Scoping systematic review of treatments for eczema

Background: Eczema is a very common chronic inflammatory skin condition.Objectives: To update the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) systematic review of treatments for atopic eczema, published in 2000, and to inform health-care professionals, commissioners and patients about key treatment developments and research gaps.Data sources: Electronic databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Skin Group Specialised Register, Latin American and Caribbean Health Sciences Literature (LILACS), Allied and Complementary Medicine Database (AMED) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched from the end of 2000 to 31 August 2013. Retrieved articles were used to identify further randomised controlled trials (RCTs).Review methods: Studies were filtered according to inclusion criteria and agreed by consensus in cases of uncertainty. Abstracts were excluded and non-English language papers were screened by international colleagues and data were extracted. Only RCTs of treatments for eczema were included, as other forms of evidence are associated with higher risks of bias. Inclusion criteria for studies included availability of data relevant to the therapeutic management of eczema; mention of randomisation; comparison of two or more treatments; and prospective data collection. Participants of all ages were included. Eczema diagnosis was determined by a clinician or according to published diagnostic criteria. The risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. We used a standardised approach to summarising the data and the assessment of risk of bias and we made a clear distinction between what the studies found and our own interpretation of study findings.Results: Of 7198 references screened, 287 new trials were identified spanning 92 treatments. Trial reporting was generally poor (randomisation method: 2% high, 36% low, 62% unclear risk of bias; allocation concealment: 3% high, 15% low, 82% unclear risk of bias; blinding of the intervention: 15% high, 28% low, 57% unclear risk of bias). Only 22 (8%) trials were considered to be at low risk of bias for all three criteria. There was reasonable evidence of benefit for the topical medications tacrolimus, pimecrolimus and various corticosteroids (with tacrolimus superior to pimecrolimus and corticosteroids) for both treatment and flare prevention; oral ciclosporin; oral azathioprine; narrow band ultraviolet B (UVB) light; Atopiclair™ and education. There was reasonable evidence to suggest no clinically useful benefit for twice-daily compared with once-daily topical corticosteroids; corticosteroids containing antibiotics for non-infected eczema; probiotics; evening primrose and borage oil; ion-exchange water softeners; protease inhibitor SRD441 (Serentis Ltd); furfuryl palmitate in emollient; cipamfylline cream; and Mycobacterium vaccae vaccine. Additional research evidence is needed for emollients, bath additives, antibacterials, specialist clothing and complementary and alternative therapies. There was no RCT evidence for topical corticosteroid dilution, impregnated bandages, soap avoidance, bathing frequency or allergy testing

Epidemiology of atopic dermatitis in adults: Results from an international survey.

Background:There are gaps in our knowledge of the prevalence of adult atopicdermatitis (AD).Objective:To estimate the prevalence of AD in adults and by disease severity.Methods:This international, cross-sectional, web-based survey was performed inthe United States, Canada, France, Germany, Italy, Spain, United Kingdom, andJapan. Adult members of online respondent panels were sent a questionnaire forAD identification and severity assessment; demographic quotas ensured populationrepresentativeness for each country. A diagnosis of AD required subjects to be posi-tive on the modified UK Working Party/ISAAC criteriaandself-report of ever hav-ing an AD diagnosis by a physician. The proportion of subjects with AD whoreported being treated for their condition was determined and also used to estimateprevalence. Severity scales were Patient-Oriented SCORAD, Patient-OrientatedEczema Measure, and Patient Global Assessment.Results:Among participants by region, the point prevalence of adult AD in the over-all/treated populations was 4.9%/3.9% in the US, 3.5%/2.6% in Canada, 4.4%/3.5% inthe EU, and 2.1%/1.5% in Japan. The prevalence was generally lower for males vsfemales, and decreased with age. Regional variability was observed within countries.Severity varied by scale and region; however, regardless of the scale or region, propor-tion of subjects reporting severe disease was lower than mild or moderate disease.Conclusions:Prevalence of adult AD ranged from 2.1% to 4.9% across countries.Severe AD represented a small proportion of the overall AD population regardlessof measure or region

