Multiple myeloma (MM) is responsible for significant morbidity and mortality, yet our knowledge regarding MM aetiology remains limited. We investigated whether a history of allergic conditions is associated with MM risk.

Incident cases (n = 782) of MM were recruited via cancer registries in Victoria and NSW. Controls (n = 733) were siblings (n = 436) or spouses (n = 297) of cases. Unconditional logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for associations between self-reported allergic conditions (asthma, eczema, food allergy, hay fever) and MM risk.

Eczema was inversely associated with MM risk (OR = 0.54, 95 %CI = 0.42-0.70), as was a combined history of food allergy and eczema (OR = 0.52, 95 %CI = 0.29-0.93). There was an inverse association between a history of any allergic condition (compared with none) and risk of MM (OR = 0.68, 95 %CI = 0.55-0.84). In the mean-centred dose-risk analysis the OR was 0.87 (95 %CI = 0.73-1.04) per additional allergic condition of interest. No notable associations were identified for food allergy, asthma, or hay fever alone.

We found that a history of allergic disease, particularly eczema, was associated with reduced MM risk. Further research is recommended to confirm findings and investigate potential mechanisms.

Over the past decades, atopic diseases have emerged as a growing global health concern. The Global Report on Atopic Dermatitis 2022 estimated that approximately 223 million people worldwide were living with atopic dermatitis in 2022, with around 43 million being children or adolescents. The financial burden associated with the treatment of this condition poses a significant challenge for both healthcare systems and patients. The current therapeutic approach for atopic diseases primarily focuses on symptomatic management, aiming to mitigate the effects of an overactive immune system. The most widely used treatments include topical or systemic corticosteroids, which suppress inflammation, and emollients, which help restore the skin barrier function. However, prolonged corticosteroid use is associated with adverse effects, including impaired immune response and reduced ability to combat external and internal threats. Consequently, there is a growing interest in developing alternative therapeutic strategies for managing atopic dermatitis. Among these emerging treatments, hyperbaric oxygen therapy (HBOT) appears particularly promising. HBOT has a beneficial effect on the vascular and immune systems, which results in improved functioning of tissues and organs. This therapy has demonstrated efficacy in promoting wound healing, particularly in conditions such as thermal burns and diabetic foot ulcers. Given these properties, HBOT is being tested as a potential adjunctive therapy for atopic dermatitis and other allergy-related diseases. In this paper, we present the current state of knowledge regarding the application of HBOT in the treatment of atopic and immune-mediated conditions, with a focus on its immunomodulatory and regenerative effects.

Atopic dermatitis (AD), or eczema, is an inflammatory skin disease related to environmental factors. As a heterogeneous disease, it presents with complex phenotypes and endotypes. A variety of intrinsic and extrinsic factors can promote the development of AD. While there has been extensive discussion on environmental exposure at the population and community levels, discourse on exposome at individual levels in AD remains insufficient. For example, allergens, microorganisms, parasites, dietary factors, and psychological factors such as stress and anxiety play important roles in AD development. Microorganisms, in particular, exhibit altered composition and diversity on the skin of AD patients, influencing skin barrier integrity and immune responses. The impact of certain microorganisms, such as fungi and viruses, on AD has garnered increasing attention because of their important role in maintaining skin homeostasis. Dietary factors, including sugar intake and histamine-rich foods, may modulate AD risk and severity, although findings are controversial. Allergens, particularly house dust mite allergens, and aeroallergens, exacerbate AD symptoms by promoting inflammation and barrier dysfunction. Since AD is often the first step in the atopic march, its primary prevention measures are crucial. Some preventive measures involving microorganisms, diet, and moisturizers remain controversial. Effective preventive strategies necessitate a clear understanding of the complex mechanisms of AD, especially host-microbe-environment interactions. This review summarizes recent advances in understanding various risk and protective factors, as well as primary prevention measures for AD.

