An approach to the Diagnosis of an Allergy Binder... · e.g. infections, autoimmunity,...
Transcript of An approach to the Diagnosis of an Allergy Binder... · e.g. infections, autoimmunity,...
Pollen
Nuts
Eggs
Cat
Mould
Milk
Drug Allergy
Fish
Wheat
Peanut
An approach to the Diagnosis of an Allergy
Your consulting pathologistsPR0520005200431www.ampath.co.za
AN APPROACH TO DRUG ALLERGY
AN APPROACH TO DRUG ALLERGY DIAGNOSIS - MADE EASY WITH A FLOW DIAGRAM
HISTORY COMPATIBLE WITH DRUG ALLERGY
POS
IMMEDIATE
NEG POS
NEG POS
DRUG IMPORTANT?PROVOCATION POSSIBLE?
REFER TO SPECIALIST
YES
DRUG PROVOCATION
NO AVOIDANCE
NEG
SPT DRUGINTRA-DERMAL TEST
ImmunoCap® CAST
• AVOID• EDUCATE• DOCUMENT
NO
POS
DELAYED
NEGPOS
NEGPOS
DRUG IMPORTANT?PROVOCATION POSSIBLE?
REFER TO SPECIALIST
DRUG PROVOCATION
NO AVOIDANCE
NEG
SPT DRUGPATCH TEST
INTRA-DERMAL TEST
CASTMELISA
• AVOID• EDUCATE• DOCUMENT
NOYES
DRUG ALLERGY CONFIRMED
• AVOID• EDUCATE• IDENTIFY SAFE ALTERNATIVE
YES
TIMING OF REACTION
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AN APPROACH TO DRUG ALLERGY
•Whentestingforpenicillinallergy,patientsshouldbetestedtothepenicillinring,major andminordeterminantsandrelevantside-chains.•Abetalactamringisalsofoundincephalosporins(2-5%penicillincross-reactivity), carbapenems(1%penicillincross-reactivity)andmonobactams(nocross-reactivity)•Quinolonesfrequentlycausedrugallergyandcross-reactswithotherquinolones.•Macrolidesdon’toftencauseallergiesandcross-reactivitybetweenmacrolidesis uncommon.•NSAIDallergyiscommon.Aspirin,diclofenacandibuprofenarethebestindicatorsof NSAIDallergy.PleasedistinguishbetweenAspirinallergyandAspirinexacerbated respiratorydisease,wherecox-inhibitionleadstogreatlyinducedleukotrineproduction. Thisisnotatrueallergyandpatientsmaypresentwithnasalpolypsandasthma.•Localanaestheticallergyiscommon,butpatientsmaytolerate1/morealternatelocal anaesthetics.•Radiocontrastmediumallergyiscausedbyanimmunologicalreactiontoquaternary iodinecomponents.Thisdoesnotcross-reactwithiodatedtablesaltorseafood.
CLINICAL PEARLS
AN APPROACH TO ECZEMA AND DERMATITIS
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FOOD ALLERGENS
ECZEMA
INFANT: Pruritic, red scaly and crusty lesions on cheeks, scalp and exterior surfaces
CHILDREN AND ADULTS: Plaques in the flexure areas, especially antecubital and popliteal fossea, volar aspects of wrists, ankles and neck
USUAL DISTRIBUTION
IF NEGATIVE
• Consider food challenge• Consider different mechanism: CAST - foods - contact aero-allergens (pets, house dust mite) - latex - colourants and preservatives MELISA - Foods - contact aero-allergens - metals
• Consider other eczematous disorders - Seborrheic dermatitis - Drug reations - Scabies - Hyper IgE syndrome - Wiscott Aldrich - Nutritional Deficiency
UNUSUAL DISTRIBUTION
PATCH TESTING - European baseline, cosmetic, hairdressing or sunscreen series.MELISA TESTING - Metals (i.e. gold, nickel, platinum, mercury) - Latex
Also consider skin prick testing or lgE testing to inhalants including pollens and
moulds
• Pet allergens• House dust mite• Latex IgE (If exposed)
CONTACT ALLERGENS
FOOD ALLERGENS• SPT/ImmunoCap® food mix (milk, egg, wheat, peanuts, cod)
+
IF HISTORY OF ASTHMA/ALLERGIC RHINITIS
AN APPROACH TO ECZEMA AND DERMATITIS
•Patientswitheczemahaveanintrinsic/impairedskinbarrierdefect,butallergenexposure causesflaresinatopicpatients.•Commonallergensarefoodallergensorcontactinhalantallergenslikedustmiteor animaldanders.•PatientswithveryhighIgElevels,asiscommonlyseeninatopiceczema,canleadto multiplepositiveallergytests(cross-reactivityandnon-specificbinding).AnISACtestis notinfluencedbynon-specificbindingandcanidentifycross-reactivity,thereforeis recommendedinthesepatients.•Patientswithanunusualdistributionoftheirrashshouldbeinvestigatedforcontact dermatitits(patchtesting).
