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Summary: Background: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID‐19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT‐PCR) for SARS‐CoV‐2 when performed, and serology was generally not performed. Methods: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID‐19 by using a standardized questionnaire. We report the results for acral manifestations. Results: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18–39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID‐19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT‐PCR‐tested patients were positive for SARS‐CoV‐2, and five of 75 (7%) serology‐tested patients had IgG anti‐SARS‐CoV‐2. Tested/untested patients or those with/without confirmed COVID‐19 did not differ in age, sex, history or acral lesion clinical characteristics. Conclusions: The results of this survey do not rule out that SARS‐CoV‐2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS‐CoV‐2 infection in the large majority of patients with acral lesions during the COVID‐19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID‐19 outbreak.Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present.Most cases did not have COVID‐19 confirmed by reverse transcription polymerase chain reaction (RT‐PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID‐19 lockdown period in France, the majority of patients tested had no evidence of SARS‐CoV‐2 infection.Overall, 70 of 75 patients were seronegative for SARS‐Cov‐2 serology and 114 of 121 patients were negative for SARS‐CoV‐2 RT‐PCR. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID‐19 outbreak.Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present.Most cases did not have COVID‐19 confirmed by reverse transcription polymerase chain reaction (RT‐PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID‐19 lockdown period in France, the majority of patients tested had no evidence of SARS‐CoV‐2 infection.Overall, 70 of 75 patients were seronegative for SARS‐Cov‐2 serology and 114 of 121 patients were negative for SARS‐CoV‐2 RT‐PCR. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: A long‐term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. Objectives: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate‐to‐severe atopic eczema, to assess the long‐term safety risk of these therapies in a routine clinical care setting. Methods: We describe a registry‐embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. Conclusions: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long‐term data on the safety of systemic immunomodulating therapies in patients with atopic eczema.Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long‐term safety profile against established therapies.Large numbers of patients with a long duration of follow‐up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries.We present a protocol for an investigator‐initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate‐to‐severe atopic eczema.This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations. Plain language summary available online [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: In the U.S.A., an Investigator's Global Assessment (IGA) score of ≤ 1 (clear or almost clear skin) has been the standard measure in regulatory outcomes for registration clinical trials in atopic dermatitis (AD), including those supporting the recent approval of dupilumab. Objectives: To evaluate the treatment effect of dupilumab in patients with IGA > 1 at the end of treatment, using other validated outcome measures for AD signs, symptoms and quality of life. Methods: LIBERTY AD SOLO 1 and 2 were two 16‐week, randomized, double‐blind trials enrolling adult patients with moderate‐to‐severe AD (IGA ≥ 3) inadequately controlled with topical treatment. We performed a post hoc analysis in patients receiving dupilumab 300 mg every 2 weeks (q2w) or placebo. Outcome measures in patients with IGA > 1 included Eczema Area and Severity Index (EASI), pruritus numerical rating scale (NRS), affected body surface area (BSA), Patient‐Oriented Eczema Measure (POEM) and Dermatology Life Quality Index (DLQI). The trials were registered at ClinicalTrials.gov: NCT02277743 and NCT02277769. Results: At week 16, 278 of 449 dupilumab q2w‐treated patients (median age 36·0 years) and 396 of 443 placebo‐treated patients had IGA > 1. Among patients with IGA > 1 at week 16, dupilumab significantly improved several outcome measures compared with placebo: EASI (−48·9% vs. −11·3%, P < 0·001), pruritus NRS (−35·2% vs. −9·1%, P < 0·001), affected BSA (−23·1% vs. −4·5%, P < 0·001), POEM score ≥ 4‐point improvement (57·4% vs. 21·0%, P < 0·001) and DLQI score ≥ 4‐point improvement (59·3% vs. 24·4%, P < 0·001). Conclusions: In patients with IGA > 1 at week 16, dupilumab induced statistically significant benefits in multiple validated outcome measures compared with placebo. The IGA ≤ 1 end point significantly underestimates clinically relevant dupilumab treatment effects. What's already known about this topic? An Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin) is considered the regulatory standard for treatment success in trials of patients with atopic dermatitis in the U.S.A.It is currently unknown whether patients receiving dupilumab treatment for moderate‐to‐severe atopic dermatitis derive clinical and quality‐of‐life benefit even if they have an end‐of‐treatment IGA score > 1. What's does this study add? This post hoc analysis of patients with an end‐of‐treatment IGA score > 1 from two randomized, placebo‐controlled trials showed that after 16 weeks of treatment dupilumab significantly improved their outcome measures compared with placebo, including measures of signs, symptoms and quality of life.These results show that the regulatory IGA ≤ 1 end point used in clinical trials significantly underestimates clinically relevant dupilumab treatment effects, underscoring potential limitations of the IGA scale. Linked Comment: de Bruin‐Weller. Br J Dermatol 2019; 181:12–13. 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: This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long‐term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole‐group and small‐group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small‐group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole‐group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long‐term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long‐term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon. [ABSTRACT FROM AUTHOR]

