric atopic dermatitis (AD)., Recent Findings: Recent investigations have highlighted the importance of type 2 immunity and interrelationships among the skin immune system, epidermal barrier, and microbiome in the pathogenesis of AD, including in infants and children. These discoveries have translated into more targeted therapy. Crisaborole ointment, a topical phosphodiesterase 4 (PDE4) inhibitor, and dupilumab, a subcutaneously injected interleukin (IL)-4 receptor inhibitor, are now Food and Drug Administration-approved. Topical agents under investigation for use in the pediatric population include Janus kinase (JAK) inhibitors, PDE4 inhibitors, an aryl hydrocarbon receptor agonist, an antimicrobial peptide, and commensal skin bacteria. Emerging systemic agents for pediatric AD include biologics targeting IL-13, the IL-31 receptor, and the IL-5 receptor, as well as oral JAK inhibitors., Summary: Increased understanding of AD pathogenesis has resulted in the development of new, more targeted therapies that show promising safety and efficacy results in Phase 2 and 3 clinical trials, although long-term safety remains to be evaluated. AD is a heterogeneous disease and having choices of therapies with different mechanisms of action will allow a broader group of children and adolescents with moderate-to-severe disease to achieve disease control., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: To provide a cutting-edge overview of recent developments in topical and systemic therapeutic approaches for the treatment of atopic dermatitis (AD)., Recent Findings: Growing knowledge about key pathways in AD and stratification of patient's subgroups have set the basis for a new era of targeted topical and systemic therapy in AD.Different aspects have to be considered in the decision process for topical versus systemic therapy. Further on, co-factors from the patient's side as well as the side of the substances determine the choice of a particular drug/drug type.Tailored medicine in AD treatment comprises drugs of the group of small molecules such as topical Janus kinases-signal transducer and activator of transcription (JAK-STAT) inhibitors or phosphodiesterase 4 inhibitors, and JAK-STAT inhibitors for oral use, as well as monoclonal antibodies for subcutaneous use, which target key cytokines or cytokine receptors in AD pathogenesis., Summary: The current stepwise treatment approaches, which are settled on basic therapy and structured patient education and gradually expanded depending on the severity of the disease by stronger topical or even systemic measures, will have to be adapted to the rapid development in the therapeutic field, mirrored by an impressive high number of ongoing clinical studies as well as novel drugs at late stages of clinical trials with so far quite promising results., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD)., Objective: Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD., Methods: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate-to-severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP-NRS), Investigator's Global Assessment (IGA), changes in sleep and responders with ≥ 4-point improvement on PP-NRS., Results: There was a significantly greater itch relief apparent by Day 2 (-22.8% vs -12.3% PP-NRS; P = 0.005) which continued to improve through week 16 (-68.5% vs -30.9% PP-NRS; P < 0.001). At week 16, PP-NRS ≥ 4-point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P ≤ 0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by Day 3 (-26.6% vs -9.0%; P < 0.001) which further improved till week 16 (-76.0% vs -36.5%; P < 0.001). Also for the EASI score a separation between groups in favour of nemolizumab was observed by week 1 (P ≤ 0.001), which increased through week 16 (-68.6% vs. -42.6%; P = 0.002). Finally, the degree of response was greater in nemolizumab-treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P < 0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P = 0.002). Nemolizumab was safe and well-tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events., Conclusions: Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥ 16 at baseline., (© 2021 Galderma SA. