1. INNOVATIONS IN ANAPHYLAXIS Diagnosis, treatment and management of anaphylaxis

2. FACULTY/PRESENTER DISCLOSURE  Faculty: Dr. Bhanu Muram  Relationships with commercial interests: none

3. LEARNING OBJECTIVES After participating in the following educational program participants should be able to: 1.Identify gaps in the diagnosis and management of anaphylaxis. 2.Describe the causes, signs, and symptoms of anaphylaxis. 3.Understand the diagnostic tests for food allergy. 4.Identify the appropriate treatment of acute anaphylaxis and long term management for patients at risk.

4. ANAPHYLAXIS PREVALENCE

5. PREVALENCE  True prevalence of anaphylaxis is unknown, but likely underestimated and underreported 1,2 However, it is increasing and in the range of 0.05% to 2%. 1,2 Highest number of cases is in children and adolescents. 2-4  Canadian studies have reported anaphylaxis rates of 0.50% to 0.95% 1 (EMS database and outpatient prescriptions for epinephrine to estimate the proportion of individuals at-risk for anaphylaxis, respectively) 1. Ben-Shoshan & Clarke. Allergy 2011;66:1-14 2. Lee & Vadas. Clinical & Experimental Allergy, 2011; 41:923–938. 3. Kim &Fischer. Allergy, Asthma & Clinical Immunology 2011;7(Suppl 1):S6. 4. Lin et al. Ann Allergy Asthma Immunol. 2008;101:387–393.

6. TRIGGERS OF ANAPHYLAXIS Most Common  Foods  Stinging insect venoms  Medications Examples of Less Common:  Natural rubber latex  Occupational allergens  Aeroallergens  Seminal fluids  Physical factors (exercise, sunlight)  Mastocytosis  Idiopathic  Others … Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

7. CANADIAN DATA – FOOD ALLERGY Approximately 6.7% of Canadians with Self Reported Food Allergy (approx. > 2.0 millions) Prevalence (%) AllergenChildrenAdultsOverall Peanut1.770.781.00 Tree nut1.731.071.22 Fish0.180.600.51 Shellfish0.551.911.60 Sesame0.230.070.10 Milk2.231.91.97 Egg1.230.670.80 Wheat0.450.860.77 Soy0.320.160.20 Soller L et al. J Allergy Clin Immunol. 2012;130(4):986-988

8. THE FOOD ALLERGY EPIDEMIC Health Care Data – CDC Hospital Discharge Dx * * Statistically significant trend SOURCE: Branum, NCHS, National Health Interview Survey No.10, Oct. 2008 Average discharges per year Average discharges in children <18 with any diagnosis related to food allergy in the USA

9. CURRENT CHALLENGES IN ANAPHYLAXIS MANAGEMENT  Definition of anaphylaxis only recently updated  Diagnosis of those at risk not always straightforward  Many food allergies are lifelong  No specific treatment or prevention strategies  Lack of access to epinephrine auto-injector and allergy specialist advice  There are many gaps in the management of anaphylaxis Waserman et al, Allergy 2010; 65: 1082–1092.

10.  Lack of knowledge Signs and symptoms to correctly diagnose anaphylaxis Epinephrine Auto-Injectors (EAI): how to use, correct dose, route of administration, inadequate or no training to patients  Management Infrequent and/or delayed administration of epinephrine Diagnostic coding infrequent or not determined  Follow-up care EAI prescribing infrequent or not the most commonly prescribed treatment Infrequent or no referral to allergy specialist after acute reaction PHYSICIANS GAPS Kastner et al. Allergy. 2010;65(4):435-444

11.  Lack of knowledge General management, signs/symptoms of anaphylaxis, food avoidance measures, lack of educational materials EAIs : receive inadequate, infrequent or no instructions on use  Anaphylaxis management Do not carry auto-injectors; carry it but do not use it No anaphylaxis management plan  Quality of life Restriction of social activities Fear and anxiety over severe reactions Lack of understanding by others, feeling of being a bother PATIENTS / COMMUNITY GAPS Kastner et al. Allergy. 2010;65(4):435-444.

