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Query Topic: Atopic dermatitis

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common chronic inflammatory skin(45)

[Janus kinase inhibitors for the treatment of atopic dermatitis-evaluation of current data and practical experience].
Atopic dermatitis is a common chronic inflammatory skin disease and has a major impact on patient's quality of life. Janus kinase inhibitors were recently approved for the treatment of atopic dermatitis. To summarize current data on efficacy and safety of Janus kinase inhibitors for the treatment of atopic dermatitis as well as guidelines for the use in clinical practice. Summary and assessment of currently available data. Three Janus kinase inhibitors are approved for the treatment of moderate to severe atopic dermatitis: baricitinib, upadacitinib and abrocitinib. Clinical trials and first real-life data demonstrate rapid and strong reduction of pruritus and clinical signs of atopic dermatitis as well as improvement of patient's quality of life. The safety profile is favorable, although data on long-term safety especially for the treatment of atopic dermatitis patients are still lacking. Janus kinase inhibitors enrich the therapeutic portfolio for the treatment of atopic dermatitis. When carefully taking into consideration contraindications, side effects, and necessary laboratory controls, they represent a highly effective and safe treatment option for affected patients. HINTERGRUND: Die atopische Dermatitis ist eine häufige chronisch entzündliche Hauterkrankung, die mit erheblichem Leidensdruck einhergeht. Januskinaseinhibitoren sind seit Kurzem für die Therapie der atopischen Dermatitis verfügbar. Es erfolgen eine Zusammenfassung der bisherigen Daten zur Wirksamkeit und Sicherheit von Januskinaseinhibitoren zur Therapie der atopischen Dermatitis sowie Darstellung praktischer Hinweise zum klinischen Einsatz. Es werden eine Zusammenfassung und Bewertung der aktuell verfügbaren Datenlage gegeben. Drei Januskinaseinhibitoren sind zur Therapie der mittelschweren bis schweren atopischen Dermatitis zugelassen: Baricitinib, Upadacitinib und Abrocitinib. In den Zulassungsstudien und ersten Real-Life-Erfahrungen wurden eine starke und schnelle Reduktion des Juckreizes und der klinischen Zeichen der atopischen Dermatitis sowie positive Effekte auf die Lebensqualität betroffener Personen demonstriert. Das aktuelle Sicherheitsprofil zeigt sich günstig, wobei jedoch Langzeitsicherheitsdaten speziell für den Einsatz bei der atopischen Dermatitis aktuell noch nicht verfügbar sind. Januskinaseinhibitoren bereichern das therapeutische Spektrum bei der Behandlung der atopischen Dermatitis. Unter Beachtung der Kontraindikationen, Nebenwirkungen und notwendigen Laboruntersuchungen stellen sie eine hocheffektive und sichere Therapieoption für betroffene Patienten dar.
Publication Date: 2022-05-25
Journal: Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete

inflammatory skin disease(249)

Managing Atopic Dermatitis with Lebrikizumab - The Evidence to Date.
Atopic dermatitis is a prevalent, inflammatory skin disease that presents with an eczematous, itchy rash. As of late, there have been many emerging monoclonal antibody inhibitor and small molecule therapies that have changed the course of eczema treatment. One of the treatments in the pipeline for atopic dermatitis is interleukin 13 monoclonal antibody inhibitor, lebrikizumab. As interleukin 13 has been identified as a pro-inflammatory cytokine in the immunological cascade of eczema, it is thought that lebrikizumab can be a great treatment choice for patients with atopic dermatitis. Lebrikizumab is currently being investigated in several studies. Thus far, lebrikizumab for the treatment of eczema has been found to be efficacious; in particular, a rapid response of pruritus improvement has been demonstrated in as early as 2 days. Additionally, it is well tolerated and has an acceptable safety profile, with reports suggesting that are decreased risks of infection when compared to dupilumab. In this review, we aim to summarize the current understanding of lebrikizumab in terms of the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, efficacy and safety, and drug indications.
Publication Date: 2022-06-16
Journal: Clinical, cosmetic and investigational dermatology

moderate-to-severe atopic dermatitis(171)

Comparative efficacy and safety of abrocitinib, baricitinib and upadacitinib for moderate-to-severe atopic dermatitis: a network meta-analysis.
Janus kinase (JAK) inhibitors have become promising treatments for atopic dermatitis (AD), however no study directly comparing JAK inhibitors with each other has been reported. We conducted this network meta-analysis to determine the comparative efficacy and safety of three common oral JAK inhibitors including abrocitinib, baricitinib and upadacitinib for moderate-to-severe AD. We firstly identified eligible studies from published meta-analyses, then we searched PubMed to obtain additional studies published between February and July 2021. Clinical efficacy and safety were evaluated as primary and secondary outcome respectively. After extracting data and assessing methodological quality, we utilized ADDIS 1.4 software to conduct pair-wise and network meta-analyses. Ten eligible studies were included in the final analysis. Pooled results that abrocitinib, baricitinib and upadacitinib obtained higher investigator global assessment (IGA), eczema area and severity index (EASI) response, however abrocitinib and upadacitinib caused more treatment-emergent adverse events (TEAEs) regardless of doses, compared with placebo. Network meta-analyses revealed that upadacitinib 30mg was superior to all regimens and upadacitinib 15mg was better than remaining regimens except for abrocitinib 200mg in terms of IGA and EASI response. Moreover, abrocitinib 200mg was superior to abrocitinib 100mg, baricitinib 1mg, 2mg, and 4mg for clinical efficacy. However, upadacitinib 30mg caused more TEAEs. Abrocitinib, baricitinib and upadacitinib were consistently effective therapies in adult and adolescent patients with AD; however, upadacitinib 30mg may be the optimal option in short-term studies. More efforts should be done to reduce the risk of TEAEs caused by upadacitinib 30mg. This article is protected by copyright. All rights reserved.
Publication Date: 2022-06-16
Journal: Dermatologic therapy

atopic dermatitis patients(128)

Characterizing real world safety profile of oral Janus kinase inhibitors among adult atopic dermatitis patients: evidence transporting from the rheumatoid arthritis population.
To address potential safety concerns of Janus Kinase Inhibitors (JAK-Is), we characterized their safety profile in the atopic dermatitis (AD) patient population. In this retrospective observational study, we used propensity score-based methods and a Poisson modeling framework to estimate the incidence of health outcomes of interest (HOI) for the AD patient. To that end, two mutually exclusive cohorts were created using a real world data resource: a rheumatoid arthritis (RA) cohort, where we directly quantify the safety risk of JAK-Is on HOIs, and an AD cohort, that comprises the target population of interest and to whom we transport the results obtained from the RA cohort. The RA cohort included all adults who filled at least one prescription for a JAK-I (tofacitinib, baricitinib, or upadacitinib) between January 1, 2017 and January 31, 2020. The AD cohort consisted of all adults diagnosed with AD during the same period. We first estimated the incidence rate of each HOI in the RA cohort, and then transported the results to the AD population. The RA and AD cohorts included 5,296 and 261,855 patients, respectively. On average, patients in the AD cohort were younger, more often male, more likely to be Asian, and had higher household income. They also had a lower prevalence of several comorbid conditions including hypertension, chronic kidney disease, obesity, and depression. Overall, the transported incidence rates of the HOIs to the AD cohort were lower than those obtained in the RA cohort by 13%-50%. We applied transportability methods to characterize the risk of the HOIs in the AD population and found absolute risks higher than that of the general population. Future work is needed to validate these conclusions in comparable populations.
Publication Date: 2022-06-15
Journal: Current medical research and opinion

scoring atopic dermatitis(98)

Therapeutic Potential of Tralokinumab in the Treatment of Atopic Dermatitis: A Review on the Emerging Clinical Data.
Atopic dermatitis (AD) is a chronic inflammatory skin disease that greatly impacts patient quality of life. Type 2 cytokine interleukin (IL)-13 is integral to the pathogenesis of AD. Tralokinumab is a fully human IgG4 monoclonal antibody that specifically targets IL-13, preventing downstream signaling of inflammatory pathways that may contribute to AD. Tralokinumab was US Food and Drug administration (FDA) recently approved for the treatment of moderate to severe AD on December 28, 2021. In our review, we will explore the efficacy and adverse effects (AEs) of tralokinumab for the treatment of patients with moderate to severe AD. A PubMed search for key articles on the emerging clinical data of tralokinumab was performed. Six randomized controlled trials of tralokinumab identified improvements in disease severity measures, including Investigator's Global Assessment (IGA) scores and Eczema Area Severity Index 75 (EASI75) scores. Four of these studies demonstrated improvements in quality of life measures with tralokinumab, including pruritus scores, sleep interference scores, Dermatology Life Quality Index, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure, and The Short Form 36 Health Survey (SF-36v2) scores. One study identified a similar immune response in patients taking tralokinumab to those taking the Tdap and meningococcal vaccines. Upper respiratory infection, conjunctivitis, and headaches were the most common adverse events. The varying criteria to assess changes in AD disease severity across different studies is a limitation of this review. Tralokinumab is another promising biologic option for the treatment of moderate to severe AD, which may reduce disease burden and improve patient quality of life.
Publication Date: 2022-06-11
Journal: Clinical, cosmetic and investigational dermatology

disease atopic dermatitis(63)

Symbiotic microorganisms: prospects for treating atopic dermatitis.
Atopic dermatitis (AD) is a common chronic recurrent inflammatory skin disease. The pathogenesis is unclear but may be related to genetic, immune, and environmental factors and abnormal skin barrier function. Symbiotic microorganisms in the gut and on the skin are associated with AD occurrence. We discuss the metabolism and distribution of intestinal and skin flora and review their relationship with AD, summarizing the recent applications of intestinal and skin flora in AD treatment, and discussing the prospect of research on these two human microbiota systems and their influence on AD treatment. The PubMed database was searched to identify relevant publications from 1949 to 2020 for the bibliometric analysis of atopic dermatitis and symbiotic microorganisms. Many studies have suggested a potential contribution of microbes in the intestine and on the skin to AD. Bacteria living on the skin can aggravate AD by secreting numerous virulence factors. Moreover, the metabolism of intestinal flora can influence AD occurrence and development via the circulatory system. Current evidence suggests that by regulating intestinal and skin flora, AD can be treated and prevented.
Publication Date: 2022-06-14
Journal: Expert opinion on biological therapy

canine atopic dermatitis(61)

