Atopic Dermatitis Research Articles

Study on the molecular mechanism of atopic dermatitis in mice based on skin and serum metabolomic analysis.

Atopic dermatitis (AD) is a common chronic inflammatory dermatosis. However, the exact molecular mechanism underlying the development of AD remain largely unclear. To investigate comprehensive metabolomic alterations in serum and skin tissue between 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mice and healthy controls, aiming to identify the potential disease biomarkers and explore the molecular mechanisms of AD. In this study, Untargeted metabolomics analysis was used to investigate both skin and serum metabolic abnormalities of 2,4-dinitrofluorobenzene (DNFB)-induced AD-like mice. Then, the metabolic differences among the groups were determined through the application of multivariate analysis. Additionally, the selection of predictive biomarkers was accomplished using the receiver operating characteristic (ROC) module. Our findings showed that levels of 220 metabolites in the skin and 94 metabolites in the serum were different in AD-like mice that were treated with DNFB compared to control mice. Uracil, N-Acetyl-L-methionine, deoxyadenosine monophoosphate, 2-acetyl-l-alkyl-sn-glycero-3-phosphcholine, and prostaglandin D2 are considered potential biomarkers of AD as obtained by integrating skin and serum differential metabolite results. Metabolomic data analysis showed that the metabolic pathways in which skin and serum are involved together include histidine metabolism, pyrimidine metabolism, alanine, aspartate, and glutamate metabolism. Our research explained the possible molecular mechanism of AD at the metabolite level and provided potential targets for the development of clinical drugs for AD.

Vitiligo Cases in the Out-Patient Department in a Tertiary Care Hospital

Background: The prevalence of vitiligo has been reported to range from 0.1% to 8% worldwide. It has a low mortality rate but a high morbidity cost because of its psychological and social effects. Type-1 diabetes mellitus, autoimmune thyroid disease and other autoimmune illnesses have been linked to this condition. This study was performed to assess the occurence of vitiligo among males and females and the epidemiological status of vitiligo in a tertiary Hospital of Dhaka, Bangladesh. Materials and methods: A cross-sectional survey was conducted among 3,212 adults (1,429 males and 1,783 females) in a community of Dhaka between October 2022 and May 2023 at OPD of Delta Medical College. Face-to face interviews were conducted at the OPD of Delta Medical College for each participant and all respondents had their skin examined by dermatologists. The risks of comorbidities associated with vitiligo were evaluated. Results: In this particular research project, most vitiligo patients were between the ages of 13 and 60 years. According to this research, the average age of vitiligo patients was 35.5 years. Here, the proportion rate for this is 2.74%. The ratio of male participants to female participants in this research was M:F = 1:1.51. Only 88 out of the 24 cases were stable, whereas around 64 were unstable. The focused kind of vitiligo was shown to be the most prevalent form of the condition in this particular research. Conclusion: Vitiligo was most common among individuals in Dhaka in their middle 30s and the incidence of the condition rise with age. In adult patients, vitiligo was connected with higher risks of alopecia areata, hypothyroidism, diabetes mellitus and atopic dermatitis. IAHS Medical Journal Vol 7(1), June 2024; 17-21

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase2b Study.

In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs). This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI). A mixed model for repeated measures was used to estimate changes in PRO scores from baseline; scores were also compared with clinically meaningful change benchmarks. The analysis included 267 subjects, mean (SD) age 37.9 (14.7) years, 40.8% female; 55.1% grade3 and 44.9% grade4 Investigator Global Assessment for AD. Mean (SD) scores were: Worst Pruritus NRS 7.5 (1.9), Sleep Disturbance NRS 5.5 (2.9), DLQI total score 12.6 (7.1). Worst Pruritus and Sleep NRS scores had low positive correlations with SCORing AD (SCORAD) score (r = 0.44, r = 0.45 respectively) and negligible correlations with Eczema Area and Severity Index (EASI) score and area affected (r < 0.30). DLQI score varied by sex, study country, race, age, longer disease duration, disease severity (EASI and SCORAD), presence of asthma, and Worst Pruritus NRS, Sleep disturbance NRS, and DLQI scores. Rocatinlimab showed benefit on all three PROs, with significant improvements from baseline at the end of the double-blind period (week18) and active treatment extension (week36). Benefits were maintained over 20weeks' post-treatment follow-up. The benefit of rocatinlimab treatment on PROs is rapid and maintained for at least 20weeks following treatment completion. This analysis demonstrates the importance of characterizing the burden of moderate-to-severe AD from the patient's perspective, alongside clinical disease measures, to develop a fuller picture of treatment benefit. ClinicalTrials.gov identifier, NCT03703102.

