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

Atopic dermatitis (AD) is a common presenting complaint by children and their caretakers to their primary care providers. On testing, children with AD frequently exhibit positive food-specific IgE levels in the absence of immediate allergic reactions. Misinterpretation of these false positive tests can lead to unnecessary food avoidance, which can have tremendous psychosocial, economic and nutritional consequences and, in some cases, facilitate the development of an immediate hypersensitivity to the food. We present a child with persistent AD who underwent broad testing that led to unnecessary food avoidance resulting in Vitamin D deficiency, growth failure and the development of an IgE-mediated food allergy. This case underscores the need for caution by primary care clinicians in using food avoidance diets as a treatment for AD and the importance of limiting allergy testing to foods only when the clinical history indicates an immediate hypersensitivity reaction.

Although Western medicine and ideas about atopic dermatitis (AD) have become popular in many Asian countries, local beliefs about the disease and its treatment often prevail. The multi- racial background of these countries as well as the influence of the diverse religions (such as Taoism and Ramadan) in these regions often lead to diverse belief systems about the causes of AD (such as the Chi concept, also known as the balance of yin and yang) and the types of treatment (e.g. herbal remedies, topical versus concoctions, and decoctions). In addition, many of the cultural practices are preserved among the Southeast Asian minorities residing in the United Kingdom and North America. Eastern treatments typically take a holistic approach to AD and emphasize the psychosomatic component of the disorder. This overview provides a summary of the difference between Conventional, Complementary, Alternative, and Integrative Medicine in terms of epidemiology, aetiology, therapy, and prognosis in children with AD. There are a number of similarities in genetic and environmental factors in epidemiology and aetiology; however, differences exist in terms of the concept of management. Complementary and alternative medicine, traditional Chinese medicine, and integrative medicine usage are not only prevalent among the Asian population but are also becoming more popular and accepted in Western societies.

BACKGROUND Dupilumab has been demonstrated to be an effective treatment for patients with moderate-to-severe atopic dermatitis (AD) in clinical trials. However, evidence of real-world experience with dupilumab in a broader population is limited to date. METHODS Adult patients with moderate-to-severe AD, defined as an Eczema Area Severity Index (EASI) score of 24 or higher, treated with dupilumab at ten Italian academic centers, were included in the study. Physician-reported outcome measures (EASI), patient-reported outcome measures (pruritus and sleep score, Dermatology Life Quality Index, DLQI) and serological markers [immunoglobulin (Ig) E and eosinophil count] after 16 weeks were analyzed. RESULTS We enrolled 543 patients with moderate-to-severe AD. Two patients (0.4%) discontinued treatment. The median ± interquartile percentage change from baseline to 16 weeks of treatment in the EASI score was -87.5±22.0 (p

Atopic dermatitis (AD) is a pruritic, inflammatory skin disease associated with various comorbidities. However, comprehensive analyses of real-world comorbidities in adult patients with AD are limited.To characterize the real-world comorbidities associated with adult AD in an ambulatory population.We queried the MarketScan Commercial Claims and Encounters database from January 1, 2017 to December 31, 2017. Multivariable logistic regressions were performed to compare comorbidities in adult patients with AD versus age- and sex-matched controls.A total of 39,779 patients with AD and 353,743 controls were identified. Increased odds of psychiatric conditions, including anxiety (odds ratio [OR] 1.44) and mood disorders (OR 1.31), were observed in patients with AD. Patients with AD had higher likelihoods of autoimmune diseases, including vitiligo (OR 4.44) and alopecia areata (OR 6.01). Adult AD was also associated with infections, including impetigo (OR 9.72), methicillin-resistant Staphylococcus aureus (OR 3.92), and cellulitis (OR 2.52). Patients with AD were more likely to have systemic conditions, including lymphoid/hematopoietic malignancy (OR 1.91), atherosclerosis (OR 1.69), and metabolic syndrome (OR 1.47). For all the above, P .001.Retrospective analysis of health care claims data.Adult AD is associated with various psychiatric and systemic comorbidities, emphasizing the systemic nature of AD and the need for the collaborative management of these patients.

Background: Dysbiosis and colonization with Staphylococcus aureus is considered to play an important role in the pathogenesis of atopic dermatitis (AD). Recovering this dysbiosis may improve AD symptoms. Omiganan is a synthetic indolicidin analogue antimicrobial peptide with activity against S aureus and could be a viable new treatment option for AD.Objective: To explore the tolerability, clinical efficacy, and pharmacodynamics of omiganan in mild to moderate AD.Methods: Eighty patients were randomized to omiganan 1%, 1.75%, or 2.5% or vehicle twice daily for 28 days on all lesions. Weekly visits included clinical scores and microbiological and pharmacodynamic assessments of 1 target lesion.Results: In all omiganan treatment groups, dysbiosis was recovered by reducing Staphylococcus species abundance and increasing diversity. A reduction of cultured S aureus was observed in all omiganan treatment groups, with a significant reduction for omiganan 2.5% compared to vehicle (-93.5%; 95% CI, -99.2 to -28.5%; P = .02). No significant clinical improvement was observed.Conclusion: Topical administration of omiganan twice daily for up to 28 days in patients with mild to moderate AD led to a recovery of dysbiosis but without clinical improvement. Therefore, a monotreatment that selectively targets the microbiome does not appear to be a successful treatment strategy in mild to moderate AD.

Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells. To elucidate this, T cells from lesional skin and from blood of 10 AD and 11 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA+) and non-skin-homing (CLA-) subfractions. Aeroallergen-specific T cell lines were grown from AD patients’ s PBMC in parallel. Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T cell clones were also detectable to a larger extent among CLA- circulating T cells. Up to 28% of infiltrating cells were identified as allergen-specific by overlapping TCR sequences. Our data shows that in line with the systemic nature of psoriasis, T cells infiltrating psoriatic skin lesions do not exclusively home to the skin and are therefore not specific to antigens that are exclusively encountered at the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens. One Sentence Summary In contrast to psoriasis, T cells driving atopic dermatitis are predominantly skin-homing and are to a certain extent allergen-specific Key Message / Significance Statement T cells that encounter their cognate antigen proliferate clonally and share the same T cell receptor (TCR). Here we describe that clonally expanded T cells from lesional skin in patients with psoriasis and atopic dermatitis (AD) can also be detected within the circulation. While in AD these are mostly homing to the skin, psoriasis-driving T cells do not appear to be exclusively skin-directed. The fact that several co-morbidities are associated with psoriasis matches this observation. In contrast, AD is commonly accompanied by allergic sensitizations. Here we demonstrate that allergen-specific T cells do indeed infiltrate lesional skin and allow a concrete estimate of their frequency.

