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An aqueous antiseptic containing "chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol" (CBB) is widely used in France. The only previous documented study dealing with allergic contact dermatitis (ACD) to this antiseptic is one small case series in children. The French Vigilance Network for Dermatology and Allergy (REVIDAL-GERDA) has collected many cases in the last few years.To evaluate the clinical and sensitization profiles of patients diagnosed with ACD to CBB.We performed a retrospective study of patients with contact dermatitis to CBB and positive tests to CBB and/or at least one of its components. All patients had to be tested with all components of CBB.A total of 102 patients (71 adults and 31 children) were included. The lesions were extensive in 63% of patients and 55% had delayed time to diagnosis. CBB patch tests were positive in 93.8% of cases. The allergen was identified in 97% of patients, mainly benzyl alcohol in adults (81.7%) and chlorhexidine digluconate in children (54.8%). About 32.4% of the patients were sensitized to several components.CBB is a cause of ACD at all ages. The components of the antiseptic should be tested. The sensitization profile seems to be different between adults and children.

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.

BACKGROUND: Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), bullous life-threatening reactions are rare. OBJECTIVES: To better define the clinical and histological features, treatment and prognosis of ICI-related severe blistering cutaneous eruptions. METHODS: This retrospective case series was conducted between 2014/05/15 to 2021/04/15 by the dermatology departments of four international registries involved in drug reactions. Inclusion criteria were age ≥ 18 years-old, skin eruption with blisters and/or detachment covering ≥ 1% body surface area and at least one mucous membrane involved, available pictures, and ICI as suspect drug. Autoimmune bullous disorders were excluded. Each participant medical team gave his own diagnosis conclusion: epidermal necrolysis (EN), severe lichenoid dermatosis (LD) or unclassified dermatosis (UD). After a standardized review of pictures, cases were reclassified by 4 experts in EN or LD/UD. Skin biopsies were blindly reviewed. RESULTS: Thirty-two patients were included. Median time to onset was 52 days [3–420]. Cases were originally diagnosed as EN in 21 cases and LD/UD in 11 cases. After review by experts, 10/21 EN were reclassified as LD/UD. The following manifestations were more frequent or severe in EN: fever, purpuric macules, blisters, ocular involvement, maximal detachment. Most patients were treated with topical and/or systemic corticosteroids. Eight patients (25%) died in the acute phase. The culprit ICI was not resumed in 92% of cases. In three patients, another ICI was given with a good tolerance. Histology did not reveal significant differences between groups. CONCLUSIONS: Severe blistering cutaneous drug reactions induced by ICI are often overdiagnosed as EN. Consensus for management is pending.

The two clinico-pathological patterns are 'Sweet-like syndrome' and 'Multiple COVID-Arm'. 'Sweet-like syndrome' presents clinically as erythematous and oedematous papules or plaques, sometimes developing vesiculation or bullae. Histology shows classical Sweet syndrome with a diffuse dermal neutrophilic infiltrate, or an infiltrate of histiocyte-like immature myeloid cells consistent with a histiocytoid Sweet syndrome. 'Multiple COVID-arm' is characterized by multiple large inflammatory plaques with histological analyses showing a perivascular and interstitial inflammatory infiltrate with eosinophils.

The repeated open application test (ROAT) is an adjuvant investigation measure to patch testing in the diagnosis of allergic contact dermatitis. ESCD recommends a 15 days duration but its overall duration varies according to publications and patients hardly adhere to prolonged ROAT duration beyond 1 week.The Dermatology and Allergy Group of the French Society of Dermatology performed a prospective study with the aim of determining the best duration for the ROAT.A total of 328 ROAT results were collected for topical products, including cosmetics (60%) and topical medications (31.1%). Fifty-nine (18%) ROATs were positive, and 16 (5%) were doubtful. All the positive ROATs occurred within 10 days, with a median time to positivity of 3 days.According to our results, a minimum duration of 10 days is necessary to achieve a positive ROAT to a topical product.

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.To report a French multicenter experience in skin testing and challenges in EN, and investigate the factors associated with tests' positivity.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.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.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.

Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccineAS Darrigade, MD1, H Theophile, MD2, P Sanchez-Pena, MD2, B Milpied, MD1, M Colbert4, MD, S Pedeboscq5, MD, T Pistone6, MD, ML Jullie, MD7, J Seneschal, MD, PhD1,31 : Department of Adult and Pediatric Dermatology, Bordeaux University Hospitals, France2 : Department of pharmacovigilancy, Bordeaux University Hospitals, France3 : Research Unit INSERM U10354 : Department of geriatry, Clinic Bordeaux Nord, Bordeaux, France5 : Department of pharmacology, Bordeaux University Hospitals, France6: Department of infectious disease, Bordeaux University Hospitals, France7: Department of anatomopathology, Bordeaux University Hospitals, FranceManuscript word count: 607Key words : sweet syndrome, SARS-CoV-2, Pfizer-BioNTech mRNA vaccine, delayed hypersensitivity, IDRCorresponding author: A.S. Darrigade, Dermatology Department, Saint-Andre Hospital, 1, rue Jean Burguet 33000 Bordeaux, FrancePhone: +33556794705Fax: +33556794975anne-sophie.darrigade@chu-bordeaux.frFunding source: No financial disclosuresFinancial Disclosure: No external funding for this manuscriptTo the editor,A 45-year-old woman, without any past medical history or allergy presented in our clinic with a rapid onset of diffuse skin eruptions. Five days earlier, she received the first injection of the SARS-CoV-2 Pfizer-BioNTech mRNA. Concomitantly she took 1000mg paracetamol to prevent any post-vaccination syndrome. She well tolerated the preceding vaccines (influenza every year) before this one.The eruption started 24h after vaccine injection and was composed at time of the clinical exam of erythematous infiltrated papulosis located all over the body, without face involvement (Figure 1). No other extracutaneous symptoms were noted. Blood exams showed increased blood count levels with increased neutrophils count (8.77G/l), hepatic cytolysis (AST 67UI/L and ALT 116UI/l) with high level of PCR (115mg/l). SARS-CoV-2 PCR test and serology were negative. Viral tests for EBV, CMV, parvovirus B19, and Herpes simplex/Herpes zoster showed only a slight EBV reactivation. Histopathological examination of the skin biopsy showed a hyperplastic epidermis with an edematous papillary dermis. A superficial and deep dermal perivascular, periadnexal and interstitial dense infiltrate composed of neutrophils, eosinophils and lymphocytes was also a feature. Leukocytoclastic vasculitis was also seen (Figure 2A-2B). Clinical and pathological exams were compatible with the diagnosis of SS induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Systemic steroid therapy (prednisone 0.5mg/kg/d) for five days was started and led to rapid improvement of the skin condition without any recurrence after treatment discontinuation. She did not receive the second vaccine injection.Patch-tests performed (14 days after steroid treatment stop, one month after SS) on both on healed and normal skin with pur SARS-CoV-2 Pfizer-BioNTech mRNA vaccine prepared less than 4 hours before were negative (Figure 1C 2-3). Then, intradermoreaction (IDR) with vaccine diluted at 1/10 on normal skin was positive in delayed reading (Figure 1C 1). Cutaneous biopsy was realized on the positive IDR reaction, showing an abundant inflammatory infiltrate predominantly with lymphocytes (Figure 2C).Cutaneous reactions after vaccine injection are rare, and heterogenous1. They could be related to the vaccine or the adjuvant. In addition, vaccine could trigger flares of chronic inflammatory conditions as it was previously reported1. At that time, minor local side effects are reported with SARS-CoV-2 vaccines such as pain, swelling or redness; hypersensitivity reactions were anaphylactic reaction but no severe delayed hypersensitivity are reported2-3. Three cases of acute febrile neutrophilic dermatosis are reported in the international bank of WHO, one in United Kingdom, one in United States of America and our case. Under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine four cases of vasculitis had been reported after injection. In France one case of relapse of neutrophilic disorder was reported one day after SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. The adjuvant associated with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine is polyethylene glycol (PEG) 20003. However our patient never received infusion containing PEG or polysorbate before. Patch-tests with PEG or polysorbate alone were not performed because of the negativity of the patch-test with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Only 10 cases of SS induced by vaccine are published so far including: 3 with seasonal influenza, 1 with influenza A, 2 with pneumococcal, 2 tuberculosis, 2 small pox4. SS is an acute inflammatory skin disease associated with important infiltration of neutrophils. Leukocytoclastic vasculitis could be present in SS5. One case of SS in a patient receiving pneumococcal vaccine showed the presence of dermal vasculitis associated with infiltration of neutrophils6. In case of anaphylactic reaction under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine, the risk of relapse with the Moderna SARS-CoV-2 mRNA vaccine or SARS-CoV-2 vaccines with an adenovirus carrier and protein subunit remains unknown3, in case of SS even more.To conclude we report the first case of SS induce by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine confirmed by positive IDR.