Atopic dermatitis (AD) is a prevalent inflammatory skin disorder in which patients experience recurrent eczematous lesions and intense itching. The colonization of Staphylococcus aureus (S. aureus) is correlated with the severity of the disease, but its role in AD development remains elusive. Using single-cell RNA sequencing, we uncovered that keratinocytes activate a distinct immune response characterized by induction of Il24 when exposed to methicillin-resistant S. aureus (MRSA). Further experiments using animal models showed that the administration of recombinant IL-24 protein worsened AD-like pathology. Genetic ablation of Il24 or the receptor Il20rb in keratinocytes alleviated allergic inflammation and atopic march. Mechanistically, IL-24 acted through its heterodimeric receptors on keratinocytes and augmented the production of IL-33, which in turn aggravated type 2 immunity and AD-like skin conditions. Overall, these findings establish IL-24 as a critical factor for onset and progression of AD and a compelling therapeutic target.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease worldwide. AD is a highly complex disease with different subtypes. Many elements of AD pathophysiology have been described, but if/how they interact with each other or which mechanisms are important in which patients is still unclear. Langerhans cells (LCs) are antigen-presenting cells (APCs) in the epidermis. Depending on the context, they can act either pro- or anti-inflammatory. Many different studies have investigated LCs in the context of AD and found them to be connected to all major mechanisms of AD pathophysiology. As APCs, LCs recruit other immune cells and shape the immune response, especially adaptive immunity via polarization of T cells. As sentinel cells, LCs are primary sensors of the skin microbiome and are important for the decision of immunity versus tolerance. LCs are also involved with the integrity of the skin barrier by influencing tight junctions. Finally, LCs are important cells in the neuro-immune crosstalk in the skin. In this review, we provide an overview about the many different roles of LCs in AD. Understanding LCs might bring us closer to a more complete understanding of this highly complex disease. Potentially, modulating LCs might offer new options for targeted therapies for AD patients.

Eczema is also known as atopic dermatitis, which goes on to affect the skin as a chronic inflammatory disease. It is associated with a constant feeling of scratchiness, erthyma and disruption of the natural skin barrier. Treatment provided at present may improve some of the symptoms, for instance use of corticosteroids or immunosuppressive agents, however, there is an overwhelming need for better focused and effective methods of treatment with minimal adverse effects. Fevipiprant, a DP2 receptor antagonist, has emerged as a promising agent targeting prostaglandin D2 (PGD2) pathways, which play a crucial role in eczema pathophysiology. This review examines the mechanism of action, pharmacological profile of Fevipiprant and present studies on preclinical and clinical development of Fevipiprant for treatment of eczema. Additionally, we provide a comparison of Fevipiprant with existing treatment options and evaluate its safety and tolerability. The evaluation gives a reason that targeting in the treatment of eczema by the use of Fevipiprant is able to effectively target the DP2 pathway which is associated with a good safetyl however presenting itself as a new treatment option in the management of eczema. Finally, long-term studies are essential to validate the feasibility, safety, and effectiveness of Fevipiprant compared to existing therapies for eczema. Novartis has taken advantage of this stat for comp… given the scarcity of effective therapies for paediatric atopic dermatitis in Japan. Exploring Fevipiprant from the Efficacy Perspective is also required because it will impact how it will enter clinical practice in therapy of eczema in the future.

Jiuwan decoction has been used to treat chronic eczema since the Qing Dynasty. According to clinical experience, Shizhenqing granules (SZQG), derived from the Jiuwan decoction, exert beneficial clinical effects on acute eczema and reduce recurrence. Therefore, we elucidated the underlying mechanisms of SZQG through network pharmacology, molecular docking, and experimental validation.

The main chemical components of SZQG were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). And the targets of SZQG against eczema were screened out through online databases. Then, the regulatory network map of the "herbal compound-potential target" and the target protein-protein interaction (PPI) network was constructed. The Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using by R language. Additionally, the interaction between the active compounds and the targets was verified by molecular docking technology. Finally, an experiment in vivo was used to verify the effect and mechanism of SZQG on eczema.

