Increased Risk of Cutaneous and Systemic Infections in Atopic Dermatitis-A Cohort Study.
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ABSTRACT:
SUBMITTER: Langan SM
PROVIDER: S-EPMC5660507 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Increased Risk of Cutaneous and Systemic Infections in Atopic Dermatitis-A Cohort Study.
Langan Sinéad M SM Abuabara Katrina K Henrickson Sarah E SE Hoffstad Ole O Margolis David J DJ
The Journal of investigative dermatology 20170212 6
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Project description:BackgroundAtopic dermatitis (AD) is associated with barrier disruption, immune dysregulation, and immunosuppressing treatments that can increase the association with an unusual number of infections.ObjectiveTo determine whether adults with AD have an unusually large number of serious infections and related outcomes.MethodsData from the 2002 to 2012 National Inpatient Sample were analyzed, including an approximately 20% sample of all US hospitalizations (n = 72,108,077 adults). Prevalence of serious infections in hospitalized patients with vs without AD, length of stay, cost of care, and inpatient mortality secondary to serious infections were determined.ResultsThe prevalence of serious infections expressed as a percentage (95% confidence interval) was higher in adults hospitalized with than in those without AD (42.1% [41.6-42.6] vs 25.4% [25.2-25.6]; P = .0002). In logistic regression models with multiple predictors (multivariable logistic regression models), AD was associated with 32 of 38 infections examined. Associated cutaneous infections included eczema herpeticum (odds ratio [95% confidence interval] adjusted for other predictors: 67.93 [47.93-96.28]), erysipelas (11.15 [9.47-13.1]), and cellulitis (4.53 [4.42-4.64]). Associated respiratory infections included aspergillosis (1.51 [1.21-1.88]) and tuberculosis (1.57 [1.41-1.76]). AD was associated with extracutaneous, multiorgan, and systemic infections, including infectious arthropathy (2.01 [1.84-2.20]), endocarditis (1.25 [1.12-1.39]), encephalitis (1.65 [1.40-1.96]), and methicillin-resistant Staphylococcus aureus infections (3.29 [3.17-3.42]). Patients with AD hospitalized with vs without any serious infection had an increased geometric mean cost of inpatient care ($8,273 [8,126-8,423] vs $7,179 [7,052-7,307]) and length of stay (5.3 days [5.2-5.3] vs 3.9 [3.9-4.0]; P = .0002), with $11 to $228 million excess annual costs from hospitalization with serious infections in adults with AD.ConclusionAdults with AD had increased cutaneous, respiratory, multiorgan, and systemic infections, which were associated with a considerable cost burden.
| S-EPMC5745030 | biostudies-literature
Project description: Not available
| S-EPMC11635927 | biostudies-literature
Project description:IntroductionAtopic dermatitis (AD) is related to other atopic diseases asthma and allergic rhinitis. It is known that those with asthma or allergic rhinitis have impaired immune responses that may predispose them to infections. This study sought to determine whether adult AD is associated with systemic infections, and whether association is strengthened in those with AD plus another atopic disease.MethodsThis cross-sectional study obtained information from adults in the 2010 and the 2012 National Health Interview Survey (NHIS). The primary exposure was history of AD without or with an additional atopic disease, asthma or allergic rhinitis. Self-reported systemic infections were the primary outcomes. Survey logistic regression was performed and adjusted odds ratios (aOR) reported.ResultsAD in NHIS 2010 was associated with increased risk of sinusitis [aOR (95% CIs): 1.65 (1.42, 1.91), P < 0.001], head or chest cold [1.31 (1.12, 1.52), P < 0.001], and gastrointestinal illness [2.39 (1.97, 2.89), P < 0.001], and in NHIS 2012, pneumonia/influenza [1.73 (1.54, 1.95), P < 0.001], strep throat/tonsillitis [1.72 (1.54, 1.92), P < 0.001], sinusitis [1.77 (1.54, 2.02), P < 0.001], head or chest cold [1.49 (1.33, 1.67), P < 0.001], and infectious disease [2.66 (2.20, 3.21), P < 0.001]. An increase in atopic disease mirrored an increase in number of infectious outcomes and was statistically significant in the combined dataset (P < 0.001).ConclusionThe associations between AD and AD plus another atopic disease with systemic infections suggest that an underlying immune defect may be contributing to microbial susceptibility. Further studies are warranted to understand the burden of infectious disease in this population.
