anaphylaxis scot a. laurie, md dallas allergy and asthma center clinical assistant professor,...

Anaphylaxis

Scot A. Laurie, MDDallas Allergy and Asthma Center

Clinical Assistant Professor,Division of Allergy & Immunology

University of Texas Southwestern Medical Center

Historical BackgroundHistorical Background

• Discovered by Portier and Richet in Discovered by Portier and Richet in 19021902– While attempting to immunize dogs to While attempting to immunize dogs to

the venom of a sea anemone, they the venom of a sea anemone, they unknowingly sensitized the dogsunknowingly sensitized the dogs•Dogs unexpectedly reacted to a previously Dogs unexpectedly reacted to a previously

nonlethal dosenonlethal dose– Coined the term “anaphylaxie”, meaning without, Coined the term “anaphylaxie”, meaning without,

or against, protectionor against, protection

DEFINITIONSDEFINITIONS• AnaphylaxisAnaphylaxis

– Systemic, immediate hypersensitivity reaction caused Systemic, immediate hypersensitivity reaction caused by IgE-mediated release of histamine and other by IgE-mediated release of histamine and other mediators from mast cells and basophilsmediators from mast cells and basophils

– Clinical syndrome with multi-organ symptomsClinical syndrome with multi-organ symptoms• cutaneouscutaneous• respiratoryrespiratory• cardiovascularcardiovascular• gastrointestinalgastrointestinal

• AnaphylactoidAnaphylactoid

– Identical symptoms as anaphylaxisIdentical symptoms as anaphylaxis– Non-IgE-mediated mechanismNon-IgE-mediated mechanism

EPIDEMIOLOGYEPIDEMIOLOGY • Hospitalization for AnaphylaxisHospitalization for Anaphylaxis

– 13 yr retrospective review of anaphylactic shock from a 13 yr retrospective review of anaphylactic shock from a hospital in Denmark hospital in Denmark • incidence of incidence of 3.2 cases per 100,0003.2 cases per 100,000 inhabitants per year inhabitants per year• mortality rate of these 20 cases was 5%mortality rate of these 20 cases was 5%

– Sørensen H et al. Allergy 1989;44:288.Sørensen H et al. Allergy 1989;44:288.

• ER Visits for AnaphylaxisER Visits for Anaphylaxis– Klein individually reviewed all 19,122 ER records during a 4 Klein individually reviewed all 19,122 ER records during a 4

month period from St. Mary’s Hospital in Rochester, MNmonth period from St. Mary’s Hospital in Rochester, MN– Incidence of anaphylaxis was 17 per 19,122 emergency visits Incidence of anaphylaxis was 17 per 19,122 emergency visits

or or 0.09%0.09% – Only 4/17 had ICD-9 codes for anaphylaxisOnly 4/17 had ICD-9 codes for anaphylaxis

• most were simply classified as having an “allergic reaction”most were simply classified as having an “allergic reaction”– Klein J, Yocum M. J Allergy Clin Immunol 1995;95:637-8.Klein J, Yocum M. J Allergy Clin Immunol 1995;95:637-8.

Epidemiology of Epidemiology of AnaphylaxisAnaphylaxis• Retrospective review Retrospective review

of 1255 cases of of 1255 cases of “anaphylaxis” “anaphylaxis” identified in Olmsted identified in Olmsted County from 1983-County from 1983-19871987

• 133 residents met 133 residents met criteria for criteria for anaphylaxis and had anaphylaxis and had 154 reactions154 reactions• 116 single episode116 single episode• 13 had 2 episodes13 had 2 episodes• 4 had 3 episodes4 had 3 episodes

• Anaphylaxis Anaphylaxis occurrence rate occurrence rate 30/100,000 person 30/100,000 person yearsyears

• Suspect allergen found Suspect allergen found 68%68%

• Allergy consultation in Allergy consultation in only 52%only 52%

• 1 patient died1 patient died• 0.65% fatality rate0.65% fatality rate

Yocum MW et al. J Allergy Clin Immunol 1999;104:452-6.

Yocum MW et al. J Allergy Clin Immunol 1999;104:452-6.

Anaphylaxis: Risk factors Anaphylaxis: Risk factors

• AgeAge– More common in More common in

adultsadults• AtopyAtopy

– FoodsFoods– ExerciseExercise– LatexLatex– RCMRCM– IdiopathicIdiopathic

• Exposure routeExposure route– Oral less likelyOral less likely

• GenderGender– MalesMales

• HymenopteraHymenoptera

– FemalesFemales• LatexLatex

• Muscle relaxantMuscle relaxant

• IdiopathicIdiopathic

Mediators of AnaphylaxisMediators of AnaphylaxisMEDIATOR PHYSIOLOGIC

EFFECT CLINICAL EFFECT

Histamine Smooth muscle contraction

Vascular permeability Vasodilatation

Flush Urticaria/angioedema

Wheezing Hypotension

PGD2 Peripheral Vasodilation Coronary vasoconstriction

Bronchoconstriction

Flushing Bronchospasm Hypotension

LTC4/D4/E4 Smooth muscle contraction

Vascular permeability Mucus production

Bronchospasm ?Hypotension

Tryptase Inactivates bradykinin Activates angiotensin I

Unknown

““SHOCK” ORGANS SHOCK” ORGANS IN ANAPHYLAXISIN ANAPHYLAXIS

•SkinSkin

•Respiratory tractRespiratory tract

•Cardiovascular Cardiovascular systemsystem

•Gastrointestinal Gastrointestinal tracttract

CUTANEOUS SYMPTOMSCUTANEOUS SYMPTOMS• PruritusPruritus

– initially palms, soles, groin, and initially palms, soles, groin, and axillaaxilla

