Search

Topical non-steroidal anti-inflammatory drugs (NSAIDs) can cause allergic contact dermatitis (ACD) and photocontact dermatitis. Although topical diclofenac is associated with fewer side effects than other topical NSAIDs, rare cases of contact dermatitis have been reported.

Resume Cas clinique Nous rapportons l’observation d’une patiente ayant presente un angiœdeme du visage de facon concomitante a une injection intraveineuse d’alteplase, comme traitement thrombolytique d’un accident vasculaire cerebral (AVC) ischemique. Le bilan allergologique (prick-test et intradermoreaction) etait negatif, et la reintroduction d’alteplase bien toleree, eliminant une hypersensibilite allergique IgE (Immunoglobuline E) dependante. Discussion La survenue d’angiœdeme est un effet secondaire classique de l’alteplase. Il est souvent spontanement resolutif, mais peut entrainer un risque vital. Les facteurs de risque sont le sexe feminin, un AVC ischemique du cortex insulaire et un traitement par IEC (inhibiteur de l’enzyme de conversion). Sa physiopathologie est mal comprise, regroupant 3 principales hypotheses : une hypersensibilite dependant des IgE, une degranulation mastocytaire non specifique ou une activation bradykinique. Les tests cutanes, suivis d’une reintroduction d’alteplase en cas de negativite, sont donc interessants pour eliminer un mecanisme IgE. L’alteplase n’etant activee qu’en presence de fibrine, sa reintroduction n’entraine pas de risque hemorragique en l’absence de thrombose. Conclusion Une meilleure connaissance des angioedemes survenant sous alteplase pourrait permettre d’ameliorer leur gestion en urgence, mais aussi leur prise en charge allergologique.

European Baseline Series (EBS) of haptens (contact allergens) is used throughout Europe, containing patch tests essential for the diagnosis of contact allergy (Tables I and II) [1]. Exposure to environmental allergens is constantly evolving and the EBS must be adapted accordingly in order to guarantee its relevance of the molecules tested, in particular by the addition of emerging allergens [1].

The cutaneous microbiota contributes to skin barrier function, ensuring effective protection against pathogens and contributing to the maintenance of epidermal integrity. Dysbiosis is frequently present in atopic dermatitis (AD), a chronic inflammatory disease associated with skin barrier defects. Dysbiosis is associated with reduced bacterial diversity and marked Staphylococcus aureus colonization, which is favoured in the case of certain local AD-specific properties such as reduced skin acidity, eased bacterial adhesion and decreased antimicrobial peptide production. Furthermore, S. aureus-associated skin dysbiosis, via the production of staphylococcal virulence factors, may also participate in the immunopathology of AD by altering the epidermal barrier and inducing an inflammatory response. However, there are currently no arguments for recommending screening for, and treatment of S. aureus-associated dysbiosis outside the setting of cutaneous superinfection. Nonetheless, modulation of the skin microbiota may hold promise for AD management. Here, we describe the relationships that exist between the skin microbiota and AD.

Background Cancer patients are being exposed to antineoplastic drugs more frequently and for longer periods, resulting in a higher risk of hypersensitivity reactions. The aim of this study was to assess the pharmaceutical time and direct cost of drug allergy explorations following immediate hypersensitivity reactions to antineoplastic agents. Methods A micro-costing method was used to collect data on consumption of human and material resources for allergy exploration preparations. The monetisation was carried out on the basis of prices and hourly wage costs applied in 2018. The number and type of allergy explorations prepared by the pharmacy as well as nature of antineoplastic drugs tested, and the number of culprit drugs reintroductions were collected. Results Almost 1.5 h is required to realise allergy tests for one patient including pharmacist time for prescription analysis and pharmacy technician's time for tests preparation. The mean manufacturing cost of these tests is estimated at €62.87 (€57.82–65.49) per culprit drug for one patient. Programming patients according to culprit drugs tested allows rationalising healthcare provider time and increasing efficiency. From January 2010 to December 2018, 277 patients were tested and 490 allergy explorations were performed, corresponding to more than 5000 preparations. Mostly, the culprit drug could be reintroduced ( n = 383, 78.2%) allowing patients to receive the best possible treatment. Conclusion Management of hypersensitivity reactions is constantly progressing, as it contributes to improving patient care in oncology. This activity is time-consuming for the pharmacy team but allows patients with previous hypersensitivity reaction to continue effective treatment.

