Prevention of infective endocarditis

Anaphylaxis is a clinical emergency, and all healthcare professionals should be familiar with its recognition and acute and ongoing management. These guidelines have been prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Taskforce on Anaphylaxis. They aim to provide evidence-based recommendations for the recognition, risk factor assessment, and the management of patients who are at risk of, are experiencing, or have experienced anaphylaxis. While the primary audience is allergists, these guidelines are also relevant to all other healthcare professionals. The development of these guidelines has been underpinned by two systematic reviews of the literature, both on the epidemiology and on clinical management of anaphylaxis. Anaphylaxis is a potentially life-threatening condition whose clinical diagnosis is based on recognition of a constellation of presenting features. First-line treatment for anaphylaxis is intramuscular adrenaline. Useful second-line interventions may include removing the trigger where possible, calling for help, correct positioning of the patient, high-flow oxygen, intravenous fluids, inhaled short-acting bronchodilators, and nebulized adrenaline. Discharge arrangements should involve an assessment of the risk of further reactions, a management plan with an anaphylaxis emergency action plan, and, where appropriate, prescribing an adrenaline auto-injector. If an adrenaline auto-injector is prescribed, education on when and how to use the device should be provided. Specialist follow-up is essential to investigate possible triggers, to perform a comprehensive risk assessment, and to prevent future episodes by developing personalized risk reduction strategies including, where possible, commencing allergen immunotherapy. Training for the patient and all caregivers is essential. There are still many gaps in the evidence base for anaphylaxis.

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Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology

Mast cells are primary effectors in allergic reactions, and may have important roles in disease by secreting histamine and various inflammatory and immunomodulatory substances. Although they are classically activated by immunoglobulin (Ig)E antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions. The pathogenic roles of these substances have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, Mrgprb2, the orthologue of the human G-protein-coupled receptor MRGPRX2. Secretagogue-induced histamine release, inflammation and airway contraction are abolished in Mrgprb2-null mutant mice. Furthermore, we show that most classes of US Food and Drug Administration (FDA)-approved peptidergic drugs associated with allergic-type injection-site reactions also activate Mrgprb2 and MRGPRX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that Mrgprb2 and MRGPRX2 are targets of many small-molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice; and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MRGPRX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.

/pdf/identification-of-a-mast-cell-specific-receptor-crucial-for-48yi47jzt9.pdf

Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions

Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.

http://allergy-society.bg/wp-content/uploads/2014/11/Skin_test_concentrations.pdf

Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

https://dash.harvard.edu/bitstream/handle/1/12406782/4038846.pdf?sequence=1

International consensus on (ICON) anaphylaxis

Background More attention should be paid to rare serious adverse events such as anaphylaxis to increase the safety of anesthesia. Objective To report the results of an 8-year survey of anaphylaxis during anesthesia in France. Methods Data from patients who experienced anaphylaxis between January 1, 1997, and December 31, 2004, were analyzed. Estimated incidences were obtained by combining this database with data from the French pharmacovigilance system by using a capture-recapture method. The number of patients exposed to the offending agents was obtained from data collected during the national survey of anesthesia practice. Results A total of 2516 patients was included. A diagnosis of IgE-mediated reaction was established in 1816 cases (72.18%). The most common causes were neuromuscular blocking agents ([NMBAs]; n = 1067; 58.08%), latex (n = 361; 19.65%), and antibiotics (n = 236; 12.85%). The median annual incidence per million procedures was higher for females 154.9 (5th-95th percentile, 117.2-193.1) than for males 55.4 (5th-95th percentile, 42.0-68.0). It reached 250.9 (5th-95th percentile, 189.8-312.9) for women in cases of allergic reactions to NMBAs. In children, a diagnosis of IgE-mediated reactions was obtained in 122 cases (45.9%). The most common causes were latex (n = 51; 41.8%), NMBAs (n = 39; 31.97%), and antibiotics (n = 11; 9.02%). In contrast with adults, no female predominance was observed. Conclusion The incidence of allergic reactions during anesthesia, estimated on a national basis, is higher than previously estimated. These results should be taken into account in the evaluation of the benefit-to-risk ratio of the various anesthetic techniques in individuals. The similar incidence of reactions according to sex before adolescence suggests a role for sex hormones in the increase of anaphylaxis observed in women.

