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BackgroundComparative, 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.ObjectivesTo 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.MethodsProposals 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.ResultsA 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.ConclusionsThis 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).

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.

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 Objective To identify clinical characteristics associated with internal neurofibromas in children with NF1, as a means of ensuring the early identification of patients at high risk for malignant peripheral nerve-sheath tumors developed from preexisting internal neurofibromas. Patients and methods We used data from two NF1 populations, in France and North America, respectively. The French database comprised 1083 patients meeting NIH diagnostic criteria for NF1 and the Neurofibromatosis Institute Database of North America comprised 703 patients. Patients younger than 17 years of age were eligible for our study if they had been evaluated for internal neurofibromas using computed tomography and/or magnetic resonance imaging. Clinical characteristics associated with internal neurofibromas by univariate analysis (P ≤ 0.15) were entered into a multiple logistic regression model after checking for potential interactions and confounding. Multiple imputation was used for missing values. Results Among the 746 children in the two databases, 357 (48%) met our inclusion criteria. Their mean age was 7.7 ± 5.0 years and there were 192 (53.8%) males. Internal neurofibromas were present in 35 (9.8%) patients. Internal neurofibromas developed earlier in females than in males and their prevalence increased during adolescence. Factors independently associated with internal neurofibromas were age (OR = 1.16 [1.07-1.27]), xanthogranulomas (OR = 5.85 [2.18-15.89]) and presence of both subcutaneous and plexiform neurofibromas (OR = 6.80 [1.52-30.44]). Conclusions Several easily recognizable clinical characteristics indicate a high risk of internal neurofibromas in children with NF1 and, therefore, a need for very close monitoring.

Abstract Objectives To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas. Patients and methods Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category). Results Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas. Conclusion The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs. Registration details ORPHA86301

In patients with moderate to severe atopic dermatitis (AD) showing an inadequate response to dupilumab 300mg/2weeks, few real-life studies reported the response to alternative regimen maintaining dupilumab. To assess and analyze the response to an increased dose of dupilumab or its combination with cyclosporin A (CsA), methotrexate (MTX), or itraconazole (ITRA), all adult AD patients from 7 French University Hospitals were retrospectively included if they achieved an inadequate response to dupilumab 300mg/2weeks and were subsequently treated with an increased dose of dupilumab (300mg every 7 or 10 days), or a combination of dupilumab 300mg/2weeks with CsA, MTX or ITRA. The response after 3 months, along with epidemiological, clinical, and therapeutic baseline characteristics, were collected. Overall, 68.75% of the 48 included patients achieved an improved response, including 45.8% of complete response (CR). No strategy proved significantly better. Patients showing an initial no response never achieved a further CR versus 52.4% of patients with an initial partial response (p = 0.025). Digestive intolerance and tachycardia led to MTX and ITRA discontinuation in 3 patients. Increasing the dose of dupilumab or combining it with CsA, MTX, or ITRA could be alternative and safe options, to be evaluated in further medico-economic studies., Competing Interests: R Strizzolo reports no competing interest. J Seneschal reports the following competing interests: Principal investigator or consultant or speaker for AbbVie, Almirall, Lilly, Sanofi, LeoPharma, Pierre Fabre, Pfizer; support for attending meetings from AbbVie. A Soria reports the following competing interests: Consultant or speaker for Novartis, Sanofi, LEO Pharma, Abbvie, Lilly, Pfizer and Bioprojet D Staumont-Sallé reports the following competing interests: Investigator, consultant and/or speaker for AbbVie, Almirall, Amgen, Astra-Zeneca, Eli Lilly, Galderma, Leo Pharma, Novartis, Pfizer, Sanofi-Regeneron, UCB. S Barbarot reports the following competing interests: principal investigator, speaker and consultant: Astrazeneca, Almirall, Sanofi-Genzyme, Abbvie, Galderma, Alexion, Novartis, Janssen, Leo-Pharma, Pfizer, Eli Lilly, UCB Pharma, Chiesi. M Viguier reports the following competing interests: travel fees, speaker, consultant and/or board member for Lilly, Abbvie, Janssen-Cilag, Galderma, Boehringer Ingelheim, Novartis, UCB, Nordic, Medac, Bristol Myers Squibb. M Jachiet reports the following competing interests: investigator, consultant and/or speaker for AbbVie, Eli Lilly, Galderma, Leo Pharma, Pfizer, Sanofi-Regeneron. A Nosbaum reports the following competing interests: investigator, consultant and/or speaker for AbbVie, Leo Pharma, Pfizer, Sanofi, Lilly, Medac. A Clément reports the following competing interests: principal investigator, speaker and/or consultant for LeoPharma, Sanofi-Regeneron, Abbvie, Lilly, Janssen. M Tauber reports the following competing interests: principal investigator, speaker and/or consultant for LeoPharma, Sanofi-Regeneron, Abbvie, Lilly, Medac, Almirall, Jenssen, Pfizer. S Mallet reports the following competing interests: principal investigator or sub investigator for Lilly, Sanofi, LeoPharma, consulting fees from Lilly, Sanofi, LeoPharma, Pfizer, speaker for Lilly, Sanofi, LeoPharma, Pfizer, support for attending meetings Lilly, Sanofi, LeoPharma, participation on advisory board: Sanofi, LeoPharma, Pfizer. A Du-Thanh reports the following competing interests: principal investigator, speaker and consultant for LeoPharma, Sanofi, Pfizer, Abbvie, Lilly., (© 2024 The Authors.)