• Urticaria & AngioedemaUrticaria & Angioedema– most common findingmost common finding– usually resolves within 24 hoursusually resolves within 24 hours– angioedema may persist for 2-3 daysangioedema may persist for 2-3 days

• WarmthWarmth

• Flushing Flushing

• ErythemaErythema

RESPIRATORY SYMPTOMSRESPIRATORY SYMPTOMS• Lower respiratory symptomsLower respiratory symptoms

– Dyspnea, wheezing, and chest tightnessDyspnea, wheezing, and chest tightness

• Upper respiratory symptomsUpper respiratory symptoms– Nasal congestion, sneezing, rhinorrheaNasal congestion, sneezing, rhinorrhea– Laryngeal edemaLaryngeal edema

– often begin with a sensation of a “lump in the often begin with a sensation of a “lump in the throat” throat”

– may progress to:may progress to:dysphoniadysphoniahoarsenesshoarsenessdrooling due to inability to swallow secretionsdrooling due to inability to swallow secretionsstridorstridorasphyxiaasphyxia

GASTROINTESTINAL GASTROINTESTINAL SYMPTOMSSYMPTOMS

• Abdominal Abdominal crampingcramping

• NauseaNausea

• VomitingVomiting

• DiarrheaDiarrhea

CARDIOVASCULARCARDIOVASCULAR

• SymptomsSymptoms– lightheadednesslightheadedness– tachycardiatachycardia– bradycardiabradycardia– hypotensionhypotension– vascular collapsevascular collapse

• SignsSigns– ArrhythmiasArrhythmias

• premature atrial premature atrial contractionscontractions

• atrial fibrillationatrial fibrillation• bundle branch blockbundle branch block• peaked P waves and peaked P waves and

right axis deviationright axis deviation• ventricular ventricular

premature premature contractionscontractions

• ventricular fibrillationventricular fibrillation• asystoleasystole• myocardial infarctionmyocardial infarction

FREQUENCY OF ANAPHYLACTIC FREQUENCY OF ANAPHYLACTIC SYMPTOMSSYMPTOMS

Signs & Symptoms Kemp et al.266 cases of anaphylaxis

Ditto et al.335 cases of IA

Urticaria, Angioedema 90% 100%

Dyspnea, Wheezing 60% 39%

Dizziness, Pre-syncope,Syncope

29% 23%

Gastrointestinal 26% 22%

Upper airway edema 24% 63%

Hypotension 20% 23%

Rhinitis 16% ND

Conjunctivitis, Periorbitaledema

12% ND

BIPHASIC & PROTRACTED BIPHASIC & PROTRACTED ANAPHYLAXISANAPHYLAXIS

• Stark & SullivanStark & Sullivan– Prospective study of 25 Prospective study of 25

patients with anaphylaxis patients with anaphylaxis at PMH at PMH

– 5 (20%) had " biphasic 5 (20%) had " biphasic anaphylaxis" anaphylaxis"

– 6 had "protracted 6 had "protracted anaphylaxis"anaphylaxis"

– Risk FactorsRisk Factors• oral agentoral agent• anaphylaxis began > 30 anaphylaxis began > 30

minutes after exposureminutes after exposure• Stark B, Sullivan T. J Stark B, Sullivan T. J

Allergy Clin Immunol Allergy Clin Immunol 1986;78:76-83.1986;78:76-83.

• Douglas et al. Douglas et al. – Biphasic anaphylaxis in only Biphasic anaphylaxis in only

5% of 44 inpatients5% of 44 inpatients• Douglas D et al. J Allergy Douglas D et al. J Allergy

Clin Immunol 1994;93:977-Clin Immunol 1994;93:977-85. 85.

• Both StudiesBoth Studies– Glucocorticoid therapy did Glucocorticoid therapy did

not prevent either recurrent not prevent either recurrent or prolonged anaphylaxisor prolonged anaphylaxis

– Patients without Patients without hypotension or laryngeal hypotension or laryngeal edema did not have edema did not have biphasic reactionsbiphasic reactions

Fatal AnaphylaxisFatal Anaphylaxis

Pumphrey RSH Clin Exp Allergy 2000:30:1144-50.


