ANAPHYLAXIS

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 inAnaphylaxis
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 (11000) 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 (11000) 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 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

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
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)

20
Drugs as immunogens

• Complete antigens - insulin, ACTH, PTH -
  enzymes chymopapain, streptokinase - foreign
  antisera e.g. tetanus antitoxin
• Incomplete antigens - drugs with MW lt
  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,cephalospori
  ns

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