Summary: Background: Genetics discoveries have allowed for a better understanding of capillary malformations (CMs) associated with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. Objectives: To identify clinical and haemodynamic factors associated with leg length discrepancy (LLD) in children with CMs of the lower limbs. Methods: Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inférieur), from children aged 2–12 years old with CMs of the lower limbs. Clinical characteristics were prospectively collected. Haemodynamic factors were measured by an sonographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥ 50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. Results: We analysed data at baseline for 96 children. The mean ± SD age was 5·6 ± 3·1 years; 49 (51%) were male; and 14 (15%) showed LLD. In total, 32 patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies and in one child a diagnosis of Parkes Weber syndrome was made. Only an increased circumference above the knee was more frequent with than without LLD (43% vs. 13%, P = 0·02). In all, 10/79 patients (13%) showed a difference in ABF ≥ 50%: four had LLD. The frequency of differences in ABF ≥ 50% was greater with than without LLD [33% (n = 4/12) vs. 9% (n = 6/67), P = 0·04]. Conclusions: ABF measured by Duplex ultrasonography is a simple, low‐cost and noninvasive complementary examination for help in detecting LLD, with a difference of ≥ 50% possibly associated. [ABSTRACT FROM AUTHOR]

Atopic eczema ( AE) is a common chronic inflammatory skin condition. While many AE treatment options are available, the evidence to support their efficacy varies in depth and quality. In 2000, a National Institute for Health Research ( NIHR) Health Technology Assessment systematic review identified and evaluated existing randomized controlled trials ( RCTs) of AE treatments. To ensure continuing utility, the NIHR commissioned an update to the review. Here, we present an overview of the updated report and its key findings. Systematic reviews and RCTs of AE treatments that included participants with AE (criteria based or diagnosed) were identified using Medline, Embase, CENTRAL, Latin American and Caribbean Health Sciences, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Cochrane Skin Group Specialised Register [searched to 31 August 2013 ( RCTs) and 31 December 2015 (systematic reviews)]. Outcome measures included symptoms, AE severity, quality of life and adverse effects. Study quality was assessed using the Cochrane Collaboration risk of bias tool. Of the 287 new RCTs identified, only 22 (8%) were judged to have a low risk of bias. When combined with RCTs from the previous review ( n = 254), we found 'reasonable evidence of benefit' for corticosteroids, calcineurin inhibitors, Atopiclair®, ciclosporin, azathioprine, ultraviolet radiation and education programmes. Interventions with reasonable evidence of 'no benefit' included some dietary interventions, ion exchange water softeners, multiple daily applications of topical corticosteroids and antibiotic-containing corticosteroids for noninfected AE. Many common treatments lack evidence of efficacy and warrant further evaluation. The evidence base for AE is still hampered by poor trial design and reporting. The trials included in this review were used to establish the Global Resource of EczemA Trials ( GREAT) database. [ABSTRACT FROM AUTHOR]

Background Erythropoietic protoporphyria ( EPP) is a rare metabolic disorder, characterized by photosensitivity, caused by errors of the haem biosynthetic pathway. Avoidance of sun exposure is recommended; however, some patients suggested a paradoxical improvement of symptoms when they move to sunny areas. Objectives In a national French study, we sought to investigate the influence of sun exposure on EPP symptoms. Materials and methods We used a national transversal observational study by questionnaire. Patients were selected from the national record of the Centre Français des Porphyries (French Porphyrias referral centre). Sun exposure level by geographic area was assessed using climate data provided by the French national meteorological service (Météo France). Results Eighty-nine patients were included. We notably observed that 40% of patients declared an improvement in their tolerance of sun exposure after repeated sun exposures. In the more sunny areas, the intensity of the pain was lower ( r = −0·26) and the duration of the sun exposure responsible for flares was longer ( r = 0·39) than in the areas that were less sunny ( P < 0·05). Conclusions This study proposes a benefit of natural progressive sun exposure for patients with EPP. [ABSTRACT FROM AUTHOR]

This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema ( HOME) initiative held in Malmö, Sweden on 23-24 April 2015 ( HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema ( AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure ( POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Clinical Manifestations of Pediatric Psoriasis: Results of a Multicenter Study in the United States," that was published in the previous issue.

