1 st Paediatric Emergency Conference Kuwait October 2011

1. 1st Paediatric Emergency Conference Kuwait October 2011 Emergency Treatment of Anaphylaxis in Infants and Children Dr. D. Anna Jarvis

2. Disclaimer I have no actual or potential conflict of interest to declare. Photographs, images, charts and information were selected from The Hospital for Sick Children teaching file, my personal collection or downloaded from the internet. Dr. D. A. Jarvis

3. Learning Objectives On completion of this session participants will: • Understand the full range of paediatric anaphylaxis presentations • Know the high risk criteria for delayed and biphasic reactions • Be prepared to treat anaphylaxis in concordance with published consensus guidelines

4. Historical Perspective 1902 Prof Richet and Dr. Porter named ana (against) and phylaxis (protection) 1904(approximately) Arthus described anaphylaxis in rabbits 1911 Auer ascribed lethal rabbit anaphylaxis to heart failure associated with impaired coagulation 1960s role of mast cells and IgE described 2005-6 collaborative symposia established Epinephrine as first-line treatment and clinical definitions of anaphylaxis confirmed

5. Challenges – Multiple definitions • World Health Organization (WHO) “anaphylaxis is a severe, life-threatening generalized or systemic hypersensitivity reaction” • National Institute of Allergy and Infection Disease (NIAID) and Food Allergy and Anaphylaxis Network (FAAN) “ a serious allergic reaction that is rapid in onset and may cause death” (clinical criteria defined)

6. Anaphylaxis – Definition 2006 Anaphylaxis is a severe, acute, potentially life-threatening medical condition caused by systemic release of mediators from mast cells and basophils, often in response to an allergen. Note: Clinical criteria described on following slides Second Symposium on the Definition and Management of Anaphylaxis: Summary Report Samson J Allergy ClinImmunol 2006; 117:391-97

7. Clinical Definition: Anaphylaxis 2006 Anaphylaxis is likely if any of the following 3 criteria is satisfied within minutes to hours of an exposure: 1.Acute onset of illness with cutaneous and / or mucosal involvement AND at least one of the following: • Respiratory compromise (example: dyspnoea, bronchospasm, stridor, hypoxia) • Cardiovascular compromise (examples: hypotension, collapse)

8. Clinical Definition: Anaphylaxis 2006 • Two or more of the following occur rapidly after exposure to a likely allergen (minutes to several hours): • Involvement of skin or mucosa (examples: generalized hives, itch, flushing, swelling) b. Respiratory compromise • Cardiovascular compromise • Persistent Gastrointestinal symptoms (examples: crampy abdominal pain, vomiting)

9. Clinical Definition: Anaphylaxis 2006 • Hypotension after exposure to known allergen for that patient (minutes to several hours): Age-specific low blood pressure or greater than 30% decline from baseline Hypotension in children is defined as: • less than 70mm Hg 1 month to 1 year • less than 70mm Hg + (2x age) from 1 to 10 year • less than 90 mm Hg from 11 to 17 years American Heart Association 2010 Guidelines

10. Challenges - Presentations • presentations vary with age and gender • marked geographical differences in incidence and triggers reported • literature has multiple small series and retrospective reviews, few prospective studies Consensus view 2011: • anaphylaxis incidence rates increasing especially in first 2 decades of life • the majority of children with anaphylaxis continue to be undertreated due to lack of recognition and/or failure to administer epinephrine

11. Anaphylaxis – Age considerations Gender:younger ages – many more males adolescents - males equal females Infants:hives and vomiting more common *many had no BP documented on chart 2 - 5 years:wheezing, hoarse voice, stridor more common Up to 5 years:generalised swelling 56% Adolescents:trouble breathing 57% trouble swallowing 48%

12. Paediatric Anaphylaxis – GermanyMehl 2005 – questionnaire paediatricians/primary care about children with anaphylaxis in previous 12 months • 103 cases – median age 5 years – 58% boys • Triggers: food 57% (peanut 20% tree nut 20%) stings 13% immunotherapy 12% unknown 8% • Previous anaphylaxis 27% (50% same allergen) • Severe anaphylaxis cases 36% received adrenalin • On discharge 17% prescribed adrenalin self injector

13. Paediatric Anaphylaxis – Melbourne, Australiade Silva 2008 – 5 year retrospective review of paediatric emergency records 123 children 117 events • Median age 2.4 years (oldest 18 years) Allergic history: 17% had previous anaphylaxis 40% eczema 32% asthma (54% on inhalers) 9% rhinitis Triggers: food 85% (peanut 18% cashew 13% cow milk 11%) • Median time from exposure to anaphylaxis 10 minutes onset to therapy 40 minutes • Presentations: respiratory 97% skin 97% gastrointestinal 29% cardiovascular 17%

14. Anaphylaxis Management • epinephrine (adrenalin) anaphylaxis • CAB (ABCs) PALS / ACLS • adequate intravenous fluids shock • H1 - antihistamines itch and hives • H 2 - antihistamines • β2 – adrenergic agonists bronchospasm • glucocorticoids may prevent protracted or biphasic symptoms NOTE: very little evidence for management exists! Consensus that epinephrine is medication of choice Simons 2009, 2010 Samson 2006

15. Epinephrine (Adrenalin) pharmacology

16. Epinepherine Intrinsic Limitations • rapidly metabolized (parental administration) • if swallowed rapidly metabolized by: catechol - o - methyltransferase - GI tract wall monoamine oxidase - GI tract wall + liver • narrow therapeutic / toxic dose range • break down in solution (12 - 18 months?) NOTE: danger of injuries during administration “missed dose” hazard with incorrect administration technique

