ANAPHYLAXIS. Dr. Peter Lee

Transcription

1 ANAPHYLAXIS Dr. Peter Lee

2 OBJECTIVES 1. To be able to define and diagnose anaphylaxis 2. Describe signs and symptoms 3. Identify patients at high risk for fatal reactions 4. Review management 1. Familiarization of treatment of specific cases of anaphylaxis

3 WHICH OF THE FOLLOWING MAY BE A SIGN OR SYMPTOM OF AN ACUTE (ANAPHYLACTIC) REACTION? A. Dyspnea B. Angioedema of tongue C. Menstrual cramping and bleeding D. Chest Pain E. A and B F. All of the above

4 WHICH OF THE FOLLOWING MAY BE A SIGN OR SYMPTOM OF AN ACUTE (ANAPHYLACTIC) REACTION? A. Dyspnea B. Angioedema of tongue C. Menstrual cramping and bleeding D. Chest Pain E. A and B F. All of the above

5 WHICH OF THE FOLLOWING IS A RISK(S) FACTOR FOR SEVERE OR FATAL ANAPHYLAXIS? A. Asthma B. ACEI C. Beta blockers D. A and C E. All of the above

6 WHICH OF THE FOLLOWING IS A RISK(S) FACTOR FOR SEVERE OR FATAL ANAPHYLAXIS? A. Asthma B. ACEI C. Beta blockers D. A and C E. All of the above

7 WHEN SHOULD A CHILD WITH ANAPHYLAXIS SWITCH FROM A 0.15MG TO 0.30MG AUTOINJECTOR? A. 20kg B. 25kg C. 30kg D. 35kg

8 WHEN SHOULD A CHILD WITH ANAPHYLAXIS SWITCH FROM A 0.15MG TO 0.30MG AUTOINJECTOR? A. 20kg B. 25kg C. 30kg D. 35kg

9 ANAPHYLAXIS: DEFINITION (SAMPSON JACI 2006;117:391) Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.

10 ANAPHYLAXIS IS HIGHLY LIKELY WHEN ANY ONE OF THE FOLLOWING THREE CRITERIA ARE FULFILLED: [SAMPSON ET AL JACI 2006;117:391] 1. Acute onset of an illness (minutes to hours) with involvement of the skin and/or mucosal tissue; and at least one of the following: a. Respiratory compromise b. Reduced blood pressure

11 ANAPHYLAXIS IS HIGHLY LIKELY WHEN ANY ONE OF THE FOLLOWING THREE CRITERIA ARE FULFILLED: [SAMPSON ET AL JACI 2006;117:391] 2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient: a) Involvement of the skin/mucosal tissue (hives, itch/flush, angioedema) b) Respiratory compromise c) Reduced BP or associated symptoms d) Persistent GI symptoms

12 ANAPHYLAXIS IS HIGHLY LIKELY WHEN ANY ONE OF THE FOLLOWING THREE CRITERIA ARE FULFILLED: [SAMPSON ET AL JACI 2006;117:391] 3. Reduced BP following exposure to a known allergen for that patient. a. Infants and children: low systolic BP (age specific) or >30% drop in systolic BP. <70mmHg from 1m to 1 year <70mmHg + [2xage] from 1-10 years b. Adults: systolic BP <90mmHg or >30% drop from the individual s baseline.

13 IGE-DEPENDENT RELEASE OF INFLAMMATORY MEDIATORS IgE FcεRI FcεRI binding site Immediate Release Granule contents: Histamine, TNF α, Proteases, Heparin Sneezing Nasal congestion Itchy, runny nose Watery eyes Wheezing Bronchoconstriction Over Minutes Lipid mediators: Prostaglandins Leukotrienes Over Hours Cytokine production: Specifically TNF α, IL 4, IL 13 Cell recruitment

14 SYMPTOMS/SIGNS OF ANAPHYLAXIS Oral: Pruritus of lips, tongue, and palate; edema of lips and tongue Cutaneous: Flushing, pruritus, urticaria, angioedema Rhinoconjunctivitis: Pruritus, congestion, rhinorrhea, and sneezing, periorbital pruritus, erythema, and edema; conjunctival erythema and tearing

15 SYMPTOMS/SIGNS OF ANAPHYLAXIS Laryngeal: Pruritus and tightness in the throat, dysphagia, dysphonia and hoarseness/stridor, cough, and sensation of itching in the external auditory canals Respiratory: Dyspnea, chest tightness, cough, and wheezing

