A. Nosbaum

Role of T cells in nonimmediate allergic drug reactions.

Purpose of reviewThis review presents the current knowledge of the role of T cells in drug allergy manifesting as exanthematous, pustular and bullous skin diseases, collectively referred to as nonimmediate allergic drug reactions. Recent findingsBoth CD4+ and CD8+ T cells producing type 1 and type 2 cytokines and endowed with cytotoxic properties are involved in nonimmediate allergic drug reactions. Recent studies have confirmed that CD8+ T cells play a major role in the pathophysiology of nonimmediate allergic drug reactions, and have characterized new cytotoxic molecular pathways responsible for the severity of the bullous forms of nonimmediate allergic drug reactions. SummaryNonimmediate allergic drug reactions are mediated by T cells and mostly affect the skin. Nonimmediate allergic drug reactions comprise several diseases ranging from the frequent and benign maculo-papular exanthema to the severe and rare toxic epidermal necrolysis. Progress in the knowledge of the pathophysiology of nonimmediate allergic drug reactions comes from a better understanding of the mechanisms of drug recognition by T cells and from a careful analysis of the phenotype and functions of CD4+ and CD8+ T cells infiltrating the skin lesions. Recent studies have confirmed that the different clinical forms of nonimmediate allergic drug reactions are associated with distinct types of T cell-mediated skin inflammation. However, CD8+ T cells appear as major effector T cells in most of the nonimmediate allergic drug reactions. Future studies to analyze the early cellular and molecular events leading to the development of the allergic skin reaction will be helpful in order to define diagnostic and therapeutic targets.

Severe immediate hypersensitivity and allergic contact dermatitis caused by hair dyes.

A 43-year-old female experienced dermatitis of the scalp and neck after each hair colouring, which was carried out every 6 weeks. She had no medical history and had never had any temporary black henna tattoo. In August 2010, the application of hair dye provoked an immediate pruritus of the scalp, with a malaise that lasted for 15 min. During the following hair dye procedure, a severe reaction occurred, with generalized pruritus and erythema, dyspnoea, vomiting, and hypotonia. The symptoms disappeared over a 2-hr period at home. The usual contact dermatitis appeared thereafter, and lasted for 8 days. The skin tests were performed under strict medical monitoring, with the consent of the patient, who had an intravenous access. The open tests were first applied for 30 seconds and read at 20 min. The results were doubtful (localized pruritus) for the hair dye (mixture of colouring cream with an oxidant, 1:1) and negative for the colouring cream and the developer tested separately. Then, open tests were applied and read at 20 min. The results were positive (strong localized urticarial reaction) for the hair

Prevention of nonsteroidal inflammatory drug-induced urticaria and/or angioedema.

BACKGROUNDnUrticaria and/or angioedema (U/AE) are the most frequent and less severe forms of nonallergic hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs). Management of NSAID-induced U/AE includes (1) the avoidance of the culprit drug and of cyclooxygenase (COX) 1 inhibitors, (2) the use of weak COX-2 inhibitors, and/or (3) desensitization to aspirin. Because these possibilities may have drawbacks, we tested the possibility of preventing NSAID-induced U/AE by the administration of antihistamines and/or a combination of antihistamines and leukotriene antagonists.nnnOBJECTIVEnTo test the preventive effect of antihistamines and/or leukotriene antagonists on the development of U/AE in patients with a history of NSAID hypersensitivity confirmed by a positive challenge result.nnnMETHODSnA single, placebo-controlled, oral challenge using the culprit NSAID was applied to 65 patients with a history of NSAID-induced U/AE. In the case of recurrence of the symptoms, another oral challenge was performed under premedication with antihistamines alone or combined antihistamines and leukotriene antagonists.nnnRESULTSnA total of 59 of 65 patients (90%) tolerated a normal dose of NSAID, confirming previous data on the poor reproducibility of nonallergic hypersensitivity reactions to NSAIDs on challenge. Of the 6 patients who experienced recurrence of the U/AE on NSAID challenge, antihistamines and combined antihistamines and leukotriene antagonists prevented the hypersensitivity reactions in 2 and 3 of them, respectively. Only 1 patient still developed a moderate NSAID-induced urticaria despite the double premedication.nnnCONCLUSIONnTreatment with NSAIDs at normal doses is possible and well tolerated in patients who have experienced NSAID-induced U/AE, which could be prevented by the concomitant use of antihistamines and leukotriene antagonists.

