Current Allergy & Clinical Immunology - ALLSA

Current Allergy &
Clinical Immunology
CONTENTS
Editors
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Prof. Heather J Zar
Founding Editor
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Prof. M Jeebhay
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Dr S Kling
Dr A Lopata
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Dr A Morris
Prof. C Motala
Dr C Obihara (The Netherlands)
Prof. P Potter
Dr A Puterman
Prof. G Todd
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Cover: Skin-prick test
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ISSN 1609-3607
GUEST EDITORIAL
102 Myths and mimics of allergy
A Fox
REVIEW ARTICLES
104 Eight myths from the food
allergy clinic
R de Boer, R Fitzsimons,
N Brathwaite
110 Mimics of food allergy
ME Levin, H Steinman
117 Hypersensitivity to local
anaesthetics – 6 facts and 7
myths
J Lukawska, MR Caballero,
S Tsabouri, P Dugué
121 Food allergy epidemic – is it
only a western phenomenon
L van der Poel, J Chen,
M Penagos
ABC OF ALLERGY
127 Allergy investigations
S Emanuel, D Hawarden
ALLERGIES IN THE WORKPLACE
ALLSA RESEARCH AWARDS REPORT
132 Approaches to diagnosing
Anisakis allergy
N Nieuwenhuizen, M Jeebhay,
AL Lopata
SNIPPETS FROM THE JOURNALS
139 AS Puterman
CONGRESS REPORTS
140 2009 ALLSA Congress, held at
the Elangeni Hotel, Durban,
10-12 July 2009
PRODUCT NEWS
144, 145, 146, 147, 148, 150
CPD QUESTIONNAIRE
151 Earn 3 CPD points
INSTRUCTIONS FOR AUTHORS
152 Instructions for submitting an
article
Sponsorship & Support
Current Allergy & Clinical Immunology is the official journal of the Allergy
Society of South Africa and is produced as a service for health care
workers to improve understanding and communication in the field of
allergy. Publication of the journal is made possible by the generous
financial and other support offered by the following pharmaceutical and
diagnostic companies.
The Allergy Society of South Africa gratefully acknowledges support from
these companies:
Abbott • AHN Pharma • AstraZeneca •
Boehringer Ingelheim • Cipla Medpro •
GlaxoSmithKline • Laboratory Specialities •
Miele • MSD • Nestlé • Novartis •
Schering-Plough
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 101

GUEST EDITORIAL
MYTHS AND MIMICS OF ALLERGY
A recent cohort study from the
UK reported that over 33% of
parents believed their child to
have a symptom related to food
hypersensitivity by the age of 3. 1
While only a small proportion of
the children were shown to have
reproducible food-related symptoms,
these data confirm that
even if the rates of true food
hypersensitivity (estimated at
5-6% in the study) are not considered
epidemic, then parental concern related to it
surely is. This rise in parental perception of allergy as a
cause of a wide variety of different symptoms is reported
by colleagues around the world.
Unfortunately, even the best resourced health services
would struggle to keep up with not only the real rise in
allergic disease, but also the dramatic increase in the
‘worried well’ although perhaps this group would be
better termed the ‘worried non-allergic’. With inadequate
provision of specialists for provision of care 2 (and
the lack of educational opportunities for non-specialists
that result from this 3 ), it should be no surprise that we
find our patients troubled by conflicting advice. Among
this conflicting advice we find a number of commonly
held myths and misconceptions. As a practising paediatric
allergist, I encounter many, often deeply held,
beliefs that influence the way parents perceive and
manage their child’s disease, yet have no clear scientific
rationale. These beliefs may have been passed on by
relatives or be influenced by the popular media. Some
are specific to certain cultures while some seem to be
universal. Unfortunately, many of these myths may be
shared and indeed propagated by health professionals.
The article by De Boer et al. reports on some of the
most commonly raised myths from the Children’s
Allergy Clinic with a brief summary of the evidence that
counters them.
However, before we dismiss beliefs that may well
reflect an accumulation of ancient wisdom, it is worth
remembering that while our knowledge and understanding
of allergology has progressed hugely over the
last few years, our speciality is still in its infancy. New
data still challenge our assumptions about the very
basics of the natural history of common allergies. 4
Furthermore, data implicating the role of food in an
increasingly broad range of symptoms from classic IgEmediated
reactions to reflux, diarrhoea, constipation,
eczema and even nephrotic syndrome 5 continues to
emerge. It therefore makes the physician’s role even
more challenging, to tease out the cases where true
allergy underlies symptoms which more often than not
are unrelated; yet parents may be convinced they play
a role. In this issue of the journal, Levin and Steinman
consider some of the conditions that may mimic what
appears to be a case of food allergy but may have an
altogether different underlying mechanism.
One area of allergy that receives relatively little attention
is local anaesthetic allergy. Lukawska et al. articulately
challenge some of the many myths that have
developed in this area of practice while Van der Pohl et
al. consider a widely held myth that food allergy is a
problem almost exclusive to the western world.
In closing, I would like to take this opportunity to reflect
on the strength of the diaspora of South African allergologists,
particularly in the UK, which I deliberately
drew very heavily from when commissioning articles
for this issue of the journal. Children around the world
continue to benefit from the quality of care that South
African doctors are delivering.
Adam Fox
Guest editor
MA (Hons), MSc, MB BS, DCH, FRCPCH, FHEA, Dip Allergy
Consultant & Honorary Senior Lecturer in Paediatric
Allergy, Guy’s & St Thomas’ Hospitals, NHS Foundation
Trust/ King’s College, London, UK
1. Venter C, Pereira B, Voigt K, et al. Prevalence and cumulative incidence
of food hypersensitivity in the first 3 years of life. Allergy
2008; 63: 354-359.
2. Lee TH. Allergy: the unmet need. Clin Med 2003; 3: 303-305.
3. Lieberman L, Hilliard RI. How well do paediatric residency programmes
prepare residents for clinical practice and their future
careers Medical Education 2006; 40 (6), 539-546.
4. Skripak JM, Matsui EC, Mudd K, et al. The natural history of IgE
mediated cow’s milk allergy. J Allergy Clin Immunol 2007; 120:
1172-77.
5. De Sousa JS, Rosa FC, Baptista A, Fonseca H, Sá G. Cow's milk
protein sensitivity: a possible cause of nephrotic syndrome in early
infancy. J Pediatr Gastroenterol Nutr 1995; 21: 235-237.
102 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

EIGHT MYTHS FROM THE FOOD
ALLERGY CLINIC
Rachel de Boer, BSc Hons, PgDip (Diet), RD
Roisin Fitzsimons, BSc Hons, RN Child, Dip HE
St Thomas Hospital, London, UK
Nicola Brathwaite, MB ChB, FCPaed(SA), FRCPCH
Kings College Hospital, London, UK
ABSTRACT
There are a number of areas of controversy and
dogma surrounding food allergy that are widely
believed by both parents of children with food allergy
and the health professionals who care for them.
Consequences of these misconceptions include
heightened anxiety, risk taking, inappropriate food
exclusion with nutritional consequences and unnecessary
omission of vaccination because of fear of an
allergic reaction. New research is improving our
understanding of the development of allergies and
their management. This article aims to address a
few of the common myths in paediatric food allergy.
Allergy and allergic conditions are common, but there
are a number of areas of controversy and dogma that
are widely believed by both parents of children with
allergies and the health professionals who care for
them. The consequences of these misconceptions
may impact significantly on the child’s health and the
family’s lifestyle. For a child or adolescent with a food
allergy, risk taking, whether deliberate or unintentional,
may result in a potentially life-threatening allergic reaction.
However for some children with food allergy and
their families, heightened anxiety about this risk can
lead to significant restriction of normal activities. Many
children with eczema are sensitised to multiple foods
on specific IgE or skin-prick tests (SPTs). Not all of
these foods will necessarily result in allergic symptoms.
Parents may exclude certain foods because of an
inaccurate belief that the food is causing their child’s
symptoms. Inappropriate food exclusion can have significant
nutritional consequences such as iron deficiency,
rickets or protein-energy malnutrition. Where allergy
to a major food group is confirmed, it is important to
ensure a suitable alternative in the diet. Children with
egg allergy may be exposed to risk of infection with
measles because of a widespread misconception
among health professionals and the public that the vaccine
is contraindicated in children with egg allergy. It is
the role of the clinician to ensure accurate diagnosis
and appropriate advice on avoidance of the foods to
which the child is allergic, to provide appropriate medication
and training on the management of allergic reactions
and to empower the child and family to lead as
normal a life as possible while ensuring the health and
safety of the child.
MYTHS
The following myths are frequently encountered in the
food allergy clinic.
Correspondence: Dr Nicola Brathwaite, Department of Child Health,
Kings College Hospital, Denmark Hill, London SE5 9RS, UK. Tel +44
20 32994647, e-mail nicola.brathwaite@kcl.ac.uk
Myth: The larger the SPT wheal, the more
severe the allergy
SPTs involve the introduction of minute amounts of an
allergen into the epidermis, eliciting a wheal and flare
response which is then measured in millimetres. 1,2
While the size of the SPT wheal helps ascertain the
likelihood of an allergy, it does not predict the severity
of a reaction. For example, a person with a 2 mm SPT
wheal has less probability of clinical allergy than one
with an 8 mm wheal, but if the person is allergic, the
smaller wheal does not necessarily mean he or she will
have a less severe reaction.
Food allergens eliciting an SPT wheal size >3 mm are
generally considered to be positive, suggesting the
child is sensitised to that allergen. 1 However the positive
predictive value of a positive SPT based on this definition
is 3 mm to be able to eat the food
tested without adverse reaction. Similarly, a child with
a wheal 95% specificity of SPT size in predicting
a positive food challenge in a group of children
where there was a strong clinical suspicion of food
allergy.
Table I. SPT wheal diameters giving >95% specificity
in predicting the outcome of food challenges 1
Allergen Size of wheal Size of wheal
in children >2 years in children

Myth: The severity of past allergic reactions
predicts the severity of future reactions
Common misconceptions in IgE-mediated food allergy
include the belief that the severity of allergic reactions
increases with subsequent exposure, and that an individual
who has previously experienced mild reactions
will only experience mild reactions in future.
The unpredictable nature of allergy means the severity
of a reaction is difficult to anticipate and depends on
multiple factors including: amount of allergen ingested;
state of the allergen, e.g. raw or cooked egg; intercurrent
illness, e.g. the presence of active asthma; concomitant
medication; consumption of alcohol; and
exercise after exposure. 2
Several studies have attempted to clarify whether the
severity of previous allergic reactions predicts the
severity of a future allergic episode. 9,10 A previous
severe reaction is a predictor of risk of future anaphylaxis,
and a history of asthma is an important risk factor
for life-threatening reactions. However the converse,
that individuals who have only experienced mild reactions
are unlikely to have a severe reaction, is not true 11
and the absence of asthma does not ensure that the
child is in a low-risk category. 12
The European Academy of Allergology and Clinical
Immunology (EAACI) taskforce for anaphylaxis in children
have identified criteria which help clinicians categorise
children who may be at higher risk of anaphylaxis
(Table II). 13
Table II. Identification of children at higher risk of an
anaphylaxis 13
Absolute risk of anaphylaxis
Coexistent asthma
Previous anaphylaxis to food, drug or insect sting
Food-dependent exercise-induced anaphylaxis (FDEIA)
Idiopathic anaphylaxis
Relative risk of anaphylaxis
Reacted to trace quantities of allergen, i.e. vapour or
topical contact
Peanut or tree nut allergy
Teenager with a food allergy
Living in a remote area, far from medical services
Myth: An adrenaline auto-injector should
be prescribed for all children with food
allergy
Adrenaline auto-injector devices (Anaguard, Epipen and
Anapen) are syringes and needles preloaded with
adrenaline. Adrenaline is the drug of choice for anaphylaxis.
To ensure the best outcome it should be given
at the first sign of an anaphylaxis. 13 There are a number
of issues to consider when deciding who should be
prescribed an adrenaline auto-injector.
As discussed previously the severity of an allergic reaction
can be difficult to predict. Those children in the
‘absolute risk of anaphylaxis’ category (Table II) should
always be prescribed an adrenaline auto-injector
device. Those in the ‘relative risk’ category should be
considered individually. 9
The prescription of an auto-injector should always be
given in conjunction with training in its use, a clear
emergency management plan and advice on allergen
avoidance. 13 The likelihood of a subsequent severe
allergic reaction is much reduced in nut allergic children
followed up in a specialist allergy clinic. 14 Although
adrenaline auto-injectors are widely prescribed in the
UK, many parents fail to administer them when their
child has anaphylaxis. 15
The Epipen and Anapen devices contain a single dose
of adrenaline. It is recommended that two devices are
carried at all times, including while children are at
school. These devices are available in a paediatric dose
for children weighing between 15 kg and 30 kg. The
Anaguard is pre-loaded with two doses of adrenaline,
but is only available in an adult dose.
A second dose of adrenaline is only required by 20% of
children with anaphylaxis; however, this may be lifesaving
for those living in remote areas, when a device
malfunctions or if the first dose is accidentally injected
into the administering caregiver. 9
The cost of an adrenaline auto-injector ranges from
US$30 to US$110 which may be prohibitive. In some
countries there is limited or no availability 16 in which
case allergen avoidance advice and education of recognition
of signs of an allergic reaction is particularly
important so that medical help can be sought at the
earliest opportunity. 17
Myth: Soya milk infant formula is a suitable
alternative to cow’s milk formula in
infants who are allergic to cow’s milk
Soya infant formula has historically been used as an
alternative to the universally standard cow’s milk formula.
An alternative formula may be sought for a number
of reasons including cultural and religious beliefs,
following a vegetarian or vegan diet, as well as the
diagnosis of a cow’s milk protein allergy (CMPA).
Despite fairly limited indications for its use, soya formula
accounts for approximately 20% of the formula
market in the USA 18 and is used by 2% of infants in the
UK. 19
In recent years concerns have arisen regarding the
safety of its use because of the high phyto-oestrogen
content. The structural similarity of isoflavones (a
member of the phyto-oestrogen family) in soya and
oestrogen has prompted studies exploring the potential
negative impact the consumption of soya at an
early age may have on sexual development and reproduction.
The majority of research thus far has been carried
out on animals and there is little evidence relating
to human infants. 19,20
The general consensus is that current evidence does
not give rise to major concern; however, further studies
are needed. As a precaution the Department of
Health in the UK recommends soya formulas should
only be used when clinically indicated. 19-21 This advice is
echoed by the UK Chief Medical Officer, who states
they should only be used in exceptional circumstances,
and the British Dietetic Association (BDA) Paediatric
Group 22 and the ESPGHAN committee on Nutrition
who recommend use of soya formula be discouraged,
particularly before 6 months when it is the sole source
of nutrition. 23
There are also concerns regarding the use of soya
infant formula as a first-line treatment in CMPA, as
some milk-allergic infants will also be soya-allergic.
Estimates of cross-reactivity vary considerably. 24,25 Up
to 60% of children with cow‘s milk protein-induced
enterocolitis (non-IgE-mediated) will be sensitive to
soya, 18 while this appears less likely in children with
IgE-mediated allergy.
Soya formulas continue to play a role for older infants
(>6 months) with IgE-mediated CMPA who refuse
extensively hydrolysed formulas (EHF). They do offer
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 105

distinct advantages over EHF with regard to palatability
and cost and may also be useful where EHF and/or
elemental formulas are not available.
Myth: Goat’s milk infant formula can be
used as an alternative to cow’s milk infant
formula in cow’s-milk-allergic infants
Goat’s milk has also long been used as an alternative to
cow’s milk as many people mistakenly believe it is suitable
for use in CMPA. Despite often being advocated
for this purpose in lay publications, these claims have
not been substantiated.
There is close homology between proteins in goat’s
milk and cow’s milk, and in fact all mammalian milk
including sheep and buffalo milk, and clinically significant
cross-allergenicity has been observed. 26 Up to
90% of infants with CMPA show IgE cross-reactivity
with the protein in goat’s milk; 27,28 therefore goat’s milk
and goat’s milk infant formula are not recommended in
CMPA. 29 Goat’s milk infant formula has been banned
from sale in the UK since March 2007, following a recommendation
by the European Food Safety Authority
(EFSA) that there is insufficient data to establish adequacy
and nutritional safety of goat’s milk protein as a
protein source in infants. 30
Unmodified goat’s milk is contraindicated in infants
because of its nutritional inadequacy, e.g. low folate
content, high renal solute load and doubtful microbial
safety. 30
First-line treatment for infants with CMPA is usually
EHF, an elemental formula or soya formula after 6
months. Soya, rice and oat milk are often used for older
children (over 2 years) with CMPA, but are not nutritionally
adequate for infants. While some studies suggest
that donkey, mare or camel milk may be well tolerated
in CMPA, these are not widely available. 31
Myth: Mothers of infants at high risk of
developing allergy should avoid high-risk
foods during pregnancy and lactation
Infants with family history of allergic disease are at
greater risk of developing allergies. 32 Most allergy prevention
advice focuses specifically on this high-risk
group. There is no convincing evidence at present for
the protective effect of maternal allergen avoidance
during pregnancy or lactation. Several studies indicate
maternal avoidance of potential allergens during breastfeeding
may reduce atopic dermatitis; however other
studies do not confirm this. 33
The American Academy of Pediatrics (AAP) previously
recommended elimination of peanuts and consideration
of elimination of eggs, cow’s milk and fish during
lactation in mothers of high-risk infants. 34 This advice
has recently been withdrawn and the new guidelines 35
now concur with the EAACI advice that there is no evidence
for maternal dietary intervention during pregnancy
and/or lactation and that this intervention may
nutritionally compromise the mother and child. 36
An area of particular contention is peanut allergy, given
its dramatic rise over the past 2 decades. In 1998 the
Department of Health in the UK issued recommendations
aiming to reduce the incidence of peanut allergy.
37 Because of the possibility that sensitisation to
peanut may be occurring in utero or during lactation,
they suggested that pregnant or breastfeeding women
might wish to avoid eating peanuts should they or their
partner have an allergic condition. This guidance is currently
under review. In recent years a new concept has
emerged – peanut sensitisation occurring through different
routes, including through the skin. 38 We still
don’t know the best strategy to prevent development
of peanut allergy, 39 but it is clear that in countries
where exposure to peanut protein at an early age is the
norm there appears to be low incidence of peanut allergy.
40 The hypothesis that early introduction of peanuts
into infants’ diet is protective is currently being tested
in a randomised interventional trial (LEAP study).
Myth: Everyone who has a peanut allergy
must avoid all types of nuts
Peanuts and tree nuts such as cashew, pistachio,
hazelnuts and almonds are often discussed interchangeably
although they do not belong to the same
botanical family. While the nuts are unrelated botanically,
up to 60% of children with peanut allergy will also
be sensitised to one or more tree nuts. 40 Considering
the potential severity of the allergy and issues with
accurate identification, peanut-allergic children are
often advised to avoid all peanuts and tree nuts.
However, many will tolerate one or more types of tree
nuts and do safely continue to consume them. 41 If
some nuts are eaten while others are avoided as they
may cause a fatal reaction, the risk of cross-contamination
is an important issue.
Cross-contamination occurs when a safe food comes
into contact with a food allergen, e.g. when different
nuts are stored together, where nuts and nut-free products
share the same factory line, or where utensils and
equipment used to prepare a nut-containing food contaminate
another food. 41 A further issue is adulteration,
where one nut is sold as another; for example, almond
desserts sold in restaurants which actually contain
peanuts.
If a peanut-allergic child continues eating other nuts,
parents must be educated on how to minimise risk.
This may include advice to offer only plain, not
processed, nuts in the home environment only when
the child is well and with a management plan of how to
avoid an allergic reaction and medication close at hand.
Many children unnecessarily avoid other foods associated
with peanut allergy, where there is risk of co-reactivity,
e.g. sesame, pine nut, legumes and lupin. 37,42
Allergy tests can help to guide advice. Avoidance of
these foods is not routinely advised unless previous
reactions are reported.
Some foods are avoided unnecessarily because their
name contains the word nut, e.g. butternut, nutmeg,
coconut. Although allergies to these foods have been
reported they are rare and do not appear to be more
common in children with nut allergies.
Refined peanut oil will not cause allergic reactions in
the majority of peanut-allergic individuals and if anyone
does suffer a reaction, it is likely to be mild. Unrefined
(crude) peanut oil is more likely to cause symptoms. 43
Myth: Children allergic to hen’s egg can
not have the measles or MMR vaccine as
it contains egg
The measles vaccine is part of the routine vaccination
programme for children across the world. 44 In South
Africa and other countries, it is given as a monovalent
vaccine at 9 and 18 months of age, whereas in Europe,
Australia and the USA it is given as a combined vaccine:
mumps, measles and rubella (MMR). 44,45 A common
misconception that these vaccines contain egg
and may cause an allergic reaction in those children
allergic to egg, alongside unfounded concerns relating
to autism, was partly to blame for the dip in the immunisation
rate for MMR in the UK in the late 1990s to
less than 80%. 46
106 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