Background Obesity is more common in adults with psoriasis than in the general population, but there is a lack of data available regarding this association in children. Objectives To evaluate whether obesity was more common in French children with psoriasis of any clinical type or severity. Methods A multicentre case-control study was performed in 23 French dermatology centres. Children without chronic or genetic inflammatory disease were selected as controls and matched for age, sex and dermatology centre. We used three weight cut-off categories to compare the two groups: overweight, overweight with abdominal obesity and overweight with obesity according to the French Health Authority guidelines. Results A total of 261 children with psoriasis were included. The mean age was 9.8 years, 126 were boys and 135 were girls. Overall, 42.5% of these children had plaque psoriasis and 32.2% had severe psoriasis. There was no difference between the psoriasis and control groups when the frequency of children who were overweight was compared (20·7% in psoriasis group vs. 17·1% in control group; P = 0·18). Overweight with abdominal obesity including obesity (18·4% vs. 10·4%; P = 0·009) and obesity alone (10·0% vs. 3·1%; P = 0·001) were more common in the psoriasis group. Conclusions This study shows that being overweight with abdominal obesity and being obese is more common in children with psoriasis than in controls. The risk factors are the same as those that affect the French general population, i.e. female sex and having a parent who was overweight. The severity and clinical type of psoriasis do not affect overweight and obesity. [ABSTRACT FROM AUTHOR]

This review provides a summary of key findings from 22 systematic reviews on atopic eczema ( AE) published over the 2-year period from January 2012 to 31 December 2013, focusing on prevention and treatment of AE. For an update of systematic reviews on the epidemiology, mechanisms of disease and methodological issues, see Part 1 of this update. Based on current systematic review evidence, the most promising intervention for the prevention of AE is the use of probiotics (and possibly prebiotics) during the late stages of pregnancy and early life. Exposure to household pets, especially dogs, may also be protective, but exclusive breastfeeding for up to 7 months does not confer benefit. The role of vitamin D in preventing AE is currently unclear. Very few of the systematic reviews provided additional evidence for the use of specific treatments for AE. Further research is required to establish the role of desensitization, Chinese herbal medicines, homeopathy and specialist clothing. Nevertheless, there is now clear evidence that evening primrose oil and borage oil are not effective for the treatment of AE. There have been no randomized controlled trials on the use of H1 anti-histamines as monotherapy for the treatment of AE. [ABSTRACT FROM AUTHOR]

This review provides a summary of key findings from nine systematic reviews on atopic eczema ( AE) published over the 2-year period from January 2012 to 31 December 2013, focusing on epidemiology, mechanisms of disease and methodological issues. There is now reasonable evidence to suggest that antibiotic exposure in early life is associated with increased incidence of AE, but delivery by caesarean section is not. The prevalence of AE is increasing in Africa, eastern Asia, western Europe and parts of northern Europe. Autoimmunity may play a part in the development and subsequent severity of AE. For researchers conducting clinical trials and other prospective studies involving patients with AE, the two best-validated scales for capturing objective clinical signs of AE are the Eczema Assessment Severity scale ( EASI) and the objective SCORing Atopic Dermatitis scale (obj SCORAD). For the assessment of quality of life in children aged 0-3 years, the Infant Dermatitis Quality of Life scale ( IDQo L) is reasonably well validated. A standardized definition of an incident case of AE for use in prevention studies is still required. [ABSTRACT FROM AUTHOR]

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure. [ABSTRACT FROM AUTHOR]

