dana v. wallace, md acaai immediate past president facaai, faaaai associate clinical professor nova...
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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
NIAID Food Allergy Guidelines 2010
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
NIAID Food Allergy Guidelines 2010
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)
NIAID Food Allergy Guidelines 2010
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
NIAID Food Allergy Guidelines 2010
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
2-adrenergicreceptor
1-adrenergicreceptor
2-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
NIAID Food Allergy Guidelines 2010
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)
NIAID Food Allergy Guidelines 2010
BIPHASIC ANAPHYLACTIC BIPHASIC ANAPHYLACTIC REACTIONSREACTIONS
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]
Ellis AK, Day JH. Ann Allergy Asthma Immunol 2007;98:64-9.
BIPHASIC ANAPHYLACTIC BIPHASIC ANAPHYLACTIC REACTIONSREACTIONS
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
Ellis AK, Day JH. Ann Allergy Asthma Immunol 2007;98:64-9.
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
NIAID Food Allergy Guidelines 2010
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
NIAID Food Allergy Guidelines 2010
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 (??)
NIAID Food Allergy Guidelines 2010
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
NIAID Food Allergy Guidelines 2010
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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