Timing of Epinephrine in Timing of Epinephrine in Fatal AnaphylaxisFatal Anaphylaxis


Self-injectable Epinephrine Self-injectable Epinephrine Use in Fatal AnaphylaxisUse in Fatal Anaphylaxis

Differential Diagnosis of Differential Diagnosis of Anaphylaxis and Anaphylactoid Anaphylaxis and Anaphylactoid

ReactionsReactions• Vasodepressor reactionsVasodepressor reactions• Flush syndromes- carcinoidFlush syndromes- carcinoid• ““Restaurant syndromes”- scombroidosisRestaurant syndromes”- scombroidosis• Excessive endogenous production of Excessive endogenous production of

histamine- mastocytosishistamine- mastocytosis• Nonorganic disease- panic disorder, vocal Nonorganic disease- panic disorder, vocal

cord disorder, undifferentiated cord disorder, undifferentiated somatoform anaphylaxissomatoform anaphylaxis

• Chronic idiopathic urticaria/angioedemaChronic idiopathic urticaria/angioedema

EVALUATION OF PATIENTS EVALUATION OF PATIENTS WITH ANAPHYLAXISWITH ANAPHYLAXIS

• Working definition of anaphylaxisWorking definition of anaphylaxis– EitherEither

•Airway obstruction Airway obstruction such as laryngeal, pharyngeal, or such as laryngeal, pharyngeal, or glossal edema or severe glossal edema or severe bronchospasmbronchospasm

– OrOr•Documented Documented hypotension or syncopehypotension or syncope

– PlusPlus•Symptoms of generalized mediator releaseSymptoms of generalized mediator release

– urticaria, angioedema, pruritus, or flushingurticaria, angioedema, pruritus, or flushing

• Review ER records for objective findingsReview ER records for objective findings

DETERMINING THE ETIOLOGY OF DETERMINING THE ETIOLOGY OF ANAPHYLAXISANAPHYLAXIS

• Detailed HistoryDetailed History– Time of dayTime of day– Relationship to exercise, meals, and Relationship to exercise, meals, and

medicationsmedications– Prescribed medications Prescribed medications

•different formulations or lots of medicationsdifferent formulations or lots of medications– Non-prescribed ingestantsNon-prescribed ingestants

•vitamins, health food supplements, vitamins, health food supplements, laxatives, and suppositorieslaxatives, and suppositories

•specific ingredients of mealsspecific ingredients of meals•within 4 hours of episode(s) within 4 hours of episode(s)

– WomenWomen•menses or intercoursemenses or intercourse

SPECIFIC IgE in ANAPHYLAXISSPECIFIC IgE in ANAPHYLAXIS• Skin testingSkin testing

– Accuracy > RAST Accuracy > RAST – Risk of fatal reactionsRisk of fatal reactions– AllergensAllergens

• medications, anesthetics, medications, anesthetics, venoms, foods, insulin, venoms, foods, insulin, latexlatex

• heterologous sera, heterologous sera, vaccines, and other foreign vaccines, and other foreign proteinsproteins

– Specificity fairly goodSpecificity fairly good– Sensitivity of many tests Sensitivity of many tests

is ?is ?– Some drugs can cause Some drugs can cause

direct histamine releasedirect histamine release– opiates, RCM , some opiates, RCM , some

muscle relaxantsmuscle relaxants

• RAST testingRAST testing– Without riskWithout risk– Limited applicability Limited applicability

due to due to • lower accuracylower accuracy

• Few allergens Few allergens availableavailable

– venoms, foods, venoms, foods, latex, and the latex, and the major determinant major determinant of penicillinof penicillin

FOOD SKIN TESTING IN FOOD SKIN TESTING IN ANAPHYLAXISANAPHYLAXIS

• Stricker et alStricker et al– Panel of 79 antigensPanel of 79 antigens– Identified 7 food-induced anaphylaxis of 102 patients with IAIdentified 7 food-induced anaphylaxis of 102 patients with IA

• Stricker W et al. J Allergy Clin Immunol 1986;77:516-519.Stricker W et al. J Allergy Clin Immunol 1986;77:516-519.

• Patients frequently unaware of foods that caused Patients frequently unaware of foods that caused reactionsreactions– Food allergic patients failed to identify causative food in Food allergic patients failed to identify causative food in

67% of positive DBPCFC67% of positive DBPCFC

• Atkins F. J Allergy Clin Immunol 1985;75:348-355.Atkins F. J Allergy Clin Immunol 1985;75:348-355.– Most all patients with fatal food-induced anaphylaxis Most all patients with fatal food-induced anaphylaxis

unknowingly ingested their fatal foodunknowingly ingested their fatal food

• Skin testing with fresh foodsSkin testing with fresh foods– Commercial food extracts may lack antigenic epitopesCommercial food extracts may lack antigenic epitopes

MEDIATOR MEASUREMENT IN MEDIATOR MEASUREMENT IN ANAPHYLAXISANAPHYLAXIS

MAST CELL MEDIATOR

BODY FLUID COMMENTS

Histamine Plasma, Urine In circulation breifly False positives in urine

Histamine metabolites (MIAA)

24 hr Urine Cumbersome More specific and sensitive than histamine measurements

Tryptase (G5 & B12) Serum B12-measured tryptase commercially available Measures total tryptase

9 ,11ß-PGF2 24 hr Urine Available from Mayo Labs

TRYPTASETRYPTASE

• Neutral protease in secretory granules of Neutral protease in secretory granules of mast cellsmast cells

• Specific for mast cellsSpecific for mast cells• very minimal amounts in basophilsvery minimal amounts in basophils

