Transcript Causes of anaphylaxis

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