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Background Objective Methods Results Conclusion Atopic dermatitis (AD) is a chronic inflammatory skin disease resulting in decreased quality of life. Histamine and specifically the H4 receptor play a key role in the inflammatory process in AD and serve as targets for novel therapeutic approaches.In the present study we aimed to elucidate the immunopathological mechanisms with which the H4 receptor impacts TH2 cells and contributes to AD pathophysiology.Total CD4+ T cells obtained from healthy or AD individuals and in vitro differentiated TH2 cells were cultured under different conditions and the mRNA expression or protein production of target molecules were determined using quantitative real‐time PCR and ELISA.H4 receptor mRNA expression was upregulated concentration dependent upon IL‐4 stimulation in in vitro differentiated TH2 cells progressively during the differentiation. Transcriptomic analysis of in vitro differentiated TH2 versus TH1 cells revealed that the H4 receptor among other genes represents one of the highly upregulated genes in TH2 cells.Most importantly, increased amounts of IL‐5 and IL‐13 mRNA expression were detected in in vitro differentiated TH2 cells as well as protein secretion in the presence of histamine or of the H4 receptor‐selective‐agonist when compared to the untreated control.We show for the first time an H4 receptor dependent upregulation of the pro‐inflammatory cytokines IL‐5 and IL‐13 in human TH2 cells by histamine. This suggests that the blockade of the H4 receptor may lead to downregulation of these cytokines and amelioration of AD symptoms as reported in first clinical studies. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in a spectrum of clinical subtypes. The application of genomics has elucidated the role of genetic variations in predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on the molecular underpinnings of AD. Proteomics explores the involvement of proteins in AD pathophysiology, while epigenomics examines the impact of environmental factors on gene expression. Lipidomics, which investigates lipid profiles, enhances our understanding of skin barrier functionalities and their perturbations in AD. This review synthesizes insights from these omics approaches, highlighting their collective importance in unraveling the intricate pathogenesis of AD. The review culminates by projecting future trajectories in AD research, particularly the promise of multi‐omics in forging personalized medicine and novel therapeutic interventions. Such an integrated multi‐omics strategy is poised to transform AD comprehension and management, steering towards more precise and efficacious treatment modalities. [ABSTRACT FROM AUTHOR]

Background: The antimicrobial ribonuclease RNase 7 is abundantly expressed in the epidermis of lesional skin of atopic dermatitis (AD). Host RNase inhibitor (RI) binds to RNase 7 and blocks its ribonuclease activity. This study aimed to evaluate the impact of RNase 7–RI interactions on AD. Methods: Cultured human primary keratinocytes, with siRNA‐mediated downregulation of RNase 7 and RI, were stimulated with the synthetic RNA polyinosinic‐polycytidylic acid (poly I:C). Induction of proinflammatory mediators was analyzed by real‐time PCR and ELISA. RI expression in AD non‐lesional and lesional skin biopsies and healthy controls was analyzed by real‐time PCR and immunostaining. RI protein release in vivo on the AD skin surface was determined by western blot. Antimicrobial and ribonuclease assays were used to investigate the functional role of RI. Results: RNase 7 inhibited the RNA‐induced expression of proinflammatory mediators in keratinocytes. Accordingly, downregulation of RNase 7 in keratinocytes enhanced RNA‐mediated induction of proinflammatory mediators, whereas downregulation of RI had the opposite effect. RI was released by damaged keratinocytes and epidermis. In vivo expression and release of RI on the skin surface were enhanced in lesional AD skin. Rinsing solution from the surface of lesional AD skin blocked the ribonuclease activity of RNase 7. The anti‐Staphylococcus aureus activity of RNase 7 was abrogated by RI. Conclusions: Our data suggest a novel role of RI as a trigger factor of inflammation in AD by blocking the ribonuclease and antimicrobial activity of RNase 7, thereby enhancing RNA‐mediated inflammation and S. aureus growth. [ABSTRACT FROM AUTHOR]

Background: Efforts to profile atopic dermatitis (AD) tissues have intensified, yet comprehensive analysis of systemic immune landscapes in severe AD remains crucial. Methods: Employing single‐cell RNA sequencing, we analyzed over 300,000 peripheral blood mononuclear cells from 12 severe AD patients (Eczema area and severity index (EASI) > 21) and six healthy controls. Results: Results revealed significant immune cell shifts in AD patients, including increased Th2 cell abundance, reduced NK cell clusters with compromised cytotoxicity, and correlated Type 2 innate lymphoid cell proportions with disease severity. Moreover, unique monocyte clusters reflecting activated innate immunity emerged in very severe AD (EASI > 30). While overall dendritic cells (DCs) counts decreased, a distinct Th2‐priming subset termed "Th2_DC" correlated strongly with disease severity, validated across skin tissue data, and flow cytometry with additional independent severe AD samples. Beyond the recognized role of Th2 adaptive immunity, our findings highlight significant innate immune cell alterations in severe AD, implicating their roles in disease pathogenesis and therapeutic potentials. Conclusion: Apart from the widely recognized role of Th2 adaptive immunity in AD pathogenesis, alterations in innate immune cells and impaired cytotoxic cells have also been observed in severe AD. The impact of these alterations on disease pathogenesis and the effectiveness of potential therapeutic targets requires further investigation. [ABSTRACT FROM AUTHOR]

The article discusses a new antibody called SM17 that targets IL-17RB and its potential in treating atopic dermatitis (AD). The study found that SM17 could inhibit the release of Th2 cytokines and suppress the proliferation of ILC2 and Th2 cells. In a mouse model of AD, SM17 demonstrated beneficial effects in reducing skin inflammation, epidermal hyperplasia, and eosinophil infiltration. The study suggests that SM17 may be a promising treatment option for AD with enhanced therapeutic effects and a superior safety profile compared to current treatments. [Extracted from the article]

