1. ANAPHYLAXIS

2. Causes of anaphylaxis Immunologic mechanisms IgE-mediated - drugs - foods - hymenoptera (stinging insects) - latex Non-IgE mediated - anaphylotoxins-mediated e.g. mismatched blood

3. 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

4. Causes of anaphylaxis Exercise-induced food-dependent, exercise-induced cold-induced idiopathic

5. Risk of anaphylaxis Yocum etal. (Rochester Epidemiology Project) 1983-1987: incidence: 21/100,000 patient-years food allergy 36%, medications 17%, insect sting 15%

6. Frequency of symptoms in Anaphylaxis

7. 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%)

8. 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.

9. 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

10. 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.

11. Treatment of anaphylaxis Benadryl (diphenhydramine) - H1 antagonist Tagamet (cimetidine) - H2 antagonist Corticosteroid therapy: hydrocortisone IV or prednisone po

12. 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

13. 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

14. Fatal Food-induced Anaphylaxis

15. 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

16. 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)

17. 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

18. DRUG ALLERGY

19. 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%)

20. 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)

21. 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

22. 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

23. 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

24. 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)

25. 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”)

26. Penicillin Allergy Skin tests: Penicillin G, Prepen (benzyl- penicilloyl-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

27. 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

28. “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

29. 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

30. 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)

31. ASA & NSAID sensitivity ASA sensitivity: cross-reactive with all NSAIDs that inhibit cyclo-oxygenase

32. 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

33. 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

34. 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).

35. 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.

36. 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