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Purpose of Review: Until recently there have been limited options for systemic therapy in atopic dermatitis, which is unresponsive to topical treatments. However, the last few years have seen a rapid progression in this field. The purpose of this review is to summarise some of the recent literature and ongoing studies in the field of biologicals in atopic dermatitis., Recent Findings: Dupilumab has been shown to be effective in moderate to severe atopic dermatitis and is now licensed in the USA and Europe. Tralokinumab is currently under review by the Food and Drug Administration and the European Medicines agency. Phase 2 and 3 studies are taking place with other biological therapies. There is increasing evidence for the use of biologicals in children and for their role in multisystem disease., Summary: The recent breakthroughs in treatment represent an opportunity to resolve an unmet need; the management of atopic dermatitis which is unresponsive to topical therapy., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Prurigo lesions in atopic dermatitis are intractable. This single-center, retrospective study examined dupilumab's clinical effects on intractable prurigo. Twenty adult atopic dermatitis patients (12 with prurigo, eight without) were administrated dupilumab. Its effects on itching and disease severity were examined with Numerical Rating Scale-Itch (NRS-I), Eczema Area and Severity Index (EASI), and Investigator Global Assessment (IGA) scores; body surface areas (BSA); and thymus- and activation-regulated chemokine (TARC), total immunoglobulin (Ig)E, and eosinophil levels. NRS-I scores, EASI scores, TARC levels, and total IgE levels before dupilumab treatment were not statistically different between the prurigo and non-prurigo groups. With dupilumab treatment, NRS-I scores, EASI scores, IGA scores, BSA, TARC levels, and total IgE levels were significantly reduced from baseline in both groups at 1-2 months and onward, but skin symptom improvement in the prurigo group was slower than in the non-prurigo group, as evidenced by significantly higher EASI scores, BSA, and TARC levels at several time points during the 12 months of dupilumab treatment. Prurigo patients were slower in EASI-50 achievement and significantly lower in EASI-90 achievement at 12 months than non-prurigo patients. Adherence to dupilumab was not different, but total equivalent amounts of concomitant therapeutic agents (corticosteroids and tacrolimus) used during dupilumab treatment were significantly higher in the prurigo group (median, 56.2 g/week) than in the non-prurigo group (median, 33.7 g/week). There were 2.2 adverse events per patient on average; ocular complaints were most frequent. Dupilumab was effective in treating intractable prurigo, but despite significantly greater concomitant therapeutic agent use, skin symptom improvement was slower in prurigo patients than in non-prurigo patients., (© 2021 Japanese Dermatological Association.)

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., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults., (© 2020 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Atopic dermatitis (AD) is a frequent, chronic remittent skin disease. The pathophysiology of AD has been increasingly understood within the last years, which may help to identify different endotypes suitable for defined therapies in the future. A patient-oriented therapy considers phenotypical features in addition to genetic and biological markers. The most recent developments in biologics and small-molecule drugs for AD treatment are presented in this article. These molecules, if approved, could change the perspectives for future therapies. Dupilumab is the first approved biologic for the treatment of moderate to severe atopic dermatitis in adolescence and adulthood and has led to a significant improvement in the treatment of this chronic disease. In the present article we present real-life data on the efficacy of dupilumab in adult dermatitis patients. We also discuss other data relevant to the use of dupilumab, and address open questions important for the standard care of atopic dermatitis patients., (© 2020 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

The transmembrane glycoprotein OX40 receptor (OX40) and its ligand, OX40L, are instrumental modulators of the adaptive immune response in humans. OX40 functions as a costimulatory molecule that promotes T cell activation, differentiation, and survival through ligation with OX40L. T cells play an integral role in the pathogenesis of several inflammatory skin conditions, including atopic dermatitis (AD). In particular, T helper 2 (TH2) cells strongly contribute to AD pathogenesis via the production of cytokines associated with type 2 inflammation (e.g., IL-4, IL-5, IL-13, and IL-31) that lead to skin barrier dysfunction and pruritus. The OX40-OX40L interaction also promotes the activation and proliferation of other T helper cell populations (e.g., TH1, TH22, and TH17), and AD patients have demonstrated higher levels of OX40 expression on peripheral blood mononuclear cells than healthy controls. As such, the OX40-OX40L pathway is a potential target for AD treatment. Novel therapies targeting the OX40 pathway are currently in development, several of which have demonstrated promising safety and efficacy results in patients with moderate-to-severe AD. Herein, we review the function of OX40 and the OX40-OX40L signaling pathway, their role in AD pathogenesis, and emerging therapies targeting OX40-OX40L that may offer insights into the future of AD management. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is an abnormal inflammatory response in the skin to food, environmental IgE, or non-IgE allergens. This disease belongs to a group of inflammatory diseases that affect both children and adults. In highly developed countries, AD is diagnosed twice as often in children than in adults, which may possibly be connected to increased urbanization. The immune system's pathomechanisms of AD involve humoral mechanisms with IgE, cellular T lymphocytes, dendritic cells occurring in the dermis, Langerhans cells occurring in the epidermis, and other cells infiltrating the site of inflammation (eosinophils, macrophages, mast cells, neutrophils, and basophils). Cytokines are small proteins that affect the interaction and communication between cells. This review characterizes cytokines and potential aspects of the treatment of atopic dermatitis, as well as new strategies that are currently being developed, including targeting cytokines and their receptors. [ABSTRACT FROM AUTHOR]

Purpose of Review: Atopic dermatitis (AD) remains a dermatological disease that imposes a significant burden on society. Air pollution has previously been linked to both the onset and severity of atopic dermatitis. As air pollution remains a critical environmental factor impacting human health, this review seeks to provide an overview of the relationship between different air pollutants and AD. Recent Findings: AD can develop from multiple causes that can be broadly grouped into epidermal barrier dysfunction and immune dysregulation. Air pollution imposes significant health risks and includes a wide variety of pollutant types. AD has been linked to outdoor air pollutants such as particulate matter (PM), volatile organic compounds (VOC), gaseous compounds, and heavy metals. Exposure to indoor pollutants such as tobacco smoke and fungal molds has also been associated with an increased incidence of AD. While different pollutants impact distinct molecular pathways in the cell, they mostly converge on ROS product, DNA damage, and dysregulated T-cell activity and cytokine production. Summary: The presented review suggests a strengthening tie between air pollution and AD. It points to opportunities for further studies to clarify, as well as potential therapeutic opportunities that leverage the mechanistic relationships between air pollution and AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by scaly, oozing skin and itch. In moderate-to-severe AD, treatment options have been historically very limited and off-label use has been a common method for disease management. For decades, ciclosporin A was the only systemic immunosuppressive drug approved in most European countries to address this major unmet medical need. However, increased understanding of the pathophysiology of AD has led to a revolution in the treatment of this potentially debilitating disease. Following the approval of the first biological therapy for AD in 2017, there has been a rapid expansion of compounds under development and four additional systemic therapies have been approved in Europe and the USA within the past 3 years alone. In this review, we underscore how key breakthroughs have transformed the therapeutic landscape of AD, leading to a major expansion of type 2 immunity-targeted biological therapies, exploration of neuroimmune modulatory agents, and interest in Janus kinase inhibition. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type 2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of T helper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemic agents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability. [ABSTRACT FROM AUTHOR]

Data from the Japanese phase 3 Nemolizumab-JP01 study (JapicCTI-173740) found that nemolizumab in combination with topical treatments reduced pruritus associated with atopic dermatitis inadequately controlled with current therapies. This post-hoc analysis examined associations between improvements in pruritus (visual analog scale [VAS]) and eczema (Eczema Area and Severity Index [EASI]), and achievement of other clinically relevant endpoints including the Insomnia Severity Index (ISI), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM). Pruritus VAS responders (≥50% improvement from baseline to week 16) showed greater improvements from baseline in these additional endpoints as early as week 1, compared with non-responders. Responders also had EASI improvement, and more than 80% achieved an ISI score ≤7, or had improvement in the DLQI or POEM. The percent change from baseline in VAS and EASI scores at week 16 was in favor of nemolizumab in all subgroups based on baseline characteristics. No specific factor affecting treatment response to nemolizumab was identified. In this post-hoc analysis, nemolizumab-treated patients who had greater pruritus reductions also showed improvements in other eczema symptoms; pruritus alleviation appeared to be responsible for the improvements in eczema, sleep and daily life. [ABSTRACT FROM AUTHOR]