Background: Tralokinumab is a monoclonal antibody that specifically neutralizes interleukin (IL)‐13, a key driver of skin inflammation and barrier abnormalities in atopic dermatitis (AD). This study evaluated early and 2‐year impacts of IL‐13 neutralization on skin and serum biomarkers following tralokinumab treatment in adults with moderate‐to‐severe AD. Methods: Skin biopsies and blood samples were evaluated from a subset of patients enrolled in the Phase 3 ECZTRA 1 (NCT03131648) and the long‐term extension ECZTEND (NCT03587805) trials. Gene expression was assessed by RNA sequencing; protein expression was assessed by immunohistochemistry and immunoassay. Results: Tralokinumab improved the transcriptomic profile of lesional skin by Week 4. Mean improvements in the expression of genes dysregulated in AD were 39% at Week 16 and 85% at 2 years with tralokinumab, with 15% worsening at Week 16 with placebo. At Week 16, tralokinumab significantly decreased type 2 serum biomarkers (CCL17/TARC, periostin, and IgE), reduced epidermal thickness versus placebo, and increased loricrin coverage versus baseline. Two years of tralokinumab treatment significantly reduced expression of genes in the Th2 (IL4R, IL31, CCL17, and CCL26), Th1 (IFNG), and Th17/Th22 (IL22, S100A7, S100A8, and S100A9) pathways as well as increased expression of epidermal differentiation and barrier genes (CLDN1 and LOR). Tralokinumab also shifted atherosclerosis signaling pathway genes (SELE, IL‐37, and S100A8) toward non‐lesional expression. Conclusion: Tralokinumab treatment improved epidermal pathology, reduced systemic markers of type 2 inflammation, and shifted expression of key AD biomarkers in skin towards non‐lesional levels, further highlighting the key role of IL‐13 in the pathogenesis of AD. Clinical Trial Registration: NCT03131648, NCT03587805. [ABSTRACT FROM AUTHOR]

Background: Skin tape‐strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape‐strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape‐strips and biopsies for studying AD. Methods: Whole‐transcriptome RNA‐sequencing was performed on paired tape‐strips and biopsies collected from lesional and non‐lesional skin from AD patients (n = 7) and non‐AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape‐strip/biopsy) and presence of AD (AD/non‐AD) were compared. Results: Tape‐strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene‐expression profiles of paired tape‐strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape‐strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non‐AD samples. Tape‐strips preferentially detected many itch (CCL3/CCL4/OSM) and immune‐response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin‐barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape‐strips identified more DEGs between AD and non‐AD (3157 DEGs) then biopsies (44 DEGs). Tape‐strips also detected higher levels of bacterial mRNA than biopsies. Conclusions: This study concludes that tape‐strips and biopsies each demonstrate respective advantages for measuring gene‐expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between neonatal skin dysbiosis and the development of infantile atopic dermatitis (AD). The study found that infants who developed AD at one year of age exhibited skin dysbiosis as early as the third day of life. The use of moisturizer was associated with a lower risk of AD and food allergy (FA) during infancy. However, the study had limitations, and further research is needed to validate the efficacy of moisturizer-based interventions in preventing AD and FA. [Extracted from the article]

The epithelial barriers of the skin, gut, and respiratory tract are critical interfaces between the environment and the host, and they orchestrate both homeostatic and pathogenic immune responses. The mechanisms underlying epithelial barrier dysfunction in allergic and inflammatory conditions, such as atopic dermatitis, food allergy, eosinophilic oesophagitis, allergic rhinitis, chronic rhinosinusitis, and asthma, are complex and influenced by the exposome, microbiome, individual genetics, and epigenetics. Here, we review the role of the epithelial barriers of the skin, digestive tract, and airways in maintaining homeostasis, how they influence the occurrence and progression of allergic and inflammatory conditions, how current treatments target the epithelium to improve symptoms of these disorders, and what the unmet needs are in the identification and treatment of epithelial disorders. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the role of interleukin 31 (IL-31) in the development of atopic dermatitis (AD) in dogs. The researchers used a naturally occurring canine model of AD to investigate IL-31 transcription in the skin during acute and chronic inflammation. They found that IL-31 transcription was low or undetectable during acute inflammation and increased during chronic inflammation. The study suggests that IL-31 transcription in atopic skin may be attributable to infiltrating cells, such as eosinophils and macrophages, rather than CD3+ T cells. Further research is needed to identify the specific cells involved in IL-31 signaling in atopic skin. [Extracted from the article]

A study was conducted to evaluate the effectiveness and safety of a topical emollient in treating mild-to-moderate atopic dermatitis (AD) in adolescents and adults. The study involved 100 participants and lasted for 24 weeks. The results showed that the group using the emollient had significant improvements in various measures compared to the placebo group. No safety concerns were reported. However, the study had limitations and further research is needed to explore other aspects of AD and the effects of the emollient. Overall, the emollient shows promise as a therapeutic option for long-term care of AD patients. [Extracted from the article]

Background: The skin barrier is vital for protection against environmental threats including insults caused by skin‐resident microbes. Dysregulation of this barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While Malassezia is the most abundant commensal fungus of the skin, little is known about the host control of this fungus in inflammatory skin diseases. Methods: In this experimental study, MC903‐treated mice were colonized with Malassezia spp. to assess the host–fungal interactions in atopic dermatitis. Additional murine models of AD and ichthyosis, including tape stripping, K5‐Nrf2 overexpression and flaky tail mice, were employed to confirm and expand the findings. Skin fungal counts were enumerated. High parameter flow cytometry was used to characterize the antifungal response in the AD‐like skin. Structural and functional alterations in the skin barrier were determined by histology and transcriptomics of bulk skin. Finally, differential expression of metabolic genes in Malassezia in atopic and control skin was quantified. Results: Malassezia grows excessively in AD‐like skin. Fungal overgrowth could, however, not be explained by the altered immune status of the atopic skin. Instead, we found that by upregulating key metabolic genes in the altered cutaneous niche, Malassezia acquired enhanced fitness to efficiently colonise the impaired skin barrier. Conclusions: This study provides evidence that structural and metabolic changes in the dysfunctional epidermal barrier environment provide increased accessibility and an altered lipid profile, to which the lipid‐dependent yeast adapts for enhanced nutrient assimilation. Our findings reveal fundamental insights into the implication of the mycobiota in the pathogenesis of common skin barrier disorders. [ABSTRACT FROM AUTHOR]