16 SYMPTOMS/SIGNS OF ANAPHYLAXIS Gastrointestinal: Nausea, abdominal pain (colicky), vomiting and diarrhea Cardiovascular: Hypotension, syncope, chest pain, dysrhythmia

17 SYMPTOMS/SIGNS OF ANAPHYLAXIS Other: lower back pain and uterine contractions/bleeding in women; aura of impending doom, seizures

18 MOST FREQUENT SIGNS AND SYMPTOMS OF ANAPHYLAXIS Manifestation Percent Urticaria/angioedema 88 Upper airway edema 56 Dyspnea/wheeze 47 Flush 46 Hypotension Gastrointestinal 30

19 WHAT IS THE CLINICAL COURSE OF ANAPHYLAXIS? Uniphasic Treatment Symptom intensity Initial symptoms Allergen exposure Time

20 WHAT IS THE CLINICAL COURSE OF ANAPHYLAXIS? Biphasic Treatment 1-72 hours Treatment Symptom intensity Initial symptoms 2 nd phase symptoms Allergen exposure Time

21 WHAT IS THE CLINICAL COURSE OF ANAPHYLAXIS? Protracted Possibly > 24 hours Symptom intensity Initial symptoms Allergen exposure Time

22 RISK FACTORS FOR DEVELOPMENT OF FOOD ALLERGY Genetics Race Increased in Asians 1 and African-Americans 2 Sex 2 Increased hygiene Vit. D Reduced consumption of omega-3- polyunsaturated fatty acids 3 Antacids 4 Route of exposure 5 and timing of exposure 6,7 Microbial factors 8,9, 1. Koplin Allergy 2012; 2. Liu JACI 2010; 3 Kull Allergy Untersmayr FASEBJ 2005; 5. Lack NEJM 2003; 6 Katz JACI Du Toit JACI 2008; 8. Sudo J Immulo 1997; 9. Bager Clin Exp Allergy 2008

23 RISK FACTORS FOR DEVELOPMENT OF FOOD ALLERGY Vitamin D <15 ng/ml increased risk of peanut sensitization 1 Higher rates of peanut and egg allergy in regions farther from equator 2 Season of birth a risk factor 3 Vit. D sufficiency protective against food allergy 4 However increased maternal Vit D levels also shown to increase food allergy 5 1. Sharief JACI Osboune JACI Vassallo JACI Allen JACI Weisee Allergy 2013

24 WHAT TRIGGERS ANAPHYLAXIS? % of Cases Food Drug/Bio Insect Sting Idiopathic Exercise Allergen Vaccines Golden 2004 Golden. Anaphylaxis, 2004

25 ANAPHYLAXIS-RELATED MORTALITY Data are scarce on mortality due to anaphylaxis under-reporting is a problem 1 Estimated incidence of fatal anaphylaxis 0.3-1/million people/year 2,3 Deaths from upper airway edema, respiratory failure or cardiovascular collapse 1. Simons JACI Pumphrey Curr Opin Allergy Clin Immnulogy Low Pathology 2006

26 FATAL REACTIONS FROM FOOD ALLERGY Bock SA, et al. J Allergy Clin Immunol

27 RISK FACTORS FOR SEVERE OR FATAL ANAPHYLAXIS Biphasic reaction Cutaneous symptoms not present Underlying asthma (especially poorly controlled) Cardiopulmonary diseases Delayed epinephrine Symptom denial Previous severe reaction Adolescents, young adults Beta blockers/acei Underlying mastocytosis Key foods: peanuts and tree nuts dominate (~90% of fatalities), fish, crustaceans Bock SA, et al. J Allergy Clin Immunol 2001;107:191 3.

28 ANAPHYLAXIS:DIAGNOSIS Serum tryptase Draw during 1 st 1-2 hours Peak minutes Persist for 6 hours

29 FUTURE INVESTIGATIONS 1. Skin tests 2. Blood tests 3. Oral challenge

30 MANAGEMENT OF ANAPHYLAXIS 1. EPINEPHRINE IS ALWAYS FIRST! 2. Always lay patient in supine position legs elevated 3. Maintain airway, supplement O2 4. Large volume fluid resuscitation (if possible) 1. Up to 35% shift in IVV within minutes 5. Other agents Boyce JACI 2010

