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This is a Test It is ONLY a Test
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A 16 y/o girl just passed out after receiving her penicillin shot for strep throat (“doesn’t swallow pills”). Which of the following will be most useful to know in treating her: A Her Blood Pressure B Her Glucose level C Her Heart Rate D Your Heart Rate
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Which of the following is the safest and most efficient route to administer epinephrine in an allergy emergency: A IV B Sub Q C IM D PR
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Which of the following potential allergens do not generally cross-react: A. COX-2 inhibitors & Ibuprofen B. Filberts & Pecans C. Peanuts & Tofurky D. Lobster & Shrimp
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A first year PEM fellow attending conference developed a sudden onset of urticaria, lip swelling and DIB. The etiology is most likely a reaction to: A smelling someone else’s lunch B a spider bite C another “billing talk” by Dr Linzer
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When advising parents/patients on how to administer an “epi-pen” you should tell them to: A. hold it against the triceps and squeeze the trigger B. “stab” it into the anterior thigh C. hold it against the lateral thigh and push
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Which is NOT a clinical presentation of anaphylaxis: A. Vomiting and Diarrhea B. Syncope C. Altered Mental Status D. Itchy Tongue
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In counseling a 50kg 15 year old after a severe episode of anaphylaxis to a bee sting your best advice is that if they get stung again they first should take A. (2) 25mg diphenhydramine capsules PO B. (5) tsp diphenhydramine elixer PO C..5mg epinephrine SQ D. 60mg prednisone PO
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Which of the following treatments has been shown to decrease the incidence of biphasic reactions: Which of the following treatments has been shown to decrease the incidence of biphasic reactions: A. Corticosteroids B. Epinephrine C. Diphenhydramine D. Ranitidine
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ANAPHYLAXIS Michael Greenwald, MD Pediatric Emergency Medicine Emory University Children’s Healthcare of Atlanta @ Egleston
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Objectives Recognize patients with, or at risk for, anaphylactic reaction Understand the immunologic basis for anaphylactic reactions Know the interventions appropriate for anaphylactic reactions Know the appropriate medical follow-up
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Historical Background ana - backward phylaxis - protection Portier and Richet: reactions in dogs exposed to sea anenome toxin First documented case: Egyptian pharoah 2640 B.C. dies after wasp sting
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Defining Anaphylaxis Acute Systemic Allergic (i.e. requires prior exposure)
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Special Features of Anaphylaxis Spectrum of severity Variety of manifestations Uniphasic, biphasic or protracted
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Epidemiology ► Top triggers: then penicillin insect venom food ► ► Top triggers: now Latex (27%) Food (25%) Drugs (16%) Venoms (15%)
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Anaphylaxis Epidemiology ► 84,000 cases/year in US 1% fatal Kids > adults ► Food Allergy under 4 y/o: 6-8% After 10 y/o: 2% 29,000 cases food induced anaphylaxis/year ► 2000 hospitalizations ► 150 deaths; high association with asthma, peanut/tree nut allergy Peanuts are # 1 and increasing in Western nations
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Hypersensitivity review: Gell and Coombs Classification Type I - Anaphylactic Type II - Cytotoxic Type III - Immune Complex Type IV - Delayed Type
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Type I - Anaphylactic ► Exposure to reaction < 30minutes ► Immediate: Exposure to reaction < 30minutes ► Exposure to reaction: 2-12 hours ► Late Phase: Exposure to reaction: 2-12 hours Exposure to reaction: <30minutes Effector cell: IgE Antigen: pollens, foods, drugs, venoms Mediators: histamine, leukotrienes Manifestations: anaphylaxis, allergic rhinitis, allergic asthma, urticaria