The impact of diets and foods on cutaneous afflictions has never been a moot point. The number of enquiries from patients and the wider public about how certain foods have impacted upon, or indeed, caused their skin eruption is increasing. While this inquisition is at the forefront of people's and physicians mind in today's modern practice, this has long been a discussion in the scientific world. Metchnikoff alluded to this at the turn of the 20th century. How foods and certain dietary programs impact on diseases has been postulated, although there is still more to learn, despite the patient's advocacy for a particular dietary regime. The study of the role of the microbiome is increasing. Gut dysbiosis, along with the interaction of the gastrointestinal tract, skin, and brain - gut-skin-brain axis is discussed . The role and impact of neuroendocrine transmitters and the skin are explored.

Objective To review recent trends in the development of targeted small molecule drugs (SMDs) for the treatment of immunologically driven disorders, including atopic dermatitis, rheumatoid arthritis, and hereditary angioedema. Data sources Data sources included peer-reviewed published literature from the PubMed database, published abstracts from scientific and medical meetings, and medication information from the Drugs@FDA database. Study selections Articles with primary or retrospective trial results, articles with patient or physician survey results, articles providing expert perspectives, and commentary on chronic immunologic disorders, Food and Drug Administration package inserts, and abstracts from scientific meetings were selected. Results Targeted biological therapies have greatly improved response rates and symptom relief for patients with long-term immunologically driven disorders over the past 2 decades. However, recent advances in the understanding of molecular pathways involved in the pathogenesis of these disorders have led to the development of novel targeted SMDs, such as tofacitinib and berotralstat, that can be delivered orally or topically. Few head-to-head studies that compare the safety and efficacy of biologics to SMDs in immunologically driven disorders exist, although some studies suggest that oral and topical modes of administration are preferred by patients and may improve patient quality of life over time. Conclusion Scientific advances have led to an increase in the development of targeted SMDs for the treatment of chronic immunologic disorders, which may revolutionize the management of these diseases. Head-to-head studies and real-world evidence are needed to fully compare treatment attributes between biologics and SMDs, including safety, efficacy, adherence, impact on quality of life, and cost-effectiveness.

Background Various atopic dermatitis (AD) phenotypes showed an enormously heterogenic risk for subsequent asthma development. Objective We aimed to investigate the association between AD phenotypes and the risk for progression to asthma. Methods We searched PubMed, Embase, and Web of Science databases for relevant publications. Pooled relative risks (RR) with 95% CI were calculated using the CMA-3.0 software. This study has been registered with PROSPERO (CRD42019129273). Results We analyzed 39 publications with 458,810 participants. The RR for asthma in AD was 2.16 (95% CI, 1.88-2.48). The risk in persistent AD (RR, 3.36; 95% CI, 2.83-3.99) was higher than in transient AD (RR, 1.52; 95% CI, 1.34-1.73), and the risk in severe AD (RR, 2.40; 95% CI, 1.96-2.94) was higher than in mild AD (RR, 1.82; 95% CI, 1.03-3.23) or moderate AD (RR, 1.51; 95% CI, 1.30-1.75). The risk for asthma in early-onset AD was slightly higher than in late-onset AD and higher in boys than in girls. Limitations The AD and asthma definitions differed across the included studies. Conclusion Patients with persistent or severe AD were at a higher risk for developing asthma. These findings further elucidate the atopic march and identify target populations for asthma prevention.

Background In the SARS-CoV-2/COVID-19 pandemic, we need to understand the impact of immunomodulatory medications on COVID-19 symptom severity in patients with inflammatory diseases, including the type 2/Th2 polarized skin disease, atopic dermatitis (AD). Objective Because it is believed that type 1/Th1 immunity controls viral infections and that there is a Th1/Th2 counter-regulation, we hypothesized that Th2 targeting with the IL-4Rα-antagonist, dupilumab, in patients with moderate-to-severe AD would rebalance the Th1/Th2 axis, potentially leading to attenuated COVID-19 symptoms. Methods A total of 1237 patients with moderate-to-severe AD in the Icahn School of Medicine at Mount Sinai Department of Dermatology were enrolled in a registry. Patients were screened for COVID-19-related symptoms and assigned a severity score (asymptomatic [0]-fatal [5]). Scores were compared among 3 treatment groups: dupilumab (n = 632), other systemic treatments (n = 107), and limited/no treatment (n = 498). Demographic and comorbid covariates were adjusted by multivariate generalized logistic regression models. Results The dupilumab-treated group showed reduced incidence and severity of COVID-19 symptoms versus other treatment groups. Dupilumab-treated patients were less likely to experience moderate-to-severe symptoms versus patients on other systemics (P = .01) and on limited/no treatment (P = .04), and less likely to experience any symptoms versus patients on other systemics (P = .01). This effect was seen in our entire cohort and in the subgroup of patients with verified COVID-19 or high-risk exposure. Conclusions Patients on dupilumab experienced less severe COVID-19 manifestations and lesser symptoms compared with patients on other systemics and on limited/no treatment. These results suggest that Th2 modulation with dupilumab may have a protective effect on anti-viral immune response in patients with AD.

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions. The knowledge on the pathogenesis of AD is driving the development of new drugs. From the research results, it has been revealed that Th2 cell-mediated immunity, skin barrier dysfunction, and pruritus cause a vicious cycle of AD. On the other hand, the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway are one of the essential signaling pathways in various inflammatory diseases including AD. In particular, TSLP, IL-4, IL-13 and IL-22 occupy an important position for Th2 cell-mediated immune reaction. Moreover, experimentally pan-JAK inhibitor suppress the STAT3 activation and improved the skin barrier function. Furthermore TSLP, IL-4, IL-13 and IL-31 contribute a lot to chronic pruritus of AD, and transmitted via JAK-STAT pathway. Therefore, JAK inhibitors are promising candidates for the treatment of severe AD. Here we review clinical trials of topical dergocitinib; a pan-JAK inhibitor, ruxolitinib; a JAK1 and JAK2 inhibitor, and tofacitinib; a JAK1, JAK2, and JAK3 inhibitor and oral baricitinib; a JAK1 and JAK2 inhibitor, abrocitinib and upadacitinib; JAK1 inhibitor. Significant improvements in the symptoms were obtained by each drug with low frequency of adverse events. In particular, oral JAK inhibitors have the ability to improve the pruritus and skin symptoms quickly. Therefore, the emergence of these topical and oral JAK inhibitors would be regarded as an innovation in the treatment of atopic dermatitis.

Summary Background Diagnosing atopic dermatitis (AD) in infants is challenging. Objectives To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. Methods A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. Results Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22–0·48] or 12 months (OR 0·49, 95% CI 0·32–0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3–43·6) or two (OR 6·5, 95% CI 4·3–9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. Conclusions Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.