31 EPINEPHRINE Epinephrine is the drug of choice for anaphylaxis available in auto-injector which is simple to use and gives reliable results reverses associated hypotension and bronchospasm Fatality rates are highest in patients in whom treatment with epinephrine is delayed There are no absolute contraindications to epinephrine administration in the setting of anaphylaxis Antihistamines must not be used as first-line treatment for anaphylactic reactions O'Dowd SC, et al. Anaphylaxis in Adults. Available at: Sampson HA, et al. N Engl J Med 1992; 327(6): Sicherer SH, et al. JACI 2005; 115(3):

32 EPINEPHRINE IM Epinephrine Adults mL of 1mg/mL (1:1000) anterolateral thigh Children 0.01mL (mg)/kg max 0.5mL May need to repeat q5-15 minutes Auto-injectors (intramuscular injection in the anterolateral thigh) Two epinephrine auto-injectors available: EpiPen /Allerject 0.3 mg and EpiPen Jr./Allerject 0.15 mg Children weighing 15 kg - 30 kg might be under-treated with junior dosing; NIH recommends switch at 25kg Second dose of epinephrine may be required Boyce JACI 2010

33 IM vs SQ Epinephrine + Intramuscular epinephrine (Epipen ) - 8 +/- 2 minutes Subcutaneous epinephrine (5 120) minutes p < Time to C max after injection (minutes) Simons FER: J Allergy Clin Immunol 2004;113:837-44

34 OTHER AGENTS Diphenhydramine 25-50mg IV or oral OR cetirizine 10mg Only helpful for itch and urticaria Continue for 2-3 days Ranitidine 50mg IV or 150mg PO Bronchodilators Corticosteroids Continue for 3 days Boyce JACI 2010

35 INADEQUATE MANAGEMENT OF ANAPHYLAXIS Survey of 1000 US patients Treatment of past reactions Only 11% received epi Treatment of future reactions 52% never received auto injector prescription 60% no epi available 37% planned to use antihistamine 34% planned to use autoinjector Overall prevalence 1.6% in adults Wood JACI Feb 2014

36 PATIENT ACTION PLAN Describe the signs and symptoms of anaphylaxis Instruct on when and how to use epinephrine Training for caregivers, family, friends etc Instruct patient to give epinephrine immediately (no contraindication to the use of epinephrine in a lifethreatening situation such as anaphylaxis) Call 911 List emergency contact information Guidelines for anaphylaxis in schools and other childcare settings are available at:

37 EXAMPLE OF AN ANAPHYLAXIS PATIENT ACTION PLAN Shown: Action plan for schools recommended by the CSACI. Available at: es.html

38 MY CHILD ONLY HAD A MILD REACTION, DO I NEED TO CARRY AN EPIPEN? Vanderleek J Pediatr 2000;137:749 55

39 HOW QUICKLY SHOULD EPINEPHRINE BE AVAILABLE? Minutes to Arrest First Epinephrine Median Range None Before After Iatrogenic Food Venom Pumphrey Clin Exp Allergy. 2000;30:

40 IS SKIN CONTACT WITH ALLERGEN HARMFUL? One gram of peanut butter was applied directly to the skin of 281 children with peanut allergy 330 tests for peanut contact sensitivity were performed; 136 (41%) were positive. No child had a systemic reaction following topical application of peanut butter. Wainstein Clin Exp Allergy. 2007;37:839 84

41 WHAT ABOUT INHALATION? 33 children with significant peanut allergy Inhalation (surface area of 6.3 square inches 12 inches from the face for 10 minutes) scent was masked with soy butter, tuna, and mint (inhalation). None experienced a systemic or respiratory reaction. Simonte JACI 2003;112:

42 DO I NEED TO AVOID TRACE AMOUNTS?

43 HOW CLEAN DO EATING SURFACES NEED TO BE? Perry, JACI 2004;113:973

44 HOW MANY DOES OF EPINEPHRINE SHOULD BE AVAILABLE? 13% required two doses 1 6% required three doses Peanuts, tree nuts, cow s milk accounted for 75% of reactions requiring epinephrine Patients should carry 2 doses (2010 Guidelines) 2 Jarvinen JACI 2008;122:133-8 Bocye JACI 2010

45 MY EPIPEN HAS EXPIRED, BUT HASN T CHANGED COLOR, CAN I KEEP USING IT? Simons JACI 2000

46 WHEN SHOULD EPINEPHRINE BE GIVEN? As early as possible after the onset of symptoms of a severe allergic reaction For people with a history of a severe cardiovascular collapse on exposure to an allergen, the physician may advise that epinephrine be administered immediately after exposure to that allergen, and before any reaction has begun It is ALWAYS better to give epinephrine if in doubt

