dana v. wallace, md acaai immediate past president facaai, faaaai associate clinical professor nova...

Dana V. Wallace, MDDana V. Wallace, MDACAAI Immediate Past PresidentACAAI Immediate Past President

FACAAI, FAAAAIFACAAI, FAAAAI

Associate Clinical ProfessorAssociate Clinical ProfessorNova Southeastern UniversityNova Southeastern University

Fort Lauderdale, FloridaFort Lauderdale, Florida

www.drdanawallace.comwww.drdanawallace.comdrdanawallace@[email protected]

The Causes of Anaphylaxis:The Causes of Anaphylaxis:Select Cases (1002)Select Cases (1002)

The Causes of Anaphylaxis:The Causes of Anaphylaxis:Select Cases (1002)Select Cases (1002)

Webb et al:J Allergy Clin Immunol 113:s241,2004

Venom ?? 11-21%

(up to 65%)

Anaphylaxis Incidence & FatalityAnaphylaxis Incidence & Fatality

Incidence (lifetime) risk 1 to 3%Incidence (lifetime) risk 1 to 3%11

Incidence rate of anaphylaxis 1-2%Incidence rate of anaphylaxis 1-2% Case-fatality rate is 0.65% to 1%Case-fatality rate is 0.65% to 1%1-21-2

Prevalence of food anaphylaxis unknownPrevalence of food anaphylaxis unknown Highest rate in Highest rate in children and adolescentschildren and adolescents Best data for incidence is from outpatient Best data for incidence is from outpatient

Rx for epinephrine auto-injectorsRx for epinephrine auto-injectors

1Kemp SF. JACI 2002; 110:341-348.2. Yocum, Michael et al: J Allergy Clin Immunol ,104:452-6. 1999

Variable Incidence of Food-Variable Incidence of Food-induced Anaphylaxisinduced Anaphylaxis

Related FactorsRelated Factors

AgeAge Regional dietsRegional diets Food preparationFood preparation Amount of exposureAmount of exposure Timing of first exposureTiming of first exposure

Boyce, J. A., A. Assa'ad, et al. "Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report." J Allergy Clin Immunol 126(6): 1105-18. [referred to as “NIAID Food Allergy Guidelines 2010” ]

ChildrenChildren Cow’s milk (1-2 %)Cow’s milk (1-2 %) Egg (1-2%)Egg (1-2%) Peanut (0.6%)Peanut (0.6%) Shellfish (0.5%) Shellfish (0.5%) Fish (.2%)Fish (.2%) SoybeanSoybean WheatWheat

AdultsAdults Shellfish (2.8%)Shellfish (2.8%) Vegetables (0.01-13.7%Vegetables (0.01-13.7% Fruits (0.02-8.5%)Fruits (0.02-8.5%) Peanuts (0.6%)Peanuts (0.6%) Tree nuts (0.4-0.5%)Tree nuts (0.4-0.5%) Fish (0.5%)Fish (0.5%)

Foods Allergy PrevalenceNIAID 2010 Guidelines

Gupta 2011 Pediatric SurveyGupta 2011 Pediatric Survey

Peanut

Gupta, R. S. Pediatrics 128(1): e9-17.

MaMajjor class 1 food allergensor class 1 food allergens

Cow's milk: Cow's milk: CaseinsCaseins ( (, , ,,), ), -lactoalbumin, -lactoalbumin, -lactoglobulin, serum -lactoglobulin, serum albuminalbumin

Chicken egg: Chicken egg: OvomucoidOvomucoid, ovalbumin, ovotransferrin, ovalbumin, ovotransferrin

Peanut: Peanut: Vicillin, conglutin, glycininVicillin, conglutin, glycinin

Soybean: Soybean: Glycinin, profilin, trypsin inhibitorGlycinin, profilin, trypsin inhibitor

Shrimp: Shrimp: TropomyosinTropomyosin ** **

Lipid transfer proteins (LTPs): ** Lipid transfer proteins (LTPs): ** Apple, apricot, peach, plum, cornApple, apricot, peach, plum, corn

POLLEN FOOD ALLERGY SYNDROMEPOLLEN FOOD ALLERGY SYNDROME

Gastrointestinal food hypersensitivities: Gastrointestinal food hypersensitivities: Pollen food allergy syndrome or oral allergy Pollen food allergy syndrome or oral allergy

syndrome (OAS) syndrome (OAS) Oral mucosal itching, swelling, tinglingOral mucosal itching, swelling, tingling Elicited by a variety of plant proteins that cross-react with Elicited by a variety of plant proteins that cross-react with

airborne allergensairborne allergens Pollen allergic patients may develop symptoms following Pollen allergic patients may develop symptoms following

the ingestion of vegetables foods:the ingestion of vegetables foods:

- - RagweedRagweed allergic patientsallergic patients: : Fresh melons and bananasFresh melons and bananas

- - Birch pollen Birch pollen allergic patientsallergic patients: : Carrots,Carrots, celery, apples, celery, apples, pears, hazelnuts and kiwipears, hazelnuts and kiwi

Immunotherapy for treating the pollen-induced rhinitis Immunotherapy for treating the pollen-induced rhinitis may or may notmay or may not reduce oral allergy symptoms reduce oral allergy symptoms

J Allergy Clin Immunol. 2004; 113:808-809

Components of Pollen Food Components of Pollen Food Allergy Syndrome (PFAS)Allergy Syndrome (PFAS)

