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Mycoses Mar 2022Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with an increasing prevalence worldwide. The aetiology and pathogenesis of AD have not been... (Review)
Review
Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with an increasing prevalence worldwide. The aetiology and pathogenesis of AD have not been fully elucidated. Previous studies have suggested the role of fungi as a triggering factor in the development AD. Here we conducted a systematic review to investigate the skin mycobiome profiles in AD and to address whether there is an association between fungal dysbiosis and AD. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between January 1st, 2010 and April 21st, 2021. A total of 11 human studies and 3 animal studies were included in this analysis. Fungal dysbiosis was observed in AD lesions with a depleted amount of Malassezia and a higher abundance of filamentous fungi. A positive correlation between Candida and Staphylococcus was also demonstrated in AD. We supposed that specific species of Malassezia spp. and Candida spp. may play a role in the pathogenesis of AD by interacting with the pathogenic bacteria. Topical application of emollients could improve the skin barrier function and restore the skin fungal flora by increasing the amount of Malassezia. Further studies focusing on the complex interplay between specific skin fungi and the host can provide better insight into the role of microorganisms in the pathogenesis of AD.
Topics: Animals; Dermatitis, Atopic; Dysbiosis; Eczema; Humans; Malassezia; Mycobiome; Skin
PubMed: 34817898
DOI: 10.1111/myc.13402 -
European Journal of Clinical... Dec 2022Janus kinase (JAK) inhibitors have been developed to treat moderate to severe atopic dermatitis, but there is little evidence comparing the safety profile of these... (Meta-Analysis)
Meta-Analysis
PURPOSE
Janus kinase (JAK) inhibitors have been developed to treat moderate to severe atopic dermatitis, but there is little evidence comparing the safety profile of these drugs. The aim of this study is to compare the relative safety of the different systemic JAK inhibitors in atopic dermatitis.
METHODS
Medline, EMBASE, and clinicaltrials.gov were searched to identify phase 2/3, clinical trials (RCTs) designed to evaluate the efficacy and safety of systemic JAK inhibitors in atopic dermatitis. Outcomes were the risk of any adverse event (AE), serious AEs, AEs leading to treatment discontinuation, any infection, serious infections, herpes zoster infection, and any cardiac or vascular event.
RESULTS
Eighteen RCTs were included. Compared with placebo, baricitinib (odds ratio [OR] 1.25, 95% credible interval [CrI] 1.03-1.55), abrocitinib (OR 1.54, 95% CrI 1.25-1.90), and upadacitinib (OR 1.46, 95% CrI 1.19-1.81) increase the risk of any adverse event. Abrocitinib (OR 1.62, 95% CrI 1.7-2.72), upadacitinib (OR 1.67, 95% CrI 1.19-2.43), and dupilumab (OR 1.69, 95% CrI 1.02-2.79) increase the risk of infections when compared with placebo. Dupilumab has a reduced risk of herpes zoster infection when compared with upadacitinib (OR 0.23; 95% CrI 0.08-0.81) No further statistically significant risk differences between treatments were identified.
CONCLUSIONS
The results suggest systemic JAK inhibitors for atopic dermatitis have a similar safety profile. However, as current data present limitations, postmarketing safety evidence will be crucial to draw definitive conclusions regarding the safety of JAK inhibitors.
Topics: Humans; Janus Kinase Inhibitors; Dermatitis, Atopic; Network Meta-Analysis; Herpes Zoster; Treatment Outcome; Severity of Illness Index
PubMed: 36207461
DOI: 10.1007/s00228-022-03400-4 -
European Child & Adolescent Psychiatry Sep 2023Autism spectrum disorder (ASD) is a disabling neurodevelopmental condition with complex etiology. Emerging evidence has pointed to maternal atopy as a possible risk... (Review)
Review
Autism spectrum disorder (ASD) is a disabling neurodevelopmental condition with complex etiology. Emerging evidence has pointed to maternal atopy as a possible risk factor. It is hypothesized that maternal atopic disease during pregnancy can lead to increased levels of inflammatory cytokines in fetal circulation via placental transfer or increased production. These cytokines can then pass through the immature blood-brain barrier, causing aberrant neurodevelopment via mechanisms including premature microglial activation. The objective of this study is to systematically review observational studies that investigate whether a maternal history of atopic disease (asthma, allergy, or eczema/atopic dermatitis) is associated with a diagnosis of ASD in offspring. A search was conducted in Ovid MEDLINE, PsycINFO, and Embase databases for relevant articles up to November 2021; this was later updated in January 2022. Observational studies published in peer-reviewed journals were included. Data were synthesized and qualitatively analyzed according to the specific atopic condition. Quality assessment was done using the Newcastle-Ottawa Scale. Nine articles were identified, with all including asthma as an exposure, alongside four each for allergy and eczema. Findings were inconsistent regarding the association between a maternal diagnosis of either asthma, allergy, or eczema, and ASD in offspring, with variations in methodology contributing to the inconclusiveness. More consistent associations were demonstrated regarding maternal asthma that was treated or diagnosed during pregnancy. Evidence suggests that symptomatic maternal asthma during pregnancy could be associated with ASD in offspring, underscoring the importance of effective management of atopic conditions during pregnancy. Further research is needed, particularly longitudinal studies that use gold-standard assessment tools and correlate clinical outcomes with laboratory and treatment data.PROSPERO Registration Number and Date: CRD42018116656, 26.11.2018.
