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The addition of montelukast to a second-generation H SB 1 sb -antihistamine, in people with CSU whose symptoms are not adequately responsive to H SB 1 sb -antihistamines alone. Prognosis Approximately 45% of people with CSU respond to H SB 1 sb -antihistamines at licensed doses,65 and reports estimate that up to two-thirds of the residual may respond to updosing.50 About two-thirds of those unresponsive to H SB 1 sb -antihistamines respond to omalizumab,66 and a similar, probably different but overlapping, proportion to ciclosporin, although there is less evidence for the latter.67 Of note, the response rates given include partial and complete responses, so full disease suppression may not be achieved in many people with CSU with these treatments alone. The GDG does not recommend routinely offering combinations of two different second-generation H SB 1 sb -antihistamines at the same time to people with CSU, although it was noted that some people may benefit.51 The safety of giving two H SB 1 sb -antihistamines at lower dosages has not been investigated and there is no published evidence on using such combination treatment. B R18 (^) b Consider montelukast, in addition to a second-generation H SB 1 sb -antihistamine, in people whose symptoms are inadequately controlled by standard and increased doses of second-generation H SB 1 sb -antihistamines. B FRR5 b Randomized controlled trials (RCTs) evaluating the safety and efficacy of updosing one second-generation H SB 1 sb -antihistamine compared with using two different second-generation H SB 1 sb -antihistamines at the same time in people with CSU. [Extracted from the article]

Iterative discussions between each dataset custodian and the harmonization bioinformaticians culminate with a dataset-specific mapping document specifying how individual variables will be transformed to the glossary-defined dataset, thus ensuring accurately harmonized data (step 4). Dear Editor, The BIOMarkers in Atopic dermatitis and Psoriasis (BIOMAP) is a large European consortium aiming to advance personalized medicine for atopic dermatitis and psoriasis by identifying biomarkers that predict therapeutic response and disease progression. The BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) glossary: developing a lingua franca to facilitate data harmonization and cross-cohort analyses. [Extracted from the article]

Summary: Background: Clinical practice guidelines (CPGs) play a critical role in standardizing and improving treatment outcomes based on the available evidence. It is unclear how many CPGs are available globally to assist clinicians in the management of patients with skin disease. Objectives: To search for and identify CPGs for dermatological conditions with the highest burden globally. Methods: We adapted a list of 12 dermatological conditions with the highest burden from the Global Burden of Disease (GBD) study 2019. A systematic literature search was done to identify CPGs published between October 2014 to October 2019. The scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) framework. Results: A total of 226 CPGs were included. Melanoma had the greatest representation in the CPGs, followed by dermatitis and psoriasis. Skin cancers had a relatively high CPG representation but with lower GBD disease burden ranking. There was an uneven distribution by geographical region, with resource‐poor settings being under‐represented. The skin disease categories of the CPGs correlated weakly with the GBD disability‐adjusted life‐years metrics. Eighty‐nine CPGs did not have funding disclosures and 34 CPGs were behind a paywall. Conclusions: The global production of dermatology CPGs showed wide variation in geographical representation, article accessibility and reporting of funding. The number of skin disease CPGs were not commensurate with its disease burden. Future work will critically appraise the methodology and quality of dermatology CPGs and lead to the production of an accessible online resource summarizing these findings. What is already known about this topic? Skin‐related diseases are leading causes of disability and disease burden globally.Clinical practice guidelines (CPGs) are important to ensure appropriate standards of care for skin conditions.The number, distribution, accessibility and quality of dermatological CPGs available globally is unknown. What does this study add? This is the first scoping review to describe the distribution of CPGs for common dermatological conditions of highest burden available internationally.Inflammatory skin conditions and skin cancers represent a higher proportion of the number of CPGs produced, largely driven by high‐income countries.Further studies to evaluate the quality of CPGs in dermatology, and the development of CPGs in skin diseases predominantly affecting resource‐poor countries, are needed. Linked Comment: T.E. Sivesind and R.P. Dellavalle. Br J Dermatol 2021; 185:690–691. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: The Global Burden of Disease (GBD) Study provides an annually updated resource to study disease‐related morbidity and mortality worldwide. Objectives: Here we present the burden estimates for atopic dermatitis (AD), including data from inception of the GBD project in 1990 until 2017. Methods: Data on the burden of AD were obtained from the GBD Study. Results: Atopic dermatitis (AD) ranks 15th among all nonfatal diseases and has the highest disease burden among skin diseases as measured by disability‐adjusted life‐years (DALYs). Overall, the global DALY rate for AD in 1990 was 121 [95% uncertainty interval (UI) 65·4–201] and remained similar in 2017 at 123 (95% UI 66·8–205). The three countries with the highest DALY rates of AD were Sweden (327, 95% UI 178–547), the UK (284, 95% UI 155–478) and Iceland (277, 95% UI 149–465), whereas Uzbekistan (85·1, 95% UI 45·2–144), Armenia (85·1, 95% UI 45·8–143) and Tajikistan (85·1, 95% UI 46·1–143) ranked lowest. Conclusions: The global prevalence rate of AD has remained stable from 1990 to 2017. However, the distribution of AD by age groups shows a bimodal curve with the highest peak in early childhood, decreasing in prevalence among young adults, and a second peak in middle‐aged and older populations. We also found a moderate positive correlation between a country's gross domestic product and disease burden. GBD data confirm the substantial worldwide burden of AD, which has remained stable since 1990 but shows significant geographical variation. Lifestyle factors, partially linked to affluence, are likely important disease drivers. However, the GBD methodology needs to be developed further to incorporate environmental risk factors, such as ultraviolet exposure, to understand better the geographical and age‐related variations in disease burden. What is already known about this topic?Atopic dermatitis (AD) is a common skin condition affecting around 20% of children and up to 10% of adults in high‐income countries.There is a sparsity of studies that have taken a truly global approach, in particular among adult populations. What does this study add?We provide the first global map of the burden of AD across age groups, including disability‐adjusted life‐years.This ranks AD 15th among nonfatal diseases overall and top among skin diseases.The burden of AD has remained stable between 1990 and 2017, with the highest prevalence rate seen during early childhood and a second rise from middle age. Plain language summary available online [ABSTRACT FROM AUTHOR]

