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Nutrients Aug 2019Research has investigated 25-hydroxyvitamin D (25(OH)D) levels in the Atopic Dermatitis (AD) population, as well as changes in AD severity after vitamin D (VitD)... (Meta-Analysis)
Meta-Analysis
Vitamin D Deficiency and Effects of Vitamin D Supplementation on Disease Severity in Patients with Atopic Dermatitis: A Systematic Review and Meta-Analysis in Adults and Children.
Research has investigated 25-hydroxyvitamin D (25(OH)D) levels in the Atopic Dermatitis (AD) population, as well as changes in AD severity after vitamin D (VitD) supplementation. We performed an up-to-date systematic review and meta-analysis of these findings. Electronic searches of MEDLINE, EMBASE and COCHRANE up to February 2018 were performed. Observational studies comparing 25(OH)D between AD patients and controls, as well as trials documenting baseline serum 25(OH)D levels and clinical severity by either SCORAD/EASI scores, were included. Of the 1085 articles retrieved, sixteen were included. A meta-analysis of eleven studies of AD patients vs. healthy controls (HC) found a mean difference of -14 nmol/L (95% CI -25 to -2) for all studies and -16 nmol/L (95% CI -31 to -1) for the paediatric studies alone. A meta-analysis of three VitD supplementation trials found lower SCORAD by -11 points (95% CI -13 to -9, < 0.00001). This surpasses the Minimal Clinical Important Difference for AD of 9.0 points (by 22%). There were greater improvements in trials lasting three months and the mean weighted dose of all trials was 1500-1600 IU/daily. Overall, the AD population, especially the paediatric subset, may be at high-risk for lower serum 25(OH)D. Supplementation with around 1600 IU/daily results in a clinically meaningful AD severity reduction.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Dermatitis, Atopic; Dietary Supplements; Female; Humans; Incidence; Infant; Male; Risk Factors; Severity of Illness Index; Treatment Outcome; Vitamin D; Vitamin D Deficiency
PubMed: 31405041
DOI: 10.3390/nu11081854 -
Journal of the American Academy of... Jun 2022Studies found associations between atopic dermatitis (AD) and various comorbidities.
BACKGROUND
Studies found associations between atopic dermatitis (AD) and various comorbidities.
OBJECTIVE
To appraise evidence of the association between AD and comorbidities among adults.
METHODS
Our multidisciplinary work group conducted a systematic review of the association between AD and selected comorbidities. We applied the Grading of Recommendations, Assessment, Development, and Evaluation for prognosis approach for assessing the certainty of the evidence, providing statements of association based on the available evidence.
RESULTS
Analysis of the evidence resulted in 32 statements. Clear evidence of the association of AD in adults and select allergic, atopic, immune-mediated mental health and bone health conditions and skin infections was identified. There is some evidence supporting an association between AD and substance use, attention deficit hyperactivity disorder, and elements of metabolic syndrome. Evidence suggests a small association with various cardiovascular conditions. The association between AD in adults and autism spectrum disorders, myocardial infarction, stroke, and metabolic syndrome is inconclusive.
LIMITATIONS
This analysis is based on the best available evidence at the time it was conducted. This guideline does not make recommendations for screening or management of comorbidities in adults with AD.
CONCLUSIONS
Clinicians should be aware of comorbidities associated with AD. Further research is needed to determine whether screening or management of comorbidities is beneficial for adults with AD.
Topics: Adult; Comorbidity; Dermatitis, Atopic; Dermatology; Humans; Metabolic Syndrome; Myocardial Infarction; United States
PubMed: 35085682
DOI: 10.1016/j.jaad.2022.01.009 -
The Cochrane Database of Systematic... Nov 2022Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eczema and food allergy are common health conditions that usually begin in early childhood and often occur in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective for preventing eczema or food allergy.
OBJECTIVES
Primary objective To assess the effects of skin care interventions such as emollients for primary prevention of eczema and food allergy in infants. Secondary objective To identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated with the greatest treatment benefit or harm for both eczema and food allergy.