Resume L’eczema de contact allergique (ECA) est une dermatose inflammatoire frequente. Il se definit comme une reaction d’hypersensibilite retardee induite suite au recrutement dans la peau de lymphocytes T (LT) specifiques d’antigenes chez des individus prealablement sensibilises. Les lesions d’eczema ont tendance se developper sur des zones prealablement atteintes et a s’aggraver au fil du temps. Cette observation clinique a conduit a s’interroger sur la contribution des lymphocytes T residents memoires (TRM) aux recidives et a la severite de l’ECA. Les TRM sont des LT memoires qui persistent a long terme dans les tissus peripheriques tels que la peau sans recirculer dans l’organisme. Bien que ces cellules assurent une surveillance immunitaire efficace contre les pathogenes, elles peuvent egalement participer au developpement et a l’aggravation de nombreuses maladies inflammatoires comme les allergies cutanees. Des travaux recents ont ainsi mis en evidence le role majeur des TRM dans la physiopathologie de l’ECA, en faisant une cible therapeutique potentielle. Cette revue se propose donc de decrire les caracteristiques generales des TRM et leur contribution dans l’ECA.

Resume Introduction Une majorite des adultes consultant pour une dermatite atopique (DA) presente une forme moderee a severe, alors qu’existent des consensus d’experts et de traitements efficaces. L’objectif de cette enquete etait d’evaluer les pratiques en soins primaires pour la prise en charge diagnostique et therapeutique de la DA de l’adulte. Methodes Une enquete de pratique a ete realisee a l’aide d’un questionnaire en ligne aupres de 2307 medecins generalistes (MG) francais de janvier a mars 2019. Resultats Les reponses de 200 MG ont ete analysees. Parmi eux, 63 % (n = 126) exprimaient des difficultes dans la prise en charge de la DA. Le diagnostic de DA etait facile pour 50 % (n = 101) des MG, avec une excellente connaissance des criteres diagnostiques de la DA. La prise en charge therapeutique comprenait les emollients en traitement de fond et les dermocorticoides (DC) pour les poussees pour 99 % (n = 198) des MG. Cependant, la prescription de DC etait : (i) reservee aux lesions severes dans 50 % des cas, (ii) de duree variable entre les MG, (iii) mal quantifiee, avec une meconnaissance de l’unite phalangette par 78 % des MG. L’inobservance aux DC etait rapportee comme etant la principale cause d’echec therapeutique dans 79 % des cas, alors meme que les conseils d’utilisation des DC semblaient discordants ou insuffisants. Conclusions Malgre une bonne connaissance theorique, des ameliorations sont necessaires dans la prise en charge pratique de la DA en soins primaires. Le developpement de fiches d’information pourrait ameliorer cette prise en charge.

Background Chronic venous disease (CVD) is secondary to venous hypertension, leading to vascular inflammation and tissue changes. The impact of CVD on skin structure and barrier function is not well characterized. Objective We aimed to assess the characteristics of skin alterations in mild-to-moderate CVD by non-invasive techniques based on a prospective exploratory study. Material & methods Female subjects (30-75 years) with CVD (Stage C2 to C4, CEAP classification) were eligible. Stage C0-C1 CVD subjects were used as controls. Women with leg surgery or a medical history that could impact the results were excluded. The skin changes on lesional (LS) and non-lesional (NLS) areas were assessed by biometric analysis including skin echography, viscoelasticity evaluation, confocal microscopy and trans epidermal water loss (TEWL) measurements. Results Thirty-four subjects were enrolled. Based on computation of 26 biometric parameters using Principal Component Analysis, a significant difference between LS and NLS zones, regardless of the CEAP class, was evidenced. C2-C4 subjects presented with dermal thickening suggesting oedema associated with decreased cell density, while no difference in skin viscoelasticity was observed compared to the C0-C1 control group. Epidermal structural modifications were associated with increased TEWL correlating with CVD severity. Conclusion Skin alterations in CVD patients are detectable by non-invasive methods. These findings may help to better assess new therapeutic strategies.