Blocking T helper 1/T helper 17 pathways has no effect on patch testing

Blocking T helper 1/T helper 17 pathways has no effect on patch testing Audrey Nosbaum1,2, Aurore Rozieres2, Brigitte Balme3, Catherine Goujon1, Jean-Francois Nicolas1,2 and Frederic Berard1,2 1Department of Allergology and Clinical Immunology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, 69495 Pierre Benite Cedex, France, 2 INSERM, U851, 21 Avenue Tony Garnier, Lyon F-69007, France, and 3Department of Pathology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon F-69007, France

Les tests épicutanés chez les patients atteints de dermatite atopique : les atopy patch tests

Exposure of atopic dermatitis (AD) patients to aeroallergens or food allergens can exacerbate or maintain the disease. Atopy patch tests (APTs) are able to identify these triggering factors and consist of the epicutaneous application of allergens for 48hours with evaluation of the resulting eczematous lesions after 48 and 72hours, according to the reading criteria of the European Task Force on Atopic Dermatitis (ETFAD). APTs show a higher specificity than skin prick and specific IgE tests, since the pathophysiological mechanism of the reaction induced is very similar to what occurs in AD lesions. The standardization of APTs to aeroallergens has brought a certain degree of reliability to this method, which is not the case for food APTs, where the positive predictive value must be improved in order to avoid any unnecessary dietary restrictions. Thus, optimization of APTs and furtherance of knowledge of the pathophysiology of eczemas could help to develop new immunobiological diagnostic methods and AD-specific immunotherapy.

Encapsulation of hydrophobic allergens into nanoparticles improves the in vitro immunological diagnosis of allergic contact dermatitis

UNLABELLEDnThe diagnosis of allergic contact dermatitis (ACD) relies on in vivo patch testing. In vitro immunological assays based on the characterization of circulating allergen-specific memory T cells represent a promising alternative to patch testing. However, their development is hampered by the technical challenge of assessing hydrophobic allergens in serum-based assays. In this study, we show that the encapsulation of fragrance mix 1 (FMI, a mixture of 8 hydrophobic allergens) into poly-ε-caprolactone nanoparticle (NP) vectors: (1) dramatically increases the solubilization of allergens in conventional cell culture media and (2) allows for a robust in vitro reactivation of allergen-specific T cells in large numbers of fragrance allergic patients. Therefore, the encapsulation of hydrophobic allergens into NP vectors opens new avenues to improve the in vitro immunobiological diagnosis of ACD.nnnFROM THE CLINICAL EDITORnAllergic Contact Dermatitis (ACD) is a delayed-type hypersensivity reaction prevalent in many individuals. Currently, skin patch testing has been the mainstay for diagnosis clinically. In this study, the authors described an improvement to in vitro immunological assays measuring circulating allergen-specific memory T cells, using nanoparticle vectors. The positive data might provide an exciting alternative to current practice of patch-testing.

Bonne tolérance de la vaccination rougeole-oreillons-rubéole chez un enfant allergique à l’œuf et sensibilisé à la gélatine

The Measles-Mumps-Rubella (MMR) vaccine is often postponed in egg-allergic patients due to fear of anaphylactic reaction at the time of injection of this vaccin produced on egg derivates. However, this vaccine is recommended by health authorities, especially in case of increased measles incidence, and international recommendations indicate that there is no need for predictive allergological work-up and that the MMR vaccine is well tolerated in egg-allergic patients. We report on the case of a 12-year-old child with severe immediate-type egg allergy. Immediate-reading intradermal skin tests performed prior to the MMR vaccine were positive. Subsequent allergological work-up revealed a gelatin sensitization, and the child tolerated injections of the vaccine given according to a tolerance induction protocol. Gelatin is used as a stabilizer in numerous vaccines and may be responsible for immediate-type hypersentivity reactions to gelatin-containing vaccines. In case of reaction induced by the MMR vaccine, one needs to explore a potential gelatin sensitization/allergy. The MMR vaccine should be given and is well tolerated in patients with immediate-type egg hypersensitivity, even when gelatin sensitization is combined.

Physiopathologie des toxidermies médicamenteuses : contribution des lymphocytes T CD4+ et CD8+

Resume Les reactions d’allergie retardee (ou reactions d’hypersensibilites) aux medicaments sont frequentes et sont dues a la presence de lymphocytes T specifiques du medicament. Leur expression clinique est variable allant des reactions d’exantheme maculo-papuleux (EMP) qui sont les plus frequentes a des reactions moins frequentes mais plus graves comme le syndrome de Lyell. Les toxidermies regroupent ainsi l’ensemble des accidents cutanes provoques par les medicaments. La physiopathologie de ces reactions et en particulier le role respectif des LT CD4+ et CD8+ reste encore tres controverse mais les donnees recentes sont en faveur d’un role majeur des LT CD8+ cytotoxiques dans le developpement de ces reactions. L’amelioration des connaissances sur la physiopathologie de ces reactions devrait permettre le developpement de nouveaux tests immunobiologiques pour leur diagnostic.