The effect of a mixed cannabidiol and cannabidiolic acid based oil on client-owned dogs with atopic dermatitis.
Cannabidiol (CBD) and cannabidiolic acid (CBDA) are reported to have antinociceptive, immunomodulatory and anti-inflammatory actions. To determine if CBD/CBDA is an effective therapy for canine atopic dermatitis (cAD). Thirty-two privately owned dogs with cAD. Prospective, randomised, double-blinded, placebo-controlled study. Concurrent therapies were allowed if remained unchanged. Dogs were randomly assigned to receive either 2 mg/kg of an equal mix of CBD/CBDA (n = 17) or placebo for 4 weeks. On Day (D)0, D14 and D28, Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) scores were determined by investigators and owners, respectively. Complete blood count, serum biochemistry profiles and cytokine bioassays were performed on serum collected on D0 and D28. There was no significant difference in CADESI-04 from D0 to D14 (p  = 0.42) or D28 (p  = 0.51) in either group. pVAS scores were significantly lower for the treatment group at D14 (p  = 0.04) and D28 (p  = 0.01) and a significant change in pVAS from baseline was seen at D14 (p  = 0.04) and not D28 (p  = 0.054) between groups. There was no significant difference in serum levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein - 1, IL-31 or IL-34 between groups at D0 or D28. Elevated alkaline phosphatase was observed in four of 17 treatment group dogs. CBD/CBDA as an adjunct therapy decreased pruritus, and not skin lesions associated with cAD in dogs. Contexte - Le cannabidiol (CBD) et l'acide cannabidiolique (CBDA) auraient des actions antinociceptives, immunomodulatrices et anti-inflammatoires. Objectifs - Déterminer si le CBD/CBDA est une thérapie efficace pour la dermatite atopique canine (cAD). Animaux - Trente-deux chiens de propriétaires privés atteints de cAD Matériels et méthodes - Étude prospective, randomisée, en double aveugle, contrôlée versus placebo. Les thérapies concomitantes étaient autorisées si elles restaient inchangées. Les chiens ont été répartis au hasard pour recevoir soit 2 mg/kg d'un mélange égal de CBD/CBDA (n = 17) soit un placebo pendant quatre semaines. Aux jours (J)0, J14 et J28, les scores Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) et prurit Visual Analog Scale (pVAS) ont été déterminés respectivement par les investigateurs et les propriétaires. Une formule sanguine complète, des profils biochimiques sériques et des dosages biologiques des cytokines ont été réalisés sur le sérum prélevé à J0 et J28. Résultats - Il n'y avait pas de différence significative au CADESI-04 de J0 à J14 (P = 0,42) ou J28 (P = 0,51) dans les deux groupes. Les scores pVAS étaient significativement inférieurs pour le groupe de traitement à J14 (P = 0,04) et J28 (P = 0,01) et un changement significatif de la pVAS par rapport à l'inclusion a été observé à J14 (P = 0,04) et non à J28 (P = 0,054) entre les groupes. Il n'y avait pas de différence significative dans les taux sériques d'interleukine (IL)-6, IL-8, protéine chimiotactique des monocytes-1, IL-31 ou IL-34 entre les groupes à J0 ou J28. Une phosphatase alcaline élevée a été observée chez quatre des 17 chiens du groupe de traitement. Conclusions et pertinence clinique - Le CBD/CBDA en tant que traitement d'appoint a diminué le prurit, et non les lésions cutanées associées à la DAC chez les chiens. Introducción- se ha descrito que el cannabidiol (CBD) y el ácido cannabidiólico (CBDA) tienen acciones antinociceptivas, inmunomoduladoras y antiinflamatorias. Objetivos- determinar si el CBD/CBDA es una terapia eficaz para la dermatitis atópica canina (CAD). Animales - Treinta y dos perros de propietarios privados con cAD Materiales y métodos - Estudio prospectivo, aleatorio, doble ciego, controlado con placebo. Se permitieron terapias concurrentes si permanecían sin cambios. Los perros fueron asignados al azar para recibir 2 mg/kg de una mezcla igual de CBD/CBDA (n = 17) o placebo durante cuatro semanas. En el día (D)0, D14 y D28, los investigadores y los propietarios determinaron las puntuaciones del índice de extensión y gravedad de la dermatitis atópica canina, cuarta revisión (CADESI-04) y la escala análoga visual de prurito (pVAS), respectivamente. Se realizaron hemogramas completos, perfiles bioquímicos séricos y bioensayos de citoquinas en suero obtenido en D0 y D28. Resultados- no hubo diferencias significativas en CADESI-04 de D0 a D14 (P = 0,42) o D28 (P = 0,51) en ninguno de los grupos. Las puntuaciones de pVAS fueron significativamente más bajas para el grupo de tratamiento en D14 (P = 0.04) y D28 (P = 0.01) y se observó un cambio significativo en pVAS desde el inicio en D14 (P = 0.04) y no en D28 (P = 0.054) entre grupos . No hubo diferencias significativas en los niveles séricos de interleuquina (IL)-6, IL-8, proteína quimioatrayente de monocitos-1, IL-31 o IL-34 entre los grupos en D0 o D28. Se observó fosfatasa alcalina elevada en cuatro de los 17 perros del grupo de tratamiento. Conclusiones y relevancia clínica- CBD/CBDA como terapia adjunta disminuyó el prurito y no las lesiones cutáneas asociadas con la CAD en perros. Hintergrund - Eine antinozizeptive, immunmodulatorische und entzündungshemmende Wirkung von Cannabidiol (CBD) und Cannabidiolsäure (CBDA) ist beschrieben. Ziele - Es sollte festgestellt werden, ob CBA/CBDA eine wirksame Therapie für die atopische Dermatitis (cAD) des Hundes darstellt. Materialien und Methoden - Es handelt sich um eine prospektive, randomisierte, doppelblinde, Plazebo-kontrollierte Studie. Begleitende Behandlungen waren erlaubt, sofern sie nicht verändert wurden. Die Hunde wurden zufällig eingeteilt, um entweder 2 mg/kg einer gleichen Mischung von CBD/CBDA (n = 17) oder Plazebo vier Wochen lang zu erhalten. Am Tag (D) 0, D14 und D28 wurden mittels Canine Atopic Dermatitis Extent and Severity Index, 4 背景 - カンナビジオール (CBD) およびカンナビジオール酸 (CBDA) は、抗侵害受容作用、免疫調節作用、抗炎症作用を有すると報告されている。 目的 - 本研究の目的は、CBD/CBDAが犬アトピー性皮膚炎 (cAD) に対して有効な治療法であるかどうかを明らかにすることであった。 被検動物 - cAD を有するオーナー所有犬 32 頭 材料と方法 - 前向き無作為化二重盲検プラセボ対照試験。併用療法は、変化がない場合は許可された。犬はCBD/CBDAの等量混合物2mg/kg(n = 17) またはプラセボのいずれかを4週間投与するよう無作為に割り当てられた。D0、D14およびD28に、犬アトピー性皮膚炎の程度および重症度指数 (CADESI-04)、痒みのビジュアルアナログスケール (pVAS) スコアをそれぞれ調査員、飼い主が決定した。D0とD28に採取した血清について、全血球数、血清生化学プロファイル、サイトカイン・バイオアッセイ法を実施した。 結果 - CADESI-04のD0からD14(P = 0.42) またはD28(P = 0.51) まで、いずれの群でも有意差はなかった。pVASスコアはD14(P = 0.04) およびD28(P = 0.01) で治療群に有意に低く、ベースラインからのpVASの有意変化はD14(P = 0.04) で見られ、D28(P = 0.054) では認められなかった。インターロイキン (IL)-6、IL-8、単球走化性タンパク質-1、IL-31、IL-34の血清レベルには、D0とD28で群間に有意な差はなかった。アルカリフォスファターゼの上昇が17頭中4頭で観察された。 結論および臨床的意義 - CBD/CBDAを補助療法として投与することで、cADに関連する皮膚病変ではなく、犬の痒みを減少させることができた。. 背景-据报告, 大麻二醇(CBD)和大麻二酚酸(CBDA)具有镇痛、免疫调节和抗炎作用。 目的-确定CBD/CBDA是否是犬特应性皮炎(cAD)的有效疗法。 动物-32只患有cAD的私家犬。 材料和方法-前瞻性、随机、双盲、安慰剂对照研究。如果保持不变, 允许合并治疗。将犬随机分配至2 mg/kg CBD/CBDA等混合物组(n = 17)或安慰剂组, 持续4周。在第(D)0天、第14天和第28天, 由研究者和犬主人分别测定犬特应性皮炎程度和严重指数、第4版(CADESI-04)和瘙痒视觉模拟量表(pVAS)评分。对D0和D28采集的血清进行全血细胞计数、血清生化特征和细胞因子生物测定。 结果-两组中从D0至D14(P = 0.42)或D28(P = 0.51)的CADESI-04无显著差异。治疗组在D14(P = 0.04)和D28(P = 0.01)的pVAS评分显著降低, 在D14(P = 0.04)而非D28(P = 0.01)观察到pVAS相对于基线的显著变化.054) 。D0或D28时, 组间血清白细胞介素(IL)-6、IL-8、单核细胞趋化蛋白-1、IL-31或IL-34水平无显著差异。在17只治疗组犬的4只中观察到碱性磷酸酶升高。 结论和临床相关性-CBD/CBDA作为辅助治疗减少了犬中的瘙痒, 而对cAD相关的皮肤病变无效。. Contexto - O canabidiol (CBD) e ácido canabidiólico (CBDA) são relatados como tendo ações antinociceptivas, imunomoduladoras e anti-inflamatórias. Objetivos - Determinar se CBD/CBDA é eficaz no tratamento da dermatite atópica canina (CAD) Animais - Trinta e dois cães de propriedade privada com DAC. Materiais e métodos - Estudo prospectivo, randomizado, duplo-cego, placebo-controle. As terapias concomitantes foram permitidas se permanecessem inalteradas. Os cães foram divididos aleatoriamente em dois grupos, o que receberia 2 mg/kg de uma mistura igual de CBD/CBDA (n = 17) ou placebo durante quatro semanas. No Dia (D) 0, D14 e D28, o Índice de Extensão e Gravidade da Dermatite Atópica Canina, 4ª iteração (CADESI-04) e os escores da Escala Visual Analógica de Prurido (pVAS) foram determinados pelos investigadores e proprietários, respectivamente. Hemograma completo, perfis bioquímicos séricos e ensaios de citocinas foram realizados no soro coletado em D0 e D28. Resultados - Não houve diferença significativa no CADESI-04 de D0 a D14 (P = 0,42) ou D28 (P = 0,51) em nenhum dos grupos. Os escores de pVAS foram significativamente menores para o grupo de tratamento no D14 (P = 0,04) e D28 (P = 0,01) e observou-se uma alteração significativa no pVAS do D0 comparado ao D14 (P = 0,04) e não ao D28 (P = 0,054) entre os grupos. Não houve diferença significativa nos níveis séricos de interleucina (IL)-6, IL-8, proteína quimiotática de monócitos-1, IL-31 ou IL-34 entre os grupos em D0 ou D28. Elevação na fosfatase alcalina foi observada em quatro dos 17 cães do grupo de tratamento. Conclusões e relevância clínica - CBD e CBDA como uma terapia adjuvante é capaz de reduzir prurido, mas não lesões cutâneas associadas à DAC em cães.
Publication Date: 2022-06-02
Journal: Veterinary dermatology

inflammatory skin disorder(54)

