food allergy highlights of the past 3 years adam fox paediatric study day cheltenham june 2004 dr...
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![Page 1: Food Allergy Highlights of the past 3 years Adam Fox Paediatric Study Day Cheltenham June 2004 Dr Adam Fox](https://reader031.vdocuments.net/reader031/viewer/2022032611/56649c805503460f94936e17/html5/thumbnails/1.jpg)
Food AllergyHighlights of the
past 3 years
Adam FoxPaediatric Study DayCheltenhamJune 2004
Dr Adam Fox
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Food Allergy Research
1991-3 1994-6 1997-9 2000-2 2003-5 2006-80
500
1000
1500
2000
2500
10051165 1258
17282068
2244
‘Food Allergy’ Pub Med articles
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Highlights of the past 3 years
• Prevalence of food allergy• Comorbidities• Natural History• Emerging Treatments
![Page 4: Food Allergy Highlights of the past 3 years Adam Fox Paediatric Study Day Cheltenham June 2004 Dr Adam Fox](https://reader031.vdocuments.net/reader031/viewer/2022032611/56649c805503460f94936e17/html5/thumbnails/4.jpg)
Highlights of the past 3 years
• Prevalence of food allergy• Comorbidities• Natural History• Emerging Treatments
![Page 5: Food Allergy Highlights of the past 3 years Adam Fox Paediatric Study Day Cheltenham June 2004 Dr Adam Fox](https://reader031.vdocuments.net/reader031/viewer/2022032611/56649c805503460f94936e17/html5/thumbnails/5.jpg)
Anaphylaxis epidemic?
• National database 1997-2005• 112 deaths (0.64/million)• 350% increase in food induced
anaphylaxis admissions over 11 yrs
Liew WK et al. Anaphylaxis fatalities and admissions in Australia. JACI Feb 2009;123:434-42.
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• But no suchincrease in deaths
?better management
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• Main increase is in 0-5 yr olds and due to peanut allergic reactions
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Is peanut allergy getting out of control?
Rates of Peanut Allergic in UK Paediatric Cohorts
Venter 2005 Hourihane 2007 duToit 20080.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
1.8%
2.0%
1.0%
1.8% 1.8%
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Peanut Allergy in USSicherer et al JACI 2010
1 2 30.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
0.4%
0.8%
1.4%
1997 2002 2008
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Venter C et al. Time Trends in the prevalence of peanut allergy: 3 cohorts of children from the same geographical location in the UK.
Allergy 2010;65:103-8.
Born 1989 Born 1994-6 Born 2001-20
0.5
1
1.5
2
2.5
3
3.5
1.3
3.3
2
0.5
1.41.2
SensitisedAllergic
n=2181 n=1273 n=891
Pre-COT Post-COT
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..and it isn’t just here
Ben-Shoshan M et al, JACI Apr 2009
2000-2002 2005-20070.00%
0.20%
0.40%
0.60%
0.80%
1.00%
1.20%
1.40%
1.60%
1.80%
1.34%
1.62%
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Highlights of the past 3 years
• Prevalence of food allergy• Comorbidities• Natural History• Emerging Treatments
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Food Allergy & Eczema – beyond reasonable doubt
What we knew:• Link between AE & likelihood of FA• Link between increasing severity of AE &
likelihood of FA
Hill DJ et al. PAI 2004;15:421-7. Hill DJ et al. J Pediatr 2000;137:475-9.Hill DJ et al. J Pediatr 2007;151:359-63.
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0
10
20
30
40
50
60
70%
wit
h F
A a
t 12 m
on
ths
0 1 2 3 4
Group
Food Allergy increases with AD severity
Hill D, Hosking C. Food Allergy and Atopic Dermatitis in infancy. Paed Allergy Immunol 2004;15:421-7.
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Food Allergy & Eczema – beyond reasonable doubt
What we knew:• Link between AE & likelihood of FA• Link between increasing severity of AE & likelihood of
FA
What we needed to know:• Is this reproducible in a large cohort, international
study• Are there other important factors to predict likelihood
of FAHill DJ et al. PAI 2004;15:421-7. Hill DJ et al. J Pediatr 2000;137:475-9.Hill DJ et al. J Pediatr 2007;151:359-63.
