Antibiotic prophylaxis for the prevention of infective endocarditis for dental procedures is not associated with fatal adverse drug reactions in France

One of the major reasons to stop antibiotic prophylaxis (AP) to prevent infective endocarditis (IE) in the United Kingdom but not in the rest of the world was that it would result in more deaths from fatal adverse drug reactions (ADRs) than the number of IE deaths. The main aim of this study was to quantify and describe the ADRs with amoxicillin or clindamycin for IE AP. The second aim was to infer a crude incidence of anaphylaxis associated with amoxicillin for IE AP. The Medical Dictionary for Regulatory Activities (MedDRA) was used to group ADRs for IE AP using the broad Standardized MedDRA Queries ?Anaphylactic reaction, Amoxicillin, Clindamycin, Clostridium Difficile infection? to the French Pharmacovigilance Database System. From this first-line collection, we selected all cases occurring for IE AP and ultimately, the cases for IE AP for a dental procedure. Then, each case was analyzed. Of 11639 first-line recorded ADRs, 100 were for IE AP but no fatal anaphylaxis to amoxicillin or clindamycin and no C. difficile infection associated with clindamycin were identified. Only 17 cases of anaphylaxis to amoxicillin related to dental procedures were highlighted. The estimation of the crude incidence rate of anaphylaxis associated with amoxicillin for IE AP for invasive dental procedure was 1/57 000 (95% CI 0.2-0.6). Fatal or severe ADRs with amoxicillin or clindamycin is not a rational argument to stop IE AP before invasive dental procedures

When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council

BackgroundAlthough most patients with atopic dermatitis (AD) are effectively managed with topical medication, a significant minority require systemic therapy. Guidelines for decision making about advancement to systemic therapy are lacking.ObjectiveTo guide those considering use of systemic therapy in AD and provide a framework for evaluation before making this therapeutic decision with the patient.MethodsA subgroup of the International Eczema Council determined aspects to consider before prescribing systemic therapy. Topics were assigned to expert reviewers who performed a topic-specific literature review, referred to guidelines when available, and provided interpretation and expert opinion.ResultsWe recommend a systematic and holistic approach to assess patients with severe signs and symptoms of AD and impact on quality of life before systemic therapy. Steps taken before commencing systemic therapy include considering alternate or concomitant diagnoses, avoiding trigger factors, optimizing topical therapy, ensuring adequate patient/caregiver education, treating coexistent infection, assessing the impact on quality of life, and considering phototherapy.LimitationsOur work is a consensus statement, not a systematic review.ConclusionThe decision to start systemic medication should include assessment of severity and quality of life while considering the individual's general health status, psychologic needs, and personal attitudes toward systemic therapies

Role of cytotoxic cells in skin delayed hypersensitivities

Les hypersensibilités retardées (HSR) cutanées sont hétérogènes, à la fois par la nature des mécanismes impliqués (allergiques versus non allergiques) mais aussi par les différents degrés de sévérité rencontrés. Seules les HSR allergiques sont dues à la présence de lymphocytes T (LT), mal caractérisés chez l'homme. Le but de ce travail est d'étudier la contribution des LT CD8 cytotoxiques dans le développement et la sévérité des HSR cutanées chez l'homme, à partir de deux pathologies fréquentes : les toxidermies aux béta lactamines et l'eczéma allergique de contact à la para-phénylènediamine (PPD). Tout d'abord, la présence de LT spécifiques de médicament au sein des toxidermies aux béta lactamines a été recherchée in vivo et in vitro. Nous avons montré que les HSR sévères étaient plus souvent d'origine allergique que les HSR bénignes. Nous avons ensuite caractérisé le rôle des LT CD8 dans les HSR allergiques. Dans les toxidermies bénignes à l'amoxicilline, l'étude de la cinétique de recrutement des LT au niveau cutané ainsi que l'analyse des LT spécifiques du sang circulant ont permis de mettre en évidence le rôle essentiel des LT CD8 cytotoxiques dans l'initiation de ces réactions. Ensuite, dans l'eczéma allergique de contact à la PPD, un recrutement épidermique précoce des LT CD8 associés à des marqueurs de cytotoxicité, a été retrouvé, corrélé avec la sévérité des lésions. Ces résultats ont été confortés par ceux obtenus dans un modèle pré-clinique d'HSR allergique à la PPD chez la souris. En conclusion, ce travail montre que les LT CD8 cytotoxiques pourraient être les principales cellules effectrices des HSR cutanées allergiques chez l'hommeSkin delayed hypersensitivity (DHS) are heterogeneous, by the nature of the mechanisms involved (allergic versus non allergic) and also by their different degrees of severity. Only allergic DHS is due to T cells, poorly characterized in humans. The aim of this work is to study the contribution of cytotoxic CD8 T cells in the development and severity of skin DHS in humans, induced by two common diseases: cutaneous adverse drug reactions to beta lactam antibiotics and allergic contact dermatitis to para-phenylenediamine (PPD). First, the presence of drug specific T cells in cutaneous adverse drug reactions to beta lactams was investigated in vivo and in vitro. We showed that severe DHS were more often allergic than benign DHS. Then, we characterized the role of CD8 T cells in allergic DHS. In benign cutaneous adverse drug reactions to amoxicillin, the study of the kinetics of skin T cell recruitment as well as the analysis of circulating specific T cells highlight the essential role of cytotoxic CD8 T cells in the initiation phase of these reactions. In allergic contact dermatitis to PPD, early recruitment of epidermal CD8 T cells associated with cytotoxic markers was found, correlated with the severity of lesions. These results were supported by those obtained in a mouse model of allergic contact dermatitis to PPD. In conclusion, this work showed that cytotoxic CD8 T cells could be the main effector cells of allergic skin DHS in human

Hypersensibilité cutanée d'allure immédiate aux anti-inflammatoires non stéroïdiens

LYON1-BU Santé (693882101) / SudocSudocFranceF

Etude clinique et physiopathologique de l'eczéma allergique de contact (modèle de la para-phénylènediamine)

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

When Joints Fail: Identifying the Allergen Helps

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