Allergy in a ‘nutshell’ GP guide to survival Dr Gillian Vance.
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Transcript of Allergy in a ‘nutshell’ GP guide to survival Dr Gillian Vance.
Allergy in a ‘nutshell’Allergy in a ‘nutshell’GP guide to survivalGP guide to survival
Dr Gillian VanceDr Gillian Vance
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’
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
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
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 +
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
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