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