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[Display omitted] Early-onset atopic dermatitis is a strong risk factor for food allergy, suggesting that early effective treatment may prevent transcutaneous sensitization. This study tested whether enhanced treatment of atopic dermatitis to clinically affected and unaffected skin is more effective in preventing hen's egg allergy than reactive treatment to clinically affected skin only. This was a multicenter, parallel-group, open-label, assessor-blind, randomized controlled trial (PACI [Prevention of Allergy via Cutaneous Intervention] study). This study enrolled infants 7-13 weeks old with atopic dermatitis and randomly assigned infants in a 1:1 ratio to enhanced early skin treatment or conventional reactive treatment using topical corticosteroids (TCSs). The primary outcome was the proportion of immediate hen's egg allergy confirmed by oral food challenge at 28 weeks of age. This study enrolled 650 infants and analyzed 640 infants (enhanced [n = 318] or conventional [n = 322] treatment). Enhanced treatment significantly reduced hen's egg allergy compared with the conventional treatment (31.4% vs 41.9%, P =.0028; risk difference: –10.5%, upper bound of a 1-sided CI: –3.0%), while it lowered body weight (mean difference: –422 g, 95% CI: –553 to –292 g) and height (mean difference: –0.8 cm, 95% CI: –1.22 to –0.33 cm) at 28 weeks of age. This study highlighted the potential of well-controlled atopic dermatitis management as a component of a hen's egg allergy prevention strategy. The enhanced treatment protocol of this trial should be modified before it can be considered as an approach to prevent hen's egg allergy in daily practice to avoid the adverse effects of TCSs. After remission induction by TCSs, maintenance therapy with lower potency TCSs or other topical therapies might be considered as alternative proactive treatments to overcome the safety concerns of TCSs. [ABSTRACT FROM AUTHOR]

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool. [ABSTRACT FROM AUTHOR]

Background: Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema patients in routine clinical care.Objectives: Prioritize outcome domains to measure atopic eczema in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain.Methods: An online survey of HOME members identified and ranked 21 possible health domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality.Results: Patient-reported symptoms was the top-prioritized domain. In accordance with psychometric properties and feasibility, there was consensus that the recommended instruments to measure atopic eczema symptoms in clinical practice are the POEM, the PO-SCORAD index, or both. The numeric rating scale for itch received support pending definition and validation in atopic eczema.Conclusion: Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD index, or both for measuring atopic eczema symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings. [ABSTRACT FROM AUTHOR]

Atopic eczema onset is described primarily in early childhood, and the frequency and characteristics of adult-onset disease remain controversial. We sought to determine the proportion of subjects who report atopic eczema symptoms between birth and midadulthood and to examine demographic, immunologic, and genetic factors associated with period of symptom onset. We conducted a longitudinal study using data from 2 nationally representative community-based birth cohorts from the United Kingdom: the British Cohort Studies 1958 and 1970. Subjects were followed from birth through age 42 to 50 years. The primary outcome was the age period of self-reported atopic eczema symptom onset based on repeated measures of self-reported atopic eczema at each survey wave. The annual period prevalence of atopic eczema ranged from 5% to 15% in 2 cohorts of more than 17,000 participants each followed from birth through middle age. There was no clear trend in prevalence by age, and among adults reporting active atopic eczema during a given year, only 38% had symptom onset reported in childhood. When compared with subjects whose eczema started in childhood, those with adult-onset disease were more likely to be women, from Scotland or Northern England, of lower childhood socioeconomic group, smokers in adulthood, and less likely to have a history of asthma. In a subanalysis using data from the 1958 cohort only, genetic mutations previously associated with atopic eczema, including filaggrin-null mutations, and allergen-specific IgE were more common among those with childhood-onset disease. Rates of self-reported atopic eczema remain high after childhood, and adult-onset atopic eczema has different risk factor associations than childhood-onset eczema. [ABSTRACT FROM AUTHOR]