Background Aplasia cutis congenita ( ACC) has been associated with all clinical forms of inherited epidermolysis bullosa ( EB), including dominant and recessive dystrophic EB ( DDEB and RDEB). To date, only a few patients with DEB specifically combined with ACC have been described and genotyped and almost all cases represent dominant forms of the condition. Objectives The aim of this study was to describe new mutations of COL7A1 in patients with DEB and ACC and investigate possible genotype-phenotype correlations. Methods Twenty-two patients with DEB and ACC were included among the 123 patients with DEB whose COL7A1 mutations have been identified in the Reference Centre in Nice. Results Seven patients presented a severe generalized RDEB phenotype ( RDEB-sev-gen), while the other 15 suffered from milder phenotypes. We identified 28 mutations in COL7A1, of which nine are novel. Patients with severe phenotypes have mostly mutations leading to premature termination codon ( PTC) and/or splice-site or missense mutations. Patients with the milder phenotypes have mostly glycine or arginine substitutions associated or not with other types of mutations. All amino acid substitutions fell within the carboxyl portion of the triple helix domain ( THD) of collagen VII, close to the THD interruptions. Conclusions Our findings suggest that ACC is a frequent manifestation in patients with DEB irrespective of the severity of the disease, and is due to leg rubbing in utero. In children with a moderate form of DEB with no or moderate skin fragility, a glycine substitution near the THD interruption domain of the collagen VII leading to thermolabile protein could explain this phenomenon. [ABSTRACT FROM AUTHOR]

Background It is not yet known whether the risk of developing atopic dermatitis ( AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a large sample of extremely preterm infants (< 29 weeks' gestation). Objectives To determine whether the risk of AD is influenced by preterm birth. Methods We investigated the relationship between gestational age ( GA) and AD using data from two independent population-based cohorts, including a total of 2329 preterm infants, of whom 479 were born extremely preterm. Results There was a lower percentage of children with AD in the extremely preterm group compared with those born at a greater GA (Epipage cohort, 2-year outcome: 13·3% for 24-28 weeks, 17·6% for 29-32 weeks, 21·8% for 33-34 weeks, P = 0·02; LIFT cohort, 5-year outcome: 11% for 24-28 weeks, 21·5% for 29-32 weeks, 19·6% for 33-34 weeks, P = 0·11). After adjusting for confounding variables, a lower GA (< 29 weeks) was significantly associated with decreased risk of AD in the Epipage cohort [adjusted odds ratio ( aOR) 0·57, 95% confidence interval (CI) 0·37-0·87; P = 0·009] and the LIFT cohort ( aOR 0·41, 95% CI 0·18-0·90; P = 0·03). Conclusions Very low GA (< 29 weeks) was associated with a lower risk of AD compared with higher GA (29-34 weeks) and full-term birth. [ABSTRACT FROM AUTHOR]

Background There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management. Objectives The European TREatment of severe Atopic eczema in children Taskforce ( TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study. Methods Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web-based survey. The multiple-response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema. Results In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first-line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second-line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first-line antibiotic of choice (78·3%). Conclusions In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe. [ABSTRACT FROM AUTHOR]

Lymphomatoid papulosis (LyP) is a rare cutaneous lymphoproliferative disorder in children, which can rarely be associated with a cutaneous or systemic lymphoma. We report a 13-year-old girl who presented with typical LyP and pathological features of subtype A. Six months later, the patient presented with rapidly progressive peripheral and systemic lymphadenopathy. On examination of a lymph-node biopsy, a lymphoid infiltrate negative for anaplastic lymphoma kinase ( ALK) and positive for CD30 was found, suggestive of systemic anaplastic large T-cell lymphoma (S- ALCL). The patient was treated with chemotherapy, followed by allogeneic bone-marrow transplant ( BMT). Over the following 6 years, she presented with biopsy-confirmed LyP relapses with complete cutaneous, peripheral-blood and bone-marrow chimerism. This is only the third reported paediatric association of S- ALCL with LyP to our knowledge, and seems to be the first paediatric case of recurrent relapses of LyP after bone-marrow allograft for S- ALCL with total (100%) cutaneous and bone-marrow chimerism. LyP occurring after allogenic BMT does not appear to be donor-derived. [ABSTRACT FROM AUTHOR]