17. Risk factors for sting anaphylaxis • angiotension converting enzyme inhibitors • pre-existing vespid allergy • male sex • serum mast cell tryptase levels above 5ng/l Bonadonna 2009 J Allergy ClinImmunol 379 patients with hymenoptera stings 11.6% had tryptase levels over 11.4 ng/l 70.5% of these had systemic anaphylaxis 34 patients with elevated levels underwent bone marrow biopsy 61.7% had systemic mastocytosis

18. Do large local reactions increase risk of future anaphylaxis? 5-10% patients with large local reactions have anaphylaxis 17% patients with anaphylaxis to stings have no history of prior exposure Golden 2009 reported 41 patients with large local reactions after controlled sting challenge, randomly assigned to venom immunotherapy then re-challenged after 7-11 weeks: 42% treated patients had smaller reactions 18% untreated patients had smaller reactions

19. Anaphylaxis: risks of biphasic reaction • Mehr2009 Clinical and Experimental Allergy 39: 1390-96 • 5 year retrospect study Australia • 109 episodes in 104 children • 95 (87%) uniphasic, 12 (11%) biphasic and 2 (2%) • protracted reactions

20. Anaphylaxis – biphasic reactions 12 children Mehr 2009 compared to first anaphylaxis episode – biphasic reaction: milder 58% similar 33% more severe 9%

21. Which patients require follow up and / or further evaluation? • systemic reactions especially “idiopathic” episodes • anaphylaxis • education about avoidance of allergens, epinephrine self injection or treatment required • candidate for skin testing, specific IgE measurement or immunotherapy • coexisting medical condition(s) which might predispose to repeated episodes

22. Epinephrine therapy: Learning from survivorsSimons et al J Allergy ClinImmunul 2009; 124: 301-6 1885 patients with clinical anaphylaxis 27% self administered epinephrine Reasons given for not administering epinephrine: 38% used antihistamine instead 28% not prescribed epinephrine

23. Epinephrine (Adrenalin) autoinjectors

24. Autoinjectors – unintentional injectionsSimons 2009 Ann Allergy Asthma Immunol • Systematic review, English Language 1966 – 2008 • 1998-2008 26 reports 69 cases (58% female) • No deaths / severe morbidity – What of “lost doses”? • Home 42% finger or thumb injury 91% • 65% assessed in emergency department: 13% no treatment / observation 25% injured area warmed 9% nitroglycerine paste 22% injection lidocaine and / or phentolamine 20% other treatments 12% no details available Note: Additional 10231 cases 1994-2005 reported

25. References Anaphylaxis: past, present and future Ben-Shoshan M, Clarke AE Allergy 2011; 66: 1-14 Emergency treatment of anaphylaxis in infants and children Cheng A, Canadian Paediatric Society, Acute Care Committee Paediatr Child Health 2011; 16: 35-40 Epinephrine and its use in anaphylaxis: current issues Simons KJ, Simons FER CurrOpinAllergy ClinImmunology 2010; 10: 354-61 Multicenter Study of Repeat Epinephrine Treatments for Food-Related Anaphylaxis Rudders SA, Banerji A, Corel B, et al Pediatrics 2010; 125: e711-18

26. References Anaphylaxis and insect allergy Demain JG, Minaei AA, Tracy JM Curr Opinion in Allergy and Clinical Immunology 2010; 10: 318-22 Voluntarily reported unintentional injections from epinephrine auto-injectors Simons FER, Edwards ES, Read EJ Jr et al J Allergy ClinImmunology 2010; 125: 419-23 Clinical predictors for biphasic reactions in children presenting with anaphylaxis Mehr S, Liew WK, Tey D, Tang MLK Clinical Et Experimental Allergy 2009; 39: 1390-96 Anaphylaxis: Recent advances in assessment and treatment Simons FE J All ClinImm 2009; 124: 625-36

27. References Predictors of severe systemic anaphylactic reactions in patients with Hymenoptera venom allergy: importance of baseline serum tryptase – a study of the European Academy of Allergology and Clinical Immunology Interest Group on Insect Venom Hypersensitivity Rueff F, Przbyilla B, Bilo MB et al J Allergy ClinImmunology 2009; 124: 1047-54 Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels Bonadonna P, Perbellini O, Passalacqua G et al J Allergy ClinImmunology 2009; 123: 680-86 Anaphylaxis in the community: Learning from the survivors Simons FER, Clark S, Camargo CA J Allergy ClinImmunology 2009; 124: 301-6 Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization Kemp SF, Lockey RF, Simons FER on behalf of the World Allergy Organization ad hoc Committee on Epinephrine in Anaphylaxis Allergy 2008; 63: 1061-70

28. References Paediatric anaphylaxis: a 5 year retrospective review de Silva IL, Mehr SS, Tey D, Tang MLK Allergy 2008; 63: 1071-76 Paediatric allergic reactions in the emergency department: a review Melville N, Beattie T Emerg Med J 2008; 655-58 Management of Anaphylaxis in Children Liberman DB, Teach SJ Pediatric Emergency Care 2008; 24: 861-69 Prevention and treatment of anaphylaxis Tang MLK, Kang LW Paediatrics and Child Health Journal (UK) 2008; 18(7); 309-16

29. References Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation of 103 patients Ellis AK, Day JH Ann Allergy, Asthma & Immunol 2007; 98:64-69 Self-injectable Epinephrine for First-Aid Management of Anaphylaxis Sicherer SS, Simons FER, and the Section on Allergy and Immunology Pediatrics 2007; 119: 638-46 Paediatric emergency department anaphylaxis different patterns from adults Braganza SC, Acworth JP, McKinnon DRL, Peake JE, Brown AFT Arch Dis Child 2006; 91: 159-63 Anaphylactic reactions children – a questionnaire-based survey in Germany Mehl A, Wahn U, Niggeman B Allergy 2005; 1440-44