Background: Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment.Objective: We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG.Methods: This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence.Results: Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence.Limitations: Our study did not include a randomized comparator.Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone. [ABSTRACT FROM AUTHOR]

Background: Investigators often use global assessments to provide a snapshot of overall disease severity in dermatologic clinical trials. Although easy to perform, the frequency of use and standardization of global assessments in studies of atopic dermatitis (AD) is unclear.Objectives: We sought to assess the frequency, definitions, and methods of analysis of Investigator Global Assessment in randomized controlled trials of AD.Methods: We conducted a systematic review using all published randomized controlled trials of AD treatments in the Global Resource of Eczema Trials database (2000-2014). We determined the frequency of global scales application and defining features.Results: Among 317 trials identified, 101 trials (32%) used an investigator-performed global assessment as an outcome measure. There was large variability in global assessments between studies in nomenclature, scale size, definitions, outcome description, and analysis. Both static and dynamic scales were identified that ranged from 4- to 7-point scales. North American studies used global assessments more commonly than studies from other countries.Limitations: The search was restricted to the Global Resource of Eczema Trials database.Conclusion: Global assessments are used frequently in studies of AD, but their complete lack of standardized definitions and implementation preclude any meaningful comparisons between studies, which in turn impedes data synthesis to inform clinical decision-making. Standardization is urgently required. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence. [ABSTRACT FROM AUTHOR]

Background Atopic dermatitis (atopic eczema) is a chronic inflammatory skin disease that has reached epidemic proportions in children worldwide and is increasing in prevalence. Because of the significant socioeconomic effect of atopic dermatitis and its effect on the quality of life of children and families, there have been decades of research focused on disease prevention, with limited success. Recent advances in cutaneous biology suggest skin barrier defects might be key initiators of atopic dermatitis and possibly allergic sensitization. Objective Our objective was to test whether skin barrier enhancement from birth represents a feasible strategy for reducing the incidence of atopic dermatitis in high-risk neonates. Methods We performed a randomized controlled trial in the United States and United Kingdom of 124 neonates at high risk for atopic dermatitis. Parents in the intervention arm were instructed to apply full-body emollient therapy at least once per day starting within 3 weeks of birth. Parents in the control arm were asked to use no emollients. The primary feasibility outcome was the percentage of families willing to be randomized. The primary clinical outcome was the cumulative incidence of atopic dermatitis at 6 months, as assessed by a trained investigator. Results Forty-two percent of eligible families agreed to be randomized into the trial. All participating families in the intervention arm found the intervention acceptable. A statistically significant protective effect was found with the use of daily emollient on the cumulative incidence of atopic dermatitis with a relative risk reduction of 50% (relative risk, 0.50; 95% CI, 0.28-0.9; P = .017). There were no emollient-related adverse events and no differences in adverse events between groups. Conclusion The results of this trial demonstrate that emollient therapy from birth represents a feasible, safe, and effective approach for atopic dermatitis prevention. If confirmed in larger trials, emollient therapy from birth would be a simple and low-cost intervention that could reduce the global burden of allergic diseases. [ABSTRACT FROM AUTHOR]

The lack of core outcome sets for atopic eczema (AE) is a major obstacle for advancing evidence-based treatment. The global Harmonising Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE trials. This article deals with the standardization of measurement instruments to assess clinical signs of AE. To resolve the current lack of standardization of the assessment of clinical signs of AE, we followed a structured process of systematic reviews and international consensus sessions to identify 1 core outcome measurement instrument for assessment of clinical signs in all future AE trials. Systematic reviews indicated that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis (SCORAD) index were identified as extensively validated. The EASI has adequate validity, responsiveness, internal consistency, and intraobserver reliability. The objective SCORAD index has adequate validity, responsiveness, and interobserver reliability but unclear intraobserver reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that the EASI is the preferred core instrument to measure clinical signs in all future AE trials. All stakeholders involved in designing, reporting, and using clinical trials on AE are asked to comply with this consensus to enable better evidence-based decision making, clearer scientific communication, and improved patient care. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a common and chronic, pruritic inflammatory skin condition that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this second of 4 sections, treatment of atopic dermatitis with nonpharmacologic interventions and pharmacologic topical therapies are reviewed. Where possible, suggestions on dosing and monitoring are given based on available evidence. [Copyright &y& Elsevier]