Introduction Le role des medicaments dans la survenue d’eruptions eczematiformes du sujet âge (EESA) a ete suggere dans une etude cas-temoin francaise montrant une frequence de prise des inhibiteurs calciques de 26 % chez les patients ayant une EESA (OR de 2,5 par rapport aux temoins sans eczema). Ces resultats ont ensuite ete confirmes par une etude retrospective americaine. Des cas isoles d’EESA ont depuis ete rapportes avec le clopidogrel, les IEC, les ARAII et les diuretiques. Notre etude initiale ayant ete realisee il y a 15 ans, nous en avons realise une nouvelle pour reevaluer l’association entre les prises medicamenteuses et les EESA. Materiel et methodes Cette etude retrospective a ete conduite dans 16 centres du GREAT, FISARD ou DAG de 2018 a 2020. Nous avons compare la frequence des 10 classes medicamenteuses les plus prescrites entre la population etudiee (patients de plus de 65 ans developpant un eczema chronique sans cause identifiee) et la population generale de reference du meme âge dont les donnees ont ete obtenues grâce a l’Echantillon Generaliste des Beneficiaires (EGB) issu de la base informatique de la Securite Sociale, apres standardisation indirecte sur le sexe et l’âge. Tous les patients inclus avaient des lesions eczematiformes etendues (plus de 20 % de la surface corporelle), depuis plus de 3 mois. Une biopsie cutanee evocatrice d’eczema devait avoir ete realisee ainsi qu’une immunofluorescence directe negative ou des anticorps BPAG 1 et 2 negatifs afin d’eliminer une pemphigoide au stade pre-bulleux. Les patients n’avaient pas d’antecedent de dermatite atopique dans l’enfance. Resultats Cent quatre vingt cinq patients (120 H et 65 F) d’âge moyen 79,5 ± 7,5 ans ont ete inclus. L’hypertension arterielle representait la comorbidite la plus frequente (69,7 % des patients). Les patients prenaient en moyenne 5,0 ± 3,2 medicaments. Les medicaments les plus frequemment prescrits etaient les inhibiteurs calciques (39,5 %), les statines (36,8 %), les antiagregants plaquettaires (31,9 %), les betabloquants (30,8 %), les ARA2 (29,2 %), les diuretiques thiazidiques (23,8 %), les IEC (22,7 %), les IPP (21,6 %), les diuretiques de l’anse (17,8 %) et les benzodiazepines (15,1 %). Un ou plusieurs medicaments etaient arretes chez 60 (32,4 %) patients. Parmi eux, 31 (51,7 %) ne presentaient plus de lesion a 6 mois. L’analyse comparative par rapport a l’EGB est en cours. Discussion Les caracteristiques des patients concordent avec celles observees dans notre etude precedente, en particulier la predominance masculine et la polymedication. La frequence de prise des inhibiteurs calciques (39,5 %) est encore plus elevee (× 1,5) que dans notre etude initiale confirmant le tres fort risque lie a cette classe medicamenteuse. La comparaison avec les donnees de l’EGB (analyse en cours avec resultats prevus prochainement) permettra peut-etre de mettre en evidence une association avec d’autres classes medicamenteuses.

Importance: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe drug reactions associated with a high rate of mortality and morbidity. There is no consensus on the treatment strategy. Objective: To explore treatment approaches across Europe and outcomes associated with the SJS/TEN disease course, as well as risk factors and culprit drugs. Design, Setting, and Participants: A retrospective pan-European multicenter cohort study including 13 referral centers belonging to the ToxiTEN ERN-skin subgroup was conducted. A total of 212 adults with SJS/TEN were included between January 1, 2015, and December 31, 2019, and data were collected from a follow-up period of 6 weeks. Main Outcomes and Measures: Risk factors for severe acute-phase complications (acute kidney failure, septicemia, and need for mechanical ventilation) and mortality 6 weeks following admission were evaluated using a multivariable-adjusted logistic regression model. One tool used in evaluation of severity was the Score of Toxic Epidermal Necrolysis (SCORTEN), which ranges from 0 to 7, with 7 the highest level of severity. Results: Of 212 patients (134 of 211 [63.7%] women; mean [SD] age, 51.0 [19.3] years), the mean (SD) body surface area detachment was 27% (32.8%). In 176 (83.0%) patients, a culprit drug was identified. Antibiotics (21.2%), followed by anticonvulsants (18.9%), nonsteroidal anti-inflammatory drugs (11.8%), allopurinol (11.3%), and sulfonamides (10.4%), were the most common suspected agents. Treatment approaches ranged from best supportive care only (38.2%) to systemic glucocorticoids (35.4%), intravenous immunoglobulins (23.6%), cyclosporine (10.4%), and antitumor necrosis factor agents (3.3%). Most patients (63.7%) developed severe acute-phase complications. The 6-week mortality rate was 20.8%. Maximal body surface area detachment (≥30%) was found to be independently associated with severe acute-phase complications (fully adjusted odds ratio [OR], 2.49; 95% CI, 1.21-5.12; P =.01) and SCORTEN greater than or equal to 2 was significantly associated with mortality (fully adjusted OR, 10.30; 95% CI, 3.82-27.78; P

Gram-negative toe-web infection can cause pain and disability, be complicated by a long healing time, management failure, and cellulitis, and recur due to persistent predisposing factors. To describe the clinical features and management of Gram-negative toe-web infection and evaluate predisposing factors and associated diseases, their management, and the effect of controlling them on the rate of recurrence, we conducted a retrospective real-life study of patients with Gram-negative toe-web infection. Among the 62 patients (sex ratio 9:1), 31 experienced more than one episode of Gram-negative toe-web infection. Pseudomonas aeruginosa was the most prominent bacteria. Predisposing factors/associated diseases were eczema (66%), suspected Tinea pedis (58%), humidity (42%), hyperhidrosis (16%), psoriasis (11%), and vascular disorders (40%). Patients in whom associated diseases, such as eczema or psoriasis, were controlled did not relapse, suggesting the benefit of management of such conditions. We suggest that management of Gram-negative toe-web infection be standardised, with a focus on diagnosis and treatment of associated diseases.

