Allergy in a ‘nutshell’Allergy in a ‘nutshell’GP guide to survivalGP guide to survival

Dr Gillian VanceDr Gillian Vance

Allergy careAllergy care

Starts with early diagnosisStarts with early diagnosis

SessionSession

Better understanding of the basic Better understanding of the basic immunological mechanisms immunological mechanisms underlying food allergic diseaseunderlying food allergic disease

Apply mechanisms to clinical Apply mechanisms to clinical evaluation & appropriate therapy evaluation & appropriate therapy

ObjectivesObjectives

Recognise typical features of allergic Recognise typical features of allergic disease disease

Appreciate areas of complexityAppreciate areas of complexity

Explain what, how & why we Explain what, how & why we evaluate at the allergy clinicevaluate at the allergy clinic

‘‘Allergy’Allergy’

11stst coined in 1906 by Austrian coined in 1906 by Austrian paediatrician, Clemens von Pirquetpaediatrician, Clemens von Pirquet

‘‘altered reactivity’ to any antigenic altered reactivity’ to any antigenic stimulation, whetherstimulation, whether

Immunity – protectionImmunity – protection

Hypersensitivity – Hypersensitivity – adverse clinical adverse clinical responseresponse

‘‘Allergy’Allergy’

‘‘An exaggerated sensitivity to a An exaggerated sensitivity to a substance (allergen) that is inhaled, substance (allergen) that is inhaled, swallowed or injected, or that comes swallowed or injected, or that comes into contact with the skin or eyes’into contact with the skin or eyes’

Allergic disease spectrumAllergic disease spectrum

Food allergyFood allergy

EczemaEczema

AsthmaAsthma

Allergic rhinitisAllergic rhinitis

Drug allergyDrug allergy

Allergy – a public health Allergy – a public health problemproblem

Prevalence of asthma & hayfever have Prevalence of asthma & hayfever have

increased over the last 20 years (3 - 8.2% increased over the last 20 years (3 - 8.2%

and 5.8 - 20% respectively) and 5.8 - 20% respectively) Upton, BMJ 2000Upton, BMJ 2000

12 million people per year may seek12 million people per year may seek

treatment for allergytreatment for allergy

Children: 20.4% asthma; 18.2% hayfever; Children: 20.4% asthma; 18.2% hayfever;

47% 1 or more current symptoms 47% 1 or more current symptoms (ISAAC study, (ISAAC study,

1999)1999)

Epidemiology of Food AllergyEpidemiology of Food Allergy

Peanut allergy (3 yr olds)Peanut allergy (3 yr olds)– Sensitisation: threefold increase 1989-1994-6 Sensitisation: threefold increase 1989-1994-6

from 1.1-3.3.%from 1.1-3.3.%– Doubling of reactivity from 0.5-1% Doubling of reactivity from 0.5-1% JACI 2001;107:S231JACI 2001;107:S231

Admission rates Admission rates Anaphylaxis risen 7-fold; 5/million 1990/1- 36 2003/4Anaphylaxis risen 7-fold; 5/million 1990/1- 36 2003/4

Food allergy risen 7-fold; 16 - 107/millionFood allergy risen 7-fold; 16 - 107/million

Urticaria doubled; 20 – 44/million – especially Urticaria doubled; 20 – 44/million – especially childrenchildren

Allergy – a primary care Allergy – a primary care problemproblem

6% of GP consultations6% of GP consultationsPrimary Care PrescribingPrimary Care Prescribing– 1991-2004: community prescriptions 1991-2004: community prescriptions

increasedincreased– Nasal allergy - by 60% (to 4.5 million)Nasal allergy - by 60% (to 4.5 million)– Anaphylaxis – 12 fold (to 124,000) Anaphylaxis – 12 fold (to 124,000) – Ocular allergy – by 50% (to 1.4 million)Ocular allergy – by 50% (to 1.4 million)Costs NHS £900 million paCosts NHS £900 million pa– Excludes costs of A&E attendances, outpatient Excludes costs of A&E attendances, outpatient

consultations, hospital treatmentconsultations, hospital treatment

BSACI, London, commissioned study, 2002BSACI, London, commissioned study, 2002

Why should children with Why should children with suspected allergy be tested?suspected allergy be tested?May be lifelongMay be lifelong– Specific treatmentSpecific treatment– Early treatment may influence severityEarly treatment may influence severity

May be life threateningMay be life threatening

Associated with poor quality of lifeAssociated with poor quality of life

May herald other allergic diseasesMay herald other allergic diseases– ‘‘Allergic March’Allergic March’