Atopic dermatitis (AD) is a chronic, pruritic, inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in the management and care of AD, providing updated and expanded recommendations based on the available evidence. In this first of 4 sections, methods for the diagnosis and monitoring of disease, outcomes measures for assessment, and common clinical associations that affect patients with AD are discussed. Known risk factors for the development of disease are also reviewed. [Copyright &y& Elsevier]

Background: Eczema prevention is now an active area of dermatologic and allergy research. Defining an incident case is therefore a prerequisite for such a study. Objective: We sought to examine how an incident case of atopic dermatitis was defined in previous atopic dermatitis prevention studies in order to make recommendations on a standard definition of new atopic dermatitis cases for use in future prevention trials. Methods: We conducted a systematic review of controlled interventional atopic dermatitis prevention studies by using searches of MEDLINE and Cochrane databases for studies published from 1980 to the end of January 2011. Studies that included atopic dermatitis as a secondary outcome, such as asthma prevention trials, were included. Results: One hundred two studies were included in the final analysis, of which 27 (26.5%) did not describe any criteria for defining an incident case of atopic dermatitis. Of the remaining 75 studies with reported disease criteria, the Hanifin-Rajka criteria were the most commonly used (28 studies). A disease definition unique to that particular study (21 studies) was the second most commonly used disease definition, although the sources for such novel definitions were not cited. Conclusions: The results from this systematic review highlight the need for improved reporting and standardization of the definition used for an incident case in atopic dermatitis prevention studies. Most prevention studies have used disease definitions such as the Hanifin-Rajka criteria that include disease chronicity. While acceptable for cumulative incidence outcomes, inclusion of disease chronicity precludes the precise measurement of disease onset. We propose a definition based on existing scientific studies that could be used in future prospective studies. [ABSTRACT FROM AUTHOR]

Randomized controlled clinical trials remain the best method for minimizing bias when evaluating dermatological treatments. Many dermatologic clinical trials have suffered from small sample sizes, selective reporting of outcomes, publication bias, poor reporting, and heterogeneous outcomes that have hampered comparability-deficiencies that can be overcome by adopting good trial planning and reporting practice encouraged by this journal. Although a profusion of explanatory placebo-controlled studies have contributed little to decision making in the clinical setting, some comparative effectiveness trials such as the use of topical corticosteroids for pemphigoid may have played a pivotal role in improving the well-being of dermatological patients. Systematic reviews (SRs) of clinical trials strive to organize the entire body of evidence while minimizing bias so that policy makers and guideline developers can base their recommendations on the appropriate strength and level of evidence. In dermatology, SRs, such as those undertaken by the Cochrane Collaboration, have produced clear clinical messages despite conflicting individual studies, and also play a key role in identifying research gaps. Future challenges include optimizing the use of research resources, adopting methodological developments in health technology assessment, and prospective registration and complete reporting of all study results. [ABSTRACT FROM AUTHOR]

Background: The association between allergic sensitization and eczema has been debated for years. Objective: We sought to determine and compare the strength of the association between allergen skin sensitization and eczema in both developing and industrialized countries. Methods: Twenty-eight thousand five hundred ninety-one randomly selected 8- to 12-year-old schoolchildren in 20 countries were physically examined for flexural eczema and received skin prick testing to Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat hair, Alternaria tenuis, mixed tree and grass pollen, and allergens of local relevance. Results: The age- and sex-adjusted odds ratios (ORs) for a positive association between flexural eczema and atopy ranged between 0.74 (95% CI, 0.31-1.81) and 4.53 (95% CI, 1.72-11.93), with a significantly stronger association in affluent compared with nonaffluent countries (combined age- and sex-adjusted ORaffluent = 2.69 [95% CI, 2.31-3.13] and ORnonaffluent = 1.17 [95% CI, 0.81-1.70]). The combined population attributable fraction for atopy in flexural eczema was 27.9% for affluent and 1.2% for nonaffluent-country centers. Correlating gross national per-capita income with either ORs or population attributable fractions for atopy in flexural eczema confirmed a highly significant positive association (P = .006 and P < .001, respectively). Conclusions: The association between atopy and flexural eczema is weak and more variable than previously suggested, and the strength of this association is positively linked to gross national income. [Copyright &y& Elsevier]