Background Increasing evidence shows that pediatric atopic dermatitis (AD) differs from adult AD on a biologic level. Broad biomarker profiling across a wide range of ages of pediatric patients with AD is lacking. Objective Our aim was to identify serum biomarker profiles in children with AD aged 0 to 17 years and compare these profiles with those previously found in adults with AD. Methods Luminex multiplex immunoassays were used to measure 145 biomarkers in serum from 240 children with AD (aged 0-17 years). Principal components analysis followed by unsupervised k-means clustering were performed to identify patient clusters. Patients were stratified into age groups (0-4 years, 5-11 years, and 12-17 years) to assess association between age and cluster membership. Results Children aged 0 to 4 years had the highest levels of TH1 cell–skewing markers and lowest levels of TH17 cell–related markers. TH2 cell–related markers did not differ significantly between age groups. Similar to the pattern in adults, cluster analysis identified 4 distinct pediatric patient clusters (TH2 cell/retinol–dominant, skin-homing–dominant, TH1 cell/TH2 cell/TH17 cell/IL-1–dominant, and TH1 cell/IL-1/eosinophil–inferior clusters). Only the TH1 cell/TH2 cell/TH17 cell/IL-1–dominant cluster resembled 1 of the previously identified adult clusters. Although no association with age or age of onset seemed to be found, disease severity was significantly associated with the skin-homing–dominant cluster. Conclusion Four distinct patient clusters based on serum biomarker profiles could be identified in a large cohort of pediatric patients with AD, of which 1 was similar to previously identified adult clusters. The identification of endotypes driven by distinct underlying immunopathologic pathways might be useful to define pediatric patients with AD who are at risk of persistent disease and may necessitate different targeted treatment approaches.

Atopic dermatitis (AD) is a heterogenous disorder and can be classified into different types. Stratification of subtypes may enable personalized medicine approaches. AD can be categorized into the IgE-high, extrinsic subtype and the IgE-normal, intrinsic subtype. While extrinsic AD is the major subtype possessing skin barrier impairment (high incidence of filaggrin mutations), intrinsic AD occupies about 20% of AD with female dominance and preserved barrier. Extrinsic AD exhibits protein allergy and food allergy, but intrinsic AD shows metal allergy possibly in association with suprabasin deficiency. In particular, accumulated knowledge of food allergy has more clearly characterized extrinsic AD. European American (EA) and Asian AD subtypes have been also proposed. Asian patients with AD are characterized by a unique blended immune dysregulation and barrier feature phenotype between EA patients with AD and those with psoriasis. In another ethnic study, filaggrin loss-of-function mutations are not prevalent in African American patients with AD, and Th1/Th17 attenuation and Th2/Th22 skewing were seen in these patients. Recent endotype classification provides new insights for AD and other allergic disorders. Endotype is defined as the molecular mechanisms underlying the visible features/phenotype. Endotype repertoire harbors activation of type 2 cytokines, type 1 cytokines, and IL-17/IL-22, impairment of epidermal barrier, and abnormalities of intercellular lipids. Classification of endotype has been attempted with serum markers. These lines of evidence indicate a need for personalized or precision medicine appropriate for each subtype of AD.

pH sensing by GPR65 regulates various inflammatory conditions, but its role in skin remains unknown. In this study, we performed a phenome-wide association study and report that the T allele of GPR65-intronic single-nucleotide polymorphism rs8005161, which reduces GPR65 signaling, showed a significant association with atopic dermatitis, in addition to inflammatory bowel diseases and asthma, as previously reported. Consistent with this genetic association in humans, we show that deficiency of GPR65 in mice resulted in markedly exacerbated disease in the MC903 experimental model of atopic dermatitis. Deficiency of GPR65 also increased neutrophil migration in vitro. Moreover, GPR65 deficiency in mice resulted in higher expression of the inflammatory cytokine TNF-α by T cells. In humans, CD4+ T cells from rs8005161 heterozygous individuals expressed higher levels of TNF-α after PMA/ionomycin stimulation, particularly under pH 6 conditions. pH sensing by GPR65 appears to be important for regulating the pathogenesis of atopic dermatitis.

Background: Mucosal-associated invariant T (MAIT) cells are unconventional T cells which recognize microbial metabolites presented by the major histocompatibility complex class I-related molecule MR1. Although MAIT cells have been shown to reside in human and murine skin, their contribution to atopic dermatitis (AD), an inflammatory skin disease associated with barrier dysfunction and microbial translocation, has not yet been determined. Methods: Genetic deletion of MR1 and topical treatment with inhibitory MR1 ligands, which result in the absence and functional inhibition of MAIT cells, respectively, were used to investigate the role of MR1-dependent immune surveillance in a MC903-driven murine model of AD. Results: The absence or inhibition of MR1 arrested AD disease progression through the blockade of both eosinophil activation and recruitment of IL-4- and IL-13-producing cells. In addition, the therapeutic efficacy of phototherapy against MC903-driven AD could be increased with prior application of folate, which photodegrades into the inhibitory MR1 ligand 6-formylpterin. Conclusion: We identified MAIT cells as sentinels and mediators of cutaneous type 2 immunity. Their pathogenic activity can be inhibited by topical application or endogenous generation, via phototherapy, of inhibitory MR1 ligands.

BACKGROUND: Ocular surface diseases (OSDs), including conjunctivitis and blepharitis, are common in atopic dermatitis (AD) patients, but the magnitude and patient characteristics are unclear.OBJECTIVES: To examine the prevalence of OSDs in adults with AD and identify patient characteristics and risk factors.METHODS: We designed a cross-sectional questionnaire-based survey and sent it via a secure public mail to all adult Danes with a hospital diagnosis of AD (ICD-10 code L20.x) registered in the National Patient Register (n=16,718) between 2000-2019 and 7,044 (42%) participated. Primary outcomes were OSDs and severity according to Ocular Surface Disease Index (OSDI). Adjusted odds ratios (aOR) were calculated with 95% confidence intervals (CIs) using logistic regression models.RESULTS: Respondents were mostly females and middle-aged (67.4%, mean [SD] age, 39.0 [15.5] years). Based on Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) 49% had mild AD, 35% moderate, 10% severe and in 6% AD was inactive. 44.3% reported physician-diagnosed asthma bronchiale and 55.8% rhinitis. The lifetime prevalence of OSDs was 66.6% for conjunctivitis, 63.5% for hordeolum, 11.0% for blepharitis, 9.7% for keratitis, 2.0% for pterygium, 1.5% for symblepharon, 1.1% for keratoconus and 12.7% reported current conjunctivitis. Factors associated with lifetime occurrence of conjunctivitis included mild, moderate, and severe AD (aOR=1.48 [95% CI, 1.02-2.14], aOR=1.73 [95% CI, 1.19-2.53], aOR=2.17 [95% CI, 1.42-3.21]), asthma bronchiale and rhinitis (aOR=1.76 [95% CI, 1.49-2.07]), childhood-onset of AD (aOR=1.34 [95% CI, 1.16-1.56]) and systemic AD treatment (aOR=1.27 [95% CI, 1.08-1.50]). Use of soft and hard contact lenses (aOR=2.15 [95% CI, 1.65-2.80], aOR=3.35 [95% CI, 1.62-6.92]) were associated with lifetime occurrence of keratitis. Moderate and severe AD, asthma bronchiale and rhinitis were also associated with a higher OSDI level.CONCLUSIONS: This study identified important patient factors associated with OSDs. Clinicians should be attentive of ocular signs and symptoms in AD patients and ask about these.