SEARCH METHODS
We performed an updated search of the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase in September 2021. We searched two trials registers in July 2021. We checked the reference lists of included studies and relevant systematic reviews, and scanned conference proceedings to identify further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (≤ 12 months) without pre-existing eczema, food allergy, or other skin condition. Eligible comparisons were standard care in the locality or no treatment. Types of skin care interventions could include moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow-up was required.
DATA COLLECTION AND ANALYSIS
This is a prospective individual participant data (IPD) meta-analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E-mediated food allergy by one to three years, both measured at the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician-assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen.
MAIN RESULTS
We identified 33 RCTs comprising 25,827 participants. Of these, 17 studies randomising 5823 participants reported information on one or more outcomes specified in this review. We included 11 studies, randomising 5217 participants, in one or more meta-analyses (range 2 to 9 studies per individual meta-analysis), with 10 of these studies providing IPD; the remaining 6 studies were included in the narrative results only. Most studies were conducted at children's hospitals. Twenty-five studies, including all those contributing data to meta-analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta-analyses recruited infants at high risk of developing eczema or food allergy, although the definition of high risk varied between studies. Durations of intervention and follow-up ranged from 24 hours to three years. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported information on our prespecified outcomes, 13 assessed emollients. We assessed most of the evidence in the review as low certainty and had some concerns about risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. We assessed the evidence for the primary food allergy outcome as high risk of bias due to the inclusion of only one trial, where findings varied based on different assumptions about missing data. Skin care interventions during infancy probably do not change the risk of eczema by one to three years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; risk difference 5 more cases per 1000 infants, 95% CI 28 less to 47 more; moderate-certainty evidence; 3075 participants, 7 trials) or time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate-certainty evidence; 3349 participants, 9 trials). Skin care interventions during infancy may increase the risk of IgE-mediated food allergy by one to three years of age (RR 2.53, 95% CI 0.99 to 6.49; low-certainty evidence; 976 participants, 1 trial) but may not change risk of allergic sensitisation to a food allergen by age one to three years (RR 1.05, 95% CI 0.64 to 1.71; low-certainty evidence; 1794 participants, 3 trials). Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low-certainty evidence; 1171 participants, 1 trial); however, this was only seen for cow's milk, and may be unreliable due to over-reporting of milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.33, 95% CI 1.01 to 1.75; risk difference 17 more cases per 1000 infants, 95% CI one more to 38 more; moderate-certainty evidence; 2728 participants, 6 trials) and may increase the risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low-certainty evidence; 2538 participants, 4 trials) and stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low-certainty evidence; 343 participants, 4 trials), although CIs for slippages and stinging/allergic reactions were wide and include the possibility of no effect or reduced risk. Preplanned subgroup analyses showed that the effects of interventions were not influenced by age, duration of intervention, hereditary risk, filaggrin (FLG) mutation, chromosome 11 intergenic variant rs2212434, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and eczema or food allergy development.
AUTHORS' CONCLUSIONS
Based on low- to moderate-certainty evidence, skin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema; may increase risk of food allergy; and probably increase risk of skin infection. Further study is needed to understand whether different approaches to infant skin care might prevent eczema or food allergy.
Topics: Female; Animals; Cattle; Emollients; Eczema; Food Hypersensitivity; Milk Hypersensitivity; Allergens
PubMed: 36373988
DOI: 10.1002/14651858.CD013534.pub3 -
Pediatric Allergy and Immunology :... Nov 2020Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked... (Meta-Analysis)
Meta-Analysis
RATIONALE
Allergic diseases are an increasing public health concern, and early life environment is critical to immune development. Maternal diet during pregnancy has been linked to offspring allergy risk. In turn, maternal diet is a potentially modifiable factor, which could be targeted as an allergy prevention strategy. In this systematic review, we focused on non-allergen-specific modifying factors of the maternal diet in pregnancy on allergy outcomes in their offspring.