EczemaEczema AsthmaAsthma

Adverse Reactions to FoodAdverse Reactions to Food

Adverse Reaction to Food

ToxicFood poisoning

Non toxic

Aversion

Non-immune mediated

Enzymatic

Pharmacological

Undefined

Immune mediated

AllergyIgE

Non IgE

Non-immune ARFNon-immune ARF

‘‘Undefined’Undefined’– Mechanism unknownMechanism unknown– Food additives, preservatives, colouringsFood additives, preservatives, colourings– ‘‘Generally Recognised as Safe products Generally Recognised as Safe products

[GRAS][GRAS]– Sulphites, nitrites, nitrates, MSGSulphites, nitrites, nitrates, MSG– Urticaria, rhinitis, asthma, migraine Urticaria, rhinitis, asthma, migraine

Food Allergy - DefinitionFood Allergy - Definition

An immune-mediated adverse An immune-mediated adverse reaction to food that occurs in reaction to food that occurs in genetically predisposed individualsgenetically predisposed individuals– IgEIgE urticaria; oral allergy; anaphylaxisurticaria; oral allergy; anaphylaxis– Non IgE Non IgE Cell-mediated; mixedCell-mediated; mixed– ConsistentConsistent– ReproducibleReproducible

HowHow does the immune system does the immune system malfunction in food allergies? malfunction in food allergies?

Step 1: SensitisationStep 1: Sensitisation

IgE production

Allergen Exposure

Processing

Presentation

Th2-biased cytokine productionTh

cell

B cell

Step 2: Activation - Effector Step 2: Activation - Effector PhasePhase

Mucosal oedema

Smooth muscle contraction

Peristalsis

Pain

Cell recruitment

Vasodilatation

Tissue remodelling

Immune Modulation

IgE induction

Clinical Manifestations: Clinical Manifestations: ImmediateImmediate

ErythemaErythemaPruritus (generalised)Pruritus (generalised)UrticariaUrticariaAngioedemaAngioedemaRhinitisRhinitisLaryngeal oedemaLaryngeal oedemaAsthmaAsthmaGI upsetGI upset

SymptomsSymptoms

ImmediateImmediate

Delayed type / Chronic Delayed type / Chronic – InflammationInflammation– Abdominal painAbdominal pain– Altered gut functionAltered gut function– Poor asthma controlPoor asthma control

Clinical Manifestations: non IgE-Clinical Manifestations: non IgE-mediated reactionsmediated reactions

Delayed typeDelayed typeSKIN: eczema flaresSKIN: eczema flaresGUT:GUT:– Mucousy / bloody stools in an infantMucousy / bloody stools in an infant– Chronic diarrhoea, vomitingChronic diarrhoea, vomiting– Failure to thriveFailure to thrive– MalabsorptionMalabsorption– Dysphagia, abdominal painDysphagia, abdominal pain

Proctitis / dietary protein enteropathy / Proctitis / dietary protein enteropathy / eosinophilic gastroenteropathieseosinophilic gastroenteropathies

What foods?What foods?

Cow’s milk, Egg white, Soybean, Wheat, Peanut, Tree nuts, Fish & Shellfish account for >90% reactions

Red flag features of allergyRed flag features of allergy

Clear temporal relationship with Clear temporal relationship with triggertrigger

Consistency of reactionConsistency of reaction

Trigger – likely allergenTrigger – likely allergen

Timing – within 2 hours of ingestionTiming – within 2 hours of ingestion

‘‘Typical’ clinical symptomsTypical’ clinical symptoms

Other features of atopyOther features of atopy

Family history of atopyFamily history of atopy

Example 1Example 1

3½ year old girl3½ year old girl

Eczema since 1 year ageEczema since 1 year age

Ate 1 salted peanut 18 months agoAte 1 salted peanut 18 months ago

Developed Developed – lip swelling & wheezelip swelling & wheeze– No rash, GI upset or respiratory distressNo rash, GI upset or respiratory distress

Mum – asthma & hayfeverMum – asthma & hayfever

Example 2Example 2

11 year old girl11 year old girl

No other atopic diseaseNo other atopic disease

Xmas - ate raisin from bowl of mixed Xmas - ate raisin from bowl of mixed nutsnuts

Developed lip swelling & local urticaria Developed lip swelling & local urticaria 5 – 10 minutes later5 – 10 minutes later

Settled with oral piriton Settled with oral piriton

Father – eczema & occasional ‘wheezeFather – eczema & occasional ‘wheeze’ ’

What’s the diagnosis?What’s the diagnosis?