Diagnosis of contact allergy (CA) to Amerchol L-101 (AL-101), a marker for lanolin allergy, is problematic. Positive patch test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance.To gain further insight on the allergic or irritant nature of skin reactions induced by AL-101 patch test.We re-tested in a dose-response fashion, 10 subjects with AL-101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real-time polymerase chain reaction [qRT-PCR]) of samples of their skin reactions.Eight of the 10 CA subjects reacted positively upon re-test, whereas two did not react. Most of AL-101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch test reactions and the concentration of AL-101 applied. However, we observed that some of the positive patch test reactions to AL-101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples.This study confirms that AL-101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis.

Background The therapeutic options in atopic dermatitis rely on consensus-based guidelines, also established for psoriasis and chronic urticaria. However, the therapeutic approach in atopic dermatitis, especially in the moderate-to-severe forms of the disease, seems less aggressive than in psoriasis and in chronic urticaria with a less frequent use of systemic agents. Objectives To compare in real-life conditions the therapeutic management of adults with atopic dermatitis with those with psoriasis and chronic urticaria. Methods A transversal analysis was performed in May 2017, using retrospective data from a monocentric database. Data on epidemiology, severity, therapeutic educational intervention and systemic treatments were analysed from 401 patients with atopic dermatitis, compared with data from 230 patients with chronic urticaria and 535 patients with psoriasis. Results A high proportion (73%) of atopic dermatitis patients presented with a moderate-to-severe form of the disease compared to only 39% of chronic urticaria and 17% of psoriasis patients. Most of atopic dermatitis patients (78%) had completed a therapeutic educational programme, while the adherence was lower in chronic urticaria (35%) and in psoriasis (3%) patients. A systemic treatment, including biologicals, was recorded in 8% of atopic dermatitis patients, while it concerned 26% and 47% of chronic urticaria and psoriasis patients, respectively. Conclusions We confirmed that atopic dermatitis treatment mostly relies on topical treatments. Only a minority of moderate-to-severe atopic dermatitis patients who are eligible for a systemic treatment receive such therapy. This may suggest promoting a more frequent use of systemic agents in moderate-to-severe atopic dermatitis.

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.To date, little is known about the contribution of skin dendritic cells (skDCs) to T-cell remodeling and EPIT efficacy.We capitalized on a preclinical model of food allergy to ovalbumin (OVA) to characterize the phenotype and functions of OVAsup+/supskDCs throughout the course of EPIT.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 OVAsup+/supLangerhans cells progressively lost their capacity to prime CD4sup+/supTsubEFF/subcells, but gained regulatory T-cell stimulatory properties. In contrast, cDC1 were inefficient in priming CD4sup+/supTsubEFF/subcells or in reactivating TsubMEM/subcells in vitro, whereas cDC2 retained moderate stimulatory properties, and progressively biased type 2 immunity toward type 1 and type 17 responses.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.

Red blood cell exchanges are frequently used to treat and prevent cerebrovascular complications in patients with sickle cell anemia (SCA). However, the low weight of young children represents serious concerns for this procedure. The Spectra Optia device can perform automatic priming using red blood cells (RBCs) (RCE/RBC-primed) which could allow RBC exchanges (RCE) to be performed in young children without hypovolemic complications, but this method requires evaluation. We prospectively analyzed the clinical safety of the RCE/RBC-primed procedure in 12 SCA low-weight children under either a chronic RCE program or emergency treatment over 65 sessions. We monitored grade 2 adverse events (AEs) such as a decrease in blood pressure, increase in heart rate, fainting sensation, or transfusion reactions and identified the critical times during the sessions in which AEs could occur. Post-apheresis hematocrit (Hct) and a fraction of cell remaining (FCR) values were compared to the expected values. We also compared the impact of automatic RCE (n = 7) vs. RCE/RBC-primed (n = 8) on blood viscosity and RBC rheology. A low incidence of complications was observed in the 65 RCE sessions with only seven episodes of transient grade 2 AEs. Post-apheresis Hct and FCR reached expected values with the RCE/RBC-primed method. Both the automatic and priming procedures improved RBC deformability and decreased the sickling tendency during deoxygenation. Blood rheological features improved in both RCE/RBC-primed and automatic RCE without priming conditions. The RCE/RBC-primed procedure provides blood rheological benefits, and is safe and efficient to treat, notably in young children with SCA in prophylactic programs or curatively when a SCA complication occurs.