METHODS
We undertook a systematic review of studies investigating the association between maternal diet during pregnancy and allergic outcomes (asthma/wheeze, hay fever/allergic rhinitis/seasonal allergies, eczema/atopic dermatitis (AD), food allergies, and allergic sensitization) in offspring. Studies evaluating the effect of food allergen intake were excluded. We searched three bibliographic databases (MEDLINE, EMBASE, and Web of Science) through February 26, 2019. Evidence was critically appraised using modified versions of the Cochrane Collaboration Risk of Bias tool for intervention trials and the National Institute for Clinical Excellence methodological checklist for cohort and case-control studies and meta-analysis performed from RCTs.
RESULTS
We identified 95 papers: 17 RCTs and 78 observational (case-control, cross-sectional, and cohort) studies. Observational studies varied in design and dietary intakes and often had contradictory findings. Based on our meta-analysis, RCTs showed that vitamin D supplementation (OR: 0.72; 95% CI: 0.56-0.92) is associated with a reduced risk of wheeze/asthma. A positive trend for omega-3 fatty acids was observed for asthma/wheeze, but this did not reach statistical significance (OR: 0.70; 95% CI: 0.45-1.08). Omega-3 supplementation was also associated with a non-significant decreased risk of allergic rhinitis (OR: 0.76; 95% CI: 0.56-1.04). Neither vitamin D nor omega-3 fatty acids were associated with an altered risk of AD or food allergy.
CONCLUSIONS
Prenatal supplementation with vitamin D may have beneficial effects for prevention of asthma. Additional nutritional factors seem to be required for modulating the risk of skin and gastrointestinal outcomes. We found no consistent evidence regarding other dietary factors, perhaps due to differences in study design and host features that were not considered. While confirmatory studies are required, there is also a need for performing RCTs beyond single nutrients/foods.
Topics: Asthma; Cross-Sectional Studies; Dermatitis, Atopic; Diet; Female; Food Hypersensitivity; Humans; Pregnancy
PubMed: 32524677
DOI: 10.1111/pai.13303 -
The British Journal of Dermatology Sep 2023On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked to the occurrence of major adverse cardiovascular events (MACE). However, these inflammatory diseases are proatherogenic; in contrast, patients with atopic dermatitis (AD) do not usually have a high cardiovascular (CV) comorbidity burden.
OBJECTIVES
To perform a systematic review and meta-analysis of MACE in patients with AD treated with JAKi.
METHODS
We systematically searched PubMed, Embase, Cochrane Library and Google Scholar from their inception to 2 September 2022. Cohort studies, randomized controlled trials and pooled safety analyses providing CV safety data on patients taking JAKi for AD were selected. We included patients aged ≥ 12 years. We built a 'controlled-period' cohort (n = 9309; 6000 exposed to JAKi and 3309 exposed to comparators) and an 'all-JAKi' cohort (n = 9118 patients exposed to a JAKi in any of the included studies). The primary outcome was a composite of acute coronary syndrome (ACS), ischaemic stroke and CV death. The broader secondary MACE outcome encompassed ACS, stroke (whether ischaemic or haemorrhagic), transient ischaemic attack and CV death. The frequency of primary and secondary MACE was assessed in both cohorts. A fixed-effects meta-analysis using the Peto method was used to calculate the odds ratio (OR) for MACE in the 'controlled-period' cohort. Evaluation of the risk of bias was done using the Cochrane risk-of-bias tool (version 2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Eight per cent of the records identified initially met the selection criteria, corresponding to 23 records included in the 'all-JAKi' cohort. Patients had been exposed to baricitinib, upadacitinib, abrocitinib, ivarmacitinib, placebo or dupilumab. Four primary events (three with JAKi and one with placebo) and five secondary events (four with JAKi and one with placebo) occurred among 9309 patients in the 'controlled-period' cohort (MACE frequency 0.04% and 0.05%, respectively). Eight primary events and 13 secondary events occurred among 9118 patients in the 'all-JAKi' cohort (MACE frequency 0.08% and 0.14%, respectively). The OR for primary MACE in patients with AD treated with JAKi vs. placebo or dupilumab was 1.35 (95% confidence interval 0.15-12.21; I2 = 12%, very low certainty of evidence).