Peanut allergyPeanut allergy

Tree-nut allergyTree-nut allergy

‘‘Other’Other’

Diagnostic AdjunctsDiagnostic Adjuncts

Skin Prick TestingSkin Prick Testing– CheapCheap– PainlessPainless– FastFast– Sensitive & specificSensitive & specific

Specific IgE measurementSpecific IgE measurement– Blood testBlood test– Hx of anaphylaxisHx of anaphylaxis– Recent antihistamine useRecent antihistamine use– Widespread eczematous skinWidespread eczematous skin

Skin prick testSkin prick test

Results - casesResults - cases

Case 1:Case 1:– SPT peanut 6 mmSPT peanut 6 mm– SPT tree nut panel negativeSPT tree nut panel negative– Specific IgE peanut 5.6 kU/LSpecific IgE peanut 5.6 kU/L

Case 2:Case 2:– SPT peanut 6 mmSPT peanut 6 mm– SPT brazil nut 4 mm; remainder negativeSPT brazil nut 4 mm; remainder negative– Specific IgE peanut 90 kU/L; brazil 2.4 kU/LSpecific IgE peanut 90 kU/L; brazil 2.4 kU/L

InterpretationInterpretation

Case 1: peanut allergicCase 1: peanut allergic

Case 2: peanut & tree-nut allergic Case 2: peanut & tree-nut allergic

SPT weal size or Specific IgE levelSPT weal size or Specific IgE level– No relation with severity of reactionNo relation with severity of reaction

Red flag features of Red flag features of managementmanagement

AAwarenesswareness

AAvoidancevoidance

AAsthma controlsthma control

AAnti-histaminenti-histamine

AAdrenaline autoinjectordrenaline autoinjector

ManagementManagement

AWARENESSAWARENESS– ParentsParents– Wider familyWider family– SchoolSchool– PhysicianPhysician

GETTING THE DIAGNOSIS GETTING THE DIAGNOSIS RIGHTRIGHT

ManagementManagement

AVOIDANCE OF ALLERGENSAVOIDANCE OF ALLERGENS

ManagementManagement

AVOIDANCEAVOIDANCE

ManagementManagement

ASTHMA CONTROLASTHMA CONTROL

ManagementManagement

ANTI-HISTAMINEANTI-HISTAMINE

ManagementManagement

ADRENALINE (EPINEPHRINE)ADRENALINE (EPINEPHRINE)

Who should get an epipen?Who should get an epipen?

Lethal anaphylaxisLethal anaphylaxis

UncommonUncommon

0.65-2% of severe anaphylaxis0.65-2% of severe anaphylaxis

‘KISS OF DEATH FOR NUT ALLERGY GIRL’

A teenage girl with an extreme allergy has died after kissing her boyfriend who had eaten a peanut-butter sandwich hours earlier.Christina Desforges, 15, from Saguenay, Canada, went into anaphylactic shock. She was given an adrenalin shot and taken to hospital but died four days later from acute respiratory failure.Doctors said that a nut allergy brought on by the kiss was the cause of death. The boy, who has not been named, had minute traces of peanut on his lips.

Nov ‘05

Lethal anaphylaxis:Lethal anaphylaxis: ‘predictable’ risk factors ‘predictable’ risk factors

Peanut / treenuts Peanut / treenuts

AsthmaAsthma

Adolescents / young adultsAdolescents / young adults

Lethal anaphylaxis: Lethal anaphylaxis: ‘unpredictable’ risk factors‘unpredictable’ risk factors

Severity history of previous food Severity history of previous food reaction reaction

PumphreyPumphrey• 22% of fatal cases had had previous 22% of fatal cases had had previous

severe reactionsevere reaction

Severity HistorySeverity History

Previous

Current None Mild / moderate

Severe

Not severe 77 74 11

Severe 15 22 8

Near fatal 1 3 1

Fatal 0 2 1

Macdougall et al, 2002, Arch Dis Child

Red flag features of epipen Red flag features of epipen prescriptionprescription

Indicated:Indicated:– History of severe reactionHistory of severe reaction– Reactions becoming more severeReactions becoming more severe– Asthma (requiring inhaled steroid use)Asthma (requiring inhaled steroid use)

Consider:Consider:– If low dose (trace) exposureIf low dose (trace) exposure– At a distance from nearest medical At a distance from nearest medical

facilityfacility– If having difficulty avoidingIf having difficulty avoiding– If parents anxious +If parents anxious +