PubMed: 37661216
DOI: 10.1007/s00787-023-02285-7 -
Frontiers in Immunology 2022Several clinical trials have evaluated the efficacy and safety of interleukin-13 (IL-13) with lebrikizumab and tralokinumab in patients with moderate to severe atopic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several clinical trials have evaluated the efficacy and safety of interleukin-13 (IL-13) with lebrikizumab and tralokinumab in patients with moderate to severe atopic dermatitis (AD). However, the safety and efficacy of IL-13 inhibitors as a potent biologic for AD remain elusive.
OBJECTIVE
To assess the efficacy and safety of IL-13 inhibitors in moderate to severe AD.
METHOD
Randomized clinical trials (RCTs), comparing IL-13 inhibitors vs placebo treatment in patients with moderate to severe AD, were identified from public database from its inception to November 9, 2021. The study was registered in PROSPERO (CRD42021254920).
RESULTS
Six studies reporting 7 RCTs involving 2946 patients with moderate-to-severe AD were included for the pooled analysis. Compared with placebo, antagonizing IL-13 with lebrikizumab and tralokinumab showed a greater improvement in percentage change of EASI (MD -20.37, 95%CI -32.28, -8.47), and a larger proportion of patients achieving numerical rating scale (NRS) with more than 4-points improvement (RR 1.59, 95%CI 1.23, 2.05). Additionally, IL-13 inhibitors also improved impaired dermatology life quality index (DLQI) (MD -14.49, 95%CI -19.23, -9.75). In terms of safety, both lebrikizumab and tralokinumab were well tolerated, with the except that they were linked to an increased risk of conjunctivitis compared to placebo treatment.
CONCLUSION
Antagonizing IL-13 with lebrikizumab and tralokinumab have demonstrated encouraging clinical efficacy against moderate-to-severe AD with excellent safety profile, albeit they did come with a higher risk of conjunctivitis than placebo treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier ID=CRD42021254920.
Topics: Conjunctivitis; Dermatitis, Atopic; Humans; Interleukin Inhibitors; Interleukin-13; Treatment Outcome
PubMed: 35967348
DOI: 10.3389/fimmu.2022.923362 -
Archives of Dermatological Research Apr 2024Patient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens.... (Meta-Analysis)
Meta-Analysis Review
Patient education in atopic dermatitis (AD) has worked in parallel to the gold standard of pharmacological treatment as a foundational component of therapeutic regimens. In addition to improving patient education, past investigations of educational interventions have demonstrated profound reductions in disease severity for patients living with AD. However, prior meta-analytical work has focused mostly on comparing in-person interventions, and thus the need to determine the effectiveness of virtual methodologies in the current post-COVID era remains. In this study, we conducted a systematic review of the literature to determine the effectiveness of online programming in AD education compared to in-person interventions. A comprehensive search was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions 2019. Studies were retrieved based on articles published up to 04 April 2023. Adherence to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement guided the reportage process for this systematic review and meta-analysis. The primary outcome of our meta-analysis was the effect of various educational modalities on atopic dermatitis severity as measured by multiple scales across the studies, the most common including SCORAD, Dermatology Life Quality Index (DLQI), Patient Oriented Eczema Measure (POEM), and Eczema Area and Severity Index (EASI). Most studies were randomized controlled trials, primarily from North America and Western Europe and focused on patient and/or caregiver education about disease management, self-care techniques, avoidance of triggers, and comprehensive understanding of the disease process. Our pooled analyses showed that targeted educational programs in understudied adult populations can be as impactful as those in pediatric groups. Moreover, virtual interventions can be employed as constructive tools for reducing barriers of access to patient education. Future research on educational interventions should utilize various methodologies to encourage individual learning preferences with a focus on adult cohorts.