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Type II - Cytotoxic Exposure to reaction: variable (minutes to hours) Exposure to reaction: variable (minutes to hours) Effector cell: IgG, IgM Effector cell: IgG, IgM Target: Red blood cells, Lung tissue Target: Red blood cells, Lung tissue Mediators: Complement Mediators: Complement Examples: Immune hemolytic anemia, Rh hemolytic disease, Goodpasture syndrome Examples: Immune hemolytic anemia, Rh hemolytic disease, Goodpasture syndrome
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Type III - Immune Complexes Exposure to reaction: 6 - 21 days Exposure to reaction: 6 - 21 days Effector cell: Antigen with Antibody Effector cell: Antigen with Antibody Target: Vascular endothelium Target: Vascular endothelium Mediators: Complement, Anaphylatoxin Mediators: Complement, Anaphylatoxin Symptoms: fever, urticaria, arthralgia, arthritis, lymphadenopathy Symptoms: fever, urticaria, arthralgia, arthritis, lymphadenopathy Examples: Serum sickness, PSGN Examples: Serum sickness, PSGN
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Type IV - Delayed Type Exposure to reaction: 24-48 hours Exposure to reaction: 24-48 hours Effector cell: Lymphocytes Effector cell: Lymphocytes Antigen: Chemicals, Mycobacterium tuberculosis Antigen: Chemicals, Mycobacterium tuberculosis Mediators: Lymphokines Mediators: Lymphokines Examples: Contact dermatitis, Tuberculin skin reactions Examples: Contact dermatitis, Tuberculin skin reactions
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Anaphylaxis and Her Cousin Anaphylaxis IgE mediated IgG - immune complex mediated Anaphylactoid direct stimulation of mast cells and basophils unknown mechanism
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IgE - mediated Anaphylaxis ► Prior exposure required ► Allergen-IgE binding induces release of mediators: histamine prostaglandins platelet activating factor tryptase
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IgG -immune complex mediated ► complement activated by immune complexes or other agents Tissue antigens - RBC, WBC, Plts Serum proteins - Immunoglobulin, cryoprecipitin ► anaphylatoxins: C3a, C5a
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Anaphylactoid : Direct stimulation ► direct stimulation of mast cells and basophils ► unknown mechanism - suspect high osmolarity ► examples: radiocontrast media (not assoc w/ iodine, shellfish allergy), mannitol, opiates, curare, dextran, chemotherapeutic agents
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Unexplained Anaphylaxis ► Unknown mechanism: ASA and other NSAIDS preservatives exercise mastocytosis cholinergic urticaria with anaphylaxis progesterone: “catamenial anaphylaxis”
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Unexplained Anaphylaxis ► Idiopathic anaphylaxis: unknown trigger up to 37% of all reactions clinically indistinguishable from other forms particularly stressful to patients
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Epidemiology ► Patients at risk: Does atopic history matter? Who gets the worst reactions? Latex
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Allergens Drugs Foods Venoms Latex
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Defining Drug Reactions Defining Drug Reactions ► Predictable Drug Reactions 80% of all adverse effects dose dependent related to known pharmacological effect ► Unpredictable Drug reactions not dose dependent occurs in susceptible individuals unrelated to known pharmacological effect
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Drugs ► Antimicrobials Penicillin: 2 potential groups of allergens Major determinant: Benzyl penicilloyl Major determinant: Benzyl penicilloyl Minor determinants: penicillin, penicilloate, penilloate, penicilloylamine Minor determinants: penicillin, penicilloate, penilloate, penicilloylamine Cephalosporins Sulfonamides
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Drugs ► NSAIDS bronchospasm in 2-10% of asthmatics unknown mechanism: IgE and mast cells not involved
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Drugs ► Macromolecules: protamine insulin IVIG ► 2 recognized mechanisms ► IgA deficiency high risk ► slow infusion and pretreat
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Drugs Chemotherapeutic agents: L-Asparaginase Vaccinations: MMR? Immunotherapy 17 fatalities reported 1985-1989 (10 million shots given annually) precautions for medical facility: observe 20 minute medications and airway support available
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Drugs Radiocontrast media mast cell degranulation from anaphlatoxins of complement cascade ► older agents: Hypaque, Renigrafin ► mild reaction in 5%, severe - 1/1000, death - 1/10- 40,000 exposures risk factors: ► atopic/asthma history ► adult