| S-EPMC5336435 | biostudies-literature
Project description:BackgroundStaphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections.ObjectivesTo determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD.MethodsWe conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections.ResultsAmong 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50-52% greater risk of HSV and 18-33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38-4·54] and adults with severe AD (HR 4·45, 95% CI 1·76-11·25). Patients with AD had a 26-40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20-1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD.ConclusionsAD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.
| S-EPMC8983460 | biostudies-literature
Project description:Atopic dermatitis (AD) is a chronic inflammatory skin disorder with bimodal incidence peaks in early childhood and middle-aged and older adults. Few studies have focused on the risk of dementia in AD. The aims of this study were to analyse the incidence, and risk factors for dementia in patients with AD. This nationwide population-based retrospective cohort study enrolled 38,391 adults ≥ 40 years of age with AD and 2,643,602 controls without AD from the Korean National Health Insurance System (NHIS) database from 2009 to 2016. The cumulative incidence probability of all-cause dementia, Alzheimer’s disease, or vascular dementia at 8 years was 50, 39, and 7 per 1,000 person-years in patients with AD, respectively. The adjusted risks of all-cause dementia (hazard ratio (HR), 1.072; 95% confidence interval (95% CI) 1.026–1.120), and Alzheimer’s disease (HR 1.051; 95% CI 1.000–1.104) were increased in patients with AD. The effect of AD on the development of all-cause dementia and Alzheimer’s dementia varied according to age and diabetes mellitus (all p for interaction, < 0.05). The risks of all-cause dementia and Alzheimer’s disease were increased in patients with AD. Management of modifiable risk factors is important for preventing dementia in patients with AD. SIGNIFICANCE Little is known about the risk of dementia in patients with atopic dermatitis. This is the first population-based study in Korea identifying the risk of dementia among patients with atopic dermatitis. Atopic dermatitis is associated with an increased risk of all-cause dementia and Alzheimer’s disease. Management of modifiable risk factors is important for preventing dementia in patients with atopic dermatitis.
| S-EPMC10158831 | biostudies-literature
Project description:To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply-sequenced RNA-seq samples using long (125b) paired-end reads. By integrating deep sequencing-based skin transcriptome profiling with systems biology analysis, we are able to provide deep characterization for the expression signatures for AD.
2023-02-07 | GSE224783 | GEO
Project description:Background: Dupilumab is an IL-4 receptor a mAb inhibiting signaling of IL-4 and IL-13, key drivers of type 2-driven inflammation, as demonstrated by its efficacy in patients with atopic/allergic diseases. Objective: This placebo-controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic type 2 biomarkers of patients with moderate-to-severe atopic dermatitis (AD). Methods: Skin biopsy specimens and blood were evaluated from 54 patients randomized 1:1 to weekly subcutaneous doses of 200 mg of dupilumab or placebo for 16 weeks. Results: Dupilumab (vs placebo) significantly improved clinical signs and symptoms of AD, was well tolerated, and progressively shifted the lesional transcriptome toward a nonlesional phenotype (weeks 4-16). Mean improvements in a meta-analysis-derived AD transcriptome (genes differentially expressed between lesional and nonlesional skin) were 68.8% and 110.8% with dupilumab and 210.5% and 55.0% with placebo (weeks 4 and 16, respectively; P < .001). Dupilumab significantly reduced expression of genes involved in type 2 inflammation (IL13, IL31, CCL17, CCL18, and CCL26), epidermal hyperplasia (keratin 16 [K16] and MKi67), T cells, dendritic cells (ICOS, CD11c, and CTLA4), and Th17/Th22 activity (IL17A, IL-22, and S100As) and concurrently increased expression of epidermal differentiation, barrier, and lipid metabolism genes (filaggrin [FLG], loricrin [LOR], claudins, and ELOVL3). Dupilumab reduced lesional epidermal thickness versus placebo (week 4, P 5 .001; week 16, P 5 .0002). Improvements in clinical and histologic measures correlated significantly with modulation of gene expression. Dupilumab also significantly suppressed type 2 serum biomarkers, including CCL17, CCL18, periostin, and total and allergen- specific IgEs. Conclusion: Dupilumab-mediated inhibition of IL-4/IL-13 signaling through IL-4 receptor a blockade significantly and progressively improved disease activity, suppressed cellular/ molecular cutaneous markers of inflammation and systemic measures of type 2 inflammation, and reversed AD-associated epidermal abnormalities. (J Allergy Clin Immunol 2019;143:155-72.)