Topics: Dermatitis, Atopic; Humans; Patient Education as Topic; Quality of Life; Severity of Illness Index; COVID-19
PubMed: 38662127
DOI: 10.1007/s00403-024-02871-y -
The Journal of Investigative Dermatology May 2024Cardiovascular guidelines recommend early screening and preventative treatment for children with chronic inflammatory diseases. Atopic dermatitis (AD) is associated with... (Meta-Analysis)
Meta-Analysis
Cardiovascular guidelines recommend early screening and preventative treatment for children with chronic inflammatory diseases. Atopic dermatitis (AD) is associated with cardiovascular risk in adults, but data in children are limited. We systematically searched for studies that examined the association between childhood AD and cardiovascular risk factors and outcomes. Data from 10 publications, including 577,148 individuals, revealed an association between AD and ischemic heart disease (n = 3, OR = 1.68, 95% confidence interval [CI] = 1.29-2.19) and diabetes (n = 4, OR = 1.31, 95% CI = 1.12-1.53), but this did not persist among studies that adjusted for potential confounders (n = 2, OR = 0.98, 95% CI = 0.35-2.75). Similarly, there was an association with lipid disorders but not across the entire population distribution (n = 7, OR = 1.24, 95% CI = 1.13-1.36, 95% prediction interval = 0.95-1.61). AD was not associated with hypertension (n = 5, OR = 1.15, 95% CI = 0.98-1.34, 95% prediction interval = 0.81-1.62) or stroke (n = 2, OR = 1.24, 95% CI = 0.94-1.62). Studies lacked detail on AD severity and important confounders such as body mass index, and the certainty of evidence was very low to low on the basis of GRADE (Grading of Recommendations, Assessment, Development and Evaluation) assessments. Currently, data do not support a clinically meaningful increase in cardiovascular risk for children with AD.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Cardiovascular Diseases; Dermatitis, Atopic; Heart Disease Risk Factors; Risk Factors
PubMed: 37972725
DOI: 10.1016/j.jid.2023.09.285 -
Dermatitis : Contact, Atopic,... 2024This systematic review and meta-analysis aimed to explore the association between atopic Dermatitis® (AD) and alopecia areata (AA). A comprehensive search was conducted... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to explore the association between atopic Dermatitis® (AD) and alopecia areata (AA). A comprehensive search was conducted in PubMed, Embase, Cochrane, and Web of Science from the inception of each database to November 10, 2022 for relevant studies. As there is a potential bilateral association between the 2 diseases, we assessed the prevalence/incidence of AA in patients with AD and the prevalence/incidence of AD in patients with AA. A total of 29 studies involving 11,233,448 participants were included in this analysis. AA was the exposure factor in 23 studies, AD in 7 studies, and both in 1 study. The meta-analysis revealed that the prevalence of AD was 11.2% (7.7%-15.1%) in patients with AA, and the prevalence of AA was 3.2% (95% confidence interval [CI]: 0.0%-11.5%) in patients with AD. The incidence of AD in AA patients was found to vary with age ( = 0.07). Based on 7 studies, there was a significant association between AD and AA when AA was the exposure factor [odds ratio, OR, = 4.537 (95% CI: 2.409-8.544)]; based on 10 studies, there was also a significant association between AD and AA when AD was the exposure factor [OR = 2.643 (95% CI: 1.737-3.995)]. In conclusion, this meta-analysis demonstrated the 2-way association between AD and AA, providing a clinical reference for disease prevention and control.
Topics: Alopecia Areata; Humans; Dermatitis, Atopic; Prevalence; Incidence
PubMed: 37471232
DOI: 10.1089/derm.2023.0114 -
Gene Jun 2024Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that is closely linked to genetic factors. Previous studies have revealed numerous single... (Meta-Analysis)
Meta-Analysis Review
AIM
Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that is closely linked to genetic factors. Previous studies have revealed numerous single nucleotide polymorphisms (SNPs) that been related to susceptibility to AD; however, the results are conflicting. Therefore, a meta-analysis was conducted to assess the associations of these polymorphisms and AD risk.
