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Background Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. Objective We sought to characterize age-related changes in the AD profile. Methods We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years). Results Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b+ and FceRI+, P Conclusion The adult AD profile varies with age. Although TH1/TH17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in TH2/TH22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.

Introduction Deficiencies in interleukin (IL)-1 receptor (IL-R) antagonist (DIRA) and IL-36R antagonist (DITRA) are rare genetic autoinflammatory diseases related to alterations in antagonists of the IL-1 pathway. IL-1 antagonists may represent therapeutic alternatives. Here, we aim to provide a scoping review of knowledge on use of IL-1-targeting drugs in DIRA and DITRA. Methods An a priori protocol was published, and the study was conducted using the methodology described in the Joanna Briggs Institute Reviewer’s Manual and the recently published PRISMA Extension for Scoping Review statement. A three-step search using MEDLINE and EMBASE databases until March 2018 with additional hand searching was performed. Data charting was performed. The search, article selection, and data extraction were carried out by two researchers independently. Results Twenty-four studies on use of anti-IL-1 drugs were included [15 studies including patients with diagnosis of DIRA (n = 19) and 9 studies including patients with diagnosis of DITRA (n = 9)]. Most studies followed a multicenter observational design. Among all patients who received treatment with anti-IL-1 drugs, nine and four mutations in IL1RN and IL36RN were found, respectively. Patients with DIRA were treated with anakinra (n = 17), canakinumab (n = 2), or rinolacept (n = 6). All patients with DITRA were treated with anakinra, and only one case was also treated with canakinumab. Time-to-response frequencies were evaluated as immediate, short, and medium–long term for DIRA (17/17, 15/17, and 9/10, respectively) and DITRA (7/9, 3/9, and 2/9, respectively). Most DITRA patients in whom anti-IL-1 treatment failed experienced good response to anti-tumor necrosis factor alpha or anti-IL-12/23 drugs. The safety profiles of treatments were similar in both diseases. Conclusions Evidence on use of anti-IL-1 drugs in DIRA and DITRA is scarce and based on observational studies. Larger studies with better methodological quality are needed to increase confidence in use of these drugs in patients with DIRA and DITRA. Electronic supplementary material The online version of this article (10.1007/s13555-018-0269-7) contains supplementary material, which is available to authorized users.

Introduction The interleukin (IL)-1 pathway has been identified as being involved in inflammatory and neoplastic skin diseases such as psoriasis, atopic dermatitis, neutrophilic dermatosis, melanoma, and squamous cell carcinoma. Drugs developed to target the IL-1 pathway are currently used to treat these pathologies, and although they are becoming more selective, they are not exempt from adverse events and high costs. Integrating the best research evidence with clinical experience and patient needs has been shown to improve care, health, and cost outcomes. This is because evidence-based guidelines rank interventions according to cost-effectiveness. However, evidence on this topic is scarce for several reasons. First, although randomized clinical trials currently provide the best evidence, they are not always available. Second, there are no secondary scientific studies that summarize the use of IL-1-targeting agents in dermatology. We therefore sought to develop an a priori protocol for broadly reviewing the available evidence on the use of IL-1-targeting drugs in the treatment of dermatological diseases. Methods We used the latest methodology to perform a scoping review as described in the Joanna Briggs Institute manual. Results/Discussion Developing and applying a methodology for evidence synthesis promotes reproducibility and increases the validity of secondary scientific investigations, making it the optimal strategy for scientifically synthesizing a broad field such as the indications for and the mechanisms of action, efficacies, safety, and costs of IL-1-targeting drugs in the treatment of dermatological diseases. Quantitative synthesis facilitates the detection of knowledge gaps and the identification of new questions that can be addressed through systematic reviews. We present an a priori protocol for exploring the available evidence on this topic.