TREATMENT OF THE INITIAL INFECTION OR FIRST CLINICAL EPISODE OF GENITAL HERPES: An initial infection or first clinical episode of genital herpes is treated with oral aciclovir 200mg×5/d for 5 to 10 days depending on clinical status. The recommended dosage for valaciclovir is 1g×2/d and treatment duration is identical to that for aciclovir. TREATMENT OF HERPES RECURRING DURING PREGNANCY: There are no studies of the efficacy of antiviral therapy on the symptoms of genital recurring during pregnancy. However, initial anti-viral treatment using aciclovir or valaciclovir may be given where warranted by symptoms (i.e. duration and severity of symptoms). Valaciclovir may be used instead (equivalent efficacy but better safety data for aciclovir). Valaciclovir may be given at a dosage of 1×500mg b.i.d. p.o. for 5 days. PROPHYLACTIC ANTI-VIRAL TREATMENT DURING PREGNANCY: In female patients presenting an initial infection or infection recurring during pregnancy, although there is no demonstrated benefit for prophylactic treatment in reducing the risk of neonatal herpes, anti-viral prophylaxis is recommended after 36 WA (weeks' amenorrhoea) to limit the need for Caesarean section due to herpetic lesions. The recommended antivirals are aciclovir at a dosage of 400mg t.i.d p.o. or valaciclovir at a dosage of 500mg b.i.d. p.o. until delivery.

Introduction L’exploration allergologique des necrolyses epidermiques (NE, syndromes de Stevens-Johnson et Lyell) est peu rapportee dans la litterature, et concerne essentiellement les patch tests (PT). Les pric-tests (P) et les tests intradermiques (IDR) sont theoriquement contre-indiques. Le but de cette etude etait de rapporter l’experience francaise des tests allergologiques des NE. Materiel et methodes Cette etude retrospective multicentrique nationale a inclus les patients ayant eu des tests allergologiques pour explorer une NE entre 2010 et 2020. Les objectifs etaient de decrire les modalites des tests, leur taux de positivite et tolerance, les medicaments impliques et les facteurs associes aux tests positifs (âge, sexe, type de NE, delai des tests, centres). Resultats Cent-dix-sept patients ont ete inclus (67 F, âge median 38 ans). Les tests etaient faits en mediane 8 mois (IQR 5–15) apres la NE. Tous les patients avaient eu des PT (total 472 PT; en peau anterieurement lesee en plus du dos n = 15), 20 patients (17 %) des tests intradermiques a lecture retardee (P et/ou IDR ; total 52 IDR) et 35 des reintroductions ou provocations medicamenteuses (TPO) (30%, dont 26 dans un seul centre; total 57 TPO). Pour 98 % des PT et 41 % des P-IDR, les concentrations etaient celles utilises dans l’exploration des autres toxidermies (PT : 10 % de principe actif ou 30 % de produit fini), plus diluees dans les autres cas (PT 1 % principe actif, IDR : dilution jusqu’a 10−4). Aucun effet indesirable n’etait rapporte lors des tests. Les PT etaient positifs chez 22 patients (19 %), dont 2 uniquement en peau anterieurement lesee. Une seule IDR etait positive au bortezomib, chez un patient avec reactions au site d’injection du medicament par le passe. Aucun P n’etait positif. L’objectif des TPO etait de restreindre les contre-indications medicamenteuses. Deux patients declenchaient une eruption benigne apres TPO. Les analyses univariees n’ont pas mis en evidence de facteurs associes a la positivite des tests. Discussion L’exploration allergologique des NE en France repose essentiellement sur les PT, realises selon les modalites des autres toxidermies. Leur taux de positivite etait de 19%, proche des series de la litterature. Si le delai de realisation apres la NE ne semble pas influencer leur resultat, la pose en peau anterieurement lesee peut augmenter leur sensibilite. Dans notre etude, l’exploration par P-IDR chez 20 patients s’est averee peu rentable mais n’a pas reactive les NE explorees. L’experience des TPO, realises essentiellement dans un seul centre, est encourageante car a permis de lever des contre-indications sans effet secondaire grave. L’indication doit etre bien pesee par des equipes habituees (imputabilite intrinseque, extrinseque et besoins therapeutiques du patient). La prise en charge allergologique des NE doit etre homogeneisee.

Introduction La folliculite decalvante (FD) est une dermatose inflammatoire folliculaire neutrophilique d’evolution longue et chronique. Bien que rare, elle represente la 2e cause d’alopecie cicatricielle primaire. Sa physiopathologie reste encore mal comprise, avec des similitudes anatomocliniques avec l’hidradenite suppuree (HS). La FD a un impact majeur sur la qualite de vie et reste un defi therapeutique. En effet, les traitements conventionnels (antibiotherapies) n’ont qu’une efficacite suspensive. L’utilisation des anti-TNFa dans la FD n’a ete rapportee que dans quelques cas isoles. L’objectif de notre etude etait d’evaluer l’efficacite des anti-TNFa dans le traitement de la FD, notamment a l’aide d’un score d’evaluation globale (FD-IGA allant de 0 a 4) cree et valide dans une sous-etude pilote. Materiel et methodes Etude retrospective monocentrique incluant les patients avec une FD refractaire aux traitements conventionnels et ayant recu un traitement par anti-TNFa entre janvier 2010 et decembre 2020. Les patients etaient consideres comme « repondeurs » par l’obtention d’un score FD-IGA ≤ 2 a M12. Nous avons evalue l’intensite du prurit par l’echelle numerique (EN) et recense les effets indesirables eventuels. Resultats Onze patients ont ete inclus. Le diagnostic de FD avait ete porte en moyenne 8,55 ± 1,26 ans avant l’introduction d’infliximab (n = 9) ou d’adalimumab (n = 2), et l’âge median etait de 23 ans (13–59 ans). Neuf patients avaient resiste a au moins 2 lignes de traitements systemiques dont l’association rifampicine + clindamycine et les cyclines avant les anti-TNFa. Le score FD-IGA median a l’initiation etait de 3 (2–4). Cinq patients sur 10 ont ete etaient « repondeurs » a M12. Un patient a ete perdu de vue apres 6 mois. Apres un an de traitement, 6/7 patients obtenaient un score EN prurit de 0 ou 1. Seuls 2 effets indesirables legers a moderes ont ete observes (cytolyse hepatique minime, vascularite des membres inferieurs). Discussion Nous rapportons la plus grande serie de patients atteints de FD traites par anti-TNFa. Une amelioration a M12 a ete observee chez la moitie des patients traites par anti-TNFa, avec une bonne tolerance. Nos resultats suggerent que l’amelioration est observee apres au moins 6 mois de traitement. Cela pourrait etre lie a la severite prealable de leur FD. On pourrait penser que l’introduction plus precoce des anti-TNFa dans l’histoire de la FD pourrait permettre de meilleurs resultats et surtout d’eviter l’alopecie definitive des FD evoluees.