Recent Developments and Advances in Atopic Dermatitis: A Focus on Epidemiology, Pathophysiology, and Treatment in the Pediatric Setting.
Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects a substantial number of children and has a significant negative impact on affected patients and their caregivers/families. Recent studies have led to significant evolutions in the understanding of AD pathogenesis, epidemiology, and treatment. The first point of contact for many patients with new-onset AD is usually with their primary care provider or pediatrician. This underscores the importance for pediatricians to understand the basic pathophysiology and current standards of care for AD. This article provides up-to-date information and reviews the basic principles of AD pathophysiology, diagnosis, and management. In addition, the article highlights recent advances in scientific research regarding the mechanisms involved in the pathogenesis of atopic dermatitis that have resulted in the discovery of novel therapeutic targets and the development of targeted biologic therapies with the potential to revolutionize AD therapy.
Publication Date: 2022-06-14
Journal: Paediatric drugs

atopic dermatitis psoriasis(48)

Current Insights Into the Role of Neuropeptide Y in Skin Physiology and Pathology.
Neuropeptide Y is widely distributed within the body and has long been implicated as a contributor to skin disease based on the correlative clinical data. However, until recently, there have been few empirical investigations to determine whether NPY has a pathophysiological role in the skin. Due to appearance-altering phenotypes of atopic dermatitis, psoriasis, and vitiligo, those suffering from these diseases often face multiple forms of negative social attention. This often results in psychological stress, which has been shown to exacerbate inflammatory skin diseases - creating a vicious cycle that perpetuates disease. This has been shown to drive severe depression, which has resulted in suicidal ideation being a comorbidity of these diseases. Herein, we review what is currently known about the associations of NPY with skin diseases and stress. We also review and provide educated guessing what the effects NPY can have in the skin. Inflammatory skin diseases can affect physical appearance to have significant, negative impacts on quality of life. No cure exists for these conditions, highlighting the need for identification of novel proteins/neuropetides, like NPY, that can be targeted therapeutically. This review sets the stage for future investigations into the role of NPY in skin biology and pathology to stimulate research on therapeutic targeting NPY signaling in order to combat inflammatory skin diseases.
Publication Date: 2022-04-15
Journal: Frontiers in endocrinology

adult atopic dermatitis(47)

The efficacy of probiotics supplementation for the treatment of atopic dermatitis in adults: a systematic review and meta-analysis.
There is a lack of certain evidence for the therapeutic efficacy of probiotics for adult atopic dermatitis (AD). PubMed, EMBASE, and the Cochrane Database were searched for relevant studies, and randomized controlled trials of AD describing treatment with single/mixed probiotic therapy were included. Changes in outcomes were calculated by standard mean difference (SMD) and 95% confidence interval (CI). Relative efficacies of the probiotics were ranked by the surface under the cumulative ranking (SUCRA). Nine studies with a total of 402 participants, including 208 AD patients who received probiotic treatments and 194 controls, were considered during the current analysis. A reduction in disease severity for probiotic supplementation compared to controls in both the short term (SMD: 0.63; 95% CI: 0.02-1.25) and the long term (SMD: 1.57; 95% CI: 0.66-2.49). There was a significant improvement in long-term quality of life after probiotic supplementation compared with controls (SMD: 0.74; 95% CI: 0.39-1.09). A mixture of L. salivarius (LS01) and Bifidobacterium (BR03) was found the highest probability of the best supplementation. Probiotic supplementation decreases clinical severity and improves the quality of life among adult AD patients. The mixture of LS01 and BR03 appeared optimal.
Publication Date: 2022-06-08
Journal: The Journal of dermatological treatment

childhood atopic dermatitis(45)

The Impact of Prenatal Nutrition on the Development of Atopic Dermatitis in Infancy and Childhood.
Atopic dermatitis (AD) is an inflammatory skin condition characterized by skin barrier disruption and inflammation that has been associated with the development of food allergies, asthma, and allergic rhinitis, known as the atopic march. The prevalence of AD has been increasing globally, with a marked increase in developed countries. Although many studies have examined environmental factors contributing to the development of AD in infancy and childhood, less is understood about the influence of prenatal factors. Several studies have examined the role of maternal diet and nutrition on the development of AD in offspring; however, formal recommendations and robust trial data are lacking. Herein, we examine the existing literature surrounding maternal diet on the development of AD in infancy and childhood.
Publication Date: 2022-06-07
Journal: Cutis

atopic dermatitis severity(40)

Validation of remote atopic dermatitis severity assessment with the Eczema Area and Severity Ondex in children using caregiver-provided photos and videos.
We sought to quantify the reliability and validity of remote atopic dermatitis (AD) severity assessment using the Eczema Area and Severity Index (EASI) applied to caregiver-provided photos (p-EASI) and videos (v-EASI). Children (0-17 years) with a physician diagnosis of AD were recruited. Caregivers took photos and a video of their child's skin. A clinician scored in-person EASI on the same day, then p-EASI and v-EASI for each participant 10 days or more between ratings. Two additional clinicians scored p-EASI and v-EASI. Lin's concordance correlation coefficient (CCC) was employed to assess criterion validity using in-person EASI as the gold standard. Intraclass correlation coefficients (ICCs) were calculated to assess interrater reliability of p-EASI and v-EASI. Fifty racially and ethnically diverse children (age [mean ± SD]: 4.3 ± 4.4 years; 42% female) with a range of AD severity (EASI: 6.3 ± 6.4) and Fitzpatrick skin types (1-2: 9%; 3-4: 60%; 5-6: 31%) were enrolled and received in-person EASI assessment. Fifty had p-EASI and 49 had v-EASI by the same in-person rater, and by two additional raters. The CCC and ICC for p-EASI were 0.89, 95% CI [0.83, 0.95] and 0.81, 95% CI [0.71, 0.89], respectively. The CCC and ICC for v-EASI were 0.75, 95% CI [0.63, 0.88] and 0.69, 95% CI [0.51, 0.81], respectively. In this diverse population with a range of skin tones, p-EASI showed good criterion validity and good interrater reliability. v-EASI showed moderate to good criterion validity and moderate interrater reliability. Both may be reliable and valid options for remote AD severity assessment.
Publication Date: 2022-05-07
Journal: Pediatric dermatology

atopic dermatitis allergic(35)

Gut microbiota in various childhood disorders: Implication and indications.
Gut microbiota has a significant role in gut development, maturation, and immune system differentiation. It exerts considerable effects on the child's physical and mental development. The gut microbiota composition and structure depend on many host and microbial factors. The host factors include age, genetic pool, general health, dietary factors, medication use, the intestine's pH, peristalsis, and transit time, mucus secretions, mucous immunoglobulin, and tissue oxidation-reduction potentials. The microbial factors include nutrient availability, bacterial cooperation or antagonism, and bacterial adhesion. Each part of the gut has its microbiota due to its specific characteristics. The gut microbiota interacts with different body parts, affecting the pathogenesis of many local and systemic diseases. Dysbiosis is a common finding in many childhood disorders such as autism, failure to thrive, nutritional disorders, coeliac disease, Necrotizing Enterocolitis, helicobacter pylori infection, functional gastrointestinal disorders of childhood, inflammatory bowel diseases, and many other gastrointestinal disorders. Dysbiosis is also observed in allergic conditions like atopic dermatitis, allergic rhinitis, and asthma. Dysbiosis can also impact the development and the progression of immune disorders and cardiac disorders, including heart failure. Probiotic supplements could provide some help in managing these disorders. However, we are still in need of more studies. In this narrative review, we will shed some light on the role of microbiota in the development and management of common childhood disorders.
Publication Date: 2022-06-07
Journal: World journal of gastroenterology

rhinitis atopic dermatitis(35)

Interleukin-33 (IL-33): A critical review of its biology and the mechanisms involved in its release as a potent extracellular cytokine.
Interleukin-33 (IL-33), a member of the IL-1 family, is an alarmin cytokine with crucial roles in tissue homeostasis and repair, type 2 immunity, allergic and non-allergic inflammation, viral infection, and cancer. IL-33 is abundant in the nuclei of tissue-derived cells, including endothelial cells from blood vessels, epithelial cells from barrier tissues, and fibroblastic stromal cells from various tissues. IL-33 is released upon cell damage or tissue injury and activates Myd88-dependent signaling pathways in cells expressing the ST2 (IL-1RL1) receptor. Analysis of patient samples and studies in murine models support an important role of IL-33/ST2 signaling in allergic inflammation in different tissues (lung, nasopharynx, skin) and diseases (asthma, chronic rhinosinusitis, allergic rhinitis, atopic dermatitis). IL33 and IL1RL1/ST2 are among the most highly replicated susceptibility loci for asthma. However, the IL-33/ST2 pathway is also important in non-allergic inflammation. Indeed, targets of IL-33 include immune cells involved in both type 2 and type 1 immunity and regulatory responses, such as group 2 innate lymphoid cells (ILC2s), mast cells, regulatory T cells (Tregs), Th2 cells, basophils, eosinophils, macrophages, dendritic cells (DCs), neutrophils, Th1 cells, CD8 T cells, NK and iNKT cells. In the main part of this review, we discuss the basic biology of the IL-33 protein (molecular characteristics, nuclear localization, cellular sources in vivo), and its mechanisms of release, and bioactive forms in various contexts. Importantly, we alert the scientific community to the problems of specificity of IL-33 reagents, we explain why studies without specificity controls with IL-33-deficient cells are misleading to the field and lead to unnecessary controversy, and we make recommendations to generate reliable results. In the final part, we review the genetic and environmental regulation of IL-33 in allergic airway inflammation and asthma, and we highlight recent studies showing clinical efficacy of anti-IL-33 antibodies in asthma and chronic obstructive pulmonary disease (COPD).
Publication Date: 2022-06-01
Journal: Cytokine

life quality index(33)