A Cochrane review examined the safety and efficacy of
the MMR vaccine but did not focus on egg allergy and
the MMR. 47 Egg allergy and the administration of the
measles or MMR vaccine was the primary outcome of
a study by Baxter 48 and a review by James et al. 49 In
these studies children with confirmed egg allergy were
given the measles or MMR vaccine and the number of
children reacting to the vaccine was low. Both vaccines
are grown on cultured chick fibroblasts and do not contain
hen’s egg protein. Reactions to these vaccines are
usually due to another component of the vaccine, such
as neomycin or gelatine, and the measles or MMR vaccine
should not pose a risk to children who are allergic
to hen’s egg, 46-49 unlike the influenza vaccine and yellow
fever vaccines which are prepared in hen’s eggs
and are contraindicated in severe egg allergy.
The WHO recommends that all children be immunised
with the measles or MMR vaccine as appropriate to
their geographical location. The current recommendation
of the British Society of Allergy and Clinical
Immunology Paediatric Allergy Group is that the MMR
vaccine may be administered to all egg-allergic children
in a routine primary care setting. 50
Declaration of conflict of interest
The authors declare no conflict of interest.
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25. Hill DJ, Ford RPK, Selton MJ, Hosking CS. A study of 100 infants
and young children with cow’s milk allergy. Clin Rev Allergy 1984;
2: 125-142.
26. Restani P, Gaiaschi A, Plebani A, et al. Cross-reactivity between
milk proteins from different animal species. Clin Exp Allergy. 1999;
29: 997-1004.
27. Bellioni-Businco B, Paganelli R, Lucenti P, Giampietro PG, Perborn
H, Businco L. Allergenicity of goat’s milk in children with cow’s milk
allergy. J Allergy Clin Immunol 1999; 103: 1191-1194.
28. Infante Pina D, Tormo Carnice R, Conde Zandueta M. Use of goat’s
milk in patients with cow’s milk allergy. Ann Pediatr 2003; 59: 138-
142.
29. Department of Health 2007. Advice on infant milks based on goat’s
milk http://www.dh.gov.uk/en/Policyandguidance/Health andsocialcaretopics/Maternalandinfantnutrition/DH_4099143
30. European Food Safety Authority Statement. Replying to applicant's
comment on the Panel's Opinion relating to the evaluation of goat’s
milk protein as a protein source for infant formulae and follow-on
formulae by the Scientific Panel on Dietetic Products, Nutrition and
Allergies (NDA). July 2006 http://www.efsa.europa.
eu/EFSA/efsa_locale-1178620753812_1178620767562.htm
31. Restani P, Beretta B, Fiocchi A, Ballabio C, Galli CL. Cross-reactivity
between mammalian proteins. Ann Allergy Asthma Immunol.
2002; 89 (6 Suppl 1): 11-15.
32. Kurukulaaratchy R, Fenn M, Matthews S, Hasan Arshad S. The
prevalence, characteristics of and early life risk factors for eczema
in 10-year-old children. Pediatr Allergy Immunol. 2003; 14: 178-183.
33. Kramer MS, Kakuma R. Maternal dietary antigen avoidance during
pregnancy or lactation, or both, for preventing or treating atopic disease
in the child. Cochrane Database Syst Rev. 2006 Jul 19; 3:
CD000133.
34. AAP (American Academy of Pediatrics). Hypoallergenic infant formulas.
Pediatrics 2000; 106: 346-349.
35. Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics
Committee on Nutrition; American Academy of Pediatrics Section
on Allergy and Immunology. Effects of early nutritional interventions
on the development of atopic disease in infants and children:
the role of maternal dietary restriction, breastfeeding, timing of
introduction of complementary foods, and hydrolyzed formulas.
Pediatrics. 2008; 121: 183-191.
36. Muraro A, Dreborg S, Halken S, et al. Dietary prevention of allergic
diseases in infants and small children. Pediatr Allergy Immunol
2004; 15: 291-307.
37. Committee on Toxicity of Chemicals in Food, Consumer Products
and the Environment (COT). Peanut Allergy. London: DoH, 1998.
38. Lack G, Fox D, Northstone K, Golding J. Factors associated with
the development of peanut allergy. N Engl J Med 2003; 348: 977-
985.
39. Burks AW. Early peanut consumption: postpone or promote
J Allergy Clin Immunol. 2009 Feb; 123(2): 417-23.
40. Du Toit G, Katz Y, Sasieni P. Early consumption of peanuts in infancy
is associated with a low prevalence of peanut allergy. J Allergy
Clin Immunol 2008; 122: 984-991.
41. Furlong TJ, DeSimone J, Sicherer SH. Peanut and tree nut allergic
reactions in restaurants and other food establishments. J Allergy
Clin Immunol. 2001; 108: 867-870.
42. Sicherer SH. Clinical implications of cross-reactive food allergens. J
Allergy Clin Immunol 2001; 108: 881-890.
43. Hourihane JO, Bedwani SJ, Dean TP, Warner JO. Randomised,
double blind, crossover challenge study of allergenicity of peanut
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 107

oils in subjects allergic to peanuts. BMJ 1997; 314: 1084-1088.
44. World Health Organisation. Measles vaccines; WHO position
paper. Weekly Epidemiological Record 2004; 14: 130-142.
45. http://www.immunisation.nhs.uk/Vaccines/MMR
46. Fox A, Lack G. Egg allergy and MMR vaccination Br J Gen Pract
2003; 53: 801-802.
47. Demicheli V, Jefferson T, Rivetti A, Price D. Vaccines for measles,
mumps and rubella in children. Cochrane Database of Systematic
Reviews 2005, Issue 4. Art. No.: CD004407. DOI: 10.1002/
14651858.CD004407.pub2.
48. Baxter DN. Measles immunization in children with a history of egg
allergy. Vaccine 2003; 14: 131-134.
49. James JM, Burks AW, Roberson PK, Sampson HA. Safe administration
of the measles vaccine to children allergic to eggs. New
Engl J Med 1995; 332: 1262-1266.
50. British Society of Allergy and Clinical Immunology Paediatric
Allergy Group (BSACI-PAG) Recommendations for combined
measles, mumps and rubella (MMR) vaccination in egg-allergic children.
PATIENT INFORMATION SHEETS –
ANOTHER ALLSA MEMBERSHIP BENEFIT
Did you know that membership of ALLSA entitles you to receive copies of our Patient Information
Sheets which provide information on various aspects of allergy in an easy-to-understand format for
your patients
Topics covered include:
Allergen Immunotherapy
Allergic Reactions to Honey Bee and Wasp Stings
Allergic Rhinitis
Bedding Protectors and Allergy Control
Cockroach Allergy
Coeliac Disease
Contact Dermatitis
Drug Allergy
Egg Allergy
Fish Allergy
Food Additives and Preservatives
Food Allergy
House-Dust Mite Allergy
Latex Allergy
Milk Allergy/Intolerance
Mould Allergy
Peanut Allergy
Pet Allergy
Seafood Allergy
Soya Allergy
Treatment of Allergic Eczema
Urticaria and Angioedema
Vacuuming and Allergy Control
Wheat Allergy
Patient information sheets can be ordered in batches of 50 from the ALLSA office, tel 021-447-9019,
email mail@allergysa.org
There is no charge for the leaflets, but we do charge for postage.
108 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

MIMICS OF FOOD ALLERGY
Michael E Levin, MB ChB, FCPaed (SA), Dip
Allergy, MMed (Paed), PhD (Linguistics)
Allergy and Asthma Service, Red Cross War Memorial
Children's Hospital, School of Child and Adolescent
Health, University of Cape Town, Rondebosch, Cape
Town, South Africa, email: luvuyo@mweb.co.za
Harris Steinman, MB ChB, DCh (SA)
Food & Allergy Consulting and Testing Services,
Milnerton, Cape Town, South Africa, email: harris@zingsolutions.com
ABSTRACT
Adverse reactions to food include diverse mechanisms,
and distinguishing between true food allergy
and other adverse reactions may not be easy as
many may mimic food allergy. The differential diagnosis
is wide, comprising psychological reactions
(food aversion), organic or anatomical reactions,
toxic reactions and non-toxic reactions (food allergy
and food intolerance/non-immune mediated food
hypersensitivity).
The classification and differential diagnosis of nonimmune
adverse food reactions is discussed and
selected examples (lactose intolerance, sucrose
intolerance, alcohol intolerance, pharmacological
reactions and unabsorbable wax esters) are discussed
in more detail.
Immune reactions (food allergies) may be difficult to
diagnose (and to identify the causative food) where
non-IgE mechanisms are implicated, where diagnostic
tests are falsely negative despite true IgEmediated
allergy and where hidden ingredients or
concomitant allergens are present.
INTRODUCTION
Up to 34% of individuals or parents think that they or
family members have a food allergy and 22% avoid particular
foods on the mere suspicion that the food may
contain an allergen. In fact only between 1% and 6%
test positive on full evaluation which may include double-blind
placebo-controlled food challenges. 1-4 Much
has been made of this discrepancy between perceived
food allergy and true food allergy, but many people
without true food allergy may indeed be suffering significant
symptoms associated with ingestion of food
which have other important and avoidable causative
factors.
The potential mimics of food allergy are extensive and
this review focuses on a limited number of more common
causes.
CLASSIFYING ADVERSE REACTIONS TO
FOODS
Adverse reactions to food can be categorised as psychological
(food aversion), organic or anatomical, toxic
and non-toxic reactions (Fig. 1). 5
Psychological reactions to food (food aversion) manifest
as food refusal, poor feeding, and somatic symptoms
such as vomiting, gagging, irritability and failure
to thrive. Food aversion leads to significant problems
and may be very difficult to diagnose and manage.
Psychological food refusal without any organic cause
may have an onset of symptoms before age 2 and be
present for longer than 1 month. Poor food intake, poor
weight gain, and vomiting do not discriminate between
organic and nonorganic causes, but factors indicating
the presence of a behavioural cause include food
refusal, food fixation, abnormal parental feeding practices,
onset after a specific trigger and presence of
anticipatory gagging. 6
Organic and anatomical problems causing food-related
problems include pyloric stenosis, hiatal hernia,
Hirschprung's disease, tracheoesophageal fistula, irritable
bowel syndrome and inflammatory bowel disease.
Several other conditions, including ulcers and
cancers of the gastrointestinal (GI) tract, may cause
some of the same symptoms as food allergy. Frey's
syndrome, or auriculotemporal gustatory sweating has
been reported to occur with orange juice, tomato,
onion, and certain non-chocolate candies and snack
foods. 7
Toxic reactions may manifest because of an inherent
ingredient in a food that has a toxic potential in its own
right. The reaction is not mediated through immune,
intolerance or pharmacological reactions but through
Adverse reaction to food
Psychological
(food aversion)
Organic
Toxic
(microbiological
pharmacological)
Non-toxic
Fig. 1. Classification of adverse reactions to food.
Correspondence: Dr Harris Steinman, Food & Allergy Consulting and Testing Services, PO Box 565, Milnerton 7435. E-mail: harris@zingsolutions.com
110 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

the implicit toxicity of the ingredient. Toxic reactions
may therefore occur in all individuals exposed to the
food. Examples include bacterial toxins in spoilt food
that may result in nausea and vomiting, which may be
ascribed to an allergy. Another example is histamine
poisoning (scombroid poisoning) resulting from the
ingestion of tuna or yellowtail. Examples of toxic reactions
are listed in Table I. Not all toxic reactions mimic
allergic symptoms – some have explicit symptoms specific
to that toxin.
Non-toxic reactions imply an individual hypersensitivity
to the food, either immune mediated (food allergy) or
not immune mediated (food intolerance) (Fig, 2). Nontoxic
reactions only occur in susceptible individuals,
and are not experienced by all people exposed to that
particular food. New nomenclature 8 refers to 'food
intolerance' as 'non-allergic food hypersensitivity'.
FOOD INTOLERANCE/NON-ALLERGIC
FOOD HYPERSENSITIVITY
Food intolerance may result from enzyme deficiencies,
pharmacological reactions and other mechanisms.
Enzyme deficiencies
The most common cause of food intolerance is related
to enzyme deficiencies. Table II lists a selected number
of food intolerance reactions occurring as a result of
enzyme intolerance.
Table I. Toxic reactions from food
Salmonella, staphylococcus Food spoilage
Cyanogenic glycosides Kernel of almonds,
apricots, cassava
Fungal aflatoxins
Peanut, apple juice
Trichothecenes
Wheat
Atropine
Mushroom
Ochratoxin
Various grains
Glucosinolates
Brassicaceous vegetables,
e.g. cabbage
Pyrrolizidine alkaloids Comfrey
Haemaglutinins
Beans
Solanine
Potatoes (raw) and related
plants
Seafood toxins
Spoiled fish, especially
scombroid fish
Tetrodotoxin
Puffer fish
Saxitoxins
Clams, oysters
Neurotoxin (lathyrism) Chickling Vetch / grass pea
Nitrates
Green vegetables, e.g.
spinach
Lactose intolerance
Approximately 2% of infants experience an adverse
reaction to milk. A great deal of the time, the problem
is not a milk allergy but caused by the body's deficiency
of the -lactase enzyme, known as lactose intolerance.
After the age of 5, approximately 15-25% of
Caucasian children and up to 95% of black individuals
will develop a partial to complete deficiency of lactase
enzyme. The symptoms are typically flatulence, abdominal
cramps, and diarrhoea, but may be difficult to separate
from those of non-IgE-mediated GI allergy. 9,10
The suspicion of lactase deficiency is raised by a history
of GI symptoms, occurring after or aggravated by
milk ingestion. This may respond or resolve completely
with avoidance of dairy products. Subjects may be
better tolerant of yoghurts and hard cheeses because
of partial breakdown of lactose during the manufacturing
process. 10
Although rarely performed, laboratory confirmation
may include a hydrogen breath test and lactose tolerance
test. More commonly, a stool sample is taken
which shows reducing substances or acidic pH. This
indicates unabsorbed osmotically active substances.
Occasionally a small intestinal biopsy is performed to
assess direct lactase enzyme activity. 10
Fructose intolerance
Although lactose intolerance is probably the most
common enzymatic deficiency condition recognised,
and often confused with allergic symptoms, the overhasty
diagnosis of lactose intolerance in infants and
toddlers has probably caused many cases of fructose
intolerance to be overlooked. 11
Fruit juice has become a significant part of young children's
diets. Marketing surveys have shown that
infants consume, on average, 150 ml of juice per day,
and about 1% consume more than 600 ml daily. 12
Fructose malabsorption can occur as frequently in normal,
healthy children and adults as in those with functional
bowel disease (such as irritable bowel disease). 13
Although symptoms may classically involve features of
food intolerance, e.g. unexplained bloating, flatus, and
distension, atypical features may be confused with
symptoms of allergy.
Non-toxic
Immune-mediated
(food allergy)
Non-immune-mediated
(food intolerance)
IgE-mediated Non-IgE-mediated Enzymatic Pharmacological Other
Fig. 2. Classification of non-toxic reactions to food.
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 111

Table II. Enzyme deficiencies
Lactase deficiency
Fructose intolerance
Sucrose intolerance
Alcohol intolerance
Sulphite intolerance
G6PD deficiency
Pancreatic insufficiency
Galactosaemia
Phenylketonuria
Lactose (milk)
Fructose, especially fruit juices
Sucrose and starch
Alcohol
Sulphite preservatives
Fava (broad) beans
Fatty food
Lactose and galactose (milk
and legumes)
Phenylalanine (high protein
foods) and aspartame
sweetener
The mechanism of fructose absorption is not completely
understood. The absorption capacity of fructose
is much more complete when fructose is given either
as sucrose to be broken down or with glucose than
when it is ingested alone. Clinical studies have demonstrated
this, with malabsorption being more apparent
when the fructose concentration exceeds that of glucose
(e.g. in apple and pear juice) than when the two
sugars are present in equal concentrations (e.g. in
white grape juice). However, when provided in appropriate
amounts (10 ml/kg body weight), these different
juices are absorbed equally well. 14 Whereas orange
juice was the major juice produced 50 years ago (primarily
to prevent scurvy), now apple juice is the juice
of choice for the under-5 age group. The result is a
higher fructose intake. 15 Fifty per cent of juice consumed
by young children is apple juice. 12 Even at
intakes of 15 ml/kg (or 240 ml in another study) at a
time, which is generally seen as an acceptable serving
size, apple juice has been associated with symptoms.
Fruit juice manufacturers often use deflavoured apple
juice to increase the volume of other fruit juices, which
increases their fructose content. Interestingly, a study
has shown that freshly pressed and unprocessed
('cloudy') apple juice did not influence stool frequency
and consistency, compared with enzymatically processed
('clear') apple juice, which significantly promoted
diarrhoea. It was suggested that, in addition to fructose,
the increased availability of non-absorbable
monosaccharides and oligosaccharides as a result of
the enzymatic processing of apple pulp is an important
aetiological factor in apple juice-induced chronic nonspecific
diarrhoea. 15
Alcohol intolerance
Alcoholic drinks are complex, consisting of hundreds of
components, which play a role in the flavour and character
of these drinks. Alcoholic drinks are involved in a
variety of reactions.
True allergy
Ethanol may rarely be responsible for anaphylactic
reactions. A 25-year-old patient suffered from urticaria
and acute anaphylactoid symptoms after ingestion of
alcoholic beverages. The skin-prick test for acetic acid
(5%) and for acetaldehyde (50% and 100%) was positive.
The symptoms could be reproduced in an oral
provocation test with pure ethanol (20%). 17
True food allergy may be experienced to a number of
minor constituents of alcoholic beverages. This may
cause diagnostic difficulty because the allergen is
'occult' or 'hidden'. Examples include allergy to wheat
in beer 18 or residual lipid transfer proteins from barley
or malt in beer. 19,20 Adverse effects to the lipid transfer
proteins in beer may be a result of cross-reactivity due
to primary peach allergy. 21
Alcohol may trigger asthma, food allergy or exerciseinduced
anaphylaxis in susceptible subjects. In addition,
there is increasing evidence that alcohol intake
may play a role as a promoter of the development of
IgE-mediated hypersensitivity to different allergens 22
and act as a histamine liberator. 23 Furthermore, alcohol
consumption is associated with increased serum IgE of
unknown specificity. 24
A case report has been described of an 18-year-old
woman with alcohol-induced anaphylaxis to grape. 25
Her first episode comprised generalised urticaria, facial
angio-oedema and nasal obstruction 20 minutes after
ingesting grape and a glass of champagne. A year later,
10 minutes after ingesting the same combination she
developed abdominal pain, vomiting, facial angio-oedema
and nasal obstruction. She remained asymptomatic
if she ate the fruit alone but not if grape was associated
with alcoholic drinks. Skin-prick test with a commercial
extract of white and red grape was negative.
No grape-specific IgE could be demonstrated and oral
challenge with grapes and champagne together were
positive (negative for 1 grape and 5 ml champagne but
positive for 12 grapes and 50 ml champagne). 25
Intolerance
Often not considered, alcohol intolerance results in a
number of symptoms that may mimic allergy or result
in an aggravation or enhancement of allergic symptoms.
These include flushing syndrome and anaphylactoid
reactions such as urticaria/angio-oedema and even
shock.
Approximately 45% of Japanese people have a partial
to severe acetaldehyde dehydrogenase 2 (ALDH2)
enzyme deficiency which may result in alcohol-induced
asthma and other symptoms. 26-28 This is the same
enzyme that is blocked by disulfiram in order to cause
reactions with alcohol ingestion in an attempt to contain
or cure alcoholism. Other drugs that cause a disulfiram-like
reaction include antibiotics (e.g. metronidazole,
sulphonamides, some cephalosporins, nitrofurantoin,
chloramphenicol), antifungals (griseofulvin) and
chloral hydrate. Rarer causes include exposure to
industrial solvents and pesticides (e.g. carbamates,
monosulfiram [Tetmosol]) and ingestion of mushrooms
(notably the otherwise delicious common ink-cap
Coprinus atramentarius).
Alcoholic drinks are complex and adverse reactions
may occur as a result of a number of other causes
which are better categorised as pharmacological or
immune related, including adverse reactions to sulphites
in wine and beer. 29 Sulphur dioxide and the sulphite
preservatives are well-known preservatives used
in a wide range of foods including alcoholic beverages
and soft drinks. They are well-known triggers of asthma.
Although not fully elucidated, the mechanism has
been considered to be sulphite oxidase deficiency,
which would classify it as an enzymatic reaction. In this
case, the deficiency is variable in severity in different
individuals, resulting in different levels of tolerance to
drinks containing sulphites. 30,31 However, the ability of
the cellular antigen stimulation test (CAST) to often
accurately indicate sulphite sensitivity suggests that
other mechanisms may also contribute.
Pharmacological reactions
Pharmacological reactions refer to constituents that
are normally present in foods, that when ingested in
excess will result in a dose-dependent drug-like effect.
However, this category is blurred by the fact that some
112 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

