Prevalence of Food Allergies in Southeast Asia

BW Lee, Dept Paediatrics National University of Singapore

Session 1: Understanding Food Allergies

2011

Food Allergy: A ‘hot’ topic

2nd wave of the allergy epidemic?

Food Allergy

J Allergy Clin Immunol 2007

Is there a Food Allergy Epidemic

in Asia?

Studies reporting Food Allergy Prevalence in preschool children < 5 years

OFC proven food allergy Symptoms and sensitisation Parental reporting

Published data only available

from 16/89 countries

(those without data not shown)

Prescott SL et al WAOJ 2013

Summary of Prevalence of Food Allergies in Singapore

Lee AJ and Shek LP Singapore Med J 2014

Peanut Allergy Around the World

0.5 0.6

1.5

3

0.47 0.43 0.4

0

11.2

0.38

1.8

2.1

0

0.5

1

1.5

2

2.5

3

3.5

UKUSA

Canad

a

Austra

lia

Singap

ore

Philip

pine

s

China

Thailan

d

% P

reva

len

ce

Shek et al, J Allergy Clin Immunol, 2010 Gusto Cohort, Singapore (unpublished) Chen et al, Pediatric Allergy Immunol 2011 Tang et al, J Allergy Clin Immunol 2012 Lao-Araya Ped Int 2012

Hourihane et al, J Allergy Clin Immunol 2007 Sicherer et al, J Allergy Clin Immunol 2010

Kagan et al, J Allergy Clin Immunol 2003 Osborne et al, J Allergy Clin Immunol 2011

(Peanut/tree nut)

Peanut Allergy and Country of Birth

3.8

5.5

Odds ratio (Compared vs

Asia born Asians)

Asian = Chinese, Malay, Indian, Filipino Western countries = Australia, New Zealand, United Kingdom, North America and Western Europe

Shek et al J Allergy Clin Immunol 2010

Born in the West

Asian

Caucasian p<0.05

Goh DL et al Allergy 1999

Data From Singapore 1999

No peanut anaphylaxis cases

Sarawak Indonesia Thailand

Unprocessed Fresh Sarawak BN

Food Anaphylaxis (n=73) Median age 6.2 years

19%

12%

12%

11% 5% 5%

4%

4%

4% 1%

8%

15%

Peanut

Seafood

Bird's Nest

Egg

Cow milk

Fruits (banana, jackfruit, mango)

Fish

Treenuts

Honey

Wheat

Others (HDM contaminated flour, Preservatives/colouring)

Unknown

Singapore (KKH) Paediatric Food Anaphylaxis Jan 2005 to Dec 2009

13 Peanut anaphylaxis over 5 years

– 12 Chinese (1 born in Canada), 1 Caucasian Liew WK et al. AP Allergy 2013

Shellfish Allergy

Common Food Allergies in Asia

0.7

5.2

0

1

2

3

4

5

6

USA Singapore/Philippines

%

(6-17yr) (14-16yr)

Sicherer S, J Allergy Clin Immunol 2004 Shek LP, J Allergy Clin Immunol 2010

Shellfish Allergy Population-based Surveys

Shellfish Most Common Cause of Anaphylaxis in Asia

• Thailand Adults and Children • Singapore Adults

• Hongkong Adults • Taiwan Adults and Children

Jirapongsaranuruk O et al Ann Allergy Immunol 2007 Thong B et al Sing Med J 2005

Smit DV et al J Emerg Med 2005 Hsin Y et al Asian Pac J Allergy Immunol 2011

http://tolweb.org/treehouses/?treehouse_id=4455

Order: Decapods

Food Challenge Provocation Dose

• Thai, children – 1g to 63g, cooked prawn Jirapongsananuruk et al Clin Exp Allergy 2008

• Singapore, Adolescents and Adults: 2g to

80g, cooked prawn Gerez et al, unpublished

• Canada, Adult (1 patient): 14g, freeze dried, capsule

Bernstein et al J Allergy Clin Immunol 1982; 70:205–10

Distribution of symptoms during the most severe reaction to shellfish

0

5

10

15

20

25

30

35

40

45

50

Hives

Swollen eyes & lips

Vomiting & Diarrhoea

Abdominal pain

Runny nose

Itchy throat

Throat tightness & Wheezing

Coughing

Feeling faint or dizzy & Loss of consciousness

Redness of skin

% o

f stu

dent

s w

ith s

ympt

om

Fig 1.

