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Allergology International.

2009;58:457-466
DOI: 10.2332!
allergolint.09-RAI-0138
REVIEW ARTICLE

Food Allergy: Review,


Classification and Diagnosis
Antonella Cianferoni1 and Jonathan M Spergel1

ABSTRACT
Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and
2% of adults in westernized countries, and their prevalence appears to be rising like all allergic diseases. In ad-
dition to well-recognized urticaria and anaphylaxis triggered by IgE antibody-mediated immune responses,
there is an increasing recognition of cell-mediated disorders such as eosinophilic esophagitis and food protein-
induced enterocolitis. New knowledge is being developed on the pathogenesis of both IgE and non-IgE medi-
ated disease. Currently, management of food allergies consists of educating the patient to avoid ingesting the
responsible allergen and initiating therapy if ingestion occurs. However, novel strategies are being studied, in-
cluding sublingual! oral immunotherapy and others with a hope for future.

KEY WORDS
allergen specific IgE, food allergy, food protein induced enterocolitis, non-IgE, peanut hypersensitivity

ABBREVIATIONS
TH2, T helper cells type 2; MHC, major histocompatibility complex; OIT, oral immunotherapy; CLA, cutaneous
lymphocyte antigen; PAF, platelet-activating factor; DBPC, double-blinded and placebo controlled.

common self-reported food allergy.3 Reactions to


INTRODUCTION foods are not new and have been described for two
Approximately 25% of the United States population thousand years. The ancient Greek physician, Hippo-
believes that they have an allergic reaction to foods. crates, describes a reaction to milk in the 1st century.
However, the actual incidence confirmed by history Anaphylactic reactions to egg and fish have been de-
and challenges suggests a prevalence rate closer to scribed as earlier as the 16th and 17th century.4
2-8% in young infants and less than 2% in adults. The
most common food allergies in the United States are CLASSIFICATION
milk, egg, peanut, soy, wheat, tree nuts, fish and Adverse food reaction is a broad term representing
shellfish. The individual food allergy does vary by cul- any abnormal clinical response associated with inges-
ture and population. Imamuras recent survey of 1383 tion of a food and they are further classified as food
Japanese patients from 878 families in found milk, intolerance or food allergy based on the pathophysi-
eggs, wheat, peanuts, and soybeans, followed by ses- ological mechanism of the reaction. Food intolerance
ame and buckwheat were the most common allergies refers to an adverse physiologic response to a food
similar to the United States.1 Birds nest allergy is the and may be due to inherent properties of the food
most common in Singapore.2 The type of food aller- (i.e. toxic contaminant, pharmacologic active compo-
gies can even vary across regions of Northern nent) or to characteristics of the host (i.e. metabolic
Europe. In Russia, Estonia, and Lithuania; citrus disorders, idiosyncratic responses, psychological dis-
fruits, chocolate, apple, hazelnut, strawberry, fish, to- order), they may not be reproducible, and they are
mato, egg, and milk were most common self-reported often dose dependent. It is believed that food intoler-
allergy. But, in Sweden and Denmark; tree nuts, ap- ance represents the majority of the adverse reactions
ple, pear, kiwi, stone fruits, and carrot were the most to food. Food allergy refers to an abnormal immu-

1Division of Allergy and Immunology, Department of Pediatrics, 3550 Market Street, Rm 3050 Philadelphia, PA 19104, USA.
The Childrens Hospital of Philadelphia, University of Pennsylvania Email: Spergel@email.chop.edu
School of Medicine, Philadelphia, USA. Received 7 July 2009.
Correspondence: Jonathan M Spergel, MD, PhD, Division of Al- !2009 Japanese Society of Allergology
lergy and Immunology, The Childrens Hospital of Philadelphia,

Allergology International Vol 58, No4, 2009 www.jsaweb.jp! 457


Cianferoni A et al.