Background: Valid and reliable outcome measurements are a prerequisite for evidence-based practice. The comparative validity and reliability of outcome measurements for assessing atopic eczema (AE) severity is unclear. Objective: We sought to assess the validity, reliability, sensitivity to change, and ease of use of outcome measurements for AE. We also sought to give recommendations on which outcomes to use in clinical research and for clinical monitoring. Methods: We performed a systematic review and survey of clinical experts and patients. Results: Twenty published outcome measurements were identified. There is evidence of adequate construct validity for 3 measurements (Severity Scoring of Atopic Dermatitis index [SCORAD], Eczema Area and Severity Index [EASI], and Three Item Severity Score), adequate internal consistency of 1 scale (Patient-oriented Eczema Measure [POEM]), adequate interobserver reliability of 5 measurements (Basic Clinical Scoring System; Nottingham Eczema Severity Score; Objective Severity Assessment of Atopic Dermatitis; Six Area, Six Sign Atopic Dermatitis severity score; and SCORAD), adequate test-retest reliability of 1 scale (POEM), and adequate sensitivity to change of 3 measurements (EASI, SCORAD, and Investigators'' Global Atopic Dermatitis Assessment). Most outcome measurements have adequate content validity, as assessed by patients and experts. Data on the time to perform the assessment was identified for 8 outcome measurements. Only SCORAD, EASI, and POEM have been tested sufficiently and performed adequately. Conclusion: There are too many published outcome measures for AE. Most have not been tested properly or perform adequately when tested, and their continued use hampers scientific communication. Clinical implications: Only SCORAD, EASI, and POEM currently perform adequately. These scales should be used in future studies. [Copyright &y& Elsevier]

When discussing treatment options with patients, clinicians often use terms such as “frequently” or “rarely” when referring to potential benefits or possible harms. Quantitative measurements of treatment benefits and harms derived from randomized clinical trials or meta-analysis such as odds ratios or risk reduction are more precise terms, yet physicians and their patients find them difficult to understand and they are not, therefore, commonly used in clinical practice. To overcome the lack of intuitiveness for traditional measures of risk estimates derived from clinical trials, the number needed to treat (NNT) has been widely recommended as a measure of effectiveness, and number needed to harm as a way of describing risk of possible adverse events. NNT is simply the number of patients who, on average, would need to be treated with a proposed intervention to demonstrate one additional gain over the standard comparator intervention. NNT is an absolute measure and it is calculated as the inverse of the absolute risk reduction. In this article we describe the usefulness and limits of the NNT with particular reference to dermatology, and compare NNT with other relative measures such as the relative risk and relative risk reduction. [Copyright &y& Elsevier]

The article reflects the opinion of the author on the importance of systematic reviews in clinical dermatology in research and publication. Significant reviews are crucial in medical researches, since it can save both lives and resources. Moreover, the author stated that proper application of metaanalysis in published and unpublished researches could create a more precise estimate of treatment effect to make small but clinically important effects become apparent among conflicting singular trial.

The article provides information on the scientific concepts underlying pragmatic clinical trials in dermatology. It discusses the objectives of pragmatic clinical trials and its comparison to explanatory clinical trials, limitations of pragmatic clinical trials, and the use of the Pragmatic-Explanatory Continuum Indicator Summary tool.