Background: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. Objectives: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). Methods: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. Results: At week 16, the proportion of patients achieving POEM scores

Background No biomarkers have been identified that can classify subtypes of hand eczema (HE). Although skin biopsies represent the golden standard for investigations of the skin, the invasive technique is not favorable when investigating skin from sensitive areas. Recent advances in the use of skin tape strips for molecular investigations enable non-invasive investigations of HE. Objective By using whole transcriptome sequencing (WTS), the molecular profile of HE according to different localizations on the hands, etiologies, and clinical/morphological subtypes was investigated. Methods Thirty adult, Danish HE patients, 12 with and 18 without concurrent atopic dermatitis (AD), as well as 16 controls were included. Tape strip samples were collected from lesional, non-lesional, and healthy skin. Total RNA was extracted, and WTS was performed. Results The largest molecular difference of HE patients with and without AD was found in non-lesional skin areas and included a downregulation of CXCL8 for HE patients without AD. Differences between allergic- and irritant contact dermatitis included promising epidermal biomarkers such as EPHA1. Conclusion Skin tape strip samples could be used to assess the gene expression profile of HE on different localizations of the hands. The skin tape strip method identified new molecular markers that showed promising result for the identification of HE subtypes. This article is protected by copyright. All rights reserved.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with an increasing prevalence worldwide. The aetiology and pathogenesis of AD have not been fully elucidated. Previous studies have suggested the role of fungi as a triggering factor in the development AD. Here we conducted a systematic review to investigate the skin mycobiome profiles in AD and to address whether there is an association between fungal dysbiosis and AD. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between January 1st, 2010 and April 21st, 2021. A total of 11 human studies and 3 animal studies were included in this analysis. Fungal dysbiosis was observed in AD lesions with a depleted amount of Malassezia and a higher abundance of filamentous fungi. A positive correlation between Candida and Staphylococcus was also demonstrated in AD. We supposed that specific species of Malassezia spp. and Candida spp. may play a role in the pathogenesis of AD by interacting with the pathogenic bacteria. Topical application of emollients could improve the skin barrier function and restore the skin fungal flora by increasing the amount of Malassezia. Further studies focusing on the complex interplay between specific skin fungi and the host can provide better insight into the role of microorganisms in the pathogenesis of AD.

The first wave of the coronavirus disease 2019 (COVID‐19) pandemic had an enormous impact on health‐care services, including on care provision for children with atopic dermatitis (AD). We investigated the impact of COVID‐19 on the care for children with moderate to severe AD at our tertiary outpatient clinic and examined satisfaction with care. We reviewed outpatient records, comparing total number and types of consultations during the first COVID‐19 wave (March until July 2020) with the corresponding months of 2019 and 2018. In addition, we conducted a questionnaire‐based study investigating the impact of COVID‐19 on clinical and psychological symptoms, and satisfaction with care. A total number of 913 consultations (466 individual children) were conducted during the first COVID‐19 wave in 2020, while 698 (391 individual children) and 591 consultations (356 individual children) were conducted in 2019 and 2018. The proportion of remote consultations was higher (56.2%) compared to 14.0% in 2019 and 12.7% in 2018. Worsening of AD was reported by 9.7% of caretakers. Overall satisfaction with provided care was high (8.6; interquartile range [IQR] = 7.3–10.0). Caretakers receiving face‐to‐face consultation were significantly (p = 0.026) more satisfied (9.0; IQR = 8.0–10.0) than caretakers receiving remote consultation (7.9; IQR = 7.0–9.5). The COVID‐19 pandemic had an unprecedented impact on care provision for children with AD, particularly on the number of remote consultations. Overall satisfaction with care was high. The impact of COVID‐19 on disease severity remained limited. Remote consultations seem to be a useful tool that can be put into practice during the COVID‐19 pandemic.

Key research advances in atopic dermatitis (AD) suggest the complexity of its endotypes. A comprehensive serum biomarker panel revealed at least four types of AD. Some represent classic TH2-dominant AD with filaggrin mutations commonly reported in Europeans, a simultaneously activated multipolar axes of cytokines often reported in Asians, and an intrinsic type characterized by TH2-inferiority. Innate lymphoid cells, including NK cells, NKT cells, and fibroblasts, play a role in AD development and heterogeneity. Here, we discuss the endotypes of AD from the perspective of antigen types (hapten vs. protein antigens), barrier function, and a novel set of immune cells. Endotypic stratification of AD may lead to the development of customized therapeutic strategies in the future.

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. Objectives In this study AD characteristics and its atopic comorbidities are compared in smoking and nonsmoking AD patients. Methods TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included into TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analyzed comparing AD disease characteristics and comorbidities in smokers versus non-smokers. Results Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n=352; 38.8%) and nonsmokers, however lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to nonsmoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than nonsmokers. Total IgE levels were more elevated in smokers and they displayed a younger age at initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to nonsmokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. Conclusions German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

The rising prevalence of atopic dermatitis (AD) in developing countries and its substantial socioeconomic impact have furthered research over the last two decades giving way to advances in its aetiopathogenesis and treatment. Topical therapies targeting newly identified AD signalling pathways are being developed. Numerous clinician-assessed disease severity outcome measurement instruments (OMIs) are available to evaluate the efficacy of investigational treatments in proof-of-concept (POC) trials for AD. However, little is known about the comparative sensitivity of these efficacy OMIs. We performed a systematic review and meta-analysis to compare the sensitivity of different OMIs in controlled trials of topical therapies for AD published between January 1, 2000 and April 7, 2020. Treatment effect size of OMIs reported at Week 4 was calculated with 95% Confidence Interval (CI). The sensitivity of OMIs was compared by pooling the standardized difference between means (Cohen's d and Cohen's h) for any two OMI-parameter combinations that were reported in ≥3 studies identified in our systematic review. Assessed parameters were difference between active and vehicle at Week 4 and change from baseline [CFB] and percentage change from baseline [%CFB] at Week 4. We identified a total of 15 studies with 3313 subjects examining 14 different OMIs were included in this quantitative meta-analysis. Continuous OMIs had a significantly higher treatment effect size vs. dichotomous OMIs (P = 0.006). Comparisons of Eczema Area and Severity Index (EASI), Investigator's Global Assessment (IGA), body surface area (BSA) and SCORing Atopic Dermatitis (SCORAD) for available parameters were performed and generally had a similar sensitivity, with BSA showing smaller overall effect size estimates. In conclusion, continuous OMIs used in topical clinical trials for AD had significantly higher treatment effect sizes when compared to dichotomous OMIs. Continuous OMIs could provide more power for POC trials with a small sample size in atopic dermatitis with topical therapies.