The skin microbiome is an extensive community of bacteria, fungi, mites, viruses and archaea colonizing the skin. Fluctuations in the composition of the skin microbiome have been observed in atopic dermatitis (AD) and food allergy (FA), particularly in early life, established disease, and associated with therapeutics. However, AD is a multifactorial disease characterized by skin barrier aberrations modulated by genetics, immunology, and environmental influences, thus the skin microbiome is not the sole feature of this disease. Future research should focus on mechanistic understanding of how early‐life skin microbial shifts may influence AD and FA onset, to guide potential early intervention strategies or as microbial biomarkers to identify high‐risk infants who may benefit from possible microbiome‐based biotherapeutic strategies. Harnessing skin microbes as AD biotherapeutics is an emerging field, but more work is needed to investigate whether this approach can lead to sustained clinical responses. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) represents the most common skin disease characterized by heterogeneous endophenotypes and a high disease burden. In Europe, six new systemic therapies for AD have been approved: the biologics dupilumab (anti‐interleukin‐4 receptor (IL‐4R) α in 2017), tralokinumab (anti‐IL‐13 in 2021), lebrikizumab (anti‐IL‐13 in 2023), and the oral janus kinase (JAK) inhibitors (JAKi) targeting JAK1/2 (baricitinib in 2020 in the EU) or JAK1 (upadacitinib in 2021 and abrocitinib in 2022). Herein, we give an update on new approvals, long‐term safety, and efficacy. Upadacitinib and abrocitinib have the highest short‐term efficacy among the approved systemic therapies. In responders, dupilumab and tralokinumab catch up regarding long‐term efficacy and incremental clinical benefit within continuous use. Recently, the European Medicines Agency has released recommendations for the use of JAKi in patients at risk (cardiovascular and thromboembolic diseases, malignancies, (former) smoking, and age ≥65 years). Furthermore, we give an overview on emerging therapies currently in Phase III trials. Among the topical therapies, tapinarof (aryl hydrocarbon receptor), ruxolitinib (JAK1/2i), delgocitinib (pan‐JAKi), asivatrep (anti‐transient receptor potential vanilloid), and phosphodiesterase‐4‐inhibitors (roflumilast, difamilast) are discussed. Among systemic therapies, current data on cord‐blood‐derived mesenchymal stem cells, CM310 (anti IL‐4Rα), nemolizumab (anti‐IL‐31RA), anti‐OX40/OX40L‐antibodies, neurokinin‐receptor‐1‐antagonists, and difelikefalin (κ‐opioid‐R) are reported. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10 climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter‐induced AD exacerbations from wildfires to the potential for indirect effects like drought‐induced food insecurity and migration. We then created maps comparing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: understanding the synergistic impacts of climatic hazards on AD, long‐term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population‐level trends. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo‐controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta‐analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta‐analysis of SCORAD outcomes was conducted using random‐effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta‐analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well‐designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Meteorin‐like protein (METRNL)/Interleukin‐41 (IL‐41) is a novel immune‐secreted cytokine/myokine involved in several inflammatory diseases. However, how METRNL exerts its regulatory properties on skin inflammation remains elusive. This study aims to elucidate the functionality and regulatory mechanism of METRNL in atopic dermatitis (AD).METRNL levels were determined in skin and serum samples from patients with AD and subsequently verified in the vitamin D3 analogue MC903‐induced AD‐like mice model. The cellular target of METRNL activity was identified by multiplex immunostaining, single‐cell RNA‐seq and RNA‐seq.METRNL was significantly upregulated in lesions and serum of patients with dermatitis compared to healthy controls (p <.05). Following repeated MC903 exposure, AD model mice displayed elevated levels of METRNL in both ears and serum. Administration of recombinant murine METRNL protein (rmMETRNL) ameliorated allergic skin inflammation and hallmarks of AD in mice, whereas blocking of METRNL signaling led to the opposite. METRNL enhanced β‐Catenin activation, limited the expression of Th2‐related molecules that attract the accumulation of Arginase‐1 (Arg1)hi macrophages, dendritic cells, and activated mast cells.METRNL can bind to KIT receptor and subsequently alleviate the allergic inflammation of AD by inhibiting the expansion of immune cells, and downregulating inflammatory gene expression by regulating the level of active WNT pathway molecule β‐Catenin. [ABSTRACT FROM AUTHOR]

This article presents a real-world study conducted at Ruijin Hospital in Shanghai, China, to evaluate the efficacy and safety of Dupilumab, a monoclonal antibody used to treat atopic dermatitis (AD) in Chinese patients. The study included 689 patients of all ages who were treated with Dupilumab. The results showed that Dupilumab was effective in reducing symptoms of AD, with the greatest improvement observed in the first 8 weeks of treatment. Factors such as age, gender, and baseline eosinophil counts were found to influence the therapeutic effect. The incidence of adverse events was generally low, with most events being mild and tolerable. Some rare infections, phenotype switching, and tumor events were also observed. The study provides valuable insights into the efficacy and safety of Dupilumab in the Chinese population. [Extracted from the article]

Background: Itch is the most common symptom of atopic dermatitis (AD) and significantly decreases the quality of life. Skin microbiome is involved in AD pathogenesis, whereas its role in the regulation of itch remains elusive. In this study, we aimed to investigate the effects of skin microbial metabolite propionate on acute and chronic pruritus and to explore the mechanism. Methods: Using various mouse models of itch, the roles of propionate were explored by behavioral tests and histopathology/immunofluorescent analysis. Primary‐cultured dorsal root ganglion neurons and HEK293 cells expressing recombinant human TRP channels were utilized for in vitro calcium imaging/in vivo miniature two‐photon imaging in combination with electrophysiology and molecular docking approaches for investigation of the mechanism. Results: Propionate significantly alleviated itch and alloknesis in various mouse models of pruritus and AD and decreased the density of intraepidermal nerve fibers. Propionate reduced the responsiveness of dorsal root ganglion neurons to pruritogens in vitro, attenuated the hyper‐excitability in sensory neurons in MC903‐induced AD model, and inhibited capsaicin‐evoked hTRPV1 currents (IC50 = 20.08 ± 1.11 μM) via interacting with the vanilloid binding site. Propionate also decreased the secretion of calcitonin gene‐related peptide by nerves in MC903‐induced AD mouse model, which further attenuated itch and skin inflammation. Conclusion: Our study revealed a protective effect of propionate against persistent itch through direct modulation of sensory TRP channels and neuropeptide production in neurons. Regulation of itch via the skin microbiome might be a novel strategy for the treatment of AD. [ABSTRACT FROM AUTHOR]

