Gardenia jasminoides fruit extract alleviates MC903-induced atopic dermatitis and reduces IL-4/IL-13-induced tight junction disruption and inflammation by regulating the phosphorylation of STAT6.

Long-term Persistence, Safety and Efficacy Profile of Dupilumab in Atopic Dermatitis: A Real-world Retrospective Multicenter Study From Spain.

Single-cell transcriptomic mendelian randomization and co-localization reveal immune-mediated regulatory mechanisms and drug targets in atopic dermatitis.

Toxocara seropositivity in patients with atopic dermatitis and chronic urticaria: Evidence from a matched case-control study.

A severe case of rhabdomyolysis, acute kidney injury, cardiogenic shock, and chronic complications caused by an excessively large dose of Tripterygium glycoside.

The effects of Polygonum capitatum in treating atopic dermatitis via modulation of the th2 cytokine pathway

Early-life bovine colostrum supplementation alleviates atopic dermatitis through gut microbiota remodeling and enhanced immune regulation

Encouraging formulation and assessment of mizolastine-loaded nanosponges for management of atopic dermatitis in animal model

Purpose: To report a rare case of infectious keratitis complicating acute corneal hydrops (ACH) in a patient with Down syndrome and to discuss risk factors, clinical features, and management strategies. Observation: A 20-year-old female with Down syndrome, atopic dermatitis, and a history of eye rubbing presented with acute corneal hydrops. Anterior segment OCT confirmed the rupture of Descemet’s membrane. Initial conservative treatment was initiated. Three days later, the patient presented with severe infectious keratitis. Corneal cultures grew Staphylococcus aureus, sensitive to topical tobramycin and ciprofloxacin. Gradual resolution of the infiltrate and the corneal edema was observed, leading to formation of a central corneal opacity after one month of treatment. Conclusion: Infectious keratitis is an uncommon but rapidly progressive complication of ACH. The reported risk factors included atopic dermatitis, eye rubbing, the use of topical corticosteroids and contact lens wear. Early detection through careful clinical assessment and imaging is critical to initiate antibiotic treatment. Despite infection control, visual prognosis remains poor due to residual corneal scarring and neovascularization. Prophylactic antibiotics may be considered in high-risk cases to prevent superinfection.

Atopic dermatitis (AD) is characterized by cutaneous dysbiosis marked by Staphylococcus aureus overgrowth, reduced commensal diversity, barrier dysfunction, and chronic inflammation. We investigated acacia gum (AG) as a topical prebiotic to modulate staphylococcal community structure and biofilm ecology in AD. Using both in vitro and in vivo approaches, we examined how AG reshaped microbial interactions and host responses. In coculture systems, AG selectively promoted Staphylococcus epidermidis while suppressing S. aureus. The S. aureus growth inhibition by AG involved direct antibacterial activity and commensal-mediated effects. We found that AG-upregulated glutamyl endopeptidase in S. epidermidis played a role in suppressing S. aureus colonization. AG disrupted both developing and established S. aureus biofilms and reduced intracellular persistence within macrophages, indicating activity across extracellular and host-associated niches. Beyond microbiota modulation, AG attenuated keratinocyte and macrophage activation via downregulation of proinflammatory cytokines and chemokines. In an AD-like mouse model, topical AG reduced S. aureus burden by three orders of magnitude, improved microbial diversity, partially restored barrier integrity, and decreased inflammatory cell infiltration without detectable toxicity. Collectively, AG reprograms staphylococcal dysbiosis and biofilm stability, supporting microbiota-directed prebiotic modulation as a mechanistically defined strategy for AD.

Janus kinase inhibitors (JAKis) have emerged as effective treatments for several skin immune-mediated inflammatory diseases (IMIDs). However, safety concerns have been raised due to boxed warnings from rheumatoid arthritis trials, and whether these risks apply to skin IMIDs remains uncertain. This multinational retrospective cohort study used the TriNetX database to compare the real-world safety of JAKis and conventional immunomodulators (cIMs) in patients aged 12 years or older with skin IMIDs (psoriatic disease, atopic dermatitis, or alopecia areata). Patients newly prescribed JAKis (tofacitinib, upadacitinib, deucravacitinib, baricitinib, abrocitinib, or ritlecitinib) were propensity score-matched (1:1) with those prescribed cIMs (methotrexate or cyclosporine) based on demographics, baseline skin IMIDs, and comorbidities, yielding 17,068 matched patients. Over 2 years, the JAKi cohort showed lower incidences of all-cause mortality (0.28% vs. 0.62%; P = 0.015) and major adverse cardiovascular events (MACE; 1.15% vs. 1.95%; P = 0.005) than the cIM cohort, corresponding to reduced risks (mortality: HR, 0.47; 95% CI, 0.25-0.88; MACE: HR, 0.63; 95% CI, 0.46-0.88). Risks of venous thromboembolism (HR, 0.80; 95% CI, 0.43-1.48) and malignancy (HR, 0.85; 95% CI, 0.63-1.16) were not increased. Subgroup analyses, including older adults and those with cardiometabolic risk factors, showed no signal of increased risk, with consistent findings across available agent-level and sensitivity analyses. These results suggest that, over 2 years, JAKis are not associated with increased risks of mortality, MACE, venous thromboembolism, or malignancy compared with conventional systemic agents in patients with skin IMIDs.

Healthy Diet Intervention for Treating Atopic Dermatitis: A Pilot Randomised Controlled Trial.

Atopic dermatitis (AD) remains a significant clinical challenge due to the limited efficacy and safety concerns associated with current therapies. To address this unmet need, we utilized structure-guided analysis and identified a previously unrecognized hydrophobic surface (S1) unique to ROCK2. Exploiting this structural feature through virtual screening led to the discovery of compound 10d, a potent ROCK2 inhibitor with markedly improved selectivity compared to the reference compound KD025. In a mouse model of MC903-induced AD, 10d effectively suppressed inflammation and achieved therapeutic efficacy superior to the model group, while maintaining a favorable safety profile. Mechanistically, we demonstrated that 10d attenuates AD pathology by downregulating S100A9, highlighting the ROCK2-S100A9 axis as a novel pathway in AD pathogenesis. Collectively, these findings establish 10d as a highly active and selective inhibitor, marking the first exploration of ROCK2-targeted therapy for AD treatment.

Messages in a vesicle: exosomes at the crossroads of skin pathology and healing.