Biologic medications are recent advances that have clinical significance in the treatment of moderate-to-severe AD. A systemic literature review was performed to examine the efficacy and safety of biologic therapies currently in phase II and phase III of clinical trials for moderate-to-severe AD. Our team searched the databases, PubMed, Google Scholar, and ClinicalTrials.gov, on September 2019 for studies pertaining to the use of biologic drugs in AD. Key words included each drug (lebrikizumab, tralokinumab, fezakinumab, etokimab, nemolizumab, tezepelumab, and GBR 830) or 'biologic drugs' or 'immunotherapies' combined with 'atopic dermatitis.' References within retrieved articles were also reviewed to identify potentially missed studies. A total of 19 articles were included in this review. Lebrikizumab, tralokinumab, fezakinumab, nemolizumab, and GBR 830 lead to statistically significant improvements in disease severity and multiple endpoint outcome scores. Tezepelumab and etokimab, however, did not demonstrate statistically significant changes in primary outcome endpoints. Further assessment of tezepelumab and etokimab are needed to assess their safety and efficacy in patients with moderate-to-severe AD. Tralokinumab, lebrikizumab, fezakinumab, nemolizumab, and GBR 830 are effective treatment options for adults with moderate-to-severe AD, but further large-scale studies are needed to confirm their efficacy as monotherapy in children with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Introduction:Several novel biological agents and janus kinase (JAK) inhibitors are being investigated for efficacy in the management of atopic dermatitis (AD). However, there is a paucity of head-to-head trials comparing agents and their effect on quality of life (QoL). Methods:A systematic review of existing studies was performed, and data was pooled for meta-analysis from eligible studies of novel systemic agents for AD which reported QoL outcomes. Sixteen week least square means differences (LSM) were pooled and compared using network meta-analysis to synthesize direct and indirect comparisons, with 95% credible intervals (Crl) provided. Results:At 16 weeks, Dermatology Life Quality Index outcomes showed dupilumab 300 mg once weekly had the highest improvement versus placebo (LSM −4.63, 95% Crl −5.46,3.79). At 16 weeks, the improvement in Patient Oriented Eczema Measure scores ranked abrocitinib 200 mg daily the highest (LSM −7.62, 95% Crl −10.26; −4.98) and improvement in Hospital Anxiety and Depression Scale ranked dupilumab 300 mg once weekly highest (LSM −2.98, 95% Crl −4.48; −1.47) The improvement in peak pruritus scores ranked lebrikizumab 250 mg fortnightly (LSM −64.90, 95% Crl-84.58; −45.22) highest. Conclusion:The present study suggests that there are various systemic options for AD for which all seem to demonstrate a degree of QoL-related efficacy. [ABSTRACT FROM AUTHOR]

Background: Flow cytometry is a well‐accepted approach for immune profiling; however, its value is restricted by the limited number of markers that can be analyzed simultaneously. Mass cytometry/CyTOF offers broad‐scale immune characterization integrating large number of parameters. While partial blood phenotyping was reported in atopic dermatitis (AD), patients' comprehensive profiling, critical for leveraging new targeted treatments, is not available. IL‐21 may be involved in inflammatory skin diseases but its role in AD is not well established. Methods: We studied T‐cell polarization in the blood of 20 moderate‐to‐severe AD and 15 controls. Using CyTOF and an unsupervised analysis, we measured the frequencies and mean metal intensities of activated polar CD4+/CD8+ T‐cell subsets. Immunohistochemistry, immunofluorescence, and qRT‐PCR were used to analyze skin samples. Results: Examining 24 surface, intracellular markers, and transcription factors, we identified six CD4+ and five CD8+ T‐cell metaclusters. A CD4+ skin‐homing IL‐13+monocytokine and a novel IL‐13+IL‐21+ multicytokine metaclusters were increased in AD vs. controls (p <.01). While IL‐13 signature characterized both clusters, levels were significantly higher in the IL‐21+ group. Both clusters correlated with AD severity (r = 0.49, p =.029). Manual gating corroborated these results and identified additional multicytokine subsets in AD. Immunohistochemistry and immunofluorescence, validated by mRNA expression, displayed significantly increasedIL‐21 counts and colocalization with IL‐13/IL‐4R in AD skin. Conclusion: A multicytokine