Breakthrough in Pediatric Atopic Dermatitis Therapy: The Role of Monoclonal Antibodies as a New Hope for Targeted Treatment in Children

Aims: Atopic dermatitis (AD) is a prevalent skin condition affecting children of all ages and ethnicities. The aim of this review paper is to explore emerging treatments for atopic dermatitis, with a focus on the latest advancements in monoclonal antibody therapy. By evaluating their benefits and potential risks, the review seeks to provide a comprehensive understanding of their efficacy and safety in managing moderate to severe AD. Highlighting recent progress in targeted therapies, this paper aims to encourage continued research into innovative, effective, and safer options that can significantly improve patients’ quality of life. Methods: A systematic review of scientific and medical literature was conducted using PubMed and Google Scholar databases. Researchers included only studies that mentioned monoclonal antibodies approved by EMA (European Medicines Agency) or that are being currently researched for use in pediatric population with AD. Results: AD is a debilitating health issue both for children and their caregivers. Advances in understanding its pathophysiology have introduced new treatment approaches. Monoclonal antibody therapies provide notable benefits for moderate to severe AD, though more pediatric-specific studies are necessary. Conclusions: Monoclonal antibody therapy appears to be a promising treatment for pediatric patients with moderate to severe AD, effectively reducing symptoms and enhancing quality of life. Despite the potential distress of injections for young children, their infrequency aids in management. Further research is required to confirm the safety and efficacy of these therapies in children. Ongoing development of new antibodies targeting various aspects of AD is crucial for improving management and outcomes.

Association Between Atopic Dermatitis and Meniere's Disease: Nationwide Cohort Study.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by relapsing and remitting episodes. Although AD is well-known for its association with other allergic conditions, its relationship with Meniere's disease has not been thoroughly investigated. This study aimed to explore the potential correlation between AD and Meniere's disease. This study utilized data from the National Health Insurance Service-National Sample Cohort, a nationwide population-based database. The AD group was selected from a cohort of 1 million individuals randomly extracted from database. A non-AD group was obtained through Propensity Score Matching. The AD group comprised 84,579 individuals, with an equal number of individuals in the non-AD (control) group. The overall hazard ratio (HR) for Meniere's disease in the AD group was 1.44 (95% confidence interval (CI): 1.31-1.6). Subgroup analysis showed an adjusted HR of 0.42 (95% CI: 0.38-0.48) for Meniere's disease in males, 4.99 (95% CI: 4.45-5.62) in the middle-aged group (40-59 years), and 8.21 (95% CI: 7.21-9.35) in the older age group (≥60 years). Additionally, the adjusted HRs for developing Meniere's disease were higher in patients with comorbidities, including allergic rhinitis (1.18 [95% CI, 1.07-1.32]), allergic contact dermatitis (1.32 [95% CI, 1.19-1.48]), and allergic conjunctivitis (1.54 [95% CI, 1.32-1.82]). Long-term follow-up revealed that the prevalence of Meniere's disease was 1.44 times higher in the AD group compared to the control group. Moreover, older age, female sex, allergic rhinitis, allergic contact dermatitis, and allergic conjunctivitis were identified as factors that increase the risk of developing Meniere's disease. 3 Laryngoscope, 2024.

Immunoglobulin-coating patterns reveal altered humoral responses to gut bacteria in pediatric cow milk allergies.

