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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: Omalizumab (OMA) dramatically improves disease control and quality of life in patients with chronic urticaria (CU)., Objective: We aimed to evaluate the discontinuation patterns of OMA and their determinants in a cohort of French patients with CU., Methods: We conducted a retrospective multicenter study in 9 French tertiary referral hospitals. All patients diagnosed with either spontaneous (CSU) and/or inducible (CIndU) CU who received at least 1 injection of OMA between 2009 and 2021 were included. We analyzed OMA drug survival and investigated possible determinants using Kaplan-Meier curves and log-rank tests., Results: A total of 878 patients were included in this study; 48.8% had CSU, 10.1% CIndU, and 41.1% a combination of both. OMA was discontinued in 408 patients, but the drug was later reintroduced in 50% of them. The main reason for discontinuing treatment was the achievement of a well-controlled disease in 50% of patients. Half of the patients were still being treated with OMA 2.4 years after the initiation of treatment. Drug survival was shorter in patients with CIndU and in those with an autoimmune background. In atopic patients, OMA was discontinued earlier in patients achieving a well-controlled disease. A longer OMA drug survival was observed in patients with a longer disease duration at initiation., Conclusion: In French patients with CU, the drug survival of OMA appears to be longer than that observed in previous studies conducted elsewhere, highlighting discrepancies in prescription and reimbursement possibilities. Further studies are warranted to develop customized OMA treatment schemes based on individual patterns., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: There are limited data on the use of skin testing, other than patch testing, and challenges in the evaluation of epidermal necrolysis (EN), including Stevens-Johnson syndrome and toxic epidermal necrolysis., Objective: To report a French multicenter experience in skin testing and challenges in EN, and investigate the factors associated with tests' positivity., Methods: All patients who were evaluated by patch tests (PTs), skin prick tests, intradermal tests (IDTs), or drug provocation tests (DPTs) for EN between 2010 and 2020 were retrospectively included through 2 French drug reaction networks., Results: In total, 113 patients were included from 8 centers. Median (interquartile range) time from EN to hypersensitivity workup was 7.9 months (5.1-15 months). All patients had PTs, 17 (15%) had skin prick tests or IDTs with delayed readings and 32 (28.3%) had DPTs. One mild reaction occurred after a DPT. Overall, 22 patients (19.5%) had positive PTs, and the only factors associated with positivity were Algorithm of Drug Causality for Epidermal Necrolysis (ALDEN) score and drug class. Only 1 IDT was positive but considered irrelevant. The DPTs were never performed to prove responsibility of a highly suspected drug but were used to confirm current tolerance of needed medications., Conclusions: Allergological workup in EN, performed by specialists involved in EN, seems safe. Skin tests, although of limited sensitivity, can be helpful for considering the reintroduction of essential drugs according to a benefit-to-risk decision. We propose an algorithm for approaching hypersensitivity testing in patients with EN, to be adapted to each patient., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Acquired cold contact urticaria (ACU) is a putatively serious condition, because of the risk of anaphylactic shock whenever patients are massively exposed to cold atmosphere/water, raising the question of the prescription of an "emergency kit" with oral antihistamines and epinephrine auto-injector. We performed an online survey to evaluate how French-speaking urticaria experts manage ACU. According to the 2016 consensus recommendations on chronic inducible urticarias, all the participants perform at least 1 of the available provocation tests and 84.2%, 77.8%, and 88.9% prescribe on-label use of second generation anti-H1 antihistamines (2GAH1) as a first line treatment, updosed 2GAH1 as a second line treatment, and omalizumab as a third line treatment, respectively. Interestingly, 44.4% of the practitioners always prescribe a continuous background treatment, versus 11.1% prescribing only on-demand therapy. Also, 11.7% of participants always prescribe an epinephrine auto-injector, 70.6% sometimes do, and 17.6% never do. Finally, 89.5% authorize swimming under strict conditions but 36.8% and 68.4% contra-indicate other water sports and occupational cold exposure, respectively., (© 2022 The Authors.)