Psoriasis is a multifactorial skin pathology resulting from genetic susceptibility and environmental triggers that lead to epidermal and immune dysfunction. There is now strong evidence that non-lesional (NL) psoriatic skin, despite its normal appearance, represents an intermediate state between healthy and lesional skin. Changes observed in NL skin mainly affect the skin barrier, keratinocytes, innate and adaptive immune responses, the microbiota and neurogenic tissue innervation. Several epidermal barrier defects are commonly observed in NL skin compared to healthy skin, including an elevated pH, delayed barrier function repair after injury and lower expression of epidermal differentiation complex proteins. NL keratinocytes also show a predisposition for activation and proliferation, and an increased sensitivity to cytokine or microbial triggers, probably linked to their unique transcriptome and proteome, associated with their intermediate state between healthy and lesional cells. In addition, the accumulation of pathogenic IL-17-producing resident memory T cells, which can (re)instigate the formation of new lesions, characterises both the NL and never-lesional skin of patients with psoriasis. Although the contribution of NL skin dysbiosis to psoriasis pathophysiology remains to be clarified, the expression of numerous pruritogenic mediators appears to be involved in disease progression due to an iterative itch-scratch cycle. In summary, the NL skin of patients with psoriasis exhibits numerous hallmarks of dormant psoriasis. The fact that these alterations are mostly located in the epidermis suggests that they are readily accessible to topical treatments, which could prevent the recurrence/spread of this chronic disease.

International audience

More than 1 million joint replacement surgeries are performed each year in the United States, and failure occurs in 10% of them, raising major health and economic burdens. The reasons for failure are multiple and include malposition, infection, and hypersensitivity (HS)/allergy to implant components. The term "hypersensitivity", defining an inflammatory reaction to the implant components, is more appropriate than the term "allergy," because the implant-induced inflammation can be mediated by innate or adaptive immunity. Implant HS, also sometimes called "adverse reaction to metal debris" or "pseudotumor- like periprosthetic tissue reactions" in the specific condition or metal-on-metal hip replacement, undoubtedly exists, but it cannot be stated to always be an allergic reaction. Innate HS, also referred to as nonallergic HS, may develop in response to the generation of metal/polymer wear debris, which causes local inflammation due to activation of macrophages, thus leading to osteoclast triggering, bone resorption, and implant loosening. There is no diagnostic test for nonallergic HS. Conversely, adaptive HS, that is, allergy to prosthesis, also called type IV HS, is mediated by specific T cells that infiltrate the periimplant tissue where they are activated by antigen-presenting cells. The main allergens are metals (nickel, chromium, cobalt) and bone cement compounds. T-cell activation leads to the recruitment of leucocytes, which will cause joint inflammation, pain, and loosening.

