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Asthma, allergic rhinitis, chronic urticaria, and atopic dermatitis are common diseases that affect hundreds of thousands of pregnant women each year. The authors discuss the use of biologics in women who are pregnant or lactating, indications, available safety information, and knowledge gaps. There are pregnant patients for which standard treatment is either inadequate or contraindicated; in those cases, monoclonal antibodies (biologics) should be considered despite the unknown risk to the fetus. In severe asthma, omalizumab is the best studied with reassuring available safety data. Insufficient safety data exist on mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab use during pregnancy and lactation.

AIM: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by severe itching, erythema and scaling, causing pain, stigmatization and social isolation. Despite the growing availability of treatment options, unmet care needs remain. This research aimed to assess the cost-effectiveness of a novel JAK inhibitor (JAKi) compared to a monoclonal antibody and to identify key drivers of cost-effectiveness.MATERIALS AND METHODS: A de novo economic model was developed to assess the cost-effectiveness of a novel JAKi compared to an established monoclonal antibody for the treatment of moderate-to-severe AD patients from a UK perspective. A targeted literature review was conducted to inform the development of the economic model with an advanced model structure. Various scenario and sensitivity analyses were performed to account for parameter- and structural uncertainty and to identify key drivers of cost-effectiveness.RESULTS: The JAKi was not cost-effective compared to the monoclonal antibody (£219,733.88 per quality-adjusted life year (QALY) gained) at selected price levels when applying the UK willingness-to-pay threshold of £30,000 per QALY gained. Key drivers of cost-effectiveness were utility values, intervention efficacy and drug acquisition costs. A decrease in JAKi's dose costs, as well as a lower dose, lead to cost-effectiveness.LIMITATIONS: Assumptions regarding parameter inputs were necessary, therefore a considerable level of uncertainty regarding efficacy and cost data is to be accounted for in the interpretation of the results. In particular, the efficacy data were based on single clinical studies.CONCLUSIONS: This research revealed the cost-effectiveness of a JAKi compared to a monoclonal antibody for the treatment of moderate-to-severe AD to be highly sensitive to the costs and effectiveness inputs and identified further cost-effectiveness drivers. It demonstrated that the JAKi could be cost-effective compared to an established monoclonal antibody with a lower dose or a reduced price.

Background: Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin condition that is associated with detrimental effects on the lives of patients and their families, including an impact on quality of life (QOL). Studies about QOL on Latin American AD patients are scarce and have generally included few patients. Objective: describing AD impact on the QOL in a large cohort in Argentina. Methods: a structured web-based survey including 1,650 AD pediatric and adult patients was performed. Results: according to retrieved data, AD symptoms onset started during childhood in most patients, but 20 % of participants reported that manifestations of AD were initially perceived during late adolescence and adulthood. Important differences were observed among country regions, with a shorter time-to-diagnosis in most populated and richer districts. Main affected domains included frustration, anger, mood alterations, stress, sleep alterations, routine alterations, pain and economic impact of AD. Limitations: biases inherent to survey design. Conclusions: we consider that our study contributes to a better understanding of AD in Argentina, as well as its physical, social and financial impact on affected patients.

Background The skin barrier is important in the pathogenesis of atopic dermatitis and stratum corneum lipids have a critical role. Skin surface lipids have been largely overlooked but also contribute to barrier function. An untargeted approach was used to compare the skin surface lipids from atopic and non-atopic West Highland White terrier dogs (WHWT). Objectives The primary hypothesis was that a difference in the lipidome would exist. The secondary hypothesis was that affected and unaffected skin lipids would differ. Animals and methods This prospective, cross-sectional, case-controlled study included thirty-nine privately owned WHWTs. Dogs were assigned to one of four disease status groups based on strict criteria. Samples for lipid analysis were collected from the skin surface of unaffected and affected sites. Lipid analysis was by untargeted liquid chromatography/mass spectrometry and utilised lipid identification software packages. Principle component analysis (PCA) and partial least-squares discriminant analysis (sPLS-DA) statistical methods analysed the association between the relative lipid abundance and disease status and affected and unaffected skin. Results Samples for lipid analysis found 421 lipid soluble features of which ten lipids were positively identified. Statistical analysis could not distinguish between non-atopic and atopic dogs but did reveal a statistically significant difference in the lipid profiles from affected and non-affected skin irrespective of disease status. Conclusions A large array of unidentified lipids from the skin surface were found with a difference between affected and unaffected skin unrelated to disease status. Investigation into the lipidome of the skin surface is an emerging area of research with clinical and therapeutic applications.

Background Patients with atopic dermatitis (AD) frequently use acupuncture (ACU) and osteopathic medicine (OM), although their therapeutic benefits are unclear. Aim To investigate the effectiveness of ACU and OM in patients with AD. Methods In a three-armed, single-centre, randomized controlled open explorative clinical trial, adult patients with AD received ACU, OM or no study intervention (control group; CG) plus routine care. Outcomes included disease severity (SCORing Atopic Dermatitis; SCORAD), itching intensity (visual analogue scale; VAS), frequency of topical corticosteroid (TCS) use over 7 days and cost-effectiveness. Endpoints were analysed by analysis of covariance adjusted for the respective baseline value and TCS use. Results Overall, 121 patients (92 women, 29 men) with a mean ± SD age of 31.4 ± 10.5 years were randomized. After 12 weeks, the adjusted means (95% CI) for ACU, OM and control were, respectively, 22.3 (18.3–26.3), 26.4 (22.6–30.2) and 23.7 (19.9–27.5) for SCORAD (P = 0.32); 27.9 (19.5–36.4), 35.0 (26.9–43.0) and 42.3 (34.7–50.0) for VAS itching (P < 0.05); and 2.3 (0.8–3.9), 1.9 (0.4–3.5) and 4.3 (2.6–6.0), for TCS use (P = 0.10). ACU and OM were not cost-effective compared with the CG. Conclusion Although no differences in disease severity were found, our findings indicate that ACU might reduce itching in patients with AD. Furthermore, ACU and OM showed a trend towards reducing TCS use.

Abstract: Probiotics are defined as “live microorganisms that confer a health benefit on the host when administered adequately.” In recent years, the cosmetic industry has tried to develop many products classified as probiotics. They can exert their benefits at the skin level because of their favorite properties, and they could prevent and treat skin diseases and represent an emerging area for skin health. The antibacterial and immunomodulatory properties make them promising candidates to target skin disorders including acne, psoriasis, and atopic dermatitis and aid wound healing. The scientific reports show that specific probiotic strains can modulate cutaneous microflora, skin immune system, lipid barrier, and skin health preservation. This review summarizes the most relevant evidence from scientific literature concerning potential topical applications of probiotics in dermatology. Altogether, the evidence reported here affords the possibility of designing new strategies based on a topical approach to prevent and treat cutaneous disorders.

Atopic dermatitis (AD) is a chronic and relapsing multifactorial inflammatory skin disease that also affects dogs. The oral and gut microbiota are associated with many disorders, including allergy. Few studies have addressed the oral and gut microbiota in dogs, although the skin microbiota has been studied relatively well in these animals. Here, we studied the AD-associated oral and gut microbiota in 16 healthy and 9 AD dogs from a purebred Shiba Inu colony. We found that the diversity of the oral microbiota was significantly different among the dogs, whereas no significant difference was observed in the gut microbiota. Moreover, a differential abundance analysis detected the Family_XIII_AD3011_group (Anaerovoracaceae) in the gut microbiota of AD dogs; however, no bacterial taxa were detected in the oral microbiota. Third, the comparison of the microbial co-occurrence patterns between AD and healthy dogs identified differential networks in which the bacteria in the oral microbiota that were most strongly associated with AD were related to human periodontitis, whereas those in the gut microbiota were related to dysbiosis and gut inflammation. These results suggest that AD can alter the oral and gut microbiota in dogs.

