anaphylaxis
DESCRIPTION
TRANSCRIPT
ANAPHYLAXIS
Causes of anaphylaxis
• Immunologic mechanismsIgE-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 inAnaphylaxis
Urticaria/angioedema 88%Upper airway edema 56%Dyspnea or wheeze 47%Flush 46%Dizziness,hypotension, syncope
33%
Gastrointestinal sx 30%Rhinitis 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 AnaphylaxisSERIES YUNGINGER
(n=7)SAMPSON(n=6)
Ages 16-43 years 2-16 years
Atopy All asthmatics
Locale 1/7 at home 1/6 at home
Allergen Peanut- 4Tree nut- 1Seafood- 2
Peanut- 3Tree nut- 2Egg- 1
Use of epinephrine inFood 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 celleg. 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 (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
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 population8-19% asthmatics30-40% 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