Summary Background To address the unmet medical need for an effective prophylactic vaccine against Ebola virus we assessed the safety and immunogenicity of three different two-dose heterologous vaccination regimens with a replication-deficient adenovirus type 26 vector-based vaccine (Ad26.ZEBOV), expressing Zaire Ebola virus glycoprotein, and a non-replicating, recombinant, modified vaccinia Ankara (MVA) vector-based vaccine, encoding glycoproteins from Zaire Ebola virus, Sudan virus, and Marburg virus, and nucleoprotein from the Tai Forest virus. Methods This randomised, observer-blind, placebo-controlled, phase 2 trial was done at seven hospitals in France and two research centres in the UK. Healthy adults (aged 18–65 years) with no history of Ebola vaccination were enrolled into four cohorts. Participants in cohorts I–III were randomly assigned (1:1:1) using computer-generated randomisation codes into three parallel groups (randomisation for cohorts II and III was stratified by country and age), in which participants were to receive an intramuscular injection of Ad26.ZEBOV on day 1, followed by intramuscular injection of MVA-BN-Filo at either 28 days (28-day interval group), 56 days (56-day interval group), or 84 days (84-day interval group) after the first vaccine. Within these three groups, participants in cohort II (14:1) and cohort III (10:3) were further randomly assigned to receive either Ad26.ZEBOV or placebo on day 1, followed by either MVA-BN-Filo or placebo on days 28, 56, or 84. Participants in cohort IV were randomly assigned (5:1) to receive one dose of either Ad26.ZEBOV or placebo on day 1 for vector shedding assessments. For cohorts II and III, study site personnel, sponsor personnel, and participants were masked to vaccine allocation until all participants in these cohorts had completed the post-MVA-BN-Filo vaccination visit at 6 months or had discontinued the trial, whereas cohort I was open-label. For cohort IV, study site personnel and participants were masked to vaccine allocation until all participants in this cohort had completed the post-vaccination visit at 28 days or had discontinued the trial. The primary outcome, analysed in all participants who had received at least one dose of vaccine or placebo (full analysis set), was the safety and tolerability of the three vaccination regimens, as assessed by participant-reported solicited local and systemic adverse events within 7 days of receiving both vaccines, unsolicited adverse events within 42 days of receiving the MVA-BN-Filo vaccine, and serious adverse events over 365 days of follow-up. The secondary outcome was humoral immunogenicity, as measured by the concentration of Ebola virus glycoprotein-binding antibodies at 21 days after receiving the MVA-BN-Filo vaccine. The secondary outcome was assessed in the per-protocol analysis set. This study is registered at ClinicalTrials.gov , NCT02416453 , and EudraCT, 2015-000596-27. Findings Between June 23, 2015, and April 27, 2016, 423 participants were enrolled: 408 in cohorts I–III were randomly assigned to the 28-day interval group (123 to receive Ad26.ZEBOV and MVA-BN-Filo, and 13 to receive placebo), the 56-day interval group (124 to receive Ad26.ZEBOV and MVA-BN-Filo, and 13 to receive placebo), and the 84-day interval group (117 to receive Ad26.ZEBOV and MVA-BN-Filo, and 18 to receive placebo), and 15 participants in cohort IV were assigned to receive Ad26.ZEBOV and MVA-BN-Filo (n=13) or to receive placebo (n=2). 421 (99·5%) participants received at least one dose of vaccine or placebo. The trial was temporarily suspended after two serious neurological adverse events were reported, one of which was considered as possibly related to vaccination, and per-protocol vaccination was disrupted for some participants. Vaccinations were generally well tolerated. Mild or moderate local adverse events (mostly pain) were reported after 206 (62%) of 332 Ad26.ZEBOV vaccinations, 136 (58%) of 236 MVA-BN-Filo vaccinations, and 11 (15%) of 72 placebo injections. Systemic adverse events were reported after 255 (77%) Ad26.ZEBOV vaccinations, 116 (49%) MVA-BN-Filo vaccinations, and 33 (46%) placebo injections, and included mostly mild or moderate fatigue, headache, or myalgia. Unsolicited adverse events occurred after 115 (35%) of 332 Ad26.ZEBOV vaccinations, 81 (34%) of 236 MVA-BN-Filo vaccinations, and 24 (33%) of 72 placebo injections. At 21 days after receiving the MVA-BN-Filo vaccine, geometric mean concentrations of Ebola virus glycoprotein-binding antibodies were 4627 ELISA units (EU)/mL (95% CI 3649–5867) in the 28-day interval group, 10 131 EU/mL (8554–11 999) in the 56-day interval group, and 11 312 mL (9072–14106) in the 84-day interval group, with antibody concentrations persisting at 1149–1205 EU/mL up to day 365. Interpretation The two-dose heterologous regimen with Ad26.ZEBOV and MVA-BN-Filo was safe, well tolerated, and immunogenic, with humoral and cellular immune responses persisting for 1 year after vaccination. Taken together, these data support the intended prophylactic indication for the vaccine regimen. Funding Innovative Medicines Initiative and Janssen Vaccines & Prevention BV. Translation For the French translation of the abstract see Supplementary Materials section.

Resume La formation en allergologie en France en 2020 est dans une periode de transition ou se cotoient deux systemes d’enseignement, dont l’un est amene a disparaitre. L’ancien systeme associe le diplome d’etudes specialisees complementaires (DESC) allergologie et immunologie clinique pour les internes ayant passe le concours de l’internat avant 2017, et la capacite d’allergologie pour les medecins theses. Le nouveau systeme, depuis 2017, associe le diplome d’etudes specialisees (DES) allergologie et la formation specialisee transversale (FST) maladies allergiques pour les internes en formation et la capacite d’allergologie pour les medecins theses. En 2020, les 4 formations (DESC, DES, FST et capacite d’allergologie) coexistent.