CLINICAL PEARLS
THE FOLLOWING FLOW-DIAGRAMS ASSISTS WITH AN APPROACH TO ACUTE AND CHRONIC URTICARIA:
ACUTE URTICARIA FLOW-DIAGRAM:
CHRONIC URTICARIA FLOW-DIAGRAM:
Underlying disease?
Drug allergy testing Investigate and treat disease
Recent acute infection?
Symptomatic treatmentAvoidance Consider Challenge
Positive Negative
• SPT/Specific IgE• CAST
YES
Recent Drug?
NO
• Treat symptomatically. • If no resolution, investigate as for chronic urticaria
PHYSICAL URTICARIANO UNUSUAL FEATURES
• SKIN BIOPSY (HISTOLOGY)
• INVESTIGATIONS TO DETERMINE CAUSE
URTICARIAL VASCULITIS
LABORATORY INVESTIGATES TO IDENTIFY UNDERLYING /TREATABLE MEDICAL CONDITIONS
• IDENTIFY BY CHALLENGE TESTING
• IF COLD URTICARIA DO CRYOGLOBILINS
AN APPROACH TO URTICARIA
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OBVIOUS REACTION TO FOOD/FOOD ADDITIVE
ACUTE URTICARIA
• HISTORY• APPEARANCE OF LESIONS
CHRONIC URTICARIA
AN APPROACH TO URTICARIA
•Urticariamaybetriggeredbymultiplefactorsingeneticallysusceptibleindividuals, e.g.infections,autoimmunity,malignancies,hypersensitivityandphysicalorpsychological factors.•Allergyisrarely(5-10%)thecauseofchronicurticaria.•Themostcommonallergensimplicatedaredrugs,foods,colourantsandpreservatives.•Urticariaisitchy,notpainful.Itmaybeassociatedwithangioedema.•Suspiciousfeaturesofurticarialvasculitisispainfulornon-itchylesionsthatlast>24hours onthesamespotandhealwithbruisingorscarring.•Physicalurticariasincludedermatographism,delayedpressureurticaria,cholinergic urticaria,aquagenicurticariaandvibrationalurticariaandshouldbediagnosedfromclinical history.
CLINICAL PEARLS
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Associated urticaria
Investigate as chronic urticaria
? ACE inhibitors? Statins? NSAIDS? PPI
Trial of substitution/ discontinuation of drug
drugsC1 inhibitorC4 levels
Positive family or history of onset at a young age No family history/ later onset
HISTORY OF ONSET, FAMILY HISTORY
AN APPROACH TO ANGIOEDEMA
FBC and Diff + ESRANA, ds DNA, ENAC4C1qIgG, A, MProtein electrophoresis B2 microglobulinUrinary Bence-Jones proteinsExamine for lymphadenopathy/ splenomegalyConsider chest/ abdominal CT
AN APPROACH TO ANGIOEDEMA
•Angioedemaisnotitchy,but“tingly”,burningorpainful.•Ifurticaria/itchisprominent,investigateandmanageasforurticaria.•Hereditaryangioedema(HAE)usuallypresentsearlyorwithapositivefamilyhistory.•AngioedemawithurticariaisnotHAE.•ThemostcommoncauseofangioedemainadultsisACEinhibitorsorNSAIDS.•Angioedema(withouturticaria)isnotanallergyandpatientsshouldbeinvestigatedfor anunderlyingdisease,.e.g.autoimmunityormalignancy.