MATERIAL AND METHODS
PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were retrieved to identify eligible studies, with selected polymorphisms being reported in a minimum of three separate studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality. Review Manager 5.3 and STATA 14.0 were used to perform the meta-analysis.
RESULTS
After screening, 64 studies involving 13 genes (24 SNPs) were selected for inclusion in the meta-analysis. Nine SNPs were positively correlated with AD susceptibility [filaggrin (FLG) R501X, FLG 2282del4, chromosome 11q13.5 rs7927894, interleukin (IL)-17A rs2275913, IL-18 -137 G/C, Toll-like receptor 2 (TLR2) rs5743708, TLR2 A-16934 T, serine protease inhibitor Kazal type-5 (SPINK5) Asn368Ser, interferon-γ (IFN-γ) T874A] and one was negatively associated with AD susceptibility (IL-4 -1098 T/G). The 14 remaining SNPs were not significantly associated with AD susceptibility.
CONCLUSIONS
Nine SNPs that may be risk factors and one SNP that may be a protective factor for AD were identified, providing a reference for AD prediction, prevention, and therapy.
Topics: Humans; Dermatitis, Atopic; Genetic Predisposition to Disease; Toll-Like Receptor 2; Polymorphism, Single Nucleotide; Skin; Intermediate Filament Proteins
PubMed: 38513928
DOI: 10.1016/j.gene.2024.148397 -
Journal of Clinical Medicine Feb 2023Tight junctions are transmembrane proteins that regulate the permeability of water, solutes including ions, and water-soluble molecules. The objective of this systematic... (Review)
Review
BACKGROUND
Tight junctions are transmembrane proteins that regulate the permeability of water, solutes including ions, and water-soluble molecules. The objective of this systematic review is to focus on the current knowledge regarding the role of tight junctions in atopic dermatitis and the possible impact on their therapeutic potential.
METHODS
A literature search was performed in PubMed, Google Scholar, and Cochrane library between 2009 and 2022. After evaluation of the literature and taking into consideration their content, 55 articles were finally included.
RESULTS
TJs' role in atopic dermatitis extends from a microscopic scale to having macroscopic effects, such as increased susceptibility to pathogens and infections and worsening of atopic dermatitis features. Impaired TJ barrier function and skin permeability in AD lesions is correlated with cldn-1 levels. Th2 inflammation inhibits the expression of cldn-1 and cldn-23. Scratching has also been reported to decrease cldn-1 expression. Dysfunctional TJs' interaction with Langerhans cells could increase allergen penetration. Susceptibility to cutaneous infections in AD patients could also be affected by TJ cohesion.
CONCLUSIONS
Dysfunction of TJs and their components, especially claudins, have a significant role in the pathogenesis and vicious circle of inflammation in AD. Discovering more basic science data regarding TJ functionality may be the key for the use of specific/targeted therapies in order to improve epidermal barrier function in AD.
PubMed: 36836073
DOI: 10.3390/jcm12041538 -
Dermatology and Therapy May 2022Atopic dermatitis (AD) is one of the most common skin diseases, and it may be associated with skin cancer risk. However, there is a controversy pertaining to whether it...
INTRODUCTION
Atopic dermatitis (AD) is one of the most common skin diseases, and it may be associated with skin cancer risk. However, there is a controversy pertaining to whether it implies a greater or decreased risk of skin cancers. We aimed to study the relationship between AD and skin cancer risk.
METHODS
PubMed and Embase databases from their inception to 4 August 2021 were systematically searched.
RESULTS
We evaluated 16 studies involving a total of 9,638,093 participants examining the contribution of AD to skin cancers. Random-effects model was applied to estimate the overall effect sizes. The pooled analysis of 16 studies indicated that AD was significantly associated with an overall increased risk of skin cancer. Subgroup pooled analyses showed that AD was statistically associated with an increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). With regard to cohort study, AD was statistically associated with an increased risk of nonmelanoma skin cancer (NMSC), BCC, and SCC, but not melanoma risk. Sensitivity analysis revealed that excluding each study in turn did not alter the overall combined results. No publication bias existed among the studies.
CONCLUSION
It can be concluded that AD is associated with risk of skin cancers; however, this association still needs to be verified in well-designed, worldwide trials (especially prospective, non-Western studies). The mechanism of AD leading to skin cancer is not clear, and further research is needed to explore the possibility of a potential pathogenesis.
PubMed: 35430723
DOI: 10.1007/s13555-022-00720-2