Liu Tang,1 Jiefang Gao,2 Xiaolei Li,2 Xiaoqin Cao,3 Benhong Zhou1 1Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2School of Pharmaceutical Sciences, Wuhan University, Wuhan, People’s Republic of China; 3School of Medicine, Jianghan University, Wuhan, People’s Republic of ChinaCorrespondence: Liu Tang; Benhong Zhou, Department of Pharmacy, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China, Email tangliu900402@whu.edu.cn; benhongzh@whu.edu.cnPurpose: To undercover the underlying mechanisms of luteolin against atopic dermatitis (AD), clinically characterized by recurrent eczematous lesions and intense itching, based on network pharmacology, molecular docking and in vivo experimental validation.Methods: TCMSP, STITCH and SwissTargetPrediction databases were utilized to screen the corresponding targets of luteolin. Targets related to AD were collected from DisGeNET, GeneCards and TTD databases. PPI network of intersection targets was constructed through STRING 11.0 database and Cytoscape 3.9.0 software. GO and KEGG enrichment analysis were performed to investigate the critical pathways of luteolin against AD. Further, the therapeutic effects and candidate targets/signaling pathways predicted from network pharmacology analysis were experimentally validated in a mouse model of AD induced by 2, 4-dinitrofluorobenzene (DNFB).Results: A total of 31 intersection targets were obtained by matching 151 targets of luteolin with 553 targets of AD. Among all, 20 core targets were identified by PPI network topology analysis, including IL-6, TNF, IL-10, VEGFA, IL-4, etc., and molecular docking indicated that luteolin binds strongly to these core targets. KEGG pathway enrichment analysis suggested that the intersected targets were significantly enriched in IL-17 signaling pathway, Th17 cell differentiation, Th1 and Th2 cell differentiation, JAK/STAT signaling pathway, etc. The in vivo experiment validated that luteolin could alleviate AD-like skin symptoms, as evidenced by the lower SCORAD score, the reduced infiltration of mast cells and the recovery of skin barrier function. Furthermore, luteolin restored immune balance by regulating the production of Th1/Th2/Th17-mediated cytokines, which were both the predicted core targets. Moreover, luteolin inhibited the phosphorylation of JAK2 and STAT3 in the lesional skin.Conclusion: Together, the present study systematically clarifies the ameliorative effects and possible molecular mechanisms of luteolin against AD through the combination of network pharmacology and experimental validation, shedding light on the future development and clinical application of luteolin.Keywords: atopic dermatitis, luteolin, network pharmacology, target prediction, experimental validation

Background: The treatment of chronic refractory moderate-to-severe atopic dermatitis (AD) has traditionally relied on broad-spectrum systemic anti-inflammatory agents. With the introduction of biologics and Janus kinase inhibitors (Jakinib), the step management of moderate-to-severe AD is rapidly changing; however, guidelines have yet to provide formal recommendations for how to best incorporate these agents into the treatment plan. Objective: To summarize the updated evidence-based medical treatment for AD, including a proposed position for biologics and Jakinibs in the treatment algorithm. Methods: A literature search of several medical literature data bases for guidelines, position papers, systematic reviews, and clinical trials from 2012 to 2022 on the treatment of moderate-to-severe AD was conducted to prepare this narrative review. Results: Emollients and topical corticosteroids are the mainstay for treating acute flares and for maintaining chronic control. Second-line topical agents include calcineurin inhibitors, e.g., tacrolimus and pimecrolimus; crisaborole; and ruxolitinib. For acute flares, cyclosporine is preferred over systemic corticosteroids. For chronic treatment, phototherapy should be considered before systemic anti-inflammatory agents. Of the traditional anti-inflammatory agents, cyclosporine is the first-line choice, with methotrexate and azathioprine equal secondary choices. Although abrocitinib may have better efficacy then dupilumab based on indirect comparisons, abrocitinib requires closer monitoring for adverse events. Based on package labeling, Jakinibs, e.g., abrocitinib and upadacitinib, should be used only after failure with other systemic agents, including biologics (e.g., dupilumab and tralokinumab). Biologics and Jakinibs should be considered before the traditional systemic anti-inflammatory agents. Conclusion: Clinicians should consider a modified step management for AD as they await the development of national and international guideline recommendations for how best to position the biologics and Jakinibs into the AD treatment algorithm.

Background Hand eczema (HE) is frequently associated with Staphylococcus aureus; however, its role in the pathogenesis of HE is poorly understood. Objective To investigate the temporal variation in S aureus subtypes, ie, clonal complex (CC) types, on the hands and relate it to S aureus colonization in the nose and severity in a cohort of HE patients. Methods S aureus from the hands and nose of 50 adult HE patients and 50 controls was prospectively identified at 5 visits over 3 weeks. Results S aureus was identified on the hands of 23 (46%) patients at 2 or more visits and on the hands of 1 control once. Of the HE patients with S aureus colonization, 78% had the same S aureus CC type over time. Twenty-one patients had the same S aureus CC type on the hands and in the nose. Persistent colonization was strongly related to an increased disease severity. Limitations A relatively small S aureus culture-positive population. Conclusion The temporal stability of S aureus CC type and high occurrence of the identical subtypes on the hands and in the nose imply that S aureus colonization in patients with HE is of a more permanent nature. Taken together with the finding that persistent colonization and HE severity are clearly related, our results indicate that S aureus may contribute to the perpetuating course of HE.

Atopic dermatitis (AD) is mainly considered an allergy, exacerbated by allergic factors. Is there evidence to suggest the existence of autoimmune components in the pathophysiology of the illness? Studies in the literature that dealt with the occurrence of autoimmunity in children with AD were analyzed. We followed the studies published in PubMed for 10 years, from 2001 to 2021. Clinical signs and symptoms were similar to other autoimmune diseases, having periods of remission and relapses. Other correlations between AD and autoimmune diseases have been described, and patients with AD can also present with a wide range of autoimmune comorbidities. Three major factors contribute to the pathogenesis of AD: damage of the skin barrier, disorders of the immune response, and imbalances of the skin microbiome—all based on genetic changes and influenced by environmental factors. Predominant activation of Th 2 cells, with the increase of Th 1, Th 17, and Th 22 subsets, promotes skin inflammation. All this evidence suggests that AD might be classified as an autoimmune disease, not just as an allergic reaction.

Background: At present, no real-world studies are available on different dupilumab dosing regimens in controlled atopic dermatitis (AD). The aim of this study was to clinically evaluate a patient-centered dupilumab dosing regimen in patients with controlled AD and to relate this to serum drug levels and serum biomarkers. Methods: Ninety adult AD patients from the prospective BioDay registry were included based on their dupilumab administration interval according to a predefined patient-centered dosing regimen. Group A (n = 30) did not fulfill the criteria for interval prolongation and continued using the standard dupilumab dosage (300 mg/2 weeks), group B (n = 30) prolonged dupilumab interval with 50% (300 mg/4 weeks), and group C (n = 30) prolonged dupilumab interval with 66%–75% (300 mg/6–8 weeks). AD severity score, patient-reported outcomes, serum dupilumab levels, and serum biomarkers were analyzed over time. Results: Disease severity scores did not significantly change over time during the tapering period in any of the groups. In groups B and C, the Numeric Rating Scale (NRS)-pruritus temporarily significantly increased after interval prolongation but remained low (median NRS-pruritus≤4). Median dupilumab levels remained stable in group A (standard dosage), but significantly decreased in groups B and C (24.1 mg/L (IQR = 17.1–45.6); 12.5 mg/L (IQR = 1.7–22.3)) compared with the levels during the standard dosage (88.2 mg/L [IQR = 67.1–123.0, p