Sweet syndrome induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccineAS Darrigade, MD1, H Theophile, MD2, P Sanchez-Pena, MD2, B Milpied, MD1, M Colbert4, MD, S Pedeboscq5, MD, T Pistone6, MD, ML Jullie, MD7, J Seneschal, MD, PhD1,31 : Department of Adult and Pediatric Dermatology, Bordeaux University Hospitals, France2 : Department of pharmacovigilancy, Bordeaux University Hospitals, France3 : Research Unit INSERM U10354 : Department of geriatry, Clinic Bordeaux Nord, Bordeaux, France5 : Department of pharmacology, Bordeaux University Hospitals, France6: Department of infectious disease, Bordeaux University Hospitals, France7: Department of anatomopathology, Bordeaux University Hospitals, FranceManuscript word count: 607Key words : sweet syndrome, SARS-CoV-2, Pfizer-BioNTech mRNA vaccine, delayed hypersensitivity, IDRCorresponding author: A.S. Darrigade, Dermatology Department, Saint-Andre Hospital, 1, rue Jean Burguet 33000 Bordeaux, FrancePhone: +33556794705Fax: +33556794975anne-sophie.darrigade@chu-bordeaux.frFunding source: No financial disclosuresFinancial Disclosure: No external funding for this manuscriptTo the editor,A 45-year-old woman, without any past medical history or allergy presented in our clinic with a rapid onset of diffuse skin eruptions. Five days earlier, she received the first injection of the SARS-CoV-2 Pfizer-BioNTech mRNA. Concomitantly she took 1000mg paracetamol to prevent any post-vaccination syndrome. She well tolerated the preceding vaccines (influenza every year) before this one.The eruption started 24h after vaccine injection and was composed at time of the clinical exam of erythematous infiltrated papulosis located all over the body, without face involvement (Figure 1). No other extracutaneous symptoms were noted. Blood exams showed increased blood count levels with increased neutrophils count (8.77G/l), hepatic cytolysis (AST 67UI/L and ALT 116UI/l) with high level of PCR (115mg/l). SARS-CoV-2 PCR test and serology were negative. Viral tests for EBV, CMV, parvovirus B19, and Herpes simplex/Herpes zoster showed only a slight EBV reactivation. Histopathological examination of the skin biopsy showed a hyperplastic epidermis with an edematous papillary dermis. A superficial and deep dermal perivascular, periadnexal and interstitial dense infiltrate composed of neutrophils, eosinophils and lymphocytes was also a feature. Leukocytoclastic vasculitis was also seen (Figure 2A-2B). Clinical and pathological exams were compatible with the diagnosis of SS induced by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Systemic steroid therapy (prednisone 0.5mg/kg/d) for five days was started and led to rapid improvement of the skin condition without any recurrence after treatment discontinuation. She did not receive the second vaccine injection.Patch-tests performed (14 days after steroid treatment stop, one month after SS) on both on healed and normal skin with pur SARS-CoV-2 Pfizer-BioNTech mRNA vaccine prepared less than 4 hours before were negative (Figure 1C 2-3). Then, intradermoreaction (IDR) with vaccine diluted at 1/10 on normal skin was positive in delayed reading (Figure 1C 1). Cutaneous biopsy was realized on the positive IDR reaction, showing an abundant inflammatory infiltrate predominantly with lymphocytes (Figure 2C).Cutaneous reactions after vaccine injection are rare, and heterogenous1. They could be related to the vaccine or the adjuvant. In addition, vaccine could trigger flares of chronic inflammatory conditions as it was previously reported1. At that time, minor local side effects are reported with SARS-CoV-2 vaccines such as pain, swelling or redness; hypersensitivity reactions were anaphylactic reaction but no severe delayed hypersensitivity are reported2-3. Three cases of acute febrile neutrophilic dermatosis are reported in the international bank of WHO, one in United Kingdom, one in United States of America and our case. Under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine four cases of vasculitis had been reported after injection. In France one case of relapse of neutrophilic disorder was reported one day after SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. The adjuvant associated with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine is polyethylene glycol (PEG) 20003. However our patient never received infusion containing PEG or polysorbate before. Patch-tests with PEG or polysorbate alone were not performed because of the negativity of the patch-test with the SARS-CoV-2 Pfizer-BioNTech mRNA vaccine. Only 10 cases of SS induced by vaccine are published so far including: 3 with seasonal influenza, 1 with influenza A, 2 with pneumococcal, 2 tuberculosis, 2 small pox4. SS is an acute inflammatory skin disease associated with important infiltration of neutrophils. Leukocytoclastic vasculitis could be present in SS5. One case of SS in a patient receiving pneumococcal vaccine showed the presence of dermal vasculitis associated with infiltration of neutrophils6. In case of anaphylactic reaction under SARS-CoV-2 Pfizer-BioNTech mRNA vaccine, the risk of relapse with the Moderna SARS-CoV-2 mRNA vaccine or SARS-CoV-2 vaccines with an adenovirus carrier and protein subunit remains unknown3, in case of SS even more.To conclude we report the first case of SS induce by SARS-CoV-2 Pfizer-BioNTech mRNA vaccine confirmed by positive IDR.