This article discusses a study that examines the risk factors associated with the progression of atopic dermatitis (AD) to allergic asthma (AA) and/or allergic rhinitis (AR), known as the Atopic March. The study focuses on a high-risk, minority, urban, low-income birth cohort and explores factors such as race/ethnicity, gender, breastfeeding, maternal obesity, preterm birth, and maternal atopy history. The findings suggest that being Black, male, exclusively breastfed, or born to mothers with obesity are risk factors for AD. Additionally, Hispanic ethnicity, nulliparity, preterm birth, and maternal atopy history are associated with the development of the Atopic March. The study provides valuable data for identifying early risk factors and potential interventions for children at high risk of the Atopic March. [Extracted from the article]

Background: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. Methods: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell‐type‐specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti‐inflammatory effects of FVE were investigated. The anti‐inflammatory effects of FVE were validated using a DNCB‐induced mouse model of AD. Anti‐inflammatory activity of compounds isolated from FVE was validated in each immune cell type. Results: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro‐inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL‐33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti‐inflammatory FVE compound. Conclusion: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them. [ABSTRACT FROM AUTHOR]

Background: This is the first report on the effects of abrocitinib, a Janus kinase 1–selective inhibitor, on the expression of skin biomarkers in patients with moderate‐to‐severe atopic dermatitis (AD). Methods: JADE MOA (NCT03915496) was a double‐blind Phase 2a trial. Adults were randomly assigned 1:1:1 to receive monotherapy with once‐daily abrocitinib 200 mg, abrocitinib 100 mg, or placebo for 12 weeks. The primary endpoint was change from baseline in markers of inflammation (matrix metalloproteinase [MMP]‐12), epidermal hyperplasia (keratin‐16 [KRT16]), T‐helper 2 (Th2) immune response (C‐C motif chemokine ligand [CCL]17, CCL18, and CCL26), and Th22 immune response (S100 calcium binding protein A8, A9, and A12 [S100A8, S100A9, and S100A12]) in skin through 12 weeks. Results: A total of 46 patients received abrocitinib 200 mg (n = 14), abrocitinib 100 mg (n = 16), or placebo (n = 16). Abrocitinib improved AD clinical signs and reduced itch. Gene expression of MMP‐12, KRT16, S100A8, S100A9, and S100A12 was significantly decreased from baseline with abrocitinib 200 mg (at Weeks 2, 4, and 12) and abrocitinib 100 mg (at Weeks 4 and 12) in a dose‐dependent manner. Abrocitinib 200 mg resulted in significant decreases from baseline in CCL17 expression at Week 12 and CCL18 expression at Weeks 2, 4, and 12; no significant decreases were observed for CCL26. Conclusions: Alongside improvements in clinical signs and symptoms of AD, 12 weeks of abrocitinib treatment resulted in downregulation of genes associated with inflammation, epidermal hyperplasia, and Th2 and Th22 immune responses in the skin of patients with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab‐associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. Methods: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non‐AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. Results: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL‐12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non‐AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. Conclusions: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD. [ABSTRACT FROM AUTHOR]

Background: RPT193 is an orally administered small molecule antagonist of the human C‐C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T‐helper Type 2 (Th2) cells. We investigated single‐ and multiple‐ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate‐to‐severe atopic dermatitis (AD). Methods: This was a first‐in‐human randomized, placebo‐controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate‐to‐severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. Results: In healthy (n = 72) and AD subjects (n = 31), once‐daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment‐emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints (p <.05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193‐treated versus placebo‐treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. Conclusions: To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic data on occupational anaphylaxis is scarce, and there is a need of more knowledge about work‐related anaphylactic episodes. Methods: Based on the data of the Anaphylaxis Registry, we identified cases related to occupational exposure and analyzed the elicitors, demographics, severity of clinical reaction and management. Results: Since 2017, 5851 cases with an information about the occupational relation of the anaphylactic episode were registered whereby 225 (3.8%) were assigned to be caused by an occupational allergen. The vast majority of these occupational anaphylaxis cases were caused by insects (n = 186, 82.7%) followed by food (n = 27, 12.0%) and drugs (n = 8, 3.6%). Latex elicited occupational anaphylaxis in only two cases. Beekeepers, gardeners, farmers, and individuals working in professions associated with food handling, for example, employees in restaurants, bakery, pastry, and cooks were most frequently affected. The comparison of the occupational insect venom‐induced anaphylaxis to a group of non‐occupational insect anaphylaxis in adults (n = 1842) revealed a significant younger age in occupational anaphylaxis (46 vs. 53 years), a predominance of bee‐induced cases (38% vs. 17%), and a higher rate of venom immunotherapy in a primary care setting (3.3% vs. 1.3%, p =.044). In the occupational‐ versus non‐occupational adults with food‐induced anaphylaxis atopic dermatitis as concomitant atopic disease was observed more frequently (n = 486; 20% vs. 10%), although this was not significant. Conclusion: Our data demonstrate the impact of venom allergy in work‐related anaphylaxis. Foods and drugs are less frequently elicitors, and latex‐induced occupational anaphylaxis was rare. More data are needed to determine risk factors associated with occupational anaphylaxis. [ABSTRACT FROM AUTHOR]