Background: Differences in atopic dermatitis (AD) disease course and manifestation with age may extend to treatment response., Objective: To evaluate response maintenance with continuous-/reduced-dose abrocitinib or withdrawal and response to treatment reintroduction after flare in adolescent and adult participants in JADE REGIMEN (NCT03627767)., Methods: Adolescents (12-17 years) and adults with moderate-to-severe AD responding to abrocitinib 200-mg induction were randomly assigned to 40-week maintenance with abrocitinib (200 mg/100 mg) or placebo. Patients who experienced flare during maintenance received rescue treatment., Results: Of 246 adolescents and 981 adults, 145/246 (58.9%) and 655/981 (66.8%), respectively, responded to induction. Similar proportions of adolescents and adults experienced flare during maintenance with abrocitinib 200 mg (14.9%/16.9%), 100 mg (42.9%/38.9%), and placebo (75.5%/78.0%). From the abrocitinib 200-mg, 100-mg, and placebo arms, respectively, Eczema Area and Severity Index response was recaptured by 28.6%, 25.0%, and 52.9% of adolescents and 34.3%, 33.7%, and 58.0% of adults; Investigator's Global Assessment response, by 42.9%, 50.0%, and 73.5% of adolescents and 34.3%, 50.6%, and 74.1% of adults. Abrocitinib had a similar safety profile regardless of age; nausea incidence was higher in adolescents., Limitations: Adolescents represented 20% of the trial population., Conclusion: Abrocitinib was effective in preventing flare in adolescents and adults.Clinicaltrials.gov listing: NCT03627767.

Background: Patients who completed the originating studies, BREEZE-AD1 (NCT03334396), BREEZE-AD2(NCT03334422), and BREEZE-AD7 (NCT03733301), were eligible for enrollment in the multicenter,phase-3, long-term extension study BREEZE-AD3 (NCT03334435)., Methods: At week 52, responders and partial responders to baricitinib 4 mg were re-randomized (1:1) into the sub-study to dose continuation (4 mg, N = 84), or dose down-titration (2 mg, N = 84). Maintenance of response was assessed from week 52 to 104 of BREEZE-AD3. Physician-rated outcomes included vIGA-AD (0,1), EASI75, and mean change from baseline in EASI. Patient-reported outcomes included DLQI, P OEM total score, HADS, and from baseline: WPAI (presenteeism, absenteeism, overall work impairment, daily activity impairment) and change from baseline in SCORAD itch and sleep loss., Results: With continuous treatment with baricitinib 4 mg, efficacy was maintained up to week 104 in vIGA-AD (0,1), EASI75, EASI mean change from baseline, SCORAD itch, SCORAD sleep loss, DLQI, P OEM, HADS, and WPAI (all scores). Patients down-titrated to 2 mg maintained most of their improvements in each of these measures., Conclusion: The sub-study of BREEZE AD3 supports flexibility in baricitinib dosing regimens. Patients who continued treatment with baricitinib 4 mg and down-titrated to 2 mg maintained improvements in skin, itch, sleep, and quality of life for up to 104 weeks.