people have a partial to complete, temporary or permanent
deficiency of an enzyme required to break
down the constituent, or that someone may have a
heightened sensitivity to the constituent, resulting in
adverse effects when the food is ingested in an average
serving. These include histamine (wine, certain
cheese, spinach, strawberry, tomato, sauerkraut and
other fermented food), caffeine (coffee, tea, cola
drinks, cocoa, chocolate), tyramine 32 (cheese, beer,
chocolate, cured meat, pickled herring, Marmite), theobromine
(chocolate), alcohol and serotonin (tomato,
banana, pineapple, walnuts). All vasoactive amines,
which include dopamine, histamine, norepinephrine,
phenylethylamine, serotonin and tyramine, have been
implicated in pharmacological reactions. 33 In scombroid
poisoning (histamine poisoning) (pharmacological reaction),
the level of histamine in the spoilt fish is markedly
high, resulting in almost everyone ingesting the fish
being affected, whereas in people with a diamine oxidase
(DAO) deficiency, histamine in wine, tomato, etc.,
may result in symptoms. Also, certain drugs, e.g. isoniazid,
may impair DAO activity. 34,35 This similarly
occurs for other constituents listed in Table III.
Other food intolerance
Selected examples of food intolerance with non-enzymatic
and non-pharmacological mechanisms include
aspirin hypersensitivity (leading to asthma and
urticaria), sensitivity to monosodium glutamate 35 (leading
to headache and flushing) and unabsorbable wax
esters in fish (leading to diarrhoea). In European countries,
acetyl-salicylic acid may be added to homemade
canned fruits, berries and vegetables, which may result
in urticaria in acetyl-salicylic-sensitive individuals. 37
Acetyl-salicylate sensitivity needs to be differentiated
from sodium salicylate sensitivity, a controversial clinical
entity. 38,39 Additives used in foods, including food
dyes, can also trigger allergies and intolerances. The
dyes most frequently associated with allergy or
adverse reactions include: carmine, tartrazine, red
FD&C No. 2, and brilliant blue. 40 These same dyes are
also used to colour certain oral medications. 41 Reports
of allergy-like reactions to sodium benzoate are
increasing. 42-44
Unabsorbable wax esters
The passage of oil through the rectum has been
observed following the ingestion of 'butterfish'.
Anecdotally this condition occurs more commonly than
reported in the literature. There have only been a few
articles in the literature on this subject: one in a South
African journal 45 and three in one issue of Communicable
Diseases Intelligence in 2002. 46-48 The incidence
is likely to increase as butterfish is eaten more
commonly, especially as sushi. In the literature, there is
some confusion about the correct names of the fish
that cause this passage of oil per rectum. Reactions
Table III. Substances in foods responsible for pharmacological
reactions
Histamine
Tyramine
Serotonin
Theobromine
Spoilt fish (scombroid poisoning),
wine, certain cheese, spinach,
strawberry, tomato, sauerkraut
and other fermented food
Cheese, beer, chocolate, cured
meat, pickled herring, Marmite
Tomato, banana, pineapple, walnuts
Chocolate
have been associated with 'escolar', 'oilfish', 'rudderfish'
and 'Lepidocybium flavobrunneum,' the latter
given as the scientific name for butterfish when this is
in fact Scatophagus spp.
In those who are susceptible, the onset of symptoms
occurs at a median of 2.5 hours and within a range of 1
to 90 hours after consumption of raw or baked fish. 48
The predominant symptom is oil being passed per rectum
(kerriorrhoea). It is difficult to contain the oil that
pools in substantial quantities in the lower rectum, and
therefore frequent evacuation is required. If prophylactic
visits to pass stools are not performed, inability to
retain rectal contents may result in soiling of clothing. 45
Approximately 10 ml of inoffensive, clear orange or
green oil is passed per occasion. Oil is mostly not contaminated
significantly by faecal material. Because
most experiences occur in the absence of bowel
cramps or abdominal discomfort, this would imply that
the frequent calls to stool are caused by the lubricant
effect of the oil, and not by an irritant action. In selected
cases severe diarrhoea with abdominal pain, nausea,
headache and vomiting may occur. 48 Most people
recover within 24 hours. 49
COMPLICATIONS OF TRUE FOOD ALLERGY
True immune-mediated food allergy can be divided into
two subgroups on the basis of the immunological
mechanisms involved: food allergen-specific IgE
responses, and non-IgE-dependent immunological
responses, either of which may be immediate or
delayed. The latter may be divided into non-IgE-mediated
reactions resulting in, among others, delayed
allergy reactions, and other immune reactions such as
coeliac disease, an autoimmune disorder of the GI tract
triggered by ingestion of gluten (wheat, barley, and
rye). It occurs in approximately 1% of the population
and is influenced by a variety of genetic and environmental
factors. 50
IgE-dependent reactions are further classified by symptom
complexes developed in the primary target
organs. Food-related allergic reactions are the leading
cause of anaphylactic reactions treated in the emergency
department, accounting for approximately
30 000 emergency department visits in the USA each
year, and 150-200 deaths. 51
Even when symptoms may be truly allergic in nature,
there are two scenarios where the causative food may
not be easily identifiable.
• When diagnostic tests are negative
• When an associated allergen is responsible for the
symptoms.
Diagnostic tests are negative
True food allergy may occur with negative diagnostic
tests when the cause is a non-IgE mechanism or in
cases where diagnostic tests are negative in spite of a
clear IgE mechanism.
Non-IgE mechanisms
The severity and immediacy of IgE-mediated food reactions
such as anaphylaxis and urticaria/angio-oedema,
(as well as easier diagnosis) results in an under-appreciation
of the significance of non-IgE-mediated mechanisms.
Non-IgE-mediated food allergy may be responsible
for approximately 30% of delayed immune-mediated
reactions to food. 52 This is illustrated in Fig. 3.
In this Australian study, three groups of reactors were
characterised: immediate, intermediate and late.
Although all patients were milk allergic, only the immediate
group (reactions within minutes of ingestion) con-
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 113

fall in the non-predictive range, but also when they are
in the ranges usually regarded as negative or conclusive.
Specialised tests such as the CAST, basophil activation
test and others, may contribute to the diagnosis.
Although the double-blinded placebo-controlled food
challenge is regarded as the gold standard in making a
food allergy diagnosis, even this test may be unhelpful
in a number of situations, e.g. if not tailored for delayed
immune mechanisms or food-dependent exerciseinduced
symptoms such as asthma or anaphylaxis.
Fig. 3. Relationship between time of onset of adverse
reactions and volume of milk ingested at that time for
100 Australian infants. 52
sistently had laboratory evidence of IgE sensitisation
with positive skin tests and radioallergosorbent tests
(RASTs). The intermediate group (reactions occurring
from 1 to 24 hours after ingestion) displayed predominantly
GI symptoms, including vomiting and diarrhoea,
and most did not exhibit features of IgE sensitisation.
The late group (symptoms occurring from 24 hours and
up to 5 days after the commencement of the challenge
procedure) presented with flares of eczema or development
of cough and wheeze and showed no IgE sensitisation
but rather in vitro evidence of T-cell sensitisation
to milk. 52 Thus a true food allergy may not have
demonstrable IgE, may manifest some hours or even
days after ingestion, and may require larger intakes of
a food than customarily expected, all potentially resulting
in a diagnosis of food allergy being rejected.
Negative tests despite IgE mediated food
allergy
Skin-prick tests and serum specific IgE tests may be
negative in spite of an overwhelmingly positive history
for an acute IgE-mediated allergy. This may occur for a
variety of reasons and depend on the diagnostic modality.
Causes for skin-prick test being negative include
defective technique, decay of allergen in the test material,
concurrent use of antihistamines 53 as well as rarer
cases where the individual may be sensitive to a
specific allergen found in a low concentration or not
present in the skin-prick test extract.
The specificity and sensitivity of serum specific IgE
measurement varies widely between different allergens
and may be low in certain food allergens. The
allergen profile of the serum specific IgE reagent may
not cover every relevant allergen present in a particular
food. For example, in a report of 2 patients who developed
anaphylactic reactions after the ingestion of fresh
mango, a skin-prick test and CAST were positive.
However, serum specific IgE tests were negative. Both
patients were sensitised to allergens which appear not
to be present in the extract used for the serum specific
IgE assay. 54
A proper history is the most important factor in the
diagnosis of food allergy. Ancillary tests such as skinprick
tests and serum specific IgE are of value in confirming
diagnosis or guiding one towards the correct
diagnosis. Cut-off ranges for 95% positive predictive
values of skin tests 55 and IgE 56 have been identified for
a limited number of allergens in specific populations.
Both tests need to be interpreted in the light of the pretest
probability which depends greatly on the clinical
diagnosis. 57 This is particularly important where results
An associated allergen is responsible for
the symptoms
One of the authors has documented five mechanisms
that may be important in the assessment of associated
allergens responsible for symptoms in an individual,
and formulated the concept of concomitant clinical sensitivity
(CCS). 58 CCS is defined as 'the propensity for a
patient to be allergic to other allergens due to one or
more of five associative mechanisms'. Proximal CCS
occurs when an adverse effect is caused not by the
apparent allergen, but by another allergen proximal to
or physically associated with it. A familiar example is
Anisakis in fish, 59 but less common examples include
red spider mite on tomato 60 or orange, 61 storage mites
in baker's asthma, 62 and hidden allergens in food, 63
medications and cosmetics. 58
Hidden allergens in food are recognised throughout the
world as a significant risk to individuals with known
food allergy. 63,64 An added diagnostic dilemma occurs
when an individual reacts for the first time to a food
allergen hidden in another food. For example, anaphylaxis
caused by the unexpected presence of casein in
salmon has been reported. 65 Buckwheat added as a
bulking agent to pepper has caused anaphylaxis. 66
Although pine nuts are traditionally used in pesto
sauce, a clinician may not consider systemic contact
dermatitis following ingestion of a pesto sauce to be
the result of allergy to raw cashew nuts. 67 An anaphylactic
reaction following ingestion of apple juice was
found to be as a result of the inclusion of juice of the
acerola fruit. 68
Hidden allergens may not necessarily be of food origin:
mite and storage mite contamination of flour and pancakes
have resulted in allergic reactions including anaphylaxis
as described in numerous studies, 69-71 including
a study of 30 atopic subjects who were first seen
with systemic anaphylaxis precipitated by the ingestion
of wheat-containing foods, of whom 16 had anaphylaxis
triggered by pancakes. 70 Similarly, allergic symptoms
in 8 patients, previously diagnosed as having Anisakis
simplex sensitisation, occurred after they ate chicken
meat. Chicken feed usually contains a high proportion
of fishmeal, which might possibly be contaminated by
this nematode. All 8 patients presented positive pricktests
and challenges to A. simplex. 72
In honey-allergic individuals primary sensitisation may
be due either to the honey itself, to airborne
Compositae pollen, sunflower pollen, or even to crossreacting
bee venom components. 73,74 The software
program, Allergy Advisor ®75 , contains over 180 examples
of 'proximal sensitisation'.
CONCLUSION
Differential diagnosis of adverse reactions to food
must take into account psychological reactions, organic
or anatomical reactions, toxic reactions and non-toxic
reactions. Non-toxic reactions imply an individual
hypersensitivity to the food, either immune mediated
(food allergy) or not immune mediated (food intolerance).
Distinguishing between true food allergy and
food intolerance may not be easy, and a wide differen-
114 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

tial should be considered. This should include enzymatic,
pharmacological and other food intolerances,
and both IgE-mediated and non-IgE-mediated food
allergy. Hidden food allergens may further complicate
diagnosis of food allergy in the case of concomitant
clinical sensitivity to associated allergens hidden in or
proximal to the food.
Declaration of conflict of interest
Dr Steinman has acted as a consultant to Phadia, Sweden.
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116 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

HYPERSENSITIVITY TO LOCAL ANAESTHETICS
– 6 FACTS AND 7 MYTHS
Joanna Lukawska, MRCP
M Rosario Caballero, PhD
Sophia Tsabouri, MD, PhD
Pierre Dugué, FRCP, MD, APH
Drug Allergy Clinic, Guy’s & St Thomas’ Hospitals, NHS
Foundation Trust, London, UK
The pharmacological differences between LAs make
certain LAs more favourable than others for specific
procedures, i.e. lignocaine is widely used for subcutaneous
injection, and bupivacaine is preferred for
epidural or gum injections.
Amino-ester LA chemical structure
ABSTRACT
Local anaesthetics (LAs) are commonly used drugs.
In spite of their widespread use, true hypersensitivity
appears to be very infrequent. In fact most of the
adverse reactions are due to pharmacological, toxic
or vasovagal effects of LAs.
Our review of the literature has shown that true
allergy to LA is in fact exceptional. Skin tests for LA
allergy, including skin-prick tests (SPT) and intradermal
(ID) tests, have poor sensitivity and specificity.
True LA allergy, when appropriate, has to be confirmed
by challenge. Provocation challenge is safe
and well tolerated.
Aromatic
group
Ester
Amine group
Since the discovery of the anaesthetic effect of
cocaine in 1884, local anaesthetics (LAs) have been
widely used. It has been estimated that 6 million people
are injected with LAs each day around the world. In
spite of their widespread use, true hypersensitivity
appears to be infrequent. However the perception of
allergy to LA among the general public is high. In our
drug allergy clinic, referrals for LA allergy are in the
same range as penicillin or aspirin allergy referrals.
In this review, based on published literature (PubMed-
Medline and EMBASE) as well as our own experience,
we attempt to explain some of the facts and reject
some of the myths surrounding allergy to LA.
LAs have two different chemical structures, which
define two different families, either amino-ester or
amino-amide. The ester family includes cocaine, procaine,
tetracaine, all spelt with a single ‘i’ while in the
amide family, each individual name contains two ‘i’s
e.g. lignocaine, prilocaine, bupivacaiine.
LAs reversibly interrupt impulse conduction along
peripheral nerve axons. This effect is achieved by
blockade of sodium channels. LA can be used topically
or injected (subcutaneously, in the gum or around a
nerve plexus or spinal cord for block anaesthesia, and
epidural). Addition of epinephrine to LA delays its
absorption by decreasing local blood flow and prolongs
the duration of anaesthetic action. Associated vasoconstriction
also decreases the peak plasma concentration
and therefore the risk of generalised toxic sideeffect.
The chemical structure of the compound (Fig. 1)
determines the duration and strength of the anaesthesia,
for example bupivacaine is 16 times more potent
than procaine. It also determines its metabolism and
toxicity. It is therefore hardly surprising that it should
also have an impact on the type of adverse drug reactions,
including allergic reactions.
Correspondence: Dr J Lukawska, Drug Allergy Clinic, Guy’s & St
Thomas’ Hospitals, NHS Foundation Trust, London, UK.
E-mail Joanna.lukawska@kcl.ac.uk
Aromatic
group
Amide
Amino-amide LA chemical structure
Amine
group
Fig. 1. Chemical structure of amino-ester and aminoamide
molecules.
FACTS AND MYTHS
Fact 1. Risk of adverse drug reaction to LA
may be increased in patients with deranged
liver function or pseudocholinesterase
dysfunction.
Ester-LAs are metabolised by pseudocholinesterase to
p-amino-benzoic acid (PABA). The risk of adverse reaction
is increased in patients with altered pseudocholinesterase
function. Amide-LAs are metabolised in
the liver; therefore patients with decreased hepatic
function are at increased risk of overdosage and toxic
reactions. 1
Fact 2. IgE-mediated hypersensitivity to
LAs is extremely rare.
Globally the tolerance of LAs is good, with low incidence
of adverse reactions. Two types of hypersensitivity
are described with LAs – the relatively more common
contact delayed hypersensitivity, mainly related to
ester-LAs, and the less common immediate hypersensitivity
associated with ester-LAs and exceptionally
with amide-LAs. However, there is some doubt as to
the reality of true allergic, IgE-mediated anaphylaxis
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 117

with amide-LAs. 2 Tsabouri et al. 3 found no IgE-mediated
reactions in 157 patients referred with LA-associated
adverse drug reactions. Similarly Gall et al. 4 tested 197
patients and found only 2 immediate-type reactions,
which were also considered not to be IgE related.
Fact 3. Sensitisation and cross-reactivity,
resulting in delayed-type IV reactions,
between ester-LAs are common.
Sensitisation to topical ester-LA resulting in contact
allergy is common. Moreover cross-reactivity between
members of the ester family is usual. One of the most
frequently used ester-LAs for topical applications is
benzocaine. It is used in several types of products such
as sun creams and haemorrhoid creams, as well as
some topical anaesthetics. Its main derivative, PABA, is
a common and potent sensitiser. It has been estimated
that 5% of individuals who have applied benzocaine will
become sensitised to it. 5 Other topical anaesthetics
such as cocaine and tetracaine are based on the same
PABA structure, which may lead to cross-reactivity.
Fact 4. Patch testing is a reliable method
of diagnosis of delayed-type IV hypersensitivity
reactions.
Type IV hypersensitivity (Gell and Coombs classification),
e.g. contact dermatitis following exposure to LA,
should be investigated by patch testing. However
delayed inflammatory reaction may in rare cases develop
following injection of LAs, eliciting localised delayed
oedema at the site of the injection. 6,7 Contact dermatitis
usually appears within 24 to 72 hours; it may, however,
be clinically detectable as soon as 2 hours post
exposure to LA. 8
Patch testing for allergic contact dermatitis caused by
LA is a good predictor of allergic type IV reactions 9 and
it should be performed according to the guidelines of
the International Contact Dermatitis Research Group. 10
Contact reactions to amide-LAs have been described,
though infrequently.
Myth 1. Amide-LAs are potent sensitisers
and commonly cross-react with ester-LAs.
Amide-LAs are rare sensitisers by topical application.
Lignocaine used topically in gel or in cream does not
cross-react with benzocaine when tested with epicutaneous
patch test. 11 Topical cross-reactivity with other
amide-LAs is described infrequently. Patch tests with
lignocaine are positive in subjects with delayed sensitisation
to lignocaine. The suggested concentration is
20% in petroleum for lignocaine 12
Clinical-cross reactivity between type IV reactions to
ester-LAs and type I reactions to amide-LAs has never
been described. Ruzicka et al. 13 found that among 104
patients sensitised to ester only 3 had positive intradermal
(ID) test results with amide although they had
no history of reaction with amide-LA.
Myth 2. Skin testing is a reliable tool
when looking for LA allergy.
Immediate-type hypersensitivity to esters was observed
frequently in the past.
However, since the introduction of lignocaine in 1948
by Nils Lofgren, amide-LAs have been used for injection
instead of ester-LAs, and as a result the incidence
of immediate allergic reaction to ester LAs has dropped
dramatically.
The value of skin testing to diagnose LA immediate
hypersensitivity is controversial and it is sometimes
bypassed altogether in favour of graded drug challenge.
14,15
We reviewed the medical literature from the last 20
years focusing on sensitivity and specificity of skin
testing with regard to challenge with LA. We found 9
series (Table I) which involved a total of 1 094 patients
who suffered adverse reaction to LA and were
assessed with skin testing and challenge. 2,4,16-22 Out of
1 094 patients only 3 suffered an immediate allergic
reaction when LA was reintroduced. None of the 3 had
positive SPT or ID results. In the same series, falsepositive
skin tests varied vastly in a range from 0% to
27%. 2,4,16,19-22
After collating all these results, we can conclude that:
• Challenges were positive in 3 patients out of 1 094
with mild reaction at reintroduction, yet those 3
patients had negative skin tests. Skin tests are therefore
a poor predictor of positive challenge.
• Skin tests may be positive in patients who are able to
tolerate reintroduction of LA during challenge.
• Most of the adverse reactions are not allergic in
nature but occur as a result of other mechanisms.
Table I. Results of skin testing (SPT, ID) and provocation challenge in published series of suspected allergic
reactions to LA
Authors Year No of pts Skin tests + Challenge Comments
SPT; IDT
Incaudo et al. 16 1978 59 5/59 0/50
De Shazo & Nelson 17 1979 90 0/90; 10/90 0/84 (4 IDT +) IDT dilute positive but
IDT neat negative
Fisher & Graham 18 1984 27 1/27 0/26
Le Sellin et al. 19 1986 25 0/25 1/25 1 hand oedema
Chandler et al. 20 1986 59 0/59 0/59 2 anaphylactic histories
had negative challenge
Escolano et al. 21 1990 35 0/35 0/35
Gall et al. 4 1996 177 0/177 3/143 1 delayed, 2 local
immediate reactions
(non IgE mediated)
Troise et al. 2 1998 387 13/386; 3/13 0/386 8 subjective reactions
Berkun et al. 22 2003 236 0/236; 0/236 1/236 1 local erythema
in patient with negative
skin test
SPT – skin-prick test, ID – intradermal
118 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