Accordingly, in 2018 the British Society of Paediatric Dermatology (BSPD) issued unified consensus guidelines for prescribing propranolol for the treatment of IH.4 We undertook a national audit to determine current prescribing patterns 2 years after the publication of this guidance. Ninety-five per cent of respondents agreed that oral propranolol was indicated; 3% considered topical timolol to be the first-line therapy. The aims of the audit were to ascertain indications for the initiation, baseline investigations, dosing and daycare admission rates for the induction of oral propranolol. [Extracted from the article]

Summary: Background: For many years dermatologists have had access to few therapies for patients with moderate‐to‐severe atopic eczema (AE). New promising therapies are entering the market but conventional phototherapies and systemic therapies have more well‐known safety profiles, lower costs and wider availability. Objectives: To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice. Methods: In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use. Results: From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience. Conclusions: This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off‐label therapies are also preferred as first‐line choice of systemic therapy. What is already known about this topic? Varying prescribing practices were found for adult (in the UK) and paediatric (in Northern America and Europe) patients with moderate‐to-severe atopic eczema (AE).Not much is known about the prescription of phototherapy and (off‐label) systemic therapy for adult patients in Europe.Although therapies like dupilumab are promising new treatment modalities, better‐known safety profiles, lower costs and better availability are reasons to improve the evidence profile of conventional systemic therapies like ciclosporin. What does this study add? Prescribing practices of European dermatologists treating adult patients with moderate‐to-severe AE show diversity.Most dermatologists prefer narrowband ultraviolet B as first‐line phototherapy, followed by psoralen plus ultraviolet A as second line.Next to ciclosporin, which is most commonly prescribed, (off‐label) methotrexate and oral corticosteroids are also frequently used as first‐line systemic agents in chronic AE.Lack of personal experience with azathioprine and mycophenolic acid was the most important reason against their prescription. What are the clinical implications of the work? The results from this study might help to improve the experience with, and prescribing of, all available conventional phototherapies and (off‐label) systemic therapies.Guidelines developers might use these results to develop and implement treatment algorithms. Linked Comment:Bruin‐Weller. Br J Dermatol 2020; 183:987–988. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Epidemiological studies indicate that gene–environment interactions play a role in atopic dermatitis (AD). Objectives: To review the evidence for gene–environment interactions in AD aetiology, focusing on filaggrin (FLG) loss‐of‐function mutations. Methods: A systematic search from inception to September 2018 in Embase, MEDLINE and BIOSIS was performed. Search terms included all synonyms for AD and filaggrin/FLG; any genetic or epidemiological study design using any statistical methods were included. Quality assessment using criteria modified from guidance (ROBINS‐I and Human Genome Epidemiology Network) for nonrandomized and genetic studies was completed, including consideration of power. Heterogeneity of study design and analyses precluded the use of meta‐analysis. Results: Of 1817 papers identified, 12 studies fulfilled the inclusion criteria required and performed formal interaction testing. There was some evidence for FLG–environment interactions in six of the studies (P‐value for interaction ≤ 0·05), including early‐life cat ownership, older siblings, water hardness, phthalate exposure, higher urinary phthalate metabolite levels (which all increased AD risk additional to FLG null genotype) and prolonged breastfeeding (which decreased AD risk in the context of FLG null genotype). Major limitations of published studies were the low numbers of individuals (ranging from five to 94) with AD and FLG loss‐of‐function mutations and exposure to specific environmental factors, and variation in exposure definitions. Conclusions: Evidence on FLG–environment interactions in AD aetiology is limited. However, many of the studies lacked large enough sample sizes to assess these interactions fully. Further research is needed with larger sample sizes and clearly defined exposure assessment. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411. What's already known about this topic? Gene–environment interactions are considered important in the aetiology of atopic dermatitis.Loss‐of-function mutations in the gene coding filaggrin (FLG) are the most consistently reported genetic variants for atopic dermatitis.Studies have reported evidence for gene–environment interaction involving FLG and a range of different environmental exposures. What does this study add? There is some evidence for FLG–environment interactions in the aetiology of atopic dermatitis; however, the evidence is limited.Studies lack large enough sample sizes to achieve adequate power in order to assess these interactions fully. Linked Comment: Park and Seo. Br J Dermatol 2020; 183:411. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Several studies have identified an association between water hardness and atopic eczema (AE); however, there is a paucity of longitudinal data in early life. Objectives: To examine whether water hardness is associated with an increased risk of AE and skin barrier dysfunction in infants and to assess effect modification by filaggrin (FLG) loss‐of‐function variants. Methods: We performed a longitudinal analysis of data from infants in the Enquiring About Tolerance (EAT) study, who were enrolled at 3 months and followed up until 36 months of age. Results: Of 1303 infants enrolled in the EAT study, 91·3% (n = 1189) attended the final clinic visit and 94·0% (n = 1225) of participants' families completed the 36‐month questionnaire. In total, 761 (58·4%) developed AE by 36 months. There was no overall association between exposure to harder (> 257 mg L−1 CaCO3) vs. softer (≤ 257 mg L−1 CaCO3) water: adjusted hazard ratio (HR) 1·07, 95% confidence interval (CI) 0·92–1·24. However, there was an increased incidence of AE in infants with FLG mutations exposed to hard water (adjusted HR 2·72, 95% CI 2·03–3·66), and statistically significant interactions between hard water plus FLG and both risk of AE (HR 1·80, 95% CI 1·17–2·78) and transepidermal water loss (0·0081 g m−2 h−1 per mg L−1 CaCO3, 95% CI 0·00028–0·016). Conclusions: There is evidence of an interaction between water hardness and FLG mutations in the development of infantile AE. What's already known about this topic? Several cross‐sectional studies have found an association between domestic water hardness exposure and atopic eczema (AE) risk.Loss‐of‐function mutations in the skin barrier gene filaggrin (FLG) are the strongest genetic risk factor for AE. What does this study add? There was no overall association between AE risk and exposure to harder vs. softer domestic water in a large, well‐phenotyped cohort of infants living in England and Wales followed up at 3–36 months of age.However, infants with at least one FLG loss‐of‐function mutation exposed to harder water have a threefold increased risk of developing AE up to age 36 months compared with infants with wild‐type FLG exposed to softer water. Linked Comment: Arents and Leonardi-Bee. Br J Dermatol 2020; 183:203–204. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey‐coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD – cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy – overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site‐ and skin‐type‐specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence. [ABSTRACT FROM AUTHOR]