CLINICAL PEARLS
AN APPROACH TO THE DIAGNOSIS OF ANAPHYLAXIS
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ANAPHYLAXIS
•Mostcelltryptase(alwaysdo abaselineafter24hours)•C3,C4
•Repeatmastcelltryptase•SpecificImmunoCap®IgE/CAST dependingonhistory: • Venoms - Bee/Wasp • Foods - Nuts,seeds,legumes - Fishandshellfish - Egg -Milk - Anyfood,includingfruit,vegetables andadditives • Drugs - Antibiotics - Radiocontrastmedia - Analgesics - Anaestheticagents,especiallymuscle relaxants - Biologicals • Latex
Latertests(after2or3weeks)ImmediateTests
•Mastcelltryptaseisveryimportanttodiagnoseanaphylaxisandispositiveinanaphylactic (IgEmediated)andanaphylactoid(non-IgEmediated)reactions.•Alwaysdoabaselinetryptaselevelatleast24hourslater.•Donotinvestigatefortheanaphylaxistriggerwithin2-3weeksofthereactionas basophilsinCASTtestsmayhaveincreasedbackgroundactivationandIgEmaybe negativeduetoincreasedconsumption.•Considerco-factordependantanaphylaxise.g.wheatinduced–exercise–induced anaphylaxis(LTP/Ω–5–gliadin),NSAIDoralcoholco-factoranaphylaxis.
CLINICAL PEARLS
AN APPROACH TO INHALANT ALLERGY
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HISTORY SUGGESTIVE OF INHALANT ALLERGY
* ALLSA/NPG panel: Bermuda grass, Rye grass, Alternaria (mould), Cladosporium (mould), Aspergillus (mould), D.pteronyssinus (mite), B.tropicalis (mite), cat, dog** Request specific allergen breakdown if CAST inhalant mix is positive and phadiatop is negative.
Phadiatop Inhalant Screen
Break down in ALLSA/NPG panel*ANDallergy tree mix/individual trees
Highveld, Free State, NorthwestKZNWestern Cape
Consider adding:• Epicoccum (mould)• Cockroach (German)
Consider adding:• Maize Pollen• Eucalyptus• Weed Mix (Cosmos, Kakhibos)
Consider adding:• Cockroach (Oriental)
Phadlatop Inhalant Screen
WHERE DOES THE PATIENT LIVE?
Symptoms worse in SpringSymptoms all year round
Break down in ALLSA/NPG panel*
Positive Negative Negative Positiveif negative
Or SPT panel
? OTHER MECHANISMCAST inhalant mix **Nasal eosinophils
AN APPROACH TO INHALANT ALLERGY
•ThemajorityofinhalantallergiesareIgEmediated,thereforeIgEmediatedtesting,e.g. Phadiatop/skinpricktestsarerecommendedasfirstlinetests.•InpatientswithahistoryhighlysuggestiveofinhalantallergiesandnegativeIgEallergy tests,consider. a) Anothermechanism -DoCASTinhalantscreen. -Donasalmucussmearforeosinophils. b) Anotherallergen -?Treepollen,animal,weed,occupationalallergen.•ThemostallergenictreepollensinSouthAfricaareplanetree,oak,olive,cypress, eucalyptus,pine,acacia,willow,poplar,mulberryashandelder.•Screeningtests(Phadiatop)forinhalantallergiesshouldalwaysbebrokendownif positive,soindividualallergenscanbeidentifiedforavoidanceorimmunotherapy.•Patientsareoftensensitizedtocross-reactivecomponentsthatoccurinpollensand foodsofplantorigin.Testforthesecomponents,nl.LTP,PR-10,ProfilinandCCDin patientssensitizedtopollensandfoodsofplantorigin.
CLINICAL PEARLS
AN APPROACH TO FOOD ALLERGY
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THE FOLLOWING DIAGNOSTIC TOOLS ARE KEY IN THE ASSESSMENT OF A POSSIBLE FOOD ALLERGY:
HISTORY SUGGESTIVE OF FOOD ALLERGY
Negative
Food allergen screen on ImmunoCap® or SPT food panel
If food IgE is positive do dietary component testing to indicate risk, severity and for dietary advice
Egg: ovomucoid Milk: casein Wheat: Ω5gliadin Soy: glym5,6storageprotein Peanut: Arah1,2,3storageprotein Codfish:parvalbumin
NB!Ifsoy,wheatandpeanutsarepositive,considerfood-pollensyndromeAdd:
•GrassmixIgE •CCD•Proflin •LTP•PR-10
Positive
Breakdown in •Eggwhite •Milk •Wheat •Soya •Peanut •Codfish
Clear history indicates a specific food
Food allergen IgE or SPT
NegativePositive