Since the first report of allergen-specific immunotherapy (AIT) by Noon et al. 110 years ago, a multitude of clinical and in vitro studies have been performed to identify the effects of the only curative treatment for allergies. However, in atopic dermatitis (AD), one of the most prevalent skin diseases, it is rarely used, despite evidence showing that aeroallergens can contribute to disease exacerbation. This review gives an overview about the studies, meta-analyses, and current guideline recommendations regarding AIT in AD patients. There is a distinct heterogeneity in the study designs, different allergens and application forms, endpoints and patient cohorts, which hinders the comparability of studies. Several trials depict a beneficial effect of AIT in AD patients suggesting that at least a subgroup of patients can benefit from treatment. Further developments in the field of AIT may advocate broader use in AD patients.Seit dem ersten Bericht über die Allergenimmuntherapie (AIT) durch Noon et al. vor 110 Jahren wurden zahlreiche klinische und grundlagenwissenschaftliche Studien durchgeführt, um die Effekte der einzigen kurativen Behandlung von Allergien zu untersuchen. Bei der atopischen Dermatitis (AD) findet sie jedoch nur selten Anwendung, obwohl es Evidenz dafür gibt, dass Aeroallergene zu Exazerbationen der Erkrankung beitragen können. Dieser Übersichtsbeitrag umfasst die aktuelle Studienlage, Metaanalysen und Leitlinienempfehlungen zur AIT bei AD-Patienten. Es zeigt sich eine große Heterogenität hinsichtlich Studiendesigns, Patientenkohorten, Allergenen, Applikationsformen und Endpunkten, wodurch die Vergleichbarkeit der Studien erschwert wird. Mehrere Untersuchungen zeigen eine positive Wirkung der AIT auf den Schweregrad der AD, was darauf hindeutet, dass zumindest eine Untergruppe von Patienten von der Behandlung profitieren kann. Weitere Entwicklungen auf dem Gebiet der AIT könnten dazu beitragen, dass die Therapie einen breiteren Einsatz bei AD-Patienten findet.

BACKGROUND Atopic dermatitis (AD) is a frequent and heterogeneous inflammatory skin disease, for which personalized medicine remains a challenge. High-throughput approaches have improved understanding of the complex pathophysiology of AD. However, a purely data-driven AD classification is still lacking. METHODS To address this question, we applied an original unsupervised approach on the largest available transcriptome dataset of AD lesional (n = 82) and healthy (n = 213) skin biopsies. RESULTS Taking into account pathological and physiological state, a variance-based filtering revealed 222 AD-specific hyper-variable genes that efficiently classified the AD samples into 4 clusters that turned out to be clinically and biologically distinct. Comparison of gene expressions between clusters identified 3 sets of upregulated genes used to derive metagenes (MGs): MG-I (19 genes) was associated with IL-1 family signaling (including IL-36A and 36G) and skin remodeling, MG-II (23 genes) with negative immune regulation (including IL-34 and 37) and skin architecture, and MG-III (17 genes) with B lymphocyte immunity. Sample clusters differed in terms of disease severity (p = .02) and S. aureus (SA) colonization (p = .02). Cluster 1 contained the most severe AD, highest SA colonization, and overexpressed MG-I. Cluster 2 was characterized by less severe AD, low SA colonization, and high MG-II expression. Cluster 3 included mild AD, mild SA colonization, and mild expression of all MGs. Cluster 4 had the same clinical features as cluster 3 but had hyper-expression of MG-III. Last, we successfully validated our method and results in an independent cohort. CONCLUSION Our study revealed unrecognized AD endotypes with specific underlying biological pathways, highlighting novel pathophysiological mechanisms. These data could provide new insights into personalized treatment strategies.

Introduction: Atopic dermatitis is a common dermatologic condition that affects millions of people worldwide, and a standardized approach to treatment was published by the American Academy of Dermatology (AAD) in 2013–14. Since 2014, new FDA-approved treatment options such as dupilumab and crisaborole have changed the landscape of AD management, and future therapies such as JAK inhibitors and anti-interleukin 13 and 31 antibodies appear effective, emphasizing the need for a comprehensive review to give clinicians an updated toolbox to aid in pharmacologic management. Areas Covered: In this review, the authors explore the updated efficacy and safety data on established therapeutic options for AD including topical corticosteroids, topical calcineurin inhibitors, cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil. In addition, the authors also explore trial data and studies on dupilumab, crisaborole, omalizumab, tofacitinib, ruxolinitib, abrocitinib, baricitinib, upadacitinib, delgocitinib, nemoliuzumab, and tralokinumab. Expert opinion: The AAD guidelines must be updated in the future to include several new treatment modalities that have revolutionized the pharmacologic management of patients with AD, including dupilumab and crisaborole. The future of AD treatment is also extremely bright, as JAK inhibitors and Il-13/31 antibodies have shown convincing results in the improvement of AD patients’ lives in various trials and studies that have been examined in this paper.

Background The real-world course of health-related quality of life (HRQoL) in atopic dermatitis (AD) is not well established. Aim To examine predictors, longitudinal course and phenotypes of HRQoL in adult patients with AD. Methods This was a prospective dermatology-practice based study of 955 patients with AD (age 18-97 years). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. HRQoL was assessed using the 10-item short-form Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health (PGH). AD severity and impact was assessed by patient-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Objective SCORing Atopic Dermatitis (O-SCORAD), Investigator's Global Assessment (IGA), Numerical Rating Scale (NRS) average and worst itch, PROMIS sleep-related impairment (SRI), and nine-item Patient Health Questionnaire (PHQ)-9. Repeated-measures regression models were constructed to examine itch over time. Results In multivariable linear regression models controlling for age, race/ethnicity, history of asthma, hay fever and food allergy, baseline PGH-physical (PGH-P4) T scores were inversely associated with patient-reported global AD severity, POEM, EASI, objective SCORAD, IGA, NRS average and worst itch, PROMIS SRI and PHQ-9, with stepwise decreases of physical health with worsening severity. PGH-mental health (PGH-M4) T scores were associated with all aforementioned severity measures aside from POEM. In multivariable repeated measures linear regression models, decreased PGH-P4 and PGH-M4 T scores and mapped five-dimension EuroQoL over time were associated with self-reported global AD severity, NRS worst and mean itch, POEM, PROMIS sleep disturbance and SRI, EASI, objective SCORAD, IGA and PHQ-9. Latent class analysis identified six classes of HRQoL, which were associated with measures of AD severity, nonwhite race, Hispanic ethnicity and having only public health insurance, but not age or sex. Conclusion Patients with AD have a heterogeneous longitudinal course and distinct patterns of HRQoL. Many patients had fluctuating HRQoL over time. Most patients with moderate to severe disease at baseline had persistent HRQoL impairment over time.