12. ANAPHYLAXIS DEFINITION

13. FINALLY ! …A CONSENSUS DEFINITION FOR ANAPHYLAXIS  Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death Sampson et al, J Allergy Clin Immunol 2006;117(2):391-397

14. Simons FE. J Allergy Clin Immunology 2009; 124 (4): 625-636 MECHANISM OF ANAPHYLAXIS

15. 3 criteria Anaphylaxis is highly likely when any of the following 3 criteria are fulfilled : Sampson et al, J Allergy Clin Immunology 2006;117(2):391-397

16. ANAPHYLAXIS IS HIGHLY LIKELY WHEN… Sudden onset of an illness (minutes to several hours), with involvement of the skin, mucosal tissue, or both (e.g. generalized hives, itching or flushing, swollen lips-tongue-uvula) AND AT LEAST ONE OF THE FOLLOWING : Sudden respiratory symptoms and signs Sudden reduced BP or symptoms of end-organ dysfunction 1 Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

17. ANAPHYLAXIS IS HIGHLY LIKELY WHEN… Two or more of the following that occur suddenly after exposure to a likely allergen or other trigger for that patient (minutes to several hours): Sudden skin or mucosal symptoms and signs Sudden respiratory symptoms and signs Sudden reduced BP or symptoms of end-organ dysfunction Sudden gastrointestinal symptoms 2 Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

18. ANAPHYLAXIS IS HIGHLY LIKELY WHEN… Reduced blood pressure (BP) after exposure to a known allergen for that patient (minutes to several hours) INFANTS AND CHILDREN: Low systolic BP (age-specific) or greater than 30% decrease in systolic BP ADULTS: Systolic BP of less than 90 mm Hg or greater than 30% decrease from that person’s baseline 3 Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

19. UNIPHASIC Initial symptoms 0 0 Treatment Antigen Exposure Time - hours Ellis and Day. Ann Allergy Asthma Immunol 2007; 98:64–69; Ellis et al. CMAJ 2003;169(4):307-312 Initial symptoms

20. BIPHASIC Initial symptoms Treatment Second-phase symptoms (classic teaching) 1-8 hours 0 Treatment Antigen Exposure Ellis and Day. Ann Allergy Asthma Immunol 2007; 98:64–69; Ellis et al. CMAJ 2003;169(4):307-312

21. PROTRACTED Initial symptoms >24 hours 0 0 Treatment Antigen Exposure Ellis and Day. Ann Allergy Asthma Immunol 2007; 98:64–69; Ellis et al. CMAJ 2003;169(4):307-312

22. COULD IT BE ANAPHYLAXIS? Waserman et al. Allergy 2010, 65:1082-1092. Simons FE. J Allergy Clin Immunol 2010;125:S161-181 Flushing, itching, urticaria, angioedema Feeling of impending doom Flushing, itching, urticaria, angioedema Stridor, wheezing, dyspnea, chest/throat tightness Tachycardia or bradycardia, arrhythmia, vascular collapse, infarction Vomiting, diarrhea (bloody), cramping, incontinence Uterine cramping, incontinence Think FAST! Any of these symptoms may appear: F F ace: itching, redness, swelling A A irway: trouble breathing, swallowing, speaking S S tomach: pain, vomiting or diarrhea T T otal: hives, rash, itching, swelling, weakness, paleness, sense of doom, loss of consciousness

23.  Co-existent asthma or other respiratory diseases (esp. if poorly controlled) 1,2  Delay in or lack of epinephrine administration, not carrying EAI 1,2  History of previous severe reaction to a food, although severity of future reaction cannot always be predicted from the individual’s history 2  Failure to inquire about or to obtain information about food ingredients 2  Risky eating behaviors, especially teens and young adults 2  Concurrent medications, like beta-blocker therapy 1 RISK FACTORS FOR FATAL FOOD-ALLERGIC REACTIONS 1.Simons FE. J Allergy Clin Immunol 2010;125:S161-181 2.Muñoz-Furlong & Weiss. Current Allergy and Asthma Reports 2009;9:57-63.