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic 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 phakomatosis pigmentovascularis 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 show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism 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 nevus spilus and capillary malformation syndromes, paving the way for better clinical management., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Surgery is a treatment option for neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (PN), but complete resection is often not feasible. Real-world studies are warranted to understand disease burden, progression, and need for medical treatment in patients with inoperable PN. CASSIOPEA was a retrospective study of French pediatric patients (aged ≥3 to <18 years) presenting at a national multidisciplinary team (MDT) review with NF1 and ≥1 symptomatic, inoperable PN. Medical records were reviewed from the time of MDT review and over a follow-up period of up to 2 years. Primary objectives were to describe patient characteristics and target PN-associated therapy patterns. A secondary objective was evolution of target PN-related morbidities. Patients with prior, ongoing, or MDT recommendation of mitogen-activated protein kinase kinase (MEK) inhibitor treatment were excluded. Overall, 78 target PN were identified in 76 patients. At MDT review, median age was 8.4 years, with approximately 30% of patients aged 3-6 years. Target PN were primarily internal (77.3%), and 43.2% were progressive. Target PN location was evenly distributed. 34 target PN had documented MDT recommendations; of these, a majority (76.5%) were for non-medication management, including surveillance. At least one follow-up visit was recorded for 74 target PN. Despite initially being considered inoperable, 12.3% of patients underwent surgery for target PN. At MDT review, most (98.7%) target PN were associated with ≥1 morbidity, primarily pain (61.5%) and deformity (24.4%); severe morbidities were identified in 10.3%. Of 74 target PN with follow-up data, 89.2% were associated with ≥1 morbidity, primarily pain (60.8%) and deformity (25.7%). Of 45 target PN associated with pain, pain improved in 26.7%, was stable in 44.4%, and deteriorated in 28.9%. Deformity improved in 15.8% and remained stable in 84.2% of 19 target PN associated with deformity. None deteriorated. In this real-world study in France, NF1-PN disease burden was considerable, and a considerable proportion of patients were very young. Most patients received only supportive care without medication for target PN management. Target PN-related morbidities were frequent, heterogeneous, and generally did not improve during follow-up. These data highlight the importance of effective treatments that target PN progression and improve disease burden., Competing Interests: Declaration of competing interest PW received consultancy fees from AstraZeneca during the conduct of the study. YC's institution received fees from AstraZeneca during the conduct of the study. MAA has received grants or contracts from Bristol Myers Squibb and Pierre Fabre, payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Bristol Myers Squibb, Pierre Fabre, and Sun Pharma, support for attending meetings and/or travel from Bristol Myers Squibb and Pierre Fabre, and has participated on a Data Safety Monitoring Board or Advisory Board for Sun Pharma. SB has received payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from AstraZeneca, Almirall, Sanofi-Genzyme, AbbVie, Novartis, Janssen, LEO Pharma, Pfizer, Eli Lilly, UCB Pharma, and Chiesi and has also received support for attending meetings and travel from Almirall, Sanofi-Genzyme, AbbVie, and Eli Lilly. CB and TR both report employment at AstraZeneca. AM reports employment at AstraZeneca during the conduct of the study. NEW reports no conflicts of interest. IA has received consulting fees from AstraZeneca and has participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca. Medical writing support for the development of this manuscript, under the direction of the authors, was provided by Emily Clark, of OPEN Health Communications, London, UK and was funded by Alexion, AstraZeneca Rare Disease and Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc., Rahway, NJ, USA, in accordance with Good Publications Practice (GPP 2022) guidelines., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Moderate to severe atopic dermatitis (AD) is associated with a significant disease burden, impacting sleep, quality of life, and treatment needs. The aim of this study was to characterize disease burden and treatment patterns for adults with moderate to severe AD in three European countries: France, Italy, and the UK., Methods: This retrospective analysis of adult patients with moderate to severe AD in Europe used medical records and physician/patient survey data collected in August 2019 to April 2020. Demographic and baseline disease characteristics, information on current comorbidities, disease flares, and current and previous treatments were collected by the physician. Patient-perceived burden was assessed using patient-reported outcome (PRO) questionnaires, which were completed on a voluntary basis and included the following instruments: Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), EuroQol five-dimensional (EQ-5D), and Work Productivity and Activity Impairment (WPAI). Disease severity was subjectively assessed by physicians and was based on their own definition of the terms mild, moderate, and severe. Data were analyzed descriptively., Results: The physician-reported sample included 912 patients with moderate to severe disease from France (n = 314), Italy (n = 309), and the UK (n = 289); approximately 30% of patients provided PRO data. Across these countries, 22-41% of patients reported current flares; mean POEM and DLQI scores were 10.6-13.1 and 9.5-11.1, respectively, indicating a high disease burden. However, systemic therapy use was low (e.g., conventional systemics were used by 18-24% of patients). Physician-assessed disease severity did not fully align with EASI scores, indicating that factors in addition to skin signs are impacting AD severity., Conclusion: Patients with moderate to severe AD report significant disease burden, highlighting unmet treatment needs, particularly with respect to the underuse of systemic treatments despite AD being a systemic disease and the associated disease burden., (© 2022. The Author(s).)

