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 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 Anaphylaxis
SERIES
Ages
YUNGINGER
(n=7)
SAMPSON
(n=6)
16-43 years 2-16 years
Atopy All asthmatics
Locale
Allergen
1/7 at home 1/6 at home
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