This study highlights the key role of polycytotoxic CD8+ T cells in the severity of toxic epidermal necrolysis., Toxic epidermal necrolysis (TEN) is a life-threatening cutaneous adverse drug reaction. To better understand why skin symptoms are so severe, we conducted a prospective immunophenotyping study on skin and blood. Mass cytometry results confirmed that effector memory polycytotoxic CD8+ T cells (CTLs) are the main leucocytes in TEN blisters at the acute phase. Deep T cell receptor (TCR) repertoire sequencing identified massive expansion of unique CDR3 clonotypes in blister cells. The same clones were highly expanded in patient’s blood, and the degree of their expansion showed significant correlation with disease severity. By transducing α and β chains of the expanded clonotypes into a TCR-defective cell line, we confirmed that those cells were drug specific. Collectively, these results suggest that the relative clonal expansion and phenotype of skin-recruited CTLs condition the clinical presentation of cutaneous adverse drug reactions.

Resume Introduction L’uvulite (œdeme de la luette) vibratoire est une urticaire physique de diagnostic simple pouvant etre traitee chirurgicalement. L’indication de l’uvulectomie est souvent meconnue et mal definie. Cas clinique Un patient de 39 ans, ayant comme principaux antecedents une urticaire a l’effort et une ronchopathie, etait adresse en consultation en novembre 2018 pour angiœdemes de la luette recidivants. Les antecedents medicaux etaient une ronchopathie avec des desaturations nocturnes importantes pendant 67 % du temps de sommeil sans apnee du sommeil objectivee par une polysomnographie en 2018, un dermographisme, une urticaire d’effort avec prurit du cuir chevelu et a la pression. Plusieurs antecedents familiaux d’hypersensibilite medicamenteuse et alimentaire. Il rapportait la survenue de 4 episodes importants d’angiœdemes de la luette en 14 ans qui avaient ete consideres jusqu’au dernier episode comme des angiœdemes larynges idiopathiques. Le premier a l’âge de 25 ans dans les suites d’un accident de la voie publique avec l’administration d’AINS au decours lors de la prise en charge aux urgences et resolutifs avec des antihistaminiques. Deux autres episodes en 2012 et 2016 presents au reveil avec une prise d’aliments histamino-liberateurs la veille resolutive spontanement et par automedication par 60 mg de SOLUPRED. Le dernier episode majeur en 2017 avait ete associe a des vomissements et avait motive une consultation aux urgences resolutive par SOLUPRED 60 mg. L’angiœdeme bradykinique avait alors ete ecarte par le dosage du C1 Inhibiteur fonctionnel et ponderal, tous deux normaux. Plusieurs episodes de moindre intensite etaient rapportes au reveil et de resolution spontanee. Un traitement par un comprime de XYZALL avait ete initie en janvier 2018 sans efficacite. L’examen clinique lors de la consultation retrouvait une luette anatomiquement longue sans autre anomalie. Le diagnostic d’uvulite vibratoire etait retenu devant une luette œdemateuse, le terrain d’urticaire physique, la ronchopathie, le caractere nocturne. La prise en charge a ete une majoration du traitement antihistaminique a 4 comprimes par jour dans l’attente d’une uvulectomie non encore realisee a ce jour. Une education therapeutique sur les cofacteurs d’urticaire a ete dispensee avec une utilisation raisonnee des AINS sans contre-indication absolue. Discussion Il n’existe pas a ce jour de recommandations de prise en charge de l’uvulite vibratoire. Van Der Brempt et al. mettent en avant le traitement des facteurs de risques (reflux gastrœsophagien, syndrome d’apnee du sommeil) tandis que Nosbaum et al. montrent le benefice de l’uvulectomie geste simple realise sous anesthesie locale. L’uvulectomie est l’une des rares indications de la chirurgie comme traitement radical d’une urticaire. Conclusion L’uvulectomie peut etre proposee pour traiter des urticaires vibratoires associees a une ronchopathie resistante aux antihistaminiques.

Contact dermatitis comprises two main groups: irritant (ICD) and allergic (ACD) contact dermatitis. It presents as acute, subacute, or chronic eczema. Although it is possible to differentiate ICD from ACD on clinical ground, both diseases can have very similar clinical, histological, and molecular presentations.