Objective: The study aimed to conduct a systematic review of the literature to verify the association between exposure to pesticides and allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) in children and adolescents. Method: A systematic review and meta-analysis were performed using the PRISMA method with the question “What is the association between exposure to pesticides and allergic diseases in children (asthma, allergic rhinitis, and atopic dermatitis)?” MEDLINE, EMBASE, SciELO, and Cochrane electronic databases were searched throughout the period in the literature up to September 2020. A total of 1296 studies were found, and 24 were selected. Results: Exposure to pesticides showed a two-fold greater risk of developing or exacerbating asthma in children and adolescents (odds ratio [OR] = 2.14 95% confidence interval [CI] 1.26-3.64, p < 0.01). There was no association between exposure to pesticides and the development of allergic rhinitis (OR = 2.73, 95% CI 0.13-57.8, p = 0.52) and atopic dermatitis (OR = 2.19, 95% CI 0.51-9.36, p = 0.29). Conclusions: Exposure to pesticides increases the risk of developing or exacerbating asthma in children and adolescents. There was no evidence of an association between exposure to pesticides and the development of allergic rhinitis and atopic dermatitis in children and adolescents, possibly due to the low number of studies found in this review.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by type 2 immune responses. Interleukin-25 (IL-25) is produced predominantly by epithelial cells. It can activate Th2 cells to produce type 2 cytokines such as IL-4, IL-5 and IL-13, contributing to host defense against nematodes. However, excessive/inappropriate production of IL-25 is considered to be involved in development of type 2 cytokine-associated allergic disorders such as asthma. On the other hand, the contribution of IL-25 to the pathogenesis of AD remains poorly understood. In the present study, we found that expression of Il25 mRNA was significantly increased in the skin of mice during oxazolone-induced chronic contact hypersensitivity (CHS), which is a mouse model of human AD. In addition, development of oxazolone-induced chronic CHS was significantly reduced in IL-25-deficient (Il25

To investigate the clinical efficacy and safety of topical difamilast in mild-to-moderate atopic dermatitis (AD). Only randomized controlled trials (RCTs) that compared topical difamilast with vehicle treatment for patients with AD were included. PubMed, Web of Science, Ovid Medline, Cochrane Library, ClinicalTrials.gov and JapicCTI were searched to 10 April 2022. Five studies enrolling a total of 1009 patients with mild-to-moderate AD were identified. Compared with the topical vehicle, topical difamilast was associated with a significantly higher success rate according to the Investigator’s Global Assessment score at week 4 (relative risk, 2.82; 95% confidence interval [CI]: 2.11–3.77). Compared with the vehicle, difamilast was associated with a significant decrease in day 28 eczema area and severity index scores (mean difference [MD], −4.10; 95% CI: −5.32 to −2.87), verbal rating scale scores (MD, −0.51; 95% CI: −0.71 to −0.32), visual analog scale scores (MD, −12.15; 95% CI: −19.70 to −4.61), patient-oriented eczema measure values (MD, −3.99; 95% CI: −4.91 to −3.07), and total affected body surface area (MD, −6.48; 95% CI: −8.09 to −4.87). No difference in treatment-related adverse events was identified. This meta-analysis suggests that topical difamilast is an effective and safe treatment for mild-to-moderate AD.

Treatment of inflammatory skin diseases, including atopic dermatitis (AD) and psoriasis, is undergoing transformative changes, highlighting the need to develop experimental models of skin inflammation in humans to predict treatment responses.We topically or intradermally administered four common sensitizers (dust mite (DM), diphencyprone (DPCP), nickel (Ni), and purified protein derivative (PPD)) to the backs of 40 healthy patients and the skin hypersensitivity response was biopsied and evaluated using immunohistochemistry, RNA-seq, and RT-PCR.All agents induced strong increases in cellular infiltrates (T-cells and dendritic cells) as compared to untreated skin (p .05), with variable T helper polarization. Overall, DPCP induced the strongest immune responses across all pathways, including innate immunity (IL-1α, IL-8), Th1 (IFNγ, CXCL10), Th2 (IL-5, CCL11), and Th17 (CAMP/LL37) products, as well as the highest regulatory tone (FOXP3, IL-34, IL-37) (FDR 0.01). Nickel induced Th17 (IL-17A), Th1 (CXCL10) and Th2 (IL-4R) immune responses to a lesser extent than DPCP (p .05). PPD induced predominantly Th1 (IFNγ, CXCL10, STAT1) and Th17 inflammation (IL-17A) (p .05). DM induced modulation of Th2 (IL-13, CCL17, CCL18), Th22 (IL-22), and Th17/Th22 (S100A7/9/12) pathways (p .05). Barrier defects that characterize both AD and psoriasis were best modeled by DPCP and Ni, followed by PPD, including downregulation of terminal differentiation (FLG, FLG2, LOR, LCEs), tight junction (CLDN1/CLDN8), and lipid metabolism (FA2H, FABP7)-related markers.Our data imply that DPCP induced the strongest immune response across all pathways, and barrier defects characteristic of AD and psoriasis.

Previous evaluations of cytokine and chemokine gene expressions [messenger (m)RNA] in the skin of allergic cats were mostly unsuccessful in detecting the T-helper 2 (Th2) pathway, which is associated with the major effector cytokines interleukin (IL)-4, IL-5 and IL-13.To evaluate differences in the mRNA expression in eosinophilic plaques of cats diagnosed with feline atopic skin syndrome (FASS) compared to healthy controls.Four client-owned cats with FASS with eosinophilic plaques and five healthy control cats.Gene expressions (mRNA) of 14 cytokines and chemokines from eosinophilic plaque skin of cats with FASS and site-matched skin samples from healthy controls were analysed using quantitative reverse-transcription PCR analysis.Eosinophilic plaques were characterized by upregulation of Th2 cytokines IL-4 (p ≤ 0.01), IL-5 (p ≤ 0.01) and IL-13 (p ≤ 0.01) and Th2-attracting chemokine CCL17 (p ≤ 0.05). Moreover, there was higher expression of S100 calcium-binding protein A 8 (p ≤ 0.01) as well as C-X-C Motif chemokine ligand 10 (CXCL10; p ≤ 0.01), IL-10 (p ≤ 0.05) and the Th17 cytokine IL-17A (p ≤ 0.01) in lesional skin compared to healthy samples. There was no difference in gene expressions of IL-12A, IL-31, IL-33, thymic stromal lymphopoietin (TSLP), tumour necrosis factor-α (TNF-α) or CCL5.Results demonstrate that eosinophilic plaques feature dominant Th2 and IL-17A inflammatory responses in the skin. Further larger-sample transcriptome studies are needed to advance our understanding of the pathogenesis of different skin lesions in FASS.Les évaluations précédentes des expressions des gènes de cytokines et de chimiokines [ARN messager (m)] dans la peau de chats allergiques n'ont pour la plupart pas réussi à détecter la voie T-helper 2 (Th2), qui est associée aux principales cytokines effectrices interleukine (IL) -4, IL-5 et IL-13. HYPOTHÈSE/OBJECTIF: Évaluer les différences d'expression de l'ARNm au sein des plaques éosinophiliques des chats diagnostiqués avec le syndrome atopique cutané félin (FASS) par rapport aux témoins sains.Quatre chats appartenant à des clients avec FASS avec plaques éosinophiles et cinq chats témoins sains. MATÉRIELS ET MÉTHODES: Les expressions géniques (ARNm) de 14 cytokines et chimiokines de peau de plaque éosinophilique de chats atteints de FASS et d'échantillons de peau correspondant au site de témoins sains ont été analysées à l'aide d'une analyse PCR quantitative à transcription inverse. RÉSULTATS: Les plaques éosinophiles ont été caractérisées par une régulation positive des cytokines Th2 IL-4 (p ≤ 0,01), IL-5 (p ≤ 0,01) et IL-13 (p ≤ 0,01) et de la chimiokine attirant les Th2 CCL17 (p ≤ 0,05). De plus, il y avait une expression plus élevée de la protéine A 8 de liaison au calcium S100 (p ≤ 0,01) ainsi que du ligand de chimiokine C-X-C Motif 10 (CXCL10; p ≤ 0,01), de l'IL-10 (p ≤ 0,05) et de la cytokine Th17 IL-17A (p ≤ 0,01) dans la peau lésionnelle par rapport aux échantillons sains. Il n'y avait aucune différence dans l'expression des gènes de l'IL-12A, de l'IL-31, de l'IL-33, de la lymphopoïétine stromale thymique (TSLP), du facteur de nécrose tumorale-α (TNF-α) ou du CCL5.Les résultats démontrent que les plaques éosinophiliques présentent des réponses inflammatoires Th2 et IL-17A dominantes dans la peau. D'autres études de transcriptome à plus grand échantillon sont nécessaires pour faire progresser notre compréhension de la pathogenie de différentes lésions cutanées dans le FASS.INTRODUCCIÓN: Las evaluaciones anteriores de las expresiones génicas de citoquinas y quimioquinas [RNA mensajero (m)] en la piel de gatos alérgicos no tuvieron éxito en la detección de la vía T-helper 2 (Th2), que está asociada con las principales citoquinas efectoras interleuquina (IL)-4, IL-5 e IL-13. HIPÓTESIS/OBJETIVO: Evaluar diferencias en la expresión de RNAm en placas eosinofílicas de gatos diagnosticados con síndrome de piel atópica felina (FASS) en comparación con controles sanos. ANIMALES: cuatro gatos de propietarios particulares con FASS desarrollando placas eosinofílicas y cinco gatos de control sanos. MATERIALES Y MÉTODOS: se analizaron las expresiones génicas (RNAm) de 14 citoquinas y quimioquinas de la piel de la placa eosinofílica de gatos con FASS y muestras de piel del mismo sitio de controles sanos mediante análisis de PCR de transcripción inversa cuantitativa. RESULTADOS: Las placas eosinofílicas se caracterizaron por la elevación de las citoquinas Th2 IL-4 (p ≤ 0,01), IL-5 (p ≤ 0,01) e IL-13 (p ≤ 0,01) y la quimioquina CCL17 que atrae a Th2 (p ≤ 0,05). Además, hubo una mayor expresión de la proteína A 8 de unión a calcio S100 (p ≤ 0,01), así como del ligando 10 de quimioquina C-X-C Motif (CXCL10; p ≤ 0,01), IL-10 (p ≤ 0,05) y la citoquina Th17 IL-17A. (p ≤ 0.01) en piel lesionada en comparación con muestras sanas. No hubo diferencias en las expresiones génicas de IL-12A, IL-31, IL-33, linfopoyetina estromal tímica (TSLP), factor de necrosis tumoral-α (TNF-α) o CCL5. CONCLUSIONES: Los resultados demuestran que las placas eosinofílicas presentan respuestas inflamatorias Th2 e IL-17A dominantes en la piel. Se necesitan más estudios transcriptómicos de muestras más grandes para avanzar en nuestra comprensión de la patogenia de diferentes lesiones cutáneas en FASS.Frühere Untersuchungen der Genexprimierung von Zytokinen und Chemokinen [Messenger (m)RNA] in der Haut allergischer Katzen zeigten wenig Erfolg bei der Bestimmung des T-Helper 2 (Th2) Pathways, der hauptsächlich mit den Zytokinen Interleukin (IL)-4, IL-5 und IL-13 in Verbindung gebracht wird.Eine Evaluierung von Unterschieden bei der mRNA Exprimierung von eosinophilen Plaques bei Katzen, die mit dem felinen atopischen Hautsyndrom (FASS) diagnostiziert worden waren, im Vergleich zu gesunden Kontrollen.Vier Katzen in Privatbesitz mit FASS, die eosinophile Plaques zeigten, und fünf gesunde Kontrollkatzen.Die Genexprimierung (mRNA) von 14 Zytokinen und Chemokinen in eosinophilen Plaques aus der Haut von Katzen mit FASS und von Hautproben gesunder Kontrolltiere, die von denselben Körperstellen stammten, wurden mittels quantitativer Reverse-Transkriptase PCR Analyse untersucht.Die eosinophilen Plaques waren durch eine Hochregulierung der Th2 Zytokine IL-4 (p ≤ 0,01), IL-5 (p ≤ 0,01) und IL-13 (p ≤ 0,01) und Th-2 anziehendes Chemokin CCL17 (p ≤ 0,05) gekennzeichnet. Darüber hinaus bestand eine höhere Exprimierung von S100 Kalzium-Bindendem Protein A 8 (p ≤ 0,01), sowie von C-X-C Motif Chemokin Ligand 10 (CXCL10; p ≤ 0,01), IL-10 (p ≤ 0,05) und Th17 Zytokin IL-17A (p ≤ 0,01), in läsionaler Haut im Vergleich zu gesunden Hautproben. Es bestand kein Unterschied bei der Genexprimierung von IL-12A, IL-31, IL-33, Thymic Stromal Lymphopoietin (TSLP), Tumor Nekrosisfaktor-α (TNF-α) oder CCL5.Die Ergebnisse zeigen, dass dominante Th2 und IL-17A Entzündungsreaktionen der Haut typische Kennzeichen eosinophiler Plaques darstellen. Weiters sind Transkriptionsstudien mit größeren Probezahlen nötig, um unser Verständnis der Pathogenese der verschiedenen Hautveränderungen bei FASS zu verbessern.背景: これまでのアレルギー猫の皮膚におけるサイトカイン・ケモカイン遺伝子発現(メッセンジャー(m)RNA)の評価では、主要エフェクターサイトカインのインターロイキン(IL)-4、IL-5、IL-13に関連するヘルパーT2(Th2)経路の検出にはほとんど成功していない。 仮説/目的: 本研究の目的は、猫アトピー性皮膚症候群(FASS)と診断された猫の好酸球性プラークにおけるmRNA発現の健常対照猫との差異を評価することであった。 対象動物: 好酸球性プラークを有する FASS のオーナー所有猫 4 頭と対照健常猫 5 頭。 材料と方法: FASSの猫の好酸球性プラークと、健常対照猫の同部位皮膚サンプルから、14種類のサイトカインおよびケモカインの遺伝子発現(mRNA)を、定量的逆転写PCR法で解析した。 結果: 好酸球性プラークは、Th2サイトカインIL-4(p≦0.01)、IL-5(p≦0.01)、IL-13(p≦0.01)およびTh2誘引ケモカインCCL17(p≦0.05)の発現上昇により特徴づけられた。さらに、病変皮膚では健常猫検体と比較して、S100 calcium-binding protein A 8 (p ≤ 0.01) のほか、C-X-C Motif chemokine ligand 10 (CXCL10; p ≤ 0.01), IL-10 (p≤ 0.05) および Th17 サイトカイン IL-17A (p≤ 0.01) が高い発現を示していることが示された。IL-12A、IL-31、IL-33、thymic stromal lymphopoietin(TSLP)、腫瘍壊死因子-α(TNF-α)、CCL5の遺伝子発現に差はなかった。 結論: 好酸球性プラークは、皮膚においてTh2およびIL-17Aの炎症反応が支配的であることを示す結果である。FASSの様々な皮膚病変の病因を理解するためには、さらに大規模なトランスクリプトーム研究が必要である。.背景: 之前对过敏猫皮肤中细胞因子和趋化因子基因表达 [信使 (m)RNA] 的评价大多未能成功检测辅助性 T 细胞 2(Th2) 通路，其与主要效应细胞因子白细胞介素 (IL)-4、IL-5和 IL-13 相关。 假设/目的: 评价诊断为特应性皮肤综合征 (FASS) 的患猫嗜酸性斑块中 mRNA 表达，与健康对照猫的差异。 动物: 4只客户拥有的 FASS 伴嗜酸性斑块猫和5只健康对照猫。 材料和方法: 使用定量逆转录 PCR 分析 FASS 猫嗜酸性斑块皮肤和健康对照部位匹配皮肤样本中14种细胞因子和趋化因子的基因表达 (mRNA)。 结果: 嗜酸性斑块的特征为 Th2 细胞因子IL-4(p≤0.01)、IL-5(p≤0.01) 和IL-13(p≤0.01) 以及 Th2 吸引趋化因子CCL17(p≤0.05) 上调。此外，与健康样本相比，病变中 S100 钙结合蛋白A 8(p≤0.01) 以及 C-X-C Motif 趋化因子配体10(CXCL10；p≤0.01)、IL-10(p≤0.05) 和 Th17 细胞因子IL-17A(p≤0.01) 的表达更高。IL-12A、IL-31、IL-33、胸腺基质淋巴细胞生成素 (TSLP)、肿瘤坏死因子-α (TNF-α) 或 CCL5 的基因表达无差异。 结论: 结果表明，皮肤的嗜酸性斑块中具有 Th2 和 IL-17A 炎性反应的突出特征。需要进一步的更大样本转录组研究来推进我们对 FASS 不同皮肤病变发病机制的认识。.Avaliações prévias sobre as expressões genéticas de citocinas e quimiocinas [(m)RNA mensageiro] na pele de gatos alérgicos não apresentaram resultados satisfatórios na detecção da via T-helper 2(Th2), que está associada com as principais citocinas efetoras interleucina (IL)-4, IL-5 e IL-13. HIPÓTESE/OBJETIVO: Avaliar as diferenças na expressão de mRNA em placas eosinofílicas de gatos diagnosticados com síndrome atópica cutânea felina (SACF), comparado a controles saudáveis.Quatro gatos de clientes com SACF apresentando placas eosinofílicas e cinco gatos controle saudáveis. MATERIAIS E MÉTODOS: As expressões gênicas (mRNA) de 14 citocinas e quimiocinas na pele de gatos com SACF com placas eosinofílicas e nas amostras cutâneas de áreas correlatas dos gatos controle saudáveis foram analisadas utilizando análise de PCR por transcrição reversa.As placas eosinofílicas foram caracterizadas pelo aumento das citocinas Th2 IL-4 (p ≤ 0,01), IL-5 (p ≤ 0,01) e IL-13 (p ≤ 0,01) e Th2-attracting chemokine CCL17 (p ≤ 0,05). Além disto, houve maior expressão da proteína A8 ligadora de cálcio S100 (p ≤ 0,01) bem como do ligante de quimiocina C-X-C 10 (CXCL10; p ≤ 0,01), IL-10 (p ≤ 0,05) e da citocina Th17 IL-17A (p ≤ 0,01) na pele lesional comparado às amostras de pele saudável. Não houve diferenças na expressão gênica de IL-12A, IL-31, IL-33, linfopoietina estromal tímica (TSLP), fator de necrose tumoral-α (TNF-α) ou CCL5. CONCLUSÕES: Os resultados demonstram que as placas eosinofílicas apresentam respostas inflamatórias Th2 e Th-17A dominantes na pele. Estudos maiores de transcriptoma são necessários para avançar os conhecimentos acerca da patogênese de diferentes lesões cutâneas na SACF.