SummaryBackground The quality of systematic reviews (SRs) and meta-analyses about psoriasis, a chronic inflammatory skin disease that severely impairs quality of life and is associated with high costs, remains unknown. Objectives To assess the methodological quality of SRs published on psoriasis. Methods After a comprehensive search in MEDLINE, EMBASE, and the Cochrane Database (PROSPERO:CDR4201604161), the quality was assessed by two raters using Assessment of Multiple Systematic Reviews (AMSTAR) tool. Article metadata and journal-related bibliometric indices were also obtained. SRs were classified as low (0-4), moderate (5-8), or high (9-11) quality. A prediction model for methodological quality was fitted using principal component and multivariate ordinal logistic regression analyses. Results We classified 220 studies as high (17.2%), moderate (55%), or low (27.7%) quality. Lower compliance rates were found for question (Q) 5 (list of studies provided, 11.3%), Q10 (publication bias assessed, 27.8%), Q4 (status of publication included, 39.5%), and Q1 (a priori design provided, 41%) AMSTAR items. Factors such as meta-analysis including (odds ratio [OR], 6.21; 95% confidence interval [CI]: 2.78-14.85), funding by academic institutions (OR, 2.89; 95% CI, 1.11-7.89), article influence score (OR, 2.13; 95% CI, 1.05-6.67), 5-year impact factor (OR, 1.34; 95% CI, 1.02-1.14), and article page count (OR, 1.08; 95% CI, 1.02-1.15) significantly predicted a higher quality; a high number of authors with a conflict of interest (OR, 0.9; 95% CI, 0.824-0.985) was significantly associated with a lower quality. Conclusions The methodological quality of SRs published about psoriasis remains suboptimal. The type of funding sources and author conflicts may compromise study quality, increasing the risk of bias. This article is protected by copyright. All rights reserved.

Background Epidemiology and the reporting characteristics of systematic reviews (SRs) and meta-analyses (MAs) are well known. However, no study has analyzed the influence of protocol features on the probability that a study’s results will be finally reported, thereby indirectly assessing the reporting bias of International Prospective Register of Systematic Reviews (PROSPERO) registration records. Objective The objective of this study is to explore which factors are associated with a higher probability that results derived from a non-Cochrane PROSPERO registration record for a systematic review will be finally reported as an original article in a scientific journal. Methods/design The PROSPERO repository will be web scraped to automatically and iteratively obtain all completed non-Cochrane registration records stored from February 2011 to December 2017. Downloaded records will be screened, and those with less than 90% fulfilled or are duplicated (i.e., those sharing titles and reviewers) will be excluded. Manual and human-supervised automatic methods will be used for data extraction, depending on the data source (fields of PROSPERO registration records, bibliometric databases, etc.). Records will be classified into published, discontinued, and abandoned review subgroups. All articles derived from published reviews will be obtained through multiple parallel searches using the full protocol “title” and/or “list reviewers” in MEDLINE/PubMed databases and Google Scholar. Reviewer, author, article, and journal metadata will be obtained using different sources. R and Python programming and analysis languages will be used to describe the datasets; perform text mining, machine learning, and deep learning analyses; and visualize the data. We will report the study according to the recommendations for meta-epidemiological studies adapted from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for SRs and MAs. Discussion This meta-epidemiological study will explore, for the first time, characteristics of PROSPERO records that may be associated with the publication of a completed systematic review. The evidence may help to improve review workflow performance in terms of research topic selection, decision-making regarding team selection, planning relationships with funding sources, implementing literature search strategies, and efficient data extraction and analysis. We expect to make our results, datasets, and R and Python code scripts publicly available during the third quarter of 2018.

Objectives No gold standard exists to assess methodological quality of systematic reviews (SRs). Although Assessing the Methodological Quality of Systematic Reviews (AMSTAR) is widely accepted for analyzing quality, the ROBIS instrument has recently been developed. This study aimed to compare the capacity of both instruments to capture the quality of SRs concerning psoriasis interventions. Study Design and Setting Systematic literature searches were undertaken on relevant databases. For each review, methodological quality and bias risk were evaluated using the AMSTAR and ROBIS tools. Descriptive and principal component analyses were conducted to describe similarities and discrepancies between both assessment tools. Results We classified 139 intervention SRs as displaying high/moderate/low methodological quality and as high/low risk of bias. A high risk of bias was detected for most SRs classified as displaying high or moderate methodological quality by AMSTAR. When comparing ROBIS result profiles, responses to domain 4 signaling questions showed the greatest differences between bias risk assessments, whereas domain 2 items showed the least. Conclusion When considering SRs published about psoriasis, methodological quality remains suboptimal, and the risk of bias is elevated, even for SRs exhibiting high methodological quality. Furthermore, the AMSTAR and ROBIS tools may be considered as complementary when conducting quality assessment of SRs.