https://www.jacionline.org/article/S0091-6749%2811%2900370-8/pdf

Anaphylaxis during anesthesia in France: An 8-year national survey

We report a documented severe immunoglobulin E-mediated hypersensitivity reaction associated with use of 1% methylene blue for detection of tubal permeability occurring during general anesthesia. Clinical symptoms, biological assessment results, and cutaneous test positivity confirmed an anaphylactic reaction to methylene blue. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the perioperative period in the event of a hypersensitivity reaction occurring during anesthesia. Anesthesiologists should be aware of the possibility of hypersensitivity reactions involving any drug or substance used during surgery.

Severe anaphylactic shock with methylene blue instillation.

Objective: To assess the efficacy of the topical application of morphine on painful chronic skin ulcers. Method: A prospective bi-centric controlled double-blind randomised study was conducted involving 24 patients with painful chronic skin ulcers using topically applied morphine versus placebo. Ten milligrams of morphine hydrochloride with Intrasite Gel or Intrasite Gel with placebo were applied daily for five days. All patients were treated with a level II analgesic treatment. A numeric pain scale lower than 4/10 and no need for a ‘rescue’ treatment (morphine sulphate) indicated that the treatment was successful. Local and systemic tolerance of the treatments was analysed daily. Results: Twenty-four patients were included in the study, but only 18 started the protocol. Only 2/11 patients were completely relieved in the morphine group compared with 1/7 in the placebo group. Local and general tolerance of morphine was good. The peripheral efficacy of morphine is under discussion. Conclusion: The results s...

Study to determine the efficacy of topical morphine on painful chronic skin ulcers.

Introduction. Le syndrome d'hypersensibilite medicamenteuse est une reaction medicamenteuse rare, dont la forme typique comprend des manifestations cutanees severes, une fievre, des adenopathies, une eosinophilie sanguine et une hepatite mixte. Observation. Nous rapportons le cas d'un syndrome d'hypersensibilite a la minocycline avec eruption pustuleuse generalisee, survenant chez une jeune femme de 16 ans traitee depuis un mois par minocycline 100 mg/j pour une acne. Les tests epicutanes realises avec de la minocycline diluee dans de la vaseline etaient positifs a la 48 e heure. Discussion. Cette observation de syndrome d'hypersensibilite a la minocycline est originale par la positivite des tests epicutanes realises a distance reproduisant les lesions cutanees initiales. Differents medicaments ont ete incrimines dans la survenue du syndrome d'hypersensibilite medicamenteuse dont les plus connus sont les anticonvulsivants. Depuis quelques annees, plusieurs publications ont rapporte des observations apres prise de minocycline. Si de telles observations sont rares, il semble que parmi les cyclines, la minocycline soit le principal responsable de tableaux cliniques tels que syndrome d'hypersensibilite medicamenteuse, lupus erythemateux aigu dissemine, pneumopathie a eosinophiles et pseudomaladie serique. Il convient de ne pas meconnaitre de tels effets secondaires et d'inciter tout malade a interrompre le traitement et a consulter si des symptomes tels qu'hyperthermie, adenopathies, douleurs articulaires, eruption apparaissent. Quatre a 6 semaines apres l'eruption, des tests epicutanes a la minocycline sont interessants a pratiquer.

Philippe Tréchot

Papers

Anaphylaxis during anesthesia in France: An 8-year national survey

Severe anaphylactic shock with methylene blue instillation.

Study to determine the efficacy of topical morphine on painful chronic skin ulcers.

Syndrome d'hypersensibilité à la minocycline

Can spontaneous adverse event reporting systems really be used to compare rates of adverse events between drugs