• Provocation challenge is safe and well tolerated.
• Based on the available literature, specificity and sensitivity
of skin tests to LA are of questionable value.
According to the European Network for Drug Allergy
(ENDA) guidelines, diagnosis has to be confirmed in
both groups of patients – those who tested positive
and those who tested negative on skin tests, with graded
challenge after cautious balance of individual benefit.
23
Myth 3. Sensitivity of intradermal skin
testing with LAs is high.
Reviewing the literature for evidence of positive challenges
after reintroduction of LA in subjects with history
of immediate reaction to LA, we found 4 anecdotal
case reports with only 5 positive challenges. 24-27
SPTs were negative in 4 cases but ID tests were positive
in 3 cases and negative in 2, although 1 subject
suffered severe anaphylaxis at introduction of ropivacaine
with negative ID test. In addition, from the series
of Gall and collaborators, 2 patients had itchy wheals
and erythema at the test sites and also on the trunk
shortly after exposure to lignocaine or articaine. Those
patients had negative ID 1/10 tests. When we collated
all the results of 7 positive challenges, we found that
SPTs were negative 6 times out of 7, ID tests were
negative 4 times out of 7.
To summarise, in the small group of patients who suffered
allergic reaction to LA confirmed by positive challenge,
the sensitivity of ID tests is low (43%), and sensitivity
of SPT even lower (14%). Negative skin tests
may not predict tolerance. Patients sensitised to one
amide-LA may be sensitised to one of several other
amide-LAs.
Myth 4. Adverse reactions to LAs are
often related to paraben preservatives.
Parahydroxybenzoates are well known contact sensitisers
and their use can result in delayed-type hypersensitivity
reaction; however their association with
immediate reactions to LAs has been debated. Simon
et al. 28 in 1984 recorded only 3 cases with immediatetype,
rare IgE-mediated reactions. Skin testing for
immediate-type reactions also appears to be of poor
value, because of 5 patients with positive skin test
results, reported by Gall et al., 4 all were able to tolerate
reintroduction of paraben-containing LA.
Myth 5. Parabens are commonly used
preservatives in injectable LAs.
Parabens as a potential cause of reaction to LA have
become less significant since fewer injectable LA
preparations contain it as an ingredient. In our practice
(UK) only a few preparations contain parabens, e.g.
Xylocaine 1% and 2%, and Citanest.
Myth 6. Sodium metabisulfite contained
in some of the LAs is a common cause of
adverse drug reaction.
Sodium metabisulfite is included in LAs containing epinephrine
to prevent oxidation. The concentration of sulphite
in these preparations ranges from 0.375 mg/ml to
0.5 mg/ml. Sulphite sensitivity primarily affects a small
subgroup of the asthmatic population.
Clinical history of metabisulfite allergy is often misleading,
and skin tests are inconsistent; therefore sulphite
sensitivity is best diagnosed with an oral doubleblind
graded challenge of ingestion of metabisulfite
from 5 mg to 200 mg. 29 In non-asthmatic subjects,
adverse reactions to sulphating agents appear to be
exceedingly rare. 30 Gall et al. 4 found 5 patients with
positive skin test results to metabisulfite and suspected
reaction to LA containing metabisulfite. When challenged
all 5 tested negative.
Although subcutaneous administration of sulphites
could theoretically provoke asthma in asthmatic individuals,
no convincing evidence for this has appeared,
although epinephrine contained in the LA may overwhelm
the bronchoconstricting effects of sulphites.
Equally the theory of asthma exacerbation in asthmatic
subjects has not been supported by the evidence in
the form of positive metabisulfite challenge. 31,32 Only
one immediate-type reaction is well documented in
the literature, where a positive parenteral provocation
test to metabisulfite was observed. 33 Other reports of
suspected reaction to metabisulfite contained in LAs
were not confirmed by reintroduction of the suspected
LA or a graded challenge. 34,35
Myth 7. When allergic reaction to LA is
suspected it is best to challenge the
patient with another LA, preferably from a
different class.
Diagnostic challenge is best done with the same drug
the patient appears to have reacted to, including any
additives the drug may have contained. Several protocols
of incremental subcutaneous injections have been
described. Challenges should be performed under
close medical supervision in a specialist allergy centre,
after informed consent has been signed and any contraindications
taken into careful consideration. The initial
dose is tailored according to the severity of the previous
reaction. It may vary from 0.01 mg to 1 mg. This
is followed by half-hourly incremental subcutaneous
injections to the therapeutic dose of 10 or 20 mg. 36,37
Using LA alone avoids the question of possible reaction
to additives, whereas using a non-suspected LA from
the same or from a different class would answer the
question of tolerance to the intended LA but gives no
clarification as to the diagnosis of the index drug. This
latter approach lends weight to the possibility of an LA
allergy that may not in fact exist.
Fact 5. An adverse reaction to LA may
occur as a result of epinephrine.
Most LAs, with the exception of cocaine, cause dilatation
of blood vessels. Addition of vasoconstrictor
diminishes local blood flow, slows the rate of absorption
of LA, decreases the serum peak and prolongs
local effect of LA. However adding epinephrine introduces
its own risk of side-effects. Adverse reactions to
epinephrine include palpitations, tachycardia, arrhythmia,
anxiety, headache, tremor, and hypertension,
which may wrongly be diagnosed as hypersensitivity.
The type of injection including high pressure, speed,
concentration of epinephrine and density of local vessels,
all conditions met in dental surgery, increases the
risk of accidental vascular injection and toxic effect. In
the dental surgery the concentration of epinephrine in
an LA cartridge is 12.5 mg/ml. It is 2.5 times more concentrated
than in a vial for subcutaneous injection and
it may, in part, explain the excess of referrals for LA
adverse reactions during dental care.
Fact 6. Toxic effect of LA may occasionally
be misdiagnosed as LA allergy.
Toxic adverse reactions associated with LA relate
either to systemic exposure or local pharmacological
effect. Peripheral toxicity may elicit transient or permanent
neurological deficit. Systemic exposure to exces-
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 119

sive quantities results in central nervous system and
cardiovascular effects. It is worth noting that nervous
system effects occur at lower blood plasma concentrations.
These initially include a feeling of inebriation
and light-headedness followed by sedation, circumoral
paraesthesia and twitching, tinnitus, tremor, dizziness,
blurred vision, and seizures followed by depression.
With increasingly greater exposure, drowsiness, loss
of consciousness, respiratory depression and apnoea
may follow; convulsions may occur in severe reactions.
On intravenous injection, convulsions and cardiovascular
collapse may occur very rapidly. Cardiovascular
effects include hypotension, bradycardia, arrhythmias,
and/or cardiac arrest. 38
Most of the reactions, however, are vasovagal and
related to the stress and the pain of the injection. It is
therefore hardly surprising that when these reactions
were investigated as many as 7% of Norwegian high
school students experienced fainting during medical
injections and 2% during dental injections. 39 In addition
other subjective reactions are likely to occur, which are
usually not reproducible by challenge.
CONCLUSION
Delayed sensitisation occurs mainly with ester-LAs,
eliciting either contact dermatitis when used topically
or delayed oedema when injected. These types of
reactions are proven by patch testing read at 24 hours
and 48 hours. Immediate adverse reactions to amide-
LAs are frequently suspected but are most commonly
subjective reactions or vasovagal reflexes related to
stress and pain. Toxic effect may occur with epinephrine
or LA molecules. Allergic hypersensitivity to
amide-LAs, metabisulfite or paraben appeiars to be
exceptional. Immediate allergic skin tests have low
sensitivity and low specificity. A negative skin test
result does not rule out LA allergy and a positive skin
test result does not confirm it. Therefore the correct
diagnosis can only be established by incremental subcutaneous
reintroduction of LA during carefully conducted
and monitored challenges.
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anaesthetic intolerance due to metabisulfite. Contact Dermatitis
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120 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

FOOD ALLERGY EPIDEMIC – IS IT ONLY A
WESTERN PHENOMENON
L van der Poel, 1 MB ChB, MRCPCH
J Chen, 2 MD
M Penagos, 1 MD, MSc
1 King’s College, London. MRC & Asthma UK Centre in
Allergic Mechanisms of Asthma. Division of Asthma,
Allergy and Lung Biology, Guy’s and St Thomas’ NHS
Foundation Trust, London, UK
2 Department of Dermatology, Shanghai Children’s
Medical Center, Affiliated to School of Medicine of
Shanghai Jiaotong University, Shanghai, China
ABSTRACT
The incidence and prevalence of allergic disease
such as asthma, eczema and allergic rhinitis is widely
reported to have increased over the past few
decades, particularly in the developed world. Patient
and public awareness of food allergy is also increasing.
While most of the medical literature around
food allergy focuses on the western world, there is
also an increasing amount of evidence that food
allergy (FA) is prevalent outside of the developed
world. The true prevalence and morbidity of FA in
the developing world is largely unknown. A literature
review of the worldwide incidence of FA was undertaken
with emphasis on the paediatric age group, for
developing areas in Asia, Latin America and Africa to
assess whether or not the 'food allergy epidemic' is
a western phenomenon. We found that there are
too few data using food challenges, the accepted
gold standard, for the diagnosis of true FA to come
to any conclusions either about the current prevalence
of FA or whether it is rising. Robust, population-based
studies are needed to establish the true
burden of disease.
A food allergy (FA) is an adverse immune response to a
food protein. 1 This may be IgE-mediated (either primary
or related to a cross-reacting pollen), or non-IgEmediated.
FA is distinct from other adverse responses
to food, such as food intolerance, pharmacological
reactions, and toxin-mediated reactions. The term food
hypersensitivity (FHS) combines allergy and intolerance.
While allergy tests can confirm IgE sensitisation,
a double-blind placebo-controlled food challenge may
be required to verify the diagnosis.
Cross-sectional studies, such as the International Study
of Asthma and Allergies in children (ISAAC) have confirmed
that atopic diseases represent a major health
problem in many countries, and that the rates of respiratory
allergy such as allergic rhinitis and asthma have
risen over time in many developed countries. The
prevalence of FA is widely believed to have risen alongside
this, although evidence for this is relatively limited.
IgE-mediated FAs are most prevalent during childhood,
affecting between 6% and 8% of children in the UK
and USA. 1 The majority of food-induced allergic reactions
in young children in the UK and USA are due to
cow's milk protein, egg, peanuts and tree nuts. Wheat
and soya cause IgE-mediated FA less frequently. With
Correspondence: Dr L van der Poel, e-mail laurivdp@doctors.org.uk
increasing age, peanuts and tree-nut allergies persist
more often than cow's milk and egg allergies, and they
are associated with significant morbidity and mortality. 2,3
The strongest evidence of an increase in FA over time
relates to peanut allergy, where studies suggest a clear
increase in prevalence in both the UK and the USA.
Two studies, using similar methodology, conducted by
Sicherer and colleagues at 5-year intervals, were very
revealing. 4 In 1997, a national random digit-dial phone
survey was used to determine the prevalence of
peanut and tree nut allergy in the USA. The follow-up
study, conducted in 2002, showed that the rate of
peanut and tree nut allergies had not increased significantly
in adults but the reported prevalence of peanut
allergies in children had doubled in the 5 years
between the surveys.
Grundy and team, in a study on the Isle of Wight, also
compared two comparable cohorts over time (6
years). 5 Of all 2 878 children born between September
1994 and September 1996, 1 273 completed questionnaires,
and of those, 1 246 had skin-prick tests (SPTs)
at the age of 3-4 years. Those with positive SPT
responses to peanut were subjected to oral peanut
challenges, unless there was a history of immediate
systemic reaction. These results were compared with
an earlier, comparable cohort of 1 456 children from the
same geographic area 6 years earlier (January 1989 to
February 1990). The aim was to determine any change
in the prevalence of peanut sensitisation and reactivity
in early childhood. The authors found a 2-fold increase
in reported peanut allergy (0.5% [6/1 218] to 1.0%
[13/1 273]), but the difference was non-significant
(p = 0.2). Peanut sensitisation increased 3-fold, with 41
(3.3%) of 1 246 children sensitised in 1994 to 1996
compared with 11 (1.1%) of 981 sensitised in the earlier
cohort (p = 0.001). Overall, 18 (1.5%) of 1 246 children
were considered to have symptomatic peanut
allergy.
Subsequent studies in Canada 6 also showed a high
prevalence of peanut allergy in schoolchildren, and
Australian data from childcare centres in the ACT and
Central Sydney Area Health Service showed while allergies
to proteins in milk, eggs and seafood have
remained steady, peanut allergies increased by 50%
between 2003 and 2006, and cashew allergies, while
less common overall, increased a staggering five
times. 7 There also appears to be an increasing number
of reactions reported to novel allergens such as
sesame 8 and kiwi fruit. 9
Although FAs appear to be on the rise, a scarcity of
data on their prevalence makes it difficult for governments
and health services to react. Collecting prevalence
data relating to FA is extremely challenging. The
most robust studies require careful evaluation of each
patient, with any allergy confirmed with double-blind,
placebo-controlled food challenges. Such studies, on a
population scale, require significant resources and thus
most researchers have opted for a questionnaire-based
approach. Unfortunately, questionnaire-based studies
greatly overestimate the prevalence of FHS. The
reported perceived prevalence of FHS using questionnaires
varies from 3.24% to 34.9%. 10
In a recent review by Venter et al. 11 of the prevalence
and cumulative incidence of FHS in the first 3 years of
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 121

life in the UK between 2001 and 2002, it was concluded
that there was no evidence of increased FHS in an
unselected population over time when compared with
a similar USA study 20 years previously. The study of a
birth cohort of 969 children at 1, 2 and 3 years concluded
that by the age of 3 years, 5-6% of children suffer
from FHS, based on food challenges and a good
clinical history. They also found large discrepancies
between reported and true FHS in young children but
were able to demonstrate that the true prevalence of
FHS decreases with age, as is expected given the tendency
of milk and egg allergy to resolve in childhood.
There is a lack of such robust data available from
developing countries.
This article considers the evidence that FA is already an
established entity outside of the developed world,
where data suggest it is a major public health concern,
allthough it is unclear whether it is a growing one.
FOOD ALLERGY IN ASIA
Most of the world’s population lives in Asia. However,
there is a paucity of adequate data on the prevalence
and clinical features of FA in this region, and specifically
of large, well-designed studies using robust diagnostic
methods. This problem is exacerbated by large
population sizes with diverse racial, cultural and socioeconomic
means and language. Asia is also unique as its
range of different cultures and eating habits result in
unique FAs. The most common cause of food-induced
anaphylaxis in a cohort of children from Singapore, for
example, is bird’s nest (27%), followed by egg and milk
(11% combined). 12 However, in recent years, data on
the prevalence of FA in some countries in Asia have
been published.
Epidemiology
The true prevalence of FA in the general population in
Asia is uncertain. Estimates from Chinese studies
range from 4.98% in the Sheng-Li oil fields of northeast
China 13 to 16.4% in a study of large-scale, unselected
rural Chinese cohorts of twins in Anqing. 14 The latter
percentage represented those diagnosed by SPT and
therefore reflects sensitisation rather than true clinical
allergy. This study found FA was more common among
children than among adults and was more prevalent
among children in their first few years, in keeping with
western data. A study using a parent-reported questionnaire
among a large cohort of Chinese preschool
children in Hong Kong reported a prevalence rate of
parent-reported FA and parent-reported, doctor-diagnosed
FA of 8.1% and 4.6%, respectively. This study
has also shown parent-reported FA was less frequent
among those born in mainland China, and who have
subsequently moved to Hong Kong, than those born
and raised in Hong Kong. 15
In the late 1990s, a parent-reported questionnaire of
children from Singapore estimated the prevalence of FA
to be 4-5%. 16 Around the same time, a Korean study
using a self-reported questionnaire in a huge cohort of
children reported a lifetime prevalence of 10.9%. 17 In
keeping with other urban-rural comparisons, there was
a slightly higher prevalence in the capital Seoul (12.4%)
compared with provincial cities (10.1%).
Similarly variable FA prevalence was noted in other Asian
countries: as high as 5.5% in a cohort of Japanese children
18 and as low as 1.2-1.7% in Israeli infants as
assessed by detailed questionnaire and SPTs. 19
A cross-sectional study of 656 children of 6 months to
6 years of age in Thailand showed a prevalence of
6.25% in children less than 6 years based on a parentreported
questionnaire survey versus the 0.45% established
through SPT and food challenge. 20 This illustrates
the discrepancy between reported and medically diagnosed
allergy, adding to the difficulties in comparison
between existing data.
Table I lists country-specific prevalence studies. 13-27
Table I. Country-specific prevalence of food allergy in children
Study n Country Age (years) Allergen Prevalence Method
(%)
Wang 13 10 144 China General population General 4.98 Questionnaire
Kim et al. 14 2 118 China General population General 25.3 SPT
Leung et al. 15 3 827 Hong Kong 2–7 General 8.1/4.6 Parents / doctors
Lee BW et al. 16 6 404 Singapore 5–12 General 4-5 Parent-reported
Lee SI et al. 17 25 000 Korea 6–12 General 10.9 Self-reported
Fukiwake et al. 18 456 Japan 0–6 General 5.5 Questionnaire
Dalal et al. 19 >9 000 Israel 0–2 General 1.2-1.7 Questionnaire + SPT
Santadusit et al. 20 656 Thailand 6 mo-6 yrs General 6.25 Questionnaire
Santadusit et al. 20 656 Thailand 6 mo-6 yrs General 0.45 SPT + food challenges
Marrugo et al. 21 3 099 Colombia Children & adults General 14.9 Self-reported
Bozzola et al. 22 944 Argentina Adults General 5.1 Phone survey
Naspitz et al. 23 457 Brazil 1–12 Fish/egg 29.5/24.4 SPT in atopic children
Naspitz et al. 23 457 Brazil 1–12 Fish/egg 11.3/4.8 SPT in children
Martinez et al. 24 408 Chile 8 mo-15 yrs Egg, milk, 7/1.1 SPT
beef/peanut
Madrigal et al. 25 291 Mexico Children General 3.7 Survey
Avila-Castañón et al. 26 1 419 Mexico 1–17 Fish/cow’s 12/7.7 SPT
milk
Karabus & Motala 27 400 South Africa Children Peanut/ 35/30 SPT in children with
egg white
atopic dermatitis &
food elimination
challenge
SPT – skin-prick test
122 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

Food as a trigger for anaphylaxis
Recent studies describing patterns of anaphylaxis
show that food is an important cause of severe allergic
reactions in Asia. Unlike the USA, Australasia and the
UK, peanut and tree nuts are rarely the cause of allergic
reactions in the region. 28
The mortality rate from FAs is 0.006 individuals per
100 000 children in the UK, 29 , while 150-200 individuals
die from FAs every year in the USA. 30 Related studies
of anaphylaxis in Asia are few, although the overall incidence
of anaphylaxis appears to be low. Common food
allergens causing anaphylaxis are milk, eggs, wheat,
peanuts, and soybeans. 31
FOOD ALLERGENS IN ASIA
Many food allergens are similar in both Asian and
western communities. Hen’s egg, cow’s milk, wheat
and to a lesser degree peanuts are known to be allergens.
31,32 However, some differences, related in part to
dietary exposure as well as the existence of geographically
specific and unique food allergens, are
apparent. Figure 1 highlights common country-specific
food allergens, but it is important to note that comparison
of specific food prevalence is made difficult as a
result of the heterogeneity in the types of studies, age
groups examined and definition and diagnosis of
FA. 3,13,19-21,23,24,26,27,33-36
In Japan, the most common allergens causing anaphylaxis
were milk, eggs, wheat, peanuts, and soybeans,
followed by sesame and buckwheat. 33 Using a questionnaire
survey in Korean children with atopic eczema,
it was found that the most common food allergens
were egg, milk, fish and seafood in 6-12-year-old children,
and seafood, peach, milk, egg and fish in 12-15-
year-old children. 34 In Singapore, a cross-sectional
study involving 75 atopic children aged under 3 years
showed the prevalence of food sensitisation was highest
for cow’s milk (45.9%) and egg white (38.7%). 35
Unusual food allergens in Asian populations include
silkworm pupa – a traditional Chinese food. 36 Oil-fired
pupa, water-boiled pupa and ground pupa powder are
eaten for their nutritional value. It was reported that
each year in China, over 1 000 patients suffer anaphylactic
reactions after consuming silkworm pupa, foreign
tourists among them. 37 Buckwheat allergy has
been described in China, Japan and Korea because it is
used to make noodles, cakes and biscuits, and is consumed
in large quantities, particularly in Japan, where
it is used to make Soba noodles. 38,39 Bird’s nest
appears to be the most common cause of foodinduced
anaphylaxis among Singaporean children. 28 It
has been documented that the reaction is IgE-mediated
and that the major allergen is a 66 kDa glycoprotein. 38
Chestnut is frequently consumed in Korea, and represented
the third most common food allergen as diagnosed
by SPT among adults and children in Korea. 39
Royal jelly is produced by worker bees as food for their
larvae, and reports of asthma exacerbations and anaphylaxis
to it have come from Hong Kong 40 and
Australia. 41 Sesame is a major food allergen in Israel
and is introduced early into the diet of children in this
country, 7 while chickpea is a staple food in India and is
introduced into the child’s diet at an early age and has
been reported as a cause of anaphylaxis. 42
The relevance of food sensitisation, especially in atopic
children, can be difficult to establish. Several Asian
countries have reported rates of food sensitisation
among atopic children below 5 years of age. The percentages
and patterns vary depending on the geography
and dietary exposures. In Northern China, around a
third of atopic children were sensitised to each of milk
and egg, while the study in Taiwanese children with
atopic dermatitis suggested high rates of sensitisation
to shrimp (62.7%), followed by egg white and milk
(both 49.2%) and then peanut (35.6%). 13 Unfortunately,
as patients sensitised to food allergens are
commonly clinically tolerant, these data tell us relatively
little about the true prevalence of clinical allergy.
ALLERGENS IN LATIN AMERICAN COUN-
TRIES
Several studies have described the occurrence of selfreported
reactions to food and many evaluations have
been conducted to assess the frequency of sensitisa-
13,36
33
26
19
21
20
34
13
24
35
23 27
Fig. 1. World map showing range of food allergens in order of decreasing frequency in specific developing
countries
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 123

tions by means of SPT and IgE assays, yet the precise
prevalence of FA in Latin American countries is not
known. 21,43
In Colombia, a large cross-sectional study was conducted
in children and adults in a randomised selection
in Cartagena City. Questions covered personal and
family history of allergies and FA. The overall prevalence
of self-reported FA was 14.9%. Fruit/vegetables
(41.8%), seafood (26.6%), and meats (20.8%), were
the most reported allergens and the most frequently
reported symptoms were skin (61.4%), gastrointestinal
(29.1%), and respiratory reactions (8.6%). 21
In Argentina, self-reported FA in adults via phone survey
was estimated at 5.1% (n = 48/944). 22
In Brazil, Naspitz et al. 23 determined total and specific
IgE serum levels to inhalant and food allergens (RAST,
UniCAP – Pharmacia) among children attending an allergy
clinic and age-matched controls. In this study a
RAST ≥ class 1 was considered as positive (R+). Both
the levels of total IgE and the frequency of R+ were
significantly higher among atopic subjects (79%) compared
with controls (26%). Although R+ to aeroallergens
were more frequently reported, sensitisations to
food allergens like fish (29.5 and 11.3%, p < 0.05), egg
(24.4 and 4.8%, p < 0.05), cow´s milk (23.1 and 3.2%,
p < 0.05), wheat (20 and 8.1%, p < 0.05), peanuts (14
and 4.8%, p < 0.05), soya (11.8 and 4.8%, p < 0.05),
and corn (10.6 and 4.8%, p < 0.05) were found in allergic
children and controls respectively. 23
In Chile, 408 allergic children between 8 months and 5
years of age were skin-prick tested for common allergens.
House-dust mite predominated but sensitisation
to cow´s milk, egg and beef was 7% each in children
younger than 3 years old. For children between 3 and
5 years old, milk, seafood, peanut (1.1%) and soya
were the most common food allergens. Soya (5.9%)
and interestingly, orange (3.1%), were the most common
sensitisations to foods in children older than 5
years old. 24
In Mexico, a prospective observational survey of mothers
from three different nurseries looked for adverse
reactions to foods. The diagnosis of FA was based on
the patient's history, and when it was necessary, food
exclusion and food challenges were performed. The
diagnoses were: lactose intolerance (1.7%), allergy to
eggs (0.6%), carrots (0.3%), food additives (0.6%),
sausages and ham (0.3%). A 3.7% prevalence of
adverse reactions to food was found in this population.
25 Another study, reviewing the clinical records of
allergic children for SPT results for food allergens noted
that 50% of the children were sensitised to only 1 food
allergen, 25% to 2 and 3% to more than 6. Fish, milk,
seafood, soya, beans, orange, onion, tomato, chicken,
nuts and strawberry were responsible for 58% of the
total of sensitisations. Fish (12%) and cow´s milk
(7.7%) were the most common. 26
Figure 2 compares the available SPT data for fish and
egg allergy in three Latin American countries. 23-26
AFRICA
There is a dearth of paediatric FA data in the literature
from African countries. However, there are some useful
data from South Africa, including a prospective
descriptive study of all children attending a Cape Town
allergy clinic over a 2-month period in 2008. Karabus
and Motala 27 analysed data from 400 children including:
age at presentation, sex, ethnic group and clinical diagnosis.
Laboratory data included: total IgE, CAP-RAST,
SPTs and elimination-challenge testing. The data are
shown in Figure 3. In patients with FA there was a high
prevalence of peanut allergy. In patients under the age
of 3 years, the most common food allergens were egg,
peanut and milk. In children over 3 years, peanut is the
most common food allergen followed by egg and milk.
Interestingly, potato is an emerging FA that may play a
role in difficult-to-treat atopic eczema – studies are in
progress to evaluate this.
Another study looking at peanut allergy in Xhosa children
in Cape Town 44 showed that, despite a 5% rate of
peanut sensitisation, none of the children was peanut
allergic (prevalence 0%: 95% CI 0.0-2.4%). The reasons
for this are under examination and are likely to be
related, in part, to cultural differences in diet and
peanut exposure in the Xhosa population.
There are very limited relevant data from other African
countries.
Fig. 2. Fish and egg allergy prevalence in Latin American children based on skin-prick test data.
124 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