Transient increases in blood eosinophil counts have been observed in dupilumab clinical trials.To assess eosinophil counts and eosinophilia-related treatment-emergent adverse events (TEAEs) across 11 dupilumab clinical trials, comparing adult and adolescent patients with asthma and adult patients with chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and eosinophilic esophagitis.Eosinophil counts, rates of eosinophilia-related TEAEs or treatment-emergent eosinophilia (1,500 cells/μL), discontinuations, clinical symptoms, and efficacy in patients with asthma or CRSwNP with treatment-emergent eosinophilia are presented.Transient increases in mean eosinophil counts were observed in dupilumab-treated patients with asthma (mean range across studies at baseline: 349-370 cells/μL; week 4: 515-578 cells/μL), CRSwNP (baseline: 440-448 cells/μL; week 16: 595 cells/μL), and atopic dermatitis (baseline: 434-600 cells/μL; week 4: 410-710 cells/μL), followed by a decline starting by week 24 to baseline or lower. No increases were seen in patients with eosinophilic esophagitis (baseline: 310 cells/μL; week 4: 230 cells/μL). In dupilumab-treated patients across all studies, rates of eosinophilia TEAEs were 0% to 13.6%. Clinical symptoms associated with increased eosinophils were rare (seven of 4,666 dupilumab-treated patients, including six cases of eosinophilic granulomatosis with polyangiitis) and occurred only in patients with asthma or CRSwNP. Eosinophilia was not associated with reduced dupilumab efficacy.Transient increases in eosinophil counts with dupilumab treatment did not affect efficacy and were rarely of clinical consequence. It remains important for physicians to base judgment on individual patient history and baseline eosinophil counts and to be alert to hypereosinophilic symptoms.

Immunobiologicals have surfaced to become a new cornerstone of treatment for a wide spectrum of inflammatory disorders with an immune basis. The targets have ranged from autoimmune conditions to transplantation, and now more into atopic inflammatory disorders with primary targets of asthma and atopic dermatitis.The clinical information garnered from these studies have provided an initial snapshot on the potential adverse effects of the immunobiologicals on the ocular surface as well as providing a potential opening of their use in the treatment of various chronic ocular surface and intraocular inflammatory disorders that have previously been relegated to limited therapeutic options primarily to the broad anti-inflammatory use of glucocorticosteroids.The use of immunobiologicals provides a more directed therapeutic approach to many of the ocular inflammatory disorders, as we continue to appreciate more of their underlying immunopathophysiology of ocular surface disorder,s including ocular allergy and tear film dysfunction.

This is an abridged edition of English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence-based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of 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. In the present revised guidelines, the description about three new drugs, namely, dupilumab, delgocitinib, and baricitinib, has been added. 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.

Atopic dermatitis (AD) is a common chronic skin disease. Only relatively scant studies from Asian countries have attempted to quantify AD-associated healthcare utilization and costs by using population-based databases. This study aims to evaluate the AD-associated annual healthcare utilization and costs in Taiwan.A retrospective matched-cohort study was conducted by matching the AD cases with controls at a 1:4 (cases:controls) ratio, with the data for both the cases and controls being sourced from the 2017 National Health Insurance Research Database (NHIRD). The AD patients were stratified by disease severity based on their treatments. Differences in the regression-adjusted frequency of care and costs between the cases and controls were compared using t-tests by the severity level of AD.The incremental frequency of outpatient visits per year increased with AD severity (9.60, 11.28, and 16.23 for mild, moderate, and severe cases, respectively). However, the frequency of inpatient care and emergency room visits per year showed no consistent pattern associated with disease severity. The incremental total costs per year were NT$9,511.64, NT$9,705.20, and NT$15,762.09 for mild, moderate, and severe cases, respectively, and the outpatient and drug costs accounted for 46.65%-54.82% and 17.01%-31.20% of the total costs, respectively.AD was found to impose significant healthcare costs, with estimated total cost burdens of NT$3.61 billion in 2017, which is 0.314% of Taiwan's national health expenditure and 0.020% of Taiwan's gross domestic product.

Additional long-term treatments are needed for moderate-to-severe atopic dermatitis (AD). An ongoing, open-label, 5-year extension trial, ECZTEND (NCT03587805), assesses tralokinumab plus optional topical corticosteroids in participants from previous tralokinumab parent trials (PTs) with moderate-to-severe AD.To evaluate the safety and efficacy of up to 2 years tralokinumab treatment in a post hoc interim analysis.Safety analyses included adults from completed PTs enrolled in ECZTEND, regardless of tralokinumab exposure duration. Efficacy analyses included adult participants treated with tralokinumab in ECZTEND for ≥1 year and subgroup analyses of those on tralokinumab for 2 years (1 year from PT, 1 year in ECZTEND). Primary end point was the number of adverse events with additional efficacy end points.Participants on tralokinumab had an exposure-adjusted rate of 237.8 adverse events/100 patient-years' exposure (N = 1174) in the safety analysis set. Exposure-adjusted incidence rates of common adverse events were comparable to PTs, although at lower rates. With 2 years of tralokinumab, improvements in extent and severity of AD were sustained, with Eczema Area and Severity Index (EASI-75) in 82.5% of participants (N = 345).Possible selection bias; no placebo arm; some participants experienced treatment gaps between PTs and ECZTEND.Over 2 years, tralokinumab was well tolerated and maintained long-term control of AD signs and symptoms.

This quality improvement study describes the revision of an internet-delivered, self-guided psychological treatment for atopic dermatitis.

Skin diseases are common in children. However, the prevalence of childhood skin diseases in Japan has not been reported extensively. In this study, dermatologists conducted face-to-face examinations of primary school children over a 10-year period to determine the prevalence of each skin disease. Atopic dermatitis (AD, 12.3%) was the most common disease among first graders, followed by eczema other than AD (9.7%), molluscum contagiosum (1.9%), and verruca vulgaris (1.1%). Among sixth graders, acne vulgaris was most common (9.6%), followed by AD (8.9%), eczema other than AD (6.7%), and verruca vulgaris (3.1%). The prevalence of AD remained stable among first graders after 2010, at approximately 10%-15%, but it increased slightly among sixth graders. Of the 87 children who had AD in first grade, 51 (58.6%) were in remission in sixth grade. On the other hand, AD was diagnosed in 30 (4.5%) sixth graders who had been among the 665 children who did not have it in first grade. The more severe the symptoms were in first grade, the more likely a child was to still have AD in sixth grade, and the more severe the later symptoms tended to be. This study investigated recent trends in skin diseases in Japanese primary school children and found that the prevalence of some skin diseases differed between first and sixth graders. It was also found that children with moderate AD in first grade were more likely to be moderate in sixth grade than those with mild AD.

