The Prevalence and Patterns of IgE-Mediated Food Allergy and Sensitisation in South African

192 Pages·2014·3.91 MB·English

Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

The Prevalence and Patterns of IgE-mediated
Food Allergy and Sensitisation in South African
Children with Atopic Dermatitis
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Dr Claudia Liesel Gray

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Thesis presentedf for the degree of
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DOCTtOR OF PHILOSOPHY
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In the Departmente of Health Sciences, Faculty of Paediatrics
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UNIVERSITY OF CAPE TOWN
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December 2014

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The copyright of this thesis vests in the author. No
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quotation from it or information derived from it is to be

published without full acknowledgeement of the source.
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The thesis is to be used for private study or non-
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commercial research purposes only.

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Published by the Universit y of Cape Town (UCT) in terms
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of the non-exclusive license granted to UCT by the author.
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

Acknowledgements:
Many thanks go to my supervisors, Professor Mike Levin and Dr George du Toit, for advice,
encouragement and wisdom
Many thanks to Thermofisher® for sponsoring the ISAC reagents and ImmunoCAP reagents
Thank you to the study nurse, Sister Lucia Volkwyn, and laboratory technician Bartha Fenemore for
their tireless work during the study
Thank you to my co-investigators Professors Paul Potter, Heather Zar and Nonhlanhla Khumalo, as
well as the late Professor Cas Motala, for their input into the study
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Thank you to Henri Carreira for statistical advice
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Special thanks to the children who participated in the study and their ever-patient and enthusiastic
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parents who made it all possible

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And lastly thank you to my husband Paul and 3 beautiful childpren Christopher, Ella-Grace and James
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for putting up with endless hours of “Mama’s PhD”
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

Abstract: The Prevalence and Patterns of IgE-mediated Food Allergy
and Sensitisation in South African Children with Atopic Dermatitis

Background: The prevalence of food allergy in South Africa is unknown, but previously thought to be
low, particularly in black South Africans. We hypothesised that food allergies would be low in Xhosa
patients, even those at increased risk of food allergy such as children with atopic dermatitis (AD). This
study aimed to determine the prevalence of, patterns and risk factors for, IgE-mediated food allergy
in South African children with moderate to severe AD. It is the first food allergy prevalence study in
South Africa to utilise controlled food challenges and component analysis, and is unique for its
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comparison of food allergy patterns between ethnic groups in the same geowgraphical area.
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Methodology: This was a prospective, observational study in a paedTiatric university hospital in Cape

Town. Children with moderate to severe AD, aged 6 months toe 10 years, were randomly recruited
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from the dermatology clinic. They were assessed for sensitisation and allergy by questionnaire, skin
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prick tests (SPT), Immuno Solid Phase Allergen Chip C(ISAC) test and incremental food challenges.
Sensitised patients were also tested for specific IgE by ImmunoCAP test.
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Results: One hundred participants (59 blacky Africans and 41 of mixed race) were enrolled, median age
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42 months. There were high overall rateis of food sensitisation (66%) and food allergy (40%). Egg (25%)
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and peanut (24%) were the most crommon allergies. Black participants had comparable sensitisation
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(69% vs 61%) but lower allergvy rates (34% vs 46%) than mixed race participants. This was especially
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evident for peanut allergyn (15% vs 37%, p=0.01). Early onset AD (< 6 months), severe eczema, and
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young age < 2 years were significant risk factors for food allergy. The ISAC test was less sensitive than
SPT and ImmunoCAP tests. Only 42% of cases of perceived food allergy were confirmed as true food
allergy.
Component tests for peanut followed similar trends in both ethnic groups with Ara h 2 being the most
strongly associated with peanut allergy. However, the likelihood of peanut allergy with a positive
Ara h 2 was significantly lower in Xhosa than mixed race patients (53% v 93%, p=0.01). Ara h 8 and 9
were associated with tolerance to peanut. The SPT to peanut achieved best Receiver Operating
Characteristic (ROC) area under the curve indicating the best predictive value for peanut allergy in
both ethnic groups. Internationally derived 95% positive predictive values (PPV) for SPT, peanut
specific IgE and ImmunoCAP Ara h 2 performed well in the mixed race group, but poorly in the Xhosa
group. High degrees of asymptomatic sensitisation in Xhosa patients could not be explained by cross-
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