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare and potentially fatal adverse reaction. It can be difficult to diagnose, even more so among children, because symptoms may mimic other commonly encountered pediatric conditions., Objective: To describe clinical and laboratory features of DRESS syndrome in the pediatric population (age ≤18 years) and establish causative agents and treatment modalities., Methods: This was a multicenter retrospective study of probable and definite DRESS cases (Registry of Sever Cutaneous Adverse Reaction score ≥ 4) in children hospitalized in 15 French university hospitals between 2000 and 2020., Results: We included 49 cases. All children had fever and rash, 69.4% had lymphadenopathy, and 65.3% had facial edema. The most common organ affected was the liver (83.7%). Treatment consisted of topical corticosteroid in only 30.6% and systemic corticosteroid in 55.1%; 12.2% received intravenous immunoglobulin. Among probable and likely culprit drugs, 65% were antibiotics and 27.5% were antiepileptics, median time to DRESS symptom onset after initiation of 15 days (13 days with antibiotics and 21 days with antiepileptics). Twenty-seven children had allergy assessment for causative agents, 65.4% of whom had positive tests., Conclusions: Culprit drugs are frequently antibiotics and antiepileptic drugs, and onset is often less than 2 weeks after treatment starts, especially with antibiotics. Treatment with topical corticosteroids appears to be sufficient in the least severe cases. Treatment by systemic corticosteroid therapy remains the reference treatment in case of severe organ damage., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Drug reactions with eosinophilia and systemic symptoms (DRESSs) and acute generalized exanthematous pustulosis (AGEP) are potentially severe cutaneous adverse drug reactions., Objective: To describe the clinical findings and sensitization profiles of DRESS and AGEP patients who had been administered iodinated contrast media (ICM)., Methods: All adult patients in the dermatologist's French Investigators for Skin Adverse Reactions to Drugs (FISARD) network diagnosed with a DRESS or AGEP highly suspected to have been caused by an ICM were included retrospectively., Results: Thirteen DRESS patients and 19 AGEP patients who had been administered ICM were included, and the median delay in DRESS and AGEP occurrence after ICM administration was short, 4 and 1 days, respectively. Five AGEP patients had systemic involvement. A high cosensitization rate (46%) was observed among the DRESS patients, mainly with beta-lactam antibiotics. Overall, 77% of our patients were sensitized to several ICM. Patch tests identified the suspected ICM for 21 cases (72%). The retrospective nature, the limited number of subjects, the absence of a control group of healthy individuals, and the lack of detailed information on previous exposure to sensitizing drugs are limitations of this study., Conclusions: We report a large series of DRESSs and AGEPs related to ICM administration. Skin tests appear useful for diagnosis and potentially to identify alternative ICM., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The absence of asthma may rule out a diagnosis of eosinophilic granulomatosis with polyangiitis in patients with hypereosinophilic syndrome (HES) and features of vasculitis., Objective: To describe eosinophilic vasculitis (EoV) as a possible manifestation of HES in asthma-free patients., Methods: We screened our hospital database and the literature for patients with HES who met the following 4 criteria: (1) histopathological or clinical features of EoV (biopsy-proven vasculitis with predominant eosinophilic infiltration of the vessel wall and/or features of vasculitis with tissue and/or blood hypereosinophilia [absolute eosinophil count >1.5 G/L]); (2) no other obvious causes of reactive eosinophilia, organ damage, and vasculitis; (3) the absence of antineutrophil cytoplasmic antibodies; and (4) the absence of current asthma., Results: Ten of our 83 (12%) asthma-free patients with HES and 107 additional cases in the literature met the criteria for EoV. After a critical analysis of the patients' clinical and laboratory characteristics and outcomes, we identified 41 cases of single-organ EoV (coronary arteritis, n = 29; temporal arteritis, n = 8; cerebral vasculitis, n = 4). Of the remaining 76 patients with EoV, the most frequent manifestations (>10%) were cutaneous vasculitis (56%), peripheral neuropathy (24%), thromboangiitis obliterans-like disease (16%), fever (13%), central nervous system involvement (13%), deep venous thrombosis (12%), and nonasthma lung manifestations (12%). Blood hypereosinophilia more than 1.5 G/L was observed in 79% of patients, and necrotizing vasculitis was observed in 44%., Conclusions: Our results suggest that idiopathic EoV (HES-associated vasculitis) can be classified as an eosinophilic-rich, necrotizing, systemic form of vasculitis that affects vessels of various sizes in asthma-free patients., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Methotrexate is currently used to treat atopic dermatitis but has never been assessed versus cyclosporine in adults., Objective: This study evaluated the efficacy and safety of methotrexate versus cyclosporine in patients with moderate-to-severe atopic dermatitis., Methods: Patients were randomized to receive either oral methotrexate (15 mg/wk) or cyclosporine (2.5 mg/kg/d) for 8 weeks. The primary end point was a patient achieving 50% improvement in the SCORing Atopic Dermatitis index (SCORAD 50) at week 8. When the primary end point was not achieved, methotrexate was increased to 25 mg and cyclosporine to 5 mg during the next 16 weeks. The secondary end points were a patient achieving a 50% reduction in the Eczema Area Severity Intensity index (EASI 50) and SCORAD 50 at each visit (ClinicalTrials.gov no. NCT00809172)., Results: A total of 97 patients received methotrexate 15 mg (n = 50) or cyclosporine 2.5 mg (n = 47). Regarding the primary end point at week 8, methotrexate was inferior to cyclosporine because the proportion of patients with SCORAD 50 was 8% (4 of 50) in the methotrexate arm versus 42% (18 of 43) in the cyclosporine arm. The difference in percentages for the 2 treatment groups (2-sided 90% CI) was -34% (-48% to -20%). At week 8, methotrexate and cyclosporine dosages were increased in 56% and 49% of the patients, respectively. Regarding EASI 50, the noninferiority end point was reached at week 20 in 92% (22 of 24) of patients in the methotrexate arm and 87% (26 of 30) of patients in the cyclosporine arm. The treatment-related adverse events were more frequent with cyclosporine (P < .0001)., Conclusions: Methotrexate 15 mg/wk was inferior to cyclosporine 2.5 mg/kg/d at week 8. Increasing the doses of methotrexate to 25 mg/wk induced a significant improvement versus cyclosporine at week 20., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)