(n=674)

Shek et al, J Allergy Clin Immunol, 2010

Challenge + -

2/39 shellfish allergy cases specific IgE to shrimp (-) shrimp tropomyosin (Pen a 1, Pen m1, Pen I 1, Lit v 1) (-) dust mite tropomyosin (Der p 10, Blo t 10) (+)

Thayalasingham M et al, Clin Exp Allergy 2015

Mild Crustacean Seafood Allergy Tropomyosin – A pan-allergen

• Inhalant-food syndrome – Dust mites as the sensitizing allergen – Crustacean shellfish as the cross reactive

allergen

Conclusions from reciprocal IgE inhibition Studies:

Mites are the primary sensitizer in humid-climate

It’s Not Always Just Food Allergy

15 year Old Girl

• Has asthma and allergic rhinitis • Ingested home-made tempura prawns – fried

coated with Japanese flour • Developed urticaria, throat discomfort, severe

wheezing 20 min later • Treated at emergency dept for anaphylaxis - SaO2 77%

Gross Appearance of Flour

Areas of light brown discolouration

Anaphylaxis to cow’s milk

formula containing short-chain galacto-oligosaccharide

(GOS)

Report of 5 Cases

Prebiotic (Carbohydrate) Triggered Anaphylaxis

Chiang et al J Allergy Clin Immunol 2012

Anaphylaxis to Cow’s

milk formula

SKIN PRICK TEST

• SPT to CMF negative • SPT to CMF without PREBIOTICS negative • SPT to CMF containing GOS positive

A: COW’S MILK FORMULA (numerical refer to diameters weal) Patient 1 2 3 4 5

Positive Histamine 7 x 5 10 x 7 5 x 5 6 x 6 9x7 Negative Control 0 0 0 0 0 Cow’s Milk 0 0 0 0 0 CMF1 with prebiotics scGOS + lcFOS 7 x 6 3 x 3 1 x 1 4 x 4 6x5 CMF1 without prebiotics 0 0 0 0 0 CMF2 with prebiotic scGOS 7 x 6 5 x 3 5 x 5 6 x 6 14x10 Std Vivinal GOS (7.2mg/ml) 3 x 3 7 x 5 0 5 x 5 3 x 3

scGOS = short chain Galacto-oligosaccharides lcFOS = long chain Fructo-oliogosaccharides Chiang et al J Allergy Clin Immunol 2012

0

100

200

300

400

500

0 0.1 1 10 0 0.1 1 10 0 0.1 1 10 0 0.1 1 10 0 0.1 1 10

CD

203c

(MF

I)

Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

a-I

gE

CM

F1

w/o

pr

ebio

tics

IcF

OS

0 0.1 1 10 0 0.1 1 10 0 0.1 1 100

100

200

300

400

500

CD

203c

(MF

I)

CMF1 CMF2 Std GOS

Basophil Activation Tests

whole blood

Actual GOS concentration in the samples (mg/ml)

0 0.1 1 10 0 0.1 1 10 0 0.1 1 100

20

40

60

80

100

120

CD

63 (%

)

whole blood

Chiang et al J Allergy Clin Immunol 2012

Cow’s milk formula Galacto-oligosaccharide

GOS GRAS dossier 2007

Structure of GOS

GOS is produced by enzymatic transgalactosylation of lactose by β-galactosidase

Variable chains of galactose with one molecule of glucose

Fractions of GOS mixture High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD)

DP=degrees of polymerization

Glu or Gal

Gal-Glu

(Gal)2-Glu

(Gal)3-Glu

(Gal)4-Glu

(Gal)5-Glu

(Gal)6-Glu

Dose-dependent effect of scGOS fractions on activation of in vitro–

sensitized control basophils

Chiang et al J Allergy Clin Immunol 2012

Inhibition of scGOS-induced basophil degranulation by the phosphatidylinositol 3-kinase inhibitor wortmannin

scGOS activation of basophils requires the PI-3-kinase pathway.

This is consistent with IgE-mediated activation.

• Milk product with GOS introduced in Sept 2009

• 3 million cartons sold a day in Vietnam

• 15/16 cases aged 2-15 years old consumed milk with GOS

• 12/15 within 3 to 20 mins of milk consumption.

• 3/15 with acute respiratory problems

What is the Primary Sensitizer?

Hoya Antigen Asthma in Japan

• Sea squirt antigen – H or Hoya antigen

• It is a hexosamine rich glycoprotein

• Causes occupational asthma in oyster shucklers

Alpha-Galactose IgE Epitopes (mammalian CCD)

• Cetuximab: N-linked oligosaccharides contains the a-gal epitopes – Immediate onset anaphylaxis

• Mammalian meat - Pork and Beef: gal-a-1,3-gal-b-

1,4-GlcNAc – Delayed anaphylaxis reaction (3-6 hours)

Commins and Platts Mills J Allergy Clin Immunol 2015

Cabohydrate Allergen Epitopes - cross-reactive carbohydrate determinants (CCD) of N-linked glycans

Aalberse RC, J Allergy Clin Immunol 1981; 68:356–364.

• Clinically insignificant – Low titre anti-glycan IgE antibodies – High affinity ‘blocking’ IgG antibodies

• ‘False positive’ specific IgE tests

Plant (pollen, vegetables, fruits and natural rubber latex)

Insect (Bee venom)

Examples of plant and insect N-glycans

Curr Opin Allergy Clin Immunol. 2013 Aug;13(4):360-4

Conclusions

• It does not appear that Asia is facing a food allergy epidemic – Better oral tolerance?

• Pattern of food allergy is different and may

be related to environmental allergens – Inhalant/environmental and food allergens