24. DIAGNOSIS Evaluation by Allergist  History Detailed clinical history helps determine the diagnostic tests o Temporal correlation is important: –When did the reaction happen after exposure? –How long did the reaction last?  Tests: Skin prick tests Allergen Specific IgE (blood test) in selected cases Food challenge Simons FE. J Allergy Clin Immunol 2010;125:S161-181

25. ANAPHYLAXIS MANAGEMENT

26. PRIMARY ANAPHYLAXIS TREATMENT? Please select one: a)Oral steroids b)Antihistamines c)Epinephrine d)All of the above e)B and C Show of hands

27. EPINEPHRINE  Epinephrine is the first-line treatment for anaphylaxis 1-3  Epinephrine is an α- and β-adrenergic receptor agonist 1,2 α increases Peripheral Vascular Resistance, increasing BP β-1 has inotropic and chronotropic effects so increases HR and strength of contraction β-2 decreases mediator release from mast cells and basophils and increases bronchodilatation 1.Sheikh A et al. Allergy 2009, 64: 204-212 2.Simons FE. J Allergy Clin Immunol 2010;125:S161-181. 3.Waserman et al. Allergy 2010, 65:1082-1092..

28. EPINEPHRINE  Fatality rates are highest in patients in whom treatment with epinephrine is delayed. 1-3  No contraindication to the use of epinephrine, if uncertain, err on the side of treatment. 4  Second dose of epinephrine may be required 2,3 if symptoms persist after first dose.  Antihistamines should not be used as first-line treatment for anaphylactic reactions. 3,4 1.Sheikh A et al. Allergy 2009, 64: 204-212 2.Muñoz-Furlong & Weiss. Current Allergy and Asthma Reports 2009;9:57-63 3.Simons FE. J Allergy Clin Immunol 2010;125:S161-181. 4.Waserman et al. Allergy 2010, 65:1082-1092.

29. BASIC MANAGEMENT OF ANAPHYLAXIS Have a written emergency protocol. 1 Remove exposure to the trigger if possible 2 Assess the patient’s circulation, airway, breathing, mental status, skin, and body weight (mass). 3 Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

30. BASIC MANAGEMENT OF ANAPHYLAXIS Call for help. Promptly and simultaneously perform steps 4, 5 and 6 Inject epinephrine (adrenaline) intramuscularly in the mid- anterolateral aspect of the thigh Record the time of the dose and repeat it in 5-15 minutes, if needed. Place patient on his back. Elevate lower extremities. Fatality can occur within seconds if patient stands or sits suddenly. 4 5 6 Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

31. BASIC MANAGEMENT OF ANAPHYLAXIS When indicated, give high-flow supplemental oxygen. Establish intravenous access. When indicated, give 1-2 litres of 0.9% (isotonic) saline rapidly. When indicated at any time, perform cardio-pulmonary resuscitation. In addition: At frequent regular intervals, monitor patient’s blood pressure, cardiac rate and function, respiratory status and oxygenation. 7 8 9 9 Simons et al, J Allergy Clin Immunology 2011;127(3):587-593

32. Anaphylaxis? Assess ABC AIRWAY BREATHING CIRCULATION IM epinephrine Call 911 SIMPLE ALGORITHM Epinephrine is the drug of choice for anaphylaxis and should be given immediately, even if diagnosis is uncertain, IM administration into the lateral thigh is recommended. Simons et al, J Allergy Clin Immunology 2011;127(3):587-593 Anaphylaxis in Schools and Other Settings. 2 nd Edition Revised March 2011

33. EPINEPHRINE AUTO-INJECTORS  EpiPen® 0.3mg and EpiPen® Jr. 0.15mg  Demonstration on how to use Epipen www.epipen.ca EpiPen Prescribing Information

34. SAFETY ATTRIBUTES OF EPIPEN  Size of the instructions which makes them easy to read  Shape of the body which makes it easy to grip  Needle cover is a bright orange colour and labeled "NEEDLE END" for quick and easy orientation  Carrier with a flip-top cap for easy access  Orange needle cover that automatically extends to cover the injection needle once EpiPen® is removed, ensuring the needle is never exposed www.epipen.ca

