Causes of Anaphylaxis

AAAAI 2014 San Diego WAF Symposium Anaphylaxis: From Mechanisms to Novel Therapies Causes of Anaphylaxis Motohiro Ebisawa, MD, Ph D, FAAAAI Sagamihara National Hospital Clinical Research Center for Allergy and Rheumatology Department of Allergy

WAO POSITION PAPER WAO Guidelines for the Assessment & Management of Anaphylaxis WAO Journal 2011; 4:13 37)

WAO POSITION PAPER WAO Guidelines for the Assessment & Management of Anaphylaxis WAO Journal 2011; 4:13 37)

Overview of Anaphylactic Triggers 35 35 30 25 20 20 20 % of Cases 20 15 10 5 5 3 0 Food Drug/Bio Insect Sting Idiopathic Exercise Allergen Vaccines Golden. Anaphylaxis, 2004 AAAAI education slide

Triggers of Anaphylaxis: Food Milk Eggs Seafood Peanuts Tree nuts Wheat Other Modified from AAAAI education slide

Case1: Food-induced anaphylaxis (A case of wheat OFC) 4 years old boy developed skin flush with wheezing and dyspnea.

Causes of food-induced anaphylaxis among children Study Country Publication year Caused by food-induced anaphylaxis 1st 2nd 3rd Järvinen KM et al. USA 2008 Peanuts Cow s milk Nuts 95 Cases (n) Rudders SA et al. USA 2010 Peanuts Cow s milk Nuts 846 Russell S et al. USA 2010 Peanuts shellfish Cow s milk 124 Ref. J Allergy Clin Immunol. J Allergy Clin Immunol. Pediatr Emerg Care. Braganza SC et al. Australia 2006 Dairy Egg Peanuts 57 Arch Dis Child. de Silva IL et al. Australia 2008 Peanuts cashew nut Cow milk 104 Allergy D. L. M. Goh et al. Singapore 1999 Bird's nest Piromrat K et al. Thailand 2008 Prawn Crustacean seafood Egg and milk 124 Allergy Asian Pac J Allergy Immunol. Imai T Japan* 2004 Hen's egg Cow s milk Wheat 408 Arerugi *: infant only

Causes of food-induced anaphylaxis among adults Study Country Publication year Caused by food-induced anaphylaxis 1st 2nd 3rd Cases (n) Greenhawt MJ et al. USA 2009 Cow s milk Nuts Shellfish 104 Asero R et al. Italy 2009 Peach Shrimp Nuts 58 Moneret-Vautrin DA et al. France 1995 Hen s egg Brown AF et al. Australia 2001 Fish and Seafood Fish or crustaceans Nuts milk or fruitlatex group Mango or Lemon drink 794 22 Ref. J Allergy Clin Immunol. Int Arch Allergy Immunol. Ann Gastroenterol Hepatol J Allergy Clin Immunol. Imai T Japan 2004 Fish Buckwheat Meat 130 Arerugi

Causes of food-induced anaphylaxis from childhood to adulthood Study Country Publication year Age Caused by food-induced anaphylaxis 1st 2nd 3rd Ross MP et al. USA 2008 2-66y Seafood nuts 23 Min-Suk Yang et al. Korea 2008 5 76y Wheat flour Buckwheat Seafood 29 Cases (n) Imamura T et al. Japan 2008 0-93y Milk Eggs Wheat 319 Cianferoni A et al. Italy 2001? Seafood 113 Ref. J Allergy Clin Immunol. Ann Allergy Asthma Immunol. Pediatr Allergy Immunol Ann Allergy Asthma Immunol.

