DRUG ALLERGY

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DRUGALLERGY

IrisM.Otani,MDAssistantProfessorofClinicalMedicine

Allergy&ImmunologyUCSFMedicalCenter

May22,2017

LearningObjectives

• Epidemiology

• TypesofAdverseDrugReactions

• TypesofHypersensitivityReactions• Diagnosis• Management

• SpecificHypersensitivityReactions

DRUG ALLERGY

AdverseDrugEvents(ADEs)• Frequency:4.2/100admissions

• Cost:$6685perevent

• SeriousADEsà 75,000– 106,000deathsperyear

• Allergicdrugreactionscomprise25%ofADEs• Penicillin,amoxicillin,andbactrim mostcommoncauses

HugBLJt Comm JQual PatientSaf 2012Jylha AInt JQual HealthCare2011Senst BLAmJHealthSyst Pharm 2001Benkhaial APharmWorldSci 2009Solensky RAnnAllergyAsthmaImmunol.2010KellyWN.AmJHealthSyst Pharm.2001

AdaptedfromDr.KimBlumenthalDRUG ALLERGY

DrugAllergy

• MostcommoncauseoffatalanaphylaxisintheUnitedStates(58%)

DRUG ALLERGY

Jerschow JACI2014

• Increasingsignificantly

• 0.27permillà 0.51permill

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TerminologyisConfusing

5

AdverseDrug

Reaction

DrugAllergy

DrugHypersensitivity

IgEmediatedreaction

DrugIntolerance

Sensitivity

Susceptibility

AdaptedfromDr.AleenaBanerjiDRUG ALLERGY

ClassificationofAdverseDrugReactions

Solensky,Immunol AllergyClin NAm2004

AdaptedfromDr.AleenaBanerjiDRUG ALLERGY: Classification

Predictable* Unpredictable

DrugIntoleranceDrugIdiosyncrasyPseudoallergic

OtherNon-immunologic

IgEMediated(I)Cytotoxic(II)

ImmuneComplex(III)CellMediated(IV)OtherImmunologic

OR

ImmuneMediatedDrugHypersensitivityReactions

Non-immuneMediatedDrugHypersensitivityReactions

Preventable NotPreventable

Solenskyetal.,DrugAllergyPracticeParameters,AnnAllergyAsthm Immunol 2010

Insulin– Hypoglycemia

ClassificationofAdverseDrugReactionsAllunintendedpharmacologiceffectsofadrug

Except:therapeuticfailures,intentionaloverdose,abuseofthedrug,orerrorsinadministration






OR





Chemotherapy– HairLoss




IgE Mediated(I)Cytotoxic(II)


OR





Penicillin– Anaphylaxis

*usuallydosedependentandrelatedtotheknownpharmacologicactionsofthedrug


RiskFactorsforHSR

• Drug risk factors• Chemical properties and molecular weight• Dose, route of administration (IV>PO),

duration of treatment, repetitive exposure, and concurrent illnesses• HIV: allergy to TMP/SMX (bactrim) 9-34%• EBV: If patients have EBV and get

AMP/AMOX, 30-100% will develop a rash• Host risk factors: Age, gender (F>M) and atopyRichJDAnnAllergyAsthmaImmunol.1997;79(5):409-14.Chovel-Sella APediatrics.2013May;131(5):e1424-7BlumenthalKAllergyAsthmaProc.201435(3):197-203

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY: Risk Factors

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GeneticRisksforDrugAllergy

• HLA-DR3 is associated with increased reactions to insulin, gold, and penicillamine

• HLA-B*5701 is associated with increased reactions to abacavir

• HLA-B*1502 increases risk of Steven Johnson Syndrome/Toxic Epidermal Necrolysis with carbamazepime

Solensky RAnnAllergyAsthmaImmunol.2010;105(4):259-73.