Fig. 3. Food allergy prevalence in a Cape Town children’s allergy clinic (n = 400).
DISCUSSION
A double-blind, placebo-controlled food challenge is the
gold standard for diagnosing FA. Studies using such
methodology have allowed an accurate picture of
prevalence of FA in the West to be drawn, albeit it one
that has few previous data for historical comparison.
Indeed, one current concern in the West is the possibility
that severe reactions may be under-reported. In
comments on the US Food & Drug Administration's
2005 Food Safety Survey, FAAN (The Food Allergy &
Anaphylaxis Network) stated that ‘Accurate and reliable
data on FA and anaphylaxis is lacking, and it is generally
believed that the limited data now available represents
an under-reporting of FA-related reactions and
deaths.’ 1
In contrast, a lack of these provocation challenges in
studies of FA in developing areas makes the determination
of true prevalence in these areas difficult. The
prevalence data for FHS in developing areas, where
found, are often in the form of questionnaire-based
studies, of limited value for the estimation of true
prevalence. It is well established that there is a significant
discrepancy between self-reported FSH (either
allergy or intolerance) and that which can be formally
diagnosed. As a result, the data from these studies,
despite their impressive cohort size and sometimes
excellent questionnaire uptake, almost certainly overestimates
true prevalence.
Various initiatives are under way to attempt to fill the
information gap in FA prevalence data worldwide.
EuroPrevall, launched in 2005, is an EU-funded multidisciplinary
integrated project (IP) involving 17
European member-states, Switzerland, Iceland, and
Ghana. Since the project began, new partners have
also joined from New Zealand, Australia, Russia, India
and China. 52 EuroPrevall aims to develop diagnostic
tools, carry out epidemiological studies and examine
the socioeconomic impact of FAs. One of its primary
objectives is to establish the prevalence of FAs in
adults and children, and the patterns of reactivity to the
five main allergenic foods across Europe. The results
are awaited in 2010.
CONCLUSION
To date, there is still a lack of convincing evidence of a
dramatic rise in FA in the West, but there is little debate
that it remains an important public health issue affecting
a large number of patients. However, the idea that
this is a problem exclusive to the developed world is
looking less credible. While data from the developing
world strongly indicate an underlying problem with FA,
it remains very difficult to
establish the true extent of
the problem. By relying on
patient-reported questionnaire
data or objective data
from allergy tests, without
confirmatory provocation
challenges, we are unable
to draw firm conclusions
either regarding current
prevalence of FA or a
change over time. Robust
studies using gold standard
diagnostic methods are
costly and time-consuming
but will be the only way
health services can truly
estimate disease burden.
Novel FAs that are found in
varying geographical locations
are also of importance
especially as exotic foods are increasingly imported
from one part of the world to another.
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11. Venter C, Pereira B, Voigt K, et al. Prevalence and cumulative incidence
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15. Leung TF, Yung E, Wong YS, Lam CW, Wong GW. Parent-reported
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16. Lee BW, Chew FT, Goh DYT. Changing prevalence of childhood
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33. Imamura T, Kanagawa Y, Ebisawa M. A survey of patients with selfreported
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36. Wieslander G, Norback D, Wang Z, et al. Buckwheat allergy and
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38. Goh DL, Chua KY, Chew FT, et al. Immunochemical characterization
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39. Kim SH, Kang HR, Kim KM, et al. The sensitization rates of food
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40. Leung R, Ho A, Chan J, et al. Royal jelly consumption and hypersensitivity
in the community. Clin Exp Allergy 1997; 27: 333-336.
41. Thien FC, Leung R, Baldo BA, et al. Asthma and anaphylaxis
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42. Niphadkar PV, Patil SP, Bapat MM. Chickpea-induced anaphylaxis.
Allergy 1997; 52: 115-116.
43. Rona RJ, Keil T, Summers C, et al. The prevalence of food allergy:
a meta-analysis. J Allergy Clin Immunol 2007; 120: 638-646.
44. Du Toit G, Levin M, Motala C, Perkin M, Stephens A, Turcanu V,
Lack G. Peanut Allergy and Peanut-specific IgG4 characteristics
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45. Characteristics of childhood peanut allergy in the Australian Capital
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46. Prifitis K, Mermiri D, Papadopoulou et al. Asthma Symptoms and
Bronchial Reactivity in School Children Sensitized to Food
Allergens in Infancy. Journal of Asthma; 45(7): 590-595
47. Sicherer SH, Sampson HA. Food allergy. J Allergy Clin Immunol
2006; 117: S470-S475
48. Roberts G, Lack G. Food allergy and asthma: what is the link
Paediatr Respir Rev 2003; 4: 205-212.
49. Kanny G, Moneret-Vautrin DA, Flabbee J et al.. Populations study
of Food allergy in France. J Allergy CLin Immunology 2001; 108:
133-140.
50. Bjorksten B. Genetic and environmental risk factors for the development
of food allergy. Curr Opin Allergy Clin Immunol. 2005 Jun;
5(3): 249-53.
51. Cataldo F, Accomando S, Fragapane ML , Montaperto D, SIGENP
and GLNBI Working Groups on Food Intolerances. Are food intolerances
and allergies increasing in immigrant children coming from
developing countries Pediatr Allergy and Immunology 2006: 17:
364-369
52. EuroPrevall (2006) WP 1.1 Birth Cohort Update, 1st Quarter 2006.
Berlin, Germany: Charité University Medical Centre.
53. Hadley C. Food allergies on the rise Determining the prevalence
of food allergies, and how quickly it is increasing, is the first step in
tackling the problem. EMBO Rep. 2006 Nov; 7(11): 1080-3
SAIS CONGRESS
The Annual Conference of the South African Immunology Society will be held from
9 to 11 December 2009 at the Vineyard Hotel in Newlands, Cape Town.
The primary focus will be science. An impressive range of international and local speakers
have accepted invitations to speak on topics in clinical and basic science immunology.
Please refer to:
http://www.saimmunology.org.za/index.phpoption=com_content&view=article&id=51&Itemid=36
for a list of the speakers and topics.
The secondary aim is for South Africans working in immunology to finally meet and discuss
how to take the Society forward.
We hope that most South Africans working in immunology will be able to attend. We now
invite you to register, and to submit an abstract. Information regarding the conference is
available at
http://www.saimmunology.org.za/index.phpoption=com_content&view=article&id=54&Itemid=37.
Please direct any specific questions to Prof. Willem Hanekom, Willem.hanekom@uct.ac.za,
interim president of the Society.
126 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

3
AB C of
Allergy
Allergy investigations
Lucretia is 9 years old.
Her mother has brought her for allergy
testing.
Dr Do-a lot is told that she was a ‘chesty’
baby. She developed eczema when she was
3 months old. When she was 3 years old she
was started on inhalers with a spacer for
asthma.
Her eczema has largely resolved, and her
asthma is controlled. She has however,
been increasingly troubled by symptoms
consistent with allergic rhinitis.
Her symptoms occur all year round, but
there is an exacerbation in spring.
Her mother is also concerned that she may
be reacting to wheat and milk as she has
large amounts of both in her diet.
She has never had an anaphylactic
reaction.
Dr Do-a lot examines Lucretia and finds
that she has typical allergic facies, pale
swollen inferior nasal turbinates, copious
clear rhinorrhoea, and a postnasal drip.
Dr Do-a lot decides to perform a skin-prick
test (SPT) in order to identify specific
triggers for her symptoms.
Shaunagh Emanuel
MB ChB
Di Hawarden
MB ChB
Allergy Diagnostic and Clinical
Research Unit (ADCRU),
UCT Lung Institute,
Mowbray, Cape Town,
South Africa
The third of our
illustrated series
highlights some of the
important issues in the
investigation of the
allergy patient.
This issue concentrates
on the skin-prick test.
We will explore testing
further in the next issue.
Potter PC. Allergic evaluation and management of the
atopic patient. SA Family Practice 2008; 50(5): 10-15.
Motala C, Hawarden D, on behalf of ALLSA. Guideline:
Diagnostic testing in allergy. S Afr Med J 2009; 99: 531-
She asks Lucretia’s mother to sign
consent for the procedure. She ticks
off common inhalant allergens on the
request form.
She can also perform SPTs for foods at
her clinic, and in view of the history of
eczema, she also ticks off Wheat, Milk,
Egg, Soya and Peanut, and asks her to
take the request form to Sister Sweet.
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 127

Sister Sweet asks Lucretia to sit on a stool, and to extend her forearm onto the counter
with her palm facing upwards.
Fortunately she does not have eczema in this area and the skin is intact.
Sister Sweet explains the procedure, and draws a series of short lines down her exposed
forearm and fetches the skin test kit from the fridge.
She places a small droplet of standardised allergen solution next to the markings that she
has made on the arm, and lightly pricks the skin with a lancet through each droplet. A saline
negative control and a histamine positive control are also applied. After 15-20 minutes, the
wheals and flares are measured with a clear ruler and recorded in mm. This is Lucretia’s
arm following her SPT.
Negative control
Dermatophagoides
pteronyssinus
D. farinae
Positive control
Grass mix
Bermuda grass
What is a skin-prick test
The characteristic raised itchy papules that
occur in a positive SPT are due to a
release of histamine in the skin. In a
sensitised individual, mast cells in the skin
will have specific IgE bound to the
surface. When allergens bind to the
specific IgE, cross-linking occurs with the
resultant release of histamine from the
mast cell (e.g. house-dust mite (HDM)
allergen in SPT solution binds to HDM IgE
on the mast cell surface).
Wheal = raised central pale bump
Flare = flat erythematous halo
Antigen
Cross-linking
Histamine
Lucretia’s SPT
Specific IgE
The specific IgE test
(RAST) is a blood test where
specific circulating IgE is
measured.
Mast cell
Diagrammatic
representation of a
mast cell with IgE
cross-linking
How does the skin-prick test compare with the specific IgE test in allergy testing
Skin-prick test (in vivo test)
- Inexpensive
- Rapid: results within 15-20 minutes
- Patient involvement . . . educational
- Sensitive (especially for foods)
- Antihistamines withdrawn for 72 hours
- Needs to be performed on ‘normal skin’
- Small risk of anaphylaxis: trained personnel and
resuscitation equipment necessary
- Reporting needs to be standardised in mm (positive
result = 3mm> negative control)
- Dermatographism: false positives
Specific IgE (RAST) (in vitro test)
- More expensive
- Safe
- No need to withdraw medication
- Not influenced by skin disease (e.g. eczema)
- Larger range of allergens
- Result delayed
- Lends itself to over testing (knee-jerk ticking of
request form)
128 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

What to tick off on the skin-prick test request form…
When inhalant allergy is suspected
on history:
When food allergy is suspected
on history:
Indoor inhalants:
House-dust mite (Der P 1 and Der f 1)
Moulds
(Cladosporium, Aspergillus, Alternaria)
Cat
Dog
Outdoor inhalants:
Grass pollen (Rye, Bermuda)
Latex
Note:
in health care workers
and hairdressers
Basic panel:
- Milk
- Egg white
- Corn
- Peanut
- Soya
- Potato (especially in atopic dermatitis)
- Fish
- Wheat
Additional foods would depend on a history of a temporal
relationship between food ingestion and clinical reaction.
Remember:
Do not perform an SPT if there is a past history of severe reactions.
It is unwise to perform an SPT in a child who has had a severe reaction to peanuts, for
example, in order to test sensitivity to that antigen.
A specific IgE blood test is safer in this case.
Why test for allergies
- Identify specific trigger/s
- Identify infants with a high risk for developing other allergic diseases
(For example: egg, mite or pollen allergy in first year of life)
- Allergen avoidance: - Environmental
- Job/Hobby/Pets/Foods
- Immunotherapy – is the patient a candidate for desensitisation
Remember that food
allergies can cause:
Asthma
Atopic dermatitis
Rhinitis
Urticaria/ angio-oedema
Anaphylaxis
Dr Do-a lot tested Lucretia in order to identify what
triggers might be playing a role in her symptoms. Lucretia
is allergic to house-dust mites and grasses which would
account for her persistent allergic rhinitis, as well as the
springtime exacerbation. The foods tested were negative.
Sister Sweet has discussed methods of allergen avoidance,
and has supplied her with the relevant ALLSA information
sheets. Monosensitive patients tend to do better on
immunotherapy. Lucretia is not monosensitive, so Dr Do-a
lot has decided to commence treatment with
antihistamines and a daily steroid nasal spray, and will
review Lucretia in 3 months’ time.
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 129

ALLERGIES IN THE WORKPLACE
ALLSA RESEARCH AWARDS REPORT
APPROACHES TO DIAGNOSING ANISAKIS
ALLERGY
Natalie Nieuwenhuizen, 1 BSc(Med) Hons, PhD
Mohamed Jeebhay, 2 MBChB, DOH, MPhil (Epi),
MPH (Occ Med), PhD
Andreas L Lopata, 1 , 3 MSc, PhD (Med Science)
1 Division of Immunology, Institute of Infectious
Diseases and Molecular Medicine, Faculty of Health
Science, University of Cape Town, South Africa
2 Centre for Occupational and Environmental Health
Research, School of Public Health and Family
Medicine, University of Cape Town, South Africa
3 Allergy Research Group, School of Applied Science,
Royal Melbourne Institute of Technology, Bundoora
West Campus, Melbourne, Australia
SUMMARY
Anisakis is a parasitic nematode which infects fish
and can cause gastrointestinal disease if accidentally
ingested. Infection can be accompanied by severe
allergic reactions such as urticaria, angio-oedema
and anaphylaxis. Furthermore, workers involved in
fish processing can develop occupational allergy to
Anisakis, including asthma, rhinoconjunctivitis and
protein contact dermatitis. Diagnosis of allergy to
Anisakis relies on skin-prick tests and the detection
of specific IgE by ImmunoCAP. Since Anisakis
infests fish, fish allergy should be investigated in
symptomatic patients. Anisakis proteins also
demonstrate considerable immunological crossreactivity
to proteins of related nematodes and other
invertebrates such as house-dust mites and cockroaches;
this needs to be borne in mind when the
diagnosis is made. This review outlines the
approaches that have been used to increase the
specificity of Anisakis diagnosis, including the use of
immunoblotting and the identification of Anisakis
allergens.
The management of anisakiasis involves physically
removing the larvae, if possible, or treating the patient
with antihelminthics, anti-inflammatories and analgesics.
3,4 The Anisakis larvae cannot survive or reproduce
in humans, but if the larvae are not removed, the
disease can become chronic as inflammatory cells surround
the larval remains and lead to symptoms which
can mimic dyspepsia, Crohn’s syndrome, appendicitis,
irritable bowel syndrome, diverticulitis, non-specific
eosinophilic enteritis, or even gastric cancer. 2
Abdominal pain, nausea, vomiting and/or diarrhoea
within 48 hours of consuming fresh seafood should
indicate the possibility of Anisakis infection. As many
cases of anisakiasis have occurred after consumption
of freshly caught fish that appeared well-cooked but
was not sufficiently heated through to kill larvae, ingestion
of raw seafood should not be the only factor meriting
further investigation. In order to kill larvae, fish
should be frozen at –20°C for at least 24 hours or
cooked so that all parts of the fish reach at least 60°C
for 10-20 minutes. 2 Smoking fish or marinating it in
lemon juice or vinegar does not kill Anisakis.
ANISAKIS ALLERGY
Of particular relevance to the physician is that Anisakis
can also cause severe allergic reactions because of its
ability to elicit strong Th2 responses. 5,6 Many patients
experience gastroallergic anisakiasis, in which infection
ANISAKIS INFECTION
Anisakis species are marine roundworms which use
sea mammals such as dolphins and whales as primary
hosts. The stage 3 larval form (L3) of Anisakis (Fig. 1)
infects fish and other seafood such as squid, and consequently
humans may become accidental hosts for
Anisakis if they consume raw or undercooked fish. 1
Infection is known as anisakiasis and is often associated
with gastrointestinal symptoms such as abdominal
pain, diarrhoea, nausea and vomiting. Patients’ reactions
range from being asymptomatic to requiring
emergency room care. Since 1960 when anisakiasis
was first described, thousands of cases have been
reported from Japan and hundreds from Europe, the
USA. and other parts of the world. 2
Correspondence: Dr N Niewenhuizen, Division of Immunology,
Institute of Infectious Diseases and Molecular Medicine, University of
Cape Town, Observatory 7935. E-mail natalie.niewenhuizen@uct.ac.za
Fig. 1. Anisakis larvae removed from Thyrsites atun
(snoek).
132 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

is accompanied by allergic reactions such as urticaria,
angio-oedema, bronchospasm and/or anaphylaxis. 7,8
This allergic response can occur without gastrointestinal
symptoms, leading to misdiagnosis of the reaction
to Anisakis as fish allergy or idiopathic urticaria/anaphylaxis.
5 Symptoms can begin anywhere between a few
hours to more than a day after ingestion of the parasite,
and patients may therefore not connect the ingestion
of the fish to the symptoms. Although some
patients tolerate dead larvae in frozen or cooked fish,
others have symptoms after eating well-cooked or
canned fish, indicating that both live and dead larvae
and their proteins can cause allergic reactions. 9-12 A history
of fish consumption prior to allergic symptoms and
the absence of sensitisation to fish indicates the need
to test for Anisakis allergy.
Currently, the diagnosis of Anisakis allergy relies on a
clear history of potential exposure to Anisakis and
symptoms of gastroallergic anisakiasis along with
Anisakis specific IgE and positive Anisakis skin-prick
tests (SPTs). 5,7 However, because many allergens of
Anisakis are heat stable, exposure to Anisakis proteins
in fish on an ongoing basis can also cause symptoms
such as chronic urticaria, protein contact dermatitis,
asthma and rhinoconjunctivitis. 13-19 In this case the clinical
history may be less clear since patients may be
exposed to many agents in their environment at the
same time. The use of specific IgE alone to diagnose
Anisakis allergy is confounded by the fact that even
asymptomatic individuals can have Anisakis specific
IgE because of cross-reactivity with other helminths
(e.g. Ascaris) or invertebrates such as dust mites, cockroaches
and shrimp. 20-22 Studies in Spain have found
that a large number of asymptomatic individuals have
Anisakis specific IgE, some related to subclinical sensitisation
and others due to false-positive results as a
result of cross-reactivity. 22-24
The muscle protein tropomyosin is an important source
of cross-reactivity with other invertebrates. Recently
we showed by allergen microarray analysis that all
patients with specific IgE antibodies to Anisakis
tropomyosin (Ani s 3) also recognised tropomyosin of
shrimp, dust mite, cockroach and snail (unpublished
data). Whether Anisakis tropomyosin is a clinically relevant
allergen is however controversial. Asturias et al . 20
have suggested that tropomyosin is not an important
allergen as asymptomatic patients were sensitised to it
whereas symptomatic patients were not. Other
researchers suggest that Anisakis tropomyosin could
play a role in eliciting food allergy after ingestion of
cooked seafood, because it closely resembles the
heat-stable shrimp tropomyosin, an important allergen
in seafood allergy. 25
THE ROLE OF IMMUNOBLOTTING IN THE
DIAGNOSIS OF ANISAKIS ALLERGY
Since cross-reactivity can cause false-positives in SPTs
and specific IgE tests, some authors have used IgE
immunoblotting to differentiate anisakiasis/Anisakis
allergy from asymptomatic Anisakis sensitisation. 24,26,27
One study found that patients with confirmed Anisakis
allergy had IgE directed at several proteins of medium
molecular weight as well as low-molecular-weight proteins,
while patients with no allergy or doubtful symptoms
were more likely to recognise either a single
medium-molecular-weight protein of approximately 40
kDa (possibly Anisakis tropomyosin) or a few mediummolecular-weight
proteins. 26 Another study also found
that asymptomatic blood donors with specific IgE to
Anisakis frequently detected a single protein of 42 kDa
whereas truly sensitised patients recognised multiple
allergens of the crude extract. 24
Only one case of food allergy to Anisakis has been documented
in South Africa 28 despite the recent popularity
of sushi, perhaps because the disease is largely
unknown to physicians and may go undiagnosed.
Recently, several case reports described adverse reactions
to Anisakis in individuals handling fish or fishmeal,
with symptoms ranging from conjunctivitis to allergic
asthma. 16,17,19 In an epidemiological study of two large
fish-processing factories in St Helena Bay on the west
coast of South Africa we found a prevalence of 8%
sensitisation to Anisakis among the fish-processing
workers, 6,29 but only 1-3% had Anisakis-related allergic
symptoms. The study also found that indviduals with
Anisakis sensitisation were twice as likely (OR = 2.24,
CI: 1.01-4.97) to have high seafood intake as measured
by elevated level of serum omega-3 fatty acids (eicosapentaenoic
acid). We therefore decided to look at patterns
of IgE-binding proteins recognised by our
sensitised workers to compare them with patterns
found in previous studies where patients had symptoms
of gastroallergic anisakiasis.
Immunoblotting using serum from 15 workers who
were ImmunoCAP or SPT positive to Anisakis (Table I)
showed diverse patterns of IgE binding to Anisakis proteins
(Fig. 2), as has been observed in previous studies.
30 Somatic Anisakis antigens were used for
immunoblotting, as the workers were likely to be
exposed to Anisakis through handling of fish, inhalation
of vapours and consumption of cooked fish. Workers
who were positive to Anisakis on ImmunoCAP were
often also positive to Ascaris lumbricoides, a human
roundworm, which is closely related to Anisakis. 31 A
subgroup analysis of sera (n = 129) demonstrated a
very high correlation (r = 0.72, p