Pediatric cow milk allergies (CMA) can occur in immunoglobulin (Ig) E and non-IgE-mediated forms. Unlike IgE-mediated allergies, the mechanisms of disease pathogenesis in non-IgE-mediated food allergy and an association with microbiome has not been well established. Previous studies have identified the presence of altered humoral responses to gut bacteria in IgE mediated allergies. Here, we analyzed IgA, IgE and IgG responses to gut bacteria in subjects with either IgE or non-IgE mediated CMA to identify relative proportions of Ig-coated bacteria and characterize unique disease specific microbial signatures. Multi-parametric flow cytometry analysis was used to identify IgA, IgE and IgG responses to gut bacteria in CMA patients. Cell sorting of Ig coated gut bacteria was subsequently performed followed by high throughput 16S rRNA gene sequencing and specific patterns of humoral responses to gut bacteria assessed in each study group. We identified significant alterations in IgA and IgG gut bacterial coating patterns in CMA subjects. Proportions of IgA-coated bacteria were decreased in IgE mediated CMA subjects without atopic dermatitis (ALL) and non-IgE mediated CMA subjects (ENP), compared to healthy controls (CON). In comparison, IgG-coated bacteria was significantly elevated in CMA subjects with atopic dermatitis (AD). Alpha and beta diversities displayed significant differences in IgA-, IgE-, and IgG-coated bacteria in AD and ENP groups. Significant differences in bacteria coated by IgA, IgE and IgG were detected at Phyla, Genus and Species levels and associated bacterial dysbiosis in IgE and non-IgE mediated allergies were identified. Linear discriminant analysis (LDA) effect size (LEFse) revealed unique disease associated bacterial signatures, including several pathogenic bacteria namely Bacteroides fragilis, Ruminococcus gnavus, Eubacterium dolichum, Fusobacterium, Clostridium neonatale and Robinsoniella peoriensis. Receiver operating characteristic curve analysis confirmed the efficiency of using the bacterial signatures identified as biomarkers for disease. Altered IgA and IgG responses to gut bacteria were identified in CMA subjects. The disease-specific responses were associated with alterations in bacterial diversity and concomitant dysbiosis of Ig-coated bacteria in IgE-mediated and non-IgE-mediated CMA pediatric subjects. The identification of pathogenic bacteria uniquely associated with different classes of allergic disease indicates a role of these bacteria in driving disease-specific pathological phenotypes.

Laboratory and clinical haemostatic aberrations in primary dermatologic disease: A review.

Inflammatory dermatologic diseases have long been viewed as a "skin limited" disease process. Current literature on inflammatory dermatologic diseases investigates their relationship and influence on thromboembolic states and thromboembolic complications and the understanding of their pathophysiology and molecular mechanisms.Studies specifically discuss known inflammatory skin diseases including alopecia areata, vitiligo, psoriasis, hidradenitis suppurativa, atopic dermatitis, chronic spontaneous urticaria, and autoimmune bullous diseases, and their effects on systemic inflammation, associated cardiovascular comorbidities, and thromboembolic or hypercoagulable states. The limited current literature shows potential for links between inflammatory skin diseases and hypercoagulable states. Biomarkers such as F1 + 2, D-dimer, eosinophilic cationic protein, and PAI-1 are currently being studied to outline the mechanisms connecting inflammatory skin disease to the coagulation system. Further study and larger amounts of data are needed to draw definitive conclusions, especially when interpreting biomarkers alone such as PAI-1.The mechanisms, rates of systemic inflammation, and clinical outcomes of traditionally "skin limited" inflammatory diseases remain chronically understudied in dermatology. Many organ systems have well established connections between inflammatory disease and hypercoagulable states, but there are significant gaps in the literature regarding skin diseases. There is a significant need for comprehensive investigation of molecular mechanisms behind inflammatory dermatologic disease and hypercoagulability, how hypercoagulability effects clinical outcomes, and proper intervention to optimize patient outcomes.

Harnessing the Anti-Inflammatory Effects of Perinatal Tissue Derived Therapies for the Treatment of Inflammatory Skin Diseases: A Comprehensive Review.