The author discusses the significance of democratizing randomized clinical trials (RCTs) in the field of dermatology in Great Britain. He explains that RCTs are essential in assessing the efficacy of skin disease treatment but its usefulness is limited in the quality of design and reporting and the clinical question that the trials address. He cites that the challenges can be addressed by forming a network of like-minded people such as the UK Dermatology Clinical Trials Network (UK DCTN).

Cleverly using records obtained from the 2003 National Survey of Children's Health (NSCH), Shaw et al. provide a pioneering glimpse into the burden of eczema across the United States. Using parental reports of a doctor's diagnosis of eczema in the past 12 months, the authors show that eczema affects around 9-18% of children age 17 and under. The study confirms reported associations such as living in metropolitan areas, higher household education level, and black ethnicity. Novel findings include the demonstration of higher eczema prevalence along the East Coast. The study correlates well with previous reports and may help point to environmental factors that contribute to the development of eczema. [ABSTRACT FROM AUTHOR]

The author reflects on the report which discusses conflicts of interests (COI) in dermatology. He stresses that the author of the report misunderstood two crucial point of the issue by making obscure differences between a circumstance and a behavior. He argues that a COI simply means that a set of conditions is operating that could have a marked influence on behavior, and for the audience to make a judgment on whether such conflicts are relevant that could have resulted in a specific behavior.

The article reports that the International Committee of Medical Journal Editors (ICMJE) is a group of the world's leading medical journals whose participants meet annually to improve standards in manuscripts submitted to biomedical journals. In September 2004, the ICMJE announced a tough new stance on registering clinical trials. All trials that start enrolling participants after July 1, 2005 must register their trial in a suitable publicly accessible register before that date in order to be considered for subsequent publication in those journals.

Background: Pyoderma gangrenosum is a rare inflammatory skin condition. Two prospective studies have evaluated treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks.Objective: Using data from both studies we assessed the predictive value of 3 early predictors for healing at 6 months: speed of healing, Investigator Global Assessment (IGA), and resolution of inflammation, recorded at 2 and 6 weeks.Methods: Logistic regression models were applied and the effectiveness of the 3 measures was assessed through estimating the positive and negative predictive values and the area under the receiver operating characteristic curve.Results: The positive and negative predictive value at 6 weeks were, respectively, 63.5% (95% confidence interval [CI] 52.4%-73.7%) and 74.6% (95% CI 62.5%-84.5%) for speed of healing; 80% (95% CI 68.7%-88.6%) and 74.2% (95% CI 64.1%-82.7%) for IGA; and 72.1% (95% CI 59.9%-82.3%) and 68.1% (95% CI 57.7%-77.3%) for resolution of inflammation. IGA had the best combined positive predictive value, negative predictive value, and area under the receiver operating characteristic curve at 2 and 6 weeks.Limitations: We were limited by data available from existing datasets.Conclusion: Speed of healing, IGA, and resolution of inflammation were all shown to be good predictors of eventual healing of pyoderma gangrenosum. [ABSTRACT FROM AUTHOR]

The article focuses on a scientific look at seasonality of symptom severity in atopic dermatitis (AD). Several papers on AD list a long number of factors that may exacerbate AD, such as stress, heat, irritants, dry skin, infections, allergens, and sweating. Yet, the basis for many of these has not been studied scientifically. Indeed, the objective study of flare factors for AD flares remains one of the major research gaps in the understanding of AD. This is perhaps surprising given that exploration of possible exacerbating or relieving features is such a common discussion point during consultations with many patients and families with AD.