International audience; Background: Diagnosing drug reaction with eosinophilia and systemic symptoms (DRESS) is challenging. Some clinicians reject this diagnosis when the delay of onset is less than 15 days after drug intake.Objectives: To assess the delay of DRESS occurrence and culprit drugs.Methods: All patients hospitalized in 3 dermatology departments with a first occurrence of DRESS for which a drug was highly suspected were included in this retrospective study. Based on the delay in DRESS occurrence, cases were classified into 2 groups: a rapid-onset group (≤15 days after exposure) and a delayed-onset group (>15 days).Results: A total of 41 patients with DRESS were included: 14 in the rapid-onset and 27 in delayed-onset groups. In the rapid-onset group, antibiotics (n = 6/14) and iodinated contrast media (n = 5/5) were the predominant culprits. Carbamazepine (n = 4/4), lamotrigine (n = 6/6), allopurinol (n = 8/8), and sulfasalazine (n = 2/2) were exclusively found in the delayed-onset group.Limitations: The retrospective nature, limited number of participants, and lack of detailed information on previous exposure to sensitizing drugs in some instances.Conclusions: DRESS is frequently related to drugs introduced 15 or fewer days before the occurrence of cutaneous adverse reactions. The time of onset of DRESS may differ depending on the medications involved.

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.

Introduction Le port de gants est source de dermites de contact irritatives ou allergiques le plus souvent dues aux accelerateurs de vulcanisation. De nouvelles sensibilisations aux gants en caoutchouc synthetique ou en vinyle ont ete rapportees. Une batterie Europeenne caoutchouc (BEC) et des patch tests avec les gants personnels sont conseilles depuis 2016 pour le diagnostic d’allergie aux gants. Depuis, une seule etude systematique a ete realisee chez les porteurs de gants. Nos objectifs etaient d’evaluer le profil clinique des patients atteints d’ECM et porteurs de gants, et l’interet des tests avec les gants personnels, la BEC et des allergenes de gants vinyle. Materiel et methodes (ou observation(s) si cas clinique(s)) Le groupe DAG de la Societe francaise de dermatologie a inclus dans une etude multicentrique tous les patients atteints d’ECM et porteurs de gants en milieu professionnel ou non, ayant beneficie, selon les regles de bonnes pratiques du groupe, d’un questionnaire enquete de pratiques dans l’ECM, d’un recueil standardise d’observation, de patch tests avec la BSE, la BEC et ses ajouts, les allergenes commercialises de gants vinyle et de tests avec des gants personnels (patch tests et tests semi-ouverts 5 × 5 cm SO). Resultats (si adapte) On avait 283 patients, d’âge moyen 38,6 ans, dont 75 % de femmes, 56 % d’atopiques, avec une duree moyenne de l’ECM 53,6 mois, et un eczema fissuraire ou vesiculeux dans plus de 50 % des cas. 43 % exercaient dans le milieu de la sante et 26 % portaient les gants plus de 2 h/jour. 62 % portaient plusieurs types de gants (latex 58 %, vinyle 47 %, nitrile 47 %, textile enduit 15 %, neoprene 7 %). Le lavage des mains etait frequent (64,8 %) ; 80 % utilisaient un savon doux et un emollient. L’ECM etait rythme par le travail dans 62,6 % des cas. Au total, 32 % des patients avaient des tests positifs a des gants personnels ou des allergenes de gants. Les allergenes principaux etaient : thiurams 13 %, (dont 20 % non depistes par la BSE), carbamates 3,2 %, benzothiazoles 3,2 %, 1,3-diphenylguanidine 5,3 % ; 48,7 % des sensibilisations n’etaient detectees que par la BEC. Sur les 55 gants positifs, 10,9 % etaient des gants vinyle et sur les 35 patients ayant eu patch tests et tests SO, 22,8 % avaient uniquement des tests SO positifs. 25 % etaient sensibilises a d’autres allergenes. 52 % de patients allergiques aux gants etaient revus avec 87 % d’evolution tres favorable apres eviction. Discussion Notre etude montre l’interet de tester la batterie europeenne caoutchouc et les gants apportes. Le taux eleve d’allergie aux gants s’explique par un biais de recrutement hospitalier. Le taux de sensibilisation aux thiurams, carbamates et benzothiazoles est similaire aux donnees de la litterature. Nous confirmons l’importance de la sensibilisation a la diphenylguanidine. Les tests semi-ouverts avec les gants sont apparus utiles. Nous soulignons une proportion significative (10,9 %) de tests positifs aux gants vinyle avec une faible pertinence des allergenes commercialises dans ces cas.