Prevalence of inherited ichthyosis in France: a study using capture-recapture method

International audienceBACKGROUND:Inherited ichthyoses represent a group of rare skin disorders characterized by scaling, hyperkeratosis and inconstant erythema, involving most of the tegument. Epidemiology remains poorly described. This study aims to evaluate the prevalence of inherited ichthyosis (excluding very mild forms) and its different clinical forms in France.METHODS:Capture - recapture method was used for this study. According to statistical requirements, 3 different lists (reference/competence centres, French association of patients with ichthyosis and internet network) were used to record such patients. The study was conducted in 5 areas during a closed period.RESULTS:The prevalence was estimated at 13.3 per million people (/M) (CI95%, [10.9 - 17.6]). With regard to autosomal recessive congenital ichthyosis, the prevalence was estimated at 7/M (CI 95% [5.7 - 9.2]), with a prevalence of lamellar ichthyosis and congenital ichthyosiform erythroderma of 4.5/M (CI 95% [3.7 - 5.9]) and 1.9/M (CI 95% [1.6 - 2.6]), respectively. Prevalence of keratinopathic forms was estimated at 1.1/M (CI 95% [0.9 - 1.5]). Prevalence of syndromic forms (all clinical forms together) was estimated at 1.9/M (CI 95% [1.6 - 2.6]).CONCLUSIONS:Our results constitute a crucial basis to properly size the necessary health measures that are required to improve patient care and design further clinical studies

Strategies for measuring long-term control in atopic dermatitis trials: a systematic review

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardised methods for capturing long-term control of AD. Objective: To identify how long-term control has been captured in published randomised controlled trials (RCTs). Resultswill initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. Methods: Systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of ≥3 months, at least one outcome measure recorded at ≥3 time-points, full paper available, and published in English. Results: 101/ 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%); and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly for trials including flare data (21/52). Medication-use was recorded based on quantity, potency and frequency of application. Limitations: Included RCT data only Conclusion: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes

PTPN11 mosaicism causes a spectrum of pigmentary and vascular neurocutaneous disorders and predisposes to melanoma

Phakomatosis pigmentovascularis (PPV) is a diagnosis which denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement including central nervous system disease, asymmetrical growth and a predisposition to malignancy. Using a tightly phenotyped group and high depth next generation sequencing of affected tissues we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of PPV type III or spilorosea. Within an individual the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to demonstrate that the same variants can cause either the specific pigmentary or vascular phenotypes alone, as well as driving melanoma development within the pigmentary lesion. Protein conformational modelling highlights that while variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modelling of the missense variants confirms downstream MAPK pathway overactivation, and widespread disruption of human endothelial cell angiogenesis. Importantly, PTPN11-mosaic patients theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of naevus spilus and capillary malformation syndromes, paving the way for better clinical management

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council

BackgroundAlthough most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking.ObjectiveTo guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient.MethodsA subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion.ResultsWe recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy.LimitationsOur work is a consensus statement, not a systematic review.ConclusionThe decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies

Priority research questions in atopic dermatitis : an International Eczema Council eDelphi consensus

Recent advances in understanding the complex pathogenesis of atopic dermatitis (AD, also known as eczema or atopic eczema), coupled with the development of new treatments, have led to increased interest from multiple stakeholders. There is a need to prioritize areas for research to inform a coordinated approach to advancing science and patient care

Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation

Purpose By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). Methods We used a multistep process, beginning with a Delphi method involving global experts and subsequently involving non-NF experts, patients, and foundations/patient advocacy groups. Results We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. Criteria for the mosaic forms of these conditions are also recommended. Conclusion The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. It is likely that continued refinement of these new criteria will be necessary as investigators (1) study the diagnostic properties of the revised criteria, (2) reconsider criteria not included in this process, and (3) identify new clinical and other features of these conditions. For this reason, we propose an initiative to update periodically the diagnostic criteria for NF1 and LGSS