Background Disease burden should be an important component for guiding research funding. Objective We sought to examine the relationship between dermatologic research funded from 2012 to 2013 by the National Institutes of Health (NIH) and US skin disease burden as measured by disability-adjusted life years in the Global Burden of Disease 2010 study. Methods A cross-sectional analysis was independently performed by 2 researchers who matched projects from the 2012 to 2013 NIH Research Portfolio Online Reporting Tools with 15 skin conditions and their respective disability-adjusted life years from Global Burden of Disease 2010. Results The NIH funded 1108 projects spanning the 15 skin conditions. Melanoma received almost half of the total skin condition budget (49.5%). Melanoma, nonmelanoma skin cancer, and leprosy were funded above what would be suggested by their disease burden, whereas dermatitis, acne vulgaris, pruritus, urticaria, decubitus ulcer, fungal skin diseases, alopecia areata, cellulitis, and scabies appeared underfunded. Bacterial skin diseases, viral skin diseases, and psoriasis were well matched with disease burden. Limitations Disease burden is one of many factors that may be used to guide priority-setting decisions. Conclusion Skin disease burden measured by disability-adjusted life year metrics partially correlates with NIH funding prioritization. Comparing US disease burden with NIH funding suggests possible underfunded and overfunded skin diseases. [ABSTRACT FROM AUTHOR]

Background Global Burden of Disease Study is a research database containing systematically compiled information from vital statistics and epidemiologic literature to inform research, public policy, and resource allocation. Objective We sought to compare mortality among conditions with skin manifestations in 50 developed and 137 developing countries from 1990 to 2010. Methods This was a cross-sectional study to calculate mean age-standardized mortality (per 100,000 persons) across countries for 10 disease categories with skin manifestations. We compared differences in mortality from these disorders by time period (year 1990 vs year 2010) and by developing versus developed country status. Results Melanoma death rates were 5.6 and 4.7 times greater in developed compared with developing countries in 1990 and 2010, respectively. Measles death rates in 1990 and 2010 were 345 and 197 times greater in developing countries, and corresponding syphilis death rates were 33 and 45 times greater. Limitations Inability to adjust for patient-, provider-, and geographic-level confounders may limit the accuracy and generalizability of these results. Conclusion The mortality burden from skin-related conditions differs between developing and developed countries, with the greatest differences observed for melanoma, measles, and syphilis. These results may help prioritize and optimize efforts to prevent and treat these disorders. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) treatment is often initiated by symptoms or visible erythema. The role of induction of remission or treatment of inflammation that is not visible is unclear. Objective: We investigated whether (1) the notion of subclinical inflammation is scientifically sound, (2) treatment corrects subclinical inflammation, and (3) different strategies for initial clearance of AD affect long-term disease control. Methods: We conducted a systematic review based on searching MEDLINE, Embase, the Cochrane register of randomized controlled trials, and the Global Resource of Eczema Trials from inception to the end of October 2012. Results: Twenty of 26 included studies presented evidence of subclinical inflammation, with a continuum of changes in skin barrier dysfunction, the proinflammatory cytokine milieu, and lymphocytic infiltration from normal-appearing skin to posttreatment lesional skin to active skin lesions in patients with AD. Such subclinical inflammation is improved, with proactive treatment aimed at maintaining remission. Failure to achieve control of AD symptoms with initial therapy was associated with a higher risk of relapse in 14 randomized controlled trials (fluticasone: risk ratio, 1.31; 95% CI, 1.02-1.68; tacrolimus: risk ratio, 1.36; 95% CI, 1.12-1.66). Three trials on systemic therapy/phototherapy suggested that induction of remission resulted in long-term remission without maintenance therapy in approximately 15% of patients. Conclusion: Induction of remission followed by maintenance therapy might prove to be an integral part of a disease-modifying strategy for treating atopic diseases. [Copyright &y& Elsevier]