reactive carbohydrate determinants or parasitaemia, or by a difference in peanut consumption
patterns.
Egg allergy was common in both ethnic groups, and the best predictive value for egg allergy was
achieved by SPT to fresh raw egg white. Internationally derived 95% PPV for egg allergy did not
perform well in our population. Cow’s milk allergy was uncommon in this study.
The prevalence of co-morbid allergic conditions, including aeroallergen sensitisation, asthma and
allergic rhinitis, was high.
Conclusion: The prevalence of food allergy is high in South African children with moderate to severe
AD, and comparable with food allergy rates in AD patients of similar severity in westernised countries.
There are ethnic differences, with significantly lower peanut allergy rates in blanck Africans compared
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to mixed race patients.
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Internationally derived 95% PPV for peanut, egg and cow’s milk allergy did not produce good

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predictive values in our study population, particularly in Xhosa patients. SPT remains an excellent test
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in both ethnic groups for diagnosing peanut allergy, and SaPT to raw egg white and fresh milk are the
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superior tests in egg and milk allergy diagnosis. Ara h 2 is the most useful component in differentiating

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between peanut sensitisation and true allergy.
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The reasons for ethnic differences in footd allergy patterns are unclear, and may reflect environmental
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or genetic differences. A change in protective environmental factors may presage an increase in food
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allergy in South Africa.
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

Contents Page:
Chapter Page
1. Introduction 6

2. The Epidemiology of Food Allergy 10
3. The Relationship between Atopic Dermatitis and Food Allergy 27
4. Food Allergy Prevalence in South Africa 43
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5. Study Aims, Objectives and Methodology 4 8
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6. Overall Results for Food Sensitisation and Allergy, and Risk 58

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Factors for Food Allergy
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7. Peanut Sensitisation, Allergy and Componenat Patterns in South 77
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African Children with Atopic Dermatitis

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8. Egg Sensitisation, Allergy and Comoponent Patterns in South 111

African Children with Atopic Dyermatitis
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9. Sensitisation and Allergy sPatterns to Cow’s Milk, Soya, Wheat, 138
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Fish and Tree Nut e
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10. Allergic Co-Moribidity of Patients with Atopic Dermatitis and 153
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Food AllergyU
11. Patterns of Introduction of Complementary Feeds and Solids 174
12. Conclusion: Clinical Application of Study Findings and the 180
Increasing Burden of Food Allergy in South Africa

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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

Chapter 1:
Introduction

Abbreviations
AD : Atopic Dermatitis
IgE : Immunoglobulin E
SPT: Skin Prick Test
ISAC: Immuno Solid Phase Allergen Chip
sIgE: Specific IgE
PPV: Positive Predictive Value n
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ROC: Receiver Operating Characteristic
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There is evidence of a significant increase in the prevalencee of food allergy, mostly studied in
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westernised countries, over the past 2-3 decades.1-3 The rise in food allergies has followed a few
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decades after a documented increase in respiratory allCergies, the latter having also been observed in
South Africa.4 Food allergy prevalence studies ar e methodologically difficult and time consuming.
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Standardised definitions of food allergy and standardised diagnostic work-ups are needed in order to

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be able to compare data between studies and regions.5
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The prevalence of food allergy in Srouth Africa is unknown. A handful of studies have looked at food
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sensitisation profiles and foovd allergy diagnosed according to self-report, but neither is a good
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representation of clinicallyn relevant food allergy. The gold standard diagnostic test in equivocal cases
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of food allergy, or when there is a discrepancy between history and screening test results, is the
controlled incremental food challenge.6 Double blind placebo controlled food challenges are
considered the gold standard, but require more time, staffing and preparation of foods. Incremental
open food challenges are usually sufficient to confirm or refute food allergy in young children, who
have few subjective symptoms.7 Prior to this study, there have been no food allergy prevalence studies
in South Africa utilising oral food challenges for the diagnosis of food allergy.
Atopic dermatitis is a significant risk factor for concomitant IgE-mediated food allergy. Children with
moderate to severe eczema have a 5-8 fold higher prevalence of IgE-mediated food allergy than the
general population. 8-10 The most common food allergies in children with atopic dermatitis are to hen’s
egg, cow’s milk, peanut, tree nuts, soya, fish and wheat. However, the prevalence of sensitisation to
foods (by skin prick test or specific IgE test) in children with atopic dermatitis far exceeds the
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