Dealing with chronic inflammatory skin conditions like atopic dermatitis and psoriasis can be extremely difficult. Current treatments, such as topical corticosteroids, often have limitations and side effects. However, researchers have discovered that the placenta's remarkable properties may provide a breakthrough in effectively addressing these skin conditions. The placenta comprises three essential tissues: decidua, placental membrane, and umbilical cord. Placental derivatives have shown significant potential in treating psoriasis by reducing inflammatory cytokines and inhibiting keratinocyte proliferation. In the case of atopic dermatitis, umbilical cord stem cells have demonstrated anti-inflammatory effects by targeting critical factors and promoting anti-inflammatory cytokines. The scope of benefits associated with placental derivatives transcends these specific applications. They also potentially address other inflammatory skin diseases, such as vitiligo, by stimulating melanin production. Moreover, these derivatives have been leveraged in the treatment of pemphigus and epidermolysis bullosa (EB), showcasing potential as a wound dressing that could eliminate the necessity for painful dressing changes in EB patients. In summary, the integration of placental derivatives stands to revolutionize our approach to inflammatory skin conditions owing to their distinct properties and the prospective benefits they offer. This comprehensive review delves into the current applications of placental derivatives in addressing inflammatory skin diseases, presenting a novel treatment approach.

Role of Vitamin D in Allergic Diseases

Introductions: Vitamin D has gained recognition in recent decades not only as a key regulator of calcium and phosphorus metabolism and bone health but also as an important factor modulating the immune system. Research indicates that vitamin D influences both innate and adaptive immune responses, which is significant in the treatment of allergic and inflammatory diseases. Vitamin D has a beneficial effect on asthma exacerbations and may help reduce respiratory inflammation, as well as alleviate symptoms of allergic rhinitis. Vitamin D deficiency may increase the risk of food allergies, worsen symptoms of atopic dermatitis, and contribute to the transition from acute to chronic urticaria. Conversely, supplementation may help prevent allergies, reduce the severity of atopic dermatitis by supporting skin barrier function and antimicrobial peptide production, and relieve symptoms in patients with chronic urticaria. Purpose of the study: The review article aims to present the current state of knowledge on the role of vitamin D in the treatment of asthma, allergic rhinitis, food allergies, atopic dermatitis, chronic urticaria, and eczema. Material and methods: To summarize the current knowledge on the topic, a literature review of English language papers with a focus on the most current literature was performed. The review was conducted with the PubMed database with 64 works used, accessed before October 2024. Conclusions: Although the impact of blood vitamin D levels on the development and progression of allergic diseases has not yet been fully clarified, scientific studies suggest its significant role in modulating immune responses. Due to its immunoregulatory properties, vitamin D offers new hope for more effective treatment and prevention of allergic diseases.

Dupilumab-Associated Bilateral Conjunctival Papillomas and Corneal Perforation.

We report a unique case of significant human papillomavirus-associated conjunctival papillomas and severe corneal ulceration leading to corneal perforation in a patient treated with dupilumab for atopic dermatitis. This study is a case report and literature review of severe corneal side effects related to dupilumab. A 27-year-old man with severe atopic dermatitis and no ocular history was administered dupilumab 300 mg via subcutaneous injections every 2 weeks with an excellent response. Following the onset of treatment, the patient developed conjunctivitis, conjunctival papillomas, and dry eyes, which were initially treated with lubricating eye drops. Fourteen months after commencing dupilumab, he had a rapid onset of painful visual loss in the OD accompanied by severe bilateral conjunctival injection and was found to have a central corneal ulcer and diffuse papillomas on the palpebral and bulbar conjunctiva. Despite management with intravenous methylprednisolone and topical dexamethasone, the patient's corneal ulcer progressed to a corneal melt, resulting in perforation 2 months after diagnosis, which necessitated a corneal graft. We present the third reported case of dupilumab-associated corneal perforation and the first case to our knowledge of dupilumab-associated conjunctival papillomas. As dupilumab usage increases, awareness of these potential complications among prescribers is essential.