Summary: Background: Comparative, real‐life and long‐term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate‐to‐severe atopic eczema (AE) is limited. Such data must come from well‐designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. Objectives: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. Methods: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face‐to‐face consensus meetings, one teleconference and via e‐mail. The frequency of follow‐up visits was determined by an expert survey. Results: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow‐up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. Conclusions: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long‐term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real‐life and long‐term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed.There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries.This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long‐term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice.Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment‐related adverse events that require large patient numbers). Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Evidence of immunomodulatory therapies to guide clinical management of atopic eczema (AE) is scarce, despite frequent and often off‐label use. Patient registries provide valuable evidence for the effects of treatments under real‐world conditions that can inform treatment guidelines, give the opportunity for health economic evaluation and the evaluation of quality of care, as well as pharmacogenetic and dynamic research, which cannot be adequately addressed in clinical trials. Objectives: The TREatment of ATopic eczema (TREAT) Registry Taskforce aims to seek international consensus on a core set of domains and items ('what to measure') for AE research registries, using a Delphi approach. Methods: Participants from six stakeholder groups were included: doctors, nurses, nonclinical researchers, patients, industry and regulatory body representatives. The eDelphi comprised three sequential online rounds, requesting participants to rate the importance of each proposed domain item. Participants could add domain items to the proposed list in round 1. A final consensus meeting was held to ratify the core set. Results: Participants (n = 479) from 36 countries accessed the eDelphi platform, of whom 86%, 79% and 74% completed rounds 1, 2 and 3, respectively. At the face‐to‐face consensus meeting attended by 42 participants the final core set was established containing 19 domains with 69 domain items (49 baseline and 20 follow‐up items). Conclusions: This core set of domains and items to be captured by national AE systemic therapy registries will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. Ultimately, it will provide greater insight into the effectiveness, safety and cost‐effectiveness of photo‐ and systemic immunomodulatory therapies. What's already known about this topic? Evidence of photo‐ and systemic immunomodulatory therapies to guide clinical management for atopic eczema (AE) is scarce, despite frequent and often off‐label use.There is a need to gather long‐term, comparative and real‐life data on the effectiveness, safety and cost‐effectiveness of these therapies beyond the confines of short‐term randomized controlled trials, especially when new biological and small‐molecule therapies are entering clinical practice.Patient registries can provide valuable data to address these issues. What does this study add? By performing an international Delphi exercise, consensus was reached on a core set of domains and items to be captured by national AE patient registries.This core set will standardize data collection and thereby allow direct comparability across registries and facilitate data pooling between countries. What are the clinical implications of this work? Ultimately, this core set will provide greater insight into the effectiveness, safety and cost‐effectiveness of photo‐ and systemic immunomodulatory therapies.This may fill the current gaps of evidence and lead to new guidelines for daily clinical practice, and thereby may contribute to the improvement of the care of children and adults with AE. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors. Methods: This is a narrative review based on a systematic literature search. Conclusions: Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high‐risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma. What's already known about this topic? Atopic dermatitis is a common and highly debilitating chronic inflammatory skin disorder.Immune dysregulation plays a key role, but recent evidence has shifted the focus to skin barrier disruption as the key precursor.Loss‐of‐function mutations in the filaggrin gene are the strongest known genetic risk factor, but there are numerous environmental and immunological factors that influence the disease manifestation and course.The current therapeutic armamentarium is limited to simple lipid‐based barrier‐enhancing emollients, topical anti‐inflammatory agents and systemic immunosuppressive therapies. What does this study add? We review how defects in structural epidermal proteins and environmental factors converge to impair skin barrier function, resulting in increased susceptibility to atopic dermatitis.We explore the impact of the defective skin barrier on immune responses and the skin microbiome, highlighting how the complex interplay between the skin barrier and immune activation determines the response to environmental factors such as allergens and microbes.We outline emerging strategies for treating and preventing atopic dermatitis. Linked Comment:Silverberg. Br J Dermatol 2019; 180:447–448. [ABSTRACT FROM AUTHOR]

Summary: 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. [ABSTRACT FROM AUTHOR]