? Other allergen •Otherfood IgE/SPT’s
Specific food allergens not implicated
? Other mechanism CAST test •Foodmix •Colourants •PreservativesMELISA/patch test
? Other disease, e.g. Coelliacs disease •HLADQ2+8 •lgA •TTGlgA •EndomysiallgA •DeamidatedGliadinlgA
? Non Immunological Mechanism i.e.lactasedeficiency•H-breathtest•Stoolreducingsubstances
? Other mechanism CAST test •Foodmix •Colourants •PreservativesMELISA/patch test
? Other disease, e.g. Coelliacs disease •HLADQ2+8 •lgA •TTGlgA •EndomysiallgA •DeamidatedGliadinlgA
? Non Immunological Mechanism i.e.lactasedeficiency•H-breathtest•Stoolreducingsubstances
AN APPROACH TO FOOD ALLERGY
•Itisimportanttodistinguishbetweenimmediate(<2hours)hypersensitivityreactions, whichareusuallyIgE/basophilmediatedanddelayedreactions,whichmayinclude otherimmunemechanisms.Testingshouldberequestedaccordingly.•Screeningwithafoodmix(IgEorCAST)shouldalwaysbebrokendownifpositive.•Considerallergytofoodadditiveslikecolourantsandpreservativesinadditiontothe specificfoodallergens.•Inpatientswithsymptomssuggestiveofwheathypersensitivityandnegativeallergy tests,pleaseconsidertestingforCoeliacdisease.•Oralallergysyndrome(OAS)isusuallycausedbypollen-foodcross-reactivity.Testfor pollenallergyandcross-reactivepollencomponents:IgEtoLTP,PR-10,profilinandCCD.•Relevantcomponentsshouldberequestediffood-specificIgEispositivetoadviseon risk,avoidanceandprognosis.•ISACtestingshouldbeconsideredinpatientswithmultiplefoodandinhalantallergies.
CLINICAL PEARLS
THE MOST IMPORTANT ALLERGEN COMPONENTS:
•Mainwheyproteins•Heatlabile•Patientsreactmoreseverely tofreshmilk.Maytolerateboiled/ bakedmilk,long-lifemilk, hardcheeseandyoghurt.
•Heatstable•Mostimportantallergen•Severeandpersistent allergy•Cross-reactsbetween mammals(eg:goats milk)
•Occursinmilkand beef/redmeat.•Heatlabile,maytolerate wellcookedmilkand dairy.•Cross-reactionwithother mammals.
•Heatlabile.•Maybeusedasa preservativeinbeef andnasalsprays.
EGG WHITE EGG YOLK
Ovomucoid Ovalbumin Conalbumin Lysozyme EggserumalbuminGald1 Gald2 Gald3 Gald4 Gald5
•Highlyallergenic •Heatlabile •Occursineggyolk,chicken•Heatstable •Maytoleratewell-cookedegg meatandfeathers•Severeandpersistent allergy
MILK Casein αlactalbumin βlactoglobin Bovineserumalbumin LactoferrinBosd8 Bosd4 Bosd5 Bosd6 Bosdlactoferrin
FISH SHELLFISHCodpavalbumin Carpparvalbumin TropomyosinCypc1 Gadc1 Pena1
•Heatstable•Broadcross-reactivity,markerforgeneralfishsensitization.•Parvalbumincontentofdifferentfishspeciesmayvary,e.g.lowerlevels intuna.
•Heatstablemuscleprotein.•Foundincrustaceans,molluscs, insectsandmiteswithclinical cross-reactivity.
MILK
FOOD ALLERGEN COMPONENTS: EGG, MILK, FISH, SHELLFISH
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Profilin
•Heatlabile•OAS
PR-10
•Heatlabile•OAS•Mildto severe symptoms
LTP
•Heatstable•OAS•Severe clinical symptoms or anaphylaxis
CCD
•Usuallyno clinical symptoms
PEANUT
•Stabletoheatanddigestion•Riskofanaphylaxis•Cross-reactivewithothernutsandseeds
Profilin PR-10 LTP CCDStorage Proteins
Ara h 1 Ara h 2 A ra h 3 Ara h 6 Ara h 5 Ara h 8 Ara h 9 CCD
SOYA
•Associatedwithseverereactions•Heatstable
Profilin Gly m 4 LTP CCDStorage Proteins
Gly m 5 Gly m 6 PR-10
•Mayhave severe reactions
WHEAT
•Riskmarkerforsystemic reactions•Wheatallergypersistence•Wheatdependentexercise inducedanaphylaxis
Profilin PR-10 Tri a 14LTP
CCDΩ 5 GliadinTri a 19
B WGliadins
•Markerofseverereactions•Markerofwheatallergy persistence.
Wheat dependent exercise induced anaphylaxis.
POLLEN CROSS REACTIVE
FOOD ALLERGEN COMPONENTS: POLLEN, PEANUT, SOYA, WHEAT
FOO
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SO
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