Dual blockade of IL-17A and IL-36 pathways via a bispecific antibody exhibits enhanced anti-inflammatory potency

Antibody drugs targeting single inflammatory cytokines have revolutionized the treatment of immune-mediated inflammatory diseases. To investigate whether dual targeting interleukin-17 (IL-17) and IL-36 enhances anti-inflammatory activity, bispecific Ab HB0043 was generated by linking the single chain fragment variables (scFvs) from humanized anti-IL-36R antibody (HB0034) to the C-terminus of the heavy chain of anti-IL-17A IgG1 (HB0017) Fc using a flexible peptide linker. HB0043 largely maintained the binding affinities and biological activities of the two parent monoclonal antibodies (mAbs) in vitro. IL-17 and IL-36 cooperated to amplify the expression of pro-inflammatory and pro-fibrotic genes in normal human dermal fibroblasts (NHDF). However, HB0043 more effectively blocked IL-6 and IL-8 production in NHDF stimulated by IL-17A and IL-36 compared to two monoclonal antibodies. In a mouse model of Oxazolone (OXA)-induced atopic dermatitis and Imiquimod (IMQ)-induced skin inflammation, administration of both anti-IL17A mAb HB0017 and anti-mouse IL-36R surrogate antibody HB0034SA showed improved effectiveness in alleviating skin thickening and inflammation based on histological assessment. Further, in cynomolgus monkeys, HB0043 showed no enhanced target-related toxicity compared with the two parental mAbs in vivo and with a moderate increase in production of anti-drug antibodies. Together, dual blockade of IL-17A and IL-36R in the form of a bispecific antibody may have advantages in blocking the overlapping and non-overlapping functions of these two cytokines in skin inflammation that could not optimally be curtailed with single mAbs. In conclusion, as monotherapy may reach therapeutic celling for certain difficult-to-treat inflammatory and fibrotic diseases, dual targeting could potentially pave a way to combat these diseases.

Changes in skin barrier integrity by electrical impedance spectroscopy during dupilumab treatment on a child with severe atopic dermatitis

Background. Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by epidermal skin barrier dysfunction and altered immune response. Electrical impedance spectroscopy (EIS) has been used as a novel tool to detect skin barrier changes in AD. EIS is a non-invasive measure of the electrical impedance of tissue and is sensitive to cellular structure and extracellular environment. Case Presentation. An 8-year-old girl presented with severe AD, starting at 3 years of age. She also had allergic rhinitis, food allergies, and sensitization to mites, eggs, and nuts. Unresponsive to other treatments, she was administered 300 mg of dupilumab, a monoclonal antibody inhibiting IL-4 and IL-13 activity. Patient’s response to the treatment and skin barrier integrity was followed for 6 months: First at the baseline (before dupilumab) and then again at the 1st, 2nd, 3rd, and 5.5th month after dupilumab with SCORing Atopic Dermatitis (SCORAD), as well as measurements of moisture by MoistureMeterSC (Delfin®) and EIS by Nevisense® (SciBase) on the forearm and antecubital fossa of the same arm. At the end of 6 months, her SCORAD improved from 96 to 37. The moisture measurements were variable. The EIS by Z1 score in the forearm increased from 72 to 141 and EIS by MIX scores increased from 2.7 to 6.2. The correlation between SCORAD and forearm EIS by Z1 and MIX scores were significant: r=-0.913, (p=0.03) and r=-0.881, (p=0.049). The correlation between forearm MIX scores with sleeplessness and itching was significant: r=-0.956, (p=0.011), r=-0.942, (p=0.017). Conclusion. As higher EIS scores reflect stronger barrier integrity, the increase in Z1 and MIX obtained from Nevisense® implies an improvement in the skin barrier integrity during dupilumab treatment. This report highlights the potential use of EIS in atopic dermatitis patients to evaluate treatment efficacy. We urge rapid and non-invasive use of EIS in pediatrics to be further investigated in clinical settings.

Erythroderma in the elderly.