35. EPINEPHRINE AUTO-INJECTORS  TwinJect™ 0.3mg and TwinJect™ 0.15mg  2 doses  1 st dose: auto-injector  2 nd dose: manual syringe www.twinject.ca

36. SAFETY ATTRIBUTES OF TWINJECT  Twinject is an epinephrine auto-injector that automatically administers a single dose of epinephrine  Twinject auto-injector comes with a backup dose  A second dose is available for manual injection following a partial disassembly of the Twinject Auto-Injector. www.twinject.ca

37. EPINEPHRINE AUTO-INJECTORS  NEW: Allerject 0.3mg and Allerject 0.15mg  Demonstration on how to use Allerject 0.3 mg 0.15mg NO DRUG TRAINER Allerject Prescribing Information

38.  Includes an electronic voice and visual prompt system that assist the user throughout the injection process If the voice instructions do not work as intended, Allerject can still be used as instructed on the device label.  Outer case that protects the epinephrine from sunlight  Red safety guard (on same end as needle) that prevents accidental activation of the injection  Retractable needle system that will automatically inject the needle upon activation, deliver epinephrine through the needle, and retract the needle fully into the housing once the injection is complete SAFETY ATTRIBUTES OF ALLERJECT Allerject Prescribing Information

39. BIOAVAILABILITY Epinephrine levels, as measured by C max, AUC 0-t and AUC inf, following injections with Allerject and with EpiPen were bioequivalent. Mean ± SD epinephrine plasma concentration vs. time following an injection of Allerject and EpiPen in healthy subjects Edwards ES, Gunn R, Simons FE, et al. J Allergy Clin Immunology 2012;129 (2 suppl):AB179 # 678. Poster Presented at the 2012 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI); Orlando, FL, USA; March 2-6, 2012.

40. OTHER MEDICATIONS MedicationTreatment Oxygen and fluid resuscitation High-flow oxygen should be administered to patients experiencing respiratory symptoms, hypoxia or hemodynamically unstable. 1 Rapid fluid resuscitation should be given to restore intravascular volume. 1,2 H 1 – and H 2 – antihistamines Not recommended for acute management. 2 Consider second line for symptomatic treatment of urticaria-angioedema and pruritus. 1 CorticosteroidsNot recommended for acute management. 1 Adjunctive medication, may help in an acute attack in preventing or shortening protracted reactions and in the treatment of recurrent idiopathic anaphylaxis. 2 Early corticosteroids treatment is beneficial in asthma. 2 Steroids do not prevent biphasic reactions. 1,2 BronchodilatorsAdjunctive medication for bronchospasms refractory to epinephrine. 1,2 GlucagonIn patients taking ß-blockers - If administration of epinephrine is ineffective, glucagon can be used. Airway protection must be ensured because glucagon causes emesis. 1 1. Sampson et al, J Allergy Clin Immunol 2006;117(2):391-397 2. Tse Y and Rylance G. Arch Dis Child Educ Pract Ed 2009;94:97-101.

41.  Refer to an Allergist 1 Few patients are being referred to a specialist after an allergic reaction  Prescribe Epinephrine Auto-Injector 1,2 Epinephrine auto-injector prescription rate is low Demonstrate when and how to use the device  Prevent / Prepare 2 Provide information about how to avoid the precipitating allergen (if known) Prepare a comprehensive anaphylaxis action plan ER DISCHARGE 1. Waserman et al, Allergy 2010; 65: 1082–1092. 2.Simons FE. J Allergy Clin Immunol 2011; 127:587-593

42. EDUCATE YOUR PATIENTS AT RISK  Avoidance of the allergy-causing substance  Let others know Wear medical identification  Supervise young children  Carry an epinephrine auto-injector at all times Re-train at least once per year (include caregivers, teachers)  Have an emergency action plan Example: www.allergysafecommunities.ca __________________________________________ Guidelines for anaphylaxis in schools and other child care settings are available at: www.allergysafecommunities.ca

43. QUESTIONS ?