Table I. Descriptive data of Anisakis-sensitised workers whose sera were investigated by immunoblotting
134 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3
Worker Symptoms Non-specific Anisakis Anisakis Ascaris Sensitisation Other sensitisations
broncho-hyper ImmunoCAP SPT ImmunoCAP to Anisakis (microarray,
responsiveness (kU/l ) (kU/l ) tropomyosin ImmunoCAP*
(NSBH) (Ani s 3) on or SPT)
microarray*
1 None No 1.4 – 0 – None
2 None No 10.4 + 0.4 Not tested ImmunoCAP: lobster, pilchard
3 None No 3.6 + 0.5 – ImmunoCAP: latex, lobster
SPT: HDM, dog, cockroach
Microarray: Api m 1,
Cup a 1, Lol p 1
4 None Not tested 2.4 + 0 – SPT: HDM
5 Work-related chest and skin symptoms Yes 3.6 – 4 – SPT: HDM
6 Work-related ocular-nasal symptoms Yes 2.8 + 5.1 + ImmuoCAP: lobster
Seafood allergy (lobster, mussels),
SPT: HDM, cockroach
reactions after ingestion Microarray: Api m 1, Gal d 4,
Pen i 1, Pen m 1, Per a 7,
Der p 10, Hel as 1
7 Work-related chest symptoms Yes 4.8 + 8 – SPT: HDM, cockroach
8 Work-related ocular-nasal symptoms No 2.5 + 1.9 – ImmunoCAP: lobster
(low – 0.58kU/L)
9 No Yes 2.1 + 4.2 – ImmunoCAP: latex, lobster,
anchovy, pilchard
SPT: cockroach
Microarray: Api m 1, Cup a 1,
Lol p 1, Ole e 1
10 Work-related chest symptoms Not tested 2 + 4.1 + ImmunoCAP: latex, lobster
SPT: HDM, cockroach, ryegrass,
raw lobster, Aspergillus
Microarray: Api m 1, Lol p 1,
Pen i 1, Per a 7, Pen m 1,
Phl p 1, Der p 10, Hel as 1
11 No Yes 2.4 + 23 – Microarray: Bos d 7, Der f 2
12 Work-related ocular-nasal and chest No 3.7 + 61.3 – ImmunoCAP: lobster
symptoms
SPT: HDM
13 No Yes 0 + 0 – None
14 Work-related chest symptoms No 0 + 0.9 – SPT: cat, dog
15 Work-related chest symptoms Yes 0 + 0 – None
* A value greater than 0.35 kU/l was considered positive.
SPT – skin-prick test, HDM – house-dust mite.

Fig. 2. IgE immunoblotting against Anisakis antigens using sera from 15 Anisakis-sensitised fish-processing workers.
Workers 1-4 had higher specific IgE to Anisakis than to Ascaris, workers 5-10 had specific IgE to both Anisakis
and Ascaris, workers 11-12 had higher levels of specific IgE to Ascaris than to Anisakis and workers 13-15 were
SPT positive to Anisakis but negative on ImmunoCAP tests.
blotting with deglycosylated Anisakis proteins or excretory-secretory
(ES) proteins to increase the specificity
of Anisakis diagnosis. 24,33 However, to avoid misdiagnosis
due to cross-reactivity, it is ideally better to use purified
or recombinant allergens that are specific for
Anisakis-allergic patients. 34 The identification of specific
Anisakis allergens which could be used in tests such
as ImmunoCAP, SPT, allergen microarray or immunoblotting
will in the long term increase the specificity of
diagnosis.
ANISAKIS ALLERGENS
Currently nine allergens of Anisakis simplex have been
identified, most of which exist in recombinant form.
Patients may be exposed primarily to somatic antigens
from dead larvae in food, ES antigens when there is
expulsion or surgical removal of the intact larvae, or
both, in cases where the larva penetrates the tissue, is
killed by the host, and subsequently degenerates
inside the host. 35 Many allergens of Anisakis are heat
and/or pepsin resistant 9,36,37 and most of them are
present in ES products.
The major allergens of Anisakis (recognised by more
than 50% of patients) are considered to be Ani s 1 and
Ani s 7, 38 although in one study Ani s 5 was recognised
by 49% of patients (41/84). The 24 kDa Ani s 1 is recognised
by 67-87% of patients with gastroallergic anisakiasis
and is not detected by asymptomatic
individuals. 23,39 This allergen is secreted by the worm
and shows homology to serine protease inhibitors. A
21 kDa isoform of Ani s 1 also exists. 39 Ani s 1 is heat
stable and can act as a food allergen, causing reactions
after ingestion of cooked fish. The other major allergen,
Ani s 7, is also an ES product of 139 kDa and is a novel
glycoprotein. 40 It was recognised by 100% of patients
with Anisakis allergy. 40 However, Ani s 7 has crossreactive
O-glycans and is better for diagnostic tests
when deglycosylated. 41
Another important allergen is Ani s 4, a heat-stable
nematode cystatin that is recognised by only 27-30%
of patients but appears to be particularly important in
eliciting anaphylaxis. 9 Heat-stable allergens such as Ani
s 4 are important even if they are classified as minor
allergens as a result of their frequency of recognition,
because these allergens are associated with allergic
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 135

136 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3
Table II. Anisakis allergens
Allergen Molecular weight Description Location Recognition in Recombinant
Anisakis-sensitised patients protein exists References
Ani s 1 24 kDa Kunitz-type serine Excretory gland, 86% (42/49) Yes Moneo et al., 23
21 kDa isoform protease inhibitor like secreted 88% (7/8) Caballero et al., 36
Heat stable (ES products) 67% (56/84) Shimakura et al. 39
Ani s 2 100 kDa Paramyosin Muscle 88% (23/26)
23% (6/26) (r Ani s 2) Yes Perez-Perez et al. 44
Ani s 3 41 kDa Tropomyosin Muscle 13% (8/62) patients with Yes Asturias et al. 20
specific IgE
0% (0/10) patients with true
Anisakis allergy
Ani s 4 9 kDa Nematode cystatin Excretory gland and 27% (8/30) Yes Moneo et al. 9
cysteine protease inhibitor) underneath the cuticle 22% (6/27) Caballero et al., 36
Heat-stable in L3 ES product 30% (25/84) Caballero & Moneo, 37
Roderiguez-Mahillo
et al. 46
Ani s 5 15 kDa Homologous with nematode Excretory gland, 49% (41/84) Yes Kobayashi et al., 34
proteins in the SXP/RAL-2 ventriculus and luminal 25% (7/28) to Caballero et al., 36
family surface of the r Ani s 5
Heat resistant
intestinal epithelium
ES protein
Ani s 6 7 kDa Serine protein inhibitor ES products 18% (5/28) to Yes Kobayashi et al. 34
rAni s 6
Ani s 7 139 kDa Novel protein. ES products 100% (60/60) No – but a recombinant Anadon et al., 38
(glycoprotein) fragment exists Rodriguez et al. 40
Ani s 8 15 kDa Heat stable ES products 25% (7/28) Yes Kobayashi et al. 43
SPX/RAL protein
Homologous with proteins
in the SXP/RAL-2 family,
including Ani s 5
Ani s 9 14 kDa Belongs to SXP/RAL-2 family ES products and crude 13.8% (5/36) Yes Rodriguez-Perez
Heat and pepsin resistant extract et al. 42
Troponin-like allergen 21 kDa Homology to nematode
troponins Muscle 20% Yes Arrieta et al. 45
ES – excretory-secretory

eactions to cooked or canned fish. 42 Therefore, frequency
of recognition is not always equal to clinical relevance.
Other minor allergens include Ani s 5 (15 kDa),
Ani s 8 (15 kDa) and Ani s 9 (14 kDa), which share
homology and are all members of the SPX/RAL-2 family,
which is specific to nematodes. They are all heat-stable
ES products, although Ani s 9 is reportedly more
abundant in crude extract, and their biological function
is unknown. 36,42,43 Another minor allergen, Ani s 6 (7
kDa), is homologous with serine protease inhibitors,
including the honeybee allergen Api m 6. 34
The remaining two allergens, Ani s 2 (41 kDa) and Ani
s 3 (100 kDa) are the muscle proteins paramyosin and
tropomyosin, respectively, and are thought to be primarily
responsible for cross-reactivity between
Anisakis and other invertebrates. 20,25,44 They do not
appear to be important in eliciting allergic reactions to
Anisakis, 20,38 but further studies are needed. A 21 kDa
protein with homology to nematode troponin has also
been identified as an allergen but has never been
named. 45
Purified Anisakis allergens have proven useful in diagnosis,
especially in combination. In one study, 95% of
64 Anisakis-allergic patients tested positive for Ani s 1
and/or Ani s 4 by immunoblotting 47 and in a follow-up
study, only 12% of patients (10/84) did not recognise
one or both of these allergens. 36 Including Ani s 5 to
the panel of allergens tested raised the sensitivity to
94%, with 79/84 patients recognising one or more of
the three allergens.
Table II lists the nine Anisakis allergens.
APPROACH TO THE DIAGNOSIS AND
MANAGEMENT OF ANISAKIS ALLERGY
The ideal diagnostic test for Anisakis allergy should
include all clinically relevant Anisakis allergens.
Currently, CAP-RAST and SPTs use whole Anisakis
extracts, while the latest allergen microarrays only contain
Ani s 1 and Ani s 3. Once a patient has confirmed
Anisakis allergy, after excluding fish allergy and taking
into consideration cross-reactivity to other helminths
(e.g. Ascaris) or invertebrates such as dust mites, cockroaches
and shrimp, identifying which allergens are
recognised by the patient will assist in making dietary
recommendations. 9 Many patients with Anisakis allergy
are able to tolerate a diet of frozen or well-cooked
fish, 48 but a small percentage of patients are particularly
sensitised to heat-stable allergens such as Ani s 4
and react badly to cooked or canned fish. 2,9,33 These
patients should avoid marine fish altogether.
Declaration of conflict of interest
The authors declare no conflicts of interest.
Acknowledgements
This work was sponsored by the Medical Research Council (MRC) and
National Research Foundation of South Africa and an Allergy Society of
South Africa (ALLSA) research award.
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138 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

SNIPPETS FROM THE JOURNALS
Allan S Puterman, MB ChB, FCP, FAAAAI
The 22 January 2009 edition of the New England
Journal of Medicine carries two articles related to the
wheezy infant that are important in understanding this
condition. Ironically the two articles are broadly contradictory
although this is not so when read in depth.
The first article is titled ‘Oral prednisolone for preschool
children with acute virus-induced wheezing’
(J Panicker and others). The authors comment that
attacks of wheezing induced by upper respiratory viral
infections are common in children aged 10 months till
6 years. Oral prednisolone is widely used to treat these
children with wheezing who present to hospital and
there is conflicting evidence regarding its efficacy.
The authors conducted a randomised, double-blind,
placebo-controlled trial comparing a 5-day course of
oral prednisolone with placebo. The dose of prednisolone
was 10 mg per day for children 24 months or
younger and 20 mg per day for children over 24
months of age. These doses were in accordance with
British Thoracic Society guidelines. (These doses are
far less than the 2 mg/kg dose used in South Africa.)
Further, the authors state that they enrolled children
between the ages of 10 months and 60 months who
had an attack of wheezing that ‘a physician judged to
be preceded by the symptoms and signs of a viral
infection of the upper respiratory tract’. The authors
also tried ‘to reduce the recruitment of infants with
wheezing associated with bronchiolitis’.
The primary outcome was the duration of hospitalisation.
Secondary outcomes were the score on the
Preschool Respiratory Assessment Measure (PRAM),
albuterol use, and a 7-day symptom score.
Of the 700 children enrolled there was no significant
difference in the duration of hospitalisation between
the placebo group and the prednisolone group [13.9
hours vs. 11.0 hours]. In addition, there was no significant
difference between the two study groups for any
of the secondary outcomes or for the number of
adverse events.
In the discussion, the authors report on the Csonka and
Tal studies that did show benefits of systemic corticosteroids.
Csonka used 2 mg/kg of oral prednisolone
and Tal used 4 mg of intramuscular methylprednisolone.
The children in this (Panicker et al.) study had
mild to moderate wheeze rather than severe wheezing
and the majority of children who were recruited ‘did
not have the classic atopic asthma phenotype that is
responsive to a short course of oral corticosteroids’.
The second article is titled ‘Preemptive use of high
dose fluticasone for virus-induced wheezing in
young children’ by FM Ducharme and others.
These Canadian authors studied 129 children aged 1 to
6 years. These children had previously had moderate to
severe wheezy episodes with upper respiratory tract
infections. The children were now randomly assigned
to receive 750 µg inhaled fluticasone or placebo twice
daily for up to 10 days after the first signs of an upper
respiratory tract infection. This was a home-based
study and parents started treatment at their discretion.
The children eligible for this study would have already
had 3 episodes or more of wheezing. Children excluded
from this study included those with allergic rhinitis
and documented positive skin tests or elevated specific
IgE levels. The primary outcome was rescue with
oral corticosteroids.
Of 2 243 children screened, 1 860 were ineligible. Of
the 383 eligible children, the parents of 199 declined
participation leaving 62 in the fluticasone group and 62
in the placebo group.
The results showed that 8% of upper respiratory tract
infections in the fluticasone group led to treatment
with rescue corticosteroids as compared with 18% in
the placebo group. A concern was that the children in
the fluticasone group had a smaller gain in height and
weight.
It is important to be aware that the efficacy of oral and
inhaled cortisone is being studied in different cohorts
of wheezy children. These cohorts include children
with bronchiolitis or children with wheeze following
upper respiratory tract infections, or children with asthma
or children with predictive scores for asthma.
These groups are further subdivided into mild or moderate
or severe wheezers. Finally, the dose and route
of the corticosteroid can range widely. One needs to
read these articles very carefully.
Finally I would like to draw readers attention to a seminal
article in the April 2009 Journal of Allergy and
Clinical Immunology. The article is titled ‘An interaction
between filaggrin mutations and early food
sensitization improves the prediction of childhood
asthma.’ (Ingo Marenholz et al.).
In this article the authors evaluated whether filaggrin
gene (FLG) mutations identified in people with eczema
can predict the development of asthma.
Loss of function mutations in the gene encoding filaggrin,
which is important for skin barrier function, were
identified to be strong genetic risk factors for eczema
and eczema-associated asthma.
FLG mutations were identified in the German
Multicenter Allergy Study (MAS) birth cohort. This
cohort of 1 314 German children was selected in 1990
and followed intensively in respect of allergy symptoms,
eczema, allergen sensitisation and asthma; 871
of these children had donated DNA samples and
formed the study population.
Of the study population, 236 children had eczema
before the age of 3 years and 168 had asthma till age
of 13 years. Within the first 3 years of life, 104 children
had detectable food allergen sensitisation.
FLG mutation alone in this cohort had a positive predictive
value for asthma of 32.5%. Early sensitisation
to food allergen alone had a positive predictive value
for asthma of 43.0%. FLG mutation plus early food
allergen sensitisation increased the positive predictive
value to 73%. The combination of FLG mutation, early
food allergen sensitisation and eczema yielded a positive
predictive value for asthma of 100%.
The clinical implication of this finding is that FLG mutations
can be used for the prediction of childhood asthma
and might facilitate the development of early
preventive subgroup-specific interventions.
Correspondence: Dr A Puterman, e-mail: putall@global.co.za
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 139

CONGRESS REPORT
2009 ALLSA CONGRESS, HELD AT THE ELANGENI
HOTEL, DURBAN, 10-12 JULY 2009
Profs Mohamed Jeebhay and Cas Motala with Dr
George du Toit.
‘Durbs’ provided a warm winter welcome to delegates
at the 2009 ALLSA Congress in July. From the opening
Eugene Weinberg Lecture on recent advances in antihistamine
treatment delivered by visiting speaker Prof
Estelle Simons from Canada to the final session on
guidelines (paediatric asthma and allergic rhinitis) and
the year’s journal articles review, the Congress offered
a varied scientific programme including the main
themes of drug allergy, food allergy and anaphylaxis.
Please see the congress issue of the journal (June
2009) for articles by some of the speakers and abstracts
of oral presentations and posters. This report captures
just a few of the outstanding papers presented.
Dr George du Toit of King’s College, London, and St
Guy’s and Thomas’ Hospitals, discussed ‘Prevention
of peanut and sesame allergy’. Food allergy presentation
appears to be changing as it’s rare to find only
one food allergy, and peanut and sesame allergy are
becoming more prevalent. Sesame is intriguing as
most children can tolerate sesame oil or loose seeds
but not concentrates like hummus. He mentioned the
dual allergen exposure hypothesis – cutaneous exposure
occurs first and then oral exposure. Many variables
are being considered to determine when allergens
have an effect – in utero, the mother’s diet while
the child is breastfed and whether cow’s milk protein
allergy plays a role.
On the protective effect of breastfeeding (weaning
advised after 4-6 months and at 6 months in the developing
world by the World Allergy Organisation), Dr du
Toit explained that among patients in the developed
world less than 1% are exclusively breastfed. Among
infants he sees in the UK 51% have received solids
before 4 months. The majority of parents are avoiding
nuts in the belief that it may cause allergy but paradoxically
peanut allergy rates have gone up.
Studies that have tried to prevent the development of
food allergy in children have not produced concrete
results. A study of premature babies who it appears
have all the risk factors for development of food allergy
showed that there is no higher rate of food allergy
in premies. Weaning before 4 months of age to more
than four foods showed an increase in atopic eczema
but no effect on food allergy. Currently the LEAP study
is investigating peanut allergy with the intervention
group being given 2 g of peanuts three times per week
while the control group are avoiding peanuts altogether
– 10% of the 4-5-month-old group have already been
excluded as they are allergic, while 40% are already
sensitised at age 4-5 months. ‘We are still trying to
answer very basic questions,’ concluded Dr du Toit.
Increasing peanut and sesame allergy is a recognised
health concern that needs to be taken seriously. At
present there is no evidence to support avoidance but
we need to wait for the results of human studies like
LEAP and EAT before we can draw conclusions.
Drs Harris Steinman, Di Hawarden and Sharon Kling at
the ALLSA stand.
Prof Estelle Simons from Cananda addressed the question
of ‘Risk assessment in anaphylaxis’. Figures in
anaphylaxis show an increase – from 21/100 000 person
years in the 80s to 50/100 000 for the 90s.
Although the incidence has doubled, it is probably still
underdiagnosed because symptoms are subjective and
there is no optimal diagnostic test. The pathogenesis
also differs around the world.
Triggers can be food, venom, latex, exercise, inhalants
or iatrogenic, and new, previously unrecognised triggers
are being reported: foods (lupin and quinoa – formerly
only found in health shops but now becoming
mainstream as they are added to wheat products);
additives (carmine); stings or bites (even mosquitoes);
drugs (heparin).
Prof Simons stressed the importance of accurate documentation
of past episodes. ‘Believe the patient’s
story even if it seems weird.’ In a case of heparin being
the trigger for children on dialysis, it was tested and
found to be contaminated; as a result heparin is now
monitored. In confirming the diagnosis, one should
retake the history, review the medical records and lab
tests, but should not use normal results to refute clinical
diagnosis. The clinical diagnosis is most important.
‘Believe the patient, believe your instincts,’ Prof Simons
140 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

Mr Robbie Moss (MSD), Dr Di Hawarden, Ms Kim
Holiday (MSD) and Ms Lindsay Cracknell (AHN
Pharma).
advised. Common differential diagnoses to be considered
are hives, asthma, panic attacks and choking.
Patients at increased risk include infants (even as
young as 1 month old), pregnant women (although rare
in pregnancy the risk is high for both mother and baby)
and the elderly. She mentioned a study of 25 deaths in
the elderly where triggers were medication, radiocontrast
media and insect bites. Almost all had cardiac or
respiratory symptoms and 21 died within half-an-hour.
The heart is a target organ in anaphylaxis as mast cells
occur throughout the myocardium, and histamine and
tryptase can lead to artery spasm. Beta-blockers carry
an increased risk of more severe anaphylaxis while it is
less common with ACE inhibitors.
Prof Simons concluded by repeating the problem that
tests may or may not confirm the diagnosis and said
that there is a huge challenge for young reserachers to
find tests that can confirm it.
‘Inhalant food allergens’ were discussed by Prof
Mohamed Jeebhay. Allergic reactions following inhalation
are increasingly being reported, especially in nonoccupational
contexts; occupational settings provide
the ideal place to study them however. In the home
cooking and food preparation are obvious sources, as
well as second-hand contact (from a family member
who is eating the food) while restaurants, airlines and
Drs Ahmed Manjra, Mike Levin and Harris Steinman.
food markets are recreational sources. Work and
school also provide potential second-hand contact as
well as food produced/sold there.
In the food handling industry allergen sources can be
food-derived protein, non-food agents and additives
(including enzymes), and the process of preparation
needs to be considered because allergen characteristics
are altered by harvesting, storage, heat and pH
treatment. Generation of bio-aerosols and dust is most
important – occurs when gutting fish, mixing dough
and blending spice, for example. Garlic and onion have
a higher allergen content in powdered and flake form.
When investigating reactions, one needs to establish if
it is a de novo inhalation, re-exposure to the inhalant or
possibly a reaction because of cross-reactivity with
another allergen. Management involves removal from
exposure, optimising pharmacological treatment, avoidance
of accidental exposure and education about food
products and labelling.
The ALLSA AGM was held at the congress and a new
Executive Committee for the 2009-2011 tenure
announced. Dr Ahmed Manjra was elected Chairman,
Dr Ahmed Manjra, new ALLSA Chairman, with Prof
Cas Motala and Dr Sharon Kling, Immediate Past
Chairman.
Dr Christo Buys, our Namibian member of the Current
Allergy & Clinical Immunology Editorial Advisory
Board.
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 141