PrognosisPrognosis

IgE mediated reactionsIgE mediated reactions

Resolve: Cow’s milk, Egg, Soya, WheatResolve: Cow’s milk, Egg, Soya, Wheat– By 5 years age, tolerance in By 5 years age, tolerance in

85% of CMA children85% of CMA children

66% of egg allergic children66% of egg allergic children

Persist: Peanut, Tree nut, Fish & ShellfishPersist: Peanut, Tree nut, Fish & Shellfish– However, around 20% of PA will resolveHowever, around 20% of PA will resolve

Youngest patientsYoungest patients

Low specific IgELow specific IgE

Mild reaction at presentationMild reaction at presentation

Frequently Asked QuestionsFrequently Asked Questions

Is a food allergy causing my Is a food allergy causing my child’s hyperactivity?child’s hyperactivity?

Number of ways in which food could affect Number of ways in which food could affect cognition & behaviour in childrencognition & behaviour in children

Mechanism not ‘allergy’Mechanism not ‘allergy’

Some benefit in ‘extreme’ subgroupsSome benefit in ‘extreme’ subgroups– Complex behavioural problems +/- Complex behavioural problems +/-

neurological deficitsneurological deficits

Possibility that food additives may have a Possibility that food additives may have a pervasive effect across the populationpervasive effect across the population

‘‘Food Allergy’ & behaviourFood Allergy’ & behaviour

• Bateman studyBateman study– 277 children277 children– Hyperactivity / atopyHyperactivity / atopy– Randomised, placebo-control, Double Randomised, placebo-control, Double

blind, cross-over: food colouring & Na blind, cross-over: food colouring & Na benzoatebenzoate

– Assessed weekly by psychologists; Assessed weekly by psychologists; parents dailyparents daily

– Parental ratings associated with dietary Parental ratings associated with dietary additivesadditives

– No association with atopyNo association with atopy

‘‘Food Allergy’ & behaviourFood Allergy’ & behaviour

Confirmed in follow on studyConfirmed in follow on study

3-year old children (n=153)3-year old children (n=153)

8/9 year old children (n=144)8/9 year old children (n=144)

Within subject crossover – 2 active Within subject crossover – 2 active mixes; 1 placebo (3 year olds x2 56g mixes; 1 placebo (3 year olds x2 56g sweets; 8 yr olds 2-4 bags sweets / daysweets; 8 yr olds 2-4 bags sweets / day

Global Hyperactivity Aggregate Global Hyperactivity Aggregate increased in both age groups with active increased in both age groups with active mixmix

My child has egg allergy – My child has egg allergy – should he have the MMR?should he have the MMR?

YESYES

UnlessUnless– ImmunocompromisedImmunocompromised– Had an anaphylactic reaction to previous MMRHad an anaphylactic reaction to previous MMR– Had an anaphylactic reaction to gelatin / Had an anaphylactic reaction to gelatin /

neomycinneomycin

Close observation ifClose observation if– Previous acute severe reaction to eggPrevious acute severe reaction to egg– Current active, chronic asthmaCurrent active, chronic asthma

(Other) Indications for (Other) Indications for referralreferral

GI symptoms: GI symptoms: – vomiting, diarrhoea, colic, FTTvomiting, diarrhoea, colic, FTT

Atopic dermatitis: Atopic dermatitis: – severe, persistent, young child, allergen-relatedsevere, persistent, young child, allergen-related

Chronic urticaria: Chronic urticaria: – duration > 6 weeksduration > 6 weeks

Wheezers / asthmaticsWheezers / asthmaticsRhinitis / conjunctivitisRhinitis / conjunctivitis– Severe, persistent, treatment-resistant, allergen-Severe, persistent, treatment-resistant, allergen-

relatedrelated

Insect allergy (not local reaction – even if large)Insect allergy (not local reaction – even if large)

What have we learned?What have we learned?

Allergy has a wide range of manifestations Allergy has a wide range of manifestations Diagnosis relies on careful history taking, Diagnosis relies on careful history taking,

& appropriate interpretation of IgE testing.& appropriate interpretation of IgE testing. Management represents a ‘package’ of Management represents a ‘package’ of

education, specific allergen avoidance education, specific allergen avoidance measures, relevant pharmacotherapy & measures, relevant pharmacotherapy & possibly desensitisation (inhalants)possibly desensitisation (inhalants)

‘‘Early’ evaluation can make a difference to Early’ evaluation can make a difference to both the child & family lifeboth the child & family life

Thank you for listeningThank you for listening

Feel free to discuss / refer your Feel free to discuss / refer your patients to the allergy team.patients to the allergy team.