Objectives: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life., Methods: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease., Results: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD., Conclusion: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Indirect treatment comparison was used to compare approved doses of baricitinib and dupilumab for treating adult patients with moderate-to-severe atopic dermatitis (AD) who are candidates for systemic therapy., Methods: Baricitinib and dupilumab were compared (Bucher method) at weeks 4 and 16. Performance in combination with topical corticosteroids (TCS) was analyzed in patients with inadequate response or inadvisable to topical therapies (population A) and cyclosporine (population B). Population A was additionally examined as monotherapy., Results: For the Eczema Area and Severity Index (EASI) 75, baricitinib and dupilumab were similar. A ≥ 4-point improvement in itch numerical rating scale (NRS) was significantly more likely with baricitinib 4 mg than dupilumab in population A as monotherapy (RR = 2.62, 95% CI 1.22, 5.61, p = 0.013) and in TCS combination at week 4. These differences were not significant by week 16. For the Dermatology Life Quality Index (DLQI), baricitinib 4 mg and dupilumab were similar on mean difference in change from baseline (MDcfb), though some differences were seen between baricitinib 2 mg and dupilumab at week 16 for the population A monotherapy (MDcfb = 2.05, 95% CI 0.53, 3.56, p = 0.016) and TCS combination therapy (MDcfb = 2.48, 95% CI 0.46, 4.50, p = 0.016) groups, and in population B (MDcfb = 3.38 95% CI 1.18, 5.58, p = 0.003)., Conclusions: Baricitinib potentially offers more rapid improvement in itch while providing similar efficacy on EASI75 and DLQI outcomes compared with dupilumab., (© 2022. The Author(s).)

Introduction: Atopic dermatitis (AD) can affect multiple body regions and is especially burdensome when involving exposed skin areas. Rapid, effective treatment of AD across body regions remains an unmet need, particularly for difficult-to-treat areas such as the head and neck area. We investigated the temporal and regional patterns of clinical improvement in AD with the use of abrocitinib, an orally available Janus kinase 1 selective inhibitor under development for the treatment of moderate-to-severe AD., Methods: We performed a post hoc analysis of data from JADE COMPARE, a phase 3, multicenter, randomized, double-blind, double-dummy trial that evaluated the efficacy and safety of abrocitinib 200 mg once daily, abrocitinib 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, and placebo in adult patients with moderate-to-severe AD who were concomitantly receiving medicated topical therapy. Assessments included the Eczema Area and Severity Index (EASI) and SCORing Atopic Dermatitis (SCORAD) index., Results: With abrocitinib 200 mg, time to ≥ 75% improvement in EASI (EASI-75) occurred at a median of 29 days across body regions, including the head and neck region. With abrocitinib 100 mg, EASI-75 response was achieved at a median of 30-32 days for the trunk and lower limbs, and at 56-57 days for the head and neck region and upper limbs. With dupilumab, EASI-75 response was achieved at a median of 43 days for the trunk and 57 days for other regions. EASI body region scores significantly improved with abrocitinib 200 mg and 100 mg versus placebo at week 2 (p < 0.0001 for all comparisons). Improvements with abrocitinib were maintained up to week 16., Conclusions: Rapid and persistent improvement in AD across all body regions was observed with abrocitinib treatment. Abrocitinib may be useful in patients with AD that affects difficult-to-treat anatomical areas or who require a rapid response., Trial Registration: Clinicaltrials.gov identifier: NCT03720470., (© 2022. The Author(s).)

