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Frontiers in Pharmacology 2024Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases. Roflumilast, apremilast, and crisaborole have been developed... (Review)
Review
Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases. Roflumilast, apremilast, and crisaborole have been developed and approved for the treatment of chronic obstructive pulmonary disease psoriatic arthritis, and atopic dermatitis. Inflammation underlies many vascular diseases, yet the role of PDE4 inhibitors in these diseases remains inadequately explored. This review elucidates the clinical applications and anti-inflammatory mechanisms of PDE4 inhibitors, as well as their potential protective effects on vascular diseases. Additionally, strategies to mitigate the adverse reactions of PDE4 inhibitors are discussed. This article emphasizes the need for further exploration of the therapeutic potential and clinical applications of PDE4 inhibitors in vascular diseases.
PubMed: 38915460
DOI: 10.3389/fphar.2024.1407871 -
The Journal of Clinical and Aesthetic... Jun 2024Atopic dermatitis (AD) is an inflammatory skin condition affecting both mental and physical health. Although research has shown reduced physical activity levels among...
Association Between Atopic Dermatitis and Impaired Mobility among Adults in the United States: Findings from the 2001-2006 National Health and Nutrition Examination Survey.
OBJECTIVE
Atopic dermatitis (AD) is an inflammatory skin condition affecting both mental and physical health. Although research has shown reduced physical activity levels among patients with AD, there is a scarcity of studies examining baseline mobility, which refers to the standard level of functional ambulation or movement capability. We analyzed the relationship between AD and baseline mobility among U.S. adults ages 20 to 59, utilizing the National Health and Nutrition Examination Survey (NHANES).
METHODS
We merged three, 2-year cycles of NHANEs data (2001-2006). Patients were categorized as having "impaired mobility" by the following question: "Because of a health problem, do you have difficulty walking without using any special equipment?" Multivariable logistic regression analyses were performed using STATA/SE 18.0.
RESULTS
Our analysis included 6,540 participants. The prevalence of impaired mobility was 7.1 percent among patients with AD and 3.9 percent among those without AD. This difference was statistically significant among patients aged 20 to 59 after adjusting for potential confounding variables (adjusted odds ratio [AOR], 1.65; 95% CI, 1.19-3.25; =0.010). Subgroup analysis showed increased rates of impaired mobility among males with AD (AOR, 2.55; 95% CI, 1.21-5.40; =0.016), and among adults aged 40 to 59 (AOR, 1.94; 95% CI, 1.03-3.68; =0.042).
LIMITATIONS
Limitations to our study include lack of specificity in the survey questionnaire, self-reporting bias, and an age limit of 59 years old.
CONCLUSION
Our study demonstrated a statistically significant elevation in impaired mobility among individuals with AD compared to those without AD. This underscores the importance of comprehensive care for AD patients.
PubMed: 38912191
DOI: No ID Found -
Allergy, Asthma & Immunology Research May 2024Severe atopic dermatitis (AD) is not a localized cutaneous disease, but a systemic disease that often accompanies comorbidities. In this nationwide population-based...
Severe atopic dermatitis (AD) is not a localized cutaneous disease, but a systemic disease that often accompanies comorbidities. In this nationwide population-based study, we aimed to analyze the prevalence of severe AD and chronic systemic diseases in Koreans aged ≤ 20 years between 2011 and 2019 using the data from the Korean Health Insurance Review and Assessment Service. Total AD and severe AD were defined according to the International Classification of Diseases-10 code L20. In children aged 6-20 years, the prevalence of severe AD significantly increased from 0.02% in 2011 to 0.04% in 2019 ( for trend < 0.001), with the ratio of severe AD to total AD increasing from 0.76% in 2011 to 1.10% in 2019 ( for trend < 0.001). The prevalence rates of severe AD significantly increased between 2011 and 2019 in children aged 6-12 years ( for trend < 0.05) and 13-18 years ( for trend < 0.001). Severe AD was more frequently found in males than in females each year (all < 0.001, from 2011 to 2019). During the period from 2011 to 2019, the prevalence rate of chronic systemic diseases was higher in subjects with severe AD than in those without AD ( < 0.001) or with mild-to-moderate AD ( < 0.001). In conclusion, our results suggest that the prevalence of severe AD is increasing in Korean children and adolescents and is higher in males and older age groups. Moreover, severe AD is associated with chronic systemic diseases. Therefore, more attention should be paid to managing severe AD.
PubMed: 38910287
DOI: 10.4168/aair.2024.16.3.300 -
Lipids in Health and Disease Jun 2024Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals....
BACKGROUND
Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway.
METHODS
We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran's Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings.
RESULTS
The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%.
CONCLUSION
Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.
Topics: Dermatitis, Atopic; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Lipids; Triglycerides; Phosphatidylethanolamines; Phosphatidylcholines; Polymorphism, Single Nucleotide
PubMed: 38909247
DOI: 10.1186/s12944-024-02134-9 -
Mucosal Immunology Jun 2024The increased risk of food allergy in infants with atopic dermatitis has long been recognized; an epidemiologic phenomenon termed "the atopic march." Current literature... (Review)
Review
The increased risk of food allergy in infants with atopic dermatitis has long been recognized; an epidemiologic phenomenon termed "the atopic march." Current literature supports the hypothesis that food antigen exposure through the disrupted skin barrier in atopic dermatitis leads to food antigen specific IgE production and food sensitization. However, there is growing evidence that inflammation in the skin drives intestinal remodeling via circulating inflammatory signals, microbiome alterations, metabolites, and the nervous system. We explore how this skin-gut axis helps to explain the link between atopic dermatitis and food allergy beyond sensitization.
PubMed: 38906220
DOI: 10.1016/j.mucimm.2024.06.005 -
International Journal of Biological... 2024Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a...
Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice ( ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF-κB P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF-κB P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF-κB and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.
Topics: Animals; Dermatitis, Atopic; Langerhans Cells; Mice; Cell Movement; Mice, Knockout; Interleukin-1; Keratinocytes; Dinitrofluorobenzene; NF-kappa B; Interleukins
PubMed: 38904012
DOI: 10.7150/ijbs.93843 -
Frontiers in Immunology 2024An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the...
An 8-year-old female child presented with patchy hair loss for 1 year, accompanied by eyebrow loss for 6 months. Microscopic examination of the hair confirmed the features of active stage alopecia areata, with a Severity of Alopecia Tool (SALT) score of 70%. The diagnosis was severe alopecia areata. The patient had a history of atopic dermatitis since infancy, with recurrent episodes of scattered papules and pruritus for 8 years. Initial treatment involved subcutaneous injections of dupilumab 300mg every 2 weeks for 6 months, resulting in a reduction of SALT score to 20% and improvement of atopic dermatitis symptoms. Discontinuation of Dupilumab and initiation of daily oral Baricitinib at a dose of 2mg for a duration of 5 months. According to the SALT score evaluation, the severity of hair loss was less than 10% and there was significant regrowth of hair. No significant adverse reactions were observed during the treatment period.
Topics: Humans; Alopecia Areata; Dermatitis, Atopic; Female; Purines; Child; Azetidines; Pyrazoles; Sulfonamides; Antibodies, Monoclonal, Humanized; Treatment Outcome; Severity of Illness Index; Drug Therapy, Combination
PubMed: 38903518
DOI: 10.3389/fimmu.2024.1395288 -
Frontiers in Immunology 2024Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. () colonization on the skin plays an...
BACKGROUND
Atopic dermatitis (AD) is a common chronic inflammatory skin diseases that seriously affects life quality of the patients. () colonization on the skin plays an important role in the pathogenesis of AD; however, the mechanism of how it modulates skin immunity to exacerbate AD remains unclear. MicroRNAs are short non-coding RNAs that act as post-transcriptional regulators of genes. They are involved in the pathogenesis of various inflammatory skin diseases.
METHODS
In this study, we established miRNA expression profiles for keratinocytes stimulated with heat-killed (HKSA). The expression of miR-939 in atopic dermatitis patients was analyzed by fluorescence in situ hybridization (FISH). miR-939 mimic was transfected to human primary keratinocyte to investigate its impact on the expression of matrix metalloproteinase genes (MMPs) . Subsequently, miR-939, along with Polyplus transfection reagent, was administered to MC903-induced atopic dermatitis skin to assess its function .
RESULTS
MiR-939 was highly upregulated in HKSA-stimulated keratinocytes and AD lesions. studies revealed that miR-939 increased the expression of matrix metalloproteinase genes, including MMP1, MMP3, and MMP9, as well as the cell adhesion molecule ICAM1 in human primary keratinocytes. studies indicated that miR-939 increased the expression of matrix metalloproteinases to promote the colonization of and exacerbated -induced AD-like skin inflammation.
CONCLUSIONS
Our work reveals miR-939 is an important regulator of skin inflammation in AD that could be used as a potential therapeutic target for AD.
Topics: Dermatitis, Atopic; Humans; MicroRNAs; Staphylococcus aureus; Keratinocytes; Animals; Mice; Matrix Metalloproteinases; Staphylococcal Infections; Female; Male; Disease Models, Animal; Skin; Cells, Cultured
PubMed: 38903509
DOI: 10.3389/fimmu.2024.1354154 -
International Immunopharmacology Jun 2024Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we...
Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we started the present study, first possible effects of SCD on AD were predicted using network pharmacology. Next, dinitrochlorobenzene was used to establish a mouse model of AD. After successful modelling, the SCD were administered intragastrically to treat the mice. Eventually, the KEGG pathway enrichment analysis indicated that SCD improved AD mainly through effects on inflammation and the gut microbiota. The experimental findings revealed that SCD treatment attenuated AD symptoms and downregulate the characteristic immune factors, namely IL-4, IL-6 and IgE. Moreover, it promoted a balance between Th1/Th2 cells. Furthermore, the itch signaling pathways involving H1R/PAR-2/TRPV1 were inhibited. The 16S rRNA sequencing results indicated that SCD administration influenced the Firmicutes/Bacteroidetes ratio at the phylum level by augmenting the relative proportions of Lactobacillaceae and Muribaculaceae at the family and genus levels, while decreasing the abundances of Lactococcus and Ruminococcus. These findings suggest that internal administration of SCD is an effective therapeutic approach for AD. We suggest that SCD may be an alternative therapy for the treatment of AD.Additionally, it could offer valuable insights into the pathogenesis of AD and the development of innovative therapeutic agents.
PubMed: 38901246
DOI: 10.1016/j.intimp.2024.112479 -
Cureus May 2024A 12-year-old boy with underlying severeand poorly controlled atopic dermatitis (AD) associated with atopic conjunctivitis and rhinitis presented with a right...
A 12-year-old boy with underlying severeand poorly controlled atopic dermatitis (AD) associated with atopic conjunctivitis and rhinitis presented with a right painless blurring of vision for two weeks. On examination, his right eye visual acuity was 1/60,with grade 1 relative afferent pupillary defect (RAPD). Anterior segment examination revealed anterior uveitis with dense posterior subcapsular cataract and hazy fundus view. B-scan ultrasound suggested a shallow total retinal detachment. Intraoperatively, a large retinal dialysis was found. This paper highlights the need for a high index of suspicion of retinal dialysis in a child with underlying AD and the importance of good control of this systemic condition to prevent ocular morbidity.
PubMed: 38899264
DOI: 10.7759/cureus.60660