This is a Test It is ONLY a Test

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

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

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

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

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

Which is NOT a clinical presentation of anaphylaxis: A. Vomiting and Diarrhea B. Syncope C. Altered Mental Status D. Itchy Tongue

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

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

ANAPHYLAXIS Michael Greenwald, MD Pediatric Emergency Medicine Emory University Children’s Healthcare of Egleston

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

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

Defining Anaphylaxis  Acute  Systemic  Allergic (i.e. requires prior exposure)

Special Features of Anaphylaxis  Spectrum of severity  Variety of manifestations  Uniphasic, biphasic or protracted

Epidemiology ► Top triggers: then  penicillin  insect venom  food ► ► Top triggers: now  Latex (27%)  Food (25%)  Drugs (16%)  Venoms (15%)

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

Hypersensitivity review: Gell and Coombs Classification Type I - Anaphylactic Type II - Cytotoxic Type III - Immune Complex Type IV - Delayed Type

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

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

Type III - Immune Complexes Exposure to reaction: days Exposure to reaction: 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

Type IV - Delayed Type Exposure to reaction: hours Exposure to reaction: 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

Anaphylaxis and Her Cousin  Anaphylaxis  IgE mediated  IgG - immune complex mediated  Anaphylactoid  direct stimulation of mast cells and basophils  unknown mechanism

IgE - mediated Anaphylaxis ► Prior exposure required ► Allergen-IgE binding induces release of mediators:  histamine  prostaglandins  platelet activating factor  tryptase

IgG -immune complex mediated ► complement activated by immune complexes or other agents  Tissue antigens - RBC, WBC, Plts  Serum proteins - Immunoglobulin, cryoprecipitin ► anaphylatoxins: C3a, C5a

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

Unexplained Anaphylaxis ► Unknown mechanism:  ASA and other NSAIDS  preservatives  exercise  mastocytosis  cholinergic urticaria with anaphylaxis  progesterone: “catamenial anaphylaxis”

Unexplained Anaphylaxis ► Idiopathic anaphylaxis: unknown trigger  up to 37% of all reactions  clinically indistinguishable from other forms  particularly stressful to patients

Epidemiology ► Patients at risk:  Does atopic history matter?  Who gets the worst reactions?  Latex

Allergens  Drugs  Foods  Venoms  Latex

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

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

Drugs ► NSAIDS  bronchospasm in 2-10% of asthmatics  unknown mechanism: IgE and mast cells not involved

Drugs ► Macromolecules:  protamine  insulin  IVIG ► 2 recognized mechanisms ► IgA deficiency high risk ► slow infusion and pretreat

Drugs  Chemotherapeutic agents: L-Asparaginase  Vaccinations: MMR?  Immunotherapy  17 fatalities reported (10 million shots given annually)  precautions for medical facility:  observe 20 minute  medications and airway support available

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

Foods  Tree nuts: 1% Americans (3 million) allergic  Legumes: 25-35% also allergic to tree nuts  Shellfish  Fish  Milk  Eggs  Food additives: sulfites

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

Venoms/Antivenins  5 major stinging insects in the US:  honeybees  wasps  yellow jackets  hornets  fire ants  Rabies and snake antivenin

Latex ► incidence low, except for risk groups: ► >1000 episodes and 15 deaths attributed ► surgical and dental procedures highest risk ► RAST testing available

Exercise-induced  Variety of forms of exercise  not heat alone  not associated with atopy/asthma  strong genetic predisposition   histamine and parasympathetic tone,  sympathetic tone

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

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

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

Skin ► Early signs:  Flushing, feeling warm  Erythema  Pruritis ► Urticaria ► Angioedema ► Pallor

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

Gastrointestinal ► not only with food triggers ► crampy abdominal pain, nausea, vomiting, watery diarrhea, gastointestinal bleeding, fecal incontinence

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

Other symptoms of anaphylaxis ► Neurologic: HA, Mental Status changes ► Uterine contraction ► Urinary incontinence ► Anxiety, Feeling of “impending doom”

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

Making the correct diagnosis ► May look just like:  Asthma exacerbation  Croup or foreign body aspiration  Cardiogenic syncope  food poisoning or gastroenteritis

Vasovagal vs. Anaphylaxis ► Vasovagal  pallor  diaphoresis  bradycardia or NSR ► Anaphylaxis  tachycardia  flushing  urticaria/pruritis/ bronchospasm

Differential Diagnosis ► Related Diseases  Serum Sickness  Systemic Mastosytosis  Urticaria Pigmentosa ► Unique presentations  MI, PE, CVA, Seizure, asphyxia, hypoglycemia

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

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

Treatment  Prevention, education and observation  Early intervention  Medications  Managing a difficult airway

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

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

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

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

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

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

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

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

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

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

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

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

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

Summary:  Various mechanisms and presentations  May resemble common illnesses  Early recognition and treatment  Prevention is critical