• -tryptase-tryptase• predominant form of tryptase in circulation in predominant form of tryptase in circulation in

both normals and mastocytosis patientsboth normals and mastocytosis patients

• -tryptase-tryptase• released from secretory granules with systemic released from secretory granules with systemic

mast cell activationmast cell activation

TRYPTASE TRYPTASE MEASUREMENTSMEASUREMENTS

• Total tryptaseTotal tryptase• measured with mAb B12measured with mAb B12• measures both measures both & & -tryptase-tryptase• normal values < 15 ng/mlnormal values < 15 ng/ml

• increases detectable earlier than G5 assayincreases detectable earlier than G5 assay

• available through commercial labsavailable through commercial labs

• -tryptase-tryptase• measured with mAb G5measured with mAb G5• normal values < 1 ng/mlnormal values < 1 ng/ml

• undetectable within 30 minutesundetectable within 30 minutes• peaks in 1-2 hourspeaks in 1-2 hours

• available through Dr. Schwartz’s lab at MCVavailable through Dr. Schwartz’s lab at MCV

CLASSIFICATION OF CLASSIFICATION OF ANAPHYLAXISANAPHYLAXIS

• IgE MediatedIgE Mediated

•Complement/Immune Complement/Immune Complex ActivationComplex Activation

•Direct Histamine ReleaseDirect Histamine Release

•Unknown MechanismsUnknown Mechanisms

IgE MEDIATED IgE MEDIATED ANAPHYLAXISANAPHYLAXIS

• AntibioticsAntibiotics– Penicillin, Cephalosporins, Penicillin, Cephalosporins,

SulfamethoxazoleSulfamethoxazole

• ProteinsProteins– Venoms, Heterologous Venoms, Heterologous

sera, Latex, Seminal fluidsera, Latex, Seminal fluid– Hormones: Hormones: ACTH, Insulin, ACTH, Insulin,

PTH, PTH, GnRH GnRH– Enzymes: Enzymes: Chymopapain, Chymopapain,

StreptokinaseStreptokinase

• FoodsFoods– Peanut, Tree nuts, Peanut, Tree nuts,

Crustaceans, Fish, Seeds, Crustaceans, Fish, Seeds, SpicesSpices

– Milk, Egg, Soy, Many othersMilk, Egg, Soy, Many others

• TherapeuticsTherapeutics– Allergen extractsAllergen extracts– Vaccines - including Vaccines - including

fillers (gelatin)fillers (gelatin)– Intraoperative agentsIntraoperative agents

• Thiopental, Muscle Thiopental, Muscle relaxants, ?relaxants, ?Protamine, Protamine, FentanylFentanyl

– Chemotherapeutics, Chemotherapeutics, Ethylene oxide gas, Ethylene oxide gas, PsylliumPsyllium

– Local anesthetics, ?Local anesthetics, ?Corticosteroids, ?Corticosteroids, ?NSAID’sNSAID’s

LOCAL ANESTHETIC LOCAL ANESTHETIC ALLERGYALLERGY

• Allergy rare and anaphylaxis extremely rareAllergy rare and anaphylaxis extremely rare– allergy to parabens also rareallergy to parabens also rare

• Non-cross-reacting local anesthetic groupsNon-cross-reacting local anesthetic groups– defined based on patch testing for contact defined based on patch testing for contact

dermatitisdermatitis– unclear if any relevance to anaphylaxisunclear if any relevance to anaphylaxis

• Skin testing & incremental challengeSkin testing & incremental challenge– validated methodvalidated method– recommended for evaluation of possible recommended for evaluation of possible

allergyallergy

IMMUNE IMMUNE COMPLEX/COMPLEMENT COMPLEX/COMPLEMENT ACTIVATIONACTIVATION• ? Radiocontrast Media? Radiocontrast Media

• Blood/Blood productsBlood/Blood products– Plasma, Serum, Plasma, Serum,

cryoprecipitatecryoprecipitate– IgE mediated anaphylaxisIgE mediated anaphylaxis

• passive sensitizationpassive sensitization

• IgE anti-IgA in IgA deficient IgE anti-IgA in IgA deficient patientspatients

• FVIIIFVIII

• Hemodialysis membranesHemodialysis membranes

• IVIGIVIG

THE MYTH OF SEAFOOD THE MYTH OF SEAFOOD ALLERGY & RCM REACTIONSALLERGY & RCM REACTIONS

• Despite the common belief that Despite the common belief that individuals with seafood allergy have a individuals with seafood allergy have a higher risk of RCM reactions, there is no higher risk of RCM reactions, there is no data to support this and it has no data to support this and it has no theoretical basistheoretical basis– Shellfish allergic patients are allergic to Shellfish allergic patients are allergic to

muscle proteins, not iodidemuscle proteins, not iodide– RCM reactions are not caused by iodide RCM reactions are not caused by iodide – Low-ionic RCM have a lower incidence of Low-ionic RCM have a lower incidence of

anaphylactoid reactions despite containing anaphylactoid reactions despite containing more iodide per particle than traditional RCMmore iodide per particle than traditional RCM

DIRECT HISTAMINE DIRECT HISTAMINE RELEASERELEASE

• Hypertonic SolutionsHypertonic Solutions– RCM, MannitolRCM, Mannitol

• Plasma ExpandersPlasma Expanders– Dextran, Hydroxyethyl starchDextran, Hydroxyethyl starch