Atopic dermatitis is a complex, chronic inflammatory skin disorder with significant morbidity. It is often a frustrating condition for both children and parents due to chronic and relapsing course. There is now an increasing understanding of the disease pathogenesis resulting in discovery of much wanted newer therapeutics and targeted therapies after a long time. Whether these interventions will result in sustained benefits or long term cure remains to be seen.

Background Primary care providers (PCPs), including pediatricians and general practitioners, are often the first to see children with eczema/atopic dermatitis (AD). Little is known about management of pediatric AD by PCPs and adherence to national guidelines. Objective To review existing literature examining management components of pediatric AD (topical corticosteroids [TCS], topical calcineurin inhibitors [TCIs], antihistamines, bathing, emollients, and diet) by PCPs. Data Sources PubMed/Medline and Embase. Study Eligibility Criteria English-language articles dated 2015 to 2020 reporting outcomes addressing management of pediatric AD by PCPs. Study Appraisal and Synthesis Methods Two authors independently screened titles/abstracts, reviewed full-text articles, extracted relevant data, and evaluated study quality. Disagreements were resolved by a third author. Results Twenty articles were included. Surveys and national database analyses were the most common methodologies (n = 7 each). PCPs commonly prescribed TCS but had a preference for low-potency agents, overprescribed nonsedating antihistamines, and avoided TCIs. PCPs commonly recommended emollients, although this was not universal. Data characterizing nonmedication management were limited. Limitations Most studies did not examine individual patient encounters, but rather relied on providers reporting their general behaviors. Provider behavior may vary based on country of practice. Conclusions and Implications of Key Findings Knowledge and management gaps exist among PCPs in treating pediatric AD in key areas including knowledge of TCS safety profiles and prescribing of TCIs. The current literature is largely limited to small studies that evaluate prescribing behaviors with limited data characterizing nonmedication management, highlighting the need for future research in this area.

Differences in consumer product availability, distribution, and use may lead to national differences in contact sensitization frequencies. Objective The aim of the study was to describe the differences in contact allergy between the United States (US) and Canada. Methods This is a retrospective cross-sectional analysis of the North American Contact Dermatitis Group data from 2005 to 2016. Frequencies of demographics, clinical characteristics, positive reactions, trends, and occupations were calculated. Results A total of 28,640 patients underwent patch testing. At least 1 positive patch test was observed in 18,599 patients (US, 11,641 [66.5%]; Canada, 6958 [62.5%]). When comparing the 2 groups, US positive reactions were more likely to occur in male patients (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.31-1.49), older than 40 years (OR = 1.30, 95% CI = 1.22-1.38), Black (OR = 2.67, 95% CI = 2.24-3.19) or Hispanic race (OR = 3.53, 95% CI = 2.61-4.78), and/or patients with scattered generalized dermatitis (OR = 1.96, 95% CI = 1.80-2.13). They were less likely to occur in patients with eczema (OR = 0.61, 95% CI = 0.57-0.65) and Asian race (OR = 0.50, 95% CI = 0.44-0.56). Nickel (US, 16.0%; Canada, 22.4%) and methylisothiazolinone (US, 13.4%; Canada, 11.0%) were the top allergens. The third most frequent was neomycin (US, 11.7%) and fragrance mix I (Canada, 10.2%). Conclusions National differences in allergen prevalence and trends exist in North America.

The clinical significance and regulators of IL-13Rα2 in itch and atopic dermatitis (AD) remain unclear. To identify disease-driven regulatory circuits of IL-13Rα2, transcriptomic/pathological analysis was performed in skin from patients with AD, psoriasis, healthy subjects, and murine AD model. Functionality was investigated in sensory neurons, keratinocytes and animal model, by using knockdown (KD), calcium imaging, RNA-seq, cytokine arrays, pharmacological assays, and behavioural investigations. In our study, an upregulated IL-13Rα2 expression was revealed in skin of AD patients, but not psoriasis, in a disease activity-dependent manner. In cultured human keratinocytes, IL-13 increased IL-13Rα2 transcription levels, and this were downregulated by IL-13Rα1KD. IL-13Rα2KD reduced transcription levels of EDNRA, CCL20, CCL26. In contrast, sensory neuron-derived IL-13Rα2 was upregulated by TLR2 heterodimer agonists, Pam3CSK4 and FSL-1. In a mouse cheek model, pre-administration of Pam3CSK4 and FSL-1 enhanced IL-13-elicited scratching behaviour. Consistently, in cultured sensory neurons Pam3CSK4 enhanced IL-13-elicted calcium transients, increased number of responders, and orchestrated chemerin, CCL17 and CCL22 release. These release was inhibited by IL-13Rα2KD. Collectively, IL-13 regulates keratinocyte-derived IL-13Rα2 and TLR2 to modulate neuronal IL-13Rα2, thereby promoting neurogenic inflammation and exacerbating AD and itch. Thus, the cutaneous IL-13-IL-13Rα2 and neuronal TLR2-IL-13Rα2 pathway represent important targets to treat AD and itch.

Background Canine atopic dermatitis (AD) is a common condition that often requires multimodal therapy. Including a diet in the multimodal management of AD may reduce medication doses, saving pet owners money and reducing side effects. The objective of this randomized, double-blind, placebo-controlled clinical trial was to determine if a diet fortified in antioxidants, polyphenols, and omega-3 fatty acids can reduce the clinical signs of AD. Forty client-owned dogs with AD were enrolled in the study and assigned to either an enriched diet (diet B) or control diet (diet A) for 60-days. CADESI-4 index scores and owner-reported pruritus scores were measured periodically. Results Total CADESI-4 index scores for dogs eating diet B were lower on day 60 compared to baseline (P = 0.003). There was no statistical difference in scores for dogs eating diet A over a 60-day period. Diet B dogs had 25 and 49% reductions in CADESI-4 index scores on days 30 and 60, respectively (P = 0.0007) while diet A had no change over the study period. When comparing the percent change in owner-reported pruritus scores, diet B also performed better than diet A. By day 60, owners feeding diet B to their dogs reported a significant reduction (P P = 0.08). Conclusions These study results demonstrate feeding a diet enriched with ingredients to improve skin health and reduce inflammation improves the clinical signs of AD in dogs.