Background: Abrocitinib efficacy by comorbidity status in patients with moderate‐to‐severe atopic dermatitis (AD) has not been previously assessed. This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with AD and allergic comorbidities. Methods: Data were pooled from patients who received abrocitinib 200 mg, 100 mg, or placebo in phase 2b (NCT02780167) and phase 3 (NCT03349060, NCT03575871) monotherapy trials. Patients with and without allergic comorbidities (allergic asthma, rhinitis, conjunctivitis, or food allergy) were evaluated for Investigator's Global Assessment (IGA) response (clear [0] or almost clear [1]), ≥75% improvement in the Eczema Area and Severity Index (EASI‐75), ≥4‐point improvement in Peak Pruritus Numerical Rating Scale (PP‐NRS4), and Dermatology Life Quality Index (DLQI) response (<2 with baseline score ≥2). Other outcomes were Patient‐Oriented Eczema Measure (POEM), SCORing Atopic Dermatitis (SCORAD), Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD), and treatment‐emergent adverse events (TEAEs). Results: Of 942 patients, 498 (53%) reported at least one allergic comorbidity (asthma only, 33%; conjunctivitis only or rhinitis only or both, 17%; food allergies only, 15%; >1 allergic comorbidity, 34%). Regardless of comorbidity status, from Week 2 to Week 12, higher percentages of patients treated with either abrocitinib dose achieved IGA 0/1, EASI‐75, PP‐NRS4, or DLQI 0/1 versus placebo‐treated patients. Changes from baseline in POEM, SCORAD, and PSAAD were greater with abrocitinib than with placebo in patients with and without allergic comorbidities. Most TEAEs were mild or moderate. Conclusions: Efficacy and safety data support abrocitinib use to manage AD in patients with or without allergic comorbidities. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) and psoriasis vulgaris (PV) are almost mutually exclusive diseases with different immune polarizations, mechanisms and therapeutic targets. Switches to the other disease ("Flip‐Flop" [FF] phenomenon) can occur with or without systemic treatment and are often referred to as paradoxical reactions under biological therapy. Methods: The objective was to develop a diagnostic algorithm by combining clinical criteria of AD and PV to identify FF patients. The algorithm was prospectively validated in patients enrolled in the CK‐CARE registry in Bonn, Germany. Afterward, algorithm refinements were implemented based on machine learning. Results: Three hundred adult Caucasian patients were included in the validation study (n = 238 with AD, n = 49 with PV, n = 13 with FF; mean age 41.2 years; n = 161 [53.7%] female). The total FF scores of the PV and AD groups differed significantly from the FF group in the validation data (p <.001). The predictive mean generalized Youden‐Index of the initial model was 78.9% [95% confidence interval 72.0%–85.6%] and the accuracy was 89.7%. Disease group‐specific sensitivity was 100% (FF), 95.0% (AD), and 61.2% (PV). The specificity was 89.2% (FF), 100% (AD), and 100% (PV), respectively. Conclusion: The FF algorithm represents the first validated tool to identify FF patients. [ABSTRACT FROM AUTHOR]

Background: Individuals with atopic dermatitis often develop other conditions. Objective: This study aimed to determine how atopic dermatitis comorbidities develop in children over time. Methods: This population‐based administrative cohort study used national health insurance data. We traced individuals born in Korea between 2002 and 2003 to 2018. The date of initial atopic dermatitis diagnosis was set as the index date. Fifty‐three childhood comorbidities of atopic dermatitis were identified as outcomes of interest by performing a comprehensive literature search and comparing the prevalence of diagnostic codes in children with and without atopic dermatitis. Four control children per individual in the atopic dermatitis group were randomly matched based on sex and index date. The association between atopic dermatitis and the development of each specified disease was assessed using proportional hazard assumption, followed by mapping of the temporal sequences of interconnected comorbidities. Results: The atopic dermatitis and control groups contained 67,632 and 270,528 individuals, respectively. The median age at the index date was 10 months, whereas the median follow‐up period was 15 years. Twenty diseases that were associated with a higher risk of atopic dermatitis were identified and a chain of interconnected conditions created. The progression began in childhood with febrile seizures, constipation, and asthma, and was later associated with the emergence of food allergy, allergic rhinitis, psychiatric disorders, and autoimmune diseases. Conclusion: Our study highlights the temporal nature of atopic dermatitis comorbidities in children, and indicates that an understanding of the comorbidities may inform its clinical management and treatment. [ABSTRACT FROM AUTHOR]

This article discusses the impact of topical anti-inflammatory therapy on the Toll-like receptor 2 (TLR2) response in epidermal dendritic cells (DC) in patients with atopic dermatitis (AD). The study found that AD patients have an inhibited maturation response in their Langerhans cells (LC), a type of DC, compared to healthy controls. However, after topical anti-inflammatory treatment, the ability of LC to respond to TLR2 ligands was restored. The study suggests that anti-inflammatory treatment can restore TLR2 signaling in DC in AD, even before visible improvements in the skin occur. [Extracted from the article]

Background: Atopic dermatitis (AD) is characterized by Staphylococcus aureus (S. aureus) colonization. Longitudinal early life data delineating relationships of S. aureus colonization, barrier function, and AD outcomes are lacking. We define longitudinal S. aureus endotypes and AD pathogenesis in early life. Methods: We defined longitudinal S. aureus skin colonization phenotypes across two annual visits (non‐colonized: V1−V2−, early transient: V1+V2−, late‐onset: V1−V2+, persistent: V1+V2+) in the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children cohort. We analyzed AD severity, sensitization, and skin barrier function across phenotypes, and performed mediation analyses between colonization and FLG expression. Results: Persistent S. aureus colonization was associated with increased SCORAD at V1 (33.5 vs. 19.0, p =.004) and V2 (40.1 vs.16.9, p <.001), and lower non‐lesional (NL) FLG at V2 (1.77 vs. 4.09, p =.029) compared to the non‐colonized phenotype, with early transient and late‐onset colonization as intermediate phenotypes. Children colonized at V2 demonstrated a decrease in NL‐FLG expression from V1 to V2 compared to those non‐colonized at V2 (p =.0012), who maintained expression. This effect remained significant even after adjusting for V1 colonization and SCORAD (p =.011). Conclusions: Our findings are the first to present longitudinal quantitative FLG expression and S. aureus skin colonization in early life and suggest that a decrease in NL‐FLG drives later colonization. Hence, therapies to maintain NL‐FLG expression may prevent S. aureus colonization. Further, a longitudinal AD endotype of persistent colonization is characterized by increased AD severity, sensitization, and decreasing NL‐FLG. [ABSTRACT FROM AUTHOR]