BACKGROUND Photoaggravated allergic contact dermatitis caused by methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) and MI has been reported. OBJECTIVES To describe the clinical characteristics and results of (photo)patch tests and photo-tests of 10 patients in Belgium and France suffering from photoaggravated contact dermatitis caused by MI. PATIENTS AND METHODS Five men and five women, with a median age of 49.5 years, were investigated between January 2012 and February 2017 because of suspected photoaggravated contact dermatitis. Patch tests, photopatch tests and/or photo-tests were performed. RESULTS Seven patients had positive patch test reactions to both MCI/MI and MI, whereas 3 patients had positive patch test reactions only to MI. In most cases, MI was the (strong) primary sensitizer. Photopatch tests with MCI/MI and/or MI gave stronger reactions than patch tests with these derivatives, indicating photoaggravation. Sensitization probably took place from cosmetics and work-related biocides, whereas elicitation of dermatitis was remarkably often related to airborne exposure to MI present in paints or industrial biocides. Four patients suffered from transient photosensitivity. CONCLUSION Photoaggravated allergic contact dermatitis and transient photosensitivity caused by MI is a peculiar clinical presentation of allergic contact dermatitis caused by this preservative, and should be considered in daily clinical practice.

Introduction Nous rapportons un premier cas d’allergie de contact a un brassard tensionnel jetable lie a un nouvel allergene acrylate. Observations Un jeune homme de 16 ans etait adresse en 2019 pour eczema en regard d’un brassard tensionnel jetable. Ce patient diabetique de type 1 avait ete hospitalise 3 fois en reanimation medicale pour acidocetose diabetique. A chaque hospitalisation, il avait developpe un eczema au contact du brassard tensionnel jetable Philips®, qu’il portait en continu. Le patient avait aussi presente un eczema en regard d’un capteur glycemique FreeStyle® fin 2017 apres quelques mois d’utilisation, ce qui en avait motive l’arret. Il tolerait par ailleurs les pansements. Nous avons realise des patch-tests avec une BSE, une batterie colles et plastiques, une batterie acrylates/methacrylates, l’isobornylacrylate 0,1 % (Chemotechnique Diagnostics®, Vellinge, Suede), le capteur Freestyle®, le brassard Philips® (faces interne et externe, tuyau), le sparadrap et tuyau du saturometre, les electrodes ECG et une lingette de desinfection, selon les recommandations de l’ESCD. Resultats Les resultats ont confirme l’eczema de contact au capteur et au brassard : patch-tests positifs au capteur (+++), aux faces et tuyau du brassard (++), electrodes ECG (++), tuyau du saturometre (++). Surtout, on trouvait une positivite a de nombreux acrylates et methacrylates : IBOA 0,1 % (+++), butyl-acrylate 0,1 % (++), tetrahydrofurfuryl methacrylate 2 % (++), ethyl acrylate 0,1 % (++), 2-hydroxyethyl acrylate 0,1 % (+), 2-hydroxypropyl methacrylate 2 % (+), ethyleneglycol dimethacrylate 2 % (+), 1,6-hexanediol diacrylate 0,1 % (+), trimethylolpropane triacrylate 0,1 % (+), triethyleneglycol diacrylate 0,1 % (+). Nous avons alors effectue une declaration a la materiovigilance et contacte Philips, ce qui ne nous a pas permis de savoir quel(s) allergene(s) potentiel(s) etaient dans le brassard. Nous avons donc adresse le brassard au Dr O. Aerts (Anvers, Belgique) pour analyse et recherche d’allergene(s). L’analyse a trouve de l’IBOA en faible quantite dans la colle servant a fixer le tuyau au brassard, et par contre en tres grande quantite du phenoxyethylacrylate (PEA) dans le velcro. Nous avons alors convoque notre patient pour un patch test au PEA 0,1 % vas. (fourni par O.A) qui s’est revele tres positif (+++). Le brassard contient donc au moins deux acrylates potentiellement responsables de l’eczema de contact chez notre patient, et pouvant probablement donner des reactions croisees. Nous pensons qu’il s‘est initialement sensibilise a l’IBOA par l’intermediaire du Freestyle et qu’il a ensuite developpe un eczema lie a la forte quantite de PEA dans le brassard. Discussion Nous rapportons un premier cas d’allergie de contact a un brassard tensionnel jetable, contenant deux allergenes acrylates pertinents et particulierement le phenoxy-ethyl-acrylate. A ce jour, aucun autre cas n’a ete mentionne en materiovigilance nationale, ni aupres du fabricant Philips.