47 TREATMENT OF SPECIFIC CASES

48 VENOM ALLERGY: CRITERIA FOR IMMUNOTHERAPY All patients with a systemic allergic reaction with a positive skin or RAST VIT generally not required for children < or = 16 with cutaneous systemic reactions only VIT generally not necessary who have large local reactions, although consider in those with unavoidable exposures VIT reduces risk of anaphylaxis from up to 70% to ~5%

49 ORAL IMMUNOTHERAPY FOR FOOD ALLERGY Oral immunotherapy reported for many foods cow s milk, egg, fish apple, orange, celery and peanut Start at a small dose and advancing to a higher maintenance dose

50 STOP II(STUDY OF TOLERANCE TO PEANUT) 75/85 (88%) able to tolerate 800 mg peanut protein daily 49/85 (58%) able to tolerate 1400 mg challenge at 26 weeks Main adverse events: Mouth itch 81% Abdominal pain 57% Nausea/vomiting 33% Wheezing 24% 2 doses of epi given during trial Withdrawals 5 withdrew because of symptoms 1 withdrew because to taste Anagnostou Lancet April 2014

51 OIT Problems Desensitization versus tolerance What do about missed doses Reactions to previously tolerated dose: physical exertion after dosing, dosing on an empty stomach, dosing during menses, concurrent febrile illness, and having suboptimally controlled asthma Anaphylaxis in 7/1692 doses, one at maint at dose Eosinophilic esophagitis OIT is INVESTIGATIONAL 1. Berlin AAAAI 2014

52 SUMMARY: KEY POINTS IN MANAGING AND COUNSELING PATIENTS Anaphylaxis is unpredictable Patient should have action plan Epinephrine is always the drug of choice Use without delay Antihistamines or inhalers are NEVER 1 st line treatment Make sure your patient knows how use auto injector Make sure auto injectors are up to date Two doses of epinephrine should be immediately available All patients with suspected anaphylaxis should seen by Allergist/Immunologist

53 QUESTIONS?

54 RISK OF SYSTEMIC REACTION IN UNTREATED SKIN TEST POSITIVE PATIENTS Original Sting Reaction Risk of Systemic Reaction Severity Age 1-9 yrs yrs Large local All 10 % 10 % Cutaneous Child 10 % 5 % systemic Adult 20 % 10 % Anaphylaxis Child 40 % 30 % Adult 60 % 40 %

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56 ENCHANCED FOOD LABELLING (AUGUST ) FOR MAIN INGREDIENTS) Must say contains: almonds, Brazil nuts, cashews, hazelnuts, macadamia nuts, pecans, pine nuts, pistachios or walnuts; peanuts; sesame seeds; wheat or triticale; eggs; milk; soybeans; crustaceans; shellfish; fish; or mustard seeds

57 HYGIENE HYPOTHESIS Epidemiology: 1. Endotoxin exposure is associated with less atopic sensitization, less AR, less atopic asthma in a dose dependant manner 1 2. Pet ownership (>2 dogs or >2cats) is associated with less atopy at age More older siblings or attending daycare at an early age (<6m) associated with less wheezing at ages 6,8,11, Serologic evidence of Toxoplasmosis, HSV1, hepatitis A associated with less atopy, AR and asthma 4 5. Atopic infants have less enterococci, bifidobacteria and more clostridia and S. Aureus 5 1. Braun-Fahrlander, NEJM Ownby JAMA Ball, Arch Ped Adolec Med Matricardi JACI Bjorksten JACI 2001

58 SPECIFIC IGE LEVELS ASSOCIATED WITH 95% RISK OF REACTION Age Group Food Serum IgE (ku/l) Child Egg 7 <2 years Egg 2 Child Cow Milk 15 <2 years Cow Milk 5 Child Peanut 14 Child Fish 20 Sampson H. J Allergy Clin Immunol 2004;113: Garcia Ara C, et al. J Allergy Clin Immunol 2001;107(1);185 90

59 ESTIMATED PREVALENCE OF FOOD ALLERGY Food Children (%) Adults (%) Cow s milk Egg Soy Peanut Tree nut Crustaceans Fish Sampson H. J Allergy Clin Immunol;113: