Antibiotic exposure during pregnancy increases risk for childhood atopic diseases: a nationwide cohort study.

PURPOSE: The prevalence of atopic diseases has increased in recent decades. A possible link between antibiotic use during pregnancy and childhood atopic disease has been proposed. The aim of this study is to explore the association of antibiotic exposure during pregnancy with childhood atopic diseases from a nationwide, population-based perspective. METHODS: This was a nationwide population-based cohort study. Taiwan's National Health Insurance Research Database was the main source of data. The pairing of mothers and children was achieved by linking the NHIRD with the Taiwan Maternal and Child Health Database. This study enrolled the first-time pregnancies from 2004 to 2010. Infants of multiple delivery, preterm delivery, and death before 5 years old were excluded. All participants were followed up at least for 5 years. Antenatal antibiotics prescribed to mothers during the pregnancy period were reviewed. Children with more than two outpatient visits, or one admission, with a main diagnosis of asthma, allergic rhinitis, or atopic dermatitis were regarded as having an atopic disease. RESULTS: A total of 900,584 children were enrolled in this study. The adjusted hazard ratios of antibiotic exposure during pregnancy to childhood atopic diseases were 1.12 for atopic dermatitis, 1.06 for asthma, and 1.08 for allergic rhinitis, all of which reached statistical significance. The trimester effect was not significant. There was a trend showing the higher the number of times a child was prenatally exposed to antibiotics, the higher the hazard ratio was for childhood atopic diseases. CONCLUSIONS: Prenatal antibiotic exposure might increase the risk of childhood atopic diseases in a dose-dependent manner.

N-benzyl-N-methyldecan-1-amine, derived from garlic, and its derivative alleviate 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

Given the intricate etiology and pathogenesis of atopic dermatitis (AD), the complete cure of AD remains challenging. This study aimed to investigate if topically applying N-benzyl-N-methyldecan-1-amine (BMDA), derived from garlic, and its derivative [decyl-(4-methoxy-benzyl)-methyl-1-amine] (DMMA) could effectively alleviate AD-like skin lesions in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Administering these compounds to the irritated skin of DNCB-treated mice significantly reduced swelling, rash, and excoriation severity, alongside a corresponding decrease in inflamed epidermis and dermis. Moreover, they inhibited spleen and lymph node enlargement and showed fewer infiltrated mast cells in the epidermis and dermis through toluidine-blue staining. Additionally, they led to a lower IgE titer in mouse sera as determined by ELISA, compared to vehicle treatment. Analyzing skin tissue from the mice revealed decreased transcript levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6), IL-4, iNOS, and COX-2, compared to control mice. Simultaneously, the compounds impeded the activation of inflammation-related signaling molecules such as JNK, p38 MAPK, and NF-κB in the mouse skin. In summary, these findings suggest that BMDA and DMMA hold the potential to be developed as a novel treatment for healing inflammatory AD.

Identification of Dihydrobenzofuran Neolignans as Novel PDE4 Inhibitors and Evaluation of Antiatopic Dermatitis Efficacy in DNCB-Induced Mice Model.

Atopic dermatitis is a chronic relapsing skin disease characterized by recurrent, pruritic, localized eczema, while PDE4 inhibitors have been reported to be effective as antiatopic dermatitis agents. 3',4-O-dimethylcedrusin (DCN) is a natural dihydrobenzofuran neolignan isolated from Magnolia biondii with moderate potency against PDE4 (IC50 = 3.26 ± 0.28 µM) and a binding mode similar to that of apremilast, an approved PDE4 inhibitor for the treatment of psoriasis. The structure-based optimization of DCN led to the identification of 7b-1 that showed high inhibitory potency on PDE4 (IC50 = 0.17 ± 0.02 µM), good anti-TNF-α activity (EC50 = 0.19 ± 0.10 µM), remarkable selectivity profile, and good skin permeability. The topical treatment of 7b-1 resulted in the significant benefits of pharmacological intervention in a DNCB-induced atopic dermatitis-like mice model, demonstrating its potential for the development of novel antiatopic dermatitis agents.

Ursodeoxycholic acid alleviates atopic dermatitis-associated inflammatory responses in HaCaT and RBL-2H3 cells and DNCB/DFE-treated mice.