Dupilumab, a standard treatment for atopic dermatitis (AD), has been associated with cutaneous T-cell lymphomas (CTCL), particularly mycosis fungoides (MF) and Sézary syndrome (SS). Nevertheless, the available data remain heterogeneous. To characterize the clinical features, timeline and outcomes of dupilumab-related CTCL emergence in order to develop consensus-based recommendations for dupilumab use in CTCL-related settings. A systematic review was conducted involving 51 studies reporting cases of CTCL in patients treated with dupilumab, followed by a modified delphi process to generate expert consensus recommendations. Data were obtained from 547 patients (mean age: 58 years; SD: 11.5; range: 10-85). New or worsening skin lesions were reported after dupilumab initiation, occurring at a mean of 8.9 months (SD 5.1; range 0.5-27 months). These were diagnosed as MF in 72% of cases, SS in 11% and other CTCL subtypes in 19%, of which 53% were at an early stage (stage ≤IIA). Dupilumab was discontinued in 75% of cases, and 62% received CTCL-directed treatment. Clinical remission was achieved in 44 of the 63 patients with available follow-up. The expert panel reached broad consensus, agreeing that dupilumab may unmask or exacerbate pre-existing CTCL and should be avoided in cases of MF/SS and mogamulizumab-induced rashes. They emphasized the importance of diagnostic vigilance, providing recommendations for skin biopsy, histology and clonality testing before and during treatment, particularly for patients with AD onset after the age of 40 or with atypical features. Dupilumab should be discontinued once CTCL confirmed, and methotrexate or phototherapy considered as alternatives. Cyclosporine and JAK inhibitors are considered unsuitable, and switching to other Th2-targeting biologics is discouraged due to insufficient data. Dupilumab may unmask or exacerbate CTCL, particularly MF and SS. The consensus-based recommendations offer practical guidance for the safe management of patients.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and eczematous lesions. Nemolizumab, an interleukin-31 receptor alpha antagonist, has shown efficacy and safety with background topical corticosteroids and/or topical calcineurin inhibitors in the ARCADIA 1&2 phase 3 trials, and is approved for the treatment of moderate-to-severe AD in individuals aged ≥12 years in several countries including, the US and Europe. However, there is a need for a study that better reflects real-world settings and routine clinical practice beyond the limitations of controlled trials. Objective: To report key design features of RE-UNITE-AD study. Methods: RE-UNITE-AD (NCT06988605) is a prospective, multicenter, non-interventional study (NIS) in adults and adolescents with moderate-to-severe AD who are newly initiated on nemolizumab per physician’s discretion in accordance with the local label. This AD study aims to enroll 1000 participants across 200 sites in Europe and North America. AD patients with peak pruritus numerical rating scale (PP-NRS) score ≥7 without prior biologic/Janus kinase inhibitors (JAKi) (or use more than 3 months before baseline) or PP-NRS ≥4 for those with recent discontinuation of biologic/JAK inhibitors (less than 3 months before baseline) are eligible for this study. Patients with any PP-NRS score may be enrolled if the reason for discontinuation of prior biologic/JAKi is safety-related. Patients who have contraindication(s) for the use of nemolizumab per the local label and/or treatment with a drug under clinical development/investigation within 3 months prior to baseline are excluded. Primary endpoints evaluated Investigator’s Global Assessment (IGA) and PP-NRS scores in clinical practice at month 6. Secondary endpoints evaluated Eczema Area and Severity Index, Scoring Atopic Dermatitis, IGA, PP-NRS, Average Pruritus-NRS, Sleep Disturbance-NRS, and Pain-NRS scores through month 12. Additional assessments include itch-scratch behaviour, quality of life, and patient-perceived benefit. Safety endpoints include serious adverse events regardless of causality and non-serious adverse drug reactions. Conclusion: This NIS reflects real-world clinical practice and is expected to complement the existing evidence from pivotal trials on the clinical effectiveness and safety of nemolizumab in patients with moderate-to-severe AD.

Staphylococcus epidermidis is a ubiquitous skin commensal with a complex and dual role in atopic dermatitis (AD). While it contributes to skin barrier function and pathogen defense, it also acts as an opportunistic pathogen in the dysbiotic AD skin environment. This review explores the complex interplay between its beneficial and pathogenic behaviors specifically in the context of AD through a comprehensive literature analysis. S. epidermidis exhibits strain-specific pathogenicity, directly contributing to AD pathology via the EcpA protease and lesional biofilms. Conversely, it engages in microbial antagonism, inhibiting Staphylococcus aureus through quorum sensing disruption and bacteriocin production, offering protective benefits in AD. Its role as a reservoir for antibiotic resistance genes, however, complicates treatment. This duality underscores the need for strain-specific approaches for managing AD to harness its benefits while mitigating its risks.