Using UHPLC-MS/MS, 158 main chemical compounds of SZQG were identified, and 72 compounds were selected according to the criteria for further analysis. All 237 potential targets of SZQG in eczema were explored using multiple online databases. The network with 14 core targets was screened out, including STAT3, RELA, TNF, JUN, MAPK3, IL-6, PIK3CA, STAT1, MAPK14, MAPK1, IL-4, NFKBIA, IL1B, and MYC. KEGG analyses indicated that the therapeutic effects of SZQG on eczema were predominantly associated with cytokine-cytokine receptor interaction, TNF, MAPK, NF-κB, toll-like receptor, T cell receptor, and Th1 and Th2 cell differentiation signaling pathways. Furthermore, the good affinity between the core compounds and core targets was verified by molecular docking technology, particularly for RELA and MAPK. Animal experiments revealed that SZQG downregulated MAPK14, RELA, T-bet, and GATA3 mRNA expression, reduced immunoglobulin E (IgE) and interleukin-4 (IL-4) serum concentrations, and improved eczema-like lesions in model rats.

This study identified potential targets and signaling pathways of SZQG in the treatment of eczema, whereby RELA and MAPK14 may constitute the main therapeutic targets of SZQG in cytokine regulation and reduction of inflammatory responses.

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.

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.

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.

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.

Atopic-like dermatitis (ALD) is a common side effect of interleukin-17A (IL-17A) inhibitors.

To determine the prevalence, risk factors, outcomes and treatment of ALD in a cohort of psoriasis patients treated with IL-17A inhibitors.

This retrospective study included 226 psoriasis patients treated with an IL-17A inhibitor in our dermatology department between July 2020 and July 2022. The patients were reviewed over 2 years. A logistic regression model in rare events data (relogit) was used to predict the risk factors for ALD.

Of the 226 patients, 14 had ALD. Data including age, body mass index, IL-17A inhibitor use, personal and family history of atopic disease, pet ownership history, and immunoglobulin E (IgE) levels were analysed using the relogit regression model. It indicated a personal history of atopic disease (odd ratio [OR] 27.830, 95% confidence interval [CI] 3.801-203.770; p = 0.001) and elevated IgE levels (OR 5.867, 95% CI 1.131-30.434; p = 0.035) as independent predictors of incident ALD. In one patient, anti-IL-17A therapy was discontinued, and treatment was switched to tofacitinib. Thirteen patients who continued with IL-17A inhibitor were treated with topical therapy and/or antihistamines, and their ALD was partially or completely resolved.

In this study, the incidence rate of ALD was 6.19%. Elevated IgE levels and a personal history of atopic disease were found to be the risk factors for ALD. Our study findings suggest that treatment should be provided based on the severity of psoriasis and incident ALD. Prior to treatment, psoriasis patients who have the risk factors for ALD should be informed of the possible development of ALD, and alternative psoriatic therapeutic options should be considered if severe ALD develops.

Canine atopic dermatitis (cAD) is a common and distressing skin condition in dogs, affecting up to 30% of the canine population. It not only impacts their quality of life but also that of their owners. Like human atopic dermatitis (hAD), cAD has a complex pathogenesis, including genetic and environmental factors. Current treatments focus on managing clinical signs, but they can be costly and have limitations. This article emphasizes the importance of preventing cAD from developing in the first place. Understanding the role of the skin's protective barrier is crucial, as its dysfunction plays a vital role in both hAD and cAD. hAD prevention studies have shown promising results in enhancing the skin barrier, but more research is needed to support more robust conclusions. While hAD primary prevention is currently a focal point of intensive investigation in human medicine, research on cAD primary prevention remains under-researched and almost non-existent. Pioneering effective prevention strategies for cAD holds immense potential to enhance the quality of life for both dogs and their owners. Additionally, it bears the promise of a translational impact on human research. Hence, further exploration of this crucial topic is not only relevant but also timely and imperative, warranting support and encouragement.