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY: Risk Factors

Evaluation:AllergyHistory• Exact drug, dose and route• Approximate date of reaction• Reaction details

• Doses/days into course• Co-administered drugs• Coincident infections• Symptoms, exam, lab (photos, outside record

review)• Treatment

• Home, office visit, ED, hospitalization• Epinephrine, steroids, antihistamines

DiounA.Curr AllergyAsthmaRep2012;12:79-84.

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY: Evaluation

TypeI,IgE-mediated

• Usually within two hours after drug exposure

• Can recur/worsen with repeat exposure

• Skin testing may be helpful

• If convincing history, or skin test positive, patients may be candidates for desensitization• Desensitization induces a state of temporary tolerance

through gradual introduction of the drug


AdaptedfromAAAAITeachingSlidesDRUG ALLERGY: Evaluation – Type I

TypeI,IgE-mediated– SymptomsandSigns• Cutaneous and mucosal: urticaria, angioedema, pruritus, rhinitis, conjunctivitis

• Gastrointestinal: nausea, throat tightness, difficulty swallowing, vomiting, diarrhea

• Respiratory: cough, dyspnea, wheezing, stridor, hypoxia

• Cardiovascular: hypotension, tachycardia

• Neurologic: confusion, loss of consciousnessDiounA.Curr AllergyAsthmaRep2012;12:79-84.

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY: Evaluation – Type I

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CommonIgE ExamFindings

Palmarerythemaandpruritus

Angioedema,oftenasymmetric

Urticaria,erythematous,raisedpruriticlesions,witheachlesionlastinghours(but<24hrs)

AdaptedfromAAAAITeachingSlides

DRUG ALLERGY: Evaluation – Type I

Evaluation:SkinTesting

• Useful for reactions with possible IgE mechanism

• All patients with an “unknown” reaction may be considered for skin testing to rule out IgE

• No role for skin testing in patients with history of Stevens-Johnson syndrome/toxic epidermal necrolysis, DRESS syndrome, acute interstitial nephritis, exfoliative dermatitis, hemolytic anemia




• Avoid antihistamines for a minimum of 5 days prior to skin testing• Benadryl/ diphenhydramine, Allegra/fexofenadine,

Claritin/loratadine, etc.

• Hold beta-blockers for 1 day prior to skin testing• blunts response to epinephrine should an anaphylactic

reaction occur

• Results are available immediately (15-20 minutes)




• Skin testing is performed in steps: skin prick (epicutaneous) and intradermal testing using increasing concentrations



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SkinTesting– Caveats

• Skin testing for drug allergy is only validated for penicillin allergy where antigenic determinants have been identified

• All other drug testing can be performed using an established non-irritating concentration with drug challenge being an important part of the evaluation

Empedrad JAllergyClin Immunol 2003;112:629-30.



Evaluation:DrugChallenges• Referred to as graded challenge or test dose• Indicated for low risk patients unlikely to be allergic

• Administration of progressively increasing doses until full dose is reached• 1/10th of a dose of IV drug (or 1/4th of a PO drug)• followed by 9/10th of a dose of IV drug (or 3/4th of PO)

• Completing a challenge or test dose without an adverse reaction shows there is no immediate (IgE-mediated) drug allergy




Management:Desensitization• For reactions that are clinically consistent with IgE

mediated hypersensitivity reactions

• Indicated when there is no acceptable treatment alternative• must be performed under the supervision of a trained allergist

• Achieved via administering increasing doses of medication in a stepwise manner, such that exposure is continuous

• Induces a state of temporary tolerance though once drug is cleared from system, state of tolerance is lost

Solensky RAnnAllergyAsthmaImmunol.2010;105(4):259-73LiuAClin Exp Allergy.2011Dec;41(12):1679-89.CastellsMCurr Opin AllergyClin Immunol.2006AdaptedfromAAAAITeachingSlides

DRUG ALLERGY: Management – Type I

DesensitizationProtocolExamplesDrug Given

(mg)Cumulative Time (min)

Cumulative Drug Dosage (mg)