Immune-mediated skin diseases induced by chemicals and drugs are mainly T-cell mediated reactions, i.e. type IV hypersensitivity of the Gell & Coombs classification. Clinical expressions depend on the exposition route of the chemical with allergic contact dermatitis in case of skin exposure and delayed drug allergy in case of oral or parenteral intake. Allergic contact dermatitis and delayed drug allergy share common pathophysiologic pathways with chemical-specific T cells recruitment to the skin to eliminate chemical-expressing keratinocytes. In this review, we discuss the pathophysiology of allergic contact dermatitis and delayed drug allergy with focus on their common pathways.

Introduction La cellulite eosinophile (CE) est une affection cutanee rare caracterisee par des plaques urticariennes prurigineuses fixes et un infiltrat inflammatoire dermique polymorphe incluant de nombreux polynucleaires eosinophiles (PNEo). Les mecanismes physiopathologiques de la CE restent mal connus : le paradigme actuel supporte l’hypothese d’une hypersensibilite de type retarde mediee par l’interleukine (IL) 5. Les traitements standards reposent essentiellement sur des immunomodulateurs (ie corticosteroides, dapsone, ciclosporine) mais de nombreux patients restent resistants sans solution therapeutique precise. Le but de cette etude etait de mieux caracteriser les voies inflammatoires impliquees dans la CE. Materiel et methodes Nous avons analyse retrospectivement des echantillons de peau provenant de 12 patients atteints de CE et de 5 temoins sains, en utilisant la RT-qPCR et l’immunomarquage phospho-STAT (pSTAT). Nous avons ensuite explore la reponse clinique et moleculaire d’un patient refractaire traite avec le nouvel inhibiteur de JAK1/JAK2, le baricitinib. Resultats Nous avons observe une augmentation significative des transcriptions d’ARNm liees a des marqueurs specifiques de l’inflammation de type 2 (IL-13 et IL-3R, mais pas IL-5) et du recrutement des eosinophiles (CCL17, CCL18 et CCL26) dans la peau lesionnelle des patients atteints de CE comparativement aux temoins. Nous avons egalement observe que presque tous les echantillons de CE etaient fortement positifs pour pSTAT-5 et, a un moindre degre, pour pSTAT-1. En comparaison, la coloration de pSTAT-3 etait negative. Comme les pSTAT-1 et -5 sont classiquement associees a l’activation de JAK1/2, nous avons ensuite traite un patient EC refractaire (echec corticosteroides, dapsone, ciclosporine et lesions actives depuis plus de 3 ans) avec du baricitinib a 4 mg/jour. Apres 1 mois de traitement le patient etait totalement blanchi et sans recidive a ce jour. De facon concomitante, les marqueurs d’inflammation de type 2, notamment IL-13, IL-3, CCL17, CCL18 et CCL26 ont ete completement normalises dans la peau guerie apres le traitement par baricitinib. Discussion Nos resultats suggerent que la CE est liee a une inflammation cutanee de type 2 avec une activation essentiellement de la voie pSTAT5 et une elevation importante des IL13 et IL3, mais pas de l’IL5. Le retrocontrole negatif de l’IL3, classiquement produite par les PNEo, sur la production d’IL5 et de son recepteur, pourrait expliquer ce resultat. Enfin, ces resultats suggerent l’efficacite des traitements ciblant specifiquement l’inflammation de type 2 dans cette pathologie et ces traitements pourraient presenter un interet majeur dans formes refractaires.

Resume La necrolyse epidermique toxique est une reaction cutanee medicamenteuse rare et severe qui se caracterise par une necrose brutale de l’epiderme, entrainant un decollement cutane plus ou moins etendu. Il s’agit d’une urgence vitale avec jusqu’a 30 % de deces a la phase aigue. L’importance de la surface decollee definit deux entites cliniques : le syndrome de Stevens-Johnson quand le decollement est inferieur a 10 % et le syndrome de Lyell quand il est superieur a 30 %. A distance, le risque de complications, notamment sous forme de synechies des muqueuses, est particulierement eleve et doit etre prevenu systematiquement. Le mecanisme physiopathologique repose essentiellement sur une reaction d’hypersensibilite medicamenteuse retardee dans laquelle les lymphocytes cytotoxiques jouent un role majeur. Le terrain genetique intervient egalement avec des associations HLA-medicament maintenant bien decrites, notamment dans les populations asiatiques. La question du traitement reste encore tres debattue : il repose essentiellement sur la corticotherapie systemique, la ciclosporine ou encore les immunoglobulines IV. Quelques etudes suggerent egalement un interet des anti-TNF-alpha.