This article presents the findings of a 15-year observational study on the relationship between allergic rhinitis (AR) and allergic contact dermatitis (ACD). The study suggests that AR may be a risk factor for the development of ACD, independent of atopic dermatitis (AD). Patients with DP-induced rhinitis are at a higher risk of developing ACD compared to those with seasonal pollen-induced rhinitis. The study also found that delayed mite sensitization, detected by DP-APT, predicts a higher incidence of new-onset ACD. The authors recommend including ACD as a comorbid disorder of AR and considering the risk of ACD in the follow-up of patients. They also suggest that DP-directed allergen immunotherapy may reduce the risk of developing ACD. The study was conducted by four authors who contributed to study design, patient assessment, data collection, statistical analysis, and manuscript writing. No funding was received for this research, and the authors declare no conflicts of interest. [Extracted from the article]

Background: Skin barrier dysfunction is associated with the development of atopic dermatitis (AD), however methods to assess skin barrier function are limited. We investigated the use of electrical impedance spectroscopy (EIS) to detect skin barrier dysfunction in children with AD of the CARE (Childhood AlleRgy, nutrition, and Environment) cohort. Methods: EIS measurements taken at multiple time points from 4 months to 3‐year‐old children, who developed AD (n = 66) and those who did not (n = 49) were investigated. Using only the EIS measurement and the AD status, we developed a machine learning algorithm that produces a score (EIS/AD score) which reflects the probability that a given measurement is from a child with active AD. We investigated the diagnostic ability of this score and its association with clinical characteristics and age. Results: Based on the EIS/AD score, the EIS algorithm was able to clearly discriminate between healthy skin and clinically unaffected skin of children with active AD (area under the curve 0.92, 95% CI 0.85–0.99). It was also able to detect a difference between healthy skin and AD skin when the child did not have active AD. There was no clear association between the EIS/AD score and the severity of AD or sensitisation to the tested allergens. The performance of the algorithm was not affected by age. Conclusions: This study shows that EIS can detect skin barrier dysfunction and differentiate skin of children with AD from healthy skin and suggests that EIS may have the ability to predict future AD development. [ABSTRACT FROM AUTHOR]

Background: Targeting IL‐13 is highly efficacious in patients with Th2‐biased atopic dermatitis (AD), but inhibition of other inflammatory molecules might also limit disease. We investigated the importance of the TNF family cytokine TNF‐like weak inducer of apoptosis (TWEAK; TNFSF12) to keratinocyte dysregulation and the pathogenesis of AD in mice and also tested if blocking TWEAK has a similar therapeutic effect as targeting IL‐13. Methods: Conditional knockout mice lacking Fn14 (TNFRSF12A), the receptor for TWEAK, only in keratinocytes, were repetitively sensitized with house dust mite allergen and analyzed for AD‐like skin inflammation. To determine the translational potential, wild‐type mice with AD were therapeutically treated with anti‐TWEAK and/or anti‐IL‐13 antibodies, and skin inflammation was assessed. Results: Mice deficient in Fn14 in keratinocytes were resistant to developing maximal clinical features of AD, exhibiting reduced epidermal hyperplasia and dermal thickening, less skin infiltration of immune cells, and downregulated inflammatory gene expression. Moreover, therapeutic neutralization of TWEAK in wild‐type mice with AD reduced all of the pathological features to a comparable extent as blocking IL‐13. Conclusions: The activity of TWEAK in keratinocytes contributes to AD development, and neutralizing TWEAK represents a future potential therapeutic option in human AD similar to targeting IL‐13. [ABSTRACT FROM AUTHOR]

This article explores the role of thrombin and fibrinogen in atopic dermatitis (AD) in both human infants and mice models. The study found that children with AD under the age of 1 had increased thrombin generation and decreased time to peak thrombin compared to children without AD. Additionally, thrombin inhibition in mice resulted in decreased AD symptoms and fibrinogen deficiency in mice led to decreased disease development. These findings suggest that thrombin and fibrinogen may contribute to AD pathogenesis and could be potential targets for therapy. The study was funded by NIH and the American Academy of Allergy, Asthma, and Immunology Foundation. [Extracted from the article]

This article explores the role of interferon‐γ‐inducible protein 10 (IP‐10) in atopic dermatitis (AD), a Th2-dominant skin disease. The study found that IP-10 expression was elevated in the lesional tissues of AD patients and in mouse models of AD. The researchers also investigated the function of IP-10 in AD pathogenesis by using IP-10 knockout mice and injecting recombinant IP-10 into AD models. They observed that IP-10 played a role in promoting Th2 immune responses and exacerbating AD symptoms. The study suggests that IP-10 could be a potential therapeutic target for AD treatment. [Extracted from the article]