A history of symptoms consistent with PFASA history of symptoms consistent with PFAS Allergic sensitization to pollenAllergic sensitization to pollen Allergic sensitization to a plant foodAllergic sensitization to a plant food A known correlation between the plant food A known correlation between the plant food

and the pollenand the pollen

Pollen Food Allergy Syndrome (PFAS)Pollen Food Allergy Syndrome (PFAS)Oral Allergy Syndrome + systemic reactionsOral Allergy Syndrome + systemic reactions

PFAS emphasizes that one may have PFAS emphasizes that one may have not only not only oropharyngeal symptoms but systemic symptoms oropharyngeal symptoms but systemic symptoms 2-10% 2-10% of the timeof the time

While usually associated only with raw foods, cooked While usually associated only with raw foods, cooked plant foods plant foods maymay provoke the PFAS provoke the PFAS

Prick-by-prick Prick-by-prick testing to fresh food is preferred for most testing to fresh food is preferred for most fruits and vegetablesfruits and vegetables

Stable allergens, e.gStable allergens, e.g. peanut, hazelnut, and pea . peanut, hazelnut, and pea may be may be best detected with commercial extractsbest detected with commercial extracts

Consider duplicate testing when extracts are availableConsider duplicate testing when extracts are available

Gastrin

ExerciseFood

Food allergy:Exercise-induced anaphylaxis

Mediator release- Histamine- Others (LTD4,PAF, etc)

Temperature

ANAPHYLAXIS

Exercise AnaphylaxisExercise AnaphylaxisFoods associatedFoods associated

Shellfish 16%Alcohol 11%Alcohol 11%Tomatoes 8%Tomatoes 8%Cheese 8%Cheese 8%Celery 7%Celery 7%Strawberries, milk, Strawberries, milk, wheat & or Omega- 5 gliadin, other

grains, peaches – each 5%, peaches – each 5%

Advise early AM exercise before eating or > 4 hrs. Advise early AM exercise before eating or > 4 hrs. after eatingafter eating

Chong s-u, 35 al. Int Arch Allergy Immunol. 2002;120:19-26.

Exercise Anaphylaxis (EA)Exercise Anaphylaxis (EA)Food-dependant

Exercise leads to Exercise leads to increased gut permeability increased gut permeability which thereby increases food allergen intakewhich thereby increases food allergen intake

Patients with Patients with low levels of sIgE low levels of sIgE food antibodies food antibodies are are tolerant until stressed by exercisetolerant until stressed by exercise

In In wheat-dependent AEwheat-dependent AE, exercises activates , exercises activates tissue transglutaminase, which results in high tissue transglutaminase, which results in high molecular-weight molecular-weight omega-5 gliadin complexes omega-5 gliadin complexes that bind IgEthat bind IgE with increased intensity leading to with increased intensity leading to anaphylaxisanaphylaxis

Lemon-Mule H. Current Allergy and Asthma Reports 2008. 8(3): 201-208.

New causes of AnaphylaxisNew causes of Anaphylaxis

Antibodies to oligosaccharide galactose-alpha-1,3 Antibodies to oligosaccharide galactose-alpha-1,3 galactose galactose present prior to Tx present prior to Tx

Felt possibly to x-react with same oligosaccharides in Felt possibly to x-react with same oligosaccharides in beef or pork;beef or pork; +/- parasites or histoplasmosis (not +/- parasites or histoplasmosis (not established) established) 11

Cat allergic patients may have IgE to the cat IGA Cat allergic patients may have IgE to the cat IGA galactose-α 1,3 galactosegalactose-α 1,3 galactoseTesting for IgE to cat has been suggested Testing for IgE to cat has been suggested 22

Desensitization protocol has been used Desensitization protocol has been used 33

1. Chung, NEJM 2008; 358-1109 2. Gronlund H et al. JACI 1009, 123:1189.2. 3. Jerath MR at al. JACI 2009, 123: 260

Cetuximab

Radiocontrast Anaphylactoid RxRadiocontrast Anaphylactoid RxNot related to shellfish allergyNot related to shellfish allergy

Seafood Allergy is NOT Seafood Allergy is NOT a risk factor: a risk factor: Possible origin of the myth:Possible origin of the myth:– In 1975 Shehadi et. al noted the following In 1975 Shehadi et. al noted the following

regarding patients reactions: regarding patients reactions: • 15% of patients gave an unconfirmed history 15% of patients gave an unconfirmed history

of shellfish allergyof shellfish allergy• They surmised iodine in shellfish was They surmised iodine in shellfish was

responsible for the allergy. [FALSE]responsible for the allergy. [FALSE]• They surmised iodine in shellfish cross-reacted They surmised iodine in shellfish cross-reacted

to iodine in RCM. [FALSE] to iodine in RCM. [FALSE] Shehadi WH. Am J Roentgenol. 1975; 124: 145-152.

Beaty AD. American Journal of Medicine. 2008; 121 (2): 158e.

