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Background: The contribution of Staphylococcus aureus to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored., Objectives: This study sought to reappraise the main bacterial factors and underlying immune mechanisms by which S aureus triggers AD-like inflammation., Methods: This study capitalized on a preclinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury., Results: The development of S aureus-induced dermatitis depended on the nature of the S aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and nonsecreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor apoptosis-associated speck-like protein containing a CARD domain- and monocyte/macrophage-deficient animals, but not in T- and B-cell-deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S aureus, and an accumulation of S aureus-specific γδ and CD4 + tissue resident memory T cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis on new bacteria exposures, but also, protected the mice from persistent bacterial colonization., Conclusions: These data highlight the induction of unique AD-like inflammation, with the generation of proinflammatory but protective tissue resident memory T cells in a context of natural exposure to pathogenic S aureus strains., Competing Interests: Disclosure statement This study was supported by institutional grants from the Institut National de la Santé et de la Recherche Médicale (INSERM) and from Pfizer. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Distinguishing between allergic and nonallergic forms of Contact Dermatitis (CD) is challenging and requires investigations based on patch-testing. Early detection of allergy biomarkers in active CD lesions could refine and simplify the management of CD patients., Objective: To characterize the molecular signatures of active CD lesions., Methods: We studied the expression of 12 allergy biomarkers by qRT-PCR in active lesions of 38 CD patients. Allergic CD (ACD) was diagnosed based on patch test (PT) results and exposure assessment. Molecular signatures of active lesions, as well as positive PT reactions, were compared with those of reference chemical allergens and irritants., Results: Nineteen of the 38 CD patients reacted positively upon patch-testing and exposure assessment confirmed ACD diagnosis for 17 of them. Gene profiling of active CD lesions revealed 2 distinct molecular patterns: patients harboring signatures similar to reference allergens (n = 23) or irritants (n = 15). Among the 23 patients with an "allergy signature," we found the 17 patients with confirmed ACD, while no culprit allergen was identified for the 6 other patients. Interestingly, the 15 patients without biomarker induction had negative PT, suggesting that they developed nonallergic CD reactions., Conclusion: Molecular signatures from active skin lesions may help to stratify CD patients and predict those suffering from ACD., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of interest Dezoteux has been an investigator and a consultant and speaker for AbbVie, Almirall, Eli Lilly, Janssen, Leo Pharma, Novartis and Sanofi-Regeneron. Jachiet has been an investigator and/or a consultant and/or speaker for AbbVie, Eli Lilly, Leo Pharma, Pfizer, Galderma and Sanofi-Regeneron. Soria has been an investigator and/or a consultant and/or speaker for AbbVie, Eli Lilly, Leo Pharma, Novartis, Pfizer and Sanofi-Regeneron. Tétart has been an investigator and/or a speaker and/or consultant for Sanofi-Regeneron. Modeste-Duval has been an investigator and/or a speaker and/or consultant fort Sanofi-Regeneron. Bursztejn has been a consultant and/or speaker for AbbVie, Almirall, Amgen, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Pfizer and Sanofi-Regeneron. Misery has been an investigator and/or a consultant and/or speaker for AbbVie, Almirall, Amgen, Astra-Zeneca, Eli Lilly, Galderma, Leo Pharma, Novartis, Pfizer and Sanofi-Regeneron. Aubin has been an investigator and/or a consultant and/or speaker for AbbVie, Almirall, Amgen, Astra-Zeneca, BMS, Eli Lilly, Galderma, Leo Pharma, MSD, Novartis, Pfizer, Pierre Fabre and Sanofi-Regeneron. Lasek has been an investigator and/or a speaker and/or consultant for Sanofi-Regeneron. Leleu has been an investigator for Leo Pharma, a consultant and/or speaker for AbbVie, Amgen, Eli Lilly, Novartis, and Sanofi-Regeneron. Du-Thanh has been an investigator for Leo Pharma, a consultant and/or speaker for AbbVie, Amgen, Eli Lilly, Novartis, and Sanofi-Regeneron. Pasteur has been an investigator and/or a consultant and/or speaker for AbbVie, Eli Lilly, Leo Pharma, Novartis, Pfizer, and Sanofi-Regeneron. Pralong has been an investigator for Eli Lilly, a speaker for AbbVie, Sanofi-Regeneron. Nosbaum has been an investigator and/or a consultant and/or speaker for AbbVie, Almirall, Amgen, Eli Lilly, Galderma, Leo Pharma, Medac, Novartis, Pfizer and Sanofi-Regeneron. Droitcourt has been an investigator and/or a consultant and/or speaker for AbbVie, Eli Lilly, Leo Pharma, Novartis, Pfizer and Sanofi-Regeneron. Viguier has been an investigator, a consultant and/or speaker for AbbVie, Almirall, Biogen, Galderma, Eli Lilly, Boehringer Ingelheim, Medac, Janssen Cilag and Bristol Myers Squibb. Seneschal has received personal fees from AbbVie, Almirall, Leo Pharma, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Sanofi-Genzyme. Barbarot has been an investigator or a speaker for AstraZeneca, Almirall, Sanofi-Genzyme, AbbVie, Novartis, Janssen, Leo Pharma, Pfizer, Eli Lilly, UCB Pharma, Chiesi. Staumont-Sallé has been an investigator and/or a consultant and/or speaker for AbbVie, Almirall, Amgen, AstraZeneca, Eli Lilly, Galderma, Leo Pharma, Novartis, Pfizer, Janssen and Sanofi-Regeneron. Tauber is a consultant for Abbvie, Eli Lilly, Janssen, Medac and a speaker for Abbvie, Eli Lilly, Janssen and Sanofi. Vanlerberghe and Martin have no conflicts of interest to declare.