• DrugsDrugs– Opiates, Vancomycin, Curare, Opiates, Vancomycin, Curare,

FluorosceinFluoroscein

Anaphylaxis with Anaphylaxis with Unknown MechanismUnknown Mechanism

• Exercise Induced AnaphylaxisExercise Induced Anaphylaxis

• Idiopathic AnaphylaxisIdiopathic Anaphylaxis

• Progesterone AnaphylaxisProgesterone Anaphylaxis

ACUTE TREATMENT OF ACUTE TREATMENT OF ANAPHYLAXISANAPHYLAXIS• Early recognition and treatmentEarly recognition and treatment

– delays in therapy are associated with fatalitiesdelays in therapy are associated with fatalities

• Assessing the nature and severity of the Assessing the nature and severity of the reactionreaction

• Brief historyBrief history– identify allergen if possibleidentify allergen if possible

• initiate steps to reduce further absorptioninitiate steps to reduce further absorption– medications (especially medications (especially -blockers)-blockers)

• General TherapyGeneral Therapy– supplemental oxygen, IVF, vital signs, cardiac supplemental oxygen, IVF, vital signs, cardiac

monitoringmonitoring

• Goals of therapyGoals of therapy– ABC’sABC’s

EPINEPHRINEEPINEPHRINE• First-line drug of First-line drug of

choice in choice in anaphylaxisanaphylaxis

• Mechanisms of actionMechanisms of action– agonistagonist

• increase BP by peripheral increase BP by peripheral vasoconstrictionvasoconstriction

– -agonist-agonist• reverse bronchoconstrictionreverse bronchoconstriction• positive ionotropic and positive ionotropic and

chronotropic activitychronotropic activity• increases cyclic AMP levelsincreases cyclic AMP levels

– inhibit further mediator inhibit further mediator release from mast cells release from mast cells and basophilsand basophils

• Subcutaneous Subcutaneous administrationadministration– dose: 0.3 to 0.5 mg of dose: 0.3 to 0.5 mg of

a 1:1,000 dilution prn q a 1:1,000 dilution prn q 10-15 min10-15 min

– IV epinephrine for IV epinephrine for cardiovascular collapsecardiovascular collapse

• Side effectsSide effects– severe hypertension, severe hypertension,

arrhythmias, arrhythmias, myocardial ischemia myocardial ischemia and infarctionand infarction

• DO NOT WITHHOLD DO NOT WITHHOLD EPINEPHRINE BECAUSE OF EPINEPHRINE BECAUSE OF CARDIAC HISTORYCARDIAC HISTORY

Simons FER et al. J Allergy Clin Immunol 1998;101:33-7.

Epinephrine Absorption: SQ vs. IMEpinephrine Absorption: SQ vs. IM

Epinephrine Subcutaneous Epinephrine Intramuscular



Outdated EpiPensOutdated EpiPens

Use of EpiPen in Children with Use of EpiPen in Children with AnaphylaxisAnaphylaxis

• Retrospective survey of children with Retrospective survey of children with anaphylaxis who attended an allergy clinic anaphylaxis who attended an allergy clinic in North Adelaide Australiain North Adelaide Australia

• 45 episodes of anaphylaxis45 episodes of anaphylaxis• EpiPen givenEpiPen given 13 (29%)13 (29%)• EpiPen not givenEpiPen not given 32 (71%)32 (71%)

• Hospitalization for anaphylaxisHospitalization for anaphylaxis• EpiPen givenEpiPen given 2 (14%) p< .052 (14%) p< .05• EpiPen not givenEpiPen not given 15 (47%)15 (47%)

Gold MS, Sainsbury R. J Allergy Clin Immunol 2000;106:171-6.

ANTIHISTAMINES IN ANTIHISTAMINES IN ANAPHYLAXISANAPHYLAXIS• Not a substitute for epinephrineNot a substitute for epinephrine

• HH11-antagonists-antagonists– useful for cutaneous symptomsuseful for cutaneous symptoms

• HH22-antagonists-antagonists– somewhat controversialsomewhat controversial

– combination of Hcombination of H11 and H and H22 antagonists was antagonists was required for optimal prevention of hypotension required for optimal prevention of hypotension in studies of histamine infusionsin studies of histamine infusions

– overall evidence favors the addition of Hoverall evidence favors the addition of H22--antagonistsantagonists• especially in the presence of hypotensionespecially in the presence of hypotension

-BLOCKED -BLOCKED ANAPHYLAXISANAPHYLAXIS

• Beta blockadeBeta blockade– increase release of increase release of

mediatorsmediators– enhance the enhance the

responsiveness of responsiveness of pulmonary, cardiovascular, pulmonary, cardiovascular, and cutaneous systems to and cutaneous systems to mediatorsmediators

– paradoxical responses to paradoxical responses to epinephrineepinephrine• bronchoconstriction bronchoconstriction

and bradycardiaand bradycardia– unopposed unopposed --

adrenergic and adrenergic and reflex vagotonic reflex vagotonic effectseffects

• May be especially May be especially refractory to therapyrefractory to therapy

• TreatmentTreatment– high doses of high doses of

isoproterenol or isoproterenol or dopaminedopamine

– atropineatropine– glucagonglucagon

• increases c-AMP increases c-AMP independent of independent of --receptorreceptor

• nausea and vomiting nausea and vomiting commoncommon

PREVENTION OF PREVENTION OF ANAPHYLAXISANAPHYLAXIS

• Referral to BC/BE allergistReferral to BC/BE allergist– Determine an etiologyDetermine an etiology

• skin testingskin testing• challengeschallenges• desensitization.desensitization.