AIMS: Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects. However, its potential effects on atopic dermatitis (AD) have not been elucidated. This study aimed to evaluate the efficacy of UDCA in inhibiting the inflammatory response and alleviating lesions in AD-like mice. MAIN METHODS: To investigate the efficacy of UDCA in AD-like inflammatory responses, tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-stimulated HaCaT cells and anti-dinitrophenyl immunoglobulin E (DNP-IgE)- and human serum albumin (HSA)-stimulated RBL-2H3 cells were used to investigate the levels of inflammatory factors and their mechanisms. AD-like lesions were induced by applying DNCB/DFE to mice. The effect of UDCA administration in AD-like mice was analyzed by assessing organ weight, serum IgE and inflammatory cytokine levels, and histopathological changes using immunohistochemical and immunofluorescent staining. KEY FINDINGS: In HaCaT cells, UDCA significantly diminished TARC, MDC, MCP-1, and IL-6 expression by inhibiting the phosphorylation of nuclear NF-κB and cytoplasmic IκB, and also increased the levels of skin barrier protein. In RBL-2H3 cells, UDCA reduced ß-hexosaminidase and IL-4 levels. In AD-like mice, UDCA suppressed organ hypertrophy, ear edema, SCORAD index, DFE-specific IgE levels, inflammatory cytokine levels, skin hypertrophy, mast cell invasion, skin barrier loss, and thymic stromal lymphopoietin-positive areas. SIGNIFICANCE: UDCA suppressed the expression of pro-inflammatory cytokines by keratinocytes and mast cells. It also alleviated atopy by suppressing symptoms without organ toxicity in AD-like mice. UDCA may be an effective and safe treatment for AD.

Supercritical CO2 fluid extract from Stellariae Radix ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by inhibit M1 macrophages polarization via AMPK activation.

Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO2 extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1ß in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1ß and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPKT172, but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder.

Calycosin enhances Treg differentiation for alleviating skin inflammation in atopic dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous, exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive. AIM OF THE STUDY: This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD. MATERIALS AND METHODS: The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-ß1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA. RESULTS: CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro, CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression. CONCLUSIONS: The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD.

Effect of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) in a mouse model of atopic dermatitis.

The effects of exposure to clothianidin (CLO), a neonicotinoid pesticide (NN), on the thymus and intestinal microbiota were recently revealed. Immune cells express nicotinic acetylcholine receptors (nAChRs), an NN target, suggesting CLO may disrupt the immune system. However, the relationship between CLO and atopic dermatitis (AD) is unknown. We administered a no-adverse-effect-level (NOAEL) dose of CLO to male NC/Nga mice with induced AD and measured, at three time points, key AD symptom indicators: epidermal thickening, mast cell number, total plasma IgE, and histamine levels. CLO increased total plasma IgE levels but reduced epidermal thickening, mast cell number, and plasma histamine levels in the early stages of AD. This demonstrates for the first time that CLO exposure inhibits AD's early symptoms.

Safety, Tolerability, Pharmacokinetics, and pharmacodynamics of YH35324, a novel Long-Acting High-Affinity IgETrap-Fc protein in subjects with Atopy: Results from the First-in-Human study.

BACKGROUND: YH35324, a long-acting IgETrap-Fc fusion protein, is a novel therapeutic agent for immunoglobulin E (IgE)-mediated allergic diseases. This randomized, double-blind, placebo/active-controlled, single ascending dose Phase 1 study assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of YH35324 in subjects with atopy. METHODS: Eligible subjects were healthy subjects or atopic adults with mild allergic rhinitis, atopic dermatitis, food allergy, or urticaria, and a serum total IgE level of 30-700 IU/mL (Part A) or > 700 IU/mL (Part B). In Part A, 35 subjects in 5 cohorts received YH35324 (0.3, 1, 3, 6, and 9 mg/kg), 8 received omalizumab (300 mg), and 9 received placebo. In Part B, 8 subjects received YH35324 and 8 received omalizumab. RESULTS: Twenty subjects (38.5 %) in Part A (YH35324: 37.1 %, omalizumab: 50.0 %, placebo: 33.3 %) and 10 subjects (62.5 %) in Part B (YH35324: 100 %; omalizumab: 25.0 %) experienced treatment-emergent adverse events (TEAEs). TEAEs were mostly grade 1/2; no serious AEs, AE-related treatment discontinuation, or anaphylaxis were reported. YH35324 exhibited dose-proportional increase in Cmax and AUClast over the dose range of 0.3-9 mg/kg. YH35324 rapidly suppressed serum-free IgE levels to a significant extent (< 25 and < 82.8 ng/mL, both P < 0.05) and with longer duration than omalizumab. CONCLUSION: This study showed that YH35324 has a favorable safety profile and is effective in reducing serum-free IgE levels in subjects with atopic conditions.

