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Severe uveitis is a rare complication of interleukin-4 receptor alpha blocking by dupilumab in topic dermatitis (AD) patients. The aim of this study was to describe five moderate-to-severe AD patients who developed uveitis during dupilumab treatment and to compare the proteomic profile of aqueous humor (AqH) of dupilumab-associated uveitis (n=3/5 available samples) with non-infectious uveitis (n=27) and cataract controls (n=11). Included patients were treated at the University Medical Center Utrecht (the Netherlands). Active dupilumab-associated uveitis complicated by serous detachment, cystoid macular edema, or secondary glaucoma developed within a median of 6.0 months (interquartile range 2.3–16.5 months) after starting dupilumab. Uveitis resolved after discontinuation of dupilumab and/or treatment with local or systemic corticosteroids. Proteomic profiling of AqH revealed that the molecular profile of dupilumab-associated uveitis resembled that of non-infectious uveitis. In conclusion, dupilumab-associated uveitis is a severe adverse event of dupilumab therapy, requiring urgent referral to an ophthalmologist. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common, chronic inflammatory skin disorder driven by an intricate interplay of genetic, environmental, and immunological factors. As a clinically heterogenous condition, AD may be stratified into subtypes based on factors including, chronicity, immunoglobulin E levels, severity, age, and ethnicity. Transcriptomic and proteomic analyses in skin and blood help elucidate the underlying molecular mechanisms of these AD subtypes, referred to as AD endotypes. Further characterizing AD endotypes using reliable biomarkers can facilitate the development of more effective and personalized therapeutics and improve our tools for monitoring disease progression and therapeutic response across a diverse subset of patients. Here, we aim to provide perspective on the latest research regarding AD stratification using skin and blood-based studies and insight into the implications of these findings on the future of AD research and clinical practice. The precise stratification of AD endotypes will allow for the development of reliable biomarkers and a more personalized medical treatment approach. Clinical practice and trials will eventually be able to bridge clinical with molecular data to optimize individualized treatments and more effectively monitor treatment response. [ABSTRACT FROM AUTHOR]

Introduction: This work was to explore the efficacy and safety of self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream in atopic dermatitis (AD) of spleen deficiency and dampness accumulation type. Material and method: 120 patients with this kind of atopic dermatitis were grouped: The Observation group (disease health education + basic treatment + mometasone furoate cream + self-made Decoction) and The Control group (disease health education + basic treatment + mometasone furoate cream), 60 cases in each group. The SCORAD score, serum IgE level, peripheral blood eosinophils, adverse events, recurrence rate, and total effective rate after treatment were observed.Result: Through treatment, SCORAD score of the observation group (29.96 ± 2.88) was lower as against controls (36.04 ± 3.12), p < 0.05. Through treatment, the peripheral blood eosinophil count in the observation group was (311.26 ± 50.19) 106/L, which was lower than (582.71 ± 54.75) 106/L in controls; the serum lgE of the observation group was (712.44 ± 93.32) IU/mL, which was lower than the controls (890.12 ± 81.25) IU/mL, p < 0.05. The Observation group (56/60, 93.33%) demonstrated superior total effective rate to the controls (34/60, 56.67%); The recurrence rate of the observation group was 4/60 (6.67%), which was lower than the controls 16/60 (26.67%), p < 0.05.Conclusion: Self-made WenyangJianpi-qushi Decoction plus mometasone furoate cream to treat atopic dermatitis of spleen deficiency and dampness accumulation type has significant efficacy and good safety. [ABSTRACT FROM AUTHOR]

Introduction: The review article explores the evolving role of Bruton's tyrosine kinase (BTK) inhibitors in immune-mediated dermatological conditions, addressing significant gaps in current treatment approaches. Areas Covered: The review comprehensively discusses the mechanisms of action of BTK inhibitors, including irreversible and reversible inhibitors. Clinical applications of BTK inhibitors in dermatological diseases such as pemphigus, chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), and atopic dermatitis are explored, highlighting recent advancements and ongoing clinical trials. Potential advantages of BTK inhibitors over existing therapies and challenges in translating preclinical findings to clinical outcomes are discussed. Expert Opinion/Commentary: BTK inhibitors represent a promising therapeutic avenue for immune-mediated dermatological conditions, offering oral administration, targeted pathway inhibition, and a favorable safety profile compared to biologic therapies. Ongoing research and clinical trials hold the potential to address unmet needs and reshape the therapeutic landscape in dermatology. Plain Language Summary: Our manuscript explores how a new class of medications called Bruton tyrosine kinase (BTK) inhibitors could revolutionize the treatment of skin conditions caused by the immune system. These conditions, like chronic spontaneous urticaria (CSU), pemphigus, and systemic lupus erythematosus (SLE), often lack effective treatments. BTK inhibitors work by targeting specific pathways in the immune system, offering hope for patients with these challenging conditions. We reviewed clinical trials and research studies to understand how BTK inhibitors could benefit patients. One significant advantage of BTK inhibitors is their ability to provide targeted therapy, meaning they can specifically block the faulty immune responses driving these conditions without affecting the entire immune system. This targeted approach could lead to fewer side effects compared to current treatments, such as corticosteroids or immunosuppressants, which can have widespread effects on the body. Overall, BTK inhibitors represent a promising new approach to treating immune-mediated skin conditions. With further research and development, they could offer safer and more effective alternatives to current treatments, improving the lives of patients worldwide. [ABSTRACT FROM AUTHOR]

Autoimmune dermatosis (AID) occurs when the body's immune system attacks skin or tissue, leading to various types of skin disorders or injuries. Recent studies show that Janus kinases (JAKs) play critical roles in autoimmune diseases including AID by regulating multiple cytokine signaling pathways. CS12192, a novel JAK3/JAK1/TBK1 inhibitor, has been reported to exert ameliorative effects in rheumatoid arthritis. However, the efficacy of CS12192 on AID is undetermined. This study aims to investigate the therapeutic efficacy of CS12192 on psoriasis (PSO), systemic lupus erythematosus (SLE) and atopic dermatitis (AD) in mouse models. Interleukin-23 (IL-23)-induced PSO model, spontaneous SLE model of MRL/MpJ-Faslpr/J (MRL/lpr) mice, and oxazolone (OXA) and dinitrochlorobenzene (DNCB)-induced murine AD models were used for the evaluation of curative effects of CS12192, respectively. The skin lesion, biochemical parameters, ear thickness, ear weight and histopathology were assessed accordingly. In PSO model, mice treated with CS12192 show reduced ear thickness and ear weight as compared with vehicle. In SLE model, CS12192 ameliorates cutaneous parameters such as lymphadenectasis and skin lesion but not systematic parameters such as proteinuria concentration and score, serum dsDNA and BUN concentration. In AD models, CS12192 dose-dependently improves ear swelling and reduces histological scores, exerting equivalent efficacy with baricitinib, a marketed JAK1/JAK2 inhibitor. Our findings suggest that the novel JAK3/JAK1/TBK1 inhibitor CS12192 is potentially to alleviate autoimmune dermatosis. [ABSTRACT FROM AUTHOR]