Introduction Tralokinumab is a high-affinity interleukin (IL)-13 inhibitor while dupilumab targets the IL-4/IL-13 pathway via inhibition of the IL-4 receptor α. Both are approved for the treatment of moderate-to-severe atopic dermatitis (AD), including on the hands where AD often presents an additional burden and treatment challenges. As no head-to-head studies have been conducted, the 16-week efficacy of tralokinumab and dupilumab were compared in patients with AD with hand involvement in a matching-adjusted indirect comparison (MAIC) based on two phase 3 trials, ADHAND and LIBERTY-AD-HAFT. Methods In the ADHAND trial (NCT05958407), adults with moderate-to-severe AD with hand involvement were randomized 2:1 to double-blind treatment with tralokinumab 300 mg or placebo every 2 weeks for 16 weeks. In LIBERTY-AD-HAFT (NCT04417894), adults and adolescents (≥12 years) with moderate-to-severe AD with hand and/or foot involvement were randomized 1:1 to dupilumab 300 mg (200 mg in adolescents with body weight <60 kg) or placebo every 2 weeks for 16 weeks. An anchored MAIC was conducted using individual patient data (IPD) from ADHAND and aggregate published data from LIBERTY-AD-HAFT, with placebo as the common anchor. IPD from ADHAND were weighted to match age, sex, race, and baseline Hand Eczema Severity Index (HECSI) score in LIBERTY-AD-HAFT. Endpoints compared at week 16 were the proportions of patients with Investigator’s Global Assessment (IGA) scores of 0/1 (IGA-Atopic Hand Eczema in ADHAND and Hand and Foot-IGA in LIBERTY-AD-HAFT), HECSI-75 and HECSI-90, percentage reduction in HECSI and ability to perform regular daily activities other than work using the Percent Routine Activity Impairment domain of the Work Productivity and Activity Index. Reductions in itch and pain (assessed with 11-point numerical rating scales) were also compared, as were proportions of patients with ≥4-point improvement in itch. There were minor differences between trials in the scales used for IGA, itch and pain. Results LIBERTY-AD-HAFT included 133 patients (dupilumab, n=67, placebo, n=66) while ADHAND included 235 patients (tralokinumab, n=156; placebo, n=79). The effective sample size after matching was 99 (tralokinumab, n=76, placebo, n=23). Anchor-adjusted relative treatment differences significantly favored tralokinumab compared with dupilumab for the proportions of patients achieving HECSI-90 (17.5 [95% CI: 0.8, 34.2]; p=0.040) and decrease in Percent Routine Activity Impairment (16.0 [95% CI: 4.8, 27.1]; p=0.005). Relative differences for other endpoints favored tralokinumab over dupilumab but were not significantly different between treatments: proportions of patients achieving IGA score 0/1 (8.4 [95% CI: −11.3, 28.1]; p=0.403) or HECSI-75 (10.7 [95% CI: −13.3, 34.7]; p=0.383), percent reduction in HECSI (20.1 [95% CI: 41.3, −1.2]; p=0.064), percent change in itch (9.8 [95% CI: −7.7, 27.4]; p=0.273), change in pain (0.8 [95% CI: −0.4, 1.9]; p=0.213) and proportions of patients with ≥4-point improvement in itch (2.4 [95% CI: −18.9, 23.6]; p=0.827). Conclusion In this MAIC, tralokinumab resulted in significantly more patients achieving HECSI-90, indicating a deeper response, and a significantly greater improvement in ability to perform regular daily activities versus dupilumab at 16 weeks. Other endpoints were numerically in favor of tralokinumab.

Itch, skin pain, and eczematous lesions are features of atopic dermatitis (AD). Skin pain is increasingly recognized as both a common and burdensome symptom of AD, reported by 61% of patients, that can impair daily activities, sleep, and mental health.Upadacitinib (UPA) is an oral selective Janus kinase 1 inhibitor approved for the treatment of AD and multiple other conditions. In this study, we assessed the efficacy of UPA in reducing skin pain in adults and adolescents with moderate-to-severe AD. This analysis evaluated integrated data from patients with moderate-to-severe AD treated with UPA monotherapy in two studies: Measure Up 1 and Measure Up 2. Patients were randomized to receive UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo for 16 weeks in the double-blind, placebo-controlled period. At week 16, patients randomized to UPA groups continued treatment, and placebo groups were re-randomized to UPA15 or UPA30 for the double-blind, long-term extension period. Skin pain (SP) was assessed using a validated patient-reported outcome (PRO) measure, the Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain numerical rating scale (NRS); the optimal outcome was defined as an SP-NRS score of 0 or 1 (SP-NRS 0/1), indicating no/minimal skin pain. Among patients who achieved SP-NRS 0/1 at week 16, long-term maintenance of response was evaluated through week 140. Patient-reported impacts of achieving SP-NRS 0/1 on sleep, daily activities, and quality of life (QOL) outcomes were assessed. Response rates were based on non-responder imputation (NRI) through week 16 and observed cases (OC) through week 140. At baseline, 85% of patients reported skin pain. Compared with placebo (n=531), patients treated with UPA15 (n=524) and UPA30 (n=543) achieved higher rates of SP-NRS 0/1 as early as day 2 (the day after treatment initiation), with response rates increasing through day 28 (UPA15: 43.7%, UPA30: 57.6%; both p<0.001). Both UPA15 and UPA30 groups had greater achievement of SP-NRS 0/1 compared with placebo at week 16 (UPA15: 41.9%; UPA30: 58.0%; placebo: 10.8%; NRI, both p<0.001). Response rates were sustained through week 140 in the overall population (UPA15: 63.8%; UPA30: 72.3%; OC) and among patients who achieved SP-NRS 0/1 at week 16 (UPA15: 78.9%; UPA30: 83.0%). Achieving SP-NRS 0/1 was associated with meaningful improvements across PROs, including sleep quality, daily functioning, and overall QOL. In summary, UPA-treated patients experienced rapid (by day 2) and durable reductions in skin pain, with most patients maintaining the optimal target (SP-NRS 0/1) through week 140. Reduction of skin pain was associated with improvements in PROs across multiple dimensions of patients’ lives, reinforcing skin pain as a meaningful and actionable therapeutic target in AD.

Introduction Atopic dermatitis (AD) is a chronic type 2 inflammatory disease, which often needs long-term treatment. The fully human monoclonal antibody dupilumab and the humanized monoclonal antibody nemolizumab have both demonstrated efficacy and safety in AD clinical trials. However, no head-to-head comparisons have been performed. In the absence of direct comparisons between medicinal products, Bucher indirect treatment comparisons (ITCs), in which treatment effects of the medicinal products are anchored to a common comparator (e.g. placebo), provide a robust and widely accepted method of evaluating relative efficacy. Objective To report the results of a placebo-anchored Bucher ITC comparing efficacy of dupilumab plus topical corticosteroids (TCS) every 2 weeks (q2w) versus nemolizumab plus TCS every 4 weeks (q4w) for moderate-to-severe AD over 16 weeks of therapy. Methods A placebo-anchored Bucher ITC was conducted using data from the published phase 3 clinical trial LIBERTY AD CHRONOS (NCT02260986) and the replicate phase 3 clinical trials ARCADIA 1 (NCT03985943) and ARCADIA 2 (NCT03989349). Data at Week 16 for the following doses were used: 300 mg dupilumab + TCS q2w, or placebo + TCS (LIBERTY AD CHRONOS), and 30 mg nemolizumab + TCS q4w, or placebo + TCS (ARCADIA 1 and 2). Non-responder imputation was used in all clinical trials for the binary outcomes, which were assessed in this ITC. Outcomes at Week 16 included proportion of patients achieving Investigator’s Global Assessment score 0/1 (IGA-0/1; clear/almost clear skin), ≥75% improvement from baseline in Eczema Area and Severity Index (EASI-75) and ≥4-point improvement from baseline in Peak Pruritus Numeric Rating Scale (PP-NRS ∆ ≥4). Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Meta-analysis ORs are provided for ARCADIA 1 and 2 combined. The number needed to treat (NNT) for achieving those outcomes were also computed to compare treatment benefits. Results Baseline disease characteristics were similar between LIBERTY AD CHRONOS and ARCADIA 1 and 2, supporting the use of Bucher ITC. Patients treated with dupilumab + TCS vs nemolizumab + TCS had a significantly higher likelihood of achieving IGA-0/1 (OR = 2.61; 95%CI 1.49, 4.57), EASI-75 (OR = 4.09, 95%CI 2.41, 6.96), and PP-NRS ∆ ≥4 (OR = 1.76, 95%CI 1.02, 3.02) at Week 16. When comparing these two treatments, dupilumab + TCS demonstrated greater treatment efficacy than nemolizumab + TCS across all 3 outcomes. The NNT to observe 1 patient achieving IGA 0/1, EASI-75, and PP-NRS ∆ ≥4 was 4, 3, and 3 respectively for dupilumab + TCS vs placebo + TCS, compared with 9, 8, and 5 respectively for nemolizumab + TCS vs placebo + TCS. Conclusions This placebo-anchored Bucher ITC analysis demonstrated that the likelihood of achieving improvements in AD signs and itch is significantly higher for patients treated with dupilumab + TCS q2w vs nemolizumab + TCS q4w at Week 16. Based on the NNT analysis, dupilumab + TCS demonstrated greater treatment efficacy across all assessed outcomes compared with nemolizumab + TCS, requiring substantially fewer patients to be treated to achieve the same clinical benefits.