signature characterizes moderate‐to‐severe AD, possibly explaining partial therapeutic responses to one cytokine targeting, particularly in severe patients. Prominent IL‐21 signature in blood and skin hints for a potential pathogenic role of IL‐21 in AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is generally considered a T helper type 2–dominated disease. Pediatric AD is usually less severe than adult AD, but it may present as moderate to severe lesions that are inadequately managed by current modalities including emollients/moisturizers, topical corticosteroids (TCSs), topical calcineurin inhibitors (TCIs), and even systemic immunosuppressants (such as cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil). In addition, systemic immunosuppressants are often not recommended for childhood AD by the current guidelines due to their toxicities. Therefore, there is still an unmet need for a safe and effective long-term therapy for pediatric AD patients whose disease is inadequately controlled or who are intolerant to current treatments. The emerging therapeutics for AD focuses on intervening in the inflammatory pathway by targeting specific cytokines/chemokines or their receptors. Monoclonal antibodies against immunoglobulin E (IgE), interleukin (IL)-4 receptor subunit α, IL-5, IL-13, IL-31 receptor subunit α, IL-33, and thymic stromal lymphopoietin (TSLP) have been evaluated clinically for AD. Encouraging results have been reported for many of the biologics, of which the most exciting is dupilumab. Other emerging systemic therapies include small molecules such as baricitinib, abrocitinib, upadacitinib, and tradipitant. Several novel topical agents are under clinical investigation for the treatment of AD, including topical phosphodiesterase 4 (PDE4) inhibitors, Janus kinase (JAK) inhibitors, aryl hydrocarbon receptor (AhR) modulating agents, and transient receptor potential vanilloid subfamily member 1 (TRPV1) antagonists. Accompanied by thorough characterization of different phenotype and endotype subsets, the application of precision medicine could provide new prospects for the optimal treatment of AD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common disease of childhood, and some patients experience a prolonged clinical course into adolescence and adulthood. Systemic management is required when AD is not adequately controlled with topical medications. Our aim is to provide a comprehensive review of commonly used systemic immunomodulating agents in childhood and adult AD, including cyclosporine A (CsA), azathioprine (AZA), methotrexate (MTX) and mycophenolate mofetil (MMF), which are prescribed off-label in the United States, as well as dupilumab, an FDA-approved biologic. We will also provide a brief overview of emerging systemic therapies currently under investigation. [ABSTRACT FROM AUTHOR]

Vitamin D supplementation with standard treatment yielded positive clinical outcomes in mild and moderate atopic dermatitis; however, the potential benefit of vitamin D in severe cases remains unclear. This study aimed to evaluate the impact of vitamin D supplementation on response to standard treatment in pediatrics with severe atopic dermatitis. The patients were randomized to receive either vitamin D 3 1600 IU/day or placebo, plus baseline therapy of topical 1% hydrocortisone cream twice daily for 12 weeks. The primary endpoints were the change in mean Eczema Area and Severity Index (EASI) score at the end of the study and the mean percent change in EASI score from baseline to week 12. Eighty-six subjects completed the study. The treated group achieved a significant higher level of 25 hydroxy vitamin D (P < .001) compared to control group at week 12. The mean EASI score was significantly lower in the treatment group compared to placebo group (P = .035). The percent change in EASI score from baseline differed significantly between the supplementation (56.44 ± 29.33) and placebo (42.09 ± 19.22) groups after intervention (P = .039). Vitamin D supplementation could be an effective adjuvant treatment that improves the clinical outcomes in severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common immunologic skin disease. Mild atopic dermatitis can be managed with emollients and topical therapies such as low potency topical steroids, which have a favorable safety profile. Severe atopic dermatitis, in contrast, is a challenging disease to treat. Topical therapies are typically inadequate for control of severe atopic dermatitis. When topical therapies fail, the mainstay of therapy for severe atopic dermatitis has traditionally been phototherapy or off-label use of systemic immunosuppressant treatment, yet systemic immunosuppressants all have significant potential toxicities, drug interactions, and contraindications, requiring close monitoring. Targeted biologics are therefore attractive treatment options for topical therapy-refractory cases of atopic dermatitis, with the potential to offer effective, safer treatment of uncontrolled atopic dermatitis. Dupilumab, as the only biologic therapy currently FDA-approved for atopic dermatitis, is effective for many patients, but there is need for continuing study of additional biologic therapies to address the needs of diverse patients with uncontrolled atopic dermatitis. [ABSTRACT FROM AUTHOR]