1 0 0.3

1 30 1.30

3 60 4.30

10 90 14.30

20 120 34.30

40 150 74.30

81 180 155.30

162 210 317.30

325 240 642.30

Sampleoraldesensitization(toAspirin325mg)

Bag#11:100

Bag#21:10

Bag#31:1

Sampleintravenousdesensitization(e.g.parenteral antibiotics,chemotherapy)


DRUG ALLERGY: Management – Type I

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OR





ClassificationofAdverseDrugReactionsAllunintendedpharmacologiceffectsofadrug

Except:therapeuticfailures,intentionaloverdose,abuseofthedrug,orerrorsinadministration






OR








IgE Mediated(I)Cytotoxic(II)


OR




Solenskyetal.,DrugAllergyPracticeParameters,AnnAllergyAsthm Immunol 2010*usuallydosedependentandrelatedtotheknownpharmacologicactionsofthedrug


Classification:HypersensitivityReactions(HSRs)

Gell & Coombs• Type I: IgE-mediated (e.g. PCN anaphylaxis)• Type II: Antibody mediated (e.g. PCN-induced

hemolytic anemia)• Type III: Immune complex (e.g. amoxicillin serum

sickness)• Type IV: Cell mediated (e.g. amoxicillin

maculopapular rash)

Gell andCoombsed.ClinicalAspectsofImmunology.Oxford,England:Blackwell;1963.p.317-37.

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY: Classification

Non-ImmediateHypersensitivity

• Type II: Hemolytic anemia, neutropenia, thrombocytopenia

• Type III: Serum sickness: fever, rash (MC urticaria), joint pains, high inflammatory markers, low complement

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY – Type II - IV

Non-ImmediateHypersensitivity

• Type IV: Morbilliform (maculopapular) rash– Onset days into therapy– May have peripheral blood eosinophilia– Usually benign and self limited– Can “treat through” with monitoring– May not recur on subsequent exposures– Cross reactivity is of less concern

Mauri-Hellweg D,JImmunol 1996;157:1071-9.Padovan E,Eur JImmunol 1996;26:42-8.


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Non-ImmediateHypersensitivity• Organ specific reactions

• Immune-mediated nephritis• Including acute interstitial nephritis d/t Nafcillin, NSAIDs,

ciprofloxacin

• Immune-mediated hepatitis

• Severe Cutaneous Adverse Reactions (SCARs)• Drug Rash Eosinophilia and Systemic Symptoms

• Stevens-Johnson Syndrome/ Toxic Epidermal Necrolysis

• Erythema Multiforme


SevereCutaneousAdverseReactions(SCARs)• Drug Rash Eosinophilia and Systemic Symptoms

• High mortality (5-40%)• Clinical criteria, AEC > 1500/mL, rash, and systemic

involvement (fever, LAD, hepatitis, nephritis)• Anticonsulvants, antimicrobials, sulfasalazine, NSAIDs,

ACE inhibitors, Beta blockers, dapsone, allopurinol, azathioprine, diltiazem, methimazole, dobutamine

• Stevens-Johnson syndrome/toxic epidermal necrolysis• Mucous membrane involvement• Mortality 5-40%• Causative agents: allopurinol, antiepileptics, NSAIDs,

sulfa-containing antibiotics, and nevirapine


SpecificDrugReactions

DRUG ALLERGY

Jerschow JACI2014

•Beta-lactam antibiotics • Sulfonamide antibiotics• Radio contrast media• Aspirin/NSAIDs• ACE inhibitors

Antibiotics

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AntibioticsarewidelyusedinUnitedStates

• 4.2-5.7%ofoutpatientpopulationbetween1999to2012

• 50%ofinpatients

• penicillins andcephalosporins =• top2soldintheUnitedStates• 60%ofalltheantibacterialdrugmarket

KantorJAMA2015MagillJAMA2014http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM319435.pdf

ANTIBIOTICS

InaccuratePCNallergylabelà AdverseOutcomes

InpatientswithreportedPCNallergy

LongerStays10%moredaysinthehospital

20-30%moredrug-resistantinfections23%moreCdiff,14%moreMRSA,30%moreVRE

>90%arenotPCN-allergic

10-15%reportPCNallergy

PCNallergycanbeaddressedeasilyusingvalidateddiagnostictests

Albin AAP2014MacyJACI2014

Rolensky JACIPractice2015BlumenthalCID2015

ANTIBIOTICS: penicillin

AdaptedfromDr.AleenaBanerjiANTIBIOTICS: penicillin AdaptedfromDr.AleenaBanerjiANTIBIOTICS: penicillin

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TheCostProblemofPenicillinAllergy• Total cost ofantibioticsprescribedforpatients

with penicillin allergy was1.82-2.58-foldhigherthanforfirst-lineantibiotics

• Duringin-hospitaltreatment,themeanantibioticcostforpenicillin-allergicpatientswas63%higher

• Caseswithpenicillin"allergy"averaged0.59(CI,0.47-0.71)moretotalhospitaldaysduring20monthsoffollowup

Lietal.,JClin Pathol 2014Sadeetal.Clin Exp Allergy2003Macyetal.,JAllergyClinImmunol 2014Solensky,JAllergyClinImmunol 2014

AdaptedfromDr.AleenaBanerjiANTIBIOTICS: penicillin

PCNAllergyEvaluation

• Gradedchallenge(testdose)withpenicillinantibiotic(amoxicillin)isgoldstandard

• Skintesting• reducesnumberofpositivetestdoses

• Serum-specificIgE notaccurate

MacyCurr Opin AllergyClin Immunol 2015MacyAAAI2010


PCNSkinTestinghasaNPV>95%

©2011UpToDate®

95%

Pre-Pen

Pre-pen


PCNSkinTestingPerformedwithPCN&PCNG

• Only1morepositiveoralchallengeper3375individuals

• Positiveoralamoxicillinchallengesofequalorlessseveritythanfoodandaspirinchallenges

PRO(useminordeterminants) CON(minordeterminantsnotneeded)

MacyJACIPractice2013Solensky andMacyJACIPractice2015


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Aminopenicillins:UniqueR-groupSideChains

• AmoxicillinoralchallengeidentifiespatientssensitizedonlytominordeterminantsorRgroupsidechain

RomanoAllergy2009


PenicillinAllergyReferrals

• Any patient with penicillin allergy can benefit• Patients who specifically benefit include

patients with:• Recurrent infections/hospitalization • Current or past infection where best therapy

includes a beta-lactam • Planned surgical procedure where a beta-

lactam antibiotic is the drug of choice • Upcoming chemotherapy or transplantation

AdaptedfromAAAAITeachingSlidesANTIBIOTICS: penicillin

AdaptedfromDr.AleenaBanerjiANTIBIOTICS: penicillin

PCNSkinTestingisCost-effective

Item $AnnualsalaryofRNwhocanperform8PCNallergytestsper8-hourshift

$118,000

Doseofpenicilloyl-poly-lysine(Pre-Pen)

$69.00

Amoxicillin250-mgtablet $0.12

Allothernecessarysupplies $3.25

Totalperpatient $131.37

Rimawi JHopMed2013;8:341-345MacyJACI2014

PCNallergytestingof146inpatients

Acuteantibioticcosts• $32,811

($225/patient)reductionover5months

• $82,000annualestimateddifference


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PCNSkinTestingisCost-effective• Total cost ofantibioticsprescribedforpatients

with penicillin allergy 1.82-2.58-foldhigherthanforfirst-lineantibiotics

• Inpatient:meanantibioticcostforpenicillin-allergicpatientswas63%higher

• Caseswithpenicillin"allergy"averaged0.59(CI,0.47-0.71)moretotalhospitaldaysduring20monthsoffollowup

Lietal.,JClin Pathol 2014Sadeetal.Clin Exp Allergy2003Macyetal.,JAllergyClinImmunol 2014Solensky,JAllergyClinImmunol 2014EstimatedcostofPCN

skintesting51,582patientswithPCN

“allergy”

$6.8million

Estimatedsavingsfromshorteninghospitalstayby0.59daysperpatient

$64.6million<<ANTIBIOTICS: penicillin

NeedforImprovedEHRAllergyDocumentation

Rimawi JHopMed2013;8:615-618

36%(20/55)patientshadPCNallergyre-documented-age,long-termcarefacility,alteredmentalstatus,dementia-


GuidelineBasedEvaluationofPCNAllergy• Guidelinetoassistproviders

withassessing allergy historyandprescribingantibioticsforpatientswithreportedpenicillinorcephalosporin allergy

• Usedastandard2-stepgradedchallengeortestdose

• Comparedtreatment21monthsbeforeguidelineimplementationwith12monthsafterguidelineimplementation

Blumenthaletal.,AnnAllergyAsthmaImmunol 2015


GuidelineBasedEvaluationofPCNAllergy:Outcomes

• Almost7-foldincreaseinthenumberoftestdosestoβ-lactams

Blumenthaletal.,AnnAllergyAsthmaImmunol 2015

Significantlydecreasedtreatmentwithalternativeantibiotics

Vancomycin 68à 37%Aztreonam 12à 1%Aminoglycosides6à 1%Fluoroquinolones 15à 3%

Nodifferenceinadversedrugreactions


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CephalosporinAllergy

©2015UpToDate®Pichichero AAAI2014

ANTIBIOTICS: cephalosporin

RomanoAJAllergyClin Immunol.2015Apr27.[Epub aheadofprint]MacyEJAllergyClin Immunol.2014;133(3):790-6

MacyEJ.AllergyClin.Immunol.135,745–52(2015).Pichichero,M.Pediatrics115,1048–57(2005).

• Hypersensitivity occurs in 0.0001-3% of administrations

• R group side chain is major factor for cross-reactivity between PCN and cephalosporins

Cephalosporin:Cross-reactivitywithPCN

Pichichero AAAI2014Campagna JEM2012Pichichero DiagnosticMicrobiologyandInfectiousDisease2007GaetaFJAllergyClin Immunol 2015;135(4):972-6RomanoAAllergy2013;68(12):1618-21Solensky RAnnAllergyAsthmaImmunol.2010;105(4):259-73.

Patientselectivelyallergictoaminopenicillins shouldavoidcephalosporins withcommonRgroupsidechain

ANTIBIOTICS: cephalosporin

• ~2% cross reactivity between PCN and 1st

generation oral cephalosporins

• <1% for PCN and 2nd/3rd/4th generation cephalosporins

Cross-reactivitybetweencephalosporinsBasedonSideChainSimilarity

ANTIBIOTICS: cephalosporinPichichero DiagnosticMicrobiologyandInfectiousDisease2007

PCNCross-reactivitywithCarbapenems andAztreonam

• <1%ofPCN-allergicpatientsreacttocarbapenem

• PCN-allergicpatientstolerateaztreonam

• Ceftazidime cross-reactswithaztreonam

©2015UpToDate®KulaCID2014GaetaJACI2015Patriarca 2008Perez-Pimiento1998

ANTIBIOTICS: beta-lactam

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SulfonamideAntibiotics• Reported in 1.5-3% of patients

• Often cause minor Type IV reactions • Most common cause of Steven Johnson Syndrome/Toxic

Epidermal Necrolysis

• Patients with a sulfonamide antibiotic allergy may be safely prescribed other medications from the non-antibiotic sulfonamide class of drug

• No validated skin testing available

StromBNEnglJMed.2003;349(17):1628-35Solensky RJAllergyClin Immunol.2014Mar;133(3):797-814

AdaptedfromAAAAITeachingSlidesANTIBIOTICS: sulfonamide

Radiocontrast Media(RCM)

IodinatedContrastMediaWidelyUsed• Millionsofstudies/year

• Reactionrate:13%à 3-5%withlow-osmolar contrast

• Riskfactors• 20– 50yearsofage• Historyofpriorreactions• Comorbidities

• Cardiovasculardisease• Asthma• Atopy

• β-blockeruseACRGuidelines2013Katayama1990Kelly1978BushAJR1991Shehadi 1975,1982Lang1993

RADIOCONTRAST MEDIA

RiskFactorsforContrastReactionsRiskFactor Whatisaffected? Numbers

Age:20-50yearsold Anyreaction 15-18%reactionrate

Historyofpriorreaction Anyreaction 17-35%reactionrate

Comorbidities

Cardiovasculardisease Life-threateningreaction OR7.71;95%CI1.04-57.23

Asthma Any reaction OR8.74;95%CI 2.36-32.35

Reactionwithbronchospasm OR 16.39;95%CI 4.30-62.46

Atopy

Anyfoodallergy Anyreaction ≈2timesmorelikely

General allergy Anyreaction ≈4timesmorelikely

β-blockeruse

Overall Reactionwithbronchospasm OR3.73;95%CI1.18-11.75

In heartdisease Reactionwithbronchospasm OR 15.75;p=.023

#priorcontrastexposures

≥5exposures Hypotension P <0.05

≥10exposures Hazardofoverallreaction

RADIOCONTRAST MEDIA

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The‘iodine/seafoodallergy’MythOsbornetreatssyphiliswithiodine-containingcompoundsà noticesurineisradio-opaque

1920

1923:Firstpyelogram

performedatMayoClinic

DolanJAMA1940Goldburgh JAMA19422deathsfollowingthe

intravenoususeofdiodrast

1983:Girard&Gambaiodineandseafoodsensitizepatientsto

contrast

1980

Stukus AAAI2015KaufmanEJIM2014Quader 2000

1940

Studiesestablishthat‘iodineallergy’

doesnotsensitize

patientstoRCM

2015:86%physiciansatacademicmedicalcentersincorrectlythinkiodineandseafoodsensitizepatientstocontrast

RADIOCONTRAST MEDIA

RCM:Pathophysiology

• Allergic-Like• Directeffectonmastcellsandbasophils• Direct/indirectactivationofcomplement,coagulation,fibrin,andkinin pathwaysà releaseofhistamine,fibrin-splitproducts,bradykinin

• Antigen-antibodyinteraction?

• Physiologic– hyperosmolarity

BushAJR1991

RADIOCONTRAST MEDIA

Low-osmolar Non-ionicHasLowerReactionRatesComparedToHigh-osmolar IonicContrast

RADIOCONTRAST MEDIABushAJR1991

PremedicationPreventsRecurrentReactions

• UseVisipaque dye(nonionic,iso-osmotic)

• Prednisone50mgevery6hoursfor3doses(13hours,7hours,and1hourbeforeRCM)

• Benadryl50mg1hourbeforeRCM

RADIOCONTRAST MEDIA

BushAJR1991

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RiskFactorsforBreakthroughReactions(BTR)

FreedAJR2001DavenportRadiology2009

AllergicRhinitisand FoodAllergyassociatedwith higherBTRrates

DrugAllergy,ChronicOralSteroids,SevereAllergies,Allergyto4+allergensincreasesriskofmoderate/severeBTR

RADIOCONTRAST MEDIA

MajorityofBTRsSame/MilderSeverityComparedtoInitialReaction

Reference

#breakthroughreactions(BTR)

PretreatmentRegimen %of BTRmoreseverethaninitialreaction

(#severereactions)Freed2001

(n=53)

• Prednisone20mgp.o. every6hoursfor 5dosesbeforeRCM 11%

(0severe)

Davenport2009

(n=128)

• Prednisone50mgp.o. every6hoursfor3dosesbeforeRCM

• Benadryl50mg1hourbeforeRCM

8%(1severe)

Bae 2013

(n=27)

• Hydrocortisone 200mgi.v. 1hourbeforeRCM

• Chlorpheniramine 4mgi.v./i.m.1hourbeforeRCM

5%(1severe)

RADIOCONTRAST MEDIA

<1%patientshavesevereBTR

ContrastReactions:Take-homePoints

• Initialreactionrate3-5%withlow-osmolar contrast

• Riskfactors• Priorreactions,heartdisease,asthma,atopy,β-blockeruse

• Premedication• UseVisipaque dye(nonionic,iso-osmotic)• Prednisone50mgevery6hoursfor3doses(13hours,7

hours,and1hourbeforeRCM)• Benadryl50mg1hourbeforeRCM

RADIOCONTRAST MEDIA

SpecificDrugHypersensitivities

DRUG ALLERGYJerschow JACI2014

• NSAIDs• ACE inhibitors

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NSAIDReactions

• 25-30% of patients taking NSAIDs• 0.5% to 5.7% in the general population

• Allergic Reactions• Pseudo-allergic Reactions

Solensky RJAllergyClin Immunol.2014Mar;133(3):797-814

AdaptedfromAAAAITeachingSlidesNSAIDs

NSAIDReactions

• Mechanism:IgE-mediated• InducedbyasingleNSAID

• Mechanism: COX enzyme inhibition

• Induced by class of NSAIDs

• Most patients tolerate acetaminophen and selective COX-2 inhibitors (e.g. celecoxib)

AllergicNSAIDReactions Pseudo-allergicReactions

Solensky RJAllergyClin Immunol.2014Mar;133(3):797-814

Pseudo-allergicReactions

Type1– asthmaandrhinosinusitis

Type2– urticaria/angioedemainpatientswithchronicurticaria

Type3– urticaria/angioedemainotherwiseasymptomaticindividuals

NSAIDs

ACEInhibitorReactions• Angioedema occurs in 0.1% to 0.7% of patients

treated with ACE inhibitors• 4 to 5- fold higher risk in African Americans, females, and

older age• most common cause of angioedema seen in the hospital and

emergency room

• Usually presents as angioedema of the face and neck (throat, tongue, lips, eyes)

• Bradykinin-mediated à therapies targeting bradykinin pathway (like Firazyr) are useful

BanerjiAAnnalsAllergyImmunol 2008;Apr;100(4):327-32Sondhi DChest2004Aug;126(2):400-4

WarnerKAnnPharmacother.2000Apr;34(4):526-8.Agah GIntensiveCareMed1997Jul;23(7):793-6.

AdaptedfromAAAAITeachingSlidesACE Inhibitors

PhotocourtesyofDr.DavidKhan7/28/2015


ACEInhibitorAngioedema

ACE inhibitors

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DrugAllergySpecialTestingClinic• 5HT3ReceptorAntagonists• Anesthetic

• General&Local• Antibiotics

• Aminoglycosides• Bactrim• Beta-Lactams• Cephalosporins• Clindamycin• Metronidazole• Macrolides• Quinolones• Vancomycin

• BenzylAlcohol• Chemotherapy• Disinfectant/Antimicrobial• Diuretics

• Immunomodulators• Glatiramer Acetate

• H2Blockers• Heparins• Insulin• IronSalts• IVContrastAgents• MonoclonalAntibodies• OphthalmicAgents• Polyethyleneglycol• Progesterone• ProtonPumpInhibitors• Steroids• VitaminB12• Vaccines• Xolair

DRUG ALLERGY

KeyTake-HomePoints• Hypersensitivity reactions are a small subset of

adverse drug reactions

• If allergy is suspected, a careful drug allergy history and physical exam is the best next step and can usually help to distinguish between HSRs that are common or severe

• Skin testing, challenges/test doses, and desensitization can be performed by allergists to help in the diagnosis and treatment

AdaptedfromAAAAITeachingSlidesDRUG ALLERGY

DRUG ALLERGY

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