Introduction L’evaluation en vie reelle du benefice de l’omalizumab (OMA) dans le traitement de l’urticaire chronique spontanee (UCS) apporte des donnees importantes, complementaires de celles recueillies dans les etudes cliniques. L’etude observationnelle post-inscription LUCIOL, demandee par la Haute Autorite de Sante, a pour objectif d’evaluer l’efficacite et la tolerance de l’OMA dans l’UCS, en conditions reelles d’utilisation en France. Les resultats finaux a un an sont presentes ici. Materiel et methodes Il s’agit d’une etude nationale, descriptive, multicentrique, prospective avec un suivi d’un an des patients presentant une UCS, âges de plus de 12 ans pour lesquels il a ete decide d’initier un traitement par OMA a l’inclusion. Le critere primaire, evalue a 6 mois de traitement (M6) etait la proportion de patients avec une activite de l’UCS bien controlee (UAS7 ≤ 6). La securite d’emploi, la tolerance et la qualite de vie etaient egalement evaluees. Observations La population de l’etude etait comparable a celle observee en pratique courante. Les investigateurs ont frequemment adapte la posologie initiale d’OMA, principalement en espacant les injections. Cependant ces adaptations n’ont pas eu d’incidence sur les resultats obtenus sur une periode de 12 mois. En effet, les analyses d’efficacite, de securite d’emploi et de qualite de vie etaient similaires a celles des etudes pivots. Resultats Un total de 265 patients a ete analyse (âge moyen, 43,7 ans ; femmes, 66,4 % ; patients resistants aux AH1, 92,1 %). Avant d’etre traites par l’OMA, 64,2 % des patients avaient recu des AH1 a 4 fois la dose approuvee, 36,6 % des patients avaient recu des AH1 a dose approuvee, 37,4 % des anti-leucotrienes et 20,4 % des corticoides oraux. La proportion de patients ayant atteint un score UAS7 ≤ 6 etait de 68,8 % a M6 (n = 143) et de 74,9 % a M12 (n = 140). Une reponse complete (UAS7 = 0) a ete observee chez 58,3 % des patients (n = 109) a M12. Le score moyen DLQI/CDLQI a diminue de 11 a 1,7 entre l’inclusion et M12. La majorite des patients avait ete traitee par OMA a la dose de 300 mg jusqu’a M12 (pour 90 % d’entre eux). La modification de posologie la plus frequente etait une augmentation du delai entre les injections. La raison principale de modification de posologie etait une reponse non satisfaisante a M3 (62,2 % des cas) et une amelioration ou remission a M6 et M12 (respectivement, 76,1 % et 81,4 % des cas). Aucun nouveau signal de securite n’est apparu pendant l’etude. Discussion Les donnees finales de cette etude permettent de confirmer l’efficacite et le profil de tolerance d’OMA dans le traitement de l’UCS en conditions reelles d’utilisation. Ces resultats a un an nous apportent des informations concernant la prise en charge de patients atteints d’UCS, dont l’optimisation reste un enjeu important.

SummaryBackground Airborne allergic contact dermatitis caused by paints containing isothiazolinones has been recognized as a health hazard. Objectives To collect epidemiological, clinical and patch test data on airborne allergic contact dermatitis caused by isothiazolinone-containing paints in France and Belgium. Methods A descriptive, retrospective study was initiated by the Dermatology and Allergy Group of the French Society of Dermatology, including methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI)- and/or MI-sensitized patients who developed airborne allergic contact dermatitis following exposure to isothiazolinone-containing paint. Results Forty-four cases were identified, with mostly non-occupational exposure (79.5%). Of the patients, 22.5% of also had mucosal symptoms. In several cases, the dermatitis required systemic corticosteroids (27.3%), hospitalization (9.1%), and/or sick leave (20.5%). A median delay of 5.5 weeks was necessary to enable patients to enter a freshly painted room without a flare-up of their dermatitis. Approximately one-fifth of the patients knew that they were allergic to MI and/or MCI/MI before the exposure to paints occurred. Conclusion Our series confirms that airborne allergic contact dermatitis caused by paints containing isothiazolinones is not rare, and may be severe and long-lasting. Better regulation of isothiazolinone concentrations in paints, and their adequate labelling, is urgently needed.

Resume Introduction Les investigations en dermato-allergologie necessitent une bonne preparation. A cette fin, le groupe dermato-allergologie de la Societe francaise de dermatologie avait propose une fiche d’information sur le deroulement des patch-tests. Le but de notre etude etait d’evaluer l’utilite et la bonne comprehension de cette fiche d’information. Methodes Une fiche d’information etait envoyee au patient avant les tests. Un questionnaire lui etait remis le jour des tests afin d’evaluer la comprehension de la fiche. Un autre questionnaire etait remis en parallele au medecin dermato-allergologue afin de verifier le respect par le patient des recommandations figurant sur la fiche. Les deux questionnaires etaient evalues independamment et apparies pour apprecier la concordance entre patient et medecin. Resultats Huit services hospitaliers de dermato-allergologie ont participe a l’etude, permettant de recueillir, sur une duree de 18 mois, 921 questionnaires patient et 921 questionnaires medecin apparies. La majorite des patients avaient lu la fiche (96,2 %), l’avaient trouvee utile (98,8 %), facile a lire (97,4 %) et adaptee (91,5 %). Cependant, 10 % des patients avaient eu des difficultes de comprehension. Conclusion Cette etude a montre que la fiche d’information etait claire et explicite pour la grande majorite des patients. Neanmoins, grâce aux remarques de certains d’entre eux, la fiche a beneficie de quelques modifications pour en ameliorer encore la comprehension.