Erythroderma is the end-stage condition caused by various inflammatory diseases, presenting with widespread generalized coalesced erythema on the trunk and extremities. Erythroderma is not a disease itself, but rather is a symptom expressing erythrodermic condition, which is frequently associated with inguinal lymphadenopathy, chills, and mild fever. The clinical characteristics include sparing the folds of the trunk and extremities (deck-chair sign), and cobblestone-like disseminated grouping prurigo; however, the deck-chair sign is not specific to papulo-erythroderma (Ofuji disease). Erythroderma is induced by various causes, such as eczema, psoriasis, atopic dermatitis, drug eruption, lymphoma, lichen planus, pityriasis rubra pilaris, autoimmune bullous diseases, graft-versus-host disease, dermatomyositis, internal malignancy, and others. By contrast, it is not uncommon for even thorough investigations to often fail to identify any significant underlying or occult diseases. Such cases are often diagnosed as idiopathic erythroderma. In elderly cases, some regard erythroderma as late-onset atopic dermatitis, even if the patient does not have a history of childhood atopic dermatitis, while others consider it as a distinct condition with immune responses similar to atopic dermatitis. The etiology of erythroderma is suggested to be a Th2-dominant condition with IL-4/IL-13 playing a central role, suggesting that therapies targeting those Th2 molecules may result in sufficient effects. In this review, the characteristics of erythroderma in the elderly and new therapeutic approaches are discussed.

Food Allergy Test-Guided Dietary Advice for Children With Atopic Dermatitis: A Consensus Study.

The use of blood specific IgE or skin prick tests (SPT) to guide dietary exclusions for disease control in children with atopic dermatitis (AD) is controversial. We undertook a consensus exercise on how to interpret SPT results and dietary history for cow's milk, hen's egg, wheat, and soy in children < 2 years old with AD. Fourteen clinicians from general practice, pediatrics, pediatric dermatology, pediatric allergy, and pediatric dietetics from UK and Ireland took part in an online modified Delphi study. Over three rounds, participants gave their anonymous opinions and received individualized and group feedback, based on the premise that all children had SPTs. The findings were discussed in an online workshop. Of 18 symptoms, 12 were identified as relevant to immediate and 7 to delayed allergy. Regarding SPTs, there was consensus over which allergens to use for wheat and soy but not cow's milk or hen's egg; for all study foods, wheal size was determined as 0-1 mm negative, ≥ 5 mm sensitized, but between 2 and 4 mm, categorization varied by food. During the final workshop, consensus was reached on dietary advice for nine combinations of SPT results and dietary history. We attained consensus on how SPTs and dietary history for four common food allergens should be interpreted in young children under 2 years of age with AD. These pragmatic recommendations may support clinician education, consistency of decision-making, and future research.

Low Infection Rates With Long-Term Dupilumab Treatment in Patients Aged 6 Months to 5 Years: An Open-Label Extension Study.

To evaluate long-term infection rates in children aged 6 months to 5 years with moderate-to-severe atopic dermatitis (AD) treated with dupilumab. This was a post hoc analysis of an ongoing open-label extension (OLE) study of dupilumab. Pediatric patients aged 6 months to 5 years with moderate-to-severe AD who had previously taken part in the LIBERTY AD PRESCHOOL phase 2 and 3 clinical trials received weight-based subcutaneous dupilumab every 2 or 4 weeks. Exposure-adjusted infection rates after a median dupilumab exposure of 52 weeks are compared with data from the earlier randomized, placebo-controlled, 16-week LIBERTY AD PRESCHOOL phase 3 trial. Infection rates were overall lower in the OLE study compared with the dupilumab and placebo groups in the earlier 16-week trial, including total infections (101.0 patients/100 patient-years [PY]), nonherpetic skin infections (22.7 patients/100PY), herpetic infections (7.3 patients/100PY), and nonskin infections (92.9 patients/100PY). The frequency of severe and serious infections was low (3.1 patients/100PY), compared with 17.1 placebo-treated patients/100PY and 0 dupilumab-treated patients in the earlier 16-week trial, and no infections leading to treatment discontinuation were observed. Systemic anti-infective medication use (58.9 patients/100PY) was lower in the OLE study compared with both the dupilumab and placebo groups in the 16-week trial. Overall, reduced infection rates are observed in infants and young children with moderate-to-severe AD treated with dupilumab long-term, supporting the known safety profile of dupilumab.