Obesity is associated with an increased risk of atopic dermatitis (AD) and may accelerate its development. Keratinocyte dysfunction has been observed in obesity-related skin diseases, including psoriasis and acanthosis nigricans, but is not fully understood in AD. In this study, we found that high-fat diet-induced obesity exacerbated AD-like dermatitis in mice, with elevated inflammatory molecules and increased CD36-SREBP1-related fatty acid accumulation in the lesional skin. Blocking CD36 or SREBP1 with chemical inhibitors effectively alleviated AD-like inflammation, decreased fatty acid accumulation, and downregulated TSLP expression in obese calcipotriol (MC903)-treated mice. Moreover, palmitic acid treatment induced TSLP overexpression in keratinocytes through the activation of the CD36-SREBP1 signaling pathway. The chromatin immunoprecipitation assay further revealed increased binding of SREBP1 to the TSLP promoter region. Our findings provide compelling evidence that obesity triggers the activation of the CD36-SREBP1-TSLP axis in keratinocytes, leading to epidermal lipid disorders and the aggravation of AD-like inflammation. By targeting CD36 or SREBP1, future combination therapies or modified treatment strategies could be developed to help manage patients with both obesity and AD.

Previous studies have shown significant associations between home environmental factors and childhood eczema. However, few studies have compared how associations differ in different regions. This study investigated associations between home environmental factors and childhood eczema ever, and related symptoms including itchy rash (IR) and being awakened by itchy rash at night (awake by IR) in 4 cities located in different regions of China, based on cross-sectional investigations during 2010-2012. We used two-step analysis to explore the associations between influencing factors and eczema/related symptoms: first, group Least Absolute Shrinkage and Selection Operator (LASSO) was conducted to identify important factors among a list of candidates; then, the associations in total study population and in each city were estimated using logistic regression. We found these home environmental factors to be risk factors for eczema or related symptoms: large residence size, shared room, air cleaner at home, abnormal smell, perceived dry air, visible mold or damp stains, cooking with coal or wood, painted wall, incense, mice, new furniture during pregnancy, abnormal smell at birth, window condensation at birth and environmental tobacco smoke at birth. Environmental protective factors were rural house location and window ventilation. Associations of factors with eczema/related symptoms differed across cities. For example, air conditioning was protective for eczema in Beijing and awakening by IR in Shanghai with ORs of 0.70 (95%CI: 0.52, 0.95) and 0.33 (95%CI: 0.14, 0.81) respectively, but not significant in other cities. Our results have implications for improving home environments to reduce the risk of childhood eczema/related symptoms in different regions of China.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease characterized by severe pruritus and eczematous lesions. Heterogeneity of AD has been reported among different racial groups according to clinical, molecular and genetic differences.

This study aimed to conduct an in-depth transcriptome analysis of AD in Chinese population.

We performed single-cell RNA sequencing (scRNA-seq) analysis of skin biopsies from five Chinese adult patients with chronic AD and from four healthy controls, combined with multiplexed immunohistochemical analysis in whole-tissue skin biopsies. We explored the functions of IL19 in vitro.

ScRNA-seq analysis was able to profile a total of 87,853 cells, with keratinocytes (KCs) in AD manifesting highly expressed keratinocyte activation and pro-inflammatory genes. KCs demonstrated a novel IL19+ IGFL1+ subpopulation that increased in AD lesions. Inflammatory cytokines IFNG, IL13, IL26 and IL22 were highly expressed in AD lesions. In vitro, IL19 directly downregulated KRT10 and LOR in HaCaT cells and activated HaCaT cells to produce TSLP.