Subsequent Reactions May Increase Subsequent Reactions May Increase in Severity with Timein Severity with Time

Subsequent Reactions May Increase Subsequent Reactions May Increase in Severity with Timein Severity with Time%

of

reac

tio

ns

Simons et al, J Allergy Clin Immunol, 2004

*

*

Proportion of reactions rated severe

0

10

20

30

40

50

60

Peanut allergen Tree nut allergen

1st Reaction

2nd Reaction

3rd Reaction

Fatal Food-induced AnaphylaxisFatal Food-induced AnaphylaxisHighest Risk Factors Highest Risk Factors

Peanuts and tree nuts account for up to 92% of account for up to 92% of fatalitiesfatalities1,21,2

Adolescents (14-17) and young adults highest risk highest risk groupgroup11

Asthma as a concurrent disease (>90% some studies), as a concurrent disease (>90% some studies), esp. poorly controlled asthmaesp. poorly controlled asthma2,32,3

Cardiovascular disease in middle-aged & older in middle-aged & older patientspatients

DelayDelay between time of symptom onset and between time of symptom onset and administration of treatment (OR up to 7.3)administration of treatment (OR up to 7.3)2,42,4

Improper epinephrine dosingImproper epinephrine dosing, usually underdosing, usually underdosing55

1. Bock, SA, et ak, JACI 2004; 107 (1) 191-3. 2. Sampson HA,et al., NEJM. 1992; 237:380-384.3. Pumphrey R. Curr Opin Allergy Clin Immunol. 2004;4:285-290. 4. Amin HS, et al. JACI 2006; 117:169-75.5. NIAID Food Allergy Guidelines 2010

ANAPHYLAXIS DX & TX

Clinical Criteria for AnaphylaxisClinical Criteria for Anaphylaxis

Acute onset (min to hrs)Acute onset (min to hrs)– Skin/mucosal symptomsSkin/mucosal symptoms

ANDAND

– Airway compromiseAirway compromise

OROR

– ↓ ↓ BP or Associated BP or Associated symptomssymptoms

Anaphylaxis is likely if 1 or 3 set of criteria are fulfilled

Hypotension within min. to hrs. after Hypotension within min. to hrs. after exposure to exposure to known allergenknown allergen

1

3

2

Symposium on the Definition and Management of Anaphylaxis: Summary report. Sampson HA, et al. JACI 2005; 115:584-59. Second symposium on the definition and management of anaphylaxis: summary report . Sampson HA, et al. JACI 2006; 117(2): p. 391-7.

Symposium on the Definition & Management Symposium on the Definition & Management of Anaphylaxis: Summary Reportof Anaphylaxis: Summary Report

“Caution: These criteria describe so calledclassic cases of anaphylaxis. Other presentations may also indicate anaphylaxis (e.g. early presentation, generalized flushing; isolated presentation, sudden hypotension only in a patient without evidence of allergen exposure; classic presentation but with a non-allergenic cause, such as exercise)”

Sampson HA et al. J Allergy Clin Immunol 2005;115:584-91.

““ANAPHYLAXIS” ANAPHYLAXIS” FUNCTIONAL DEFINITIONFUNCTIONAL DEFINITION

An acute allergic reaction for which it is known An acute allergic reaction for which it is known that there is potential for fatality that there is potential for fatality

– Regardless of the severity of the presenting Regardless of the severity of the presenting symptomssymptoms

– For which immediate treatment has been shown For which immediate treatment has been shown to to prevent progression of the disease processprevent progression of the disease process

Can Anaphylaxis occur on first Can Anaphylaxis occur on first ingestion of a food? ingestion of a food?

Usually, Usually, but not alwaysbut not always,, there is a history there is a history of food allergy, with or without anaphylaxisof food allergy, with or without anaphylaxis

First-time food ingestion First-time food ingestion can occur at any can occur at any age, more common in age, more common in young childrenyoung children

20% first time 20% first time anaphylaxis events anaphylaxis events (to a (to a specific food exposure) occur in the specific food exposure) occur in the school settingschool setting

NIAID Food Allergy Guidelines 2010

Characteristics of Food-induced Characteristics of Food-induced AnaphylaxisAnaphylaxis

Increasing in incidence in industrialized countriesIncreasing in incidence in industrialized countries Food-induced anaphylaxis is not easily recognized, Food-induced anaphylaxis is not easily recognized,

delaying diagnosisdelaying diagnosis Dx heavily dependent on Dx heavily dependent on

– Early recognition of specific signs and symptoms Early recognition of specific signs and symptoms – Timing of the reactionTiming of the reaction– Concomitant factors and disease processesConcomitant factors and disease processes

No tests, including prick, sIgE, challenge studies, can predict the severity of IgE mediated reactions to foods


25

Most Frequent Signs and Symptoms of Most Frequent Signs and Symptoms of Anaphylaxis: Regardless of causeAnaphylaxis: Regardless of cause

1. Lieberman P. Immunol Allergy Clin North Am. 2001;21:813-825.

ManifestationManifestation PercentPercent

Urticaria/angioedema 87

Flush 50

Dyspnea/wheeze 46

Hypotension 30

Gastrointestinal 30

26

Less Frequent Signs and Less Frequent Signs and Symptoms of AnaphylaxisSymptoms of Anaphylaxis

1. Lieberman P. Immunol Allergy Clin North Am. 2001;21:813-825.

ManifestationManifestation PercentPercent

Rhinitis 16

Headache 15

Substernal pain 6

Itch without rash 4.5

Seizure 1.5

Signs and Symptoms of Food-induced AnaphylaxisAre they different?