2019-05-02 | GSE130588 | GEO
Project description:Atopic dermatitis (AD) is a chronic or chronically relapsing inflammatory skin disease which results from a complex, multifaceted interaction between environmental factors in genetically predisposed patients. Epidermal barrier impairment, alteration of the cutaneous microbiota, effect of external antigens, neurosensory dysfunction, and inflammatory and immune dysregulation all play a pivotal role in inducing and maintaining AD lesions. AD significantly impacts the patient's quality of life and general well-being and is often associated with anxiety and/or depressive symptoms. Classical treatment options include topical corticosteroids and calcineurin inhibitors, phototherapy, and systemic immunosuppression with oral corticosteroids, cyclosporine, methotrexate, and azathioprine in more severe cases. A turning point in facing AD was accomplished when the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor α subunit, led to its approval for the treatment of moderate-to-severe or severe AD in children, adolescents, and adults. Subsequently, a more extensive understanding of AD etiology and pathogenesis has allowed the development of several topical and systemic novel therapy options. Most of these drugs are monoclonal antibodies which interfere with the type 2 inflammatory cascade, especially its key cytokines IL-4 and IL-13, or its downstream Janus kinase signaling pathway. However, considering the relevance of other subtypes of T helper (Th) cells, such as Th1 and Th22, and the important role of specific cytokines (IL-31) in generating pruritus, the horizon of potential therapeutic targets has widened extremely. In this review, we aim to present the most promising systemic agents currently under investigation and illustrate the most significant aspects of their efficacy, safety, and tolerability.
| S-EPMC10149421 | biostudies-literature
Project description:Atopic dermatitis (AD) is a multifactorial inflammatory skin disease resulting from interactions between genetic susceptibility and environmental factors. The pathogenesis of AD is poorly understood, and the treatment of recalcitrant AD is still challenging. There is accumulating evidence for new gene polymorphisms related to the epidermal barrier function and innate and adaptive immunity in patients with AD. Newly-found T cells and dendritic cell subsets, cytokines, chemokines and signaling pathways have extended our understanding of the molecular pathomechanism underlying AD. Genetic changes caused by environmental factors have been shown to contribute to the pathogenesis of AD. We herein present a review of the genetics, epigenetics, barrier dysfunction and immunological abnormalities in AD with a focus on updated molecular biology.
| S-EPMC5000632 | biostudies-literature
Project description:ObjectiveThe pathogenesis of keloid is largely unknown. Because keloid and atopic dermatitis have overlapping pathophysiological mechanisms, we aimed to evaluate keloid risk in patients with atopic dermatitis.Study designPopulation-based retrospective cohort study.SettingThe Taiwan National Health Insurance Research Database was used to analyse data for people who had been diagnosed with atopic dermatitis.ParticipantsWe identified 8371 patients with newly diagnosed atopic dermatitis during 1996-2010. An additional 33 484 controls without atopic dermatitis were randomly identified and frequency matched at a one-to-four ratio.Primary and secondary outcome measureThe association between atopic dermatitis and keloid risk was estimated using Cox proportional hazard regression models.ResultsAfter adjustment for covariates, the atopic dermatitis patients have a 3.19-fold greater risk of developing keloid compared with the non-atopic dermatitis group (3.19vs1.07 per 1000 person-years, respectively). During the study period, 163 patients with atopic dermatitis and 532 patients without atopic dermatitis developed keloid. Notably, keloid risk increased with severity of atopic dermatitis, particularly in patients with moderate to severe atopic dermatitis.ConclusionsOur results indicate that patients with atopic dermatitis had a higher than normal risk of developing keloid and suggest that atopic dermatitis may be an independent risk factor for keloid.
| S-EPMC6059319 | biostudies-literature