Abnormal proliferation and differentiation of keratinocytes contribute immensely to the pathogenesis of AD, whereas AD chronic lesions have witnessed significant presence of IL19+ IGFL1+ KCs, which may be involved in the disruption of the skin barrier, the connection and magnification of Th2 and Th17 inflammatory responses, and mediation of skin pruritus. Furthermore, progressive activation of multiple immune axes dominated by Type 2 inflammatory reaction occur in AD chronic lesions.

Staphylococcus aureus is the critical pathogenic bacterium of eczema. The relationship between nasal colonization by S. aureus and eczema has not been well studied. We aimed to evaluate the associations between nasal colonization by S. aureus and eczema of multiple body sites, including persistent and ever-reported eczema. We further examined the associations between eczema and different subtypes of S. aureus, that is, methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA).

The real-world data from the US National Health and Nutrition Examination Survey were used. The associations were calculated using survey-weighted multinomial logistic regression models and further calculated in subgroups stratified by demographic factors.

In total, 2,941 adults were included. The prevalence rate of S. aureus nasal carriage was significantly higher in adults with persistent hand eczema (51.0%) than in those with ever-reported hand eczema (23.3%) and never eczema (26.9%). S. aureus nasal colonization was associated with an approximately two-fold increased risk of persistent hand eczema (odds ratios ranges in different models: 2.86-3.06) without significant heterogeneity in the association by demographic factors. No significant associations between S. aureus nasal colonization and persistent eczema of other body sites or ever-reported eczema of multiple body sites (including hands) were observed. Furthermore, similar significant association between nasal colonization of MSSA and persistent hand eczema was seen; the association was much stronger (odds ratios ranges in different models: 4.64-6.54) for MRSA, although with borderline significant.

Nasal colonization of S. aureus was associated with increased risk of persistent hand eczema. Our findings imply that preventive measures targeting S. aureus for the anterior nares should be considered in preventing and treating eczema.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with complex pathogenesis for which the cellular and molecular crosstalk in AD skin has not been fully understood.

Skin tissues examined for spatial gene expression were derived from the upper arm of 6 healthy control (HC) donors and 7 AD patients (lesion and nonlesion). We performed spatial transcriptomics sequencing to characterize the cellular infiltrate in lesional skin. For single-cell analysis, we analyzed the single-cell data from suction blister material from AD lesions and HC skin at the antecubital fossa skin (4 ADs and 5 HCs) and full-thickness skin biopsies (4 ADs and 2 HCs). The multiple proximity extension assays were performed in the serum samples from 36 AD patients and 28 HCs.

The single-cell analysis identified unique clusters of fibroblasts, dendritic cells, and macrophages in the lesional AD skin. Spatial transcriptomics analysis showed the upregulation of COL6A5, COL4A1, TNC, and CCL19 in COL18A1-expressing fibroblasts in the leukocyte-infiltrated areas in AD skin. CCR7-expressing dendritic cells (DCs) showed a similar distribution in the lesions. Additionally, M2 macrophages expressed CCL13 and CCL18 in this area. Ligand-receptor interaction analysis of the spatial transcriptome identified neighboring infiltration and interaction between activated COL18A1-expressing fibroblasts, CCL13- and CCL18-expressing M2 macrophages, CCR7- and LAMP3-expressing DCs, and T cells. As observed in skin lesions, serum levels of TNC and CCL18 were significantly elevated in AD, and correlated with clinical disease severity.

In this study, we show the unknown cellular crosstalk in leukocyte-infiltrated area in lesional skin. Our findings provide a comprehensive in-depth knowledge of the nature of AD skin lesions to guide the development of better treatments.