Summary: Background: Oral systemic immunomodulatory medication is regularly used off‐licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost‐effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children. Objectives: To assess whether there is a difference in the speed of onset, effectiveness, side‐effect profile and reduction in flares post‐treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost‐effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune–metabolic effects of CyA and MTX. Methods: Multicentre, parallel group, assessor‐blind, pragmatic RCT of 36 weeks' duration with a 24‐week follow‐up period. In total, 102 children aged 2–16 years with moderate‐to‐severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg−1 per week) or CyA (4 mg kg−1 per day). Results: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o‐SCORAD) and time to first significant flare following treatment cessation. Conclusions: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice. What's already known about this topic? Oral systemic immunomodulatory medication is regularly used off‐licence in children with severe atopic eczema.Ciclosporin is the commonest first‐line systemic agent used in this context, but methotrexate has emerged as an important therapeutic alternative.There is currently no adequately powered randomized controlled trial that compares both treatments in children. What does this study add? The TREatment of severe Atopic eczema Trial (TREAT) addresses this gap and compares the effectiveness, safety, cost‐effectiveness and impact on patient's quality of life of these two drugs.TREAT also examines the effects of both drugs using systemic and cutaneous markers of inflammation and the effect of filaggrin (FLG) genotype and T‐cell cytokine signatures on treatment response.Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

AI can refer to either machine learning or deep learning.1 The potential for AI and machine learning to improve the management of skin diseases is immense. Artificial intelligence (AI) can be defined simply as the ability of computers to simulate intelligent human behaviour. [Extracted from the article]

If a trial registration number could not be identified, the trial intervention was searched for on ICTRP. A limitation is that our sample is not representative of all dermatology RCTs: we assessed a single year, did not include all dermatology journals, and did not include RCTs published in general medical journals. Comparison of clinical trial changes in primary outcome and reported intervention effect size between trial registration and publication. [Extracted from the article]

Systematic reviews have become an increasingly popular tool to assess best evidence and have an established place at the top of the evidence pyramid, above individual randomized controlled trials (RCTs). Meta-analyses are useful as they provide estimates of effect from more than one study and therefore will have increased statistical power (through larger sample size) and have improved estimates of precision (through smaller standard errors), thus yielding narrower confidence intervals (CIs) for the effect estimate; therefore, the more certain we are that the effect estimate reflects the true effect size. It is important to remember that subgroup and sensitivity analyses are observational associations, not causal, as any observed effect could be due to confounding, bias or chance. [Extracted from the article]

Summary: Background: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations–haemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. Objectives: To provide unified guidelines for the treatment of IH with propranolol. Methods: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face‐to‐face multidisciplinary panel meeting and anonymous voting. Results: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. Conclusions: These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision‐making. [ABSTRACT FROM AUTHOR]

Summary: Case reports and case series remain an important part of journals and are often first to document medical breakthroughs. This article reviews their characteristics, aims and limitations. It provides information on how to increase the validity of the bedside decision‐making process that these studies report, using tools such as validated outcomes and split‐body or n‐of‐1 trials. A section describing tools to improve writing of case reports and case series provides suggestions for detailed reporting and good evaluation of novelty, validity and relevance. It includes general and British Journal of Dermatology‐specific guidance. [ABSTRACT FROM AUTHOR]

Summary: Background: Routinely collected electronic health data obtained for administrative and clinical purposes are increasingly used to study atopic dermatitis (AD). Methods for identifying AD patients in routinely collected electronic health data differ, and it is unknown how this might affect study results. Objectives: To evaluate how patients with AD have been identified in studies using routinely collected electronic health data, to determine whether these methods were validated and to estimate how the method for identifying patients with AD affected variability in prevalence estimates. Methods: We systematically searched PubMed, Embase and Web of Science for studies using routinely collected electronic health data that reported on AD as a primary outcome. Studies of localized AD and other types of dermatitis were excluded. The protocol for this review was registered in PROSPERO (CRD42016037968). Results: In total, 59 studies met eligibility criteria. Medical diagnosis codes for inclusion and exclusion, number of occasions of a code, type of provider associated with a code and prescription data were used to identify patients with AD. Only two studies described validation of their methods and no study reported on disease severity. Prevalence estimates ranged from 0·18% to 38·33% (median 4·91%) and up to threefold variation in prevalence was introduced by differences in the method for identifying patients with AD. Conclusions: This systematic review highlights the need for clear reporting of methods for identifying patients with AD in routinely collected electronic health data to allow for meaningful interpretation and comparison of results. [ABSTRACT FROM AUTHOR]

Summary: Background: Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread. Objectives: To reach consensus among an international group of AD experts on the use of systemic corticosteroids for AD. Methods: A survey consisting of statements accompanied by visual analogue scales ranging from ‘strongly disagree’ to ‘neutral’ to ‘strongly agree’ was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if < 30% of respondents marked to the left of ‘neutral’ towards ‘strongly disagree’. Results: Sixty of 77 (78%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe AD under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to the short term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high‐quality published evidence. If more stringent consensus criteria were applied (e.g. requiring < 20% of respondents marking towards ‘strongly disagree’), consensus would have been reached on fewer statements. Conclusions: Based on expert opinion from the IEC, routine use of systemic corticosteroids for AD is generally discouraged and should be reserved for special circumstances. [ABSTRACT FROM AUTHOR]

Critically appraised topics ( CATs) are essential tools for busy clinicians who wish to ensure that their daily clinical practice is underpinned by evidence-based medicine. CATs are short summaries of the most up-to-date, high-quality available evidence that is found using thorough structured methods. They can be used to answer specific, patient-orientated questions that arise recurrently in real-life practice. This article provides readers with a detailed guide to performing their own CATs. It is split into four main sections reflecting the four main steps involved in performing a CAT: formulation of a focused question, a search for the most relevant and highest-quality evidence, critical appraisal of the evidence and application of the results back to the patient scenario. As well as helping to improve patient care on an individual basis by answering specific clinical questions that arise, CATs can help spread and share knowledge with colleagues on an international level through publication in the evidence-based dermatology section of the British Journal of Dermatology. [ABSTRACT FROM AUTHOR]