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Hill DJ et al. Confirmation of the Association between high levels of IgE food sensitisation & eczema in infancy:
an international study. Clin Exp Allergy;38:161-8.
• 2222 children from 94 centres in 12 countries (mean 17months) with AE and allergic FHx
• SCORAD for eczema severity• SpIgE to egg, milk and peanut• Used previously validated ‘decision points’
based on 90% PPV to define HR-IgE-FS
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Relationship between eczema & HR-IgE-FS
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Limitations
• No DBPCFC but....• Used validated cut offs• High specificity of cut offs means many true
food allergics would have been missed• Probably underestimating food allergy as only
3 allergens tested.
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Summary
• In infants with AE, the earlier the age of onset and the more severe the eczema, the more likely there is to be food allergy
Clinical Implication:• Food allergies should be routinely assessed for
in infants with moderate or severe eczema
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Highlights of the past 3 years
• Prevalence of food allergy• Comorbidities• Natural History• Emerging Treatments
![Page 21: Food Allergy Highlights of the past 3 years Adam Fox Paediatric Study Day Cheltenham June 2004 Dr Adam Fox](https://reader031.vdocuments.net/reader031/viewer/2022032611/56649c805503460f94936e17/html5/thumbnails/21.jpg)
Outgrowing Food Allergy
What we knew:• Upto 75% of IgE mediated milk allergy is outgrown by 3
years•Danneus A et al 1981, Host A et al Allergy 1990, Bishop J et al J Paediatr 1990
• Tolerance is unlikely if not obtained by school age– Hill DJ et al CEA 1993, Saarinen KM et al JACI 2005
• SPT/SpIgE wheal size relates to likelihood of clinical allergy
What we needed to know:• Is this reproducible in a larger, more recent studies• What predicts tolerance?
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Skripak JM et al. The Natural History of IgE mediated Cow’s Milk Allergy. JACI;120:1172-77.
• Retrospective review of over 1000 IgE mediated milk allergic patients seen by author over 15 years
• Clinical history, test results and outcome collected on 807 patients
• Patients considered tolerant after they passed a challenge or experienced no reactions in the past 12 months and had a cow’s milk IgE <3 kU/L.
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Natural History of IgE mediated milk allergy
81
58
36
21
0
10
20
30
40
50
60
70
80
90
<4 yrs <8 yrs <12 yrs <16 yrs
Resolution of CMPA n=807
% allergic to CMP
Skripak JM et al. The Natural History of IgE mediated Cow’s Milk Allergy. JACI Nov 2007.
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Limitations
• Skewed tertiary care population• Possible underestimation of tolerance
– Lost to follow up probably more likely to be tolerant
– Some not challenged due to high SPT/SpIgE may have outgrown
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• Patients with persistent CMPA had higher IgE levels in first 2 years of life
• The higher the peak IgE level, the lower the chance of tolerance
• Similar for egg
Savage J et al. The Natural History of egg Allergy. JACI 2007Benhamou et al. PAI 2008.
Can Allergy Tests Predict Outgrowing?
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Clinical Implication:
• Tolerance may be taking longer than expected but may still develop in adolescence – don’t stop following them up
• Initial allergy test results should be considered when counselling parents regarding prognosis
• Is milk allergy becoming a more persistent disease?
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Highlights of the past 3 years
• Prevalence of food allergy• Comorbidities• Natural History• Emerging Treatments
![Page 29: Food Allergy Highlights of the past 3 years Adam Fox Paediatric Study Day Cheltenham June 2004 Dr Adam Fox](https://reader031.vdocuments.net/reader031/viewer/2022032611/56649c805503460f94936e17/html5/thumbnails/29.jpg)
Managing Food Allergy - MilkWhat we knew:• Allergen avoidance is the optimal management strategy• Children who outgrew milk allergy had milk-specific IgE antibodies
primarily directed against conformational epitopes.• Children with persistent milk allergy also had IgE antibodies
directed against specific sequential epitopes.