Ovalbumin (OVA) is the most abundant protein in egg white, with excellent functional properties (e.g., gelling, foaming, emulsifying properties). Nevertheless, OVA has strong allergenicity, which is usually mediated by specific IgE thus results in gut microbiota dysbiosis and causes atopic dermatitis, asthma, and other inflammation actions. Processing technologies and the interactions with other active ingredients can influence the functional properties and allergic epitopes of OVA. This review focuses on the non-thermal processing technologies effects on the functional properties and allergenicity of OVA. Moreover, the research advance about immunomodulatory mechanisms of OVA-mediated food allergy and the role of gut microbiota in OVA allergy was summarized. Finally, the interactions between OVA and active ingredients (such as polyphenols and polysaccharides) and OVA-based delivery systems construction are summarized. Compared with traditional thermal processing technologies, novel non-thermal processing techniques have less damage to OVA nutritional value, which also improve OVA properties. OVA can interact with various active ingredients by covalent and non-covalent interactions during processing, which can alter the structure or allergic epitopes to affect OVA/active components properties. The interactions can promote OVA-based delivery systems construction, such as emulsions, hydrogels, microencapsulation, nanoparticles to encapsulate bioactive components and monitor freshness for improving foods quality and safety. [ABSTRACT FROM AUTHOR]

To evaluate the association between three allergic diseases (allergic dermatitis, allergic rhinitis, and asthma) and the development of retinal vein occlusion (RVO), a major retinal disease that causes visual impairment. This study used data obtained from the Korean National Health Insurance Claims database between 2009 and 2018. The association between the three atopic triads (allergic dermatitis, allergic rhinitis, and asthma) and the occurrence of sight-threatening RVO, as determined by diagnostic and treatment codes, were analyzed. Multivariate adjusted Cox regression analysis was used to determine the hazard ratios (HRs) and 95% confidence intervals for RVO development in the presence of allergic disease. In this population-based study, 2,160,195 (54.6%) individuals were male, 1,794,968 (45.4%) were female, and 620,938 (15.7%) were diagnosed with allergic diseases. Patients with either asthma or allergic rhinitis had a greater risk of RVO (adjusted hazard ratio (aHR) = 1.101, 95% confidence interval [CI] = 1.029–1.178 for asthma; aHR = 1.181, 95% CI = 1.147–1.215 for allergic rhinitis) compared to those without asthma or allergic rhinitis; however, patients with atopic dermatitis did not show a significant association with RVO (aHR = 1.071, 95% CI = 0.889–1.290), after adjusting for other risk factors. Our study revealed that allergic rhinitis, asthma, and coexisting multiple allergic conditions were associated with an increased risk of RVO. Thus, it may be advisable to suggest an ophthalmological examination for patients with allergies due to the increased possibility of the occurrence of retinal vascular disease. [ABSTRACT FROM AUTHOR]

Kimchi is a traditional fermented vegetable side dish in Korea and has become a global health food. Kimchi undergoes spontaneous fermentation, mainly by lactic acid bacteria (LAB) originating from its raw ingredients. Numerous LAB, including the genera Leuconostoc, Weissella, and Lactobacillus, participate in kimchi fermentation, reaching approximately 9–10 log colony forming units per gram or milliliter of food. The several health benefits of LAB (e.g., antioxidant and anti-inflammatory properties) combined with their probiotic potential in complex diseases including obesity, cancer, atopic dermatitis, and immunomodulatory effect have generated an interest in the health effects of LAB present in kimchi. In order to estimate the potential of kimchi as a probiotic food, we comprehensively surveyed the health functionalities of kimchi and kimchi LAB, and their effects on human gut environment, highlighting the probiotics function. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-4 and IL-13 are considered key drivers of type 2 inflammatory diseases. Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for IL-4 and IL-13, thus inhibiting signaling of both cytokines. We report a case of a patient with uncontrolled severe asthma and other T2 inflammatory diseases (atopic dermatitis, chronic rhinosinusitis with nasal polyposis and eosinophilic esophagitis) treated with dupilumab. After one year of treatment, dupilumab improved asthma control together with lung function parameters and airway inflammation. Additionally, a positive impact on quality of life (QoL), evaluated by validated questionnaires, across all the diseases was observed. In this case report, a positive and objectively measurable of global improvement on QoL across all four T2 comorbidities was observed after treatment with dupilumab, demonstrating the important role of IL-4 and IL-13 and the existence of a unifying pathological mechanism in T2 diseases. [ABSTRACT FROM AUTHOR]

Purtscher-like retinopathy is a rare and vision-threatening eye disease, which is usually associated with acute pancreatitis, autoimmune diseases, and renal failure. We here reported a case of Purtscher-like retinopathy after dupilumab treatment in atopic dermatitis. A 48-year-old woman with a history of severe atopic dermatitis developed ocular manifestations after second exposure to dupilumab. Best-corrected visual acuity (BCVA) was count fingers at 2 feet in the right eye and 20/133 in the left eye when she referred to our hospital. Fundus examination demonstrated bilateral serous macular off, thickening of papillomacular bundle, intraretinal hemorrhage, cotton-wool spots and Purtscher flecken surrounding the optic disc. Optical coherence tomography (OCT) angiography showed flow void in the superficial and deep capillary plexuses. And early hypofluorescence corresponding to grayish-white retinal thickening was observed in fundus fluorescein angiography. Laboratory tests revealed hypereosinophilia after symptoms appeared. A diagnosis of Purtscher-like retinopathy was made, which may associate with dupilumab. The patient accepted the treatment with glucocorticoids. At six months follow up, BCVA was 20/40 in the right eye and 20/25 in the left eye. The Purtscher-like retinopathy we report may be the adverse event of dupilumab. Rare adverse reactions to biologics deserve the attention of ophthalmologists. [ABSTRACT FROM AUTHOR]

AbstractLimosillactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., stands out as the most extensively researched probiotic. Its remarkable intestinal adhesion has led to widespread applications in both the food and medical sectors. Notably, recent research highlights the probiotic efficacy of L. reuteri sourced from breast milk, particularly in influencing social behavior and mitigating atopic dermatitis. In this review, our emphasis is on surveying recent literature regarding the promotion of host’s health by L. reuteri. We aim to provide a concise summary of the latest regulatory effects and potential mechanisms attributed to L. reuteri in the realms of metabolism, brain- and immune-related functions. The mechanism through which L. reuteri promotes host health by modulating the intestinal microenvironment primarily involves promoting intestinal epithelial renewal, bolstering intestinal barrier function, regulating gut microbiota and its metabolites, and suppressing inflammation and immune responses. Additionally, this review delves into new technologies, identifies shortcomings, and addresses challenges in current L. reuteri research. Finally, the application prospects of L. reuteri are provided. Therefore, a better understanding of the role and mechanisms of L. reuteri will contribute significantly to the development of new probiotic functional foods and enable precise, targeted interventions for various diseases. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionThe daily lives of adolescents have changed significantly because of COVID-19 pandemic. We investigated the effects of changes in daily life attributed to COVID-19 on allergic diseases among Korean adolescents.Data from the 2021 Korea Youth Risk Behavior Survey were used. In total, 54,848 survey participants were included in the analysis. Allergic diseases included allergic rhinitis, atopic dermatitis, and asthma. Changes attributed to COVID-19 included family economic difficulties, physical activity, breakfast skipping frequency, alcohol consumption, smoking, and depressive moods. Chi-square tests and multiple logistic regression analyses were conducted to examine the impact of changes in daily life attributed to COVID-19 on allergic diseases.Among the Korean adolescents surveyed, 29.8% experienced a deterioration in their economic status due to COVID-19, 49.1% reported decreased physical activity, 2.8% reported increased alcohol consumption, 1.0% reported an increase in their smoking behavior, and 36.9% reported an increase in depressive moods. Those diagnosed with atopic dermatitis, allergic rhinitis, or asthma within the previous 12 months accounted for 17.1%, 6.2%, and 1.0% of the population, respectively. Adolescents who were significantly affected by COVID-19 in their daily lives were frequently diagnosed with allergic diseases within the last 12 months.Changes in daily life due to COVID-19, including decreased physical activity and increased depressive mood, were common in adolescents and were associated with an increased prevalence of allergic diseases. Since changes in daily life due to the pandemic may increase the burden of allergic disease, additional interventions for disease management should be considered. [ABSTRACT FROM AUTHOR]