Dupilumab is approved for multiple type 2 inflammatory diseases. In the treatment procedure, the changes of IgE levels need further analysis. We evaluated the changes of IgE levels through meta-analysis, aiming to provide a more comprehensive result.Databases were searched to select eligible publications. After being included, study quality was assessed. The standardized mean difference (SMD) was used as an evaluation.Seven studies were included. At week 4, the level of IgE did not decrease significantly, with SMD = -0.12 (95%CI: -0.31, 0.07) (Levels of IgE can be significantly decreased in patients with dupilumab treatment. In AD patients, the efficacy was related to total dose; for patients with high IgE levels, efficacy may be better with the dose increased.

Summary Background Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis (AD). Objectives To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate-to-severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). Methods In this double-blind, randomized, placebo-controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. Results Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night-time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment-emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported. Conclusions Baricitinib 4 mg + TCS improved the signs and symptoms of moderate-to-severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate-to-severe AD. What is already known about this topic? Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients. Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate-to-severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids. What does this study add? Baricitinib combined with background low- or moderate-potency topical corticosteroids provided improvements in the signs and symptoms of moderate-to-severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A. The most common treatment-emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache. The safety profile was consistent with previous studies in patients with moderate-to-severe atopic dermatitis.

Background: Interactions between the skin barrier, immune system, and microbiome underlie the development of atopic dermatitis (AD). Objective: To investigate the skin and nasal microbiome in relation to filaggrin gene (FLG) mutations. Methods: A cross-sectional study including 77 children with difficult-to-treat AD. The entire encoding region of FLG was screened for mutations using single molecule molecular inversion probes and next-generation sequencing. Bacterial swabs from the anterior nares, lesional and nonlesional skin were analyzed using 16S rRNA sequencing. For skin samples, additional qPCR was performed for Staphylococcus aureus and Staphylococcus epidermidis. Results: The prevalence of patients with a mutation in FLG was 40%, including 10 different mutations. Analyzing bacterial swabs from all three niches showed a significant effect for both niche and FLG mutation status on the overall microbiome composition. Using a subset analysis to test the effect of FLG mutation status per niche separately did not show a significant association to the microbiome. Shannon diversity and S. aureus abundance were significantly affected by the niche, but not by the presence of an FLG mutation. Conclusions: Our results suggest only a minor role for FLG mutation status on the overall microbiome, which is rather caused by differences in the present genera than by microbe richness and evenness.

The microbiome plays an important role in the pathogenesis of allergic diseases. This review updates the reader on studies aimed at influencing allergic diseases through modulation of the gut microflora. A nonsystematic review of the literature was performed, focusing on relevant trials evaluating the effect of probiotics/prebiotics/symbiotics in the prevention and treatment of allergic disease. For each allergic disease, we were able to find not only a substantial number of clinical trials but also systematic reviews. Specific guidelines, based on systematic reviews and meta-analyses, are available for the prevention of allergic disease and for the treatment of food allergy. In each of the areas examined-allergic rhinitis, allergic asthma, atopic dermatitis, food allergy, and gastrointestinal allergies-there are substantial uncertainties in the efficacy of gut microflora modulation in prevention and treatment. At present, practicing clinicians can avail themselves of intestinal flora modulators as an adjunct in the prevention of atopic dermatitis but not of other forms of allergic diseases. Their effects on the treatment of allergic diseases remain controversial.

Dupilumab has proven safe and effective in children and adolescents with atopic dermatitis (AD) in clinical trials. However, comprehensive real-world studies in the pediatric AD population are still needed.To characterize the long-term treatment responses and adverse events of dupilumab-treated children and adolescents with AD during dermatology follow-up assessments.We reviewed electronic medical records from March 2017 to September 2021 of moderate to severe AD patients starting dupilumab at less than age 18 years. Demographics, AD scores (body surface area [BSA], Eczema Area and Severity Index [EASI], and Investigator's Global Assessment [IGA]) as well as safety data were collected.A total of 89 patients, 50 females (56.2%) and 39 males (43.8%), were included. Mean ± SD treatment duration was 1.3 ± 0.9 years. Of these, 73 had score assessments at baseline and weeks 12 to 24. Mean ± SD improvements in BSA, EASI, and IGA were 63.1% ± 29.2%, 39.6% ± 29.9%, and 59.6% ± 30.7%, respectively. All patients (n = 23) who received dupilumab for 1 year or more achieved 75% improvement in EASI and IGA 0/1, and 60.8% achieved 90% improvement in EASI. Positive history of atopy was associated with greater percent improvement in BSA at weeks 12 to 24 (P.05). Twelve patients had adverse events (13.5%), of which conjunctivitis (5.6%) and joint pain (2.2%) were most common. There were no serious adverse events.Dupilumab was well-tolerated and effective in treating pediatric and adolescent AD regardless of age, sex, race, or ethnicity.

Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis.This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to15 kg: 200 mg; bodyweight ≥15 kg to30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434.Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation.Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults.Sanofi and Regeneron Pharmaceuticals.

Atopic dermatitis (AD) is associated with eczematous lesions, pruritus, pain, and sleep disturbance, which may negatively impact mental health over time.To determine the predictors and longitudinal course of depressive symptoms in adults with AD.A prospective, dermatology practice-based study was performed (N = 695). AD signs, symptoms, and severity and patient health questionnaire-9 (PHQ-9) were assessed.At baseline, of the 695 participants, 454 (65.32%) had minimal, 139 (20.00%) had mild, 57 (8.20%) had moderate, 27 (3.88%) had moderately severe, and 8 (2.59%) had severe depression. Most had fluctuating levels of depressive symptoms. Feeling bad, thoughts of self-harm, difficulty concentrating, and slow movement were most persistent. Predictors of persistent depression included older age, non-White race, male sex, public or no insurance, more severe itch, skin pain, facial erythema, nipple eczema, sleep disturbance, and presence of pityriasis alba.Single center study.Depressive symptoms are closely related to and fluctuate with AD severity over time. Improved control of AD signs and symptoms, particularly itch, may secondarily improve mental health.

Jin Kyeong Choi1 &ast;, Jun-Young Park2 &ast;, Soyoung Lee,3 Young-Ae Choi,4 Song Kwon,2 Min Jun Shin,2,5 Hui-Suk Yun,6 Yong Hyun Jang,7 Jinjoo Kang,4 Namkyung Kim,4 Dongwoo Khang,2,5,8 Sang-Hyun Kim4 1Department of Immunology, Jeonbuk National University Medical School, Jeonju, 54907, Republic of Korea1; 2Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea; 3Immunoregulatory Materials Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea; 4CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea; 5Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21999, Republic of Korea; 6Powder & Ceramics Division, Korea Institute of Materials Science, Changwon, 51508, Republic of Korea; 7Department of Dermatology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea; 8Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Dongwoo Khang, Department of Physiology, School of Medicine, Gachon University, Incheon, 21999, Republic of Korea, Tel +82 32 899 6515, Email dkhang@gachon.ac.kr Sang-Hyun Kim, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea, Tel +82 53 420 4838, Email shkim72@knu.ac.krPurpose: The protein corona surrounding nanoparticles has attracted considerable attention as it induces subsequent inflammatory responses. Although mesoporous silica nanoparticles (MSN) are commonly used in medicines, cosmetics, and packaging, the inflammatory effects of the MSN protein corona on the cutaneous system have not been investigated till date.Methods: We examined the greater plasma protein adsorption on MSN leads to serious inflammatory reactions in Dermatophagoides farinae extract (DFE)-induced mouse atopic dermatitis (AD)-like skin inflammation because of increased uptake by keratinocytes.Results: We compare the AD lesions induced by MSN and colloidal (non-porous) silica nanoparticles (CSN), which exhibit different pore architectures but similar dimensions and surface chemistry. MSN-corona treatment of severe skin inflammation in a DFE-induced in vivo AD model greatly increases mouse ear epidermal thickness and infiltration of immune cells compared with the CSN-corona treatment. Moreover, MSN-corona significantly increase AD-specific immunoglobulins, serum histamine, and Th1/Th2/Th17 cytokines in the ear and lymph nodes. MSN-corona induce more severe cutaneous inflammation than CSN by significantly decreasing claudin-1 expression.Conclusion: This study demonstrates the novel impact of the MSN protein corona in inducing inflammatory responses through claudin-1 downregulation and suggests useful clinical guidelines for MSN application in cosmetics and drug delivery systems.Graphical Abstract: Keywords: protein Corona, atopic dermatitis, mesoporous silica, colloidal silica, claudin-1, immunotoxicity

