Atopic dermatitis and bone health: a systematic review.

Atopic dermatitis (AD) is associated with systemic inflammation and systemic corticosteroid use which can lead to poor bone health. The aim of this systematic review is to investigate the relationship between AD and bone mineral density (BMD), osteoporosis and fractures. We searched Web of Science, Cochrane Database of Systematic Reviews, MEDLINE and Embase. Title, abstract and full-text screening, and data extraction were done in duplicate. Quality appraisal was performed using the Agency for Healthcare Research and Quality Methodology Checklist (cross-sectional studies) and Newcastle-Ottawa Scale (cohort studies). We screened 3800 abstracts and included fifteen studies (twelve cross-sectional, three cohort). In cross-sectional studies, AD was associated with decreased BMD and increased fractures. In cross-sectional studies and a cohort study, AD was associated with a higher prevalence of osteoporosis compared to controls. There was inconsistency across studies, with some finding no association. In a large cohort study, AD was associated with increased risk of fractures of the hip (HR: 1.06, 95% CI: 1.02 to 1.11), spine (HR: 1.14, 95% CI: 1.06 to 1.23) and wrist (HR: 1.06, 95% CI: 1.01 to 1.10), with further increased risk with more severe AD. Differences between studies precluded quantitative synthesis. There is some evidence supporting an association between AD and poor bone health. Research is needed to clarify this association, underlying mechanisms and develop strategies to improve bone health of individuals with AD.

Development of a core outcome set for cutaneous squamous cell carcinoma trials: identification of core domains and outcomes.

BACKGROUND: The lack of uniformity in the outcomes reported in clinical studies of the treatment of cutaneous squamous cell carcinoma (cSCC) complicates efforts to compare treatment effectiveness across trials. OBJECTIVES: To develop a core outcome set (COS), a minimum set of agreed-upon outcomes to be measured in all clinical trials of a given disease or outcome, for the treatment of cSCC. METHODS: One hundred and nine outcomes were identified via a systematic literature review and interviews with 28 stakeholders. After consolidation of this long list, 55 candidate outcomes were rated by 19 physician and 10 patient stakeholders, in two rounds of Delphi exercises. Outcomes scored 'critically important' (score of 7, 8 or 9) by ≥ 70% of patients and ≥ 70% of physicians were provisionally included. At the consensus meeting, after discussion and voting of 44 international experts and patients, the provisional list was reduced to a final core set, for which consensus was achieved among all meeting participants. RESULTS: A core set of seven outcomes was finalized at the consensus meeting: (i) serious or persistent adverse events, (ii) patient-reported quality of life, (iii) complete response, (iv) partial response, (v) recurrence-free survival, (vi) progression-free survival and (vii) disease-specific survival. CONCLUSIONS: In order to increase the comparability of results across trials and to reduce selective reporting bias, cSCC researchers should consider reporting these core outcomes. Further work needs to be performed to identify the measures that should be reported for each of these outcomes.

Quality of reporting in systematic reviews published in dermatology journals.

BACKGROUND: Reporting of systematic reviews (SRs) using PRISMA increases transparency and reproducibility; adherence in the dermatology literature has not been assessed. OBJECTIVES: To assess selected, primarily methodological items from the PRISMA reporting guideline among SRs published in dermatology journals. METHODS: We reviewed SRs published from 2013 to 2017 in the five highest-impact dermatology journals according to the Science Citation Index. We descriptively assessed reporting of selected PRISMA items, the proportion of PRISMA items fully and partially reported, and whether SRs described using a preregistered protocol. We used univariate and multivariate linear regression to evaluate associations between exposures (year, protocol registration, funding source, type of included study, disease and journal), and outcomes (proportion of PRISMA items fully reported, and fully and partially reported, for each SR). RESULTS: We identified 136 SRs. All had more than one inadequately reported PRISMA item. Protocol registration (73%) and risk of bias (38%) were most often unreported. Reporting improved over time in our primary multivariate analysis [fully reported vs. partially and not reported, ß = 2·48; 95% confidence interval (CI) 0·73-4·27] and secondary analysis (fully and partially reported vs. not reported, ß = 1·28, 95% CI 0·06-2·50). Only 15% (20 of 136) of SRs stated that their protocols were registered; this was associated with PRISMA adherence to the evaluated PRISMA items in our primary multivariate analysis (ß = 10·05, 95% CI 2·89-17·2) and secondary analysis (ß = 8·87, 95% CI 3·84-13·9). CONCLUSIONS: SR reporting in dermatology journals is often inadequate but improving over time; protocol registration is associated with better reporting. What's already known about this topic? No studies to date have examined the adherence of dermatology systematic reviews (SRs) to reporting guidelines, such as PRISMA. In other medical fields, reporting is variable with some improvement in adherence to reporting standards over time. What does this study add? Among SRs published in five dermatology journals from 2013 to 2017, all (n = 136) had at least one inadequately reported PRISMA item, while 93% (127 of 136) had at least one fully nonreported item. Reporting improved over time and SRs that stated use of a preregistered protocol were associated with better reporting. Several items remain commonly underreported in dermatology SRs. Authors, reviewers, journal editors and editorial committees should encourage preregistration of SR protocols and improved SR reporting.

Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

BACKGROUND: Conjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab. OBJECTIVE: To survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC). METHODS: Electronic survey and in-person discussion of management strategies. RESULTS: Forty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist. LIMITATIONS: The study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey. CONCLUSION: The IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.

BACKGROUND: Epidemiologic studies of atopic dermatitis (AD) are often limited by case definitions that have not been validated. OBJECTIVE: In this study, we assessed the accuracy of self-report of AD in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of AD in the cohort. METHODS: We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of AD. This questionnaire was designed to confirm cases of AD using previously validated algorithms with >85% specificity. We assessed the association of AD with asthma, comparing the results when different definitions of AD were applied. We also inquired about various aspects of participants' AD. RESULTS: Responses were received from 2509 of 5126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1996/2509, 80%) reiterated their previously reported clinician diagnosis of AD. Application of the two diagnostic algorithms yielded confirmation of 1538 and 1293 prevalent cases, respectively. The association of AD with asthma was stronger when more stringent AD case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult-onset disease. CONCLUSIONS: Self-report of AD diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed AD subgroups.

Network meta-analyses of systemic treatments for psoriasis: a critical appraisal: Original Articles: Jabbar-Lopez ZK, Yiu ZZN, Ward V et al. Quantitative evaluation of biologic therapy options for psoriasis: a systematic review and network meta-analysis. J Invest Dermatol 2017; 137:1646-54. Sbidian E, Chaimani A, Garcia-Doval I et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis. Cochrane Database Syst Rev 2017; 12:CD011535.

AIM: There are numerous systemic medications in use for psoriasis, with additional investigational agents being studied. However, head-to-head, randomized clinical trials are rare and cannot feasibly compare all treatments. A network meta-analysis (NMA) synthesizes the available evidence to provide estimates for all pairwise comparisons. Here, we summarize and appraise two recent NMAs that assessed systemic therapies for moderate-to-severe psoriasis. SETTING AND DESIGN: Two systematic reviews searched databases and the grey literature to identify relevant randomized clinical trials. STUDY PARTICIPANTS: The reviews mostly included trials that involved adults with moderate-to-severe psoriasis. One of the reviews also included two trials involving children. STUDY EXPOSURE: Interventions common to both reviews include adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, secukinumab and methotrexate. One of the reviews included additional interventions, primarily other biological agents along with new small-molecule treatments and systemic conventional treatments. PRIMARY OUTCOMES: One review focused on 'clear/nearly clear' and withdrawals from adverse events as study outcomes, while the second review focused on improvement of ≥ 90% measured on the Psoriasis Area and Severity Index (PASI 90) and serious adverse events. OUTCOMES: Additional outcomes included quality of life, PASI 75, Physician's Global Assessment of 0/1 and any adverse event. RESULTS: Overall, both NMAs are of high quality and provide a comprehensive summary of the evidence base and treatment effects. Results, in terms of both estimates and rankings, suggest that newer biologics targeting the interleukin (IL)-12/23 and IL-17 axes appear to be more effective than older biologics and oral agents. CONCLUSIONS: Patients, clinicians and policy makers can use the relative efficacy assessments of NMAs to inform decision making regarding the clearance of psoriasis skin lesions at relevant time points and improvement in quality of life.