Up to Up to 20% 20% have have no cutaneous symptomssymptoms Up to Up to 70% of cases have 70% of cases have respiratory

involvement (upper or lower airway)(upper or lower airway) Up to Up to 40% have 40% have GI Symptoms Up to Up to 35% have 35% have cardiovascular symptoms Other symptoms: anxiety, mental confusion, Other symptoms: anxiety, mental confusion,

lethargy, and seizureslethargy, and seizures


Cardiovascular co-morbidity Increased Increased heart mast cells heart mast cells present with present with

ischemic heart dx & cardiomyopathyischemic heart dx & cardiomyopathy Mast cells accumulate at sites of Mast cells accumulate at sites of

coronary atherosclerotic plaquescoronary atherosclerotic plaques IgE antibodies IgE antibodies bound to heart mast bound to heart mast

cells can trigger degranulationcells can trigger degranulation Anaphylaxis may trigger myocardial Anaphylaxis may trigger myocardial

ischemia due to ischemia due to plaque ruptureplaque rupture 15% of severe anaphylaxis present with 15% of severe anaphylaxis present with

chest pain chest pain 7% severe anaphylaxis present with an 7% severe anaphylaxis present with an

arrhythmiaarrhythmia

1. Kemp SF et al. Allergy 2008. 63(8): 1061-70.2. Lieberman P et al. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J ACI 2010. 126 (3) 477-80, (AKA 2010 JTF Anaphylaxis PP)

LABORATORY TESTS IN THE DIAGNOSIS LABORATORY TESTS IN THE DIAGNOSIS

OF ANAPHYLAXISOF ANAPHYLAXIS

0 30 60 90 120 150 180 210 240 270 300 330

Plasma histamine

Serum tryptase

24-hr Urinary histamine metabolite

MINUTES

AMOUNT

Serum TryptaseSerum Tryptase

Total Serum Tryptase in anaphylaxis may remain Total Serum Tryptase in anaphylaxis may remain within nl range, but if > 2 ng/ml above baseline it within nl range, but if > 2 ng/ml above baseline it has 0.73 sensitivity & 0.98 specificity for dx of has 0.73 sensitivity & 0.98 specificity for dx of anaphylaxisanaphylaxis11

Usually Usually not ↑ in food-induced anaphylaxis

↑ more likely in hypotensive anaphylaxis

* Dr. Larry Schwartz lab, Virginia Commonwealth University

1. Brown SG et al. Emerg Med Austral 2004; 16:120

Time Course of Food-induced Time Course of Food-induced AnaphylaxisAnaphylaxis

Onset is usuallyOnset is usually minutesminutes (e.g. 3-5) to a (e.g. 3-5) to a few few hourshours after exposure to after exposure to food food allergenallergen

Biphasic reactions occur in up to reactions occur in up to 20% of of cases (usually cases (usually < 8 hours in food < 8 hours in food allergy)allergy)


Biphasic AnaphylaxisBiphasic Anaphylaxis

Antigen Exposure

Treatment

Initial Symptoms

0

Second-Phase

Symptoms

Treatment

1-8 hours

Classic Model

New Evidence

1-48 hours

Time

BIPHASIC ANAPHYLACTIC BIPHASIC ANAPHYLACTIC REACTIONSREACTIONS

CharacteristicsCharacteristics

Etiology not always clearEtiology not always clear– Immunological, e.g. late-phase response– Pharmacologic-medication effect has ended

Usually involves same organ system Cannot be predicted based on severity of initial

reaction

Ellis AK, Day JH. Ann Allergy Asthma Immunol 2007;98:64-9.

Time Course of Food-induced Time Course of Food-induced AnaphylaxisAnaphylaxis

Onset is usually minutes (e.g. 3-5) to a few Onset is usually minutes (e.g. 3-5) to a few hours after exposure to food allergenhours after exposure to food allergen

Biphasic reactions occur in up to 20% of Biphasic reactions occur in up to 20% of cases (usually < 8 hours in food allergy)cases (usually < 8 hours in food allergy)

Prolonged reactions occur in up to 20% of Prolonged reactions occur in up to 20% of casescases

Deaths reported 30 minutes to 2 hours Deaths reported 30 minutes to 2 hours following exposure to foodfollowing exposure to food


Onset of Anaphylaxis to Onset of Anaphylaxis to Cardiopulmonary ArrestCardiopulmonary Arrest

Pumphrey R. Curr Opin Allergy Clin Immunol. 2004;4:285Y290

Clinical Factors Affecting Clinical Factors Affecting Anaphylaxis Severity & FatalityAnaphylaxis Severity & Fatality

Psychiatric diseasePsychiatric disease Substance abuseSubstance abuse Beta-blockersBeta-blockers COPDCOPD

PAF acetylhydrolase PAF acetylhydrolase factor deficiencyfactor deficiency

Subclinical mastocytosisSubclinical mastocytosis Previous anaphylaxisPrevious anaphylaxis

Simons, E. et al. J Allergy Clin Immunol 2007;120:S2-24.)