Allergic diseases exclusively affect tissues that face environmental challenges and harbor endogenous bacterial microbiota. The microbes inhabiting the affected tissues may not be mere bystanders in this process but actively affect the risk of allergic sensitization, disease development, and exacerbation or abatement of symptoms. Experimental evidence provides several plausible means by which the human microbiota could influence the development of allergic diseases including, but not limited to, effects on antigen presentation and induction of tolerance and allergen permeation by endorsing or disrupting epithelial barrier integrity. Epidemiological evidence attests to the significance of age-appropriate, nonpathogenic microbiota development in skin, gastrointestinal tract, and airways for protection against allergic disease development. Thus, there exist potential targets for preventive actions either in the prenatal or postnatal period. These could include maternal dietary interventions, antibiotic stewardship for both the mother and infant, reducing elective cesarean deliveries, and understanding barriers to breastfeeding and timing of food diversification. In here, we will review the current understanding and evidence of allergy-associated human microbiota patterns, their role in the development of allergic diseases, and how we could harness these associations to our benefit against allergies.

Atopic dermatitis (AD) is an inflammatory skin condition with dry, scaly, and intensely itchy skin. Treatment failure is the result of poor adherence.In this study, we assessed the impact of an internet-based survey on adherence to topical crisaborole 2% ointment in patients with mild AD.Participants were randomized to the intervention or control group. The intervention group received weekly email surveys regarding adherence for 6 weeks, then monthly for 12 months. All participants came in for 5 visits over the year.Twenty-eight subjects were recruited for the study (n=19 adults, n=9 pediatrics). Adherence for adults that remained in study (n=6) was 60%. Adherence of the adult control and intervention groups were 49% and 45%, respectively (Pgt;0.05). Adherence for pediatric participants that remained in study (n=2) was 6%. The adherence of the pediatric control and intervention groups were 27% and 29%, respectively (Pgt;0.05).Medication adherence was low. The survey intervention did not improve adherence. However, more participants in the intervention group completed the study than in the control group of adults. Regular communication from the provider may help patients feel supported and continue treatment.gov identifier: NCT03250663 J Drugs Dermatol. 2022;21(10):1043-1048. doi:10.36849/JDD.6280.

Background: Atopic dermatitis (AD) may develop by 6 months of age, and its severity assessment is essential for appropriate treatments. Scoring Atopic Dermatitis (SCORAD) is suggested to evaluate the severity of AD but is cumbersome for routine clinical use. The serum thymus and activation-regulated chemokine (TARC) is used as a marker of AD severity. However, the normal range of the TARC levels varies by age, and its usefulness for the evaluation of AD severity has not been established in patients ages < 6 months. Here, we evaluated the correlation between serum TARC levels and SCORAD scores in early infancy and sought the optimal cutoff level to indicate AD severity. Methods: The subjects were 35 patients with AD (16 girls and 19 boys; 3‐5 months of age) who visited our clinic between April 2015 and March 2017. All the patients were physically examined by a board-certified allergist. The AD severity was determined by using the SCORAD, together with serum levels of TARC, total immunoglobulin E (IgE), lactate dehydrogenase, and peripheral eosinophil counts. Receiver operating characteristic curve analysis was performed to determine the cutoff levels of serum TARC to indicate AD severity. Results: Significant correlations were observed between SCORAD scores and the serum TARC levels, peripheral eosinophil counts, and serum IgE levels (r = 0.640, r = 0.723, r = 0.533, respectively). The optimal cutoff levels of serum TARC to indicate mild and severe AD were 6192 pg/mL (AUC = 0.833), respectively. Conclusion: Although this study had limitations, we suggest that serum TARC is useful as a marker of AD severity in patients

To inform readers of the current and forthcoming skin barrier interventions that have clinically relevant implications in the prevention of allergic sensitization and atopic diseases.Peer-reviewed journal articles indexed on PubMed and clinical trials referenced on clinicaltrials.gov were analyzed.Literature searches from PubMed and clinicaltrials.gov were performed using combinations of the following search terms: prevention, allergy, atopy, skin, cutaneous, microbiome, microbiota, Staphylococcus aureus, atopic dermatitis, eczema, food allergy, and asthma.The skin barrier represents an entry point for allergic sensitization and TThe skin barrier is a promising target for prevention of allergic disease, though clinical trial results thus far have been mixed, at best.

House dust mite is a common cause of atopic dermatitis (AD) both in humans and dogs. Detection of serum IgE to allergens is commonly used to diagnose allergic diseases. However, false-positive reactions due to cross-reactivity and non-specific reactivity may lead to misdiagnosis. We compared human and canine IgE reactivities to mite component allergens. Canine IgE-reactive components of Dermatophagoides farinae and Tyrophagus putrescentiae were identified by tandem mass spectrometry. Recombinant proteins were produced and IgE reactivities to component allergens were assessed by ELISA and inhibition assays using sera from AD patients and dogs. Canine IgE-reactive proteins (Der f 1, Der f 11, Tyr p 4, Tyr p 8, Tyr p 11, Tyr p 28) were identified by proteome analysis. Most patients were sensitized to Der f 1 (93.3%) and Der f 2 (86.7%). Dogs showed high sensitization to Der f 2 (94.1%) and Der f 18 (84.6%). Both patients and dogs showed low IgE binding frequency to Tyr p 8, 43.3% and 4%, respectively. The ELISA inhibition study indicated that canine IgE reactivity to T. putrescentiae is mostly due to non-specific reaction and cross-reaction with D. farinae. Different IgE sensitization patterns were shown between allergic humans and dogs with AD, especially to Der f 18, for the first time in Korea. Furthermore, non-specific canine IgE reactivity to storage mite indicates the possibility of misdiagnoses. Standardizations focused on the major canine allergen content of extracts should be developed. This will allow precision diagnosis and individuated treatments for each patient and atopic dog.

The pathophysiology of atopic dermatitis (AD) is multifactorial, influenced by genetics, skin barrier dysfunction, and environmental stressors. There is a lack of research comparing the etiologies and pathologic mechanisms accounting for differences in facial vs body eczema.To explore reasons why facial eczema may differ from body eczema.There are key differences in the environments of the face and body that may lead to AD exacerbation. These include differences in the skin microbiome, sebaceous glands concentration, and levels of natural moisturizing factor. The face is exposed to more environmental stress compared with the rest of the body. These stresses include aeroallergens, ultraviolet radiation, and cosmetic products. Management of facial eczema also differs from that of body eczema due to the avoidance of high potency topical steroids on the face. Topical steroids increase microbiome diversity, and lack of topical steroid use on the face can lead to decreased microbiome diversity and increased AD severity.Facial and body eczema differ due to differences seen in anatomical structure and environmental exposures. These differences should be further researched and used in the management of facial vs body eczema and can also be used in the development of new AD treatments. J Drugs Dermatol. 2022;21(10): 1119-1123. doi:10.36849/JDD.6354.

Many risk factors such as atopic dermatitis (AD) have shown to associate with hand eczema (HE). However, studies concerning other atopic diseases, parental or longitudinal risk factors of HE are scarce.To examine the association between HE and atopic diseases, parental factors, environmental factors (keeping animals, exposure to moulds) and lifestyle factors (obesity, tobacco smoking, alcohol consumption and physical activity) at population level.Subjects belonging to the Northern Finland Birth Cohort 1966 Study (NFBC1966) (n = 6830) answered a comprehensive health questionnaire. The data was completed with parental information.HE was reported in 900 (13.3%) individuals. All atopic diseases, parental allergy, female gender and obesity increased the risk of HE whereas physical activity decreased the risk of HE. A statistically significant association was not found between HE and tobacco smoking or alcohol consumption.All atopic diseases, not only AD, seem to have influence on the presence of HE. In addition, parental and environmental factors associated with HE.