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.

Purpose Topical calcineurin inhibitors (TCIs) are an important anti-inflammatory drug for treating atopic dermatitis (AD). However, those treatment responses are variable. In this study, we stratified AD patients by patterns of response to remission maintenance therapy (proactive therapy) with topical tacrolimus, a typical TCI. Thereafter, we explored patient features that predict the success or failure of proactive therapy using TCI (TCI proactive therapy). Methods A single-arm open-label clinical study aimed to evaluate the efficacy of TCI proactive therapy was conducted in 31 patients with AD. Patients were treated with TCS to induce remission (remission-induction period) followed by daily TCI ointment (0.1% tacrolimus) application for 4 weeks (maintenance therapy period), and twice-weekly application for 12 weeks (proactive therapy period). Based on its results, treatment outcomes were correlated with the patients’ clinical and laboratory findings. Results Of the 31 patients enrolled in the study, 21 successfully completed maintenance therapy (TCI responders). Among them, 13 completed (proactive-completed group) and 8 failed proactive therapy (proactive-dropout group). At the beginning of maintenance therapy, the serum IgE level was significantly higher in the TCI responders than in those who failed maintenance therapy (p = 0.049). At the beginning of proactive therapy, the mean-SCORing Atopic Dermatitis (SCORAD) score was significantly different between the proactive-completed (11.7 ± 4.6) and proactive-dropout (16.6 ± 4.2) groups (p = 0.025). In proactive-dropout group patients, worsened disease activity correlated well with the elevation of serum lactate dehydrogenase (LDH) and Thymus and activation-regulated chemokine (TARC) levels and peripheral eosinophil count. Conclusion AD patients were stratified into three different response patterns to TCI proactive therapy. Patients with less involvement of IgE in the pathogenesis and inadequate remission induction by TCS may not be expected to respond well to TCI proactive therapy.Key messagesAD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy.The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels.TCI proactive therapy should be done after the achievement of adequate remission induction by TCS.

There is evidence that Staphylococcus aureus colonisation is linked to severity of atopic dermatitis. As no gold standard for S. aureus sampling on atopic dermatitis skin lesions exists, this study compared three commonly used methods. In addition, effectiveness of standard skin disinfection to remove S. aureus colonisation from these inflamed skin lesions was investigated. In 30 atopic dermatitis patients, three different S. aureus sampling methods, i.e. detergent scrubbing, moist swabbing and tape stripping, were performed on naïve and disinfected skin lesions. Two different S. aureus selective media, mannitol salt agar and chromID agar, were used for bacterial growing. Quantifying the S. aureus load varied significantly between the different sampling methods on naïve skin lesions ranging from mean 51 to 1.5 × 104 CFU/cm2 (p p S. aureus load (p S. aureus selection agar plates to implement further clinical studies for the effectiveness of topical anti-staphylococcal antibiotics. Other disinfection regimes should be considered in atopic dermatitis patients when complete de-colonisation of certain skin areas is required, e.g. for surgical procedures.

Mesenchymal stem cells (MSCs) have emerged as a new therapy for various immune-mediated inflammatory diseases. In this study we perform the first double-blinded, placebo-controlled evaluation of the efficacy of adipose-derived allogenic canine MSCs for the treatment of canine atopic dermatitis (cAD). Enrolled canine patients were randomly divided into placebo (PBS saline), low-dose (5 × 105 cells/kg), and high-dose (5 × 106 cells/kg) treatment groups. Each patient received three subcutaneous MSCs treatments or PBS saline at four-week intervals with injections at five sites. Patients were monitored by physical exams, pruritus visual analog scales (PVAS) signed by the primary caretaker, canine atopic dermatitis extent and severity index-4 (CADESI-4) scores by two veterinarians, and complete blood count and serum chemistry analysis along with laboratory analysis for potential biomarkers. Patients were kept off any immune-modulating drugs during the study period, and oral antibiotics and topicals were used for managing pruritus and secondary infections. The PVAS scores and the serum miR-483 levels were significantly lower in the high dose group compared to the placebo group at day90 post first-treatment. The CADESI-4 scores of the high dose group also showed downward trends. No severe adverse effects were observed in any patient in this study. The high dose MSC treatment is efficacious in alleviating the clinical signs of cAD until 30 days after the last subcutaneous administration of MSCs, and miRNA-483 may be a reliable prognostic biomarker for cAD. The MSCs efficacy and potential biomarkers should be further explored by a larger scale clinical trial.

Background: Localization of atopic dermatitis (AD) in exposed areas such as the hands, head, and neck has been considered as a negative factor impacting on dupilumab response, although a comparison of exposed versus unexposed areas is not currently available. Objectives: The aim of this study is to evaluate the clinical response to dupilumab depending on the presence or persistency of AD skin manifestations in specific body areas. Methods: The study retrospectively collected clinical and demographic data of adult patients affected by moderate to severe AD. Based on the anatomical sites involved, 5 subcohorts of patients were identified. Results: A total of 41 patients were included in the study. Disease amelioration was detected during the study period, although baseline head/neck and hand localization was associated with a significantly lower likelihood of achieving an Eczema Area Severity Index (EASI) ≤1. In addition, patients with head/neck persistency showed a significantly lower response when compared to patients without persistency of head/neck AD in terms of both mean EASI and Dermatology Life Quality Index (DLQI) reduction. Conclusion: AD localization in exposed areas at the baseline and AD persistency at the head/neck may have a negative impact on certain treatment response parameters to dupilumab therapy.