Worldwide cases of fatal food-induced anaphylaxis USA 1994-1999 32 cases* Peanut 20 Tree nuts 10 Milk 1 Fish 1 *Including a case of antigen suspected USA to cause JACI 2001,107:191-2001-2006 3 31 cases Peanut 17 Tree nuts 8 Milk 4 Shrimp 1 JACI 2007,119:1016-8 UK 1999-2006 48 cases Peanut 9 Nuts 9 Milk 6 Fish 1 Shellfish 1 Snail 1 Sesame 1 Egg 1 Tomato 1 (uncertain 18) JACI 2007,119:1018-9 Australia 1997-2005 7 cases Peanut 3 Fish 1 (no information 1) (undetermined 2) JACI 2009,123:434-42 Japan 1999-2004 4 cases Shrimp 1 Buckwheat1 Fish 1 Chocolate 1 Nihon Kyukyu Igakukai Zasshi2005,16:564-6

Anaphylaxis from ingestion of mites: Pancake anaphylaxis J Allergy Clin Immunol 2013;131:31-5 J Allergy Clin Immunol 2013;131:31-5

Clinical group Gelatin sensitization Positive test results No. tested Percent positive Red meat 30 40 75 Gelatin colloid 2 2 100 Venom allergy 1 * 242 * 0.4 Idiopathic anaphylaxis 4 172 2.3 Drug allergy 4 368 1.1 Nonmeat food allergy 0 222 0 Miscellaneous 0 290 0 Totals 40 * 1335 2.9 One thousand three hundred twenty-five patients underwent IDTs with gelatin colloid between 1997 and 2011. *One patient returned with red meat induced anaphylaxis 5 years after investigation for insect venom allergy and was reclassified into the red meat allergy group. J Allergy Clin Immunol 2012;129:1334-42.

Patient no. Sex Clinical features of subjects presenting with anaphylaxis to CMF with scgos Atopy phenotype 1 F AR, AS, AD, AC Age at reaction No. of episodes 5 y, 6 mo 3 Gain IQ Step3 (CMF2) 2 F AR, AD 6 y, 6 mo 1 Mamil Gold Step4 (CMF1) 3 M AR 38 y 1 Mamil Gold Step3 (CMF1) 4 F AR 6 y 1 Mamil Gold Step4 (CMF1) 5 M AD, AR, AS 8 y 1 Gain IQ Step3 (CMF2) Milk eliciting reaction Volume eliciting reaction (ml) (1) 100 (2) 120* (3) 40 Time (min) Reaction 10 RS, Resp 250 30 AE, RS Resp 180 10 AE, RS Resp 250 15 AE, GU, GI RS, Resp 180 5 AE, GU, RS Resp CMF1 and CMF2 denote the respective CMF brands, as listed above. These abbreviations are also referred to as such in the main text. AC, Allergic conjunctivitis; AD, atopic dermatitis; AE, angioedema; AH, antihistamines; AR, allergic rhinitis; AS, asthma; F, female; GI, vomiting; GU, generalized urticaria; LU, localized urticaria; M, male; Resp, wheeze, dry persistent cough, or dyspnea; RS, rhinorrhea and bouts of sneezing. *The patient underwent an oral provocation challenge with CMF2 in the hospital and had similar respiratory-related symptoms. J Allergy Clin Immunol 2012;130:1361-7.

Triggers of Anaphylaxis: Insect Stings and Bites Bees Vespids Fire ants and other ants Scorpions Deer & horse flies Mosquitoes Modified from AAAAI education slide

Iatrogenic Triggers of Anaphylaxis Diagnostic agents Contrast media Medications Antibiotics Aspirin and other NSAIDs Biological response modifiers Anti-venoms Monoclonal antibodies Blood transfusions Allergen immunotherapy Joint Task Force on Practice Parameters: AAAAI, ACAAI, and JCAAI. J Allergy Clin Immunol 2005;115:S483-523

Triggers of Anaphylaxis: Anaphylaxis during Anesthesia Causal agent Reactions (%) No. of patients NMBAs neuromuscular blocking agents 58.08 1067 Succinylcholine 356 Rocuronium 313 Atracurium 206 Atracurium 109 Latex 19.65 361 Antibiotics 12.85 236 Penicillin 115 Cephalosporin 88 Others 9.42 187 Total 1851 Agents involved in IgE-mediated reactions during anesthesia (1816 patients, 1851 substances) between Jan 1, 1997, and Dec 31, 2004 J Allergy Clin Immunol 2011;128:366-73