CONCLUSIONS
Our review highlights rare cases of MACE among JAKi users for AD. JAKi may have little-to-no effect on the occurrence of MACE in patients with AD vs. comparators, but the evidence is uncertain. Real-life long-term population-level safety studies are needed.
Topics: Humans; Janus Kinase Inhibitors; Dermatitis, Atopic; Brain Ischemia; Stroke; Inflammatory Bowel Diseases
PubMed: 37410552
DOI: 10.1093/bjd/ljad229 -
The British Journal of Dermatology Jan 2024Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures.
OBJECTIVES
To compare binary efficacy outcomes of systemic treatments for AD.
METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes included the proportion of patients achieving at least 50%, 75% and 90% improvements in Eczema Area and Severity Index (EASI 50, EASI 75 and EASI 90, respectively) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian NMAs to calculate odds ratios (OR) and 95% credible intervals (CrIs) between each intervention for each outcome.
RESULTS
Eighty-three trials with 22 122 participants were included in the systematic review. In analyses limited to trials of 8-16 weeks' duration with predominantly adult populations, abrocitinib 200 mg daily (OR 1.5, 95% CrI 1.1-2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9-3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3-5.0) were associated with higher odds of achieving EASI 50 vs. dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5-1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3-0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3-0.7), and tralokinumab (OR 0.4, 95% CrI 0.3-0.6) were associated with lower odds of achieving EASI 50 vs. dupilumab. Results were similar for EASI 75, EASI 90 and IGA success.
CONCLUSIONS
Supporting results for continuous outcome measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regard to binary efficacy endpoints up to 16 weeks in adults with moderate-to-severe AD, followed by upadacitinib 15 mg daily, dupilumab and abrocitinib 100 mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2 mg daily and tralokinumab.
Topics: Adult; Humans; Azetidines; Bayes Theorem; Dermatitis, Atopic; Eczema; Network Meta-Analysis; Purines; Pyrazoles; Pyrimidines; Severity of Illness Index; Sulfonamides; Treatment Outcome
PubMed: 37831594
DOI: 10.1093/bjd/ljad393 -
Cells Dec 2023Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent... (Review)
Review
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and presents a major public health problem worldwide. It is characterized by a recurrent and/or chronic course of inflammatory skin lesions with intense pruritus. Its pathophysiologic features include barrier dysfunction, aberrant immune cell infiltration, and alterations in the microbiome that are associated with genetic and environmental factors. There is a complex crosstalk between these components, which is primarily mediated by cytokines. Epidermal barrier dysfunction is the hallmark of AD and is caused by the disruption of proteins and lipids responsible for establishing the skin barrier. To better define the role of cytokines in stratum corneum lipid abnormalities related to AD, we conducted a systematic review of biomedical literature in PubMed from its inception to 5 September 2023. Consistent with the dominant T2 skewness seen in AD, type 2 cytokines were featured prominently as possessing a central role in epidermal lipid alterations in AD skin. The cytokines associated with T1 and T17 were also identified to affect barrier lipids. Considering the broad cytokine dysregulation observed in AD pathophysiology, understanding the role of each of these in lipid abnormalities and barrier dysfunction will help in developing therapeutics to best achieve barrier homeostasis in AD patients.