Severity of disease and the quality of life indexes in infants with atopic dermatitis.
Atopic dermatitis (AD) is a chronic, relapsing, inflammatory skin disease. In this study, the relationship between the severity of AD and the quality of life (QoL) of patients and their families were evaluated; also, the factors that predict the severity of AD and the QoL index were determined. Infants with AD were enrolled in the study. Pruritus, sleep disturbance, and dermatitis severity scores were obtained. The QoL of infants was assessed using the Infants' Dermatitis Quality of Life Index (IDQOL), while the Family Dermatology Life Quality Index (FDLQI) was used to assess the impact of disease on the QoL of parents. 122 patients diagnosed with AD were enrolled in the study. The correlation analysis of score showed a positive correlation between IDQOL and FDLQI (r = 0.444, p < 0.0001). Positive correlations between the pruritus, sleep disturbance, Severity Scoring of Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), and dermatitis severity scores and the QoL indexes were found. While pruritus, sleep disturbance scores, and EASI were the most significant parameters for predicting a severe SCORAD score, IDOQL, FDLQI, and SCORAD were the most significant parameters for predicting severe EASI. In the analysis of QoL indexes, sleep disturbance and FDLQI were the most significant parameters for predicting severe IDQOL index, while IDQOL was the most significant parameter for predicting severe FDLQI scores. AD has a negative effect on the QoL of infants and their parents. Pruritus and sleep disturbance should be evaluated during clinical practice due to their strong relationship with disease severity and QoL index.
Publication Date: 2022-05-10
Journal: Allergologia et immunopathologia

allergic rhinitis atopic(31)

Feeding a Higher Intensity, Proportion, or Amount of Human Milk by Bottle Versus By Breast and Food Allergies, Allergic Rhinitis, Atopic Dermatitis, and Asthma: A Systematic Review
BACKGROUND: This systematic review was conducted as part of the U.S. Department of Agriculture and Department of Health and Human Services Pregnancy and Birth to 24 Months Project. The goal of this systematic review was to examine the following question: What is the relationship between feeding a higher intensity, proportion, or amount of human milk by bottle versus by breast and food allergies, allergic rhinitis, atopic dermatitis, and asthma? This systematic review examines comparisons of infants fed different intensities, proportions, or amounts of human milk by bottle and by breast.
Publication Date: 2019-01-01
Journal: nan

chronic spontaneous urticaria(24)

Bruton's Kinase Inhibitors for the Treatment of Immunological Diseases: Current Status and Perspectives.
The use of Bruton's tyrosine kinase (BTK) inhibitors has changed the management of patients with B-cell lymphoid malignancies. BTK is an important molecule that interconnects B-cell antigen receptor (BCR) signaling. BTK inhibitors (BTKis) are classified into three categories, namely covalent irreversible inhibitors, covalent reversible inhibitors, and non-covalent reversible inhibitors. Ibrutinib is the first covalent, irreversible BTK inhibitor approved in 2013 as a breakthrough therapy for chronic lymphocytic leukemia patients. Subsequently, two other covalent, irreversible, second-generation BTKis, acalabrutinib and zanubrutinib, have been developed for lymphoid malignancies to reduce the ibrutinib-mediated adverse effects. More recently, irreversible and reversible BTKis have been under development for immune-mediated diseases, including autoimmune hemolytic anemia, immune thrombocytopenia, multiple sclerosis, pemphigus vulgaris, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, and chronic spontaneous urticaria, among others. This review article summarizes the preclinical and clinical evidence supporting the role of BTKis in various autoimmune, allergic, and inflammatory conditions.
Publication Date: 2022-05-29
Journal: Journal of clinical medicine

patient-oriented eczema measure(22)

The Family Impact of Atopic Dermatitis in the Pediatric Population: Results from an International Cross-sectional Study.
To evaluate the impact of atopic dermatitis on families of pediatric patients. This cross-sectional, web-based survey of children/adolescents (6 months to <18 years old) with atopic dermatitis and their parents and caregivers was conducted in 18 countries encompassing North America, Latin America, Europe, Middle East/Eurasia, and East Asia. Children and adolescents with atopic dermatitis and their parents and caregivers were identified by the International Study of Asthma and Allergies in Childhood criteria and ever being told by a physician that they had "eczema". Atopic dermatitis severity was assessed using the Patient-Oriented Eczema Measure and the Patient Global Assessment. Atopic dermatitis impact on families' lives was evaluated using the Dermatitis Family Impact questionnaire and stand-alone questions on hours of atopic dermatitis-related care (past week) and missed work days (past 4 weeks) owing to their child's atopic dermatitis. A total of 7465 pairs of pediatric participants with atopic dermatitis and their parents or caregivers were surveyed. Across age groups, the Dermatitis Family Impact questionnaire total score for all regions ranged from 7.1 to 8.6, 13.2 to 14.9, and 17.0 to 17.2 for Patient-Oriented Eczema Measure mild, moderate, and severe atopic dermatitis, respectively. Subscale scores showed that greater atopic dermatitis severity had a greater impact on all family life domains, including sleep and tiredness. No specific patterns or trends were observed across age groups. Time spent on childcare and missed work days increased with atopic dermatitis severity. Across pediatric age groups and geographic regions, greater atopic dermatitis severity was associated with a greater negative impact on physical, emotional, social, and economic components of family life.
Publication Date: 2022-05-02
Journal: The Journal of pediatrics

skin diseases(206)

Sleep impairment in patients with chronic inflammatory skin diseases: A review of mechanisms and management.
Chronic inflammatory skin diseases (CISD), such as atopic dermatitis and psoriasis, are associated with nocturnal sleep disturbances, which may in turn exacerbate inflammation. To summarize the complex factors that underlie the relationship between CISD and sleep impairment. We conducted a focused review of the published literature, including retrospective, prospective, and interventional studies, clinical trials, reviews, and consensus guidelines. The results of our literature review identified a complex interplay among various physiological, psychosocial, and behavioral factors mediating the relationship between sleep loss and CISD alongside targeted management strategies. We highlight treatment strategies that target these pathways, providing a practical framework for clinicians managing sleep loss in patients with CISD. Current guidelines by dermatology societies on the management of sleep disturbances in patients with CISD are limited and largely focus mostly on AD and psoriasis. We recommend that sleep problems be regularly assessed and managed in patients with CISD. Updated clinician guidelines are needed to better recognize and address the multifactorial nature of sleep loss in patients with CISD.
Publication Date: 2022-06-15
Journal: Journal of the American Academy of Dermatology

skin barrier(163)

Contact sensitization in pediatric patients with atopic dermatitis: a purpose for a new patch testing serie for the Portuguese population.
Atopic dermatitis is a common illness in pediatric age. Children with atopic dermatitis are prone to develop cutaneous sensitization due to skin barrier dysfunction and immune dysregulation. Recent studies have shown a higher prevalence of certain allergens, which identification may be clinically relevant and have implications for atopic dermatitis management. Considering the most prevalent and relevant allergens based on a retrospective analysis of 145 pediatric patients, 44.1% (n = 63) with atopic dermatitis, and comparing the positive results, we propose the application of an adapted baseline series with the most relevant 20 allergens for the Portuguese pediatric population with atopic dermatitis with recommendation for an evaluation of allergic contact dermatitis.
Publication Date: 2022-06-11
Journal: European annals of allergy and clinical immunology

contact dermatitis(152)

Role of IL-36 cytokines in psoriasis and other inflammatory skin conditions.
The IL-36 family of cytokines includes three pro-inflammatory agonists (IL-36α, IL-36β, and IL-36γ) and a receptor antagonist (IL-36Ra), which bind and signal through a heterodimeric receptor composed of IL-36R and the IL-1R accessory protein (IL-1RAcP). Individuals with inactivating mutations in the gene encoding IL-36Ra develop generalized pustular psoriasis, a severe form of psoriasis, a finding which clearly links dysregulated IL-36 pathway activation to inflammatory skin conditions. The purpose of this review is to highlight the cellular source of IL-36 cytokines, the effects of IL-36 signaling across cell types, and the association of IL-36 to a spectrum of inflammatory skin diseases including various forms of psoriasis as well as hidradenitis suppurativa, atopic dermatitis, and allergic contact dermatitis.
Publication Date: 2022-06-10
Journal: Cytokine

food allergy(131)

Prevalence of Food Allergy Diagnosis in Pediatric Patients with Atopic Dermatitis Referred to Allergy and/or Dermatology Subspecialty Clinics.
Publication Date: 2022-06-12
Journal: The journal of allergy and clinical immunology. In practice

systematic review(104)

The effect of probiotics on the clinical status of adult patients with atopic dermatitis: a systematic review.
To describe, through a literature review, the results and benefits of oral and topical probiotics for adult patients with atopic dermatitis. A systematic review of articles published over a 13-year period was conducted to answer the following questions: (1) what information is given in the scientific literature concerning the use of probiotics in adult patients with atopic dermatitis? (2) Was there an improvement in the clinical status of the patients? (3) Was there a change in the microbial profile in patients after using such approaches? (4) Among the probiotics used, which was the most used in adult AD patients? (5) What was the average time of these interventions? (6) What were the outcomes? Seven studies with different sample sizes, ranging from 16 to 109 patients, were included in this review. These studies were all clinical trials (7/7), and probiotics (7/7) was the model of intervention chosen. Probiotics showed a potential to relieve the symptoms of the study groups with a reduction of pruritus and SCORAD when compared to the placebo groups. However, their effectiveness varied according to the strain, period, and form of administration. Many studies have demonstrated that probiotics improve the symptoms of atopic dermatitis and even its prevention. However, there is still much controversy and divergence concerning the real benefits. Despite this, probiotics have demonstrated a fair ability in improving AD adult patients' symptoms in terms of decreasing pruritus and severity related to SCORAD.
Publication Date: 2022-06-15
Journal: European journal of medical research

type 2(77)

Tissue-specific immunity in helminth infections.
A characteristic feature of host responses to helminth infections is the development of profound systemic and tissue-localised Type 2 immune responses that play critical roles in immunity, tissue repair and tolerance of the parasite at tissue sites. These same Type 2 responses are also seen in the tissue-associated immune-pathologies seen in asthma, atopic dermatitis and many forms of allergies. The recent identification of new subtypes of immune cells and cytokine pathways that influence both immune and non-immune cells and tissues creates the opportunity for reviewing helminth parasite-host responses in the context of tissue specific immunity. This review focuses on the new discoveries of the cells and cytokines involved in tissue specific immune responses to helminths and how these contribute to host immunity against helminth infection and allow the host to accommodate the presence of parasites when they cannot be eliminated.
Publication Date: 2022-06-11
Journal: Mucosal immunology

dermatitis scorad(72)