AbstractObjectiveDesign and methodsSubjectsResultsConclusionTo explore how the parents of children with atopic dermatitis and allergic diseases such as food allergy, allergic rhinoconjunctivitis, and asthma experience interactions with the Danish healthcare system over time.A qualitative design with individual in-depth interviews. The analysis was inspired by Systematic Text Condensation.Eleven parents of children with atopic dermatitis and allergic diseases who received treatment at hospitals in the Capital Region of Denmark. The families had experiences of cross-sectoral patient care.Despite having the same diseases, the children’s care pathways were very different. Mapping demonstrated the intricacy of care pathways for this group of children. We identified three aspects that impacted interaction with healthcare: responsibility, tasks, and roles. The families experienced care when the distribution of tasks and responsibilities associated with treatment and system navigation were consistent with both their expectations and their actual experiences. At the same time, families frequently experienced limited collaboration between healthcare professionals resulting in perceived fragmented care and an extended role for parents as care coordinators. Families felt cared for when healthcare professionals knew both their biomedical and biographical circumstances, and adjusted the level of support and care in accordance with the families’ particular needs, expectations, and evolving competences.We suggest that a possible pathway to improve care may be through a partnership approach as part of family-centered care, with general practitioners having a key role in helping to articulate the individual needs and expectations of each family. [ABSTRACT FROM AUTHOR]

Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease often associated with non-atopic comorbidities. Recently, a severity-dependent relationship between AD and sleep/mental health diseases has been proposed. However, few studies investigated these comorbidities and their association with AD severity through validated questionnaires. This study aimed to use a set of validated instruments to assess the impact of AD on sleep and psychological disorders and estimate the association of itch and AD severity with sleep disorders and psychological symptoms, distinguishing between clinical-oriented and patient-oriented measures. Methods: We conducted a case-control study, recruiting 57 adult AD patients (mean age ± std. dev. 34.28 years ± 13.07; 27 males) matched for age and sex with 57 healthy adults (34.39 years ± 13.09; 27 males). To investigate the differences in sleep quality, insomnia, depression, and anxiety between the two groups, we performed independent sample t-Tests. Moreover, we conducted univariate linear regression analyses to examine the relationship between itch and objective/subjective severity of AD and sleep quality, insomnia, and psychological symptoms. Results: AD patients reported lower sleep quality (p = 0.002), more severe insomnia (p = 0.006) and depression (p = 0.013), and higher stress levels than healthy adults (p = 0.049). Itch intensity was linked to sleep disturbances and psychological symptoms (R2range = 0.13–0.19, prange = 0.02–<0.001). Objective and subjective AD severity were similarly associated with worse sleep quality (R2 = 0.26, p < 0.001; R2 = 0.24, p < 0.001; respectively), anxiety (R2 = 0.15, p = 0.04; R2 = 0.17, p = 0.001; respectively), and self-perceived stress (R2 = 0.10, p = 0.02; R2 = 0.07, p = 0.049; respectively). However, subjective AD severity was more strongly associated with insomnia (R2 = 0.31, p < 0.001) and depression (R2 = 0.20, p < 0.001) than clinical-oriented AD severity (R2 = 0.19, p < 0.001; R2 = 0.05, p = 0.098; respectively). Conclusions: The study demonstrated poor sleep quality and high levels of insomnia, depression, and stress in AD patients, with an aggravated psychological status for adults with more severe skin disease. We suggest implementing a multidisciplinary approach to AD management/treatment that considers objective and subjective measures of disease severity. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) has become a common childhood disease that affects a large number of children worldwide and has become a chronic skin disease that causes huge economical and psychological damage to the whole family. Despite the use of steroids, immunosuppressants, and various topical preparation, the prognosis is still poor. Hence, this review aimed to explore the potential of using essential oils (EO) as an active ingredient in managing AD. The review was completed by using Pubmed, Scopus, and Medline to search for relevant articles that study the pathophysiology of AD, the properties of EO, the use of EO in managing AD, and the suitable advanced formulation to incorporate EO. From the review conducted, it was concluded that EO have huge potential in managing AD and can be used as complimentary therapeutic agents in AD treatment. Scientists and industries should venture into commercializing more topical products with EO to help manage AD more effectively. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) diagnosis in elderly is challenging, due to its clinical polymorphism and the lack of diagnostic biomarkers. Moreover, the chronicity of the disease and the complex pathogenetic mechanism, make elderly AD management challenging. A narrative review of the current literature was performed using the PubMed, Medline, Embase, and Cochrane Skin databases, by researching the following terms: 'atopic dermatitis,' 'clinical phenotypes,' 'eczema,' 'elderly patients,' 'elderly type atopic dermatitis,' 'eczema clinical presentation.' The aim was to report the current knowledge on pathogenesis, clinical presentation, and treatment options of elderly AD. Elderly type AD has recently been identified as a separate entity, with an increasing prevalence. With aging, both immunosenescence and barrier alterations can cause or modify AD presentation. Moreover, a chronic proinflammatory state (so-called 'inflammaging') is often present in elderly subjects. Older patients with AD may present with peculiar immunophenotypic profile, making AD diagnosis challenging. Similarly, the chronicity of the disease and the complex pathogenetic mechanism, make AD management a challenge. Indeed, systemic therapies for AD are often contraindicated or not tolerated and the management of elderly type AD is often burdened with numerous difficulties, leading to undertreated disease. Even if dupilumab and tralokinumab represent a valuable therapeutic weapon, more data on safety of JAK inhibitors are required. [ABSTRACT FROM AUTHOR]

Allergic contact dermatitis (ACD) is a common cutaneous inflammatory skin disorder that is diagnosed via epicutaneous patch testing (PT). ACD may also coexist with other systemic inflammatory conditions such as atopic dermatitis and psoriasis. Many of the treatments used to manage severe ACD, along with other systemic conditions, interact with and suppress the immune system, thereby potentially interfering with the mechanism of PT. There is uncertainty in the literature regarding the effects of immunosuppression on the results of PT. A comprehensive literature review was conducted using PubMed and Google Scholar to identify articles relevant to the topic of this review. Only articles available in English were included. This review discusses the impact of immunomodulating therapies on the results of PT. We summarize the available evidence and provide updated recommendations for several immunomodulating drugs commonly used in patients undergoing PT. In general, the results of PT are most reliable when performed without immunosuppression. If this is not feasible, it is best to have patients on as low a dose of immunosuppression as possible, but it may not be necessary to stop or change an immunomodulating drug prior to PT. [ABSTRACT FROM AUTHOR]

Atopic Dermatitis (AD) is the most common inflammatory skin disease with a complex and multifactorial pathogenesis. The use of proteomics in understanding AD has yielded the discovery of novel biomarkers and may further expand therapeutic options. This review summarizes the most recent proteomic studies and the methodologies used in AD. It describes novel biomarkers that may monitor disease course and therapeutic response. The review also highlights skin and blood biomarkers characterizing different AD phenotypes and differentiates AD from other inflammatory skin disorders. A literature search was conducted by querying Scopus, Google Scholar, Pubmed/Medline, and Clinicaltrials.gov up to June 2023. The integration of proteomics into research efforts in atopic dermatitis has broadened our understanding of the molecular profile of AD through the discovery of new biomarkers. In addition, proteomics may contribute to the development of targeted treatments ultimately improving personalized medicine. An increasing number of studies are utilizing proteomics to explore this heterogeneous disease. [ABSTRACT FROM AUTHOR]