Our objective was to examine the prevalence and predictors of delayed medical care due to transportation barriers among children with atopic dermatitis (AD) living in the United States (US). We analyzed data from the 1998-2018 National Health Interview Survey, a nationally representative survey of US households. In 2018, transport-delayed care was reported for 3.4% of US children with AD, representing approximately 279,000 children annually given the National Health Interview Survey's weighted survey design, and was more common among patients of lower socioeconomic status. Targeted interventions aimed at reducing transportation barriers to healthcare among at-risk AD patients may reduce health disparities related to AD.

Autoimmune inflammatory diseases are primarily characterized by deregulated expression of cytokines, which drive pathogenesis of these diseases. A number of approved and experimental therapies utilize monoclonal antibodies against cytokine proteins. Cytokines can be classified into different families including the interleukins, which are secreted and act on leukocytes, the tumor necrosis factor (TNF) family, as well as chemokine proteins. In this review article, we focus on the interleukin family of cytokines, of which 39 members have been identified to this date. We outline the role of each of these interleukins in the immune system, and various dermatological inflammatory diseases with a focused discussion on the pathogenesis of psoriasis and atopic dermatitis. In addition, we describe the roles of various interleukins in psychiatric, cardiovascular, and gastrointestinal comorbidities. Finally, we review clinical efficacy and safety data from emerging late-phase anti-interleukin therapies under development for psoriasis and atopic dermatitis. Collectively, additional fundamental and clinical research remains necessary to fully elucidate the roles of various interleukin proteins in the pathogenesis of inflammatory dermatologic diseases, and treatment outcomes in patients.

We evaluated the efficacy and safety of upadacitinib, janus kinase 1 inhibitor for atopic dermatitis (AD) in real-world practice. From September 2021 to March 2022, 31 patients with moderate-to-severe AD, aged ≥12 years were treated with oral upadacitinib 15 mg/day plus topical corticosteroids. Upadacitinib reduced clinical indexes compared to baseline levels: percent reduction at week 4 and 12 (median) was 73.6% and 85.6% in eczema area and severity index (EASI); 81.3% and 81.3% in AD control tool (ADCT); and 70% and 75% in peak pruritus numerical rating score (PP-NRS), respectively. The achievement rate of EASI 75 was 51.6% and 67.7% at week 4 and 12, respectively. Upadacitinib reduced serum lactate dehydrogenase and total eosinophil count (TEC) at week 4 and 12, and thymus and activation-regulated chemokine and immunoglobulin E at week 4, compared to baseline levels. Percent reduction of TEC was correlated with that of EASI at week 4 and 12. Baseline TEC was positively correlated with the percent reduction of EASI at week 4. Percent reduction of EASI in female patients was higher than that in male patients at week 4 and 12. Linear multivariate regression analyses revealed that high percent reduction of EASI at week 4 or 12 was associated with high baseline TEC or female gender, respectively. There were no serious treatment-emergent adverse events. Adverse events include acne (5%), elevation of creatine phosphokinase (9.7%), herpes zoster (1%), and AD (1%). Upadacitinib plus topical corticosteroids for patients with AD in the real-world practice was well tolerated and gave therapeutic effects comparable with those in previous clinical trials. The ADCT and PP-NRS rapidly reduced at week 4 while EASI gradually reduced until week 12. The TEC might act both as a predictive factor of response at week 4 and as a biomarker reflecting therapeutic effects in upadacitinib treatment for AD.

Air pollution is strongly associated with asthma, but has not been determined to induce new-onset asthma development in children with atopic dermatitis (AD).To assess whether prenatal/postnatal exposure to air pollutants triggers new-onset asthma development in children with AD.Retrospective cohort study.Data of patientsage 18 years diagnosed with eczema or AD between 2009 and 2019 were extracted from the multicenter Kaohsiung Medical University Hospital Research Database. Patients diagnosed with new-onset asthma were in the asthma group and patients without asthma history were in the non-asthma group.The monthly average concentration of air pollutants for 1, 3, and 5 years before the index date, and 3, 6, and 9 months prenatally were analyzed and further stratified by age, immunoglobulin (Ig) E, and the percentage of eosinophil and eosinophil cationic protein (ECP).Postnatal exposure to airborne particulate matter (PMPrenatal and postnatal exposure to air pollution have an association with asthma development in AD patients.

Background Studies on the association between severity of atopic dermatitis (AD) and lifestyle factors in adults have not been conducted in the Netherlands to date. Aim To explore the association between moderate to severe AD and lifestyle factors in adults in the Dutch general population. Methods We conducted this cross-sectional study within the Lifelines Cohort Study by sending a digital AD questionnaire to 135 950 adults in 2020. We extracted data on lifestyle factors from baseline, collected between 2006 and 2013. We analysed the association between lifestyle factors and presence of AD of any severity and of moderate to severe AD, using binary logistic regression and linear regression models. Results We enrolled 56 896 participants (mean age 55.8 years, 39.7% males). The lifetime prevalence of self-reported physician-diagnosed AD was 9.1%, and the point prevalence of any AD and of moderate to severe AD was 3.3% and 2.3%, respectively. We found that moderate to severe AD was associated with smoking habit of > 15 pack-years, alcohol consumption of > 2 drinks per day, chronic stress, Class I obesity, and both shorter and longer sleep duration. Moreover, we found dose–response associations with increases in smoking pack-years and level of chronic stress. We observed no associations with abdominal obesity, physical activity, diet quality or a vegetarian/vegan diet. Conclusion We found associations between moderate to severe AD and some modifiable lifestyle factors. Our findings indicate that more screening and counselling for lifestyle factors, particularly smoking, alcohol use, stress, obesity and sleep disturbances, appears warranted in patients with moderate to severe AD. Further longitudinal studies are required to better characterize the direction of these associations and to develop strategies for prevention.

Zhenxing Su,1 Yaqin Kang2 1Dermatology, First Hospital of Shanxi Medical University, Taiyuan City, People’s Republic of China; 2Pediatrics, First Hospital of Shanxi Medical University, Taiyuan City, People’s Republic of ChinaCorrespondence: Zhenxing Su, Dermatology, First Hospital of Shanxi Medical University, No. 85, Jiefang South Road, Yingze District, Taiyuan City, People’s Republic of China, Email zhenxingsu@outlook.comObjective: Infantile eczema (IE), a common pediatric allergic skin disease caused by multiple inherent and external factors, is common in infants and young children, with skin lesions and itching as the main clinical manifestations. At present, its pathological mechanism has not been thoroughly clarified, but scholars believe that it is related to the joint action of various internal and external factors. This research aims to investigate the influences of bifid triple viable capsules plus cetirizine (CTZ) on gut microbiota (GMB) and immunity in children with eczema.Methods: The complete clinical data of 162 cases of IE presented between July 2019 and July 2020 to the First Hospital of Shanxi Medical University were retrospectively analyzed. Children treated by CTZ alone were assigned to the control group (n = 81) and those by CTZ plus bifid triple viable capsules were included in the observation group (n = 81). Therapeutic efficacy, adverse reactions (ARs), disease recurrence, as well as changes in GMB, inflammatory factors (IFs) and immunoglobulins (Igs) were observed.Results: The observation group was observed with a higher overall response rate and increased fecal Lactobacillus, Escherichia coli (E. coli) and Bifidobacterium counts after treatment versus the control group. After treatment, reduced IgG and IgM, as well as IFs, were found in both groups, with lower levels in the observation group. A lower incidence of ARs was determined in the observation group.Conclusion: With high efficacy for the treatment of IE, bifid triple viable capsules plus CTZ can validly regulate the GMB of children, improve their immune function and clinical symptoms, and reduce the disease recurrence rate, which is worthy of clinical promotion.Keywords: bifid triple viable capsules, cetirizine, eczema, gut microbiota, immune function