– Educate the patient on avoidanceEducate the patient on avoidance• proper use and indications of injectable proper use and indications of injectable

epinephrineepinephrine• when to seek medical attentionwhen to seek medical attention• obtain a Medic-Alert® braceletobtain a Medic-Alert® bracelet

– Develop a management planDevelop a management plan• prevent and reduce further anaphylactic episodesprevent and reduce further anaphylactic episodes

• Select an alternative drug if on Select an alternative drug if on -blocker-blocker

ACUTE DESENSITIZATIONACUTE DESENSITIZATION• IndicationsIndications

– Patients allergic to an essential therapeutic agentPatients allergic to an essential therapeutic agent– Systemic reactions to venoms (optional)Systemic reactions to venoms (optional)

• TechniqueTechnique– Escalating doses of antigen administered over a brief Escalating doses of antigen administered over a brief

periodperiod– Oral route preferred when possibleOral route preferred when possible

• Desensitization procedures are dangerousDesensitization procedures are dangerous• Mechanism of desensitizationMechanism of desensitization

– UnknownUnknown– Desensitized state is antigen specificDesensitized state is antigen specific

• not due to tachyphylaxis to mediators, mast cell not due to tachyphylaxis to mediators, mast cell depletion, or unresponsiveness to any IgE signaldepletion, or unresponsiveness to any IgE signal

CASE REPORTCASE REPORT• LB is a 62 yo WM who presented with LB is a 62 yo WM who presented with

recurrent syncopal episodes. These recurrent syncopal episodes. These episodes were associated with pruritus, episodes were associated with pruritus, urticaria, lightheadedness, and syncope urticaria, lightheadedness, and syncope with urinary & fecal incontinence and with urinary & fecal incontinence and occurred after playing basketball or ping-occurred after playing basketball or ping-pong. However, he has performed more pong. However, he has performed more vigorous exercise without reactions. An vigorous exercise without reactions. An echocardiogram, Holter monitor and echocardiogram, Holter monitor and head CT were all normal.head CT were all normal.

• Physical examination was unremarkablePhysical examination was unremarkable

EXERCISE-INDUCED EXERCISE-INDUCED ANAPHYLAXISANAPHYLAXIS

• ClassificationClassification– Food dependent EIA Food dependent EIA

•Specific food dependent EIA Specific food dependent EIA – occurs only if exercise after eating specific occurs only if exercise after eating specific

food(s)food(s)– implicated foodsimplicated foods

shellfish, wheat, celery, tomato, apple, shellfish, wheat, celery, tomato, apple, grapes, litchi, hazlenut, chestnut, peanut, grapes, litchi, hazlenut, chestnut, peanut, milk, rice, potato milk, rice, potato

•Non-specific food dependent EIANon-specific food dependent EIA– occurs if exercising after eating any foodoccurs if exercising after eating any food

– Food independent EIAFood independent EIA

POSSIBLE MECHANISMS OF EIAPOSSIBLE MECHANISMS OF EIA• Subthreshold amount of mast cell associated IgE cross-Subthreshold amount of mast cell associated IgE cross-

linkinglinking– Endogenous opioid stimulus can trigger primed Endogenous opioid stimulus can trigger primed

mast cells to degranulatemast cells to degranulate– Increases in codeine skin test reactivity after exercise Increases in codeine skin test reactivity after exercise – Increased wheal response to compound 48/80 in Increased wheal response to compound 48/80 in

individuals with food-dependent EIA, but only after individuals with food-dependent EIA, but only after challenges with specific foods and exercise.challenges with specific foods and exercise.

– Gastrin can stimulate mediator release from mast Gastrin can stimulate mediator release from mast cellscells

• Abnormal responses of the autonomic nervous systemAbnormal responses of the autonomic nervous system– Increases in parasympathetic responsesIncreases in parasympathetic responses– Decreases in sympathetic activity Decreases in sympathetic activity

CLINICAL FEATURES OF EIACLINICAL FEATURES OF EIA

• 7% of anaphylaxis due to EIA7% of anaphylaxis due to EIA• Symptoms & signs of EIA Symptoms & signs of EIA

similar to other forms of similar to other forms of anaphylaxisanaphylaxis– premonitory symptomspremonitory symptoms

• generalized warmth, generalized warmth, prurituspruritus

• urticaria are usually urticaria are usually 10-15 mm in diameter10-15 mm in diameter

• angioedema of face, angioedema of face, palms, and solespalms, and soles

– reactions occur while reactions occur while exercising or shortly exercising or shortly thereafterthereafter