Severe atopic dermatitis, which affects both adults and children, is a debilitating disorder with a significant decline of patients' quality of life. Although aetiopathogenic factors are currently a topic of study and interpretation, the main features of atopic eczema are skin barrier disturbance and immune dysregulation. Severe refractory disease that fails to improve with conventional therapy may benefit from biologic therapy. Progress in understanding immunopathology of atopic dermatitis have allowed identification of therapeutic molecular targets in the field of biological therapy. We reviewed the different biological treatments with a focus on novel targeted agents: Systemic immunotherapy (Omalizumab, Dupilumab, Lebrikizumab, Tralokinumab, Nemolizumab, Ustekinumab, Fezakinumab, Tezepelumab, Apremilast, allergen specific immunotherapy), and topical agents (Tofacitinib, Crisaborole). [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) inhibitors are promising treatments for atopic dermatitis (AD). The aim of this study was to assess the efficacy and safety of JAK inhibitors for AD treatment via the "Grading of Recommendations Assessment, Development, and Evaluation" approach. We identified 15 randomized controlled trials comparing oral or topical JAK inhibitors against placebo to treat AD. A random-effects meta-analysis was performed, and the numbers-needed-to-treat (NNTs)/numbers-needed-to-harm (NNHs) were calculated. Patients treated with JAK inhibitors were associated with higher rates of achieving eczema area and severity index-75 (rate ratio (RR): 2.84; 95% confidence interval (CI): 2.20–3.67; I2: 38.9%; NNT = 3.97), Investigator's Global Assessment response (RR: 2.99; 95% CI: 2.26–3.95; I2: 0%; NNT = 5.72), and pruritus numerical rating scale response (RR: 2.52; 95% CI: 1.90–3.35; I2: 39.4%; NNT = 4.91) than those treated with placebo. Moreover, patients treated with JAK inhibitors had a higher risk of treatment-emergent adverse events (RR: 1.14; 95% CI: 1.02–1.28; I2: 52%; NNH = 14.80) but not adverse events leading to drug discontinuation. According to the evidence-based results, JAK inhibitors are potentially effective strategies (certainty of evidence: "moderate") for treating AD with tolerable side effects (certainty of evidence: "low"). Nevertheless, long-term follow-up is required. [ABSTRACT FROM AUTHOR]

Purpose of Review: An update on new therapies currently approved or potentially useful in the future for the management of patients suffering moderate-to-severe atopic dermatitis. Recent Findings: New pathogenic mechanisms involved in atopic dermatitis have permitted to propose novel therapeutic approaches devised to control the inflammatory process observed in involved cutaneous tissues by neutralizing mediators, cytokines, and their receptors. Summary: Recent research findings have disclosed important and previously unrecognized pathogenic mechanisms that have resulted in innovative targeted therapies, such as dupilumab, and potentially other biologicals and small molecules. Further studies should permit the sub-classification of patients according to the relevance of different mediators and inflammatory cells. It can be concluded that the treatment of atopic dermatitis has entered into the era of personalized/precision medicine. [ABSTRACT FROM AUTHOR]

Purpose of Review: Severe atopic dermatitis (AD) in childhood leads to significant morbidity including psychosocial problems and infectious complications. There are only a few approved treatment options for these patients. These include topical corticosteroids and tacrolimus ointment, which are associated with potential side effects.Recent Findings: In order to find better and safer treatments, further understanding of AD mechanisms is needed. Primary skin barrier defects play an important role in the pathogenesis of AD. In addition, the suppression of skin barrier functions by Th2 inflammation also plays an important role in the persistence and recurrence of AD. Cytokines in the Th2 pathway, which includes IL-4, IL-13, TSLP, IL-25, IL-31, and IL-33, are potential therapeutic targets in AD. Other potential targets of AD are Janus kinase, phospholipase A2, aryl hydrocarbon receptor, and skin microbiota.Summary: A better understanding of the pathogenesis of AD will provide future direction for treatment. [ABSTRACT FROM AUTHOR]