Backround Propranolol is now widely used to treat severe infantile haemangiomas ( IHs). Very few cases of propranolol-resistant IH ( PRIH) are mentioned in the literature. Objectives To describe the characteristics of PRIHs. Methods A national, multicentre, retrospective, observational study was conducted from February 2011 to December 2011. All patients with PRIH evaluated by the members of the Groupe de Recherche Clinique en Dermatologie Pédiatrique from 1 January 2007 to 1 December 2011 were eligible. Results Among 1130 patients treated with propranolol for infantile haemangioma, 10 (0·9%) had PRIHs. Haemangioma propranolol resistance was observed at all ages during early childhood and at any proliferation stage. Conclusions PRIH is a rare phenomenon that raises questions and merits further investigation. [ABSTRACT FROM AUTHOR]

Summary Background Management of inherited ichthyoses is symptomatic. Despite treatment, skin symptoms have a major impact on patients' quality of life (QoL). Objectives To assess the short- and medium-term efficacy of hydrotherapy on QoL and clinical symptoms of patients with inherited ichthyosis. Methods In this 9-month prospective, open-label, multicentre study, 20 children and 24 adults with ichthyosis were enrolled in several French reference and competence centres, 2 months before undergoing a 3-week treatment with specific hydrotherapeutic management at Avène Hydrotherapy Centre. At baseline (2 months before hydrotherapy), beginning (D0) and end of hydrotherapy (D18), and 3 and 6 months later at the reference and competence centres, patients self-assessed QoL using the Dermatology Life Quality Index (DLQI) or its paediatric version (Children's DLQI), and investigators evaluated ichthyosis severity using a specific clinical ichthyosis score. Results The DLQI scores were significantly improved not only at the end of the hydrotherapy treatment (−56% vs. baseline; mean ± SD 3·59 ± 4·30 at D18 vs. 8·35 ± 5·71 at D0; P < 0·0001), but also at 3 months (−28% vs. baseline; P = 0·01) and 6 months after hydrotherapy (−26% vs. baseline; mean ± SD 5·21 ± 5·11 vs. 6·89 ± 5·38; P = 0·03) (primary criterion). Clinical symptoms were also significantly improved at all post-treatment visits, with a decrease of the mean clinical ichthyosis score by −38% between D0 and D18, by −30% at 3 months and by −31% at 6 months vs. baseline. Conclusions A 3-week treatment at Avène Hydrotherapy Centre provided significant and persisting improvement of QoL and clinical symptoms in patients with inherited ichthyoses. [ABSTRACT FROM AUTHOR]

Summary Background Topical corticosteroids remain the mainstay of atopic dermatitis therapy. Many atopic dermatitis therapeutic failures appear to be attributable to poor adherence to treatment due to topical corticosteroid phobia. Objectives To assess the facets, origins and frequency of fear of topical corticosteroid use among patients with atopic dermatitis. Methods A questionnaire comprising 69 items, generated from information gathered during interviews with 21 patients and 15 health professionals, was given to consecutive patients consulting at the outpatient dermatology departments of five regional university hospitals or with 53 dermatologists in private practice. Results A total of 208 questionnaires were analysed (including 144 from parents and 87 from adult patients, 27 of whom were also parents); 80·7% of the respondents reported having fears about topical corticosteroids and 36% admitted nonadherence to treatment. A correlation was found between topical corticosteroid phobia and the need for reassurance, the belief that topical corticosteroids pass through the skin into the bloodstream, a prior adverse event, inconsistent information about the quantity of cream to apply, a desire to self-treat for the shortest time possible or poor treatment adherence. Topical corticosteroid phobia was not correlated with atopic dermatitis severity. Conclusion Topical corticosteroid phobia is a genuine and complex phenomenon, common among French patients with atopic dermatitis, that has an important impact on treatment compliance. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

The article discusses aspects related to learning disabilities in patients suffering from segmental neurofibromatosis. Topics discussed include demonstration of neurofibromas and complications in paediatrics psoriasis, statistical analysis of patients having learning difficulties, and brain magnetic resonance imaging.

The author argues in favor of dermatoepidemiology that aims to improve people's understanding of skin diseases, has clinical relevance and/or improves patient care and/or disease prevention. Topics discussed include the upside and downside of the hypothesis-generating aspect of epidemiological studies, the impact of the digital revolution on epidemiology, and the role of epidemiology in reporting and interpreting observational research. The future challenges for dermatoepidemiology are cited.

Background Idiopathic facial aseptic granuloma (IFAG) was recently described in a single-centre retrospective study as a skin condition that occurs specifically in childhood. Objectives To improve our epidemiological, clinical and pathological knowledge on IFAG, to search for an infectious aetiology, and to assess therapeutic recommendations. Methods Children presenting with one or several acquired nodules on the face, lasting for at least 1 month, with no evidence of any other recognizable clinical entity such as infantile acne, pilomatrixoma, furuncle, tumour or vascular malformation, were enrolled in a prospective multicentre study from June 2001 to June 2004, involving the main French paediatric dermatology outpatient units. We recorded clinical details about the nodule and its duration, ultrasound study pattern, cultures for bacteria and mycobacteria, and Bartonella henselae and Afipia felis antibody testing. Results Thirty children (17 boys and 13 girls, mean age 3·8 years) were enrolled. Ultrasound studies revealed a solid well-demarcated hypoechoic lesion without calcium deposit. Cultures for bacteria were negative in 70% of cases. Cultures for mycobacteria and cat scratch disease serologies were negative. Antibiotic therapy was ineffective; the lesion healed spontaneously with a mean duration of 11 months. Histological examination, performed in five cases, showed a chronic dermal lymphohistiocytic granuloma with numerous foreign body-type giant cells. Conclusions IFAG is characterized by a painless facial nodule, presenting as a single lesion localized on the cheek, with a prolonged course but spontaneous healing. Oral or local antibiotics are usually ineffective. Regarding the pathophysiology, our study rules out a primary infectious disease, and allows considering IFAG either as a granulomatous process appearing around an embryological residue or as a manifestation to include in the spectrum of granulomatous rosacea in childhood. [ABSTRACT FROM AUTHOR]

Dear Editor, Tumour necrosis factor (TNF) inhibitors are used to treat a range of chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. In two recent large cohorts of patients with inflammatory bowel disease treated with TNF inhibitors ( I n i = 1315), skin infections were the most common dermatological complication, with a prevalence of 12-13-5%.[[1]] Among these patients, 22 cases (1-7%) were labelled as having staphylococcal nasal infection. [Extracted from the article]

The article presents the case of a child patient with severe neonatal-onset pustular psoriasis that is recurrently exacerbated. He also experienced high fever related to complex developmental syndrome such as microcephaly, aortic stenosis and osteomyelitis. He was diagnosed with generalized pustular psoriasis (GPP), which is a severe inflammatory skin disease.

Summary Background There is limited information regarding quality of life in patients with inherited ichthyosis. Objectives To identify factors influencing quality of life in patients with inherited ichthyosis. Methods The study used focus groups and involved adult patients suffering from inherited ichthyosis from three French hospital centres. Group discussions were conducted by two facilitators and were continued until data saturation was reached. The verbatim transcripts were analysed independently by two investigators. Categories considered as key factors in the modulation of quality of life were negotiated until agreement was obtained. Results Data saturation was reached after the fifth group. A total of 25 patients affected by various forms of ichthyosis attended these focus groups. The identified factors influencing quality of life were related to physical health, daily life, relations with others or oneself. However, together with difficulties related to ichthyosis, patients also underlined some positive aspects of the disease and described specific measures used to improve their quality of life. Conclusions This is the first study investigating the different factors that could impact quality of life in patients with ichthyosis. This provides an essential framework from which physicians can develop strategies to improve patient care and quality of life and to develop a specific quality of life questionnaire. [ABSTRACT FROM AUTHOR]

Summary: 特应性湿疹(也称为"特应性皮炎"或简称"湿疹")是一种常见的皮肤病。大多数患有特应性湿疹的人可以通过局部治疗(直接涂抹在皮肤上)来控制湿疹,比如润肤剂和局部皮质类固醇。 然而,一些患有中度至重度疾病的患者,不能用这些疗法很好地治疗疾病。这些人需要使用片剂或注射剂进行全身药物治疗(作用于全身的治疗),以有效减轻他们的症状。 Dupilumab 是一种新的全身性药物 (自 2018 年以来), 用于治疗中度至重度湿疹患者。它已经在美国和欧盟获批用于治疗 12 岁或以上的患者。 为了比较 Dupilumab 与其他全身药物治疗的安全性,研究人员需要所有这些药物在实际应用中的安全性数据。TREAT 登记工作组的登记处收集了所有全身药物治疗特应性湿疹的有效性和安全性的数据。英国、爱尔兰、美国、德国、荷兰、丹麦、瑞典、法国、意大利、西班牙和葡萄牙等国家都参与了 TREAT。所有这些国家都以相同的方式收集数据,因此数据具有可比性。 这篇文章描述了如何使用所有这些国际数据来比较 Dupilumab 与其他全身药物治疗安全性的研究方案。这对医生和患者都很重要,这可以让他们在知情的情况下决定哪种治疗对他们来说是最好的。 本摘要涉及研究: 特应性湿疹的治疗 (TREAT) 登记工作组: 一项针对特应性湿疹患者中 Dupilumab 和其他全身药物疗法的欧洲安全性研究的研究方案 Linked Article: Bosma et al. Br J Dermatol 2020; 182:1423–1429 [ABSTRACT FROM AUTHOR]