We investigate a confirmatory two-stage adaptive procedure for assessing average bioequivalence and provide some insights to its theoretical properties. Effectively, we perform Two One-Sided Tests (TOST) to reach an overall decision about each of the two traditional null-hypotheses involved in declaring average bioequivalence. The tests are performed as combination tests separately for each hypothesis based on the corresponding pair of stagewise p-values. Features of the procedure include a built in futility, sample size reassessment, and the ability to simultaneously assess average bioequivalence with respect to multiple endpoints while controlling the familywise error rate. To facilitate inference at the end of a trial we consider confidence limits that match the decision reached on each one sided hypothesis and provide theory ensuring their appropriateness. The performance is assessed by simulation in the context of planning a study to compare two different administrations of an antibody treatment of atopic dermatitis. [ABSTRACT FROM AUTHOR]

HY-072808 is a novel phosphodiesterase 4 inhibitor clinically used for topical atopic dermatitis treatment. Cytochrome P450 enzymes are involved in transforming it into major metabolite ZZ-24. An efficient UPLC–MS/MS method was established to detect HY-072808 and ZZ-24 in plasma and skin tissues of minipigs.One-step protein precipitation was performed with acetonitrile. Subsequently, elution was served with a methanol and water gradient containing 0.1% formic acid for 3.5 min. The plasma and skin tissue concentrations of HY-072808 and ZZ-24 showed good linearity from 0.200 to 200 ng/mL.The experimental minipigs exhibited low systemic exposure and bioavailability of 3.1–7.6% after transdermal application of 1–4% HY-072808 ointment. Multiple topical administrations over seven consecutive days showed a minor accumulation in systemic exposure, with accumulation factors of 2.3 and 4.0 for HY-072808 and ZZ-24, respectively.The distribution of HY-072808 ointment among different cortical layers in minipigs was studied for the first time. Following transdermal application of 2% HY-072808 ointment, the concentration in plasma and skin tissues in the order of epidermis > dermis > subcutaneous tissue ≈ subcutaneous muscle ≈ plasma; at 48 h after the administration, the epidermis and dermis still had a high concentration of the drug. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a prevalent skin condition causing dry, pruritic, inflammatory skin lesions that can result in patient distress. Various emerging classes of therapy, including biologics and Janus kinase inhibitors, have been developed in recent years. A literature search of PubMed was conducted to explore existing literature and clinical trials. Treatment options and adverse effects were summarized by class and severity. JAK inhibitors and biologics are efficacious options for adults with severe atopic dermatitis. Using the Eczema Area and Severity Index (EASI) from 11 randomized control trials, the highest efficacy was seen with upadacitinib 30 mg with 70% of patients achieving EASI-75. Older, immune-inhibiting treatment options are still appropriate options to improve patient conditions. A meta-analysis of 39 randomized control trials concluded high dose cyclosporine is more effective at improving quality of life and itch when compared to azathioprine and methotrexate. Newly developed topical and systemic medications improve disease and itch severity and can be considered in patients without adequate control with their initial treatment regimen. Adverse effects must be considered when using the newer options, although major adverse events were not seen. Current management options are efficacious, but adherence is required for any effect. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, intensely pruritic disease associated with significant patient burden. Recent advancements in AD pathogenesis have expanded its therapeutics pipeline. Tralokinumab is a fully human monoclonal antibody that binds specifically Interleukin (IL)-13, inhibiting the downstream IL-13 signaling. Phase 3 clinical trials and some real-world studies showed that tralokinumab, as monotherapy or in combination with topical corticosteroids, is efficacious and safe in adult patients with moderate-to-severe AD. Similar results were reported in a phase 3 trial in adolescents (aged ≥12 years). We review the role of IL-13 in AD and discuss the value of tralokinumab for treating moderate-to-severe AD, comparing efficacy and safety results derived from clinical trials and real-life data. The role of IL-13 in AD supports a targeted therapeutic approach. Tralokinumab has proven efficacious and well-tolerated in a large proportion of patients confirming its value for treating moderate-to-severe AD from age 12 years onwards; it quickly improves itching and can maintain a high-level of response over time; it can be administered with flexible dosing schedules. Future studies will further clarify the role of IL-13 pathway and which patients would be best suited to tralokinumab, shifting AD treatment into an era of precision medicine. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) can be classified into intrinsic AD(IAD) and extrinsic AD(EAD). However, the differences in clinical features and pathogenesis between these two subtypes of AD are currently unclear. This study aimed to analyse the differences in clinical features and peripheral blood biomarkers between Chinese patients with severe IAD and EAD in order to elucidate the physiopathogenesis of AD. A total of 316 hospitalised patients definitively diagnosed with severe AD were included in this study. There were 72 cases of severe IAD and 244 cases of severe EAD. The clinical features of the patients were recorded in details. Serum total IgE, IgA, IgG, IgM, complementC3/C4, peripheral blood cell counts, lactate dehydrogenase (LDH), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-2R, IL-6, IL-8, and TNF-α in AD patients and 60 age-matched healthy controls were analysed. IAD and EAD had similar severity/Scoring Atopic Dermatitis (SCORAD) scores. Compared with healthy controls, IAD patients had significantly higher total IgE, eosinophils, monocytes, LDH, CRP, IL-2R, IL-6, IL-8 and TNF-α, and lower IgM and C4. EAD patients had significantly higher total IgE, IgA, eosinophils, white blood cell (WBC) counts, neutrophils, monocytes, basophils, LDH, CRP, IL-2R, IL-6, IL-8, TNF-α and lower IgM than healthy controls. IAD patients had a higher percentage of rural/urban living and female/male, a shorter course of disease and lower total IgE, eosinophils, WBC counts, neutrophils, monocytes, basophils, LDH, IgG and C4 than EAD patients. SCORAD scores, eosinophils, LDH expression levels increased with total IgE uniquely in patients with EAD. IAD and EAD exhibit specific clinical features and molecular changes. IAD has a more complex physiopathogenesis, and deserves further investigation. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, inflammatory, often severely itching skin disorder. It may worsen due to stress, depression, or anxiety. Calcitonin gene-related peptide (CGRP) may be involved in inflammation signaling. CGRP has also been suggested in relation to stress, depression, and anxiety. This study aimed to investigate the expression of CGRP in the skin of patients with AD. Twenty-seven adult patients with AD, characterized with clinical and psychodemographic parameters, were investigated regarding CGRP expression in skin biopsies, using an immunohistochemical technique. The total number of CGRP-positive nerve-like fibers was found to be higher in lesional skin than in non-lesional skin. Moreover, more inflammatory cells of dendritic shape intruded into the epidermis in lesional skin compared to non-lesional skin. Keratinocytes showing expression of CGRP were also found in lesional skin. Interestingly, the number of CGRP-positive nerve-like fibers in lesional skin correlated with depressive and anxiety scores. Correlation with depressive score was also found for round CGRP-positive inflammatory cells in the epidermis. CGRP may have a role in both the inflammatory process and distress, in AD. [ABSTRACT FROM AUTHOR]

