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  2. 2. Causes of anaphylaxis <ul><li>Immunologic mechanisms IgE-mediated - drugs - foods - hymenoptera (stinging insects) - latex Non-IgE mediated - anaphylotoxins-mediated e.g. mismatched blood </li></ul>
  3. 3. Causes of anaphylaxis <ul><li>Direct activation of mast cells - opiates, tubocurare, dextran, radiocontrast dyes </li></ul><ul><li>Mediators of arachidonic acid metabolism - Aspirin (ASA) - Nonsteroidal anti-inflammatory drugs (NSAIDs) </li></ul><ul><li>Mechanism unknown - Sulphites </li></ul>
  4. 4. Causes of anaphylaxis <ul><li>Exercise-induced </li></ul><ul><li>food-dependent, exercise-induced </li></ul><ul><li>cold-induced </li></ul><ul><li>idiopathic </li></ul>
  5. 5. Risk of anaphylaxis <ul><li>Yocum etal. (Rochester Epidemiology Project) 1983-1987: incidence: 21/100,000 patient-years </li></ul><ul><li>food allergy 36%, medications 17%, insect sting 15% </li></ul>
  6. 6. Frequency of symptoms in Anaphylaxis
  7. 7. Anaphylaxis <ul><li>Onset of symptoms of anaphylaxis: usually in 5 to 30 minutes; can be hours later </li></ul><ul><li>A more prolonged latent period has been thought to be associated with a more benign course. </li></ul><ul><li>Mortality: due to respiratory events (70%), cardiovascular events (24%) </li></ul>
  8. 8. Prevention of anaphylaxis <ul><li>Avoid the responsible allergen (e.g. food, drug, latex, etc.). </li></ul><ul><li>Keep an adrenaline kit (e.g. Epipen) and Benadryl on hand at all times. </li></ul><ul><li>Medic Alert bracelets should be worn. </li></ul><ul><li>Venom immunotherapy is highly effective in protecting insect-allergic individuals. </li></ul>
  9. 9. Treatment of anaphylaxis <ul><li>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. </li></ul><ul><li>EPINEPHRINE intravenously (IV) - used for anaphylactic shock not responding to therapy - monitor for cardiac arrhythmias </li></ul><ul><li>EPINEPHRINE via endotracheal tube </li></ul>
  10. 10. Treatment of anaphylaxis <ul><li>Place patient in Trendelenburg position. </li></ul><ul><li>Establish and maintain airway. </li></ul><ul><li>Give oxygen via nasal cannula as needed. </li></ul><ul><li>Place a tourniquet above the reaction site (insect sting or injection site). </li></ul><ul><li>Epinephrine (1:1000) 0.1-0.3 ml at the site of antigen injection </li></ul><ul><li>Start IV with normal saline. </li></ul>
  11. 11. Treatment of anaphylaxis <ul><li>Benadryl (diphenhydramine) - H1 antagonist </li></ul><ul><li>Tagamet (cimetidine) - H2 antagonist </li></ul><ul><li>Corticosteroid therapy: hydrocortisone IV or prednisone po </li></ul>
  12. 12. Treatment of anaphylaxis <ul><li>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 </li></ul>
  13. 13. Treatment of Anaphylaxis in Beta Blocked Patients <ul><li>Give epinephrine initially. </li></ul><ul><li>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 </li></ul>
  14. 14. Fatal Food-induced Anaphylaxis
  15. 15. Use of epinephrine in Food Allergy <ul><li>Epinephrine should be used immediately after accidental ingestion of foods that have caused anaphylactic reactions in the past. </li></ul><ul><li>An individual who is allergic to peanut, nuts**, shellfish, and fish should immediately take epinephrine if they consume one of these foods. </li></ul><ul><li>A mild allergic reaction to other foods (e.g. minor hives,vomiting) may be treated with an antihistamine </li></ul>
  16. 16. Exercise-induced anaphylaxis <ul><li>Exercise induces warmth, pruritus, urticaria. </li></ul><ul><li>Hypotension and upper airway obstruction may follow. </li></ul><ul><li>Some types: associated with food allergies (e.g. celery, nuts, shellfish, wheat) </li></ul><ul><li>In other patients, anaphylaxis may occur after eating any meal (mechanism has not been identified) </li></ul>
  17. 17. Cold-induced anaphylaxis <ul><li>Cold exposure leads to urticaria. </li></ul><ul><li>Drastic lowering of the whole body temperature (e.g. swimming in a cold lake): hypotensive event in addition to urticaria </li></ul><ul><li>mechanism: unknown </li></ul>
  18. 18. DRUG ALLERGY
  19. 19. DRUG ALLERGY <ul><li>Adverse drug reactions - majority of iatrogenic illnesses - 1% to 15% of drug courses </li></ul><ul><li>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) </li></ul><ul><li>Immunologic (5-10%) </li></ul>
  20. 20. Drugs as immunogens <ul><li>Complete antigens - insulin, ACTH, PTH - enzymes: chymopapain, streptokinase - foreign antisera e.g. tetanus antitoxin </li></ul><ul><li>Incomplete antigens - drugs with MW < 1000 - drugs acting as haptens bind to macromolecules (e.g. proteins, polysaccharides, cell membranes) </li></ul>