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Foods Tree nuts: 1% Americans (3 million) allergic Legumes: 25-35% also allergic to tree nuts Shellfish Fish Milk Eggs Food additives: sulfites
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Foods That May Contain Peanut Oil ► Arachis oil (peanut oil) ► Baked Goods and mixes ► Biscuits, cookies, pastries ► Candy ► Cereals ► Chocolate ► Emulsifiers, flavorings ► Ethnic foods: African, Chinese, Mexican, Thai, Vietnamese ► Ice Cream ► Margarine ► Milk formula ► Satay Sauce (thai sauce) ► Soft drinks ► Soups ► Sunflower seeds ► Vegetable fats and oils
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Venoms/Antivenins 5 major stinging insects in the US: honeybees wasps yellow jackets hornets fire ants Rabies and snake antivenin
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Latex ► incidence low, except for risk groups: ► >1000 episodes and 15 deaths attributed ► surgical and dental procedures highest risk ► RAST testing available
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Exercise-induced Variety of forms of exercise not heat alone not associated with atopy/asthma strong genetic predisposition histamine and parasympathetic tone, sympathetic tone
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Exercise-induced ► 4 phases: Prodrome: fatigue, warmth, pruritis & erythema Early: urticaria, angioedema Fully established: (30’- 4 hours) stridor, choking, N/V/D, syncope, hypotension Late: fatigue, warmth, headache, lasts up to 72 hours
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Exercise-induced ► Diagnosis: may resemble asthma or cholinergic urticaria very unpredictable; some associated with foods ► Management: recognize early signs and rest avoid hot, humid weather exercise with a partner
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Symptoms ► Manifestations in the “shock organs” skin, respiratory tract, gastrointestinal tract, cardiovascular system ► Why there? rich in mast cells sensitive to effects of mast cell mediators exposure to high concentrations of antigen
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Skin ► Early signs: Flushing, feeling warm Erythema Pruritis ► Urticaria ► Angioedema ► Pallor
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Respiratory ► Upper airway Nose & eyes: pruritis and watery discharge, sneezing Lips & tongue: swelling and pruritis Larynx & epiglottis: edema with hoarseness, dysphonia to asphyxia ► Bronchi: bronchospasm with wheezing, decreased aeration, to apnea, asphyxia
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Gastrointestinal ► not only with food triggers ► crampy abdominal pain, nausea, vomiting, watery diarrhea, gastointestinal bleeding, fecal incontinence
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Cardiovascular ► Intravascular volume depletion ► Direct effects on the heart: arrythmias reduced contractility reduced coronary blood flow ► dizziness and confusion ► Early: dizziness and confusion ► syncope, seizures, loss of consciousness shock, cardiac arrest ► May progress to: syncope, seizures, loss of consciousness shock, cardiac arrest
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Other symptoms of anaphylaxis ► Neurologic: HA, Mental Status changes ► Uterine contraction ► Urinary incontinence ► Anxiety, Feeling of “impending doom”
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Natural history of anaphylactic reactions ► Onset of reaction after exposure: seconds to several hours. Depends on patient’s sensitivity dose of allergen route of entry ► Biphasic reactions (1 – 28 hrs) 5-23% in adults; 6% in kids Food, venom, medication induced anaphylaxis Second reaction may be worse
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Making the correct diagnosis ► May look just like: Asthma exacerbation Croup or foreign body aspiration Cardiogenic syncope food poisoning or gastroenteritis
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Vasovagal vs. Anaphylaxis ► Vasovagal pallor diaphoresis bradycardia or NSR ► Anaphylaxis tachycardia flushing urticaria/pruritis/ bronchospasm
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Differential Diagnosis ► Related Diseases Serum Sickness Systemic Mastosytosis Urticaria Pigmentosa ► Unique presentations MI, PE, CVA, Seizure, asphyxia, hypoglycemia
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Making the correct diagnosis ► Detailed history as close to the event as possible All foods in prior 6-12 hours Consider all ingredients Look for likely suspects: e.g. legumes Write it and keep it ► Prick skin tests: Best Screening test high false positives; very low false negatives may require food challenge