Immunogenicity of dupilumab in adult and pediatric patients with atopic dermatitis

BackgroundDevelopment of anti-drug antibodies (ADAs) and neutralizing antibodies (NAbs) to monoclonal antibodies may adversely impact pharmacokinetics, efficacy, and/or safety.ObjectiveTo describe incidence, titer, and persistence of dupilumab ADAs and NAbs, and their effects on pharmacokinetics, efficacy, and safety in patients with atopic dermatitis (AD).MethodsThis analysis included seven phase 3 randomized, placebo-controlled (N=2,992) and two long-term open-label extension (N=2,287) trials of subcutaneous dupilumab in adults and pediatric patients with moderate-to-severe AD. ADA, NAb, and dupilumab concentration in serum were assessed using validated immunoassays. ADA impacts on efficacy (EASI) and safety were assessed.ResultsTreatment-emergent ADAs were observed in up to 8.6% (aged ≥18 years), 16.0% (12-17 years), 5.3% (6-11 years), and 2.0% (6 months to 5 years) dupilumab-treated patients. Among dupilumab-treated patients, ≤3.7% had persistent responses, &amp;lt;1% had high titers (≥10,000), and ≤5.1% were NAb-positive. NAbs were more common in patients with moderate- and high-titer ADA responses. High-titer ADAs, while infrequent, were the variable most associated with lower dupilumab concentrations in serum and loss of efficacy, independent of NAb status. Efficacy was generally similar in ADA-positive and -negative patients. For most patients with high- or moderate-titer ADAs, titers decreased and efficacy improved over time with continued dupilumab treatment. ADA-positive and -negative patients had similar incidences of treatment-emergent and serious treatment-emergent adverse events. One patient with high-titer ADAs developed serum sickness.ConclusionIn patients with AD, ADAs and NAbs had minimal impact on dupilumab concentration, efficacy, and safety, except for high-titer ADAs in a small number of patients.Clinical trial registrationClinicalTrials.gov, identifiers (NCT02277743, NCT02277769, NCT02260986, NCT02395133, NCT01949311, NCT03054428, NCT03345914, NCT02612454, and NCT03346434).

Longer-term safety and efficacy of baricitinib for atopic dermatitis in pediatric patients 2 to

Background Baricitinib, an oral selective Janus kinase inhibitor, improved clinical signs and symptoms of moderate-to-severe atopic dermatitis (AD) at week 16 in the phase 3 pediatric study BREEZE-AD-PEDS. Objective To assess longer-term efficacy and safety of baricitinib in pediatric patients aged 2 to <18 years. Methods In BREEZE-AD-PEDS long-term extension, responders and partial responders (validated Investigator Global Assessment-Atopic Dermatitis [vIGA-AD®] 0/1/2) at Week 16 remained on double-blind treatment to which they were randomized (placebo, baricitinib [1-mg equivalent, 2-mg equivalent, or 4-mg equivalent); non-responders (vIGA-AD 3 or 4) at Week 16 transitioned to open-label baricitinib 4-mg equivalent. Safety was summarized for all randomized patients who received ≥1 dose of study treatment. Results In total 467 patients received baricitinib for 750.7 patient-years. Proportion of responders/partial responders (at Week 16) who achieved vIGA-AD 0/1 at Week 52 was greater for baricitinib 4-mg equivalent (56.8%) versus all other treatment groups (42.2%, 47.7%, and 39.7% for 2-mg equivalent, 1-mg equivalent, and placebo, respectively). Most treatment-emergent adverse events were mild/moderate in severity. No deaths, pulmonary emboli, deep vein thromboses or arterial thrombotic events, major adverse cardiovascular events, malignancies, tuberculosis events, or gastrointestinal perforations were reported. Conclusions Baricitinib demonstrated sustained long-term efficacy. No new safety signals were identified. Trial Registration ClinicalTrials.gov Identifier: NCT03952559