1. Bock, SA, et ak, JACI 2004; . Sampson HA,et al., NEJM. 1992; 237:380-384.3. Pumphrey R. Curr Opin 4. NIAID Food Allergy Guidelines 2010

Additional Risk Factors for Additional Risk Factors for FA Anaphylaxis FatalityFA Anaphylaxis Fatality

Multiple food allergens (Multiple food allergens (3x3x increase) increase) Shellfish (Shellfish (#1 allergen #1 allergen after age 14)after age 14) Ingestant of allergen (Ingestant of allergen (NoNo known report of known report of fatalityfatality when when

only only skin contactskin contact)) If there is no skin manifestations of anaphylaxis (delay in If there is no skin manifestations of anaphylaxis (delay in

diagnosis)diagnosis)

Many Mediators Cause Many Mediators Cause Anaphylactic Symptoms Anaphylactic Symptoms

LeukotrienesLeukotrienes ProstagandinsProstagandins KininsKinins

• Platelet activating factor

• Interleukins

• Tumor necrosis factor

• Histamine

Actions of Epinephrine: Actions of Epinephrine: Antagonize Effects of All MediatorsAntagonize Effects of All Mediators

↑ Vasoconstriction↑ Peripheral vascular resistance↓ Mucosal edema

Insulin release ↑ Inotropy↑ Chronotropy

↑ Bronchodilation↑ Vasodilation↑ Glycogenolysis↓ Mediator release

1-adrenergicreceptor




Epinephrine

Simons KJ, Simons FER. Curr Opin Allergy Clin Immunol. 2010;10:354-361.

Epinephrine Cardiovascular Epinephrine Cardiovascular EffectsEffects

Enhances coronary blood flowEnhances coronary blood flow– Increased duration of diastole (vs. systole) Increased duration of diastole (vs. systole) – Vasodilator effects caused by increased Vasodilator effects caused by increased

myocardial contractilitymyocardial contractility

VasoconstrictorVasoconstrictor effects on coronary arteries effects on coronary arteries would seem to be undesirable but it iswould seem to be undesirable but it is– Felt to be a Felt to be a minor effect minor effect compared to above compared to above

benefitbenefit

Kemp SF et al. Allergy 2008. 63(8): 1061-70.

False Sense of SecurityFalse Sense of Security

Food-induced anaphylaxis can have a mild Food-induced anaphylaxis can have a mild course and resolve spontaneouslycourse and resolve spontaneously– Most likely related to endogenous Most likely related to endogenous

production of vasoconstrictorsproduction of vasoconstrictors• EpinephrineEpinephrine

• Endothelin-IEndothelin-I

• Angiotensin IIAngiotensin II


Beta Blockers & ACE Inhibitors Exposure to β-adrenergic blocking agents is a Exposure to β-adrenergic blocking agents is a risk factor for factor for

more serious & Tx resistant anaphylaxis1,2,3

– May reduce the effect of exogenous epinephrine

– May reduce the effect of endogenous epinephrine ACE inhibitors (OR 2.7) ACE inhibitors (OR 2.7) are a risk for are a risk for more severe

anaphylaxis (e.g. with anaphylaxis (e.g. with venom immunotherapy) immunotherapy)1,21,2

ACE inhibitors ACE inhibitors “may” interfere with endogenous interfere with endogenous compensatory mechanisms, resulting compensatory mechanisms, resulting in more severe or in more severe or prolonged symptoms of food-induced anaphylaxisprolonged symptoms of food-induced anaphylaxis33

No evidence of increased risk for ACE receptor blockers

1. 2010 JTF Anaphylaxis PP) 2. Cox L. Allergy Immunotherapy- a practice parameter third update. JACI 127(1 supp) S1-55. 3. NIAID Food Allergy Guidelines 2010

Steps in Treatment of Steps in Treatment of AnaphylaxisAnaphylaxis

#1 Remove Allergen#1 Remove Allergen

#2 Administer #2 Administer EpinephrineEpinephrine

#3 Call for help

Supplies and Equipment for Anaphylaxis Treatment in office

“NECESSARY” Stethoscope and Stethoscope and

sphygmomanometersphygmomanometer Epinephrine 1:1000Epinephrine 1:1000 OxygenOxygen IV FluidsIV Fluids Tourniquets, syringes, Tourniquets, syringes,

hypodermic needles, hypodermic needles, large-bore needles large-bore needles

“CONSIDER HAVING”” One-way valve facemaskOne-way valve facemask Diphenhydramine inj.Diphenhydramine inj. Corticosteroids inj.Corticosteroids inj.

“MAYBE” Vasopressor (Dopamine)Vasopressor (Dopamine) GlucagonGlucagon Automatic defibrillatorAutomatic defibrillator Oral airwayOral airway

2010 JTF Anaphylaxis PP

KEY POINTS ON GENERAL KEY POINTS ON GENERAL ANAPHYLAXIS DX AND TXANAPHYLAXIS DX AND TX

Anaphylaxis protocols are based on Anaphylaxis protocols are based on consensus –consensus –not on evidencenot on evidence

The The more rapid the onset of signs and of signs and symptoms following exposure to offending symptoms following exposure to offending stimulus, the stimulus, the more likely the reaction will the reaction will be be severe and life-threatening.