Latilactobacillus sakei is used extensively in industrial production and food fermentations. The species is primarily derived from fermented meat and vegetable products and is also found in human feces. Genomics and metabolomics have revealed unique metabolic pathways in L. sakei and molecular mechanisms underlying its competitive advantages in different habitats, which are mostly attributed to its flexible carbohydrate metabolism, cold tolerance, acid and salt tolerance, ability to cope with oxygen changes, and heme uptake. In recent years, probiotic effects of L. sakei and its metabolites have been identified, including the ability to effectively alleviate metabolic syndrome, inflammatory bowel disease, and atopic dermatitis. This review summarizes the genomic and metabolic characteristics of L. sakei and its metabolites and describes their applications, laying a foundation for their expanded use across the food and healthcare industries. [ABSTRACT FROM AUTHOR]

Inflammatory skin diseases account for most chronic skin conditions. 3D bioprinting is an exciting technology that can revolutionize the understanding and approach to treatment of atopic dermatitis and graft-versus-host disease. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a prevalent chronic skin disease affecting all age groups. The connection with the gut microbiome led to oral probiotics as a therapeutic strategy. However, being viable microorganisms, probiotics might present risks. Thus, non-viable postbiotics have been considered as an alternative. We aimed to evaluate the efficacy of oral Lactobacillus postbiotics for managing symptoms of AD in pediatric and adult patients. A systematic review was conducted following PRISMA guidelines. Nine randomized controlled trials assessing the effects of non-viable Lactobacillus spp. administered orally to patients diagnosed with AD were included in the review, in which 512 subjects were evaluated after the intervention. Most studies allowed the concomitant usage of corticosteroids. Three studies focused on adults and indicated symptom improvement. In contrast, three out of six trials evaluating pediatric patients did not report postbiotics-favoring results. The dosage seems to be relevant for outcome determination. Two trials compared postbiotics with their viable analogs, and only one reported positive results in both groups. Postbiotics-associated shifts in gut microbial communities were reported in one trial. Mild adverse effects were detected by a single study. The overall results suggested that Lactobacillus postbiotics might be successfully used as adjuvant AD therapy in adults. Thus far, data do not indicate efficacy in pediatric patients. Standardizing nomenclatures and experimental procedures, as well as expanding the studies to more geographic locations and assessing comprehensively the effects on the gut microbiome would provide better perspectives of postbiotics as a therapeutic option for AD. The usage of oral probiotics has been driven by the recognized connection between atopic dermatitis (AD) and the gut microbiome. Probiotics might offer risks as they are viable microorganisms and non-viable postbiotics have been considered as an alternative. However, their effectiveness and safety in AD patients is not totally clear. This systematic review of clinical trials evaluated the effects of non-viable Lactobacillus spp. administered orally to AD patients. Results suggested that adult patients might benefit from oral Lactobacillus postbiotics; however, the efficacy in pediatric patients is uncertain. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) increases the risk of bacterial and viral cutaneous infections. This study assesses the risk of skin infections related to dupilumab monotherapy in moderate-to-severe AD. We searched PubMed/Medline, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library. For gray literature, Google Scholar was searched. A meta-analysis of randomized clinical trials (RCTs) for overall skin infections, eczema herpeticum, nonherpetic skin infections and subgroup meta-analysis based on overall herpetic infection type was performed. We observed a statistically significant (p < 0.005) lower incidence rate in the dupilumab group compared to placebo for overall skin infections (Risk Ratio [RR] = 0.59, 95% confidence interval [CI]: [0.47, 0.75], P < 0.0001) and nonherpetic skin infections (RR = 0.42, 95% CI: [0.27, 0.66], P = 0.0001). For herpetic infections in 2b phase studies a meta‐analysis demonstrated significantly higher events in dupilumab group compared to placebo (RR = 3.38, 95% CI: [1.98, 5.76], P < 0.00001, test for subgroup differences: P = 0.02, I2 = 65.6%). In moderate-to-severe AD, dupilumab in monotherapy may be an effective and safe therapeutic approach, not associated with an increased risk of overall skin infections and nonherpetic skin infections. Due to the lack of statistical significance in heterogeneity associated with potential confounders in some cases, results should be interpreted cautiously. The meta-analysis was registered in PROSPERO, ID: CRD42023441346 [ABSTRACT FROM AUTHOR]

New biologic and small molecule therapeutics have emerged for the treatment of moderate-to-severe atopic dermatitis (AD), including oral Janus kinase (JAK) inhibitors such as baricitinib. While JAK inhibitors are commonly used to treat rheumatoid arthritis and inflammatory bowel disease, these agents are relatively new in the field of dermatology. In this review, we outline the efficacy and safety data of phase III randomized controlled trials investigating the use of baricitinib for moderate-to-severe AD. A literature search was performed using PubMed.gov to identify articles relevant to the topic published before August 2023. Oral JAK inhibitors in AD management are highly efficacious, whether used alone, in conjunction with topical corticosteroids, or in patients who have failed other conventional systemic medications for AD. JAK inhibitors appear to be well tolerated in the AD patient population with fewer major safety risks than what has been seen in other patient populations. Assessing patient risk factors for cardiovascular, thromboembolic, and oncologic diseases is now an important part of the office visit for patients in whom you may consider using a JAK inhibitor. [ABSTRACT FROM AUTHOR]

The current knowledge on the associations between coeliac disease and different skin diseases is contradictory and the patient's perspective on the burden of these is lacking. This study aimed to investigate patient-reported frequency, severity and quality of life effects of skin disorders in coeliac disease patients compared to controls and moreover to study the impacts of gluten-free diet on these skin diseases. A study questionnaire designed for the purposes of this study and a validated Dermatology Life Quality Index (DLQI) questionnaire were posted to 600 adult members of the Finnish Coeliac Society and 1173 matched controls. Responses from 327 coeliac disease patients and 382 non-coeliac controls were compared. Coeliac disease patients were shown to be at no increased risk of atopic dermatitis, acne, rosacea, psoriasis, alopecia areata, vitiligo or chronic urticaria. The severity of these skin diseases did not differ between study groups, but the risk for at least moderate effects on quality of life caused by dermatological diseases was increased among those with coeliac disease. Positive response from gluten-free diet was most commonly experienced by coeliac disease patients with atopic dermatitis. Even though the risk for skin diseases was shown not to be increased among coeliac disease patients, there is still an increased burden related to experienced skin symptoms among these patients, which non-dermatologists treating coeliac disease patients should acknowledge. [ABSTRACT FROM AUTHOR]

The aim of the study is to evaluate the clinical reactions to tomatoes in atopic dermatitis (AD) patients, and to analyse the results of specific IgE to allergens of tomatoes and to molecular components of pollen, seeds, fruits, vegetables and latex with the use of ALEX2 Allergy Xplorer test. According to our results, 15% of AD patients suffer from clinical reactions to tomatoes; we confirmed the low sensitivity and low positive predictive value of specific IgE to molecular component Sola l 6 and allergen extract Sola l, the specificity of this test is higher. The significantly higher sensitisation to other nonspecific lipid transfer proteins is observed in patients sensitised to tomato allergens. An elimination diet and an exposure test are recommended to detect a reaction to tomatoes. ALEX2 Allergy Xplorer test gives us a comprehensive picture of sensitisation and the possibility of evaluation of cross-reacting allergens. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases. The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development. BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin. Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses. The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD. [ABSTRACT FROM AUTHOR]