Role of Eosinophils in Immunity, Allergy, and Inflammation: Friend or Foe

Eosinophils are multifunctional granulocytes involved in both protective and pathological immune responses. Traditionally recognized for their role in host defense against parasitic infections, eosinophils have gained significant attention for their involvement in allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis, where they are often considered detrimental. Eosinophils contribute to tissue damage and inflammation by releasing cytotoxic granule proteins, cytokines, and chemokines, perpetuating chronic inflammation. In conditions such as eosinophilic gastrointestinal disorders and hypereosinophilic syndrome, eosinophils infiltrate tissues and exacerbate inflammation, leading to organ dysfunction. However, eosinophils also exhibit beneficial roles, including modulating immune responses, promoting tissue repair, and maintaining tissue homeostasis. Recent research has highlighted their regulatory functions, where they interact with other immune cells to mediate both pro- and anti-inflammatory responses. The dual nature of eosinophils—both as protectors in immunity and contributors to pathology—presents a complex challenge in understanding their full impact on health and disease. Advances in biologic therapies targeting eosinophil activity, such as IL-5 inhibitors, offer promising treatment options for eosinophil-associated disorders. This review explores the diverse roles of eosinophils in immunity, allergy, and inflammation, examining both their protective and harmful functions, while discussing therapeutic strategies aimed at modulating eosinophil activity in various diseases. Keywords: Eosinophils, allergy, inflammation, immune regulation, IL-5 therapy

Effects of TMEM232 Variant on Infant Atopic Dermatitis According to Maternal Factors

Background: Atopic dermatitis (AD) is caused by interactions between genetic susceptibility and environmental factors. Transmembrane protein 232 (TMEM232) is one of the genes strongly implicated in AD. Methods: In the present study, we aimed to investigate the association between AD with variants within TMEM232 based on maternal factors, including a history of allergic diseases, and sensitization to Der f. We performed a candidate gene association study involving the Cohort for Childhood Origins of Asthma and Allergic Diseases. Results: A single variant of the TMEM232 gene, rs17132261, was found to be significantly associated with AD. Subjects carrying the wild-type allele (C) of rs17132261 had higher total IgE than those carrying the variant rs17132261 (T). Multiple logistic regression analysis showed a statistically significant association between TMEM232 gene polymorphism and an increased risk of AD in one-year-old infants. Moreover, rs17132261 was associated with increased total IgE in infants with a maternal history of allergic disease. The group with the CC genotype showed a higher risk of developing AD compared to carriers of CT and TT genotypes when the mother had a history of allergic diseases or was sensitized to Der f. Conclusions: Our findings demonstrate that the TMEM232 risk allele, in combination with maternal factors, higher the total IgE, which could be a potential risk factor for AD.

Transcriptomic evidence for atopic dermatitis as a systemic disease in NC/Nga mice

BackgroundIn the current study, we evaluated whether atopic dermatitis (AD) affects the entire body rather than being limited to skin barrier damage and inflammation. We hypothesized that medium-term exposure of distant organs to systemic inflammatory cytokines in sub-chronic inflammatory skin diseases has detrimental effects on distant tissues.ResultsOur findings demonstrated the dysregulation of genes and pathways associated with inflammation and the skin barrier, as well as genes and pathways involved in muscle development that respond to chemicals or stress in muscle tissues, all of which were reversed by hydrocortisone (Hc) administration. The expression of Ces1d showed significant differences during disease onset and after treatment in both skin and skeletal muscle, suggesting that Ces1d is likely responsible for the alleviation of subchronic AD.ConclusionsUsing NC/Nga mice with AD-like symptoms, we compared the transcriptomes of the skeletal muscle (a tissue that is relatively distant from the skin) with those of the skin (the lesion induction site) before and after disease induction, after which Hc was administered. Although further study is needed to better understand the effects of Ces1d on AD, skeletal muscle was associated with AD pathogenesis, and AD-like symptoms appeared to affect the body in a systemic manner. Given the importance of evidence-based medicine and the development of precision medicine, our findings provide insights into the mechanisms of AD onset and progression.