Plasma Levels of Bioactive Vitamin D and A5 Ligands Positively Correlate with Clinical Atopic Dermatitis Markers.
Over the past decade, several controversial studies described a relationship between vitamin D and atopic diseases. Low plasma vitamin D levels or even vitamin D deficiency was associated with an increased incidence of atopic disease, postulating that a higher dietary intake of vitamin D may be a beneficial strategy against atopic diseases such as atopic dermatitis (AD). Our aim was to determine the relationship between plasma 25-hydroxyvitamin D3 (25(OH)D3) levels, the levels of the ligand of the vitamin D receptor (VDR) heterodimerization partner as well as the retinoid X receptor (RXR) and the active vitamin A5 derivative 9-cis-13,14-dihydroretinoic acid (9CDHRA) and AD severity. Samples from AD patients (n = 20) and healthy volunteers (n = 20) were assessed. In our study, the frequently measured VDR ligand precursor 25(OH)D3 in addition to the VDR-ligand 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and 9CDHRA displayed no different levels when compared with the plasma of AD patients and healthy volunteers. When performing further correlation studies focusing on AD patients, plasma 25(OH)D3 levels showed a negative correlation with eosinophils in blood (EOS) and SCORing Atopic Dermatitis (SCORAD) values, while 1,25(OH)2D3 and 9CDHRA levels correlated positively with plasma IgE, EOS, and SCORAD values. In consequence, the metabolic activation of vitamin D from 25(OH)D3 towards 1,25(OH)2D3 as well as the co-liganding of the RXR by 9CDHRA may be an important signalling mechanism, an important marker for AD development and severity as well as the basis for novel nutritional and pharmaceutical AD treatment options.
Publication Date: 2022-05-25
Journal: Dermatology (Basel, Switzerland)

severity index(70)

General and Skin-Specific Health-Related Quality of Life in Patients With Atopic Dermatitis Before and During the COVID-19 Pandemic.
Few studies have investigated health-related quality of life (HRQoL) in patients with atopic dermatitis (AD) during the COVID-19 pandemic. The objectives of this study were to compare HRQoL in adult AD patients before and during the pandemic and to assess measurement performance of 4 HRQoL measures. Between 2018 and 2021, a multicenter, cross-sectional survey was conducted, involving 218 adult AD patients. Health-related quality of life outcomes included the EQ-5D-5L, Skindex-16, Dermatology Life Quality Index (DLQI), and DLQI-Relevant (DLQI-R). Severity was measured using objective SCORing Atopic Dermatitis, Eczema Area and Severity Index, and Investigator Global Assessment. The mean ± SD EQ-5D-5L utility, Skindex-16, DLQI, and DLQI-R scores were 0.82 ± 0.22, 56.84 ± 27.46, 13.44 ± 8.46, and 13.76 ± 8.60, respectively. The patients reported more problems during the pandemic (P < 0.05) regarding pain/discomfort (odds ratio [OR], 1.78), worrying (OR, 1.89), concerns about persistence/reoccurrence of disease (OR, 1.88), and social relationships (OR, 1.69). The HRQoL outcomes showed strong correlations with each other (range of rs, |0.69| to |0.99|). The Skindex-16, DLQI, and DLQI-R were able to discriminate between severity groups with large (η2 = 0.20-0.23), whereas the EQ-5D-5L with moderate effect sizes (η2 = 0.08-0.11). Atopic dermatitis patients experienced significantly more problems in some areas of HRQoL during the pandemic. The EQ-5D-5L, Skindex-16, DLQI, and DLQI-R demonstrated good convergent and known-group validity and can be suitable instruments for HRQoL assessment in clinical and research settings.
Publication Date: 2022-06-09
Journal: Dermatitis : contact, atopic, occupational, drug

clinical trials(70)

Facial Erythema in Patients with Atopic Dermatitis Treated with Dupilumab- A Descriptive Study of Morphology and Etiology.
The development of dermatitis on face and neck, which was not described in phase 3 clinical trials, has been reported in the literature in patients treated with dupilumab. Little is known regarding the causes or defining features of the facial dermatitis. We conducted surveys of consecutive patients with AD on dupilumab to describe its clinical features, morphology, and etiology. A multicenter prospective cohort study was conducted from January 1, 2020, to December 31, 2020. A total of 162 patients under dupilumab treatment were asked to complete a questionnaire and patients were evaluated by dermatologists. Out of all 162 patients, 137 (84.6%) patients reported pre-existing facial dermatitis prior to dupilumab therapy. 121 (88.3%) patients with pre-existing facial dermatitis reported improvement of their facial dermatitis with dupilumab therapy, 9 (6.6%) patients reported no change after the treatment, and 7 (4.3%) patients of them got worse after the treatment (exacerbation group). Out of 25 patients who reported no pre-existing active facial dermatitis, 6 (24%) patients reported new-onset facial erythema after the starting dupilumab therapy (new-onset group). A large proportion of the patients in both the exacerbation (86%) and new-onset groups (67%) had a history of facial TCS use. Both groups showed similar clinical manifestations and distribution with few differences. The vast majority of patients treated with dupilumab in academic institutions from Korea and U.S. experienced improvement in their facial dermatitis with dupilumab therapy. A small proportion of patients had new onset and exacerbation. Although the mechanisms of this adverse event remains unclear, steroid withdrawal should be considered as a diagnosis of the erythema in some patients.
Publication Date: 2022-06-14
Journal: Journal of the European Academy of Dermatology and Venereology : JEADV

skin lesions(66)

Jiu-Wei-Yong-An Formula suppresses JAK1/STAT3 and MAPK signaling alleviates atopic dermatitis-like skin lesions.
Jiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have anti-inflammatory and antipruritic properties. However, the mechanism of JWYA remains unclear. This study aimed to investigate the effect of JWYA on an experimental mouse AD model. Mice were sensitized with 2,4-dinitrochlorobenzene (DNCB) and intragastrically administered with JWYA for 14 days. The therapeutic effect was assessed using a grade four dermatitis score, skin moisture, thickness measurements, and a mouse behavior tests. H&E and toluidine blue staining were used to observe epidermal inflammatory thickening and mast cells in mouse skin lesions. Serum IgE levels and skin TNF-α and IL-4 levels were determined using ELISAs. The TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ mRNA expression levels in skin lesions were detected using qPCR. Network pharmacology analysis based on serum active components was performed to elucidate the mechanism, and the results were verified by Western blotting. Finally, we tested the binding affinity between the active ingredients of JWYA and JAK1 via molecular docking. JWYA improved the skin lesions of AD mice, relieved itching and reduced skin thickening. Additionally, JWYA decreased the serum IgE level and the levels of TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ in skin. Moreover, JWYA inhibited the activation of JAK1/STAT3 and MAPK (p38, ERK, and JNK) signaling. Molecular docking showed that kaempferol, luteolin, and forsythin have high affinity for JAK1. JWYA alleviates AD-like skin lesions and inhibited inflammation and skin itch. The effect of JWYA is attributed to blocking the JAK1/STAT3 and MAPK signaling pathways. We suggest that JWYA may be an alternative therapy for the treatment of AD.
Publication Date: 2022-06-07
Journal: Journal of ethnopharmacology

asthma allergic(62)

Keratinocytes: An Enigmatic Factor in Atopic Dermatitis.
Atopic dermatitis (AD), characterized by rashes, itching, and pruritus, is a chronic inflammatory condition of the skin with a marked infiltration of inflammatory cells into the lesion. It usually commences in early childhood and coexists with other atopic diseases such as allergic rhinitis, bronchial asthma, allergic conjunctivitis, etc. With a prevalence rate of 1-20% in adults and children worldwide, AD is gradually becoming a major health concern. Immunological aspects have been frequently focused on in the pathogenesis of AD, including the role of the epidermal barrier and the consequent abnormal cytokine expressions. Disrupted epidermal barriers, as well as allergic triggers (food allergy), contact allergens, irritants, microbes, aggravating factors, and ultraviolet light directly initiate the inflammatory response by inducing epidermal keratinocytes, resulting in the abnormal release of various pro-inflammatory mediators, inflammatory cytokines, and chemokines from keratinocytes. In addition, abnormal proteinases, gene mutations, or single nucleotide polymorphisms (SNP) affecting the function of the epidermal barrier can also contribute towards disease pathophysiology. Apart from this, imbalances in cholinergic or adrenergic responses in the epidermis or the role played by immune cells in the epidermis such as Langerhans cells or antigen-presenting cells can also aggravate pathophysiology. The dearth of specific biomarkers for proper diagnosis and the lack of a permanent cure for AD necessitate investigation in this area. In this context, the widespread role played by keratinocytes in the pathogenesis of AD will be reviewed in this article to facilitate the opening up of new avenues of treatment for AD.
Publication Date: 2022-05-29
Journal: Cells

asthma atopic(61)

Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of
Publication Date: 2022-03-04
Journal: Gut microbes

food allergies(55)

Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation.
Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic disorders, for example, food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD-like skin inflammation, we report that a fermentable fibre-rich diet alleviates systemic allergen sensitization and disease severity. The gut-skin axis underpins this phenomenon through SCFA production, particularly butyrate, which strengthens skin barrier function by altering mitochondrial metabolism of epidermal keratinocytes and the production of key structural components. Our results demonstrate that dietary fibre and SCFA improve epidermal barrier integrity, ultimately limiting early allergen sensitization and disease development.
Publication Date: 2022-06-08
Journal: Mucosal immunology

atopic march(52)

Prenatal antibiotic exposure, asthma and the atopic march: A systematic review and meta-analysis.
Antibiotic use during pregnancy may increase the risk for asthma in children. We performed a meta-analysis assessing prenatal antibiotic exposure and the risk for childhood wheeze or asthma, as well as for diseases associated with the atopic march. A systematic literature search protocol (PROSPERO-ID: CRD42020191940) was registered and searches were completed using Medline, Proquest, Embase, and the Cochrane central register of controlled trials. Screening for inclusion criteria: published in English, German, French, Dutch or Arabic, intervention (use of any antibiotic at any time point during pregnancy), and disease (reporting atopic disease incidence in children with a primary outcome of asthma or wheeze), and exclusion criteria: reviews, preclinical data, and descriptive studies, yielded 27 studies. Study quality was assessed using the Newcastle-Ottawa Assessment Scale. Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Our meta-analysis demonstrates that antibiotic use during pregnancy is associated with an increased relative risk (RR) of developing wheeze RR 1.51 (95% CI: 1.17-1.94) or asthma RR 1.28 (95% CI 1.22-1.34) during childhood. Assessment of the atopic march in association with asthma or wheeze revealed that antibiotic use during pregnancy also increases risk for eczema/dermatitis RR 1.28 (95% CI: 1.06 -1.53) and allergic rhinitis RR 1.13 (95% CI: 1.02 -1.25). One study found an increase in food allergy RR 1.81 (95% CI: 1.11 -2.95). Maternal antibiotic use during pregnancy is associated with an increased risk for wheeze or asthma development in children, as well as for diseases involved in the atopic march. There was high heterogeneity in the data, and the certainty of the evidence was determined to be low quality, highlighting the need for more high-quality studies on this topic. These results have importance for antibiotics stewardship throughout the prenatal period. This work was supported by the Konrad Adenauer Foundation.
Publication Date: 2022-06-12
Journal: Allergy

alopecia areata(51)