The role of autoimmunity in atopic dermatitis (AD) is unclear. We sought to critically examine the occurrence, correlation with severity, and possible causative role of autoreactivity in patients with AD. Our systematic review of studies identified from MEDLINE included 31 experiments that described autoreactivity in patients with AD. We defined autoreactivity as in vitro or in vivo evidence of immune response to autologous human, generic human, or recombinant human proteins or other tissue/cellular components. Autoreactivity prevalence in patients with AD ranged from 23% to 91% in 14 studies involving 2644 participants, although it did not appear to vary with age, sex, or disease duration. In contrast to studies of AD, IgE autoreactivity was not found in healthy subjects or in those with allergic rhinoconjunctivitis, psoriasis, systemic lupus erythematosus, or other inflammatory diseases (8 studies of 816 participants). Two reports found a positive correlation between autoreactivity and AD severity. We suggest that autoreactivity might be playing a causative role in AD based on the magnitude and specificity of the associations found; plausible mechanisms through IgE autoantibodies, IgG autoantibodies, and TH1 autoreactivity; and experimental elicitation of eczematous lesions after provocation. Whether autoantibodies contribute to AD chronicity now needs to be examined in longitudinal studies. [ABSTRACT FROM AUTHOR]

The Global Burden of Disease (GBD) Study 2010 estimated the GBD attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases, we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess, and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine nonfatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases, and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies, and molluscum contagiosum. Collectively, skin conditions ranged from the 2nd to 11th leading cause of years lived with disability at the country level. At the global level, skin conditions were the fourth leading cause of nonfatal disease burden. Using more data than has been used previously, the burden due to these diseases is enormous in both high- and low-income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency. [ABSTRACT FROM AUTHOR]

We assessed completeness of trial registration and the extent of outcome-reporting bias in published randomized controlled trials (RCTs) of eczema (atopic dermatitis) treatments by surveying all relevant RCTs published from January 2007 to July 2011 located in a database called the Global Resource of Eczema Trials (GREAT). The GREAT database is compiled by searching six bibliographic databases, including EMBASE and MEDLINE. Out of 109 identified RCTs, only 37 (34%) had been registered on an approved trial register. Only 18 out of 109 trials (17%) had been registered 'properly' in terms of submitting the registration before the trial end date and nominating a primary outcome. The proportion of 'any registered' and 'properly registered' RCTs increased from 19% and 10% in 2007 to 57% and 36% in 2011, respectively. Assessment of selective outcome-reporting bias was difficult even among the properly registered trials owing to unclear primary outcome description especially with regard to timing. Only 5 out of the 109 trials (5%) provided enough information for us to be confident that the outcomes reported in the published trial were consistent with the original registration. Adequate trial registration and description of primary outcomes for eczema RCTs is currently poor. [ABSTRACT FROM AUTHOR]

A response by Jochen Schmitt, Carsten Flohr, and Hywel C. Williams to a letter to the editor on their article "Core outcome domains for controlled trials and clinical recordkeeping in eczema: international multiperspective Delphi consensus process" in an issue in 2011 is presented.

A letter to the editor in response to the article "The Nature of Clinical Evidence: Floating Currencies Rather than Gold Standards," by J. Rees in the previously published issue is presented.

Core outcome sets (COSs) are consensus-derived minimum sets of outcomes to be assessed in a specific situation. COSs are being increasingly developed to limit outcome-reporting bias, allow comparisons across trials, and strengthen clinical decision making. Despite the increasing interest in outcomes research, methods to develop COSs have not yet been standardized. The aim of this paper is to present the Harmonizing Outcomes Measures for Eczema (HOME) roadmap for the development and implementation of COSs, which was developed on the basis of our experience in the standardization of outcome measurements for atopic eczema. Following the establishment of a panel representing all relevant stakeholders and a research team experienced in outcomes research, the scope and setting of the core set should be defined. The next steps are the definition of a core set of outcome domains such as symptoms or quality of life, followed by the identification or development and validation of appropriate outcome measurement instruments to measure these core domains. Finally, the consented COS needs to be disseminated, implemented, and reviewed. We believe that the HOME roadmap is a useful methodological framework to develop COSs in dermatology, with the ultimate goal of better decision making and promoting patient-centered health care. [ABSTRACT FROM AUTHOR]

