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 Atopy Locale Allergen 1/7 at home Peanut- 4 Tree nut- 1 Seafood- 2 YUNGINGER SAMPSON (n=7) (n=6) 16-43 years 2-16 years All asthmatics 1/6 at home 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