Tofacitinib in the treatment of refractory eczemas - a case series.
Janus Kinase inhibitors have been shown to be effective in the treatment of various dermatoses such as alopecia areata, psoriasis, vitiligo and atopic dermatitis. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is a common junction for the signaling of several dermatologically significant cytokines and the inhibition of this pathway by JAK inhibitors may be broadly useful in the treatment of various other dermatological disorders. A case series is presented of twelve patients (M:6, F:6) with a mean age 47.1 years, presenting with various eczematous dermatoses (histopathology showing spongiotic dermatitis) who had failed to respond to conventional therapy. These patients were prescribed tofacitinib. All 12 patients improved and 10 patients had improvement to clear or almost clear (physician global assessment score 0/1) after 1 month of therapy. No hematological or biochemical abnormalities were noted during the treatment period. Infections were the most common adverse events observed. Conventional treatment options like systemic steroids and steroid sparing agents are the cornerstone in the treatment of chronic eczematous disorders, however, in patients who do not respond to conventional agents, tofacitinib may represent a viable treatment option.
Publication Date: 2022-06-02
Journal: The Journal of dermatological treatment

hidradenitis suppurativa(44)

Alexithymia and Cutaneous Disease Morbidity: A Systematic Review.
Alexithymia is a psychological construct that describes one's difficulty in understanding and describing their own emotions as well as differentiating feelings from bodily signals of arousal. In the general population, alexithymia's prevalence is approximately 10%. Alexithymia may act as a triggering factor for many medical and psychiatric disorders. In patients with physical disease, alexithymia's prevalence reaches up to 63%. Additionally, alexithymia is associated with worse outcomes and heightened psychosocial comorbidities. This review continues where an earlier review (Willemsen, 2008) left off to (1) clarify alexithymia's prevalence in dermatology patients and (2) further investigate alexithymia's impact on disease burden, psychosocial comorbidities, and treatment. Systematic searches on alexithymia and dermatologic conditions were conducted using PubMed, Embase, PsycInfo, and Web of Science databases from March 8, 2021, to March 12, 2021. Data from eligible publications, which were full-text, clinical studies published after September 1, 2008, and available in English, were extracted by two medical students and summarized. Despite a small number of publications (n = 37), data showed a markedly greater prevalence and severity of alexithymia in patients with alopecia, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic idiopathic urticaria, and primary focal hyperhidrosis compared to healthy controls. Further, data consistently demonstrate a complex interplay between alexithymia, disease burden, and psychosocial comorbidity. Identifying and addressing alexithymia in dermatology patients may improve treatment outcomes, associated comorbidities, and health-related quality of life.
Publication Date: 2022-06-01
Journal: Dermatology (Basel, Switzerland)

chronic rhinosinusitis(44)

Dupilumab-induced hypereosinophilia: review of the literature and algorithm proposal for clinical management.
Dupilumab is a human monoclonal antibody that targets both IL-4 and IL-13 signaling. It is currently indicated for the treatment of asthma, moderate-to-severe atopic dermatitis and chronic rhinosinusitis with nasal polyps (CRSwNP). Eosinophilia has been reported as a potential adverse event in treated patients. A selective search on PubMed and Medline up to January 2022 was performed, by focusing on dupilumab-induced hypereosinophilia described in clinical trials, real-life studies and case reports. The possible mechanisms underlying dupilumab-induced hypereosinophilia and the eosinophils-related morbidity have also been explored. Dealing with dupilumab-induced hypereosinophilia represents a clinica challenge for clinicians managing patients on dupilumab therapy. An algorithm for the practical management of dupilumab-induced hypereosinophilia has been proposed, in order to properly investigate potential eosinophlis-related morbidity and avoid unnecessary drug discontinuation.
Publication Date: 2022-06-16
Journal: Expert review of respiratory medicine

bronchial asthma(42)

Characterization of the L-Arginine/Nitric Oxide Pathway and Oxidative Stress in Pediatric Patients with Atopic Diseases.
L-Arginine (Arg) is a semi-essential amino acid. Constitutive and inducible nitric oxide synthase (NOS) isoforms convert Arg to nitric oxide (NO), a potent vaso- and bronchodilator with multiple biological functions. Atopic dermatitis (AD) and bronchial asthma (BA) are atopic diseases affecting many children globally. Several studies analyzed NO in airways, yet the systemic synthesis of NO in AD and BA in children with BA, AD or both is elusive. In a multicenter study, blood and urine were obtained from 130 of 302 participating children for the measurement of metabolites of the Arg/NO pathway (BA 31.5%; AD 5.4%; AD + BA 36.1%; attention deficit hyperactivity disorder (ADHD) 12.3%). In plasma and urine amino acids Arg and homoarginine (hArg), both substrates of NOS, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), both inhibitors of NOS, dimethylamine (DMA), and nitrite and nitrate, were measured by gas chromatography-mass spectrometry. Malondialdehyde (MDA) was measured in plasma and urine samples to evaluate possible effects of oxidative stress. There were no differences in the Arg/NO pathway between the groups of children with different atopic diseases. In comparison to children with ADHD, children with AD, BA or AD and BA had higher plasma nitrite ( The Arg/NO pathway is activated in atopic diseases independent of severity. Systemic NO synthesis is increased in children with an atopic disease. Plasma and urinary MDA levels did not differ between the groups, suggesting no effect of oxidative stress on the Arg/NO pathway in atopic diseases.
Publication Date: 2022-02-27
Journal: International journal of molecular sciences

rhinitis ar(35)

New Insight into Drugs to Alleviate Atopic March via Network Pharmacology-Based Analysis.
In the present study, a subject of atopic dermatitis (AD) is exposed progressively to allergic rhinitis (AR) and asthma (AS), which is defined as atopic march (AM). However, both the targets and compounds against AM are still largely unknown. Hence, we investigated the overlapping targets related directly to the occurrence and development of AD, AR, and AS through public databases (DisGeNET, and OMIM). The final overlapping targets were considered as key targets of AM, which were visualized by a Venn diagram. The protein-protein interaction (PPI) network was constructed using R package software. We retrieved the association between targets and ligands via scientific journals, and the ligands were filtered by physicochemical properties. Lastly, we performed a molecular docking test (MDT) to identify the significant ligand on each target. A total of 229 overlapping targets were considered as AM causal elements, and 210 out of them were interconnected with each other. We adopted 65 targets representing the top 30% highest in degree centrality among 210 targets. Then, we obtained 20 targets representing the top 30% greatest in betweenness centrality among 65 targets. The network analysis unveiled key targets against AM, and the MDT confirmed the affinity between significant compounds and targets. In this study, we described the significance of the eight uppermost targets (CCL2, CTLA4, CXCL8, ICAM1, IL10, IL17A, IL1B, and IL2) and eight ligands (Bindarit, CTLA-4 inhibitor, Danirixin, A-205804, AX-24 HCl, Y-320, T-5224, and Apilimod) against AM, providing a scientific basis for further experiments.
Publication Date: 2022-06-10
Journal: Current issues in molecular biology

rheumatoid arthritis(34)

Old drugs, new tricks: Emerging role of drug repurposing in the management of atopic dermatitis.
Atopic dermatitis is a chronic recurring pruritic inflammatory skin disease manifested by increased pro-inflammatory mediators which lead to dry, thickened, cracked, scaly skin. The current treatment options for atopic dermatitis management comprise drawbacks and leave unmet effective clinical needs. So, the approach for repurposing existing drugs for atopic dermatitis management may potentially overcome these unmet needs. Diseases that share the common pathophysiological pathways with atopic dermatitis can serve as a foundation for the repurposing of drugs. Drugs used in the management of cancer, rheumatoid arthritis, and other immune-mediated diseases such as psoriasis are under investigation to know the potential in atopic dermatitis management by utilizing repurposing strategies for a novel therapeutic indication. This review mainly envisages the probable repurposing of drugs for the management of atopic dermatitis disease; the barriers and regulatory aspects involved in the repurposing of existing drugs.
Publication Date: 2022-05-14
Journal: Cytokine & growth factor reviews

odds ratio(30)

Living with Atopic Dermatitis as a Young Adult in Relation to Health-related Quality of Life and Healthcare Contacts: A Population-based Study.
Most studies of health-related quality of life (HRQoL) and atopic dermatitis are based on data from dermatology clinics. The aim of this study was to determine whether atopic dermatitis affects HRQoL in adolescence and young adulthood, based on data from the population-based cohort BAMSE (Children, Allergy, Environmental, Stockholm, Epidemiology). A further aim was to determine if the use of topical corticosteroids and healthcare contacts affect HRQoL. Participants with data from birth to young adulthood (n=3,064) were included. Two generic instruments were used to measure HRQoL:General Health at age 12, 16 and 24 years and EQ-5D-3L, including EQ-visual analogue scale (EQ-VAS) at age 24 years. In addition, the disease-specific Dermatology Quality Life Index (DLQI) was used at 24 years. Healthcare consultations for atopic dermatitis were obtained from Stockholm Regional Healthcare Data Warehouse (n = 1,944). Participants with atopic dermatitis had an increased odds ratio (OR) of not feeling completely healthy (adjusted OR 1.50; 95% confidence interval (95% CI): 1.30-1.73). Participants with persistent atopic dermatitis, fulfilling atopic dermatitis criteria in the 12- and/or 16- and 24-year follow-ups reported worse EQ-VAS value 70.0 (95% CI 67.3-72.7) in the 25th percentile, than peers without atopic dermatitis. Over an 8-year period, contact with healthcare was limited (mean number 0.96). In conclusion, atopic dermatitis had a negative impact on HRQoL in young adults from adolescence to adulthood and healthcare consultations were few.
Publication Date: 2022-03-22
Journal: Acta dermato-venereologica

index easi(27)