Triggers of Anaphylaxis: Latex Some groups are at increased risk Healthcare workers Children with spina bifida Patients with multiple surgeries Increased incidence during the 1990 s was due largely to implementation of universal precautions. Incidence has decreased since non-powder gloves have become available Kelly KJ et al, J Allergy Clin Immunol 1994;93:813-6

Triggers of Anaphylaxis: Physical Exercise-induced Food or medication are often co-triggers Wheat, celery, peanut and multiple others May be more common than previously noted. Cold-induced Heat-induced Burgess B. EMedHome.com

Summary of world wide multiple food-dependent exercise-induced anaphylaxis case reports Publication Caused by FEIAn Study Country Age year 1st 2nd 3rd Shellfish or Kano H et al. Japan 2000 9-43y Wheat Shrimp fish Cases (n) Ref. 18 Arerugi Harada S et al. Japan 2000 >20 Wheat Shrimp 167 Arerugi Harada S et al. Japan 2000 <20 Shrimp Wheat 167 Arerugi Aihara Y et al. Japan 2001 12-15y Shrimps and crab Yang MS et al. Korea 2008 5-76y Wheat Wheat Apple or shrimp Grapes Vegetables buckwheat Teo SL et al. Singapore 2009 9-20y Shellfish 5 Mathelier-Fusade P et al. France 2002? Wheat Corn, barley, shrimp, apple, paprika, mustard Romano A et al. Italy 2001? Tomatoes Wheat Peanuts 54 Shadick NA et al. USA 1999 13-77y Shellfish Alcohol Tomatoes 13 18 7 279 (EIA patients) J Allergy Clin Immunol Ann Allergy Asthma Immunol Ann Acad Med Singapore Ann Dermatol Venereol Int Arch Allergy Immunol J Allergy Clin Immunol

Case 2: A case of food-dependent exercise-induced anaphylaxis Fourteen years old junior high school student developed anaphylaxis after eating seafood in his lunch and playing football with his friends

Age distribution of Food-dependent exercise-induced anaphylaxis (n) reported from 1979 to 2004 40 30 20 10 Ag e n=84 0 0-10- 20-30- 40-50- 60-70- (by Aihara Y arerugi 2007)

Causative foods of FEIAn reported from 1979 to 2004 Food Case (n) (%) Wheat 29 (38.2) Vegetable 24 (31.6) Nut 16 (21.1) Fruit 7 (9.2) Plant oil 4 (5.3) Shellfish 3 (3.9) Others 6 (7.9) Total 76 (by Aihara Y arerugi 2007)

WAO POSITION PAPER WAO Guidelines for the Assessment & Management of Anaphylaxis

Co-morbid conditions and risk factors for food-induced anaphylaxis and Food-dependent exercise-induced anaphylaxis Factors FIA FEIA Ref. Disease Asthma* JACI. 2009; 124: 625 Cardiovascular disease Clin Exp Immunol. 2008;153:7 Curr Opin Allergy Clin Immunol. 2007; 7:337 Infection JACI. 2010; 125: S161 Other disorder** JACI. 2010; 125: S161 Medication Beta-adrenergic blockers Curr Allergy Asthma Rep. 2008; 8: 37 Angiotensin-converting enzyme (ACE) inhibitors Curr Allergy Asthma Rep. 2008; 8: 37 Alpha-adrenergic blockers Curr Allergy Asthma Rep. 2008; 8: 37 Antidepressants Curr Allergy Asthma Rep. 2008; 8: 37 NSAIDs, aspirin J Dermatol Sci. 2007; 47: 109 Br J Dermatol. 2001; 145: 336 Other Alcohol intake Addict Biol. 2004; 9:195 Fatigue JACI. 2010; 125: S161 Stress JACI. 2010; 125: S161 Type of exercise JACI. 2010; 125: S161 Atmospheric condition and seasonal JACI. 2010; 125: S161 * ** especially if poorly controlled 1) mastocytosis and clonal mast cell disorder, 2) chronic lung disease 3) anatomical airway obstruction, 4) Depression and other psychiatric disease