Background: Hand eczema (HE) is common in health care workers (HCWs). During the last decade, new recommendations have supported increased use of alcohol-based hand rub (ABHR) to partially replace hand washings to lower the prevalence of HE. However, newer data on this recommendation is lacking. Objectives: To assess current 1-year prevalence of HE in HCWs, to investigate exposure, and the extent of subjective discomfort to hand washings and ABHR. Methods: A digital questionnaire was sent to 4876 HCWs from April to May 2020. Results: Of 2125 respondents (1779 women, 346 men), 14.7% reported HE within the last year. In total, 9.1% reported >20 hand washings per shift and 76.0% reported ABHR use >20 times per shift. HE was significantly associated with hand washings (adjusted odds ratio [OR] 1.73 [95% confidence interval [CI] 1.26-2.36]) and glove use on wet skin (adjusted OR 1.99 [95% CI 1.27-3.12]). Subjective discomfort to ABHR was reported significantly more often than to hand washings (P

The recent advent of numerous clinical trials for the treatment of moderate-to-severe atopic dermatitis has led to new and emerging therapeutic options for this chronic inflammatory skin disease. With this rapid development has come a lack of consistency in study designs, trial conduct, and statistical analyses. Healthcare providers are challenged to interpret how variations in study parameters may influence clinical trial results. Based on literature review and our experience as clinical trialists, we compiled a list of 22 key study parameters of contemporary clinical trials in moderate-to-severe atopic dermatitis and ranked the top study parameters that may have a significant effect on efficacy results. The top parameters included study comparators, rules for rescue treatment, washout periods for topical and systemic treatments, inclusion criteria such as disease severity by Eczema Area and Severity Index and/or Investigator Global Assessment scores, and the duration of the screening period. We describe considerations for these key parameters, with a focus on between-parameter interactions and effect on efficacy results. This may serve to inform the interpretation of atopic dermatitis clinical trials and raise the profile of the need to harmonize the clinical trial design., Plain Language Summary Atopic dermatitis (AD) is a skin disease characterized by red, itchy skin that is highly burdensome for patients. Patients with moderate-to-severe disease have large, inflamed skin areas with frequent itching. Recently, the number of clinical trials for drugs that treat moderate-to-severe AD has rapidly increased, with differences in how these trials are designed. There is a need for healthcare providers examining results from different clinical trials to understand how trial design factors might influence study outcomes. In this article, we identify key trial design factors that impact study outcomes, detail how these factors can impact clinical trial results, and explore how these factors interact with one another to affect study outcomes. The five most important design factors, as determined via author surveys, were study comparators (a placebo and/or another drug to which the drug being studied is compared); the rules for the use of rescue treatment (a form of treatment given if an enrolled participant has uncontrolled AD symptoms); washout periods (the time before the trial when previous treatments are stopped to allow them to be cleared from a patient’s system); inclusion criteria (that determine which participants are included); and the length of the screening period (the time when patients are assessed to determine if they qualify for participation). By understanding how these key trial design factors impact on study outcomes, healthcare providers may be equipped to better interpret different AD clinical trials. This work also emphasizes the value of harmonizing the AD clinical trial design. Graphic abstract

BACKGROUND Phototherapies could represent an efficient option for the treatment of atopic dermatitis (AD), but the evidences available for clinical choices were contradictory. OBJECTIVE This study aimed to evaluate the efficacy of different phototherapies on AD. METHODS This systematic review and network meta-analysis included randomized controlled trials (RCTs) through searching keywords from PubMed, EMBASE, and the Cochrane library. We summarized different phototherapy types and scoring systems. Scoring Atopic Dermatitis (SCORAD) absolute score changes were estimated by mean differences (MDs) and standard deviations (SDs) and then included in the network meta-analysis. The effect sizes of comparison of different phototherapies were presented as MDs and 95% confidence intervals (CIs). Egger's test was used to evaluate publication bias. RESULTS Eleven RCTs were included in the systematic review and 4 studies in the network meta-analysis. Based on the pooled estimates, medium-dose ultraviolet A1 (UVA1) cold light was superior to medium-dose UVA1 (MD 8.92; 95% CI: 5.60-12.24) but no significant difference between high-dose (UVA1) and medium-dose UVA1 cold light (MD 0.66; 95% CI: -5.57 to 6.90). Publication bias was not supported by Egger's test (P = .168). CONCLUSIONS Due to possible long-term adverse effects of high-dose UVA1, medium-dose UVA1 cold light appears to be the superior form for AD.

Dilute sodium hypochlorite (bleach) baths have been used in routine care for many dermatologic conditions, namely atopic dermatitis. The benefits of bleach baths in reducing bacterial carriage have been well documented; however, the instructions often require subjective interpretation of bathtub size and may result in varying concentrations of bleach. Herein, we review the evidence for use of bleach baths and provide a method for ensuring that proper bleach concentrations are achieved.

Diet has long been understood to have an intricate association with atopic dermatitis, although much remains unelucidated. Skin barrier dysfunction with dysbiosis and consequent impairment of immune tolerance likely underly the pathogenesis of coincident atopic dermatitis and food allergy. There is a wide range of possible skin reactions to food, complicating the diagnosis and understanding of food allergies. Many patients, parents, and providers incorrectly suspect diet as causative of atopic dermatitis symptoms and many have tried elimination diets. This frequently leads to inaccurate labeling of food allergies, contributing to a dangerous spiral of inappropriate testing, referrals, and dietary changes, while neglecting established atopic dermatitis treatment essentials. Alternatively, certain dietary supplements or the introduction of certain foods may be beneficial for atopic dermatitis management or prevention. Greater consensus on the role of diet among providers of patients with atopic dermatitis is strongly encouraged to improve the management of atopic dermatitis.

Background/aim Determining the characteristics and risk factors of severe disease is extremely important to combat atopic dermatitis (AD), which has recently shown increasing prevalence. In this study, we aimed to investigate the clinical characteristics of pediatric patients with AD and identifying the factors associated with the severity of the disease. Materials and methods A total of 304 pediatric patients diagnosed with atopic dermatitis were included in the study. The patients’ age at admission, age at onset of symptoms, the presence of atopy history in their family, eosinophil levels obtained from blood counts were recorded, together with the data of cigarette exposure, and area of residence. Disease severity was determined according to the SCORAD index. Epidermal prick tests (EPT) were applied to all patients. Results There was a negative correlation between the SCORAD score and both age at admission (r = 0.277, p < 0.001) and age at onset of the symptoms (r = –0.474, p < 0.001). Food sensitization rates were higher in individuals with moderate-severe disease (90.7% vs. 23.1%; p < 0.001) and patients with food allergy (FA) had significantly higher SCORAD scores [33 (IQR: 22–44) vs. 14 (IQR: 12–16); p < 0.001]. SCORAD scores of the individuals living in rural areas were higher than the ones living in urban [22 (IQR: 15–39.5) vs. 15 (IQR: 12–22); p < 0.001]. Familial atopy history was more common in patients with moderate-severe disease (66.5% vs. 17.5%; p < 0.001). The SCORAD scores were higher in patients exposed to passive smoking [21 (IQR:14.75–38) vs. 13 (IQR: 12–16); p < 0.001]. The eosinophil count found to be positively correlated with SCORAD scores (r = 0.531, p < 0.001). Conclusion Our findings show that early-onset, food sensitivity, living in rural areas, having familial atopy history and passive cigarette smoke exposure play a role in severe AD. Since it is remarkably correlated with SCORAD scores, eosinophil count can be used as a marker to assess the severity of AD in children.