Delayed onset of anaphylaxis, with delayed Delayed onset of anaphylaxis, with delayed Tx, also introduces high riskTx, also introduces high risk

# 1 DRUG F0R ANAPHYLAXIS# 1 DRUG F0R ANAPHYLAXISEPINEPHRINEEPINEPHRINE

Adult- 1:1000 0.2-0.5 ml - 1:1000 0.2-0.5 ml q 5 minutes (or less) (or less) PRNPRN

Child-0.01 mg/kg , max 0.3 mg -0.01 mg/kg , max 0.3 mg q 5 minutes (or less) (or less) PRNPRN

IM in Lateral thigh (speaker preference)in Lateral thigh (speaker preference)

KEY POINT

1”

EPINEPHRINEEPINEPHRINE PREVENTS

Blocks further mediator releaseBlocks further mediator release

TREATSReverses the end-organ effects of effects of

AnaphylaxisAnaphylaxis

IM vs. SQ Epinephrine in ChildrenIM vs. SQ Epinephrine in Children

Simons: J Allergy Clin Immunol 113:838, 2004

(EpiPen®)(EpiPen®)

Time to Cmax after injection (minutes)Time to Cmax after injection (minutes)

8 2 minutes8 2 minutes++--

34 14 (5 – 120) minutes p < 0.0534 14 (5 – 120) minutes p < 0.05--++

SHORTEST ONSET OF ACTION

Vastus Lateralis

Deltoid

Epinephrine IM: Time to OnsetEpinephrine IM: Time to Onset

Adapted from Simons FER, et al. J Allergy Clin Immunol. 1998;101:33-37.

Maximum pharmacodynamic effect occurs before 10 min

Auto injectorsAuto injectorsTwinject

Epi-PenAdrenaclick

Needle Length found on auto injectors

• 1.43 cm• May not penetrate vastus lateralis muscle

•42% women 1

•2% men1

•12% children2

1. Song TT et al. Ann Allergy Asthma Immunol 2005;94:539-42.2. Stecher D et al. Pediatrics 2009; 124 (1): 55-70.

Fatal Anaphylactic ReactionsFatal Anaphylactic Reactions

Most fatal reactions Most fatal reactions are unpredictableare unpredictable

– Appropriate management after recovery from a Appropriate management after recovery from a severe reaction may be protective against a fatal severe reaction may be protective against a fatal recurrencerecurrence22

– Epinephrine used in 62% of fatal reactionsEpinephrine used in 62% of fatal reactions• 14% of time before cardiac arrest14% of time before cardiac arrest33

• 86% of time after cardiac arrest86% of time after cardiac arrest

51

1. Sampson HA, et al. N Engl J Med. 1992;327:380-384.2. Pumphrey R. Curr Opin Allergy Clin Immunol. 2004;4:285-290. 3. Pumphrey RS. Clin Exp Allergy. 2000;30:1144-1150.

Epinephrine: Multiple doses

Pt with food-induced anaphylaxis need Pt with food-induced anaphylaxis need TWO doses of epinephrine required up to doses of epinephrine required up to 20% 20% of the time before recoveryof the time before recovery

Repeat dosing may be required after Repeat dosing may be required after 5-15 minutes (optimal dosing interval unknown)(optimal dosing interval unknown)



TreatmentTreatment

An insufficient dose of epinephrine given for the primary response is considered a risk factor

Steroids do not prevent, but there seems to be a trend toward lower dose of corticosteroids administered in patients with biphasic rx [Administer adequate doses]



Severity of 2Severity of 2ndnd event is variable but can be fatal event is variable but can be fatal No biphasic response occurred in patients who No biphasic response occurred in patients who

had complete resolution of anaphylaxis had complete resolution of anaphylaxis symptoms in < 30 minutessymptoms in < 30 minutes

If occurs, consider If occurs, consider overnight hospital observation


Lieberman P. Ann Allergy Asthma Immunol 2005;95:217-26

Epinephrine IM: Potential Side Effect [These [These should not should not limit appropriate use]limit appropriate use]

Anxiety, fear, restlessnessAnxiety, fear, restlessness Headache, dizziness, tremor, pallorHeadache, dizziness, tremor, pallor Palpitations, tachycardiaPalpitations, tachycardia Increased risk with concurrent use of monamine Increased risk with concurrent use of monamine

oxidase inhibitors, tricyclic antidepressants, stimulant oxidase inhibitors, tricyclic antidepressants, stimulant medications, cocaine abusemedications, cocaine abuse

Increased risk with pre-existing cardiovascular disease, Increased risk with pre-existing cardiovascular disease, aortic aneurysm, uncontrolled hypertension, recent aortic aneurysm, uncontrolled hypertension, recent intracranial surgeryintracranial surgery


Epinephrine IM: Potential Side Effect [These [These should not should not limit appropriate use]limit appropriate use]

Rare side effects:Rare side effects:– AnginaAngina– Ventricular arrhythmiasVentricular arrhythmias– Myocardial infarctionMyocardial infarction– Pulmonary edemaPulmonary edema– Sudden sharp increase in BPSudden sharp increase in BP– Intracranial hemorrhageIntracranial hemorrhage

More common with overdose any routeMore common with overdose any route More common with IV administrationMore common with IV administration


Severe Anaphylaxis PositionSevere Anaphylaxis Position

*

Position Patient SupinePosition Patient SupineFatal cases associated with posture changesFatal cases associated with posture changes

(Pumphrey RSH. JACI 2003;112:451-2.)(Pumphrey RSH. JACI 2003;112:451-2.)