Background: Our knowledge of etiopathogenesis of atopic dermatitis (AD) is largely derived from skin biopsies, which are associated with pain, scarring and infection. In contrast, tape‐stripping is a minimally invasive, nonscarring technique to collect skin samples. Methods: To construct a global AD skin transcriptomic profile comparing tape‐strips to whole‐skin biopsies, we performed RNA‐seq on tape‐strips and biopsies taken from the lesional skin of 20 moderate‐to‐severe AD patients and the skin of 20 controls. Differentially expressed genes (DEGs) were defined by fold‐change (FCH) ≥2.0 and false discovery rate <0.05. Results: We detected 4104 (2513 Up; 1591 Down) and 1273 (546 Up; 727 Down) DEGs in AD versus controls, in tape‐strips and biopsies, respectively. Although both techniques captured dysregulation of key immune genes, tape‐strips showed higher FCHs for innate immunity (IL‐1B, IL‐8), dendritic cell (ITGAX/CD11C, FCER1A), Th2 (IL‐13, CCL17, TNFRSF4/OX40), and Th17 (CCL20, CXCL1) products, while biopsies showed higher upregulation of Th22 associated genes (IL‐22, S100As) and dermal cytokines (IFN‐γ, CCL26). Itch‐related genes (IL‐31, TRPV3) were preferentially captured by tape‐strips. Epidermal barrier abnormalities were detected in both techniques, with terminal differentiation defects (FLG2, PSORS1C2) better represented by tape‐strips and epidermal hyperplasia changes (KRT16, MKI67) better detected by biopsies. Conclusions: Tape‐strips and biopsies capture overlapping but distinct features of the AD molecular signature, suggesting their respective utility for monitoring specific AD‐related immune, itch, and barrier abnormalities in clinical trials and longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: Immunological traits and functions have been consistently associated with environmental exposures and are thought to shape allergic disease susceptibility and protection. In particular, specific exposures in early life may have more significant effects on the developing immune system, with potentially long‐term impacts. Methods: We performed RNA‐Seq on peripheral blood mononuclear cells (PBMCs) from 150 children with atopic dermatitis and healthy nonallergic children in rural and urban settings from the same ethnolinguistic AmaXhosa background in South Africa. We measured environmental exposures using questionnaires. Results: A distinct PBMC gene expression pattern was observed in those children with atopic dermatitis (132 differentially expressed genes [DEGs]). However, the predominant influences on the immune cell transcriptome were related to early life exposures including animals, time outdoors, and types of cooking and heating fuels. Sample clustering revealed two rural groups (Rural_1 and Rural_2) that separated from the urban group (3413 and 2647 DEGs, respectively). The most significantly regulated pathways in Rural_1 children were related to innate activation of the immune system (e.g., TLR and cytokine signaling), changes in lymphocyte polarization (e.g., TH17 cells), and immune cell metabolism (i.e., oxidative phosphorylation). The Rural_2 group displayed evidence for ongoing lymphocyte activation (e.g., T cell receptor signaling), with changes in immune cell survival and proliferation (e.g., mTOR signaling, insulin signaling). Conclusions: This study highlights the importance of the exposome on immune development in early life and identifies potentially protective (e.g., animal) exposures and potentially detrimental (e.g., pollutant) exposures that impact key immunological pathways. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, pruritic and inflammatory, dry skin condition with many known comorbidities. These include airway disease, food allergies, atopic eye disease and autoimmune conditions. Furthermore, there is often significant sleep disturbance as well as increased psychological distress and mental health problems. Severe AD therefore often has a significant impact on the quality of life of both patients and their families. In this review we discuss recent findings on the putative links between AD, its association with itch, sleep disturbance and neuropsychiatric morbidity, including the role of inflammation in these conditions. Itch was thought to predominantly drive sleep disruption in AD. We now understand changes in sleep influence immune cell distribution and the associated inflammatory cytokines, which suggests a bidirectional relationship between AD and sleep. We also increasingly recognize inflammation as a key driver in psychological symptoms and disorders. The link between cutaneous, systemic and possible brain inflammation could at least in part be driven by the sleep deprivation and itch‐driven neuronal proliferation seen in AD. [ABSTRACT FROM AUTHOR]

This article discusses the expression and regulation of the transient receptor potential vanilloid 1 (TRPV1) channel in human basophils and its potential role in atopic dermatitis (AD). The study found that basophils express TRPV1 at the mRNA and protein levels, and its expression is higher in basophils compared to other immune cells. Activation of TRPV1 in basophils resulted in changes in calcium levels, IL-6 release, and apoptosis. TRPV1 expression was also found to be upregulated in AD, and its surface content was modulated by inflammatory mediators. These findings suggest that TRPV1 may play a pro-inflammatory and pruritic role in basophil function, making it a potential therapeutic target for AD and other basophil-associated inflammatory skin diseases. [Extracted from the article]

Circulating skin‐homing cutaneous lymphocyte‐associated antigen (CLA)+ T cells constitute a small subset of human memory T cells involved in several aspects of atopic dermatitis: Staphylococcus aureus related mechanisms, the abnormal Th2 immune response, biomarkers, clinical aspects of the patients, pruritus, and the mechanism of action of targeted therapies. Superantigens, IL‐13, IL‐31, pruritus, CCL17 and early effects on dupilumab‐treated patients have in common that they are associated with the CLA+ T cell mechanisms in atopic dermatitis patients. The function of CLA+ T cells corresponds with the role of T cells belonging to the skin‐associated lymphoid tissue and could be a reason why they reflect different mechanisms of atopic dermatitis and many other T cell mediated skin diseases. The goal of this review is to gather all this translational information of atopic dermatitis pathology. [ABSTRACT FROM AUTHOR]

The article discusses the concept of the "atopic march," which refers to the sequential development of different atopic conditions in childhood. While not all children follow this sequence or develop all four atopic conditions (atopic dermatitis, food allergy, recurrent wheezing/asthma, and allergic rhinitis), there is a higher risk of developing another atopic condition if a child already has one. The article focuses on the potential link between skin barrier dysfunction and asthma, suggesting that impaired skin barrier function and lower lung function at age 3 months increase the risk of asthma at age 3 years. However, further validation is needed before these associations can be used clinically for diagnosis or prognosis. The article also explores the possibility of preventing asthma through interventions that improve the skin barrier. [Extracted from the article]

Phytotherapy, the use of medicinal plants as a cure, has a long history dating back to ancient times. Despite the global reliance on botanical drugs, scientific publications on phytotherapy have been declining. However, natural entities continue to inspire the creation of therapeutic agents. This article highlights a recent study on the mode of action of a plant extract that can modulate atopic dermatitis, emphasizing the need for further research and clinical studies. The preservation of plant biodiversity is crucial for identifying novel compounds for drug development and protecting traditional knowledge. [Extracted from the article]

This document is a compilation of summaries of various articles published in the journal Allergy. The articles cover a range of topics related to allergies and immunology. Some of the topics include the recognition of epitopes in birch pollen allergic patients, the correlation between blood eosinophils and asthma severity, the role of heat shock protein 10 in chronic spontaneous urticaria, the prevalence of IgE autoantibodies in atopic dermatitis, the co-localization of IgG4 and cow's milk proteins in eosinophilic esophagitis, the comparison of different food challenge methods in peanut allergy, the safe doses of sesame in sesame allergic patients, the immunogenicity of thermostable allergens in canned fish, the food-induced immediate response of the esophagus in pediatric eosinophilic esophagitis, and the potential use of specific IgE as a biomarker in alpha-gal red meat allergy. These summaries provide a brief overview of each article's findings and can be useful for library patrons conducting research on these specific topics. [Extracted from the article]