– duration of 0.5 to 4 hoursduration of 0.5 to 4 hours

• Exercise triggersExercise triggers– Tennis, warmups, Tennis, warmups,

dancing, soccer, dancing, soccer, basketball, runningbasketball, running

– vaginal deliveryvaginal delivery• Predisposing factorsPredisposing factors

– personal or family history personal or family history of atopyof atopy• familial EIA has been familial EIA has been

reportedreported– aspirin ingestion prior to aspirin ingestion prior to

exercise may trigger 30%exercise may trigger 30%– exercising in warm or exercising in warm or

humid weatherhumid weather– mensesmenses

THERAPY OF EIATHERAPY OF EIA• Acute treatmentAcute treatment

– epinephrineepinephrine• available while exercisingavailable while exercising

• PreventionPrevention– exercise with a partnerexercise with a partner– limiting or discontinuing exercise at the first sign of limiting or discontinuing exercise at the first sign of

prodromal symptomsprodromal symptoms– avoid NSAID’savoid NSAID’s– avoiding foods for 4-5 hours prior to exercise avoiding foods for 4-5 hours prior to exercise – antihistamines - unable to totally prevent attacksantihistamines - unable to totally prevent attacks– oral disodium cromoglycateoral disodium cromoglycate– ““exercise desensitization”exercise desensitization”

Natural History of EIANatural History of EIA• 279 EIA patients completed mailed survey279 EIA patients completed mailed survey• Clinical courseClinical course

– Attacks/yr decreased from 14.5 to 8.3Attacks/yr decreased from 14.5 to 8.3– 47% decrease in attacks47% decrease in attacks– 46% same46% same– 7% increased7% increased

• Food Associated EIAFood Associated EIA– 37% patients37% patients– Shellfish, alcohol, tomato most common triggersShellfish, alcohol, tomato most common triggers

• Avoidance behaviorsAvoidance behaviors– Avoid exercise in extreme hot/cold or allergy seasonAvoid exercise in extreme hot/cold or allergy season– Avoid eating before exerciseAvoid eating before exercise

Shadick NA et al. J Allergy Clin Immunol 1999;104:123-7.

Case ReportCase Report

• CW is a 14 yo WF with a history of large CW is a 14 yo WF with a history of large local reactions to “bees”. 3 weeks prior local reactions to “bees”. 3 weeks prior to evaluation she was bit in the forehead to evaluation she was bit in the forehead by an ant and within 5 minutes by an ant and within 5 minutes developed facial urticaria, chest developed facial urticaria, chest tightness, and throat tightness which tightness, and throat tightness which improved with Himproved with H11 & H & H22 antagonists antagonists administered by her father a cardiologist.administered by her father a cardiologist.– Prick testing to imported fire ants was Prick testing to imported fire ants was

positivepositive

IMPORTED FIRE ANTSIMPORTED FIRE ANTS• IFA most common cause of anaphylaxis IFA most common cause of anaphylaxis

to stinging insects in this areato stinging insects in this area

• Imported fire ant speciesImported fire ant species– Solenopsis richteri Solenopsis richteri

• introduced from Uruguay or Argentina introduced from Uruguay or Argentina accidentally into the USA through the port of accidentally into the USA through the port of Mobile, Alabama in 1918 Mobile, Alabama in 1918

• localized to northeastern Mississippi and localized to northeastern Mississippi and northwestern Alabamanorthwestern Alabama

– Solenopsis invicta Solenopsis invicta • Brazilian species introduced later between 1933-Brazilian species introduced later between 1933-

1941 1941

Fire Ant AnaphylaxisFire Ant Anaphylaxis• 0.6% to 2% of patients requiring medical treatment for stings0.6% to 2% of patients requiring medical treatment for stings• Texas has the 2nd highest number of IFA sting fatalitiesTexas has the 2nd highest number of IFA sting fatalities• DiagnosisDiagnosis

– anaphylaxis history after sting with development of a pustuleanaphylaxis history after sting with development of a pustule– fire ant-specific IgE by skin testsfire ant-specific IgE by skin tests

• 25% of nonallergic individuals in endemic areas have IFA 25% of nonallergic individuals in endemic areas have IFA specific IgEspecific IgE

• Immunotherapy Immunotherapy – Indicated for patients with systemic reactions, especially Indicated for patients with systemic reactions, especially

anaphylaxisanaphylaxis– IFA whole body immunotherapy efficacyIFA whole body immunotherapy efficacy

• field re-stingsfield re-stings– 2.1% risk of anaphylaxis2.1% risk of anaphylaxis

• intentional sting challengeintentional sting challenge– 0/30 reactions0/30 reactions

• Optimal duration of immunotherapy unknownOptimal duration of immunotherapy unknown

CASE REPORTCASE REPORT• 34 yo BF with recurrent episodes of pruritus, 34 yo BF with recurrent episodes of pruritus,

urticaria, angioedema, chest tightness, and urticaria, angioedema, chest tightness, and syncope. One episode required ER treatment and syncope. One episode required ER treatment and hypotension was documented. All episodes hypotension was documented. All episodes occurred shortly after sexual intercourse. She was occurred shortly after sexual intercourse. She was seen initially by a neurologist who thought she was seen initially by a neurologist who thought she was having hypoglycemic attacks and recommended having hypoglycemic attacks and recommended eating prior to intercourse which did not help. She eating prior to intercourse which did not help. She also had an ETT performed and the cardiologist also had an ETT performed and the cardiologist thought she “was crazy”. thought she “was crazy”.