Summary: Atopic eczema (also called 'atopic dermatitis' or just 'eczema') is a common skin disease. Most people with atopic eczema can control their eczema with topical therapies (applied directly to the skin) such as emollients and topical corticosteroids. Some people, however, have moderate‐to‐severe disease that cannot be well managed with those therapies. Systemic therapy (acting on the whole body), with tablets or injections, is needed in these people to improve their symptoms effectively. Dupilumab is a new systemic medication (since 2018) for treating people with moderate‐to‐severe eczema. It has been approved both in the U.S.A. and the E.U. for people who are 12 years or older. In order to compare the safety of dupilumab with other systemic therapies, researchers need data on the safety of all those medications in real practice. The registries of the TREAT Registry Taskforce collect data on both the effectiveness and safety of all systemic therapies for atopic eczema. Countries such as the U.K., Ireland, the U.S.A., Germany, the Netherlands, Denmark, Sweden, France, Italy, Spain and Portugal are participating in TREAT. All those countries collect data the same way, so that the data are comparable. This article describes a protocol on how to use all these international data to compare the safety of dupilumab with other systemic treatments. This is important both for physicians and patients, to allow them to make informed decisions on which treatment is best for them. This is a summary of the study: TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema Linked Article: Bosma et al. Br J Dermatol 2020; 182:1423–1429 [ABSTRACT FROM AUTHOR]

The article offers information on a study which deals with atopic eczema (AE) which is the most common chronic inflammatory skin disease. It mentions information on association between AE severity and the likelihood to use emollients and topical steroids. It states that topical steroids and emollients remain the mainstay of treatment but there are many barriers to medication adherence, including topical steroid phobia and the daily burden of complex topical treatments.

Summary: 中重度特应性湿疹 (AE) 常通过光疗(光线治疗)或全身治疗(通过全身发挥作用的药物)来治疗。目前尚无关于这些治疗有效性和安全性的长期数据。为了解决这一问题,应在国家研究注册中收集正在现实生活环境中或曾经在此环境中使用这些治疗的儿童和成人患者的相关数据。理想情况下,这些国家注册应是可以相容的,从而可以合并尽可能多的患者数据,并加以分析(举例而言,这对于发现罕见副作用是必须的)。因此,所有国家都需要以相同方式收集相同的数据。为此,建立了国际特应性湿疹治疗 (TREAT) 注册任务组。它已经标准化了需要测量的项目(例如疾病严重程度、副作用)。这项研究解决了两个剩余问题:如何和何时测量这些项目。为了确定如何测量这些项目(即,使用何种测量工具),作者们使用了来自湿疹结局测量一致化 (HOME) 行动中的推荐意见、相关文献(已发表的科学研究)、德国已有的 AE 注册和专家意见。在多次会议上和通过电子邮件讨论了这些提案。这导致就如何测量已标准化的项目集达成了一致(共识)。通过在线调查解决了何时测量这些项目的问题(随访频率)。就开始治疗后 4 周,后续治疗中每 3 个月一次,停止治疗后每 6 个月一次的最低随访频率达成了共识。完整核心数据集线现已可用,将帮助标准化儿童和成人 AE 患者光疗和全身治疗数据的采集。这将有助于及时回答这些治疗长期有效性和安全性的问题,并改善中重度 AE 患者的治疗。 Linked Article: Vermeulen et al. Br J Dermatol 2019; 181:492–504 [ABSTRACT FROM AUTHOR]