Gala Dinner
142 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

Prof Estelle Simons enjoying the evening with her
husband Keith Simons and Prof Cas Motala.
Overseas speakers, Prof Estelle Simons and Dr
George du Toit receiving their awards.
Dr Andrew Halkas is the Secretary and Prof Cas Motala
the treasurer. Other Excom members are Prof Robin
Green, Prof Matt Haus, Dr Di Hawarden, Prof
Mohamed Jeebhay, Dr Sharon Kling, Dr Sam Risenga
and Dr Andre van Niekerk.
The gala dinner was a glittering occasion with a talented
trio providing saxophone, violin and vocal musical
accompaniment to create a relaxing vibe. Visiting
speakers were honoured with Honorary Life
Membership of ALLSA and presented with gifts reflecting
the cultural art of Durban. A Distinguished Service
Award was presented to Prof Heather Zar in recognition
of her outstanding contribution to ALLSA while
serving on the ALLSA Excom for many years. The
Current Allergy & Clinical Immunology journal awards
were announced: Drs Sebastiana Kalula and Kathleen
Ross won the Best Article award and a cheque for
R1 000 each for their article ‘Immunosenescense –
inevitable or prevantable’ and the Best Photograph
(Graphic) award and a cheque for R1 000 were presented
to Dr Shaunagh Emanuel for her cover design of
the November 2008 issue and the illustrations for her
‘Angelina Angio-oedema’ article in the same issue.
Research awards were presented to Dr S Karabus
(ALLSA/GSK/MSD award), Mrs ME Ratshikhopha
(ALLSA/UCB award) and Dr H Steinman (ALLSA/Cipla
Medpro Award). Ms R Baatjies won the ALLSA Travel
Award.
Anne Hahn
Dr Ahmed Manjra, Congress Convenor, presenting Ms
Roslynn Baatjies with the ALLSA Travel Award.
Photographs: Shahnaz Arnold
Prof Heather Zar accepting her Distinguished Service
Award.
Don’t miss the
ALLSA congress
next year!
See p. 138
for the first
announcement.
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 143

PRODUCT NEWS
DUE TO ITS PERSISTENT RECEPTOR OCCUPANCY,
XYZAL ® REMAINS THE LAST WORD IN ALLERGY
Because antihistamines work by blocking the action of histamine,
receptor occupancy is an accurate model to predict
clinical effectiveness. 1 Compared to desloratadine and fexofenadine,
Xyzal ® , containing 5 mg levocetirizine 2HCL*,
rapidly occupies a high proportion of histamine receptors
resulting in a fast and sustained clinical response. 1,2
Thus, Xyzal ® can be said to work faster at inhibiting the allergic
response more effectively. 3
Compared to other antihistamines, Xyzal ® produced a
potent, sustained and consistent blockade of histamineinduced
reactions. 3 Wheal and flare response decreased
rapidly and was maximal at 4 hours, 3 while complete inhibition
was maintained throughout 12 hours. In this particular
study Xyzal ® was superior to the other treatments (placebo,
fexofenadine, ebastine, mizolastine and loratadine), at most
time points, throughout 24 hours. 3
In a study against desloratadine, Xyzal ® also achieved significantly
lower pruritus scores from day 1 of treatment, while
throughout the 4 week duration of the study, composite
scores were markedly lower with Xyzal ® . 4
Further studies also showed that Xyzal ® efficiently relieves
the symptoms of persistent allergic rhinitis 5 with symptoms
such as nasal and ocular pruritus, sneezing and rhinorrhea
improving as early as during the first week. 6 In addition nasal
congestion was improved from 3 months 6 while Xyzal ® was
associated with reduced prevalence of co-morbidities,
reduced absenteeism and improved quality of life. 6
Xyzal ® was also shown to control the symptoms of seasonal
7 and perennial allergic rhinitis 8 efficiently. In the case of
perennial allergic rhinitis, relative improvement for major
symptoms during the first week measured 86% 8 while
improvement in nasal congestion over 6 weeks was 83%. 8
When compared to desloratadine, once more, Xyzal ® provided
more effective relief from nasal obstruction. 7 Xyzal ® was
also found to have a similar safety profile in adults and children,
8,9 compared to placebo. Additionally Xyzal ® proved to
be non-sedating 9 and without measurable effect on psychomotor
or cognitive performance. 9
For full prescribing information refer to package insert
S2 Xyzal ® 5 mg tablets. Each tablet contains 5 mg levocetirizine 2HCI. Reg. No:
36/5.7.1/0425.
AHN Pharma (Pty) Ltd. Reg. No.: 1957/003938/07. P.O. Box 31036,
Braamfontein, 2017, South Africa. Tel. no.: (011) 239 6370
• Further information on S2 Xyzal ® , Reg No. 36/5.7.1/0425,
may be obtained from AHN Pharma (Pty) Ltd. Tel. no.: (011)
239 6370.
References: 1. Gillman S, Gillard M, Benedetti MS. The concept of receptor occupancy to predict
clinical efficacy: A comparison of second generation H1 antihistamines. All Asthma Proc
2009; 30:1-00. DOI 10.2500/aap.2009.30.3226. 2. Gillard M, Benedetti MS, Chatelain P, et al.
Histamine H1 receptor occupancy and pharmacodynamics of second generation H1-antihistamines.
Inflamm Res 2005; 54:1-3. 3. Grant JA, Riethuisen J-M, Moulaert B, et al A double-blind,
randomized, single-dose, crossover comparison of levocetirizine with ebastine, fexofenadine,
loratadine, mizolastine, and placebo: suppression of histamine-induced wheal-and-flare response
during 24 hours in healthy male subjects. Ann Allergy Asthma Immunol 2002; 88:190-197. 4.
Potter PC, Kapp A, Maurer M, et al. Comparison of the efficacy of levocetirizine 5 mg and desloratadine
5 mg in chronic idiopathic urticaria patients. Allergy 2008. DOI 10.1111/j.1398-
9995.2008.01893.x. 5. Mullol J, Bachert C, Bousquet J. Management of persistent allergic rhinitis:
evidence-based treatment with levocetirizine. Ther Clin Risk Management 2005; 1(4):265-
271. 6. Bachert C, Bousquet J, Canonica W, et al. Levocetirizine improves quality of life and
reduces costs in long-term management of persistent allergic rhinitis. J All Clin Immunol 2004;
114(4):838-844. 7. Day JH, Briscoe MP, Rafeiro E, et al. Comparative clinical efficacy, onset and
duration of action of levocetirizine and desloratidine for symptoms of seasonal allergic rhinitis in
subjects evaluated in the Environmental Exposure Unit (EEU). Int J Clin Pract 2004; 58(2):109-
118. 8. Potter PC, on behalf of the Study Group.
Levocetirizine is effective for symptom relief
including nasal congestion in adolescent and
adult (PAR) sensitized to house dust mites.
Allergy 2003; 58:893-899. 9. Hindmarch I,
Johnson S, Meadows R, et all. The acute and
sub-chronic effects of levocetirizine, loratidine,
promethazine and placebo on cognitive function,
psychomotor performance, and wheal and flare.
Curr Med Res Opin 2001; 17(4): 241-255. The last word in allergy
MIELE LAUNCHES TOP-CLASS RANGE OF
VACUUM CLEANERS
A fact of modern life is the increase in allergies, with
more and more adults and children suffering from
asthma, rhinitis and hay fever. Allergies are made
worse by household pets, and dust mites in carpets,
mattresses and soft furnishings. In response to the
growing need for appliances that can help alleviate
the problems suffered by allergy sufferers Miele have
developed a number of features and accessories to
ensure excellent levels of cleanliness in the home.
The S5281 MedicAir Vacuum
Cleaner is supplied with all the features
and accessories to meet the
specific needs of allergy sufferers.
The unit is equipped with an innovation
that offers additional security
and comfort; the Allergotec Sensor
floorhead for visible hygienic cleanliness.
Miele offers a choice of three filters placed behind
the motor. Because of the airtight design, any air leaving
the vacuum cleaner only leaves via the final filter.
The Miele Super AirClean filter removes nearly
94% of the particles as small as 0.3 µ and, for this
reason is the most suitable for everyday households.
The Miele Active AirClean filter incorporates the
Super AirClean filter and is designed for customers
who have to vacuum up items with unpleasant
odours. A tight-fitting filter cassette with a rubber seal
prevents any air escaping. The active charcoal component
absorbs and neutralises odours. The Miele
Active HEPA filter solves the problems of allergy sufferers.
The Active HEPA filter retains 99.5% of particles.
For the true pet lover – the S5261 in Capri Blue and
S5361 in Tayberry Red are Miele's Cat & Dog range of
vacuum cleaners. Stubborn pet hairs do not stand a
chance with the Miele Cat & Dog's Turbo Brush. This
special floorhead is driven by the suction of the cleaner
and rotates evenly to pick up hair and dirt from
most types of carpets, while the smooth running floor
head SBD takes care of most hard floor surfaces. The
Miele Cat & Dog vacuum cleaner is specially fitted
with an ActiveAirClean filter. The activated charcoal
filling ensures any smell arising from the contents of
the dustbag is absorbed before it leaves the cleaner
and that the exhausted air is always fresh too.
Miele (Pty) Ltd Gallery of Fine
Living (Head Office),
PO Box 69434, Bryanston, 2021,
ashley.merson@miele.co.za,
www.miele.co.za, info@miele.co.za,
Share call: 0860 000 622,
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144 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

PRODUCT NEWS
NEW WORLD, NEW RELIEF FOR NOSES AND
EYES
Allergic rhinitis is a common condition that affects the
airways, nose and eyes. 1 In a survey conducted to
establish the burden of allergic rhinitis, 71% of people
with the condition reported that they experience
both nasal symptoms and ocular symptoms. 1 Many
allergic rhinitis patients resort to polypharmacy to
control their symptoms. 1 Allergic rhinitis has a significant
impact on the patient’s quality of life and on society
in terms of socioeconomic and health care
costs. 1,2
Avamys, from GlaxoSmithKline, is a new treatment
for allergic rhinitis that delivers relief for both nasal
and ocular symptoms. 3-5 Ocular symptom relief is registered
for patients from 12 years. New Avamys contains
a single active, fluticasone furoate, a glucocorticoid
with a novel molecular structure. 6 Fluticasone
furoate is characterised by its potent and selective
glucocorticoid activity, rapid uptake, sustained pharmacological
action, and enhanced binding affinity for
the glucocorticoid receptor. 2 It has proven 24 hour
efficacy in treating the nasal and ocular symptoms of
allergic rhinitis in adults and adolescents. 2 New
Avamys is registered for use in adults and children
from 2 years.
The Avamys delivery system was designed with the
patient in mind. 2 Its ergonomic design allows for
improved handling and comfort during use, and the
system delivers a consistent dose. 2 The fluticasone
furoate nasal spray itself has a favourable profile in
terms of its sensory attributes, including reduced
taste and scent, reduced dosing volume and fine consistent
mist. 2
The world of allergic rhinitis treatment will never be
the same again.
1. Canonica GW. A survey of the burden of allergic rhinitis in Europe. Allergy
2007; 62(85): 17-25.
2. Berger WE, Godfrey JW, Slater AL. Intranasal corticosteroids: the development
of a drug delivery device for fluticasone furoate as a potential step
toward improved compliance. Submitted to Expert Opin Drug Deliv.
3. Fokkens WJ, Jogi R, Reinartz S, et al. Once daily fluticasone furoate nasal
spray is effective in seasonal allergic rhinitis caused by grass pollen. Allergy
2007; 62: 1078-1084.
4. Martin BG, Ratner PH, Hampel FC, et al.. Optimal dose selection of fluticasone
furoate nasal spray for the treatment of seasonal allergic rhinitis in adults
and adolescents. Allergy Asthma Proc 2007; 28(2): 216-225.
5. Kaiser HB, Nacliero RM, Given J, et al.. Fluticasone furoate spray; a single
treatment option for the symptoms of seasonal allergic rhinitis. J Allergy Clin
Immunol 2007; 119(6): 1430-
1437.
6. Salter M, Biggadike K, Matthews
JL, et al.. Pharmacological properties
of the enhanced-affinity
glucocorticoid fluticasone furoate
in vitro and in an in vivo model of
respiratory inflammatory disease.
Am J Physiol Lung Cell Mol
Physiol 2007; 293: 660-667.
GlaxoSmithKline South Africa
(Pty) Ltd, (co. reg. no.:
1948/030135/07), 57 Sloane
Street, Bryanston 2021. Tel:
+27 (0)11 745 6000. Fax +27
(0)11 745 7000.
Long-chain polyunsaturated
fatty acids influence
the immune system of infants
Gottrand F. EA 3925, IFR 114,
Faculty of Medicine and University of Lille 2,
Lille, France. fgottrand@chru-lille.fr
Several events occur during the first months of
life that allow the immune system to become
competent and functional. The aim of this article
is to review the rationale and evidence of an
influence of (n-3) long-chain PUFA (LCPUFA) on
the immune system of infants. The (n-3) LCPU-
FA exert their immunomodulatory activities at
different levels. The (n-3) LCPUFA metabolites
induce eicosanoid production, alter gene
expression, and modify lipid raft composition,
altering T-cell signalling; all contribute to
immunological functional changes. However,
the roles of these mechanisms and the types of
T or other immunological cells involved remain
unclear at present. Moreover, the effect of (n-3)
LCPUFA on the immune system of infants may
vary according to dose, time of exposure, and
profile of the immune system (T-helper,
Th1/Th2). Most of the interventional studies in
infancy have been performed for the prevention
of allergy. They all confirmed influence on T-cell
function and cytokine profiles, but clinically beneficial
effects are more conflicting.
Supplementation of the maternal diet in pregnancy
or early childhood with (n-3) LCPUFA is
potentially a noninvasive intervention strategy
to prevent the development of allergy, infection,
and possibly other immune-mediated diseases.
However, any long-term in vivo effects on (n-3)
LCPUFA early in life for immunomodulatory
defense in infants and later on immune status
and health remain to be assessed.
J Nutr 2008; 138(9): 1807S-1812S.
For more information please contact Nestle
Consumer Services on 0860 09 67 89
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 145

PRODUCT NEWS
PIMECROLIMUS CREAM 1% IN ATOPIC
DERMATITIS: A 6-MONTH, OPEN-LABEL
TRIAL IN PAEDIATRIC PATIENTS
Pimecrolimus, a new, non-steroid, inflammatorycytokine
inhibitor, has been shown to prevent progression
to flare in atopic dermatitis (AD) and to
improve long-term disease control when applied as a
1% cream. In this 6-month, open-label, multinational
study, 177 infants aged 3-23 months and 489 children
aged 2-17 years, with mild to severe AD, were included.
The study was designed to evaluate the efficacy
and safety of pimecrolimus cream 1% used as a firstline
treatment. Treatment consisted of an initial bid
regimen, for as long as signs and symptoms of disease
persisted; this was followed by treatment as
required at the first signs and symptoms of AD.
Emollients were allowed as per the physician's normal
practice, and topical corticosteroids could be used to
treat severe flares at the discretion of the physician.
Efficacy was assessed by evaluations of pruritus, and
total-body and facial Investigators' Global
Assessment (IGA). Results from the first return visit
(day 7) showed an improvement from baseline of 1
in total-body and facial IGA for infants (59.1% and
72.8% of patients, respectively) and children (59.3%
and 62.2%, respectively). Pruritus was absent or mild
in 67.8% and 65.4% of infants and children, respectively.
This level of improvement in the patient population
was maintained throughout the 6-month study.
Adverse events occurred in 75.7% of infants and
71.1% of children. Most adverse events were common
childhood illnesses that would be expected in
this population (e.g. nasopharyngitis (infants 22.0%,
children 12.8%), upper respiratory tract infection
(infants 18.6%, children 11.9%) and cough (infants
8.5%, children 10.1%)). Concerning pimecrolimus's
local tolerability, application-site burning occurred in
2.3% of infants and 7.0% of children, and local pruritus
occurred in 0.6% infants and 1.0% children.
Application-site reactions were most frequently
reported during the first 6 weeks of treatment and
were mild to moderate in intensity. In conclusion,
pimecrolimus cream 1% was effective in the treatment
of the early signs and symptoms of AD (including pruritus)
in infants and children, and demonstrated a
good safety profile.
Reference available on request.
Contact Claudine Spadoni, 011-929-9111
Foratec HFA
Foratec HFA is another exciting addition to Cipla's
range of respiratory products, emphasising our
commitment to offering solutions for Total Asthma
Control!
Foratec HFA (formoterol fumarate 12µg) is:
• a long-acting 2 -agonist, giving up to 12 hours
bronchodilation 1
• as fast-acting as salbutamol, 2 between 1-3 minutes 1
• the only available formoterol fumarate MDI
• a 120-dose MDI; 2 months' supply (at 1 puff b.d.)
• CFC-free, re-enforcing our global commitment to
preserving our planet within our sphere of influence
• indicated as add-on therapy to inhaled corticosteroids in patients with chronic persistent asthma (GINA step
3) 3 and for prophylaxis and treatment of symptoms in patients with COPD 1 ,
• priced at R69.60 SEP (excl VAT), the most cost-effective long-acting 2 -agonist in SA! 5
Isn't this enough reason to prescribe Foratec HFA
Cipla offers you Total Asthma Control through choice of molecules, choice of devices and a choice
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Prescribing information available on request. Please contact Elizma Kemp on 021-917-5620.
1. Foratec HFA Package Insert
2. Van Noord J, et al. Salmeterol versus formoterol in patients with moderately severe asthma: onset and duration of action. Eur Respir J 1996;
9: 1684-1688
3. Asthma Guidelne Iimplementation Project. Primary care management of adults with chronic asthma. Revised 2006. SA Family Practice
Journal. June 2007; 49: 19-31
4. Bateman ED, Feldman C, O'Brien J, Plit M, Joubert JR. Guideline for the management of chronic obstructive pulmonary disease (COPD):
Revised 2004. S Afr Med J. 2004; 94(7 Pt 2): 559-575.
5. SEP (excl. VAT) as per PCD, July 2008
146 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

PRODUCT NEWS
GIVING TODDLERS A HEAD START IN LIFE
Abbott, leaders in Science-Based Nutrition, are proud to
announce the launch of Isomil 3 Advance Plus, the first soybased
follow-on formula to contain the essential long-chain
polyunsaturated fatty acids, arachidonic acid (ARA) and
docosahexaenoic acid (DHA).
The importance of DHA and ARA, naturally found in breast
milk and added to infant formulas to support brain development,
was recognised by the rapid accretion of these fatty
acids in the infant brain. 1,2 Reports of enhanced intellectual
development in breastfed children and the recognition of the
physiological importance of DHA in visual and neural systems,
led to clinical trials that evaluated whether infant formulas
supplemented with DHA and ARA would enhance
visual and cognitive development. 1
Evidence for a beneficial effect of ARA plus DHA supplementation
on central nervous system (CNS) development is
strong. 3 A randomised study evaluated visual and cognitive
development in infants at 14 and 39 months of age and compared
infants fed standard formula, formula supplemented
with DHA or formula supplemented with DHA and ARA. 1
This study, with the longest follow-up period reported to
date, showed that DHA and ARA supplementation support
visual and cognitive development in infants from birth to children
39 months of age. 1
Isomil 3 Advance Plus is a milk- and lactose-free, soy-based
formula that is specifically designed for children from 1 year
of age who have IgE-mediated cow’s milk allergy, are lactose
intolerant or suffer from digestive symptoms such as gas,
diarrhoea or regurgitation. 4
In addition to the patented combination of DHA and ARA,
Isomil 3 Advance Plus contains:
• Taurine and choline, which together with DHA and ARA are
required for brain development. 5,6
• Soy protein isolate, equivalent to animal protein in quality
and a rich source of nucleotides, required for normal
immune development. 7
• A vegetable oil blend that optimizes calcium and fat absorption
and is associated with a lower incidence of gastrointestinal
intolerance than infant formulas containing animal
fats or palm olein oil. 8 Stool characteristics of infants fed with
this unique vegetable oil
blend closely resemble
those of infants fed human
milk. 8
• Two sources of carbohydrate,
which use two different
digestive enzymes and
two different non-competing
absorptive pathways,
thereby enhancing carbohydrate
absorption. 9
Isomil 3 Advance Plus is a nutritionally complete, follow-on
soy formula for growing toddlers from 1 year of age. It has
been tested in clinical trials and is the scientifically supported
soy formula with the patented EYE Q system of brain nutrients
that support brain development. 1
Isomil 3 Advance Plus is competitively priced and is available
at pharmacies, supermarkets and baby stores. For more
information on Isomil 3 Advance Plus, please contact the
brand manager, Yvonne MacLeod, at Abbott Nutrition, tel
011-858-2000.
1. Auestad N, Scott Dt, Janowsky JS, et al. Visual, cognitive and language
assessments at 39 months: A follow-up study of children fed formulas containing
long-chain polyunsaturated fatty acids to 1 year of age. Pediatrics
2003; 112(3): e177-183.
2. Fernstrom JD. Can nutrient supplements modify brain function Am J Clin
Nutr 2000; 71(suppl): 1669S-1673S.
3. Uauy R, Hoffman DR, Peirano P, et al. Essential fatty acids in visual and brain
development. Lipids 2001; 36: 885-895.
4. Isomil ® 3 Advance Plus Product Monograph.
5. Chesney RW, Helms RA, Christensen M, et al. The role of taurine in infant
nutrition. Adv Exp Med Biol 1998; 442: 463-476.
6. Zeisel SH. The fetal origins of memory: The role of dietary choline in optimal
brain development. J Pediatr 2006; 149: S131-136.
7. Ostrom KM, Cordle CT, Schaller JP, et al. Immune status of infants fed soybased
formulas with or without added nucleotides for 1 year: Vaccine
responses and morbidity. J Pediatr Gastroenterol & Nutr 2002; 34: 137-144.
8. Alarcon PA, Tressler RL, Mulvaney A, et al. Gastrointestinal tolerance of a new
infant milk formula in healthy babies: An international study conducted in 17
countries. Nutrition 2002; 18: 484-489.
9. Kerzner B, Sloan HR, McClung HJ, et al. Jejunal absorption of sucrose and
glucose oligomers in the absence of pancreatic amylase. Pediatr Res 1983;
17(4): 191A.
Abbott Nutrition International, Abbott Place, 219 Golf Club Terrace, Constantia
Kloof, 1709. PO Box 7208, Weltevreden Park, 1715, South Africa. Tel 011-858-
2000, fax 011-858-2041. 0007-0708-P871-A-0708, August 2008.
ACCURATE ALLERGEN IDENTIFICATION
NOW A REALITY
Labspec (Pty) Ltd is pleased to announce the launch
of a national allergen-testing awareness campaign
across South Africa, to let consumers and medical
practitioners alike know that highly accurate, specific
allergen identification is now within everyone’s reach.
Being able to identify exactly which allergen elicits an
allergic response within an individual, may result in
more specific treatment, an accurate overview of any
lifestyle changes that may need to be made in the
affected individual, and ultimately, enhanced quality
of life.
As a subsidiary of Phadia, the world leader in diagnostics,
Labspec is committed to helping medical
practitioners make accurate diagnoses and sound
management decisions.
We at Labspec have also initiated a national print
media campaign both to consumers and medical
staff, and a dedicated sales force will highlight the
benefits to paediatricians and general practitioners
across the country.
Possibly the best part of requesting a Labspec allergen
test, is the fact that the procedure is covered by
most medical aids, thereby making the decision of
whether to be tested or not, an easy one.
Please contact Labspec on 011-792-6790/1/2/3, or
visit www.labspec.co.za.
Contact:
Charles Duff 011-792-6790/1/2/3
Maria Ramsay 082-410-6053
Angela Neveling 083-407-7654
Jacque Larsen 083-273-2604
A PHADIA COMPANY
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 147