Eczema can have profoundly negative effects on the lives of affected children and their families. Having observed parents' difficulties in a hospital setting, this practice-research study sought to explore parents' experiences in caring for a child with eczema. Semi-structured interviews were conducted with 14 parents whose children attended a dermatology clinic in Singapore and 'Framework' approach was employed for data analysis. Four overarching themes were identified: (1) Eczema - Living with it; (2) Managing child's eczema - tasks and responsibilities; (3) Shifting illness-related responsibilities - supporting effective self-management; and (4) Parental support needs. The chronicrelapsing skin condition entails complex management tasks that shift between parent and child as the latter assumes autonomy during adolescence. Parents face challenges during this transition. This study highlights the areas that social work practitioners need to respond to when tailoring interventions for parents and children with eczema. [ABSTRACT FROM AUTHOR]

Malassezia spp. are a group of lipid-dependent basidiomycetes yeasts acting as commensal organisms of the human and animal skin. However, under some not well-defined circumstances, these yeasts may switch to opportunistic pathogens triggering a number of skin disorders with different clinical presentations. The genus comprises of 18 lipid-dependent species with a variable distribution in the hosts and pathologies thus suggesting a host- and microbe-specific interactions. This review highlighted and discussed the most recent literature regarding the genus Malassezia as a commensal or pathogenic organisms highlighting Malassezia-associated skin disorders in humans and animals and their antifungal susceptibility profile. A literature search of Malassezia associated skin disorders was performed via PubMed and Google scholar (up to May 2023), using the different keywords mainly associated with Malassezia skin disorders and Malassezia antifungal resistance. Malassezia yeasts are part of the skin mycobiota and their life cycle is strictly associated with the environment in which they live. The biochemical, physiological, or immunological condition of the host skin selects Malassezia spp. or genotypes able to survive in a specific environment by changing their metabolisms, thus producing virulence factors or metabolites which can cause skin disorders with different clinical presentations. [ABSTRACT FROM AUTHOR]

A comprehensive review of the English-language medical literature was performed searching for ongoing and closed clinical trials concerning new and emerging monoclonal antibody therapies for moderate-to-severe atopic dermatitis in adults. Atopic dermatitis is a chronic inflammatory cutaneous disease with a complex pathogenesis. In the last years, numerous advances in understanding the atopic dermatitis pathogenesis allowed to obtain several therapeutic options, such as numerous monoclonal antibodies. Some monoclonal antibodies, such as dupilumab (anti-IL-4 Rα) and tralokinumab (anti-IL13) are already approved for the treatment of moderate-to-severe atopic dermatitis, and numerous articles in the literature have demonstrated their efficacy and safety. As there are numerous drugs under investigation, this review focuses on emerging monoclonal antibody therapies. There are numerous monoclonal antibodies under investigation that may be approved in the near future for the treatment of atopic dermatitis. Data from phase 2b and phase III clinical trials in moderate-to-severe atopic dermatitis in adults indicate that these drugs have a promising efficacy and safety profile. Monoclonal antibodies currently under investigation will be available in the coming years to enrich the therapeutic choice of new alternatives that are valid both in terms of efficacy and safety. [ABSTRACT FROM AUTHOR]

A chronic skin disorder called atopic dermatitis (AD) is brought on by the deterioration of the skin's barrier function marked by inflammation, dryness, and bacterial infection along with immunological changes. Althaea officinalis (AO), known for its anti-inflammatory and immunomodulatory properties, has been explored as a potential treatment for AD. This study aimed to develop and evaluate a novel transliposomes (TL) formulation containing AO for AD treatment. Using rotary evaporation, AO-TL formulations were created and optimized employing Box Behnken Design. The optimized AO-TL formulation showed consistent characteristics: vesicle size of 145.8nm, polydispersity index of 0.201, zeta potential of -28.22mV, and entrapment efficiency of 86.21%. TEM imaging shows the spherical shapes of the vesicle. These findings demonstrate the formulation's stability and ability to encapsulate AO effectively. In vitro drug release studies revealed that the AO-TL formulation released 81.28% of the drug, outperforming conventional AO dispersion (56.80%). Additionally, when applied to rat skin, the TL gel demonstrated deeper penetration (30μm) in comparison to the standard solution (5.0μm) based on confocal laser scanning microscopy (CLSM). Ex vivo and dermatokinetics studies showed improved penetration of drug-loaded transliposomes gel in rat skin than the conventional AO gel. Overall, the optimized AO-TL formulation offers promising characteristics and performance for the topical treatment of AD. Its drug release, antioxidant activity, and deeper penetration suggest enhanced therapeutic effects. Further research and clinical trials are needed to validate its efficacy and safety in AD patients. [ABSTRACT FROM AUTHOR]

This study aimed to describe the tinnitus severity in patients with chronic otitis media (COM) and describe the sociodemographic and clinical variables associated with tinnitus severity. Cross-sectional study. Two otology-referral centers in Bogotá (Colombia) were included. Sociodemographic, clinical associated factors and quality of life questionnaires were applied. Otoscopic evaluation and audiometric data were collected. About 231 adults with COM. Up to 51.5% of the patients reported severe tinnitus discomfort, 21.7% moderate discomfort, and 26.8% minor discomfort. Factor associated with increased tinnitus severity in patients with COM were older age (aOR: 1.02; 95% CI: 1.01–1.05), higher education (aOR: 2.24; 95% CI: 1.03–4.87), ear discharge during childhood (aOR: 1.88; 95% CI: 1.02–3.45), cholesteatoma in one ear (aOR: 2.26; 95% CI: 1.05–4.88), and pure-tone air average over 15 dB (aOR: 2.08; 95% CI: 1.28–3.36). Differences of 10-points in symptoms severity and 15-points in the total score of the "Chronic Suppurative Otitis Media Questionnaire-12" were found between the tinnitus severity groups. Our results highlight the need for further research on the associated factors of tinnitus severity on COM patients. COM patients with higher tinnitus severity presented worse audiometric results and worse quality of life outcomes. [ABSTRACT FROM AUTHOR]