Atopic dermatitis (AD) is the most common chronically relapsing inflammatory skin disease, predominantly common in children; it is characterized by an eczematous pattern generally referable to skin dryness and itchy papules that become excoriated and lichenified in the more advanced stages of the disease. Although the pathophysiology of AD is not completely understood, numerous studies have demonstrated the complex interaction between genetic, immunological, and environmental factors, which acts to disrupt skin barrier function. Free radicals play a key role by directly damaging skin structure, inducing inflammation and weakening of the skin barrier. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a membrane-permeable radical scavenger, known to be a stable nitroxide, which exhibits excellent antioxidant effects in several human disorders, such as osteoarthritis and inflammatory bowel diseases. Considering the few existing studies on dermatological pathologies, this study aimed to evaluate tempol, in a cream formulation, in a murine model of AD. Dermatitis was induced in mice via dorsal skin application of 0.5% Oxazolone, three times a week for two weeks. After induction, mice were treated with tempol-based cream for another two weeks at three different doses of 0.5%, 1% and 2%. Our results demonstrated the ability of tempol, at the highest percentages, to counteract AD by reducing the histological damage, decreasing mast cell infiltration, and improving the skin barrier properties, by restoring the tight junction (TJs) and filaggrin. Moreover, tempol, at 1% and 2%, was able to modulate inflammation by reducing the nuclear factor kappa-light-chain-enhancer of the activated B cell (NF-κB) pathway, as well as tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression. Topical treatment also attenuated oxidative stress by modulating nuclear factor erythroid 2-related factor 2 (Nrf2), manganese superoxide dismutase (MnSOD), and heme oxygenase I (HO-1) expression levels. The obtained results demonstrate the numerous advantages provided by the topical administration of a tempol-based cream formulation, in reducing inflammation and oxidative stress through modulation of the NF-κB/Nrf2 signaling pathways. Therefore, tempol could represent an alternative anti-atopic approach to treating AD, thereby improving skin barrier function.

Molecular skin profiling techniques, typically performed on skin samples taken by punch biopsy, have enhanced the understanding of the pathophysiology of atopic dermatitis (AD), thereby enabling the development of novel targeted therapeutics. However, punch biopsies are not always feasible or desirable, and novel minimally invasive methods such as skin tape stripping have been developed.

To develop, optimize and validate a novel tape stripping method guided by noninvasive in vivo skin imaging to sample atopic skin in children.

Skin tape stripping-based procedures were compared and optimized using data from 30 healthy controls (HCs: 5 adults, 25 children) and 39 atopic children. Evaluations were guided by high-resolution photography, reflectance confocal microscopy, optical coherence tomography and transepidermal water loss measurements. We assessed and compared adverse events (AEs), the time needed to perform the sampling and the cDNA levels obtained from the tapes.

Tape stripping methods based on previously described protocols resulted in erosions in all participants and required a median time of 65 min to perform (range 60-70 min), but provided good cDNA yield. Shorter durations appeared less invasive but provided lower cDNA yield. The final optimized tape stripping protocol, using 11 tapes of 22 mm in diameter, each applied twice for 5 s with 90° rotation, did not produce significant AEs, was completed within a median time of 7 min (range 5-15 min) and provided good cDNA yield both in HCs and atopic children.

Our minimally invasive method is safe and reliable, and provides reproducible acquisition of cDNA in atopic children. In addition, it enables rapid sample collection, a crucial factor in clinical practice.

The physical barrier function of the skin is significantly supported by the (epi-)dermal immune system and the skin's own microbiome. Atopic dermatitis is characterized by an imbalance of all these three factors. The skin microbiome establishes itself immediately after birth and plays an important role in the development and maintenance of immune homeostasis. The clinical picture of atopic dermatitis shows, among other things, changes in the skin microbiome. Particularly during an acute phase, a strongly reduced bacterial diversity as well as the dominance of a single pathogen, Staphylococcus aureus, is observed. Staphylococcus aureus exacerbates the inflammatory process; furthermore, the bacteria produce proteases and toxins that further weaken the already severely compromised barrier function of the skin of patients with atopic dermatitis. However, knowledge of dermal dysbiosis also yields new treatment options for the therapy of the disease. In particular, the application of active bacteria represents a direct influence on the skin microbiome. Results of initial clinical studies on various approaches demonstrate promising results; this article provides an overview of work in this area.