• Skin testing with her partners semen at 1:1,000 Skin testing with her partners semen at 1:1,000 dilution was markedly positive while her partner dilution was markedly positive while her partner was skin test negative was skin test negative

• Condom use was recommended and prevented the Condom use was recommended and prevented the attacksattacks

HUMAN SEMINAL PLASMA HUMAN SEMINAL PLASMA ANAPHYLAXISANAPHYLAXIS

• First reported by Specken in 1958First reported by Specken in 1958• PathogenesisPathogenesis

– Halpern et al. (1967)Halpern et al. (1967)• Evaluated a woman with anaphylaxis occurring 15-30 Evaluated a woman with anaphylaxis occurring 15-30

minutes after coitusminutes after coitus• Scratch tests were positive toScratch tests were positive to

– husband’s whole sperm & seminal fluid devoid of husband’s whole sperm & seminal fluid devoid of spermatozoaspermatozoa

– donor seminal fluid devoid of spermatozoadonor seminal fluid devoid of spermatozoa

• Scratch tests negative toScratch tests negative to– husband’s serumhusband’s serum– semen from rabbit, guinea-pig, horse and bullsemen from rabbit, guinea-pig, horse and bull

• Passive transfer (Prausnitz-Küstner reaction)Passive transfer (Prausnitz-Küstner reaction)– positive in 5 female controls as well as in monkeyspositive in 5 female controls as well as in monkeys

• Chromatography and electrophoresis of seminal fluid Chromatography and electrophoresis of seminal fluid identified basic protein fractions that were the most identified basic protein fractions that were the most antigenicantigenic

HUMAN SEMINAL PLASMA HUMAN SEMINAL PLASMA ANAPHYLAXISANAPHYLAXIS

• AntigensAntigens– Isolated to seminal plasmaIsolated to seminal plasma

• reactions can occur with vasectomized partnersreactions can occur with vasectomized partners

• only one case reported of a women reactive to only one case reported of a women reactive to spermatozoa and HSPspermatozoa and HSP

• canine sperm can also induce anaphylaxis due to canine sperm can also induce anaphylaxis due to bestialitybestiality

– Antigenic fraction of seminal fluidAntigenic fraction of seminal fluid• MW of 20,000 to 30,000 daltonsMW of 20,000 to 30,000 daltons

• heat stableheat stable

• prostatic originprostatic origin

• prostate specific antigen (PSA) may be a major allergenprostate specific antigen (PSA) may be a major allergen

THERAPY OF HSP THERAPY OF HSP ANAPHYLAXISANAPHYLAXIS

• CondomsCondoms– universally successfuluniversally successful– may induce remission if may induce remission if

used for prolonged used for prolonged periodsperiods

• Prophylactic Prophylactic antihistaminesantihistamines– may control local HSP may control local HSP

reactionsreactions– ineffective for systemic ineffective for systemic

reactionsreactions

• PregnancyPregnancy– successful impregnation successful impregnation

may be achieved using may be achieved using artificial insemination with artificial insemination with isolated spermatozoaisolated spermatozoa

• ImmunotherapyImmunotherapy– extracts of antigenic extracts of antigenic

fractions of HSP most fractions of HSP most successfulsuccessful• Immunologic changes Immunologic changes

variablevariable– decrease in IgE decrease in IgE – progressive rise in progressive rise in

IgGIgG– rapid desensitizationrapid desensitization

• parenteral and local parenteral and local (intravaginal)(intravaginal)

– long term successlong term success• up to 8 years after up to 8 years after

immunotherapyimmunotherapy• maintaining sexual maintaining sexual

activity 2-3 times per activity 2-3 times per weekweek

Idiopathic AnaphylaxisIdiopathic Anaphylaxis

• Diagnosis of exclusionDiagnosis of exclusion– Careful evaluation for known causes should be Careful evaluation for known causes should be

performedperformed

• Mechanism is unknownMechanism is unknown• Patients present with the same constellation of Patients present with the same constellation of

symptoms as others with anaphylaxissymptoms as others with anaphylaxis• Treatment approach is the sameTreatment approach is the same

– Preventative therapy with qd or qod prednisone may be Preventative therapy with qd or qod prednisone may be requiredrequired

• Patients require education and support as part of Patients require education and support as part of their disease managementtheir disease management

CONCLUSIONSCONCLUSIONS

• Anaphylaxis is the most dramatic and Anaphylaxis is the most dramatic and potentially fatal manifestation of immediate potentially fatal manifestation of immediate hypersensitivityhypersensitivity

• Majority of reactions are due to medications, Majority of reactions are due to medications, insect stings, radiocontrast media and food, insect stings, radiocontrast media and food, however many are idiopathichowever many are idiopathic

• Most anaphylactic reactions respond to Most anaphylactic reactions respond to aggressive therapy, but fatalities still occur, aggressive therapy, but fatalities still occur, especially if treatment is delayedespecially if treatment is delayed

• Epinephrine is still underutilized in many Epinephrine is still underutilized in many patientspatients

• Almost all cases of anaphylaxis should be Almost all cases of anaphylaxis should be referred to an allergistreferred to an allergist

anaphylaxis scot a. laurie, md dallas allergy and asthma center clinical assistant professor,...

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