4 deaths occurred within seconds of a 4 deaths occurred within seconds of a change to a more upright position

6 deaths occurred in individuals supported sitting up after shock Postulated mechanisms

– • With sitting or standing venous return stops– • Vena cava will empty within seconds– • No blood flow to left heart results in pulseless electrical

activity– • In this scenario epinephrine would likely not work

# 2 DRUG OXYGEN

Optimally with all patients with anaphylaxis Any patient with Hypotension or respiratory

distress Any patient with 02 sat <95% Any patient requiring more than one Epi

injection Face maskFace mask recommended over nasal prongs. recommended over nasal prongs. Start with Start with 6-8 Liter/minute6-8 Liter/minute

#3 Drug IV FLUIDS For Hypotension (systolic <100) or any one For Hypotension (systolic <100) or any one

who who has not responded has not responded toto first first IM EpinephrineIM Epinephrine When there is shock in spite of increased When there is shock in spite of increased

vascular resistance vascular resistance 10% severe anaphylaxis not reversible

with Epi* Select IV FluidsSelect IV Fluids

– .9 NaCl (isotonic crystalloid).9 NaCl (isotonic crystalloid)– Hydroxyethyl starch (Hespan) (colloid) if saline not Hydroxyethyl starch (Hespan) (colloid) if saline not

effectiveeffective

Bock SA, Munoz-Furlong A, Sampson HA. J Allergy Clin Immunol. 2001;107:191–193.

IV FLUIDSIV FLUIDS Administer rapidly 5-10 mg/kg 5-10 mg/kg

crystalloid over first 5-10 minutes, crystalloid over first 5-10 minutes, and total of 20-30 ml/kg first hourand total of 20-30 ml/kg first hour

Apply BP cuff to bag of fluid or or withdraw fluid and use a stopcock to withdraw fluid and use a stopcock to infuse with a large 50 cc syringe (see infuse with a large 50 cc syringe (see picture)picture)

You may need to administer up to You may need to administer up to 50% of the intravascular volume

Second line drugs (office setting)

Diphenhydramine 1-2 mg/kg parentally Diphenhydramine 1-2 mg/kg parentally Ranitidine 50 mg (1 mg/kg children)Ranitidine 50 mg (1 mg/kg children)

• IM same as IV for onset of actionIM same as IV for onset of action

• If IV administer over 5 minutesIf IV administer over 5 minutes

Leukotriene modifiers: no recommendation for or Leukotriene modifiers: no recommendation for or againstagainst

AtropineAtropine BradycardiaBradycardia Βeta-Blocked anaphylaxisΒeta-Blocked anaphylaxis

DopamineDopamine

Antihistamines: Time to SuppressionAntihistamines: Time to Suppression

51.7 min

79.2 min

101.2 min

Time to 50% suppression

Jones DH, et al. Ann Allergy Asthma Immunol. 2008;100(5):452-456.

Fexofenadine Diphenhydramine IM Diphenhydramine PO

Antihistamines[A 2nd, 3rd, or 4th line drug]

““The use of antihistamines is the most common The use of antihistamines is the most common reason reported for reason reported for NOTNOT using epinephrine and using epinephrine and may place a patient at significantly increased risk may place a patient at significantly increased risk for progression toward a life-threatening for progression toward a life-threatening reaction.”reaction.”

H1 antihistamines are H1 antihistamines are only useful for itching and useful for itching and urticariaurticaria

22ndnd generation H1 AH may be considered as rapid generation H1 AH may be considered as rapid onset and less sedation (e.g. cetirizine)onset and less sedation (e.g. cetirizine)

H2 antihistamine use has minimal supportH2 antihistamine use has minimal supportNIAID Food Allergy Guidelines 2010

H2-antihistamines In vitro studies suggest a benefitIn vitro studies suggest a benefit No adequate randomized and quasi-randomized No adequate randomized and quasi-randomized

controlled trialscontrolled trials comparing H2-antihistamines with comparing H2-antihistamines with placebo or no interventionplacebo or no intervention11

– No recommendations for clinical practiceNo recommendations for clinical practice

Avoid with food-induced anaphylaxis as may interfere with food allergen digestion and potentially augment a reaction2-3

1. Sheikh A, et al. Cochrane Database of Systematic Reviews 2007, Issue 1 .2. Untersmavr E, et al. JACI 2003; 112:626-23. 3. Scholl I, et al. AM J Clin Nutr 2005; 81:154-60.

Additional Medications to consider

Nebulized albuterol or levalbuterol for Nebulized albuterol or levalbuterol for bronchospasmbronchospasm11

1. 2010 JTF Anaphylaxis PP. JACI (in publication). 2. Brown SGA et al. Emerg Med J 2004;21:149-54. 3. Kill C et al. Int Arch Allergy Immunol 2004; 134:260-1. 4. Wenzel V et al. N Engl J Med 2004; 350:105-13

Albuterol does not relieve airways edema!