Objectives: During the COVID-19 pandemic, numerous cases of chilblains have been reported. However, in most cases, RT-PCR or serology did not confirm SARS-CoV-2 infection. Hypotheses have been raised about an interferon-mediated immunological response to SARS-CoV-2, leading to effective clearance of the SARS-CoV-2 without the involvement of humoral immunity. Our objective was to explore the association between chilblains and exposure to SARS-CoV-2., Methods: In this multicentre case-control study, cases were the 102 individuals referred to five referral hospitals for chilblains occurring during the first lockdown (March to May 2020). Controls were recruited from healthy volunteers' files held by the same hospitals. All members of their households were included, resulting in 77 case households (262 individuals) and 74 control households (230 individuals). Household exposure to SARS-CoV-2 during the first lockdown was categorized as high, intermediate or low, using a pre-established algorithm based on individual data on symptoms, high-risk contacts, activities outside the home and RT-PCR testing. Participants were offered a SARS-CoV-2 serological test., Results: After adjustment for age, the association between chilblains and viral exposure was estimated at OR 3.3, 95% CI (1.4-7.3) for an intermediate household exposure, and 6.9 (2.5-19.5) for a high household exposure to SARS-CoV-2. Out of 57 case households tested, six (11%) had positive serology for SARS-CoV-2, whereas all control households tested (n = 50) were seronegative (p = 0.03). The effect of potential misclassification on exposure has been assessed in a bias analysis., Discussion: This case-control study demonstrates the association between chilblains occurring during the lockdown and household exposure to SARS-CoV-2., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Atopic dermatitis (AD) is a chronic, pruritic, inflammatory disease that occurs most frequently in children but also affects many adults. Social media have become key tools for finding and disseminating medical information., Objective: The aims of this study were to identify the main themes of discussion, the difficulties encountered by patients with respect to AD, the impact of the pathology on quality of life (QoL; physical, psychological, social, or financial), and to study the perception of patients regarding their treatment., Methods: A retrospective study was carried out by collecting social media posts in French language written by internet users mentioning their experience with AD, their QoL, and their treatments. Messages related to AD discomfort posted between July 1, 2010, and October 23, 2020, were extracted from French-speaking publicly available online forums. Automatic and manual extractions were implemented to create a general corpus and 2 subcorpuses depending on the level of control of the disease., Results: A total of 33,115 messages associated with AD were included in the analysis corpus after extraction and cleaning. These messages were posted by 15,857 separate web users, most of them being women younger than 40 years. Tips to manage AD and everyday hygiene/treatments were among the most discussed topics for controlled AD subcorpus, while baby-related topics and therapeutic failure were among the most discussed topics for insufficiently controlled AD subcorpus. QoL was discussed in both subcorpuses with a higher proportion in the controlled AD subcorpus. Treatments and their perception were also discussed by web users., Conclusions: More than just emotional or peer support, patients with AD turn to online forums to discuss their health. Our findings show the need for an intersection between social media and health care and the importance of developing new approaches such as the Atopic Dermatitis Control Tool, which is a patient-related disease severity assessment tool focused on patients with AD., (©Paméla Voillot, Brigitte Riche, Michel Portafax, Pierre Foulquié, Anaïs Gedik, Sébastien Barbarot, Laurent Misery, Stéphane Héas, Adel Mebarki, Nathalie Texier, Stéphane Schück. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.01.2022.)

Food allergy is associated with alterations in the gut microbiota, epithelial barrier, and immune tolerance. These dysfunctions are observed within the first months of life, indicating that early intervention is crucial for disease prevention. Preventive nutritional strategies with prebiotics are an attractive option, as prebiotics such as galacto-oligosaccharides and inulin can promote tolerance, epithelial barrier reinforcement, and gut microbiota modulation. Nonetheless, the ideal period for intervention remains unknown. Here, we investigated whether galacto-oligosaccharide/inulin supplementation during gestation could protect offspring from wheat allergy development in BALB/cJRj mice. We demonstrated that gestational prebiotic supplementation promoted the presence of beneficial strains in the fecal microbiota of dams during gestation and partially during mid-lactation. This specific microbiota was transferred to their offspring and maintained to adulthood. The presence of B and T regulatory immune cell subsets was also increased in the lymph nodes of offspring born from supplemented mothers, suggestive of a more tolerogenic immune environment. Indeed, antenatal prebiotic supplementation reduced the development of wheat allergy symptoms in offspring. Our study thus demonstrates that prebiotic supplementation during pregnancy induces, in the offspring, a tolerogenic environment and a microbial imprint that mitigates food allergy development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Selle, Brosseau, Dijk, Duval, Bouchaud, Rousseaux, Bruneau, Cherbuy, Mariadassou, Cariou, Barbarot and Bodinier.)