Syndrome de Gianotti–Crosti post-vaccinal : une manifestation d’hypersensibilité retardée aux vaccins

Introduction Nous decrivons un cas de syndrome de Gianotti et Crosti survenu apres une vaccination par ROR (PRIORIX®, vaccin rougeole, oreillons et rubeole). Methodes Une femme de 27 ans nous etait adressee en consultation pour hypersensibilite au vaccin PRIORIX®. Elle avait presente en juin 2017, 5xa0jours apres sa premiere injection de PRIORIX®, un prurit des jambes, suivi de l’apparition de lesions erythematopapuleuses. Quelques jours plus tard, l’eruption s’etendait aux 4xa0membres. Un traitement par dermocorticoides locaux a permis la regression de l’eruption en 7xa0jours. Discussion Le syndrome de Gianotti et Crosti est une eruption rencontree principalement chez l’enfant, plus rarement chez l’adulte jeune. Ce syndrome a ete decrit en association avec le virus de l’hepatite B, mais est associe a des etiologies virales variees (EBV, CMV, coksackies, parvovirus B19, VRS). Des formes post-vaccinales sont rapportees (vaccins contre l’hepatite B et A, poliomyelite, ROR). Il s’agit d’une eruption monomorphe, tantot sous forme de multiples papules planes erythemateuses ou couleur chair, tantot de forme papulovesiculeuses. Elle touche surtout les faces d’extension des membres. Les lesions peuvent persister plusieurs semaines et sont prurigineuses. Dans les formes typiques, le diagnostic est clinique. En l’absence d’orientation etiologique ou dans les formes de l’adulte, un bilan minimal comportant un hemogramme, des transaminases et des serologies virales (VHB, VHC, VIH) est suffisant. Le traitement est symptomatique (anti-histaminiques oraux et dermocorticoides) ( Fig. 1 ). Conclusion Nous rapportons un cas de syndrome de Gianotti et Crosti post-vaccinal. Il s’agit d’un diagnostic d’hypersensibilite retarde aux vaccins auquel les allergologues peuvent etre confrontes. Sa survenue ne contre-indique pas les vaccinations ulterieures.

Hypersensibilité retardée aux héparines : faible sensibilité des tests cutanés et nécessité des tests sous-cutanés de réintroduction

Introduction Les heparines peuvent entrainer des reactions d’hypersensibilite retardees allergiques (HSRA), se manifestant par des lesions nodulaires ou eczematiformes aux points d’injection, prurigineuses. Le bilan allergologique comprend classiquement la realisation de patch test (PT) et intradermoreaction (IDR), mais souvent seul le test de reintroduction permet de faire le diagnostic. Nous presentons un cas d’HSRA a une heparine de bas poids moleculaire (HBPM) chez lequel les tests cutanes etaient negatifs, alors que les tests sous-cutanes (SC) ont permis de poser le diagnostic. Cas clinique Une patiente de 64xa0ans, debute un traitement par tinzaparine et fluindione pour une phlebite profonde. Au deuxieme jour, des lesions nodulaires maculopapuleuses prurigineuses apparaissent aux points d’injection, s’etendant secondairement. Les traitements sont stoppes, avec un relais par apixaban. Initialement, l’eruption regresse sans desquamation, mais recidive apres 5xa0jours de traitement par apixaban. Ce tableau clinique nous evoque une HSRA. Un bilan allergologique est realisexa0: –xa0IDR de Tinzaparine (14xa0500xa0UantiXa/mL) d’enoxaparine (4000xa0UantiXa/mL) et de calciparine (12xa0500xa0UI/mL) diluees au centiemexa0; –xa0SC de 0,1xa0mL de ces 3xa0HBPM puresxa0; –xa0PT d’apixaban pur. Resultats Les tests sont lus a 72xa0heuresxa0: le PT et les IDR sont negatifs, en revanche les SC sont positives pour toutes les molecules. Le fondaparinux et le danaparoide sont testes comme alternatives. Les IDR et SC sont negativesxa0; ces deux molecules sont reintroduites avec une bonne tolerance. Discussion Ce cas montre que les IDR sont insuffisamment sensibles pour faire le diagnostic d’HSRA. Nous n’avons pas pose de PT aux heparines car ils sont peu sensibles et les IDR sont a preferer, selon la litterature. Des SC pures de petits volumes (0,1xa0mL) realisees en meme temps que les tests ont permis dexa0: (i) confirmer le diagnostic d’HSRAxa0; (ii) caracteriser les HBPM responsables des reactionsxa0; (iii) identifier les molecules denuees de reactivite croisee.