Review of Ruxolitinib in the Treatment of Atopic Dermatitis.
To review the pharmacokinetics, efficacy, and safety of a newly approved topical Janus kinase 1 (JAK) inhibitor, ruxolitinib (RUX), in patients with atopic dermatitis (AD). A literature search was completed May 1, 2022. The term RUX and AD was queried in MEDLINE (PubMed) and EMBASE databases. Peer-reviewed articles written in English and published prior to May 1, 2022 were included. In the phase II clinical trial, more patients treated with 1.5% topical RUX twice a day had a mean percentage improvement in Eczema Area and Severity Index (EASI) scores from baseline to 4 weeks, when compared to vehicle (71.6% vs 15.5%; Atopic dermatitis is a highly prevalent long-term inflammatory skin condition. Pruritus is the main contributor of decreased quality of life in patients with AD. Topical RUX inhibits JAK1 and JAK2 producing antiinflammatory and antipruritic effects. Patients experienced a reduction in pruritus within 2 days. This decreased pruritus translated to increased quality of life and less sleep disturbances. Data from phase II and III clinical trials in adult patients suggest RUX is an effective and safe therapy for AD.
Publication Date: 2022-06-09
Journal: The Annals of pharmacotherapy

confidence interval(27)

Associations of Four sensitization patterns revealed by Latent Class Analysis with Clinical symptoms: A multi-center study of China.
Because of the significant regional differences in the distribution of allergens, the relationship between anaphylaxis and allergic sensitization is complex in China. Using this large-scale epidemiologic survey, we explore the potential patterns of sensitization to common allergens in mainland China and investigate their relationship with various clinical symptoms. The participants were recruited from 13 medical centers in mainland China from October 2019 to June 2021. Skin prick test (SPT) results that cover 18 common allergens were utilized to diagnose atopic sensitization. The demographic characteristics and clinical information were collected through questionnaires during routine medical follow-up. Latent class analysis (LCA) was conducted to determine the optimal sensitization patterns. The logistic regression was used to assess the associations of different sensitization patterns with allergy symptoms. A total of 1089 patients who had a positive SPT to at least one of 18 allergens were included for formal analysis. An optimal LCA model with 4 classes was obtained in this study, and the corresponding labels were as follows: Class1, house dust mite sensitization; Class2, low pollen sensitization; Class3, middle pollen sensitization; Class4, high pollen sensitization. The prevalence of different classes varied widely in geographical distribution, which was characterized by Class1 being very common in south and east as well as Class2 in north and west of China. Compared with patients in Class1, those in middle and high pollen sensitization clusters had the higher odds ratios (ORs) of allergic rhinitis and allergic conjunctivitis when controlling for other confounders. However, there was no significant difference between low pollen sensitization and house dust mite sensitization groups in the risks for various clinical performances except dermatitis. Additionally, the adjusted ORs (95% confidence interval) of allergic conjunctivitis and dermatitis for participants in pollen sensitization clusters (Class2, 3 and 4) were 1.56 (1.18, 2.06) and 1.43 (1.09, 1.88) respectively compared with those in Class1. In this study, we identified four sensitization clusters with specific risks of various clinical symptoms using common allergens by adopting LCA. Our findings may contribute to improved diagnosis and potential immunotherapy approaches to allergy in mainland China. This study was supported by the National Natural Science Foundation of China (81802076 and 81871736), the Guangzhou Science and Technology Foundation (202102010327), the Foundation of SKLRD (MS-2019-06 and Z-2022-09), and the Foundation of GYYY (ZH201904) and ZNSA-2020012.
Publication Date: 2022-03-26
Journal: EClinicalMedicine

dermatitis asthma(18)

Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans.
A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68-0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62-0.85) but not ICC (aHR, 0.95; 95% CI 0.73-1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62-0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52-0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71-1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71-1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44-0.81) and 0.77 (95% CI 0.64-0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63-0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.
Publication Date: 2022-06-15
Journal: Scientific reports

n 1(5)

Lirentelimab for severe and chronic forms of allergic conjunctivitis.
Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.
Publication Date: 2022-04-08
Journal: The Journal of allergy and clinical immunology


Break on through: The role of innate immunity and barrier defence in atopic dermatitis and psoriasis.
The human skin can be affected by a multitude of diseases including inflammatory conditions such as atopic dermatitis and psoriasis. Here, we describe how skin barrier integrity and immunity become dysregulated during these two most common inflammatory skin conditions. We summarise recent advances made in the field of the skin innate immune system and its interaction with adaptive immunity. We review gene variants associated with atopic dermatitis and psoriasis that affect innate immune mechanisms and skin barrier integrity. Finally, we discuss how current and future therapies may affect innate immune responses and skin barrier integrity in a generalized or more targeted approach in order to ameliorate disease in patients.
Publication Date: 2022-06-10
Journal: Skin health and disease


Effect of 6,7-dimethoxy-2,2-dimethyl-2H-chromene (agerarin) on the recovery of filaggrin expression through targeting of Janus kinases in the inflammatory skin.
Filaggrin (FLG) is a structural component of the stratum corneum that is essential for maintaining the barrier function of the skin and for the formation of natural moisturizing factors. 6,7-Dimethoxy-2,2-dimethyl-2H-chromene (Agerarin) is a bioactive compound derived from Ageratum houstonianum, a plant that is used as a traditional medicine to treat skin diseases. This study aimed to evaluate the effect of agerarin on skin inflammation in a dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. We found that the topical administration of agerarin ameliorates atopic dermatitis-like skin lesions. We also showed that agerarin restores the reduced filaggrin (FLG) expression in DNCB-applied skin sections. Moreover, agerarin decreased phosphorylation of JAK1 and JAK2 kinases to enhance FLG expression, which was reduced by TNFα+IFNγ and IL4+IL13 treatment, in HaCaT keratinocytes. These results demonstrate the feasibility of agerarin as a possible therapeutic against conditions of skin inflammation, such as atopic dermatitis, by improving the upregulation of FLG expression.
Publication Date: 2020-09-15
Journal: Journal of food and drug analysis


Neuro-allergology: Mast cell-nerve cross-talk.
Mast cells (MCs) are derived from hematopoietic stem cells in the bone marrow, and their maturation is regulated by the tissue environment, such as the skin, lung and gut, leading to host defense. Peripheral nerve fibers located in various tissues are involved in diverse physiological and pathological processes. Anatomical relationships between MCs and nerve fibers were reported to have been observed in various organs. Moreover, MCs are positive for a large number of receptors for classical neurotransmitters (e.g., acetylcholine and corticotropin-releasing hormone) and neuropeptides (e.g., substance P, calcitonin gene-related peptides and hemokinin), and MC's functions are regulated by those nerve-derived factors. Also, histamine and proteases produced and released by MCs modulate nerve fiber functions. This functional cross-talk between MCs and nerve fibers can play physiological and pathological roles. MCs are key effector cells of allergic inflammation, such as atopic dermatitis, airway inflammation and food allergy. Here, we summarize and discuss the molecular mechanisms underlying the functional and anatomical cross-talk between MCs and nerve fibers in allergic inflamed tissues.
Publication Date: 2022-06-11
Journal: Allergology international : official journal of the Japanese Society of Allergology


Efficacy and Safety of Multiple Dupilumab Dose Regimens in Patients with Moderate-To-Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Dupilumab ameliorates the signs and symptoms of atopic dermatitis (AD) and improves the patient's quality of life. Multiple-dose regimens of dupilumab have been applied by clinicians, but the efficacy of some regimens remains unclear. The aim of the study was to systematically evaluate the efficacy and safety of multiple dupilumab dose regimens in patients with moderate-to-severe AD in terms of comprehensive outcomes. We searched electronic databases and subjected the selected studies to risk-of-bias assessment and network meta-analysis (NMA). Efficacy and safety outcomes were compared using a random-effects NMA to estimate pooled relative risk ratio (RR) of direct and indirect comparisons among multiple dupilumab dose regimens. The Eczema Area Severity Index, Investigator's Global Assessment, and pruritus numerical rating scale were analyzed to assess the efficacy, while adverse events (AEs) and serious adverse events to represent the safety. Eight randomized controlled trials involving 3,679 patients were identified. Most patients received therapy for 16 weeks. Multiple dupilumab dose regimens, including 300 mg weekly (QW), 300 mg every 2 weeks (Q2W), 200 mg Q2W, 300 mg monthly (QM), 300 mg every 2 months (Q2M), and 100 mg QM were analyzed. All regimens, except 100 mg QM, had significantly better efficacy than placebo. 300 mg QW and 300 mg Q2W appeared to have similar efficacy. Notably, both 300 mg QW and 300 mg Q2W had no significantly better efficacy than 300 mg QM. As for 300 mg Q2M, significantly reduced efficacy was noted in only one efficacy outcome when compared to 300 mg QW and 300 mg Q2W. In terms of safety outcomes, AEs occurring with any of the regimens were comparable with the placebo. No significant inconsistency was noted within the network in all efficacy outcomes. Our NMA indicated that the administration of the following dupilumab regimens was effective for patients with moderate-to-severe AD: 300 mg QW, 300 mg Q2W, 200 mg Q2W, 300 mg QM, and 300 mg Q2M. Our data can improve the understanding of the relative efficacy and safety of multiple dupilumab dose regimens, which will help in shared decision-making between clinicians and patients.
Publication Date: 2022-06-14
Journal: Dermatology (Basel, Switzerland)


Severe and ChRonic ATopic Dermatitis CoHort (SCRATCH): A Danish Real-world Evidence Atopic Dermatitis Treatment Registry.
Data from real-world use of new systemic treatments in atopic dermatitis (AD) is important for assessing safety and efficacy. The aim of this study is to de-scribe the baseline characteristics of adult patients with moderate-to-severe AD enrolled in the Danish nationwide Severe and ChRonic ATopic dermatitis CoHort (SCRATCH) database, between October 2017 and August 2021. A total of 282 adult patients were included. Most (62%) were men, the median age at baseline was 43 years (interquartile range (IQR) 29-54 years), and median age at onset of AD was 1 year (IQR 0-6 years). The median Eczema Area and Severity Index at treatment initiation was 19.1 (IQR 11.9-25.7); median Patient Oriented Eczema Measure 21.0 (IQR 16.0-25.0); median Dermatology Life Quality Index 13.0 (IQR 7.0-19.0); and median itch and sleep numerical rating scale scores 8.0 (IQR 6.0-9.0) and 6.0 (IQR 4.0-8.0). Differences were found between the sexes. This registry will provide a source for future efficacy and safety studies.
Publication Date: 2022-06-08
Journal: Acta dermato-venereologica