Numerous cases of chilblains have been observed in the course if the COVID-19 pandemic. The aims of this study were to provide comprehensive follow-up data for patients reporting chilblains, and to determine the risk factors for incomplete recovery. Patients referred to 5 hospitals in France between March and May 2020 for chilblains were surveyed on December 2020. A teleconsultation was offered. Among 82 patients reporting chilblains, 27 (33%) reported complete recovery, 33 (40%) had recurrences of chilblains after their hands and feet had returned to normal, and 22 (27%) developed persistent acral manifestations, mostly acrocyanosis, with or without further recurrences of chilblains. Most recurrences of chilblains occurred during the following autumn and winter. A past history of chilblains was not associated with recurrences or persistent acral manifestations. Women had a significantly higher risk of developing recurrences or persistent acral manifestations (odds ratio 1.30; 95% confidence interval 1.06-1.59). In conclusion, two-thirds of patients reporting chilblains at the start of the COVID-19 pandemic experienced persistent or recurrent acral manifestations after a 10-month follow-up.

Background: To examine the impact of executive function disorders on health-related quality of life (QoL) in children with neurofibromatosis type 1 (NF1), we conducted a prospective single-center study among 40 children with NF1 aged 8-12 years (mean = 9.7, SD = 1.4) and their parents, comparing them with 56 healthy control children matched for age, sex, parental education level, and handedness. We collected children's self-reports and parents' proxy reports of QoL with the Kidscreen-52 questionnaire, and measured executive functions by combining seven performance-based tests and a daily life questionnaire completed by parents and teachers., Results: Several QoL domains were significantly impaired in the children with NF1, compared with healthy controls, mainly according to their parents' reports (3 out of 9 scales; Cohen's d: 0.57-0.76), with particularly low scores in the social support and peers and school environment domains. Executive function difficulties (Cohen's d: 0.64-1.72) significantly predicted the impairment of QoL domains as perceived by the children or their parents, regardless of the indirect indicators of learning disabilities., Conclusions: Both performance-based executive function scores and behavioral ratings of executive functions in daily life by parents and teachers were associated with low QoL levels in the children with NF1. The school environment and social integration appear to be particularly affected and should therefore be targeted in the management of the disease., (© 2021. The Author(s).)

The gut microbiota is influenced by environmental factors such as food. Maternal diet during pregnancy modifies the gut microbiota composition and function, leading to the production of specific compounds that are transferred to the fetus and enhance the ontogeny and maturation of the immune system. Prebiotics are fermented by gut bacteria, leading to the release of short-chain fatty acids that can specifically interact with the immune system, inducing a switch toward tolerogenic populations and therefore conferring health benefits. In this study, pregnant BALB/cJRj mice were fed either a control diet or a diet enriched in prebiotics (Galacto-oligosaccharides/Inulin). We hypothesized that galacto-oligosaccharides/inulin supplementation during gestation could modify the maternal microbiota, favoring healthy immune imprinting in the fetus. Galacto-oligosaccharides/inulin supplementation during gestation increases the abundance of Bacteroidetes and decreases that of Firmicutes in the gut microbiota, leading to increased production of fecal acetate, which was found for the first time in amniotic fluid. Prebiotic supplementation increased the abundance of regulatory B and T cells in gestational tissues and in the fetus. Interestingly, these regulatory cells remained later in life. In conclusion, prebiotic supplementation during pregnancy leads to the transmission of specific microbial and immune factors from mother to child, allowing the establishment of tolerogenic immune imprinting in the fetus that may be beneficial for infant health outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Brosseau, Selle, Duval, Misme-Aucouturier, Chesneau, Brouard, Cherbuy, Cariou, Bouchaud, Mincham, Strickland, Barbarot and Bodinier.)

Breastmilk is known to be very important for infants because it provides nutrients and immunological compounds. Among these compounds, human milk oligosaccharides (HMOs) represent the third most important component of breastmilk after lipids and lactose. Several experiments demonstrated the beneficial effects of these components on the microbiota, the immune system and epithelial barriers, which are three major biological systems. Indeed, HMOs induce bacterial colonization in the intestinal tract, which is beneficial for health. The gut bacteria can act directly and indirectly on the immune system by stimulating innate immunity and controlling inflammatory reactions and by inducing an adaptive immune response and a tolerogenic environment. In parallel, HMOs directly strengthen the intestinal epithelial barrier, protecting the host against pathogens. Here, we review the molecular mechanisms of HMOs in these different compartments and highlight their potential use as new therapeutic agents, especially in allergy prevention., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Rousseaux, Brosseau, Le Gall, Piloquet, Barbarot and Bodinier.)