With the widespread adoption of mobile computing devices and smartphones, most of us are familiar with and expect software updates in technology every few months. The method of updating LSR and living guideline publication will depend on whether new evidence changes the certainty of recommendations. [Extracted from the article]

Background Little is known about U.K. dermatologists' treatment approaches towards adult patients with recalcitrant moderate-to-severe atopic eczema. Objectives We wanted to learn about (i) treatment approaches used for this disease in the U.K.; (ii) factors that influence treatment decisions and (iii) perceived gaps in evidence on treatment safety and efficacy, and priorities for future trials. Methods We conducted an online survey of consultant-level dermatologists in the U.K. Results Sixty-one respondents from over 30 centres reported on management of moderate-to-severe atopic eczema in adults, outwith the context of an acute flare. Phototherapy or psoralen-ultraviolet A was the most common therapeutic modality chosen first line (46%), and this was usually narrowband ultraviolet B. Systemic therapy was chosen as a first-line approach by 36% of dermatologists. Azathioprine was the commonest drug reported being used as first line followed by oral corticosteroids, ciclosporin and methotrexate. Methotrexate was the most common second-line treatment of respondents. The key factors that influenced decision making on the use of phototherapy and systemic agents were the respondent's clinical experience, results of baseline tests (systemic agents) and knowledge of both efficacy and acute and chronic side-effect profiles. The most important evidence gaps identified were the relative effectiveness of treatments, the alternatives to current approaches and the safety of long-term maintenance treatment. With regard to future trials, respondents suggested that priority should be given to studies involving methotrexate. Conclusions While survey study designs have limitations, we found that phototherapy, in particular narrowband ultraviolet B, was respondents' preferred first-line treatment for adults with recalcitrant moderate-to-severe atopic eczema, perhaps reflecting access to, and clinical experience of, this approach. Azathioprine is widely used as a longer-term maintenance treatment. [ABSTRACT FROM AUTHOR]

Background Quality of life (QoL) is one of the core outcome domains identified by the Harmonising Outcome Measures for Eczema (HOME) initiative to be assessed in every eczema trial. There is uncertainty about the most appropriate QoL instrument to measure this domain in infants, children and adolescents. Objectives To systematically evaluate the measurement properties of existing measurement instruments developed and/or validated for the measurement of QoL in infants, children and adolescents with eczema. Methods A systematic literature search in PubMed and Embase, complemented by a thorough hand search of reference lists, retrieved studies on measurement properties of eczema QoL instruments for infants, children and adolescents. For all eligible studies, we judged the adequacy of the measurement properties and the methodological study quality with the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results from different studies were summarized in a best-evidence synthesis and formed the basis to assign four degrees of recommendation. Results Seventeen articles, three of which were found by hand search, were included. These 17 articles reported on 24 instruments. No instrument can be recommended for use in all eczema trials because none fulfilled all required adequacy criteria. With adequate internal consistency, reliability and hypothesis testing, the U.S. version of the Childhood Atopic Dermatitis Impact Scale (CADIS), a proxy-reported instrument, has the potential to be recommended depending on the results of further validation studies. All other instruments, including all self-reported ones, lacked significant validation data. Conclusions Currently, no QoL instrument for infants, children and adolescents with eczema can be highly recommended. Future validation research should primarily focus on the CADIS, but also attempt to broaden the evidence base for the validity of self-reported instruments. [ABSTRACT FROM AUTHOR]

Lichen sclerosus is one of the dermatoses that specifically affects the anogenital skin. It has peaks of incidence in prepubertal girls and postmenopausal women. The objective of this critical appraisal was to review systematically the evidence for efficacy and safety of different treatments. There are no randomized controlled studies of treatment in prepubertal girls and most studies are small case series or case reports. There is little focus on quality of life. [ABSTRACT FROM AUTHOR]

Conventional culture-based studies have suggested that a reduction in microbial exposure in early life predisposes to atopic eczema and allergies. However, molecular microbiological methods have shown that conventional culture fails to grow around 80% of the bacterial flora. More recent work reviewed in this paper has employed next generation sequencing to study the influence of the gut and skin microbiota, both with regard to the risk of developing atopic eczema but also the role of pathogenic and commensal bacteria in established disease. Birth cohorts investigating the gastrointestinal tract reported reduced faecal microbiota diversity among those who later developed atopic eczema, using gel electrophoresis, real-time PCR or 16S ribosomal RNA gene pyrosequencing. However, the inverse association with reduced faecal bacterial diversity was not confirmed in cross-sectional studies among patients with established atopic eczema. Only two studies investigated the cutaneous microbiota in a longitudinal study design and both were unable to provide evidence that Staphylococcus aureus colonisation precedes the development of atopic eczema. Next generation sequencing has confirmed the cross-sectional association between atopic eczema and S. aureus colonisation. The two studies that used this approach have also shown that disease flares are associated with a significant fall in skin microbiota diversity and an increase in the relative abundance of both S. aureus and epidermidis. Interestingly, S. aureus elimination does not appear to be the main reason why atopic eczema improves after a flare and antimicrobial and anti-inflammatory therapy enhances bacterial diversity. Further, well-phenotyped birth cohorts that take key confounders, such as antibiotic exposure, into account are required. [ABSTRACT FROM AUTHOR]

The article discusses a 2019 survey of the treatment of patients with severe chronic spontaneous urticaria (CSU) in Great Britain. Topics covered include the condition's manifestations and usual management, the common use of omalizumab and ciclosporin as first-line agents, and the varying prescriptions of agents by dermatology, allergy, and immunology consultants. Also noted is the prime barrier of potential adverse effects (AE) in prescribing systemic medications.