There are a few studies about the relationship between inflammatory bowel disease (IBD) and atopic dermatitis (AD). It is implied that both diseases have common pathophysiologic mechanisms and can affect each other. However, little information is available on the effect of AD on the clinical course of patients with IBD. This is a multi-center, retrospective, observational study. We define AD as a chronic eczematoid dermatosis diagnosed by dermatologists. Patients with concurrent IBD and AD were defined as a case group. Age, gender, and IBD subtype-matched patients without AD were included as a reference group. The numbers of patients in the case and reference groups were 61 and 122 respectively. There was a significantly shorter biologics-free survival in the case group than that in the reference group according to the multivariable-adjusted Cox regression analysis with the onset age, disease duration, smoking status, use of steroid, use of immunomodulator, initial C-reactive protein, initial erythrocyte sedimentation rate, presence of other allergic diseases and initial disease severity [hazard ratio (HR) 1.828, 95% confidence interval (CI) 1.022–3.271, p =.042]. The trend was consistent in the subgroup analysis with ulcerative colitis (HR 3.498, 95% CI 1.066–11.481, p =.039), but not with Crohn's disease (HR 1.542, 95% CI 0.720–3.301, p =.265). AD showed a significant effect on the biologics-free survival of patients with IBD and especially the UC subtype. Further mechanistic research is required to elucidate the pathogenesis of AD on the clinical course of IBD. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, skin pain, and sleep impacts, which are only reportable by patients themselves. The goal of this research is to evaluate the reliability, validity, and interpretability of the scores from three patient-reported outcome measures within the context of a clinical trial for adolescents and adults with moderate to severe AD. Data from a Phase 3 randomized, double-blind, placebo-controlled, multinational clinical trial for individuals 12–75 years of age with moderate to severe AD (AD Up [ClinicalTrials.gov NCT03568318]) were used to assess the reliability, validity, and interpretability of scores on the Worst Pruritus Numerical Rating Scale (NRS) and the Atopic Dermatitis Symptom and Impact Scales (ADerm-SS and ADerm-IS). Analyses were conducted separately for the adult and adolescent subgroups. Of the 882 participants included in the psychometric analyses, the majority were adults (n = 769, 87.2%), male (n = 536, 60.8%), and white (n = 630, 71.4%). Multi-item scores from the ADerm-SS and ADerm-IS had good internal consistency reliability, and most scores demonstrated acceptable test-retest reliability. Scores from the three questionnaires demonstrated adequate validity, exhibiting correlations with other conceptually related outcome assessments and score differences between clinically distinct subgroups. Finally, the score interpretation analyses provide estimates for meaningful within-person change and between-groups difference thresholds that may be useful for future research in adults and adolescents with moderate to severe AD. These results provide evidence that the scores produced by the Worst Pruritus NRS, ADerm-SS, and ADerm-IS are reliable and construct-valid when completed by adults and adolescents with moderate to severe AD in a clinical trial setting. The results presented here expand upon the previous qualitative evidence of these tools and provide further support for their use in future clinical studies. While results are specific to clinical trials, next steps would be to evaluate the use of these questionnaires in clinical practice. This can provide clinicians and dermatologists a window into the patient's disease experience outside of the clinic, aid in shared decision making, and support a patient-centric approach to management of moderate to severe AD. [ABSTRACT FROM AUTHOR]

Asthma in preschool children is poorly defined, proving to be a challenge for early detection. The Breathmobile Case Identification Survey (BCIS) has been shown to be a feasible screening tool in older SCD children and could be effective in younger children. We attempted to validate the BCIS as an asthma screening tool in preschool children with SCD. This is a prospective, single-center study of 50 children aged 2–5 years with SCD. BCIS was administered to all patients and a pulmonologist blinded to the results evaluated patients for asthma. Demographic, clinical, and laboratory data were obtained to assess risk factors for asthma and acute chest syndrome in this population. Asthma prevalence (n = 3/50; 6%) was lower than atopic dermatitis (20%) and allergic rhinitis (32%). Sensitivity (100%), specificity (85%), positive predictive value (30%), and negative predictive value (100%) of the BCIS were high. Clinical demographics, atopic dermatitis, allergic rhinitis, asthma, viral respiratory infection, hematology parameters, sickle hemoglobin subtype, tobacco smoke exposure, and hydroxyurea were not different between patients with or without history of ACS, although eosinophil was significantly lower in the ACS group (p = 0.0093). All those with asthma had ACS, known viral respiratory infection resulting in hospitalization (3 RSV and 1 influenza), and HbSS (homozygous Hemoglobin SS) subtype. The BCIS is an effective asthma screening tool in preschool children with SCD. Asthma prevalence in young children with SCD is low. Previously known ACS risk factors were not seen, possibly from the beneficial effects of early life initiation of hydroxyurea. [ABSTRACT FROM AUTHOR]

Aim: Styrene monomer (SM) is a basic chemical used as a raw material for polystyrene and unsaturated polyester resins and in the production of synthetic resins, synthetic rubbers, paints, and adhesives. To date, it is unclear whether SM is associated with the aggravation of atopic dermatitis. The aim was to investigate the effects of SM on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. Methods: Male mice were injected intradermally with mite allergen on their right ears. In the presence of an allergen, SM (3.5 or 350 μg/animal/week) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expressions of cytokines and chemokines. Results: Macroscopic and microscopic examinations demonstrated that exposure to SM at a dose of 3.5 μg caused an exacerbation of atopic dermatitis-like skin lesions related to mite allergen. These changes were consistent with the level of histamine in the ear tissue as an overall trend. In contrast, 350-μg SM did not show significant enhancement effects. Conclusion: These results indicate that SM exacerbated atopic dermatitis-like skin lesions at hundred-fold lower levels than the level that causes no observed adverse effects as determined by histologic changes in rodent livers. SM could be at least partly responsible for the recent increase in atopic dermatitis. Styrene monomer (SM) is classified as an International Agency for Research on Cancer group 2B carcinogen and includes neurotoxicity and respiratory disorders. However, the effects of SM as a chemical substance on existing allergic pathophysiology have not been elucidated yet. This study demonstrated that SM exacerbated murine atopic dermatitis-like skin lesions at hundred-fold lower levels than the level that causes no observed adverse effects as determined by histologic changes in rodent livers, which was concomitant with the local level of histamine. These data hasten a need for comprehensive research to clarify the chemical pollutants' effects of doses much lower than NOAEL on vulnerable pathophysiologies such as allergy/atopy. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that Janus kinase (JAK) plays a crucial role in signal transduction by directly affecting various cytokine receptors involved in inflammatory diseases such as atopic dermatitis (AD). Large-scale clinical trials on AD utilizing JAK inhibitors and biologic reagents, such as dupilumab, which targets the IL-4Rα receptor subunit of the Th2 cytokines IL-4 and IL-13, have yielded highly favorable results in comparison to traditional therapies. This indicates that therapeutic strategies based on molecular biology are efficacious in clinical settings. However, in September 2021, the U.S. Food and Drug Administration (FDA) indicated that tofacitinib, a JAK inhibitor, may carry various risks, including severe heart disease. Similar concerns have been raised for other JAK inhibitors, and further safety evaluations are underway. Thus, human biology involving JAKs appeared more complicated than we expected. In this article, we provide an overview of the molecular mechanisms of AD and examine the molecular targeting drugs for AD from the perspective of JAK-related biology. [ABSTRACT FROM AUTHOR]

The present work aims to formulate nanoemulgel of crisaborole (CB) and evaluate its effectiveness against 2,4-Di-nitrochlorobenzene induced (DNCB) atopic dermatitis (AD) in mice. AD is a chronic inflammation of the skin affecting the quality of life. CB is a topical PDE4 inhibitor marketed as a 2% ointment. It, however, possesses poor aqueous solubility. An o/w nanoemulsion shall exhibit an enhanced therapeutic effect owing to the increased solubility of CB and an augmented skin penetration. The addition of a gelling agent to form a nanoemulgel further provides ease of application to the patients. Nanoemulsion was prepared by aqueous titration method using caproyl PGMC, cremophore EL and propylene glycol as the oil, surfactant, and cosurfactant respectively. The formulations were characterized by their size, zeta potential and polydispersity index (PDI). 1% Carbopol 934 was used as the gelling agent to formulate nanoemulgel comprising of optimized nanoemulsion (NE 9). Ex vivo skin permeation of the CB nanoemulgel was compared with the CB ointment. Its therapeutic effect was evaluated in Balb/c mice. NE 9 comprised of 7.49% oil, 37.45% Smix (1:3) and water 55.06%. Its particle size, PDI and zeta potential were 15.45 ± 5.265 nm, 0.098 and −17.9 ± 8.00 mV respectively. The nanoemulgel exhibited a 3-fold higher permeation flux as compared to the ointment. In vivo studies demonstrated that the nanoemulgel provided better therapeutic effect than the ointment. We can thereby conclude that nanoemulgel formulation can be a successful drug delivery strategy for enhancing the therapeutic effect of CB. [ABSTRACT FROM AUTHOR]

