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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: 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: Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site., Objective: The ability of eosinophils to promote AHR and lung inflammation independently of lymphocytes was investigated., Methods: Adoptive transfers of resting or activated eosinophils from IL-5 transgenic mice were performed into naive BALB/c mice, mice with severe combined immunodeficiency, and IFN-gamma-deficient BALB/c recipients., Results: Adoptively transferred eosinophils induced lung inflammation, fibrosis, collagen deposition, and AHR not only in BALB/c mice but also in recipient mice with severe combined immunodeficiency. Surprisingly, IFN-gamma expression was increased in lungs from eosinophil-transferred animals. Furthermore, IFN-gamma neutralization in recipients partially inhibited eosinophil-induced AHR. Moreover, IFN-gamma-deficient eosinophils or eosinophils treated with a blocking anti-IFN-gamma receptor antibody failed to induce AHR in IFN-gamma-deficient recipients. Finally, in vitro and at low concentrations, IFN-gamma increased eosinophil peroxidase release, potentiated chemotaxis, and prolonged survival, suggesting the existence of an autocrine mechanism., Conclusions: These results support the important and previously unsuspected contribution of eosinophils to lung inflammation independently of lymphocytes through production of IFN-gamma, the prototypical T(H)1 cytokine.

Background: The peroxisome proliferator-activated receptors (PPARs) alpha, beta/delta, and gamma are ligand-activated transcription factors belonging to the nuclear receptor superfamily. In addition to their regulatory role on lipid and glucose metabolism, they exert anti-inflammatory properties. In skin both PPAR-alpha and PPAR-beta/delta regulate keratinocyte proliferation/differentiation and contribute to wound healing. The 3 PPAR isoforms are expressed by several cell types recruited into the dermis during inflammation., Objective: We have investigated the role of PPAR-alpha in the regulation of atopic dermatitis (AD), a common skin inflammatory disease., Methods: We chose a mouse model of inflammatory dermatosis with immunologic features of AD and used epicutaneous sensitization with ovalbumin in the absence of adjuvant, which mimics the human pathology., Results: On antigen sensitization, PPAR-alpha-deficient mice display increased epidermal thickening, dermal recruitment of inflammatory cells, lung inflammation, airway hyperresponsiveness, and IgE and IgG2a production compared with their wild-type counterparts. Increased inflammation was correlated to an enhancement of TH2 and, to a greater extent, TH1 responses and to increased skin expression of nuclear factor kappaB. Interestingly, PPAR-alpha expression was decreased in eczematous skin from patients with AD compared with skin from nonatopic donors, suggesting that defective PPAR-alpha expression might contribute to the pathology. Topical application of WY14643, a specific PPAR-alpha agonist, significantly decreased antigen-induced skin inflammation in the AD model., Conclusion: PPAR-alpha acts as a negative regulator of skin inflammation in AD.