The article discusses research which examined a randomised controlled trial to assess the effectiveness of oral immunotherapy (OIT) in desensitizing peanut allergy in children. Topics discussed include the potential of food allergen consumption in treating and preventing food allergy and the success of OIT in inducing desensitization in peanut-allergic children.

An introduction to the journal is presented in which the editor discusses the Evidence-Based Dermatology section of the periodical which feature Systematic Reviews, Critically Appraised Research Papers (PPiP), and Critically Appraised Topics (CATs).

A letter to the editor commenting on the study on advances in DNA sequencing technologies on disease gene discovery strategies is presented.

A number of studies have suggested that early life exposure to antibiotics can lead to an increased risk of developing eczema. This systematic review and meta-analysis of observational studies, involving children or young adults aged 0-25 years, assessed the impact of antibiotic exposure either in utero or during the first 12 months of life on subsequent eczema risk. Twenty studies examined the association between prenatal and/or postnatal exposure to antibiotics and development of eczema. The pooled odds ratio ( OR) for the 17 studies examining postnatal antibiotic exposure was 1·41 [95% confidence interval ( CI) 1·30-1·53]. The pooled OR for the 10 longitudinal studies was 1·40 (95% CI 1·19-1·64), compared with a pooled OR of 1·43 (95% CI 1·36-1·51) for the seven cross-sectional studies. There was a significant dose-response association, suggesting a 7% increase in the risk of eczema for each additional antibiotic course received during the first year of life [pooled OR 1·07 (95% CI 1·02-1·11)]. Finally, the pooled OR for the four studies relating to antenatal exposure was 1·30 (95% CI 0·86-1·95). We conclude that exposure to antibiotics in the first year of life, but not prenatally, is more common in children with eczema. [ABSTRACT FROM AUTHOR]

Skin diseases are the fourth most common cause of all human disease, affecting almost one-third of the world's population, yet their burden is often underestimated, despite their visibility.1,2 Burden of disease is a concept that was first developed in the 1990s by the Harvard School of Public Health, the World Bank and the World Health Organization (WHO) to describe death and loss of health due to diseases, injuries and risk factors for all regions of the world. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. [Extracted from the article]

Summary Background Exclusive breastfeeding for at least 4 months is recommended by many governments and allergy organizations to prevent allergic disease. Objectives To investigate whether exclusive breastfeeding protects against childhood eczema. Methods Study subjects comprised 51 119 randomly selected 8- to 12-year-old schoolchildren in 21 countries. Information on eczema and breastfeeding was gathered by parental questionnaire. Children were also examined for flexural eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for each study centre and then pooled across populations. Results There was a small increase in the risk of reported 'eczema ever' in association with 'breastfeeding ever' and breastfeeding < 6 months [pooled adjusted OR 1·11, 95% confidence interval (CI) 1·00-1·22 and OR 1·10, 95% CI 1·02-1·20, respectively]. There was no significant association between reported 'eczema ever' and breastfeeding > 6 months (pooled adjusted OR 1·09, 95% CI 0·94-1·26). Risk estimates were very similar for exclusive breastfeeding < 2 months, 2-4 months and > 4 months and for eczema symptoms in the past 12 months and eczema on skin examination. As for more severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed eczema (pooled adjusted OR 0·71, 95% CI 0·53-0·96), but this effect was lost where children had been exclusively breastfed for > 4 months (pooled adjusted OR 1·02, 95% CI 0·67-1·54). Allergic sensitization and a history of maternal allergic disease did not modify any of these findings. Conclusions Although there was a protective effect of ever having been breastfed on more severe disease, we found no evidence that exclusive breastfeeding for 4 months or longer protects against eczema. Our results are consistent with findings from a recent systematic review of prospective studies. The U.K. breastfeeding guidelines with regard to eczema should be reviewed. Intervention studies are now required to explore how and when solids should be introduced alongside breastfeeding to aid protection against eczema and other allergic diseases. [ABSTRACT FROM AUTHOR]

Summary Aim Hwang et al. aimed to evaluate the risk of malignancy among individuals with eczema, allergic rhinitis (AR) and asthma, compared with the general Taiwanese population. Hypothesis People with atopic conditions, including eczema, have an altered risk of malignancy. Setting and design This was a prospective nationwide cohort study. The authors used the Taiwanese National Health Insurance Research Database (NHIRD) to compare the incidence of cancers among people with established allergic disease relative to the risk in the general population. Study exposure Exposure was the presence of one or more atopic conditions (eczema, AR or asthma). Data were extracted on 997 729 randomly selected people registered on the NHIRD at any time point between 1996 and 2008. Eczema was identified via ICD-9-CM codes with the diagnosis being made by a dermatologist, paediatrician or allergist. Follow-up was until 2008, date of first cancer or death. Outcomes The outcome was a new diagnosis of malignancy, identified via catastrophic illness insurance certificates, again using ICD-9-CM diagnostic codes. Primary outcome measure Standardized incidence ratios (SIRs) for cancers overall and different types of malignancy among patients with eczema, AR or asthma were calculated against the expected number of cancer cases in the general population, adjusted for age and sex. Results The number of patients identified with eczema, AR and asthma was 34 263, 225 315 and 107 601, respectively. Overall cancer rates in patients with these conditions were not significantly different from those in the general population [SIR eczema = 0·97 (95% confidence interval 0·87-1·09), SIR AR = 1·02 (0·98-1·05) and SIR asthma = 1·01 (0·97-1·04)]. However, when the results for eczema were stratified by age, people aged between 20 and 39 years appeared to have a 56% increase in risk in relation to 'any cancer' [SIR = 1·56 (1·13-2·09)]. Looking at individual cancer types in patients with eczema, only the risk of brain cancer was significantly raised [SIR = 2·52 (1·15-4·79)]. Patients who had had all three allergic conditions had a reduced SIR for 'cancers overall' [SIR = 0·59 (0·37-0·88)]. This inverse association was less strong for those with eczema and asthma [SIR = 0·73 (0·55-0·97)] or asthma and AR [SIR = 0·79 (0·73-0·84)] and statistically only of borderline significance for those with eczema and AR [SIR = 0·85 (0·67-1·07)]. Conclusions Hwang et al. conclude that the relationship between allergic diseases and cancer risk is complex and site specific. The risk of malignancy was highest in all atopic conditions in the 20-39-year age group. In patients with eczema, the incidence of brain cancer was higher than expected, which the authors note is at odds with previous studies. However, numbers were too small to allow stratification by histological subtypes. The authors warn against deriving conclusions for rarer cancers and that borderline SIRs must be interpreted with caution. [ABSTRACT FROM AUTHOR]

Filaggrin loss-of-function ( FLG) mutations are associated with eczema and skin barrier impairment, but it is unclear whether skin barrier impairment precedes phenotypic eczema in FLG mutation carriers. To study the association between FLG mutations, skin barrier impairment and clinical eczema at 3 months of age. A total of 88 infants were examined for eczema. Disease severity was determined by the SCORAD eczema severity score. Transepidermal water loss (TEWL) was measured on unaffected forearm skin. Venous blood samples were screened for the four most common FLG mutations found in the U.K. white population (R501X, 2282del4, R2447X and S3247X). Median SCORAD and TEWL measurements in children with and without eczema and FLG mutations were compared. Thirty-three per cent (29/88) of children had clinical eczema. Median SCORAD was 10·6 (range 3·5-31·0). TEWL (g m h) was higher in children with eczema compared with unaffected infants (median TEWL 14·24 vs. 11·24, P < 0·001). Higher TEWL was associated with more severe disease ( r = 0·59, P < 0·001, median TEWL, SCORAD < 15, 13·1 vs. 29·6, SCORAD ≥ 15, P = 0·029). Clinically dry skin was associated with higher TEWL, even in the absence of eczema (median TEWL 17·55 vs. 11·08, P = 0·008). Seventeen per cent (15/88) of children carried at least one FLG mutation. FLG mutation carriers were significantly more likely to have clinically dry skin, even in the absence of eczema [odds ratio (OR) 8·50, 95% confidence interval (CI) 1·09-66·58, P = 0·042]. FLG mutation carriers were also more likely to have eczema by 3 months of age (OR 4·26, 95% CI 1·34-13·57, P = 0·014). FLG mutations were significantly associated with higher median TEWL (all children, FLG'yes' 21·59 vs. FLG'no' 11·24, P < 0·001), even without clinical eczema ( FLG'yes' 15·99 vs. FLG'no' 10·82, P = 0·01). By the age of 3 months, FLG mutations are associated with an eczema phenotype, dry skin and TEWL. The observation that TEWL is elevated in unaffected FLG mutation carriers suggests that skin barrier impairment precedes clinical eczema. [ABSTRACT FROM AUTHOR]

This is a synopsis of the significant research and clinical papers presented at the British Association of Dermatologists meeting held during 7–10 July 2009 in Glasgow, U.K. The conference and satellite symposia highlighted the recent biological, epidemiological and therapeutic advances in dermatology. This report is not meant as a substitute for reading the conference proceedings and related references quoted in this article. [ABSTRACT FROM AUTHOR]

Background Questionnaires are widely used in epidemiological studies to measure eczema symptom prevalence, but there are concerns regarding their accuracy if used as a diagnostic tool. Objectives To compare the performance of a validated eczema symptom questionnaire and a standardized skin examination protocol employed in the second phase of the International Study of Asthma and Allergies in Childhood (ISAAC). Methods A total of 30 358 schoolchildren aged 8–12 years from 18 countries were examined for flexural eczema. Parents also completed an eczema symptom questionnaire. We compared prevalence estimates at the population level based on the questionnaire vs. physical examination. We also compared the skin examination and the ISAAC questionnaire in making a diagnosis of flexural eczema. Results The point prevalences for flexural eczema at centre level based on a single examination were lower than the questionnaire-based 12-month period prevalences (mean centre prevalence 3·9% vs. 9·4%). Correlation between prevalences of both outcome measures was high ( r = 0·77, P < 0·001). At the individual level, questionnaire-derived symptoms of ‘persistent flexural eczema in the past 12 months’ missed < 10% of cases of flexural eczema detected on physical examination. However, between 33% and 100% of questionnaire-based symptoms of ‘persistent flexural eczema in the past 12 months’ were not confirmed on examination. Conclusions ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used. [ABSTRACT FROM AUTHOR]

Linked Editorial:Yiu et al. Br J Dermatol 2020; 183:1–2. [ABSTRACT FROM AUTHOR]

Linked Article: Yiu et al. Br J Dermatol 2020; 183:188–189. [ABSTRACT FROM AUTHOR]