CORTICOSTEROIDSCORTICOSTEROIDS Limited data supporting usefulness in anaphylaxisLimited data supporting usefulness in anaphylaxis Never a substitute for Epi Minimal benefit for initial treatmentMinimal benefit for initial treatment 4-6 hours before onset of action Consider when a history of asthmaConsider when a history of asthma Questionable benefit for severe, prolonged and biphasic Questionable benefit for severe, prolonged and biphasic

reactionsreactions No difference in outcomes in severe IT anaphylaxis (37% No difference in outcomes in severe IT anaphylaxis (37%

of non-fatal did not get steroids)of non-fatal did not get steroids) Dosage is unknown (recommended dose is usually (recommended dose is usually

methylprednisolone 1-2 mg/kg IV, 80-125 mg max or methylprednisolone 1-2 mg/kg IV, 80-125 mg max or prednisone 1 mg/kg PO, 60-80 mg max)prednisone 1 mg/kg PO, 60-80 mg max)

2010 Anaphylaxis PP. JACI) NIAID Food Allergy Guidelines 2010

Additional Medications to consider Intravenous Epinephrine Intravenous Epinephrine

– Bolus Dosage (1:10,000 dilution)10-20 mcg (0.1-0.2 ml of a Bolus Dosage (1:10,000 dilution)10-20 mcg (0.1-0.2 ml of a 1:10,000 dilution) at initial dose of 0.75-1.5 mcg/kg1:10,000 dilution) at initial dose of 0.75-1.5 mcg/kg22

– Repeat as necessaryRepeat as necessary

Vasopressors (Dopamine) for unresponsive hypotensionVasopressors (Dopamine) for unresponsive hypotension– Evidence suggest to use ≥ 10 mcg/kg/min IV2

Vasopressin: esp. for cardiac arrest. It is a potent vasoconstrictor, & inhibits NO and prostaglandin generation generation 3-43-4

1. 2010 JTF Anaphylaxis PP. JACI (in publication). 2. Brown SGA et al. Emerg Med J 2004;21:149-54. 3. Kill C et al. Int Arch Allergy Immunol 2004; 134:260-1. 4. Wenzel V et al. N Engl J Med 2004; 350:105-13

Glucagon

For refractory hypotension in patients on β-Blockers

Initial dose of 1 to 5 mg IV followed by infusion of Initial dose of 1 to 5 mg IV followed by infusion of 5-15 mcg/min titrated against blood pressure5-15 mcg/min titrated against blood pressure

Glucagon bypasses the β-adrenergic receptors Glucagon increases cAMP via stimulation of its own

receptor, , producing bronchodilation and helping to producing bronchodilation and helping to reverse hypotensionreverse hypotension

Glucagon may induce nausea and vomitingGlucagon may induce nausea and vomiting

2010 JTF Anaphylaxis PP. JACI (in publication).

Epinephrine Auto-injectionsEpinephrine Auto-injectionsWho needs one? Who needs one?

Prescribe two doses of epinephrine for:Prescribe two doses of epinephrine for:– Hx of prior systemic allergic reactionHx of prior systemic allergic reaction– Patient with Patient with Food allergy (without hx of Food allergy (without hx of

anaphylaxis) anaphylaxis) and concomitant asthmaand concomitant asthma– Known Known food allergy food allergy to peanut, tree nut, fish, and to peanut, tree nut, fish, and

crustacean shellfishcrustacean shellfish

((Even if no hx of Even if no hx of

anaphylaxisanaphylaxis))– FPAS (oral allergy)FPAS (oral allergy)– All food allergic pts (??)All food allergic pts (??)


Epinephrine for PFAS: Should one Rx?Epinephrine for PFAS: Should one Rx?

Up to 10% of patients with PFAS are at risk for a systemic Up to 10% of patients with PFAS are at risk for a systemic reactionreaction

Severe reactions can occur upon the first ingestion of a Severe reactions can occur upon the first ingestion of a food with cross-reactive allergensfood with cross-reactive allergens

Systemic reactions to previously tolerated foods can occurSystemic reactions to previously tolerated foods can occur The natural history of PFAS is unknownThe natural history of PFAS is unknown Peach, peanut, tree nuts, and mustard are high risk foods Peach, peanut, tree nuts, and mustard are high risk foods

for PFAS with systemic symptoms for PFAS with systemic symptoms Rx for reactions of any severity to cooked plant foodsRx for reactions of any severity to cooked plant foods

Discharge Plan for Patients with Food-Induced Anaphylaxis

Epinephrine (2 doses) must be available at Epinephrine (2 doses) must be available at all times for patients at risk (e.g. school)all times for patients at risk (e.g. school)

Anaphylaxis emergency action planAnaphylaxis emergency action plan Plan for monitoring auto-injector expiration Plan for monitoring auto-injector expiration

datesdates Plan for arranging further evaluation and/or Plan for arranging further evaluation and/or

follow-upfollow-up Printed info about anaphylaxis and its TxPrinted info about anaphylaxis and its Tx


GO TO www.acaai.org and search for “SAFE”

DeathDeath

[We [We

MustMust

Prevent]Prevent]

Patient ResourcesPatient Resources http://www.ncbi.nlm.nih.gov/pubmedhealthhttp://www.ncbi.nlm.nih.gov/pubmedhealth http://www.niaid.nih.gov/topics/http://www.niaid.nih.gov/topics/

foodallergy/clinical/documents/foodallergy/clinical/documents/faguidelinesexecsummary.pdffaguidelinesexecsummary.pdf

Physician ResourcesPhysician Resources http://www.jacionline.org/article/S0091-http://www.jacionline.org/article/S0091-

6749(10)01566-6/fulltext6749(10)01566-6/fulltext http://allergyparameters.org/file_depot/0-http://allergyparameters.org/file_depot/0-

10000000/30000-40000/30326/folder/10000000/30000-40000/30326/folder/73825/2005%20Anaphylaxis73825/2005%20Anaphylaxis

Thank You DANA WALLACE, [email protected]

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dana v. wallace, md acaai immediate past president facaai, faaaai associate clinical professor nova...

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