Atopic Dermatitis as a Paradoxical Reaction to Secukinumab in a Patient With Plaque Psoriasis.

Paradoxical reactions to biologic agents used in the treatment of psoriasis are rare but have been reported with tumor necrosis factor (TNF) blockers and, more recently, with interleukin (IL)-17A inhibitors. Secukinumab, an IL-17A inhibitor, is an effective treatment for moderate-to-severe plaque psoriasis but has been implicated in the development or exacerbation of eczematous-like reactions in rare cases. We present a patient with a history of plaque psoriasis who developed an eczematous eruption after four months of secukinumab therapy, necessitating systemic intervention for adequate control. Five months after a loading dose of dupilumab, the patient appeared in the clinic with the return of classic, thick psoriatic plaques, affecting 15% BSA. The patient declined further treatment and was subsequently lost to follow-up despite multiple attempts to contact her. This case adds to the limited, but growing body of knowledge on IL-17 blocker-induced eczematous reactions and underscores the need for careful monitoring and prompt recognition of this adverse event in patients receiving this class of drugs. J Drugs Dermatol. 2024;23(2):97-99.     doi:10.36849/JDD.7639  .

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

Immunomodulatory and anti-angiogenesis effects of excavatolide B and its derivatives in alleviating atopic dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin condition primarily driven by T helper 2 (Th2) cytokines, resulting in skin barrier defects, angiogenesis, and inflammatory responses. The marine natural product excavatolide B (EXCB), isolated from the Formosan Gorgonian coral Briareum stechei, exhibits anti-inflammatory and analgesic properties. To enhance solubility, EXCB is chemically modified into the derivatives EXCB-61 salt and EXCB-79. The study aims to investigate the therapeutic effects of these compounds on dinitrochlorbenzene (DNCB)-induced skin damage and to elucidate the underlying anti-inflammatory and anti-angiogenesis mechanism. In vitro, using lipopolysaccharide (LPS)-induced RAW 264.7 cells, all compounds at 10 µM significantly inhibited expression of inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2), vascular endothelial growth factor (VEGF), and cytokines (interleukin (IL)-1ß, IL-6, and IL-17A). In vivo, topical application of these compounds on DNCB-induced AD mice alleviated skin symptoms, reduced serum levels of IgE, IL-4, IL-13, IL-17, and interferon-γ, and moderated histological phenomena such as hyperplasia, inflammatory cell infiltration, and angiogenesis. The three compounds restored the expression of skin barrier-related proteins (loricrin, filaggrin, and claudin-1) and reduced the expression of angiogenesis-related proteins (VEGF and platelet endothelial cell adhesion molecule-CD31) in the tissues. This is the first study to indicate that EXCB, EXCB-61 salt, and EXCB-79 can treat AD disease by reducing inflammation and angiogenesis. Hence, they may be considered potential candidates for the development of new drugs for AD.

Erigeron annuus Extract Improves DNCB-Induced Atopic Dermatitis in a Mouse Model via the Nrf2/HO-1 Pathway.

Atopic dermatitis (AD) is a persistent inflammatory skin condition resulting from an intricate interplay among genetic, immunological, and environmental factors. Erigeron annuus (EA), an annual winter plant belonging to the family Asteraceae, possesses anti-inflammatory, cytoprotective, and antioxidant activities. In this study, we hypothesized that Erigeron annuus extract (EAE) could be an effective agent for ameliorating AD-like symptoms. To confirm this hypothesis in vitro, we used H2O2-stimulated human keratinocytes (HaCaT cells) to demonstrate that pre-treatment with EAE protected against oxidative stress. HaCaT cells pretreated with EAE and stimulated with H2O2 showed decreased intracellular malondialdehyde content, increased superoxide dismutase activity, and reduced intracellular reactive oxygen species accumulation. To verify the in vivo hypothesis based on the intracellular results, an AD disease mouse model was induced with 1-chloro-2,4-dinitrobenzene (DNCB), and EAE was orally administered at a non-toxic concentration according to the toxicity evaluation results. The results showed that AD disease models in BALB/c mice exhibited reduced ear epidermal thickness, scratching behavior, and mast cell infiltration. In conclusion, our results indicate that EAE has the potential to improve AD by upregulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway.

Epigenetic Methylation Changes in Pregnant Women: Bisphenol Exposure and Atopic Dermatitis.

Bisphenol is a chemical substance widely used in plastic products and food containers. In this study, we observed a relationship between DNA methylation and atopic dermatitis (AD) in the peripheral blood mononuclear cells (PBMCs) of pregnant women exposed to bisphenol A (BPA) and its alternatives, bisphenol S (BPS) and bisphenol F (BPF). DNA methylation is an epigenetic mechanism that regulates gene expression, which can be altered by environmental factors, and affects the onset and progression of diseases. We found that genes belonging to the JAK-STAT and PI3K-AKT signaling pathways were hypomethylated in the blood of pregnant women exposed to bisphenols. These genes play important roles in skin barrier function and immune responses, and may influence AD. Therefore, we suggest that not only BPA, but also BPS and BPF, which are used as alternatives, can have a negative impact on AD through epigenetic mechanisms.

Anti-Inflammatory Effect of Fermented Cabbage Extract Containing Nitric Oxide Metabolites with Silica.

The aim of this study was to evaluate the anti-inflammatory effect of fermented cabbage extract (FC) containing nitric oxide metabolites with silica (FCS) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) in BALB/c mice. Atopic dermatitis-like allergic contact dermatitis was induced by DNFB challenge in the ear after DNFB sensitization on the dorsal skin of mice. FCS alleviated the severity of atopic dermatitis-like skin lesions. In addition, epidermis thickness of the ear and penetration of inflammatory cells in atopic dermatitis-like skin lesions were decreased after topical application of FCS. The serum levels of TNF-α and IL-4 were measured in atopic dermatitis mice using ELISA kits, which were observed to be significantly decreased after topical application of FCS. This study demonstrates that the FCS can be used as a potential therapeutic for the treatment and prevention of AD.

Association between environmental mercury exposure and allergic disorders in Korean children: Korean National Environmental Health Survey (KoNEHS) cycles 3-4 (2015-2020).

Although previous studies have suggested potential adverse effects of mercury on a child's immune system, the associations have been inconsistent. We aimed to determine the association between urinary mercury levels and allergic diseases in Korean children with high mercury exposure. Data from 853 and 710 children aged 6-11 years in the Korean National Environmental Health Survey (KoNEHS) cycle 3 (2015-2017) and cycle 4 (2018-2020) were analyzed. We examined the association between mercury exposure and the prevalence of atopic dermatitis (AD), asthma, allergic rhinitis (AR), and allergic multimorbidity. After adjusting for all covariates, the urinary mercury level was positively associated with AD in the 2015-2017 study (OR = 1.34, 95% CI = 1.01, 1.79) and AR in 2018-2020 study (OR = 1.46, 95% CI = 1.01, 2.10). Pooled effects showed OR of 1.34 (95% CI = 1.01, 1.79) for AD and 1.47 (95% CI = 1.01, 2.12) for allergic multimorbidity. The association with allergic multimorbidity was greater in boys (OR = 1.88, 95% CI = 1.01, 3.49) than in girls (OR = 1.25, 95% CI = 0.73, 2.14). These results suggest that environmental mercury exposure may exacerbate symptoms of atopic dermatitis and allergic multimorbidity in children.

Qing-Re-Chu-shi decoction ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis in NC/Nga mice through anti-inflammation and immunoregulatory mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood. AIM OF THE STUDY: Atopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model. MATERIALS AND METHODS: Network pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions. RESULTS: The construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment. CONCLUSIONS: The study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.

Exposure to biocides and its association with atopic dermatitis among children and adolescents: A population-based cross-sectional study in South Korea.

BACKGROUND: Biocides have emerged as a contributor to the rising cases of atopic dermatitis among children and adolescents. Previous animal studies suggested that phenols, parabens, and pyrethroid insecticides present in these products might play a role in atopic dermatitis. However, there's limited epidemiological evidence confirming the individual or combined effects of exposure to these chemicals on atopic dermatitis in young populations. This study aimed to investigate the association between phenol, paraben, and pyrethroid metabolite levels in urine and atopic dermatitis among Korean children and adolescents METHODS: We analyzed 556 preschool children (3-5 years), 701 schoolchildren (6-11 years), and 731 adolescents (12-17 years) enrolled in the 4th Korean National Environmental Health Survey (KoNEHS) (2018-2020). We used logistic regression and Bayesian kernel machine regression to evaluate the association between atopic dermatitis and individual or mixed exposure to urinary triclosan (TCS), parabens (methylparaben, ethylparaben, propylparaben, and butylparaben), and 3-phenoxybenzoic acid (3-PBA) levels. RESULTS: Urinary TCS levels were positively associated with atopic dermatitis in schoolchildren. When stratified by sex, male schoolchildren exhibited an increasing prevalence of atopic dermatitis as their urinary TCS and 3-PBA levels increased. The combined effect of biocide mixtures on atopic dermatitis was also significantly increased in male schoolchildren, with TCS as the main contributor. CONCLUSIONS: These study findings suggest that biocides at levels found in Korean children and adolescents affect atopic dermatitis.

Safety, efficacy, and pharmacokinetics of delgocitinib ointment in infants with atopic dermatitis: A phase 3, open-label, and long-term study.

BACKGROUND: Delgocitinib ointment, a topical Janus kinase inhibitor, is used as treatment of patients with atopic dermatitis (AD) aged ≥2 years in Japan. Although initiating appropriate and early treatment upon the onset of AD in childhood is important, the safety and efficacy of delgocitinib ointment in infants with AD have not been established. METHODS: This phase 3 study was conducted from October 2020 to June 2022 (number JapicCTI-205412). Eligible Japanese infants with AD aged 6 to <24 months received 0.25% or 0.5% of delgocitinib ointment twice daily for 52 weeks in an open-label uncontrolled manner. Topical corticosteroids were allowed to apply for worsening AD during the treatment period at the investigators' discretion. RESULTS: A total of 22 infants were enrolled. Adverse events (AEs) were reported in 21 (95.5%) infants and were mostly mild. No treatment-related AEs were reported. The Modified Eczema Area and Severity Index (mEASI) score continuously decreased until week 4, and the score reduction was maintained until week 52. The mean percent changes in the mEASI score from baseline were -73.5% at week 4, -81.7% at week 28, and -81.9% at week 52. Delgocitinib was not detected in the plasma of most infants (68.2%-95.2%). CONCLUSIONS: Delgocitinib ointment is well tolerated and effective for up to 52 weeks when applied to Japanese infants with AD.

A Review of Dupilumab-Induced Adverse Events to Dermatologists and the Potential Pathogenesis in the Treatment of Atopic Dermatitis.

Dupilumab, a monoclonal antibody targeting interleukin-4 antibody, is approved for use in many type 2 inflammatory diseases, including atopic dermatitis. It is generally well tolerated with no need of routine laboratory monitoring. However, several adverse events have been reported during real-world practice and in pivotal trials. We conducted a systematic literature research of the PubMed, Medline, and Embase databases to identify articles recording the clinical manifestation and potential pathogenesis of these adverse events with interests (AEIs) to dermatologists. In total, 547 cases from 134 studies have developed 39 AEIs 1 day to 2.5 years after dupilumab treatment. The most common AEIs are facial and neck dermatitis (299 cases), psoriasis (70 cases), arthralgia (56 cases), alopecia (21 cases), cutaneous T cell lymphoma (19 cases), severe ocular diseases (19 cases), and drug eruption (6 cases). Most of the AEIs recorded in this review resolved or improved after dupilumab discontinuation or the addition of another treatment, whereas 3 of the cases died of severe AEI. The potential pathogenesis included T help type 1 (Th1)/T help type 2 (Th2) imbalance, Th2/T help type 17 (Th17) imbalance, immune reconstitution, hypersensitivity reaction, transient hypereosinophilia related, and Th1 suppression. Clinicians should be alert of these AEIs for timely diagnosis and appropriate treatment.

Safety and efficacy of eblasakimab, an interleukin 13 receptor α1 monoclonal antibody, in adults with moderate-to-severe atopic dermatitis: A phase 1b, multiple-ascending dose study.

BACKGROUND: Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor. OBJECTIVE: The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD). METHODS: In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events. Secondary outcomes included percentage change in the Eczema Area and Severity Index from baseline; Eczema Area and Severity Index improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline. RESULTS: Treatment-emergent adverse events were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in Eczema Area and Severity Index versus placebo (-65% vs -27%, P = .014). Other key secondary physician- and patient-reported end points were met. LIMITATIONS: Longer studies are required to confirm eblasakimab safety and efficacy in AD patients. CONCLUSIONS: Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements versus placebo.