Background: Human immunoglobulins are used for treating diverse inflammatory and autoimmune disorders. Eczema is an adverse event reported but poorly described., Objectives: To describe the clinical presentation, severity, outcome, and therapeutic management of immunoglobulin-associated eczema., Methods: This retrospective and descriptive study included a query of the French national pharmacovigilance database, together with a national call for cases among dermatologists., Results: We included 322 patients. Eczema occurred preferentially in men (78.9%) and in patients treated for neurological pathologies (76%). The clinical presentation consisted mainly of dyshidrosis (32.7%) and dry palmoplantar eczema (32.6%); 5% of cases exhibited erythroderma. Sixty-two percent of the eczema flares occurred after the first immunoglobulin course. Eczema was observed with 13 intravenous or subcutaneous immunoglobulin types and recurred in 84% of patients who maintained the same treatment and in 68% who switched the immunoglobulin type. After immunoglobulin discontinuation, 30% of patients still had persistent eczema., Limitations: Retrospective study, with possible missing data or memory bias., Conclusion: Immunoglobulin-associated eczema occurred with all immunoglobulin types, preferentially in patients with neurologic diseases who required prolonged immunoglobulin treatment. Recurrence was frequent, even after switching the immunoglobulin type, which can lead to a challenging therapeutic situation when immunoglobulin maintenance is required., Competing Interests: Conflicts of interest None disclosed., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Epicutaneous immunotherapy (EPIT) protocols have recently been developed to restore tolerance in patients with food allergy. The mechanisms by which EPIT protocols promote desensitization rely on a profound immune deviation of pathogenic T- and B-cell responses., Objective: To date, little is known about the contribution of skin dendritic cells (skDCs) to T-cell remodeling and EPIT efficacy., Methods: We capitalized on a preclinical model of food allergy to ovalbumin (OVA) to characterize the phenotype and functions of OVA + skDCs throughout the course of EPIT., Results: Our results showed that both Langerhans cells and dermal conventional cDC1 and cDC2 subsets retained their ability to capture OVA in the skin and to migrate toward the skin-draining lymph nodes during EPIT. However, their activation/maturation status was significantly impaired, as evidenced by the gradual and selective reduction of CD86, CD40, and OVA protein expression in respective subsets. Phenotypic changes during EPIT were also characterized by a progressive diversification of single-cell gene signatures within each DC subset. Interestingly, we observed that OVA + Langerhans cells progressively lost their capacity to prime CD4 + T EFF cells, but gained regulatory T-cell stimulatory properties. In contrast, cDC1 were inefficient in priming CD4 + T EFF cells or in reactivating T MEM cells in vitro, whereas cDC2 retained moderate stimulatory properties, and progressively biased type 2 immunity toward type 1 and type 17 responses., Conclusions: Our results therefore emphasize that the acquisition of distinct phenotypic and functional specializations by skDCs during EPIT is at the cornerstone of the desensitization process., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials., Objective: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort., Methods: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up., Results: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10 -9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10 -9 , respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm 3 ) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10 -6 ). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs., Limitations: No control group, missing data., Conclusion: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia., (Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Tissue-resident memory T (Trm) cells are detrimental in patients with numerous chronic inflammatory diseases, including allergic contact dermatitis (ACD)., Objectives: We sought to analyze the contribution of Trm cells to the chronicity and severity of ACD and to define the local parameters regulating their development and functions., Methods: We used an experimental model of ACD (ie, contact hypersensitivity to 2,4-dinitrofluorobenzene) that is mediated by CD8 + T cells., Results: Our data show that early effector T cells accumulated in the skin during the acute contact hypersensitivity reaction and gave rise to epidermal CD8 + Trm cells expressing a specific set of inhibitory checkpoint receptors (ICRs), such as programmed cell death protein 1 (PD-1) and T cell immunoglobulin and mucin domain 3 (TIM-3). Those Trm cells remained in the epidermis for several weeks and mediated the eczema exacerbations, which developed on allergen re-exposure without the contribution of circulating specific T cells. Furthermore, allergen-induced Trm cell reactivation was constrained because treatment with ICR antagonists dramatically enhanced the magnitude and severity of eczema exacerbations. Finally, we show that the persistence of the allergen in the epidermis for long periods of time was responsible for both the development and maintenance of epidermal Trm cells, as well as the sustained expression of ICRs., Conclusion: Although CD8 + Trm cells are key for the pathophysiology of ACD, intrinsic mechanisms control their reactivation to prevent damaging immunopathology. Developing strategies targeting the reactivation of skin Trm cells in situ through their ICRs should open new perspectives for the treatment of ACD., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Although most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking., Objective: To guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient., Methods: A subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion., Results: We recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy., Limitations: Our work is a consensus statement, not a systematic review., Conclusion: The decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies., (Copyright © 2017 American Academy of Dermatology, Inc. All rights reserved.)