Chatchatee P et al. CEA 2001;31:1256-62. Chatchatee P et al. JACI 2001;107:379-83.Jarvinen KM et al. JACI 2002;110:293-7. Vila L et al. CEA 2001;31:1599-606.
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Jarvinen K-M et al. Allergy 2007
Linear/sequential Conformational
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Managing Food Allergy - MilkWhat we knew:• Allergen avoidance is the optimal management strategy• Children who outgrew milk allergy had milk-specific IgE antibodies
primarily directed against conformational epitopes.• Children with persistent milk allergy also had IgE antibodies
directed against specific sequential epitopes. What we needed to know:• Can those with IgE to conformational epitopes tolerate cooked
milk? – do they represent a milder phenotype & if so, how can we identify them?
• Will regular allergen exposure impact on tolerance?• In other words.....
Chatchatee P et al. CEA 2001;31:1256-62. Chatchatee P et al. JACI 2001;107:379-83.Jarvinen KM et al. JACI 2002;110:293-7. Vila L et al. CEA 2001;31:1599-606.
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All mild
Are we being too strict?
• After 3 months of HM – no effect on growth or intestinal permeability• HM tolerant had smaller SPT & lower bLG/Casein SpIgE• None with SPT<5 reacted to HM. 5kU was 90% cut off for reacting
Nowak-Wegrzyn A et al. JACI, August 2008
100 Milk allergic children (2-17 yrs) with +ve allergy tests
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Summary:
• 2 different phenotypes in IgE mediated milk allergy• Mild – tolerate baked milk, milder reactions, smaller
test and outgrow earlier• Severe – don’t tolerate baked milk, severe
reactions, larger test and outgrow later
Clinical Implications:• When do I start challenging....?
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Impact on tolerance development?Kim et al JACI 2011
• 3 groups– Heated milk tolerant (mild phenotype)
– Heated milk reactive (severe phenotype)
– Comparison Group (retrospective age/sex/IgE matched controls who had ‘standard care’)
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HM tolerant vs HM reactive
80% vs 24% tolerant of unheated milk over 5 years
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HM tolerant vs comparison group
80% vs 33% tolerant of unheated milk over 5 years
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Conclusions
• Baked milk, if tolerated, is safe convenient and well accepted
• Appears to enhance development of tolerance but prospective controlled study still to be done
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Oral tolerance induction to peanut
• 4 confirmed peanut allergics• Gradually increased doses of oral peanut • 2 weekly supervised increments to 800mg• All tolerated at least 10 peanuts at challenge• 18 more patients successfully treated• RCTs to follow....• ? Long term effect and ?safety
Clarke A et al. Allergy 2009.
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Desensitisation vs Tolerance
• Desensitisation – a change is threshold of allergen required to cause allergic symptoms
• Tolerance – induction of long term immunologic changes associated with the ability to ingest allergen without symptoms or ongoing therapy
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Blumchen et al. Oral peanut Immunotherapy in children with peanut
anaphylaxis, JACI 2010• 23 kids
aged 3-14
• Unstable asthma excluded
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Results• Only 5/23 achieved 500mg dose on rush
protocol . 1 too anxious to complete.• 5 who achieved 500mg with rush had
significantly lower peanut SpIgE than others• Long term build up more successful – 14
reached 500mg dose• Mean 4 fold increase in dose tolerated at final
OFC, compared to initial OFC• 3 patients tolerated less than their
maintenance at final OFC whilst 3 tolerated 4g top dose
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Results
• 4 patients withdrawn due to SE• All worsening of pre-existing asthma• No adrenaline used (but trained to use
salbutamol first for moderate respiratory symptoms
• 0.9% of doses required salbutamol• Peanut specific downregulation of IL2, IL4 &
IL5 (but no increase in IL10) and increased IgG4
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Implications
• Rush protocol does not seem suitable (except possibly for those with low SpIgE)
• Long term build up seems to be safe and effective at reaching clinically relevant thresholds
• Possible early evidence of long term tolerance induction
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