Topics: Humans; Dermatitis, Atopic; Cytokines; Epidermis; Skin; Lipids
PubMed: 38132113
DOI: 10.3390/cells12242793 -
Journal of the American Academy of... May 2023
Topics: Humans; Sezary Syndrome; Mycosis Fungoides; Antibodies, Monoclonal, Humanized; Skin Neoplasms
PubMed: 36481378
DOI: 10.1016/j.jaad.2022.12.001 -
Cureus Sep 2023Atopic dermatitis is a complex, recurrent, chronic inflammatory skin condition. It frequently begins to manifest in early childhood and may last throughout adulthood.... (Review)
Review
Atopic dermatitis is a complex, recurrent, chronic inflammatory skin condition. It frequently begins to manifest in early childhood and may last throughout adulthood. The need for clinical practice guidelines that are based on evidence is critical for efficient and secure care. Little is known about how primary care providers (PCPs) should handle pediatric and adult atopic dermatitis cases and whether they should follow national recommendations. Our systemic review aimed to examine management strategies for treating adult and pediatric (family) atopic dermatitis, including topical calcineurin inhibitors (TCIs), topical corticosteroids (TCS), skin emollients, oral antihistamines, and diet. Data sources were PubMed (MEDLINE) and Embase. Our review investigated English-language articles from 2014 to 2023 that studied the management of adult and children atopic dermatitis. Overall, there were 15 articles included. Surveys and analyses of national databases were the most widely used methods (n=7). The use of TCS by PCPs was common, but they also overprescribed nonsedating antihistamines, favored low-potency drugs, and avoided TCIs. Most studies relied on healthcare personnel reporting their typical behaviors rather than looking at specific patient encounters and it is considered a limitation. Finally, there are gaps in knowledge and management of critical topics such as prescribing TCIs and understanding the safety profiles of TCS, when it comes to treating adult and pediatric atopic dermatitis. Future research in this area is urgently needed because the current systemic assessment is mostly restricted to small studies that assess prescribing behaviors with scant information describing nonmedication management.
PubMed: 37789992
DOI: 10.7759/cureus.44560 -
Life (Basel, Switzerland) Nov 2021Atopic dermatitis (AD) is a chronic inflammatory disease of the skin whose main symptom is pruritus and may affect all age ranges. Regarding the prevalence, it has been... (Review)
Review
Atopic dermatitis (AD) is a chronic inflammatory disease of the skin whose main symptom is pruritus and may affect all age ranges. Regarding the prevalence, it has been estimated at around 10% of the world population. Many concomitant diseases have been associated with AD, but the causal relationship between AD and psychological impairment has not been clearly established. Scientific literature studying the probable association between male or female sexual dysfunction and dermatological pathology is limited, even more so in AD. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines and the Cochrane Collaboration methodology for systematic reviews. All relevant articles in English were identified through a search from inception to 10 December 2020, including the following databases: Medline (via PubMed), Scopus, Web of Science Core Collection, and SciELO. The results of the search were compiled using the COVIDENCE software for systematic reviews. The methodological quality of the included studies was done using the "Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies" and the "Quality Assessment of Case-Control Studies" developed by the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH). Our search yielded potentially relevant studies. Five studies that evaluated the prevalence of sexual dysfunction in atopic dermatitis were retrieved after applying the selection criteria. The present systematic review achieved data from 8088 patients with atopic dermatitis from four articles. Sample sizes for atopic dermatitis patients ranged from 266 to 3997. We identified one cohort study with four years of follow-up, three studies with a cross-sectional design, and one case-control study. Three studies reported data disaggregated by the severity of atopic dermatitis. Two studies included healthy controls with a total sample size of 1,747,755 subjects. Two studies compared data with other dermatological conditions such as psoriasis. In conclusion, we can establish that unlike other psychological comorbidities such as anxiety and depression, sexual dysfunction is a field scarcely explored in the literature. This sexual dysfunction focuses on the male sex in large population studies and in clinical diagnoses without exploring it through specific and validated questionnaires in this regard. Further studies focused on both genders are needed. It is important to correlate this sexual dysfunction with the severity of the disease, previous treatments, and cardiovascular comorbidities.
PubMed: 34947845
DOI: 10.3390/life11121314