Summary: Background: Basal-cell carcinoma is the most common form of skin cancer and its incidence is increasing worldwide. We aimed to assess the effectiveness of imiquimod cream versus surgical excision in patients with low-risk basal-cell carcinoma. Methods: We did a multicentre, parallel-group, pragmatic, non-inferiority, randomised controlled trial at 12 centres in the UK, in which patients were recruited between June 19, 2003, and Feb 22, 2007, with 3 year follow-up from June 26, 2006, to May 26, 2010. Participants of any age were eligible if they had histologically confirmed primary nodular or superficial basal-cell carcinoma at low-risk sites. We excluded patients with morphoeic or recurrent basal-cell carcinoma and those with Gorlin syndrome. Participants were randomly assigned (1:1) via computer-generated blocked randomisation, stratified by centre and tumour type, to receive either imiquimod 5% cream once daily for 6 weeks (superficial) or 12 weeks (nodular), or surgical excision with a 4 mm margin. The randomisation sequence was concealed from study investigators. Because of the nature of the interventions, masking of participants was not possible and masking of outcome assessors was only partly possible. The trial statistician was masked to allocation until all analyses had been done. The primary outcome was the proportion of participants with clinical success, defined as absence of initial treatment failure or signs of recurrence at 3 years from start of treatment. We used a prespecified non-inferiority margin of a relative risk (RR) of 0·87. Analysis was by a modified intention-to-treat population and per protocol. This study is registered as an International Standard Randomised Controlled Trial (ISRCTN48755084), and with ClinicalTrials.gov, number NCT00066872. Findings: 501 participants were randomly assigned to the imiquimod group (n=254) or the surgical excision group (n=247). At year 3, 401 (80%) patients were included in the modified intention-to-treat group. At 3 years, 178 (84%) of 213 participants in the imiquimod group were treated successfully compared with 185 (98%) of 188 participants in the surgery group (RR 0·84, 98% CI 0·78–0·91; p<0·0001). No clear difference was noted between groups in patient-assessed cosmetic outcomes. The most common adverse events were itching (211 patients in the imiquimod group vs 129 in the surgery group) and weeping (160 vs 81). We recorded serious adverse events in 99 (40%) of 249 participants in the imiquimod group and 97 (42%) of 229 in the surgery group had serious adverse events, but none were regarded as related to treatment. 12 (5%) participants in the imiquimod group withdrew because of adverse events compared with four (2%) in the surgery group. Interpretation: Imiquimod was inferior to surgery according to our predefined non-inferiority criterion. Although excisional surgery remains the best treatment for low-risk basal-cell carcinoma, imiquimod cream might still be a useful treatment option for small low-risk superficial or nodular basal-cell carcinoma dependent on factors such as patient preference, size and site of the lesion, and whether the patient has more than one lesion. Funding: Cancer Research UK. [ABSTRACT FROM AUTHOR]

There is wide variation in the use of outcome measures for eczema. We performed a three-stage web-based international Delphi exercise to develop consensus-based sets of core outcome domains for eczema for 'controlled trials' and 'clinical recordkeeping'. A total of 57 individuals from four stakeholder groups (consumers, clinical experts, regulatory agency representatives, and journal editors) representing 13 countries were asked to rate the importance of 19 outcome domains for eczema and to choose which domains should be included in two core sets of outcomes. Forty-six individuals (81%) participated. Participants received standardized feedback, including the group median, interquartile range, and previous responses, and the assessment was repeated in two subsequent rounds. We defined consensus a priori if at least 60% of the members of at least three stakeholder groups, including consumers, recommended domain inclusion in the core set. Consensus was achieved for inclusion of symptoms, physician-assessed clinical signs, and a measurement for long-term control of flares in the core set of outcome domains for eczema trials. We recommend including these three core outcomes in future eczema trials in order to enhance clinical interpretability and to enable meta-analyses across different studies. For recordkeeping, consensus was reached to regularly monitor eczema symptoms in clinical practice. Future work is needed to select which existing or new scales should be used to measure the domains identified as relevant for the core set. [ABSTRACT FROM AUTHOR]