prevalence of true food allergy, thus there are many cases of “false positives” if sensitisation is taken
as a measure of food allergy. Therefore, in the assessment of food allergy, a thorough history should
always be combined with results of laboratory tests, and in equivocal cases an oral food challenge is
necessary.
As food challenges are time and resource consuming, and carry the risk of the patient reacting, an
attempt has been made at reducing the number of food challenges by the creation of “95%” or “100%”
positive predictive values (PPVs) for skin prick tests or specific IgE, which differ for each individual
food. 11,12 If the patient’s result for that test falls above the 95% PPV, the chance of the patient
reacting to that food during a challenge is deemed to be ≥ 95%. These internationally derived PPVs
are used in clinical practice to diagnose patients with values ≥ 95% PPV as allergic without needing to
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perform a food challenge. However, 95% PPVs are population specific, and may be affected by
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selection criteria of that population, environmental, socio-economic and ethnic factors.
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This study investigated sensitisation and allergy patterns to commonly allergenic foods in 100 children

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with atopic dermatitis, attending a dermatology clinic at a university hospital in Cape Town, South
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Africa (Red Cross Children’s Hospital). These children werae all of South African descent, either Xhosa
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(black African from the Western Cape) or mixed race (of mixed black African and Caucasian descent).

These 2 ethnic groups make up by far the majofrity of children attending the Red Cross Children’s
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Hospital hence could be recruited in meaning ful numbers. One of the main drivers for undertaking our
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study was the widespread perception tthat food allergy is uncommon in South African children,
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particularly in children of black South African origin. We chose a population of children with moderate
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to severe atopic dermatitis to evaluate the prevalence of food allergy in a population at high risk for
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food allergy. ni
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The thesis is structured as follows:
Chapters 2 and 3 review the epidemiology of food allergy and the relationship between atopic
dermatitis and food allergy. Studies on food allergy prevalence in South Africa are detailed in chapter
4. In chapter 5, the aims, objectives and methodology of our study are described in detail. Results of
the study for sensitisation and food allergy patterns, as well as risk factors for food allergy, are
described in chapter 6, including an analysis of ethnic differences. More detail on patterns for
individual foods are provided in chapters 7 (peanut), 8 (egg) and 9 (other foods). Children with atopic
dermatitis, as well as food allergy, are at increased risk for other atopic conditions: allergic co-
morbidity is described in chapter 10, looking at the interaction between eczema, food allergy,
aeroallergen sensitisation, asthma and allergic rhinitis. Chapter 11 focuses on food consumption
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

patterns, including the timing of introduction of commonly allergenic foods and more detail on peanut
consumption patterns, to try and ascertain whether this may influence food allergy patterns. Finally,
chapter 12 concludes the study findings and looks at some of the possible reasons why food allergy
may be on the rise in a country such as South Africa.

This study has several unique features which have helped to create a vast database of information:
Firstly it is unique in its utilisation of controlled food challenges as part of a diagnostic algorithm for
food allergy, giving accurate results for food allergy prevalence.
Secondly it is unique in the use of component derived diagnostics for food allergy testing. The study
utilises the ImmunoCAP ISAC technology, a microchip technology allowing tesnting to 103 allergenic
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components simultaneously. At the commencement of the study, this technology was new to South
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Africa.
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Patients who were sensitised by skin prick test or ISAC test aleso underwent standard ImmunoCAP
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testing for specific IgE’s to whole extracts as well as components. Therefore in this study we are also
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able to compare the performance of 3 diagnostic tests inC the prediction of food allergy: skin prick tests,

ISAC test and ImmunoCAP tests. This allowed analysis of sensitivities and specificities of a variety of
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tests, as well as analysis of positive predictive values, and Receiver Operating Characteristic (ROC)

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curve production for various diagnostic etntities.
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Lastly, the study is unique in thart it analyses ethnic differences in food sensitisation and allergy
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patterns within the same devfined geographical area. This study compares food sensitisation and
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allergy patterns in Xhosa pnatients with those of mixed race origin to assess whether there are clinically
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relevant differences.

References
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Claudia Gray PhD Thesis: Food Allergy in South African Children with Atopic Dermatitis

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