Introduction Une patiente de 48 ans presente le lendemain de la premiere injection de sa premiere cure de chimiotherapie par Paclitaxel (Taxol®) un exantheme maculo papuleux generalise sans gravite clinico-biologique resolutif en quelques jours (preciser). L’exploration allergologique retrouve une IDR positive a 48 h pour le Paclitaxel. L’hypothese d’une fausse positivite par un mecanisme irritatif est evoquee. Une analyse moleculaire de l’inflammation cutanee a ete realisee sur une biopsie de l’IDR Paclitaxel. Methodes Trois biopsies de peau ont ete realisees : (1) Biopsie d’une IDR negative a un autre medicament pris par la patiente (Ondansetron) ; (2) Biopsie de l’IDR Paclitaxel ; (3) Biopsie de peau saine. Une analyse RT-PCR quantitative mesurant les transcrits ARN des CD4, CD8, GrzB et IFNγ a ete realise sur les 3 biopsies. Resultats Les resultats sont presentes sous la forme d’un fold change, comparant l’expression des transcrits ARN dans la biopsie de l’IDR negative et la biopsie de l’IDR Paclitaxel, par rapport a l’expression des transcrits ARN dans la peau saine. Il est observe une forte augmentation de l’expression de CD4, CD8, GrzB et IFNγ dans l’IDR Paclitaxel. Discussion Les resultats sont en faveur d’une infiltration de lymphocytes T activites et cytotoxiques dans l’IDR Paclitaxel, nous ayant permis de conclure a un exantheme maculo papuleux allergique. La patiente s’est peut-etre sensibilise prealablement au Cremophor EL entrant dans la composition de la chimiotherapie, ce qui expliquerait une reaction des la premiere injection. Conclusion L’analyse moleculaire de l’inflammation cutanee des tests allergologiques permet de differencier allergie (activation de l’immunite adaptative) et irritation (activation de l’immunite innee).

Introduction Les patients atteints de mucoviscidose (MV) sont regulierement traites par antibiotiques (ATB) pour des infections respiratoires, et rapportent frequemment des reactions d’hypersensibilite (HSR). Le but de cette etude etait de mettre en lumiere les caracteristiques cliniques, les ATB impliques et la prevalence des HSR aux ATB dans la population MV. Methodes Dans cette etude retrospective, les dossiers medicaux de tous les patients MV suivis au Centre Hospitalier Universitaire de Lyon ont ete etudies et les suspicions d’HSR aux ATB, leurs caracteristiques cliniques et les explorations allergologiques ont ete analysees. Resultats Sur les 601 patients MV suivis a Lyon, 60 ont presente 95 suspicions d’HSR (prevalence de 10,0 %). Les β-lactamines etaient les ATB les plus souvent en cause, mais le cotrimoxazole etait egalement frequemment implique. 76 sur 95 suspicions d’HSR ont ete evalue par tests cutanes (TC)(43/76 reactions) et/ou reintroduction complete de l’ATB (73/76 reactions). Sur les 43 suspicions d’HSR evalues par TC, seules 3 etaient associees a un TC positif et n’ont pas ete suivies d’une reintroduction de l’ATB. Les 73 suspicions d’HSR restantes ont ete evaluees par reintroduction complete de l’ATB : des symptomes d’HSR ont recidive dans 10/73 cas, confirmant le diagnostic d’HSR. Les 63 autres reintroductions n’ont pas induit de recidive des symptomes, excluant le diagnostic d’HSR. En definitive, seulement 13/76 suspicions d’HSR a un ATB ont ete confirme par l’exploration allergologique. Discussion De meme que dans la population generale, la majorite des suspicions d’HSR a un ATB ont eu un diagnostic exclu par l’exploration allergologique. Par ailleurs, la plus forte prevalence de suspicions d’HSR au cotrimoxazole dans la population MV pourrait etre en lien avec la mutation CFTR caracteristique de la maladie. Conclusion La prevalence des reactions d’HS a un ATB suspectes et confirmees par exploration allergologique chez les patients MV est similaire a celle rapportee dans la population generale. Ainsi, une telle exploration apparait indispensable pour poser un diagnostic clair et ne pas induire d’eviction medicamenteuse inutile dans une population necessitant de nombreuses prises d’ATB.