Quality of Life Among Family of Patients with Atopic Dermatitis and Psoriasis.
Chronic inflammatory skin diseases like atopic dermatitis (AD) and psoriasis can severely impact patients' quality of life (QOL). However, the effect of these diseases can diminish the QOL of patients' family members as well. The objective of this study was to understand the impact on QOL for family members of patients diagnosed with AD or psoriasis. We conducted focus groups and interviews with 23 individuals; 12 had a family member with AD, and 11 had a family member with psoriasis. After investigators independently coded the transcripts, thematic analysis was conducted. Three major themes emerged: (1) lifestyle consequences-many daily activities for family members, including but not limited to leisure activities, sleep, and cleaning, were affected by AD or psoriasis; (2) emotional consequences-family members felt frustrated, worried, or embarrassed, among other concerns, because of their loved ones' AD or psoriasis; (3) relationships-relationships between family members and their loved ones with AD or psoriasis could become strained, and though family members might try to be sympathetic, doing so could be difficult because of their lack of understanding of how these diseases feel and personally affect their loved ones. This study highlights the impacts of AD and psoriasis on the whole family. Clinicians should be mindful of the effects on QOL not only for patients but also for family members who live with and care about these patients. Especially when family members assist with treatments, it is important to understand family members' experiences when making treatment decisions.
Publication Date: 2022-05-27
Journal: International journal of behavioral medicine


Narrative review on the management of moderate-severe atopic dermatitis in pediatric age of the Italian Society of Pediatric Allergology and Immunology (SIAIP), of the Italian Society of Pediatric Dermatology (SIDerP) and of the Italian Society of Pediatrics (SIP).
Currently, there are a few detailed guidelines on the overall management of children and adolescents with moderate-severe atopic dermatitis. AD ​​is a complex disease presenting with different clinical phenotypes, which require an individualized and multidisciplinary approach. Therefore, appropriate interaction between primary care pediatricians, pediatric allergists, and pediatric dermatologists is crucial to finding the best management strategy. In this manuscript, members of the Italian Society of Pediatric Allergology and Immunology (SIAIP), the Italian Society of Pediatric Dermatology (SIDerP), and the Italian Society of Pediatrics (SIP) with expertise in the management of moderate-severe atopic dermatitis have reviewed the latest scientific evidence in the field. This narrative review aims to define a pathway to appropriately managing children and adolescents with moderate-severe atopic dermatitis.
Publication Date: 2022-06-15
Journal: Italian journal of pediatrics


Influence of FLG loss-of-function mutations in host-microbe interactions during atopic skin inflammation.
Loss-of-function mutations in the filaggrin (FLG) gene directly alter skin barrier function and critically influence atopic inflammation. While skin barrier dysfunction, Th2-associated inflammation and bacterial dysbiosis are well-known characteristics of atopic dermatitis (AD), the mechanisms interconnecting genotype, transcriptome and microbiome remain largely elusive. In-depth analysis of FLG genotype-associated skin gene expression alterations and host-microbe interactions in AD. Multi-omics characterization of a cohort of AD patients carrying heterozygous loss-of-function mutations in the FLG gene (AD In the context of filaggrin dysfunction, the transcriptome was characterized by dysregulation of barrier function and water homeostasis, while the lesional skin of AD Our integrative approach provides molecular insights for the concept that FLG loss-of-function mutations are a genetic shortcut to atopic inflammation and unravels the complex interplay between genotype, transcriptome and microbiome in the human holobiont.
Publication Date: 2022-05-11
Journal: Journal of dermatological science


Medihoney Derma Cream Treatment for Mild to Moderate Atopic Dermatitis in Children: An Open-Label Randomized Pilot Study.
Publication Date: 2022-06-16
Journal: Dermatitis : contact, atopic, occupational, drug


Peripheral itch sensitization in atopic dermatitis.
Atopic dermatitis is a skin disorder caused by skin dryness and barrier dysfunction, resulting in skin inflammation and chronic itch (or pruritus). The pathogenesis of atopic dermatitis is thought to be initiated by a lowering of the itch threshold due to dry skin. This lowering of the itch threshold is at least partially due to the increase in intraepidermal nerve fibers and sensitization of sensory nerves by interleukin (IL)-33 produced and secreted by keratinocytes. Such skin is easily prone to itch due to mechanical stimuli, such as rubbing of clothing and chemical stimuli from itch mediators. In patients with atopic dermatitis, once itch occurs, further itch is induced by scratching, and the associated scratching breaks down the skin barrier. Disruption of the skin barrier allows entry into the epidermis of external foreign substances, such as allergens derived from house dust mites, leading to an increased induction of type 2 inflammatory responses. As a result, type 2 cytokines IL-4, IL-13, and IL-31 are mainly secreted by Th2 cells, and their action on sensory nerve fibers causes further itch sensitization. These sequences of events are thought to occur simultaneously in patients with atopic dermatitis, leading to a vicious itch-scratch cycle. This vicious cycle becomes a negative spiral that leads to disease burden. Therefore, controlling itch is essential for the treatment of atopic dermatitis. In this review, we summarize and discuss advances in the mechanisms of peripheral itch sensitization in atopic dermatitis, focusing on skin barrier-neuro-immune triadic connectivity.
Publication Date: 2022-05-28
Journal: Allergology international : official journal of the Japanese Society of Allergology


Climate change, the cutaneous microbiome and skin disease: implications for a warming world.
The skin plays an important role in human health by providing barrier protection against environmental stressors. In addition to human skin cells, the cutaneous barrier is also home to a network of organisms that have co-evolved with humans, referred to as the cutaneous microbiome. This network has been demonstrated to play an active role in skin health and the manifestation of cutaneous disease. Here, we review how a warming world and its attendant changes in climatic variables, including temperature, humidity, ultraviolet radiation, and air pollution, influence the cutaneous microbiome and, in turn, skin health. Studies indicate that the cutaneous microbiome is affected by these factors, and these changes may influence the epidemiology and severity of cutaneous disorders including atopic dermatitis, acne vulgaris, psoriasis, and skin cancer. Further investigation into how the cutaneous microbiome changes in response to climate change and subsequently influences skin disease is needed to better anticipate future dermatologic needs and potentially generate novel therapeutic solutions in response.
Publication Date: 2022-05-23
Journal: International journal of dermatology


The Risk Reduction Effect of a Nutritional Intervention With a Partially Hydrolyzed Whey-Based Formula on Cow's Milk Protein Allergy and Atopic Dermatitis in High-Risk Infants Within the First 6 Months of Life: The Allergy Reduction Trial (A.R.T.), a Multicenter Double-Blinded Randomized Controlled Study.
The role of partially hydrolyzed formulas (pHF) as part of nutritional interventions to prevent the development of allergic manifestations (AM) is questioned, and efficacy of each specific pHF should be substantiated. To investigate the risk-reduction effect of a whey-based pHF on the development of cow's milk protein allergy (CMPA) and atopic dermatitis (AD) in infants at high-risk for allergy within the first 6 months of life. In a multicenter double-blinded randomized controlled setting, healthy non-exclusively breastfed full-term infants, received either a specific whey-based pHF or a standard cow's milk-based formula (SF) and were clinically assessed for AM at 2, 4, and 6 months of age, supported by the objective scoring tools SCORAD and CoMiSS. CMPA was confirmed by open food challenge. Intention-to-Treat (ITT) and Per-Protocol (PP) analyses were performed. Of 331 randomized subjects (ITT analysis set), 160 received the pHF and 171 the SF. Six (3.8%) infants in the pHF and 12 (7%) in the SF group developed CMPA ( This specific whey-based pHF reduced the risk of AD development, particularly in those with a family history of AD, and tended to reduce the development of CMPA in non-exclusively breastfed infants at high-risk for allergy. The A.R.T. study suggests that this particular pHF may contribute to measures aimed at prevention of allergic manifestations. However, further studies are needed to confirm this risk-reduction effect.
Publication Date: 2022-06-14
Journal: Frontiers in nutrition


Epidemiological, Clinical, and Allergy Profile of Patients With Atopic Dermatitis and Hand Eczema: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC).
Hand eczema is common in patients with atopic dermatitis (AD), but few studies have described the characteristics of these patients in large, representative populations from different geographic regions and occupational settings. To describe the epidemiological, clinical, and allergy profile of patients with hand eczema who underwent patch testing and compare patients with and without AD. Analysis of data from the Spanish Contact Dermatitis Registry, a multicenter registry of patients who undergo patch testing in Spain. We included 1466 patients with hand eczema who were patch tested between January 2018 and June 2020. Those with AD were younger and had had symptoms for longer before testing. They were also more likely to have been exposed to occupational triggers (38% vs 53% for patients without AD). The only profession for which significant differences were found was hairdressing. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, cobalt chloride, potassium dichromate, fragrance mixes I and II, and formaldehyde. The most common diagnoses were allergic contact dermatitis (24% vs 31% in patients with and without AD, P=.0224) and irritant contact dermatitis (18% and 35% respectively, P<.001). AD is common in patients with predominant hand eczema who undergo patch testing. Patients with hand eczema and AD have different clinical and epidemiological characteristics to hand eczema patients in general and their final diagnosis following patch testing is also different.
Publication Date: 2022-05-09
Journal: Actas dermo-sifiliograficas


Patch testing with glucosides: The North American Contact Dermatitis Group experience, 2009-2018.
Alkyl glucosides are nonionic surfactants that are increasingly used in personal care products. To characterize positive patch test reactions to decyl glucoside (5% petrolatum, tested 2009-2018) and lauryl glucoside (3% petrolatum, tested 2017-2018). Retrospective analysis of patients tested by the North American Contact Dermatitis Group. Of 24,097 patients patch tested to decyl and/or lauryl glucoside, 470 (2.0%) had positive reactions. Compared with glucoside-negative patients, glucoside-positive patients had higher odds of occupational skin disease (13.4% vs 10.1%; P = .0207), history of hay fever (38.5% vs 31.6%; P = .0014), atopic dermatitis (39.0% vs 28.6%; P < .0001), and/or asthma (21.8% vs 16.5%; P = .0023). Most glucoside reactions (83.9%) were currently relevant. The most common source was personal care products (63.0%), especially hair products (16.5%) and skin cleansers (15.2%). Of 4933 patients tested to decyl and lauryl glucoside, 134 (2.7%) were positive to 1 or both; 43.4% (43 of 99) of decyl-positive patients were also positive to lauryl glucoside and 55.1% (43/78) of lauryl glucoside patients were also positive to decyl glucoside. The cohort predominantly reflects a referral population, and follow-up after testing was not captured. Glucoside positivity occurred in 2.0% of the tested patients. Reactions were often clinically relevant and linked to personal care products. Cross-reactivity was >40%.
Publication Date: 2022-05-14
Journal: Journal of the American Academy of Dermatology