Drug AllergyDrug Allergy

HSJHSJ

19/09/201119/09/2011

BSACI GuidelinesBSACI Guidelines

�� DefinitionsDefinitions

�� MechanismsMechanisms

�� Clinical FeaturesClinical Features

�� Risk factorsRisk factors

�� DiagnosisDiagnosis

�� InvestigationsInvestigations

�� Criteria for referral/InvestigationCriteria for referral/Investigation

MirakianMirakian et al. et al. ClinClin Exp All 2008 ; 39: 43Exp All 2008 ; 39: 43--6161

DefinitionsDefinitions

ADR = Adverse drug reactionADR = Adverse drug reaction

ADE = Adverse drug event (ADE = Adverse drug event (ieie prscriptionprscription error)error)

ADR ADR –– Type A Type A

�� may affect anyone may affect anyone –– ‘‘Side EffectSide Effect’’

�� PhysiologicalPhysiological

ADR ADR –– Type BType B

�� Affects only susceptible individuals Affects only susceptible individuals –– ‘‘AllergyAllergy’’

�� ImmunologicalImmunological

�� NonNon--immune immune egeg geneticgenetic

Mechanisms Mechanisms -- ImmunologicalImmunological

Type IType I

�� IgEIgE--mediated, immediate, mediated, immediate, egeg PenicillinPenicillin

�� anaphylaxis, anaphylaxis, urticariaurticaria, , brochospasmbrochospasm etcetc

Type IIType II

�� IG IG –– mediated mediated cytotoxiccytotoxic egeg HeparinHeparin

�� Anaemia, Anaemia, cytopeniacytopenia

Type IIIType III

�� IG IG –– mediated immune complexes mediated immune complexes egeg ACEI, ACEI,

alllopurinolalllopurinol

�� VasculitisVasculitis, fever, LN, , fever, LN, arthropathyarthropathy, serum sickness, serum sickness

Type IVType IV

�� T Cell driven, variety of T Cell driven, variety of effectoreffector mechanismsmechanisms

�� Inc Inc monocytesmonocytes, , eosinophilseosinophils, CD8 cells, , CD8 cells, neutrophilsneutrophils

�� Contact Dermatitis Contact Dermatitis egeg NeomycinNeomycin

�� Classical Classical MaculopapularMaculopapular Drug eruption Drug eruption egeg PenicillinPenicillin

�� PustularPustular ExanthemExanthem (AGEP) (AGEP) egeg ItraconazoleItraconazole

�� BullousBullous eruptions eruptions egeg TEN, StevensTEN, Stevens--Johnson Johnson

syndrome syndrome egeg sulphonamidessulphonamides

Mechanisms Mechanisms -- ImmunologicalImmunological

OrganOrgan--specificspecific

LungLung

�� AsthmaAsthma NSAIDNSAID

�� CoughCough ACEACE

�� Interstitial Interstitial pneumonitispneumonitis MTXMTX

�� EosinophiliaEosinophilia NSAIDNSAID

�� Organising PneumoniaOrganising Pneumonia AmiodaroneAmiodarone

LiverLiver

CholestasisCholestasis, Hepatitis, Hepatitis

RenalRenal

Interstitial nephritisInterstitial nephritis

SystemicSystemic

�� AnaphylactoidAnaphylactoid

�� Serum sicknessSerum sickness

�� LupusLupus--likelike

�� DRESS DRESS –– drug rash with drug rash with eosinophiliaeosinophilia systemic systemic

symptoms symptoms egeg anticonvulsantsanticonvulsants

�� TENTEN

�� SJSSJS

SkinSkin

�� Urticaria/AngioedemaUrticaria/Angioedema

�� MaculopapularMaculopapular rashrash

�� Contact DermatitisContact Dermatitis

�� PhotodermatitisPhotodermatitis egeg tetracyclinetetracycline

�� AGEP AGEP –– Acute generalised Acute generalised exenthamatousexenthamatous pustulosispustulosis

�� FDE FDE –– fixed drug eruptionfixed drug eruption

�� ErythemaErythema MultiformeMultiforme

History TakingHistory Taking

�� Detailed Detailed decsriptiondecsription of reactionof reaction

•• Symptom sequence and durationSymptom sequence and duration

•• Treatment, outcomeTreatment, outcome

•• Witness Witness desriptiondesription

•• Photos, compare to reference imagesPhotos, compare to reference images

�� Timing of Timing of symtomssymtoms in relation to drug administrationin relation to drug administration

�� How long had the drug been taken for?How long had the drug been taken for?

�� Had the drug been taken previously?Had the drug been taken previously?

�� Drugs of similar class taken previously?Drugs of similar class taken previously?

�� Indication for drugIndication for drug

�� Other drugs taken (inc OTC and complimentary)Other drugs taken (inc OTC and complimentary)

�� PrevPrev drug allergydrug allergy

�� Other allergic conditionsOther allergic conditions

InvestigationInvestigation

�� Use known mechanisms, especially Use known mechanisms, especially IgEIgEmediationmediation

�� Many reactions need no further Many reactions need no further investigation, investigation, espesp organ specific and nonorgan specific and non--immuneimmune

�� Contraindicated in certain severe reactions Contraindicated in certain severe reactions ((egeg TEN)TEN)

�� Depends on clinical contextDepends on clinical context

�� EgEg In penicillin In penicillin alllergyalllergy, indicated where:, indicated where:•• Reaction occurred when on multiple drugs Reaction occurred when on multiple drugs egeg GAGA

•• Allergy to multiple antibiotics, Allergy to multiple antibiotics, espesp if chronic if chronic diseasedisease

•• Absolute indication for penicillin Absolute indication for penicillin egeg splenectomysplenectomy

�� Serum Serum tryptasetryptase, acute and baseline, acute and baseline

�� RAST (specific RAST (specific IgEIgE))

�� Skin prick testingSkin prick testing

�� IntradermalIntradermal skin testingskin testing

�� Patch testingPatch testing

�� Delayed Delayed intradermalintradermal testtest

�� BasophilBasophil release assaysrelease assays

�� Oral provocation test Oral provocation test –– Gold standardGold standard

•• With index drug to confirm/refute diagnosisWith index drug to confirm/refute diagnosis

•• With alternative/related drug to define safe alternative With alternative/related drug to define safe alternative

InvestigationInvestigation

Accuracy of HistoryAccuracy of History

�� CaubetCaubet et al. J Allergy et al. J Allergy ClinClin ImmunolImmunol 20102010

�� 88 children labelled as allergic to Penicillin, on basis 88 children labelled as allergic to Penicillin, on basis

of delayed onset of delayed onset urticariaurticaria or or maculopapularmaculopapular rashrash

�� All underwent detailed workAll underwent detailed work--upup

�� 11 had positive 11 had positive intradermalintradermal testtest

�� 2 had positive RAST2 had positive RAST

�� 6 had positive oral challenge test (6.8%) 6 had positive oral challenge test (6.8%)

�� 65% of OCT 65% of OCT negneg children had positive viral studychildren had positive viral study

�� Conclusion Conclusion –– BB--lactamlactam allergy is clearly allergy is clearly

overdiagnosedoverdiagnosed in childhood infective illness, only in childhood infective illness, only

confirmed in 6.8%confirmed in 6.8%

Importance of Challenge testImportance of Challenge test

�� Torres et al, Torres et al, ClinClin Exp Allergy 2002; 32 (2): 270Exp Allergy 2002; 32 (2): 270--276276

�� 300 pt with good 300 pt with good hxhx of penicillin allergyof penicillin allergy

�� 241 had positive result on SPT, IDT or RAST241 had positive result on SPT, IDT or RAST

�� 89 patients negative on all tests, underwent OCT89 patients negative on all tests, underwent OCT

�� 49 developed immediate allergic reaction49 developed immediate allergic reaction

•• 22 penicillin, 27 amoxicillin22 penicillin, 27 amoxicillin

�� ConcConc –– skin tests and Specific skin tests and Specific IgEIgE are are insufficentinsufficent to to

exclude diagnosis of penicillin allergyexclude diagnosis of penicillin allergy

CephalosporinsCephalosporins

�� XX--reactivity (with Pen) does exist, but is exaggeratedreactivity (with Pen) does exist, but is exaggerated

�� 44--10%10%

�� Greater with early generation Greater with early generation cephscephs

�� Usually predicted by side chain homologyUsually predicted by side chain homology

•• EgEg amoxicillin with amoxicillin with cefaclorcefaclor, , cephalexincephalexin, , cefadroxilcefadroxil

•• Not Not cefiximecefixime, , cefuroximecefuroxime, , ceftraxoneceftraxone

�� Usual testing protocols can be usedUsual testing protocols can be used

�� OCT is reasonable for a patient with Pen allergyOCT is reasonable for a patient with Pen allergy

Female, 42, ? Penicillin AllergyFemale, 42, ? Penicillin Allergy

After 1 tab After 1 tab amoxylamoxyl, tongue/throat swelling, lips, ears, tongue/throat swelling, lips, ears

Collapse, given adrenalineCollapse, given adrenaline

Had Had amoxycillinamoxycillin several times beforeseveral times before

2 months later stroked cat (on antibiotics) 2 months later stroked cat (on antibiotics) –– lip/eye swelling, lip/eye swelling, itch faceitch face

? Will react to traces in hospital? Will react to traces in hospital

RAST RAST –– Penicillin Penicillin –– negneg

SPT SPT –– NegNeg –– Major and Minor determinantsMajor and Minor determinants

Strong Positive Strong Positive –– AmoxycillinAmoxycillin –– proximal tracking, systemic proximal tracking, systemic itchitch

Diagnosis Diagnosis –– Severe Allergy Severe Allergy AmoxycillinAmoxycillin, reaction to trace , reaction to trace quantitiesquantities

Drug AllergyDrug Allergy

ConclusionsConclusions

�� A history of penicillin allergy is common and can limit A history of penicillin allergy is common and can limit

treatment optionstreatment options

�� If in doubt, donIf in doubt, don’’t givet give

�� Accurate history is crucialAccurate history is crucial

�� Diagnosis is confirmed on objective testing in 10Diagnosis is confirmed on objective testing in 10--

20% of cases, increasing where history is more 20% of cases, increasing where history is more

recent and more convincingrecent and more convincing

�� Testing indicated in defined clinical scenariosTesting indicated in defined clinical scenarios

�� Testing protocol should involve RAST, SPT, IDT, OCTTesting protocol should involve RAST, SPT, IDT, OCT

Drug AllergyDrug Allergy

Female, 46, ? Anaphylaxis during GA, further surgery Female, 46, ? Anaphylaxis during GA, further surgery neededneeded

2008 2008 –– Obstruction (slipped gastric band)Obstruction (slipped gastric band)

Severe anaphylaxis after induction Severe anaphylaxis after induction –– larngeallarngeal oedema, oedema, hypoensionhypoension, , bradycardiabradycardia, raised airway pressures. , raised airway pressures. TryptaseTryptase 3636

ThiopentoneThiopentone, , FentanylFentanyl, , SuxamethoniumSuxamethonium, Colloid, Colloid

Hay fever, cat allergyHay fever, cat allergy

SPTsSPTs –– Negative (neat, 1/10) all except Negative (neat, 1/10) all except vecuroniumvecuronium, , SuxSux neatneat

IntradermalIntradermal testing testing –– SuxSux strong positive, strong positive, Pancuronium/RocuroniumPancuronium/Rocuronium also positive. also positive. AtrocuriumAtrocuriumnegativenegative

Diagnosis Diagnosis –– SuxamethoniumSuxamethonium allergy, cross sensitivityallergy, cross sensitivity

Male, 56, dramatic anaphylaxis during anaesthesia for hernia Male, 56, dramatic anaphylaxis during anaesthesia for hernia at private hospital. Transferred ITU. Max at private hospital. Transferred ITU. Max tryptasetryptase 9292

FentanylFentanyl, , propofolpropofol, , dexdex, , ondansetronondansetron, , vecuroniumvecuronium

AugmentinAugmentin, Morphine , Morphine –– hypotension, hypotension, urticariaurticaria, , bronchospasmbronchospasm

No No h/oh/o atopyatopy or penicillin allergyor penicillin allergy

SPT/IDT negative for NMBA, SPT/IDT negative for NMBA, FentFent, , propofolpropofol, , AugmentinAugmentin, Pen , Pen MajMaj and minor determinants, Latex, and minor determinants, Latex, ChlorhexidineChlorhexidine, Colloid, Colloid

RAST penicillin RAST penicillin –– negativenegative

Baseline Baseline tryptasetryptase 20.620.6

Diagnosis Diagnosis -- ? Isolated systemic ? Isolated systemic mastocytosismastocytosis. Anaphylaxis ? . Anaphylaxis ? Morphine ? Morphine ? augmentinaugmentin

Drug AllergyDrug Allergy

Female, 42, ? Penicillin AllergyFemale, 42, ? Penicillin Allergy

After 1 tab After 1 tab amoxylamoxyl, tongue/throat swelling, lips, ears, tongue/throat swelling, lips, ears

Collapse, given adrenalineCollapse, given adrenaline

Had Had amoxycillinamoxycillin several times beforeseveral times before

2 months later stroked cat (on antibiotics) 2 months later stroked cat (on antibiotics) –– lip/eye swelling, lip/eye swelling, itch faceitch face

? Will react to traces in hospital? Will react to traces in hospital

RAST RAST –– Penicillin Penicillin –– negneg

SPT SPT –– NegNeg –– Major and Minor determinantsMajor and Minor determinants

Strong Positive Strong Positive –– AmoxycillinAmoxycillin –– proximal tracking, systemic proximal tracking, systemic itchitch

Diagnosis Diagnosis –– Severe Allergy Severe Allergy AmoxycillinAmoxycillin, reaction to trace , reaction to trace quantitiesquantities

Drug AllergyDrug Allergy

Male 63, Surgical referral ? Male 63, Surgical referral ? CholecystitisCholecystitis

RUQ pain, vomiting, feverRUQ pain, vomiting, fever

PMH PMH –– nilnil

Penicillin Allergy recorded on GP letter summaryPenicillin Allergy recorded on GP letter summary

Mild Mild angioedemaangioedema many years previouslymany years previously

Rx IV Rx IV AugmentinAugmentin

Pt denied recollection of allergy when asked by Dr and Pt denied recollection of allergy when asked by Dr and

NurseNurse

Fatal anaphylactic reactionFatal anaphylactic reaction

AngioedemaAngioedema/Anaphylaxis/Anaphylaxis

Female, 38 ? Allergy to steroidsFemale, 38 ? Allergy to steroids

KenalogueKenalogue intra intra articulararticular –– 2 hours, itch/swelling upper 2 hours, itch/swelling upper lip, throat tightness. OK previously with lip, throat tightness. OK previously with depomedronedepomedrone

Severe hip pain Severe hip pain –– keen on further steroid injectionkeen on further steroid injection

Mild HF, penicillin allergyMild HF, penicillin allergy

SPT SPT –– negative (neat, 1/10) negative (neat, 1/10) depomedronedepomedrone, , kenaloguekenalogue

IDT IDT –– negative to bothnegative to both

I/M challenge I/M challenge –– kenaloguekenalogue –– positivepositive

I/M challenge I/M challenge –– depomedronedepomedrone –– negativenegative

Diagnosis Diagnosis –– Allergy Allergy KenalogueKenalogue ? Steroid component ? ? Steroid component ? excipientexcipient

Drug AllergyDrug Allergy

Drug AllergyDrug Allergy

�� 42 year old female42 year old female

�� Very bad painful teeth, infectedVery bad painful teeth, infected

�� Not been to dentist many yearsNot been to dentist many years

�� PrevPrev told by dentist could not have LAtold by dentist could not have LA

�� When in teens, several episodes of collapse, LOC When in teens, several episodes of collapse, LOC after LAafter LA

�� SPT negative SPT negative –– LignocaineLignocaine, , bupivicainebupivicaine

�� IDT, serial dilutions, negativeIDT, serial dilutions, negative

�� SubcutSubcut challenge test, challenge test, ¼¼ full dose full dose –– negativenegative

�� No evidence of LA allergyNo evidence of LA allergy