  21. 21. Factors that influence the development of drug allergy <ul><li>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 </li></ul><ul><li>Scheduling of administration: -intermittent courses: predispose to sensitization </li></ul>
  22. 22. Factors that influence the development of drug allergy <ul><li>Nature of the drug: - 80% of allergic drug reactions due to: - penicillin - cephalosporins - sulphonamides (sulpha drugs) - ASA/NSAIDs </li></ul>
  23. 23. Gell and Coombs reactions <ul><li>Type 1: Immediate Hypersensitivity - IgE-mediated - occurs within minutes to 4-6 hours of drug exposure </li></ul><ul><li>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 </li></ul>
  24. 24. Gell and Coombs reactions <ul><li>Type 3: Serum sickness - fever, rash (urticaria, angioedema, palpable purpura), lymphadenopathy, splenomegaly, arthralgias - onset: 2 days up to 4 weeks - penicillin commonest cause </li></ul><ul><li>Type 4: Delayed type hypersensitivity - sensitized to drug, the vehicle, or preservative (e.g. PABA, parabens, thimerosal) </li></ul>
  25. 25. Penicillin Allergy <ul><li>beta lactam antibiotic </li></ul><ul><li>Type 1 reactions: 2% of penicillin courses </li></ul><ul><li>Penicillin metabolites: - 95%: benzylpenicilloyl moiety (the “major determinant”) - 5%: benzyl penicillin G, penilloates, penicilloates (the “minor determinants”) </li></ul>
  26. 26. Penicillin Allergy <ul><li>Skin tests: Penicillin G, Prepen (benzyl-penicilloyl-polylysine): false negative rate of up to 7% </li></ul><ul><li>Resolution of penicillin allergy - 50% lose penicillin allergy in 5 yr - 80-90% lose penicillin allergy in 10 yr </li></ul>
  27. 27. Cephalosporin allergy <ul><li>beta-lactam ring and amide side chain similar to penicillin </li></ul><ul><li>degree of cross-reactivity in those with penicillin allergy: 5% to 16% </li></ul><ul><li>skin testing with penicillin determinants detects most but not all patients with cephalsporin allergy </li></ul>
  28. 28. “ Ampicillin rash” <ul><li>non-immunologic rash </li></ul><ul><li>maculopapular, non-pruritic rash </li></ul><ul><li>onsets 3 to 8 days into the antibiotic course </li></ul><ul><li>incidence: 5% to 9% of ampicillin or amoxicillin courses; 69% to 100% in those with infectious mononucleosis or acute lymphocytic leukemia </li></ul><ul><li>must be distinguished from hives secondary to ampicillin or amoxicillin </li></ul>
  29. 29. Sulphonamide hypersensitivity <ul><li>sulpha drugs more antigenic than beta lactam antibiotics </li></ul><ul><li>common reactions: drug eruptions (e.g. maculopapular or morbilliform rashes, erythema multiforme, etc.) Type 1 reactions: urticaria, anaphylaxis, etc. </li></ul><ul><li>no reliable skin tests for sulpha drugs </li></ul><ul><li>re-exposure: may cause exfoliative dermatitis, Stevens-Johnson syndrome </li></ul>
  30. 30. ASA and NSAID sensitivity <ul><li>Pseudoallergic reactions - urticaria/angioedema - asthma - anaphylactoid reaction </li></ul><ul><li>prevalence: 0.2% general population 8-19% asthmatics 30-40% polyps & sinusitis </li></ul><ul><li>ASA quatrad: A sthma, S inuitis, A SA sensitivity, nasal P olyps (ASAP syndrome) </li></ul>
  31. 31. ASA & NSAID sensitivity <ul><li>ASA sensitivity: cross-reactive with all NSAIDs that inhibit cyclo-oxygenase </li></ul>
  32. 32. ASA & NSAID sensitivity <ul><li>no skin test or in vitro test to detect ASA or NSAID sensitivity </li></ul><ul><li>to prove or disprove ASA sensitivity: oral challenge to ASA (in hospital setting) </li></ul><ul><li>ASA desensitization: highly successful with ASA-induced asthma; less successful with ASA-induced urticaria </li></ul>
  33. 33. Allergy skin testing <ul><li>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 </li></ul>
  34. 34. Management of drug allergy <ul><li>Identify most likely drugs (based on history). </li></ul><ul><li>Perform allergy skin tests (if available). </li></ul><ul><li>Avoidance of identified drug or suspected drug(s) is essential. </li></ul><ul><li>Avoid potential cross-reacting drugs (e.g. avoid cephalosporins in penicillin-allergic individuals). </li></ul>
  35. 35. Management of drug allergy <ul><li>A Medic-Alert bracelet is recommended. </li></ul><ul><li>Use alternative medications, if at all possible. </li></ul><ul><li>Desensitize to implicated drug, if this drug is deemed essential. </li></ul>
  36. 36. Desensitization to medications <ul><li>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 </li></ul>