Dear Editor, Research waste is a major issue in atopic eczema.[1] One contributor is the premature discontinuation of trials. Although termination of trials is essential when participants are exposed to harm, many trials terminate for potentially avoidable reasons.[[2]] Such avoidable trial termination presents many issues. Three types of trial status on ClinicalTrials.gov were considered discontinued: trials that commenced recruitment, enrolling participants, but later discontinued ("terminated"); trials that discontinued before commencing recruitment ("withdrawn"); and trials that were active but had not updated the study record for two or more years ("unknown").[4] Trial discontinuation and reported reasons are presented as frequencies and percentages. [Extracted from the article]

Linked Article: van Zuuren et al. Br J Dermatol 2020; 182:1504–1506. [ABSTRACT FROM AUTHOR]

The so-called‘hygiene hypothesis’ postulates an inverse relationship between atopic dermatitis (AD) and an environment that leads to increased pathogen exposure.We sought to systematically identify, summarize and critically appraise: (i) the epidemiological evidence to suggest that environmental exposures that lead to an increase in microbial burden reduce the risk of AD; (ii) whether any specific infections have been shown to reduce AD risk; (iii) whether there is a link between immunizations, use of antibiotics and AD risk; and (iv) to comment on the new therapeutic approaches in AD that have evolved out of the‘hygiene hypothesis’.We searched Medline from 1966 until August 2004 to identify relevant studies for inclusion. Differences in study design and populations did not allow formal meta-analysis. Studies were therefore described qualitatively.We identified 64 studies that were relevant to our review, 27 (42%) of which were of prospective design. There was prospective evidence to support an inverse relationship between AD and endotoxins, early day care and animal exposure. Two well-designed cohort studies have found a positive association between infections in early life and AD, and measles vaccination and AD. Antibiotic use was consistently associated with an increase in AD risk even into the antenatal period, although a few studies did not reach conventional statistical significance. A few small randomized controlled trials have suggested that probiotics can reduce AD severity and that probiotics may also be able to prevent AD to some degree.Although population-based studies have suggested a consistent inverse relationship between AD and increasing family size, this does not seem to be explained by a straightforward increased exposure to a single environmental pathogen. The effect seen with early day care, endotoxin and animal exposure may be due to a nonpathogenic microbial stimulus of a chronic or recurrent nature. This would also explain the risk increase associated with antibiotic use. Caution should prevail in the prescribing of antibiotics early in life, especially in children with a family history of AD. Larger well-designed pragmatic trials on probiotics and the prevention and treatment of AD are now needed to inform whether such interventions should be used in routine clinical practice. [ABSTRACT FROM AUTHOR]

Summary The past three decades have witnessed a marked rise in the prevalence of atopic diseases in industrialized countries and urban centres in less developed regions. This has led to an intense search for aetiological factors that may explain such a pattern. Epidemiological and immunological data suggest the eradication of nonparasitic and endoparasitic infections as possible aetiological elements. This has been formulated as the ‘hygiene hypothesis’, linking a reduced frequency of childhood infections with allergy. So far, most work in this area has focused on asthma. The potential relationship between endoparasites and atopic dermatitis has received much less attention. This paper reviews the scientific literature on the links between atopic dermatitis and endoparasites. At present, there is no clear evidence for a direct relationship between the two. This may be due to the overall small number of studies and insufficient methodological rigour in the existing body of research. [ABSTRACT FROM AUTHOR]

Aim El-Khalawany et al. ( Eur J Pediatr 2012; 172: 351-6) aimed to compare the efficacy and safety of methotrexate vs. ciclosporin in the treatment of children with severe atopic eczema. Setting and design This multicentre, parallel group (ratio 1 : 1), randomized controlled trial was conducted in a secondary care setting in Egypt. Study exposure Children with severe atopic eczema were randomly assigned to receive either methotrexate (7·5 mg weekly) or ciclosporin (2·5 mg kg−1 daily) for 12 weeks, followed by a 12-week follow-up period. Outcomes Eczema severity was measured using the SCORing of Atopic Dermatitis ( SCORAD) index. The authors also recorded the number of patients on each therapy experiencing adverse effects. Primary outcome measures The primary outcome was the mean change in SCORAD after 12 weeks of treatment. Results Forty patients with a mean age of 11·6 ± 1·52 years were included in the trial. At week 12, patients in the methotrexate group had a mean ± SD absolute reduction in SCORAD of 26·25 ± 7·03, compared with 25·02 ± 8·21 in the ciclosporin group ( P = 0·93). Both drugs were associated with minor adverse effects, none of which necessitated changing the treatment regimen. Conclusions El-Khalawany et al. conclude that both methotrexate and ciclosporin in low doses are clinically effective, relatively safe, and well tolerated as treatments for severe atopic eczema in children. [ABSTRACT FROM AUTHOR]

Dear Editor, Studies with statistically significant positive results are more likely to be published than studies with negative or inconclusive results.[1] An example in dermatology were the studies with imiquimod for viral warts, which were "negative" but never published by the funding pharmaceutical companies.[2] Turner I et al i .[3] compared published data with publicly accessible data held by the U.S. Food and Drug Administration (FDA) and found that reporting biases (in particular outcome switching and study publication bias) inflated the effect size of antidepressants by 32%. The data from the literature used in our study were originally extracted as part of the systematic literature searches and data extraction for the 2018 German and European evidence-based guidelines for treatment of psoriasis.[[5]]. [Extracted from the article]

The article presents a case study of a 67-year-old man with psoriasiform lesion on the medial aspect of his right thigh which started out as a birthmark and slowly enlarged. A biopsy showed a dense inflammatory infiltrate in the dermis with granulomas and it was found that the causative organism was Mycobacterium bovis which can be transmitted from cattle to humans. He was treated with rifampicin, ethambutol and isoniazid for two months and the lesion became flatter and softer.