PRODUCT NEWS
NASONEX IS NOW INDICATED FROM
THE AGE OF 2 YEARS!
Nasonex Aqueous Nasal Spray is indicated for use in
adults, adolescents and children between the ages
of 2 and 11 years to treat the symptoms of seasonal
allergic or perennial allergic rhinitis.
In patients who have a history of moderate to severe
symptoms of seasonal allergic rhinitis, prophylactic
treatment with Nasonex Aqueous Nasal Spray is recommended
prior to the anticipated start of the pollen
season.
Dosage and directions for use
Adults and adolescents: The usual recommended
dose for prophylaxis and treatment is two sprays (50
µg/spray) into each nostril once daily (total dose
200 µg). Once symptoms are controlled, dose reduction
to one spray into each nostril (total dose 100 µg)
may be effective in some patients for maintenance.
Children between the ages of 2 and 11 years: The
usual recommended dose is one spray (50 µg/spray)
in each nostril once daily (total dose 100 µg).
For more information contact
Gary Vine,
Schering-Plough (Pty) Ltd,
011-922-3300.
BOEHRINGER INGELHEIM LAUNCHES
INFLANAZE ® 100.
It is with great pleasure and excitement that Boehringer
Ingelheim, a leader in respiratory care, announces the
launch of Inflanaze ® 100.
Allergic rhinitis is a highly prevalent chronic respiratory
disease that impacts significantly on the quality of life of
patients. 1 The prevalence of allergic rhinitis is rising with
a huge indirect and direct economic burden. 1 In addition
nearly 80 % of asthmatic patients have coexisting allergic
rhinitis. 2 Topical corticosteroids are highly effective
first-line treatment of allergic rhinitis. 3 Budesonide is
comparatively an effective corticosteroid which is well
tolerated for all classifications of allergic rhinitis. 4
Inflanaze ® 100, 100µg budesonide per metered spray,
provides another option for healthcare professionals to
treat this common respiratory disease. Inflanaze ® 100
provides high dose budesonide for the allergic rhinitis
patient and allows tapering down of medication to the
lowest dose adequate to control symptoms. 5 With its
less number of sprays per day, the new 100 dosage
allows for better patient compliance. 1 It is registered
from the age of 6 years allowing for use in children.
Inflanaze ® 50 and 100 possess a broad actuator making
the administration of medication to children and patients
who struggle to use nasal sprays easy and comfortable.
Inflanaze ® 100 contains 200 doses, contains no alcohol
and has potassium sorbate as its preservative. 6
This product addition shows that Boehringer Ingelheim,
with its wide range of medication for asthma and allergic
rhinitis, is committed to optimising respiratory care.
References:
1. Yawn B. Comparison of Once-Daily Intranasal Corticosteroids for
the Treatment of Allergic Rhinitis: Are they all the same
Medscape General Medicine 2006; 8(1): 23.
2. Grossman J. One Airway, One Disease. Chest 1997; 111(2)(Suppl):
11S-16S.
3. Van Cauwenberge P. Consensus Statement on the Treatment of
Allergic Rhinitis. Allergy 2000; 55: 116-134.
4. Stanaland B. Once-Daily Budesonide Aqueous Nasal Spray for
Allergic Rhinitis: A Review. Clinical Therapeutics 2004; Vol.26(4):
473492.
5. Inflanaze ® 100 Package Insert.
6. Data on File
S3 Inflanaze ® 50 Aqueous Nasal Spray. Each metered dose contains
50g budesonide. Reg. No 32/21.5.1/0532
S3 Inflanaze ® 100 Aqueous Nasal Spray. Each metered dose contains
100g micronised budesonide. Reg. No. 41/21.5.1/0238
For full prescribing information refer to the package insert.
Applicant details: Ingelheim Pharmaceuticals (Pty) Ltd,
407 Pine Ave, Randburg. Tel: +27 (011) 348-2400.
Fax: +27 (011) 787-3766. Cpy Reg. No. 1966/008618/07.
BI Ref. No. 72/2009 (Mar 09).
NOPQ
148 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

ALLSA MEMBERSHIP 2009
Support your society, it supports allergology in South Africa
ALLSA remains one of the world’s most pro-active and innovative allergy societies. Our pioneering website and
patient information resources have spurred other national societies to follow suit.
ALLSA relies on an active membership base to continue to provide excellent resources to healthcare workers in
Southern Africa. We welcome new members from all over Southern Africa and membership is open to all healthcare
workers with an interest in allergology. Our current membership includes medical practitioners (general practitioners,
physicians, pulmonologists, ENT specialists, dermatologists, ophthalmologists, paediatricians and
anaesthetists), nurses, dieticians, medical technologists, pharmaceutical industry staff and medical students .
Membership currently costs only R200 annually; this is a tax-deductible expense.
Members enjoy a number of privileges which include:
• The highly rated ALLSA journal – Current Allergy & Clinical Immunology, which is edited by Profs Weinberg and
Zar, and published quarterly. This journal is available on-line.
• Access to ALLSA’s comprehensive allergy website at www.allergysa.org.
• On-line CPD accreditation.
• Patient information guides and leaflets on common allergic disorders.
• Discounted ALLSA congress registration fees for our annual congress.
• Regional allergy courses, meetings and journal clubs.
• Support with examination preparation for the Diploma in Allergology of the Colleges of Medicine of SA.
• Access to allergy research funding and annual ALLSA research awards of up to R50 000 per research study.
For more details on membership and privileges please contact Ruwayda Adams on tel 021-447-9019,
fax 021-448-0846, or e-mail enquiries to mail@allergysa.org
Please cut out the membership application form and post together with your payment.
ALLSA Membership Application
R200 annual subscription
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Post to: Allergy Society of South Africa, PO Box 88, Observatory 7935
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Cheques payable to Allergy Society of South Africa
For direct deposits: Kindly fax your bank deposit slip as proof of payment (Fax No. 021-448-0846)
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 149

PRODUCT NEWS
NEW DESIGN FOR SYMBICORD
AstraZeneca is proud to introduce a new design for
Symbicord boxes and packaging. The purpose of the
packaging change is to standardise the colours and
design globally, so that wherever in the world you
may be, the Symbicord packaging will look the same.
In line with these changes, we are also keeping these
colours for our promotional and educational material,
so that the design is standardised throughout. The
new look is bold, positive, professional and modern,
with an emphasis on clinically relevant and clear information.
The approach is future-focused, to reflect the
constant innovation and challenging of conventions
that is the basis of our approach to medicine at
AstraZeneca.
Please note that the ingredients and doses of
Symbicord will remain the same.
In conjunction with the new look, AstraZeneca
intends to introduce user-friendly educational and
support material to assist and support people with
asthma.
The new material is aimed at providing the busy
physician and his/her patients with the tools that they
need so that people with asthma can take responsibility
for their own asthma control.
S 3
Symbicord® Turbuhaler® 80:4,5 µg/dose (Inhaler), Reg No.
35/21.5.1/0404. Each delivered dose contains as active constituents:
Budesonide 80 micrograms and formoterol fumarate
dihydrate 4,5 micrograms.
S 3
S 3
Symbicord® Turbuhaler® 160:4,5 µg/dose (Inhaler), Reg
No. 35/21.5.1/0405. Each delivered dose contains as active
constituents: 160 micrograms and formoterol fumarate dihydrate
4,5 micrograms.
Symbicord® Turbuhaler® 320:9 µg/dose (Inhaler), Reg No.
38/21.5.1/0187. Each delivered dose contains as active constituents:
Budesonide 320 micrograms and formoterol
fumarate dihydrate 9 micrograms
NAME AND BUSINESS ADDRESS OF THE HOLDER
OF THE CERTIFICATE OF REGISTRATION:
AstraZeneca Pharmaceuticals (Pty) Limited, 5 Leeuwkop Road,
Sunninghill, 2157, South Africa. Reg No. 92/05854/07.
Tel: +27 11 797 6000. Fax: +27 11 797 6001. www.astrazeneca.co.za
MSD (Pty) Ltd is proud to announce the introduction of
SINGULAIR 4 mg. Studies have shown that asthma in children
under the age of six is on the increase worldwide. 1
SINGULAIR 4 mg is the first asthma controller therapy, that
is not a steroid, to be approved in South Africa for children
as young as 2 years old. 2
Studies have shown improvements in symptom and activity
scores from as early as day one, affirming the efficacy of
SINGULAIR 4 mg in this age group. 3 The current guidelines
for treatment of asthma in children, as compiled by the
Allergy Society of South Africa (ALLSA), call for the introduction
of a leukotriene antagonist as a controller agent in
this age group at step 2, after the use of short-acting reliever
medication has proven to be inadequate in controlling
asthma symptoms. In other words using leukotriene antagonist
as a first line controller agent. 4 At present, of the
leukotriene receptor antagonists, only SINGULAIR is indicated
for use in children under the age of 12. 2
SINGULAIR 4 mg is indicated for the prophylactic treatment
of mild to moderate asthma in the 2-5 year old age group.
SINGULAIR 4 mg is presented in a 28-day pack and one
tablet should be taken once daily at bedtime. 2 To date worldwide
use is more than 2.2 million children in more than 90
countries. This puts SINGULAIR in the unique position of
being the only controller therapy to be registered and indicated
for asthmatic patients from 2 years old and up. 2
The
FREEDOM
to
be a Child!
REFERENCES:
1 Ehrlich, R. The Prevalence of Asthma in South Africa. Current
Allergy and Clinical Immunology March 2002; Vol 15: 4-8.
2 Data on File.
3 Knorr B, Franchi LM, Bisgaard H, et al. Montelukast, a leukotriene
receptor antagonist, for the treatment of persistent asthma in
children aged 2 to 5 years. Pediatrics 2001;108(3):1-10.
4 Motala C, Kling S, Gie R, et al. Guidline for the management of
Chronic Asthma in Children – 2000 Update. SAMJ. 2000; 90:
524-539.
MSD (Pty) Ltd (Reg. No. 1996/003791/07), Private Bag 3, Halfway
House 1685.
Copyright © MERCK & CO., INC., Whitehouse Station, N.J., U.S.A.
1999. ® Registered Trademark of MERCK & CO., INC., Whitehouse
Station, N.J., U.S.A. Before prescribing, please refer to the full package
insert. 06-2004-SGA-03-ZA-230-O
Reg. No: 35/10.2.2/0397, SINGULAIR 4 mg S3
150 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3

CPD QUESTIONNAIRE
Earn 3 CPD points after you have read the journal by completing
the following questionnaire online on the ALLSA website
at www.allergysa.org/cpd or follow the links from the
home page. To earn points, you will need to register and fill in
personal details (make sure you have your HPCSA number
handy and decide on a password beforehand). Once you have
registered, you can answer the questionnaire. If you have registered
for a previous questionnaire, you'll need your HPCSA
number and password to logon. Please note that there is only
one correct answer per question, and you will have only one
opportunity to submit the questionnaire, so please check
answers carefully. You will be able to change anwers if you
click the wrong one by mistake, but once you click 'Submit
Answers' the test will be submitted and marked.
Points will be submitted electronically to the HPCSA.
The closing date for submission of this questionnaire is 30
September 2009.
MIMICS OF FOOD ALLERGY
1. True or false: Histamine reactions are dose-dependent.
a) True
b) False
2. Choose ONE correct answer: An adverse reaction to eating
tuna in white sauce may be as a result of:
a) A histamine reaction
b). Tuna fish allergy
c) A ‘hidden’ allergen
d). a and b
e). a, b and c
3. True or false: A 1-year-old child reacts with diarrhoea following
the ingestion of milk for the first time. Skin and
serum specific IgE tests for milk are negative. An oral challenge
with 1 ml of milk is negative. The child is therefore
not milk allergic.
a) True
b) False
4. Choose ONE correct answer: Which of the following
ingredients in wine is not a common cause of adverse
reactions
a) Alcohol
b) Lipid transfer proteins
c) Histamine
d) Tannins
e) Sulphur dioxide
HYPERSENSITIVITY TO LOCAL ANAESTHETICS
1. True or false: Patients with decreased hepatic function
are at increased risk of overdosage and toxic reactions
from amide local anaesthetics (LAs).
a) True
b) False
2. True or false: Skin-prick testing is a reliable method of
diagnosis of IgE-mediated reaction to LA.
a) True
b) False
3. True or false: Patch testing is a reliable method of diagnosis
of delayed-type IV hypersensitivity reactions to ester-
LAs.
a) True
b) False
4. True or false: When investigating allergic reaction to LA it
is best to challenge the patient with another LA, preferably
from a different class and one that does not contain any
additives, e.g. parabens or metabisulfite.
a) True
b) False
EIGHT MYTHS FROM THE FOOD ALLERGY CLINIC
1. Choose ONE correct answer: Select the most suitable
alternative to cow’s milk formula for use in a 4-month-old
infant with cow’s milk allergy.
a) Soya infant formula
b) Extensively hydrolysed formula
c) Goat milk infant formula
d) Fresh goat milk
e) Rice milk
2. Choose ONE correct answer: Which of the following
statements is true
a) A skin-prick test (SPT) wheal of >3 mm confirms allergy
to the food tested.
b) The size of the SPT wheal predicts the severity of the
allergic reaction.
c) The larger the SPT wheal, the greater the likelihood of
allergic symptoms to the food tested.
d) Oral provocation tests are always needed to confirm
the diagnosis of food allergy.
e) A negative SPT rules out allergy to the food tested.
3. Choose ONE correct answer: The following statements
about the risk of anaphylaxis are true EXCEPT:
a) Coexistent asthma increases the risk of anaphylaxis.
b) Education and assessment in a specialist allergy clinic
reduces the risk of a subsequent anaphylactic reaction.
c) A second dose of adrenaline is needed in 20% of children
experiencing anaphylaxis.
d) A previous mild allergic reaction only on ingestion of
nuts means future severe reactions are unlikely.
e) Previous anaphylaxis increases the risk of future anaphylaxis.
4. Choose ONE correct answer: The following vaccines are
contraindicated in children with anaphylaxis to egg:
a) Influenza and yellow fever
b) Measles and MMR
c) Influenza and MMR
d) Measles, MMR and Influenza
e) Yellow fever and DPT
FOOD ALLERGY EPIDEMIC – IS IT ONLY A WESTERN PHE-
NOMENON
1. True or false: According to the International Study of
Asthma and Allergies in Children (ISAAC), the prevalence
of respiratory allergy such as allergic rhinitis and asthma
has decreased over time in many developed countries.
a) True
b) False
2. True or false: Hen’s egg, cow’s milk, wheat and peanuts
have been identified as common allergens in subjects with
food allergy in Asian countries.
a) True
b) False
3. Choose ONE correct answer: In the study conducted by
Karabus and Motala in Cape Town, which food allergen
was found to be the most common in children attending an
allergy clinic
a) Cow’s milk
b) Hen’s egg
c) Peanut
d) Soya
e) Potato
4. True or false: Skin-prick tests are the gold standard for the
diagnosis of food allergy.
a) True
b) False
APPROACHES TO DIAGNOSING ANISAKIS ALLERGY
1. True or false: Smoking or marinating fish kills the Anisakis
larvae.
a) True
b) False
2. True or false: Anisakis is a unique parasite with no crossreactivity
to other species.
a) True
b) False
ABC OF ALLERGY
1. True or false: The specific IgE Test (RAST) is a blood test
which measures specific circulating IgE, whereas the skinprick
test measures specific IgE bound to the surface of
mast cells in the skin.
a) True
b) False
2. True or false: If a patient has a history of a severe reaction
to an allergen (like respiratory difficulty following peanut
ingestion), a skin-prick test is not a safe choice of test in
order to establish sensitivity.
a) True
b) False
Accredited by the Colleges of Medicine of South Africa
Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3 151

INSTRUCTIONS FOR AUTHORS
Current Allergy & Clinical Immunology publishes
articles concerned with the understanding and
practice of allergic diseases or clinical immunology.
Material submitted for publication to Current
Allergy & Clinical Immunology is accepted on
condition that it has not been published elsewhere.
The management reserves the copyright
of the material published. All named authors
must give consent to publication. Current Allergy
& Clinical Immunology does not hold itself
responsible for statements made by contributors.
Original research, review articles, case reports,
brief research reports or photographs may be submitted.
Letters to the editor are welcome and if
suitable will be published in a correspondence section.
All articles will be subject to peer review.
Electronic submission is preferable. However, if
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article may be posted to the correspondence
address listed at the end of these instructions.
Manuscript preparation
1. Articles may be submitted electronically online
at www.allergysa.org/articles or follow the
links from the homepage www.allergysa.org.
To register, you need to enter your name, personal
details, HPCSA number and a password.
Once you have registered, you will receive an
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figures and 3 tables. Short reports should be a
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2 tables or illustrations. Case reports should
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conform to the usual structure: abstract (not
more than 50 words), introduction, methods,
results, discussion.
2. Each article should be accompanied by a summary
of not more than 200 words (50 words for
short reports). A structured abstract is required
for original research papers.
3. Authors are requested to declare conflict of
interest and source of funding relating to the
article. Authors should disclose any relationship
within the last 2 years with pharmaceutical
companies in the following categories if
pertinent to the article: research grants, educational
support (sponsorship at conference),
advisory boards, speaker, consultant or shares
in companies. This must be stated at the end
of the manuscript before the references.
Details of ethical approval obtained must be
included in all original research articles.
4. All abbreviations should be spelt out when first
used in the text and thereafter used consistently.
5. Scientific measurements should be expressed in
SI units.
6. Tables should be labelled with Roman numerals,
thus: I, II, III, etc. and illustrations with
Arabic numerals, thus: 1, 2, 3, etc. Tables and
figures should be submitted as part of the manuscript
file. Please do not submit photographs
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be submitted separately from the manuscript
file and clearly labelled.
7. Where identification of a patient is possible from
a photograph the author must submit a consent
to publication signed by the patient, or by the
parent or guardian in the case of a minor.
8. If any tables or illustrations submitted have been
published elsewhere, written consent to republication
should be obtained by the author from
the copyright holder and the author(s).
References
1. References should be inserted in the text as
superior numbers, and should be listed at the
end of the article in numerical order.
2. References should be set out in the Vancouver
style, and only approved abbreviations of journal
titles should be used; consult the January issue
of Index Medicus (No. 1 Part 1) for these details.
Names and initials of all authors should be given
unless there are more than six, in which case the
first three names should be given followed by ‘et
al.’ First and last page numbers should be given.
Example:
1. Khakoo G, Lack G. Recommendations for
using MMR vaccine in children allergic to
eggs. BMJ 2000; 320: 929-932.
3. References for books should include author,
title, town, publisher and date.
Example:
1. Abbas AK, Lichtman AH. Basic Immunology.
Philadelphia: WB Saunders, 2001.
4. ‘Unpublished observations’ and ‘personal communications’
may be cited in the text, but not in
the reference list. Articles accepted but not yet
published can be included as references followed
by ‘(in press)’.
All correspondence should be addressed to:
The Editors, Current Allergy & Clinical Immunology,
Allergy Society of South Africa, PO Box 88,
Observatory 7935, South Africa.
E-mail: mail@allergysa.org
152 Current Allergy & Clinical Immunology, August 2009 Vol 22, No. 3