Probiotics consumption has been associated with various health promoting benefits, including disease prevention and even treatment by modulating gut microbiota. Contrary to this, probiotics may also overstimulate the immune system, trigger systemic infections, harmful metabolic activities, and promote gene transfer. in children, the fragile immune system and impaired intestinal barrier may boost the occurrence of adverse effects following probiotics' consumption. To overcome these health challenges, the key focus has been shifted toward non-viable probiotics, also called paraprobiotics. Cell wall polysaccharides, peptidoglycans, surface proteins and teichoic acid present on cell's surface are involved in the interaction of paraprobiotics with the host, ultimately providing health benefits. Among other benefits, paraprobiotics possess the ability to regulate innate and adaptive immunity, exert anti-adhesion, anti-biofilm, anti-hypertensive, anti-inflammatory, antioxidant, anti-proliferative, and antagonistic effects against pathogens, while also enhance clinical impact and general safety when administered in children in comparison to probiotics. Clinical evidence have underlined the paraprobiotics impact in children and young infants against atopic dermatitis, respiratory and gastrointestinal infections, in addition to be useful for immunocompromised individuals. Therefore, this review focuses on probiotics-related issues in children's health and also discusses the Lactobacillus and Bifidobacterium spp. qualities for qualifying as paraprobiotics and their role in promoting the children's health. [ABSTRACT FROM AUTHOR]

To describe the relationship between history of atopic disease on systemic and ocular manifestations of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN). Retrospective chart review of patients with SJS/TEN patients. Those with and without prior atopic diagnosis were compared. In total, 200 patients with SJS/TEN were identified. A total of 23 patients also had an atopic diagnosis. Four, 10, and 18 had atopic dermatitis, allergic rhinitis, and asthma respectively. Acute ocular severity was significantly worse in the atopic cohort. No significant differences in overall systemic severity of SJS or mortality were found between the atopic and non-atopic cohorts. Compared to our hospital system's general population, prevalence of an atopic diagnosis was significantly higher in those with SJS/TEN. Patients with a history of an atopic diagnosis appear to have more significant acute ocular involvement during their SJS/TEN hospitalization. Atopic conditions appear to occur more frequently in the SJS/TEN population compared to the general population. [ABSTRACT FROM AUTHOR]

Ozone is widely used to inactivate bacteria, fungi, and viruses. In recent years, the treatment of itchy skin diseases (eczema and atopic dermatitis) using trace ozone has also received attention. However, the feasibility of using trace ozone to replace personal care products (PCPs) has rarely been analyzed. In this study, the applicability of trace ozone was evaluated in terms of its efficiency for microbial inactivation in three types of skin microbiomes, cleaning performance on simulated human hair and epidermis, safety for simulated human hair, and contribution to emission reduction. The results revealed that at a 10:1 ratio of ozonated water to bacterial suspension, the inactivation ratios of Malassezia, C. albicans, and S. epidermidis reached 99.63%, 83.47%, and 100%, respectively. In addition, the cleaning performance of an ozone solution (0.4 mg/L) for simulated human skin contaminated with carbon black and sebum could reach 95.89% and 95.63%, respectively, with 5 min of washing. The average scores were 0.40 and 0.37 after 5 min and 10 min of ozone treatments, respectively, indicating that trace ozone does not significantly damage simulated human hair. Results also revealed that the total emissions of COD, TP, and TN would be reduced by 1.29×106, 3.55×103, and 3.63×103 mg/ (household · year), respectively, if PCPs are replaced by trace ozone. In short, our findings indicate that trace ozone is a potential alternative to PCPs. By replacing PCPs with trace ozone, the use of synthetic chemical products can be reduced and carbon emissions from oil extraction can be countered. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a widespread disease that can be associated with other conditions, including conjunctivitis, rhinosinusitis, asthma, food allergy, and atopic dermatitis. Diagnosis is based on the history and documentation of sensitization, such as the production of allergen-specific IgE, preferably using molecular diagnostics. Treatments are based on patient education, non-pharmacological and pharmacological remedies, allergen-specific immunotherapy (AIT), and surgery. Symptomatic treatments mainly concern intranasal/oral antihistamines and/or nasal corticosteroids. This review discusses current and emerging management strategies for AR, covering pharmacological and non-pharmacological remedies, AIT, and biologics in selected cases with associated severe asthma. However, AIT presently remains the unique causal treatment for AR. The management of allergic rhinitis could include new strategies. In this regard, particular interest should be considered in the fixed association between intranasal antihistamines and corticosteroids, probiotics and other natural substances, and new formulations (tablets) of AIT. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease where patients are more susceptible to infection and inflammation. The most salient symptoms of atopic dermatitis (AD) are skin dysbiosis and ceramide deficiency. Here, the effect of AD conditions on S. aureus resilience was investigated. S. aureus and S. epidermidis biofilms were co-inoculated at healthy and AD bacterial ratios and exposed to various sphingosine dosing regimens. In both healthy (S. epidermidis dominant) and AD (S. aureus dominant) conditions the viability of the non-dominant bacterial species was affected. Quorum sensing (QS)-impaired S. aureus was overall more susceptible to sphingosine. Despite the general resilience of QS-intact S. aureus against sphingosine, modulation of S. epidermidis (healthy ratio) and sphingosine (healthy Sph) led to a lack of recovery from its initial killing. Overall, it was found that when in biofilms, S. epidermidis increases S. aureus resilience to sphingosine, possibly enhancing the pathogen's recalcitrance in AD skin. [ABSTRACT FROM AUTHOR]

The relationship between atopic dermatitis and atopic diseases such as food allergies, asthma, and allergic rhinitis in terms of co-occurrence, underlying mechanisms, and therapy is well documented. There is increasing evidence that atopic dermatitis is associated with non-atopic comorbidities such as cardiac, autoimmune, and neuropsychological comorbidities, as well as cutaneous and extracutaneous infections, establishing atopic dermatitis as a systemic disease. The authors reviewed evidence on atopic and non-atopic comorbidities of atopic dermatitis. A literature search was conducted in PubMed for peer-reviewed articles published until October 2022. Atopic and non-atopic diseases coexist with atopic dermatitis more often than would be expected by chance. The effect of biologics and small molecules on atopic and non-atopic comorbidities may contribute to a better understanding of the relationship between atopic dermatitis and its comorbidities. Their relationship needs to be explored further to dismantle the underlying mechanism and move toward an atopic dermatitis endotype-based therapeutic approach. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic, recurrent, itchy inflammatory skin disease with a vast influence on a patient's quality of life (QoL). Mild-moderate AD was classically managed with the use of topical corticosteroid (TCS) and calcineurin inhibitors (TCI). It was proven that the JAK pathway plays an important role in the development of AD. The introduction of topical JAK inhibitors may revolutionize the classical approach to the management of mild-to-moderate atopic dermatitis. This review discussed the role of the JAK pathway in the development and exacerbations of AD with an emphasis on the newly introduced, topical selective JAK1 and JAK2 inhibitor – Ruxolitinib (RUX) cream. It provides an extensive review of pharmacokinetics and pharmacodynamics, efficacy, and safety of RUX cream in clinical trials. Results from phase II and two phase III clinical trials have shown that RUX cream could be a promising topical treatment of mild-moderate AD. Its favorable safety profile and good efficacy make RUX cream a beneficial modality for patients with chronic TCSs and TCIs use. Future studies on younger patients and with a longer observational period are necessary to adequately assess the efficacy and safety of RUX cream in the whole AD population. [ABSTRACT FROM AUTHOR]