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Less common lab tests ► histamine vs. tryptase level transient Tryptase NOT elevated in food-induced anaphylaxis ► RAST: ► RAST: measures specific IgE, less sensitive than skin prick Useful in pt.s who can’t d/c antihistamines or w/skin condition ► Coombs test - Type II ► complement levels - Type III ► patch testing - Type IV
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Treatment Prevention, education and observation Early intervention Medications Managing a difficult airway
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Early intervention: epinephrine ► Injection Kits: Epipen, Ana-kit, Anaguard ► When to give? ► How to administer? location: SC vs IM, site of stinger dosing Inhaled epinephrine ► Precautions: Beta-blockers and Tricyclics
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Medical adjuncts ► Antihistamines Use in all cases H1 blockers: route and type H2 blockers ► Steroids Use in all significant cases PO (liquid), IM or IV: 2mg/kg (max 60 mg?) Prevents delayed reactions ► Bronchodilators & aminophylline
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Supportive treatment and airway issues ► Hypotension may not respond to epinephrine ► Aggressive use of IVF + Trendelenberg, vasopressors if necessary ► MAST trousers, glucagon and naloxone also reported helpful ► Laryngeal edema and angioedema of the face pose critical airway challenges
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Prevention Food allergies: Avoid entire food group if sensitive to one member (unless proven safe) Canned fish (heated) may be tolerated if tested under controlled setting Beware baked goods Learn ingredients, pseudonyms and synonyms Drug allergies: desensitization: a temporary measure premedicate and observe closely
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Prevention, education and observation Venom allergies: Don’t entice the insects: sights and smells Who gets venom immunotherapy? Educate all caretakers 4 hour observation/ hospital observation if not resolving rapidly
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Which of the following is the safest and most efficient route to administer epinephrine in an allergy emergency: A IV B Sub Q C IM D PR
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Syncope after shot A 16 y/o girl just passed out after receiving her penicillin shot for strep throat (“doesn’t swallow pills”). Which of the following will be most useful to know in treating her: A Her Blood Pressure B Her Glucose level C Her Heart Rate D Your Heart Rate
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A first year PEM fellow attending conference developed a sudden onset of urticaria, lip swelling and DIB. The etiology is most likely a reaction to: A smelling someone else’s lunch B a spider bite C another “billing talk” by Dr Linzer
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Allergen Families Which of the following potential allergens do not generally cross-react: A. COX-2 inhibitors & Ibuprofen B. Filberts & Pecans C. Peanuts & Tofurky D. Lobster & Shrimp
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Using the “Epi-Pen” When advising parents/patients on how to administer an “epipen” you should tell them to: A. hold it against the triceps and squeeze the trigger B. “stab” it into the anterior thigh C. hold it against the lateral thigh and push
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Presentations of Anaphylaxis Which is NOT a clinical presentation of anaphylaxis: A. Vomiting and Diarrhea B. Syncope C. Altered Mental Status D. Itchy Tongue E. None of the above
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First line therapy In counseling a 50kg 15 year old after a severe episode of anaphylaxis to a bee sting your best advice is that if they get stung again they first should take A. (2) 25mg diphenhydramine capsules PO B. (5) tsp diphenhydramine elixer PO C..5mg epinephrine SQ D. 60mg prednisone PO
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Which of the following treatments has been shown to decrease the incidence of biphasic reactions: Which of the following treatments has been shown to decrease the incidence of biphasic reactions: A. Corticosteroids B. Epinephrine C. Diphenhydramine D. Ranitidine
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Summary: Various mechanisms and presentations May resemble common illnesses Early recognition and treatment Prevention is critical
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