Summary: Moderate‐to‐severe atopic eczema (AE) is often treated with phototherapy (light treatment) or systemic therapy (medication that works throughout the whole body). Long‐term data on effectiveness and safety of these treatments is currently missing. To address this issue, data on paediatric and adult patients who use or used these treatments in a real‐life setting should be collected in national research registries. Ideally, these national registries should be compatible, so that data can be combined and analysed from as many patients as possible (which is needed to find rare side‐effects, for example). Therefore, every country needs to collect the same data in the same way. For this purpose the international TREatment of ATopic eczema (TREAT) Registry Taskforce has been established. It has already standardised which items need to be measured (e.g. disease severity, side effects). This study addresses the two remaining issues: how and when to measure these items. To determine how to measure the items (i.e. which measurement instruments to use), the authors used the recommendations from the Harmonising Outcome Measures for Eczema (HOME) initiative, relevant literature (published scientific studies), an already existing AE registry in Germany, and expert opinions. The proposals were discussed at multiple meetings and via email. This resulted in agreement (consensus) on how to measure the already standardised item‐set. The issue of when to measure the items, the follow‐up frequency, was resolved with an online survey. Consensus was reached on a minimum follow‐up frequency of 4 weeks after starting treatment, then every 3 months whilst on treatment and every 6 months whilst off treatment. A complete core dataset is now available that will help with the standardised collection of data of paediatric and adult AE patients on photo‐ and systemic therapies. This will help, in time, answer questions on the long‐term effectiveness and safety of these treatments and improve care for moderate‐to‐severe AE patients. Linked Article: Vermeulen et al. Br J Dermatol 2019; 181:492–504 [ABSTRACT FROM AUTHOR]

Linked Article: Gerbens et al. Br J Dermatol 2019; 180:790–801 [ABSTRACT FROM AUTHOR]

Summary: Atopic eczema (AE) is sometimes severe enough to need strong medicines, but there is not much information available to help doctors select the right treatment. Published trials of different drugs are difficult to assess because they include carefully selected patients and measure responses in different ways. Data from patients actually using these drugs outside of research trials, collected in a registry, could provide a much better picture of long‐term, real‐life experience, but only if everyone reports their observations in the same terms ("outcome measures"). In this study the international TREatment of ATopic eczema (TREAT) Registry Taskforce conducted an online exercise to agree a minimum set of variables that should be measured and reported to AE registries. An initial list of 119 possible items was sent to 479 participants in 36 countries: mostly doctors but also nurses, researchers, patients, industry and regulatory body representatives; 86% responded, rating each item from 0 (not important) to 9 (critical). The list was whittled down through two further rounds; after each round, a summary of the responses was fed back and participants were invited to either keep or change their original answers. Finally, 42 participants attended a consensus meeting and agreed a core set of 49 baseline items and 20 follow‐up items. Hopefully standardising outcome measures in future trials will fill the current gaps of evidence and improve the care of people with AE. However, as the accompanying editorial points out, agreeing outcome measures is only one of many challenges in developing effective registries. Linked Article: Gerbens et al. Br J Dermatol 2019; 180:790–801 [ABSTRACT FROM AUTHOR]

The authors reflect on the need to validate eczema diagnosis to improve the reliability of epidemiological studies. They reference the article "Assessment of atopic dermatitis using self-report and caregiver report: a multicentre validation study" by JI Silverberg and colleagues which appeared within the issue.

The article discusses research on the use of magnetic resonance imaging (MRI) in children suffering from congenital melanocytic naevi (CMN). Topics covered include the impacts of mutations in neuroblastoma ras gene, extracutaneous symptoms of CMN, and characteristics of neurocutaneous melanosis (NCM). The importance of early central nervous system MRI in children with CMN is also mentioned.

The article offers information on the case of a 31-year-old African woman diagnosed with aquagenic palmoplantar keratoderma (APPK) linked with the features of acrokeratoelastoidosis (AKE). It mentions that thick orthokeratotic hyperkeratosis, acanthosis, and hypergranulosis were shown by a punch biopsy. It notes that the iontophoresis was used to treat the patient.

The article comments on a study by C. H. Lin and colleagues which investigated the link between atopic dermatitis (AD) and type 1 diabetes (T1DM). Topics discussed include the higher incidence of AD in patients with T1DM, the use of Cox proportional hazards regression model to analyze AD risk, and the possibility of the existence of different endophenotypes within the AD and T1DM spectrum.

A letter to the editor is presented in response to the article about the efficiency of ciclosporin in treating Kimura's disease, which appeared within the issue.

A letter to the editor is presented in response to the article about neurofibromatosis 1 (NF1).