Background: Autoreactive immunoglobulin E (IgE) antibodies to self‐peptides within the epidermis have been identified in patients with atopic dermatitis (AD). Prevalence, concomitant diseases, patient characteristics, and risk factors of IgE autoantibody development remain elusive. We aimed to determine IgE autoantibodies in serum samples (n = 672) from well‐characterized patients with AD and controls (1.2–88.9 years). Methods: Atopic dermatitis patients were sub‐grouped in AD with comorbid Type‐2 diseases ("AD + Type 2"; asthma, allergic rhinitis, food allergy, n = 431) or "solely AD" (n = 115). Also, subjects without AD but with Type‐2 diseases ("atopic controls," n = 52) and non‐atopic "healthy controls" (n = 74) were included. Total proteins from primary human keratinocytes were used for the immunoassay to detect IgE autoantibodies. Values were compared to already known positive and negative serum samples. Results: Immunoglobulin E autoantibodies were found in 15.0% (82/546) of all analyzed AD‐patients. "AD + Type 2" showed a higher prevalence (16.4%) than "solely AD" (9.6%). "Atopic controls" (9.6%) were comparable with "solely AD" patients, while 2.7% of healthy controls showed IgE autoantibodies. Of those with high levels of IgE autoantibodies, 15 out of 16 were patients with "AD + Type 2". AD patients with IgE autoantibodies were younger than those without. Patients with IgE autoreactivity also displayed higher total serum IgE levels. Factors that affected IgE autoantibody development were as follows: birth between January and June, cesarean‐section and diversity of domestic pets. Conclusions: Immunoglobulin E autoantibodies in AD seem to associate with the presence of atopic comorbidities and environmental factors. The potential value of IgE autoantibodies as a predictive biomarker for the course of AD, including the atopic march, needs further exploration. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory, intensely pruritic skin disorder associated with significant patient burden. Interleukin (IL)‐13 is a cytokine that acts as a driver of immune dysregulation, skin‐barrier dysfunction, and microbiome dysbiosis that characterizes AD, and is consistently overexpressed in AD skin. Tralokinumab is a fully human immunoglobulin (Ig) G4 monoclonal antibody that binds specifically to IL‐13 with high affinity, thereby inhibiting subsequent downstream IL‐13 signaling. Three pivotal phase 3 clinical trials demonstrated that tralokinumab 300 mg every other week, as monotherapy or in combination with topical corticosteroids as needed, provides significant improvements in signs and symptoms of moderate‐to‐severe AD, as measured by Investigator's Global Assessment 0/1 (clear/almost clear) and Eczema Area and Severity Index‐75 at Week 16. Improvements were observed soon after tralokinumab initiation and were maintained over 52 weeks of therapy. Tralokinumab significantly improved patient‐reported outcomes such as itch and sleep, and demonstrated a safety profile comparable with placebo; conjunctivitis during tralokinumab therapy was generally mild. Similar results were observed in a phase 3 adolescent trial. The role of IL‐13 in the pathophysiology of AD justifies a targeted approach and a wealth of clinical data supports tralokinumab as a new therapeutic option for people with moderate‐to‐severe AD. [ABSTRACT FROM AUTHOR]

Four endotypes were identified; endotypes 1, 2 and 3 had higher proportions of AD (67%), asthma (60%), and allergic march (75%), respectively, and endotype 4 had more control members (70%; Figure 1B, Table S1). AD, atopic dermatitis; As, asthma; AM, allergic march. gl Endotypes were classified clearly by the omics features showing different intensities (Figure 1D, Tables S3-S5). [Extracted from the article]

Background: While the microbiome is increasingly seen as a targetable contributor to atopic dermatitis (AD), questions remain as to whether the dysbiosis is secondary to diseased skin or if it predates symptom onset. Previous work has evaluated how the skin microbiome changes with age and established the influence of factors like delivery mode and breastfeeding on global microbiome diversity. However, these studies were unable to identify taxa which predict subsequent AD. Methods: Skin swab samples were collected from the first week of life for 72 children in the neonatal intensive care unit (NICU) at a single site hospital. Participants were followed for 3 years to determine their health status. We applied shotgun metagenomic sequencing to assess the microbiome differences between 31 children who went on to develop AD and 41 controls. Results: We identified that subsequent development of AD was associated with differential abundance of several bacterial and fungal taxa as well as several metabolic pathways, each of which have been previously associated with active AD. Conclusions: Our work provides evidence of reproducibility for the previously reported dysbiotic signatures predating AD onset while also expanding prior findings through the first use of metagenomic assessment prior to AD onset. While extrapolation of our findings beyond the pre‐term, NICU cohort is limited, our findings add to the evidence that the dysbiosis associated with AD pre‐dates disease onset rather than reflect a secondary consequence of skin inflammation. [ABSTRACT FROM AUTHOR]

A recent study published in the journal Allergy investigated the use of diquafosol eye drops as a prophylactic measure for dupilumab-associated conjunctivitis in patients with severe atopic dermatitis. Dupilumab, a treatment for atopic dermatitis, is known to be linked to conjunctivitis, but there are currently no established guidelines for prevention. The study found that the incidence of conjunctivitis was significantly lower in the group using diquafosol eye drops compared to the control group. The authors suggest considering the prophylactic use of diquafosol eye drops for patients starting dupilumab treatment to prevent this adverse effect. [Extracted from the article]

This article discusses a clinical trial that explores the use of epicutaneous immunotherapy (EPIT) as a potential treatment for canine atopic dermatitis (cAD), a common allergic skin disease in dogs. The study aimed to assess the feasibility, effectiveness, and safety of EPIT in dogs with cAD over a six-month period. The results showed that EPIT effectively improved the dogs' clinical condition, with significant reductions in pruritus (itching), skin lesions, and improvements in quality of life. The study also found that EPIT was well-tolerated and safe, with a high adherence rate among dog owners. This pilot study suggests that EPIT could be a promising and practical treatment option for cAD in dogs, warranting further investigation. [Extracted from the article]

A large cohort study conducted in Germany found that individuals who had previously been infected with COVID-19 had a 33% increased risk of developing atopic dermatitis (AD), a chronic inflammatory skin disease. The study analyzed routine healthcare data and matched 641,704 COVID-19 patients with 1,907,992 control cases. The risk of new-onset AD was significantly increased in all age groups, both sexes, and medication groups. However, the study's observational nature means that causal conclusions should be drawn with caution. Further research is needed to understand the impact of the COVID-19 pandemic on the global burden of AD. [Extracted from the article]