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ANAPHYLAXIS Causes of anaphylaxis • Immunologic mechanisms IgE-mediated - drugs - foods - hymenoptera (stinging insects) - latex Non-IgE mediated - anaphylotoxins-mediated e.g. mismatched blood Causes of anaphylaxis • Direct activation of mast cells - opiates, tubocurare, dextran, radiocontrast dyes • Mediators of arachidonic acid metabolism - Aspirin (ASA) - Nonsteroidal anti-inflammatory drugs (NSAIDs) • Mechanism unknown - Sulphites Causes of anaphylaxis • • • • Exercise-induced food-dependent, exercise-induced cold-induced idiopathic Risk of anaphylaxis • Yocum etal. (Rochester Epidemiology Project) 1983-1987: incidence: 21/100,000 patient-years • food allergy 36%, medications 17%, insect sting 15% Frequency of symptoms in Anaphylaxis Urticaria/angioedema Upper airway edema Dyspnea or wheeze Flush Dizziness, hypotension, syncope Gastrointestinal sx Rhinitis 88% 56% 47% 46% 33% 30% 16% Anaphylaxis • Onset of symptoms of anaphylaxis: usually in 5 to 30 minutes; can be hours later • A more prolonged latent period has been thought to be associated with a more benign course. • Mortality: due to respiratory events (70%), cardiovascular events (24%) Prevention of anaphylaxis • Avoid the responsible allergen (e.g. food, drug, latex, etc.). • Keep an adrenaline kit (e.g. Epipen) and Benadryl on hand at all times. • Medic Alert bracelets should be worn. • Venom immunotherapy is highly effective in protecting insect-allergic individuals. Treatment of anaphylaxis • EPINEPHRINE (1:1000) SC or IM - 0.01 mg/kg (maximal dose 0.3-0.5 ml) - administer in a proximal extremity - may repeat every 10-15 min, p.r.n. • EPINEPHRINE intravenously (IV) - used for anaphylactic shock not responding to therapy - monitor for cardiac arrhythmias • EPINEPHRINE via endotracheal tube Treatment of anaphylaxis • • • • Place patient in Trendelenburg position. Establish and maintain airway. Give oxygen via nasal cannula as needed. Place a tourniquet above the reaction site (insect sting or injection site). • Epinephrine (1:1000) 0.1-0.3 ml at the site of antigen injection • Start IV with normal saline. Treatment of anaphylaxis • Benadryl (diphenhydramine) - H1 antagonist • Tagamet (cimetidine) - H2 antagonist • Corticosteroid therapy: hydrocortisone IV or prednisone po Treatment of anaphylaxis • Biphasic courses in some cases of anaphylaxis: - Recurrence of symptoms: 1-8 hrs later - In those with severe anaphylaxis, observe for 6 hours or longer. - In milder cases, treat with prednisone; Benadryl every 4 to 6 hours; advise to return immediately for recurrent symptoms Treatment of Anaphylaxis in Beta Blocked Patients • Give epinephrine initially. • If patient does not respond to epinephrine and other usual therapy: - Isoproterenol (a pure beta-agonist) 1 mg in 500 ml D5W starting at 0.1 mcg/kg/min - Glucagon 1 mg IV over 2 minutes Fatal Food-induced Anaphylaxis SERIES Ages YUNGINGER SAMPSON (n=7) (n=6) 16-43 years 2-16 years Atopy All asthmatics Locale 1/7 at home 1/6 at home Allergen Peanut- 4 Tree nut- 1 Seafood- 2 Peanut- 3 Tree nut- 2 Egg- 1 Use of epinephrine in Food Allergy • Epinephrine should be used immediately after accidental ingestion of foods that have caused anaphylactic reactions in the past. • An individual who is allergic to peanut, nuts**, shellfish, and fish should immediately take epinephrine if they consume one of these foods. • A mild allergic reaction to other foods (e.g. minor hives,vomiting) may be treated with an antihistamine Exercise-induced anaphylaxis • Exercise induces warmth, pruritus, urticaria. • Hypotension and upper airway obstruction may follow. • Some types: associated with food allergies (e.g. celery, nuts, shellfish, wheat) • In other patients, anaphylaxis may occur after eating any meal (mechanism has not been identified) Cold-induced anaphylaxis • Cold exposure leads to urticaria. • Drastic lowering of the whole body temperature (e.g. swimming in a cold lake): hypotensive event in addition to urticaria • mechanism: unknown DRUG ALLERGY DRUG ALLERGY • Adverse drug reactions - majority of iatrogenic illnesses - 1% to 15% of drug courses • Non-immunologic (90-95%): side effects, toxic reactions, drug interactions, secondary or indirect effects (eg. bacterial overgrowth) pseudoallergic drug rx (e.g. opiate reactions, ASA/NSAID reactions) • Immunologic (5-10%) Drugs as immunogens • Complete antigens - insulin, ACTH, PTH - enzymes: chymopapain, streptokinase - foreign antisera e.g. tetanus antitoxin • Incomplete antigens - drugs with MW < 1000 - drugs acting as haptens bind to macromolecules (e.g. proteins, polysaccharides, cell membranes) Factors that influence the development of drug allergy • Route of administration: - parenteral route more likely than oral route to cause sensitization and anaphylaxis - inhalational route: respiratory or conjunctival manifestations only - topical: high incidence of sensitization • Scheduling of administration: -intermittent courses: predispose to sensitization Factors that influence the development of drug allergy • Nature of the drug: - 80% of allergic drug reactions due to: - penicillin - cephalosporins - sulphonamides (sulpha drugs) - ASA/NSAIDs Gell and Coombs reactions • Type 1: Immediate Hypersensitivity - IgE-mediated - occurs within minutes to 4-6 hours of drug exposure • Type 2: Cytotoxic reactions - antibody-drug interaction on the cell surface results in destruction of the cell eg. hemolytic anemia due to penicillin, quinidine, quinine,cephalosporins Gell and Coombs reactions • Type 3: Serum sickness - fever, rash (urticaria, angioedema, palpable purpura), lymphadenopathy, splenomegaly, arthralgias - onset: 2 days up to 4 weeks - penicillin commonest cause • Type 4: Delayed type hypersensitivity - sensitized to drug, the vehicle, or preservative (e.g. PABA, parabens, thimerosal) Penicillin Allergy • beta lactam antibiotic • Type 1 reactions: 2% of penicillin courses • Penicillin metabolites: - 95%: benzylpenicilloyl moiety (the “major determinant”) - 5%: benzyl penicillin G, penilloates, penicilloates (the “minor determinants”) Penicillin Allergy • Skin tests: Penicillin G, Prepen (benzylpenicilloyl-polylysine): false negative rate of up to 7% • Resolution of penicillin allergy - 50% lose penicillin allergy in 5 yr - 80-90% lose penicillin allergy in 10 yr Cephalosporin allergy • beta-lactam ring and amide side chain similar to penicillin • degree of cross-reactivity in those with penicillin allergy: 5% to 16% • skin testing with penicillin determinants detects most but not all patients with cephalsporin allergy “Ampicillin rash” • • • • non-immunologic rash maculopapular, non-pruritic rash onsets 3 to 8 days into the antibiotic course incidence: 5% to 9% of ampicillin or amoxicillin courses; 69% to 100% in those with infectious mononucleosis or acute lymphocytic leukemia • must be distinguished from hives secondary to ampicillin or amoxicillin Sulphonamide hypersensitivity • sulpha drugs more antigenic than beta lactam antibiotics • common reactions: drug eruptions (e.g. maculopapular or morbilliform rashes, erythema multiforme, etc.) Type 1 reactions: urticaria, anaphylaxis, etc. • no reliable skin tests for sulpha drugs • re-exposure: may cause exfoliative dermatitis, Stevens-Johnson syndrome ASA and NSAID sensitivity • Pseudoallergic reactions - urticaria/angioedema - asthma - anaphylactoid reaction • prevalence: 0.2% general population 8-19% asthmatics 30-40% polyps & sinusitis • ASA quatrad: Asthma, Sinuitis, ASA sensitivity, nasal Polyps (ASAP syndrome) ASA & NSAID sensitivity • ASA sensitivity: cross-reactive with all NSAIDs that inhibit cyclo-oxygenase ASA & NSAID sensitivity • no skin test or in vitro test to detect ASA or NSAID sensitivity • to prove or disprove ASA sensitivity: oral challenge to ASA (in hospital setting) • ASA desensitization: highly successful with ASA-induced asthma; less successful with ASA-induced urticaria Allergy skin testing • Skin tests to detect IgE-mediated drug reactions is limited to: Complete antigens - insulin, ACTH, PTH - chymopapain, streptokinase - foreign antisera Incomplete antigens (drugs acting as haptens) - penicillins - local anesthetics - general anesthetics Management of drug allergy • Identify most likely drugs (based on history). • Perform allergy skin tests (if available). • Avoidance of identified drug or suspected drug(s) is essential. • Avoid potential cross-reacting drugs (e.g. avoid cephalosporins in penicillin-allergic individuals). Management of drug allergy • A Medic-Alert bracelet is recommended. • Use alternative medications, if at all possible. • Desensitize to implicated drug, if this drug is deemed essential. Desensitization to medications • Basic approach: administer gradually increasing doses of the drug over a period of hours to days, typically beginning with one ten-thousandth of a conventional dose