Adverse food
reaction

Food Food Allergy


Intolerance

Food Host Mixed Non-lgE


characteristics characteristics IgE-mediated mediated

Pharmacologic
(caffeine, Contact
Metabolic Anaphylaxis dermatitis
tyramine) (lactase or
fructase Urticaria Atopic Dermatitis
deficiency) dermatis Herpetiformis
Angioedema
Eosinophilic Proctocolitis
Oral allergy Esophagitis
syndrome FPIES
Eosinophilic
Toxin enteritis Celiac disease
(bacterial, Acute rhinitis
sgombroid Acute Asthma Heiners
fish Psychological Syndrome
poisoning) (panic
disorder)

Fi
g.1 Cl
assi
f
icat
i
onofadver
ser
eact
i
onst
ofoods.

nologic response to a food that occurs in a suscepti- ern Europe and the United States. Food allergy alone
ble host. These reactions are reproducible each time in the United States appears to account for approxi-
the food is ingested and they are often not dose de- mately 30,000 anaphylactic reactions, 2,000 hospitali-
pendent. Based on the immunological mechanism in- zations, and possibly 200 deaths each year.16 In chil-
volved, food allergies may be further classified in a) dren, food allergy is the most common cause of ana-
IgE-mediated, which are mediated by antibodies be- phylaxis.17,18 Children with moderate to severe atopic
longing to the Immunoglobulin E (IgE) and are the dermatitis have a higher prevalence of IgE-mediated
best-characterized food allergy reactions; b) cell- food allergy, estimated at about 10-30% depending on
mediated when the cell component of the immune the severity of atopic dermatitis.19-21 Food allergies
system is responsible of the food allergy and mostly appear to play a role in over 90% of children with
involve the gastrointestinal tract; c) mixed IgE eosinophilic esophagitis.22,23
mediated-cell mediated when both IgE and immune The most common food allergens in the pediatric
cells are involved in the reaction (Fig. 1).5-8 population include cows milk, eggs, peanuts, tree
nuts, soy, wheat, fish, and shellfish, whereas peanuts,
EPIDEMIOLOGY tree nuts, fish, and shellfish predominate in adults in
Many studies in the past few decades have shown the United States (US).11,12,14,24 The prevalence of
that although 40%-60% of parents believed their childs sensitization to the specific food allergens varies
symptoms are related to food consumption, only 4%- based on the age and characteristics of the studied
8% of children have symptoms reproduced by oral population, but studies incorporating diagnostic food
food challenges.9-12 The prevalence of food allergy is challenges currently estimate that the prevalence of
highest in infants and toddlers (6-8%) and decreases cows milk allergy in infants is 2.5%, egg hypersensi-
slightly with age, affecting almost 4% of the adults.13- tivity prevalence in young children is 1.6% and peanut
15 allergy is estimated to be between 0.8 and 1.5% in
Food allergy is the leading cause of anaphylaxis young children in US and England.25-27 Most infants
treated in hospital emergency departments in West- with non-IgE mediated cows milk allergy outgrow

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Food Allergy

their sensitivity by the third year of life, but about 10- tients with atopic dermatitis and food hypersensitivity
25% of infant with IgE mediated cows milk allergy re- have higher rates of spontaneous release of hista-
tain their sensitivity and about 50% develop sensitivity mine from basophils that normalizes after the offend-
to other foods.28,29 Most children with egg allergy are ing food has been removed from the diet. Normal se-
also likely to develop egg tolerance by late childhood, rum tryptase levels (a specific marker of mast cell ac-
with the exception of patients with an egg IgE greater tivation) in patients with food-induced anaphylaxis
than 50 kU! L, who are unlikely to develop egg toler- have been reported on occasion suggesting an in-
ance.30 Peanut, sesame seeds and tree nuts allergies volvement of histamine release from tryptase nega-
are more persistent with a chance of becoming toler- tive cells, such as basophils.45,46
ant is about 20% for peanut and sesame seeds and The intrinsic properties of the food allergens may
about 10% for tree nuts.31-33 contribute to whether the allergen favors allergic im-
Sensitization to either cows milk or egg in infancy mune responses. Indeed relatively few foods (egg,
are associated with an increased risk of environ- milk, peanut, tree nuts, fish, shellfish, wheat, and
mental allergy sensitization and asthma.21,34,35 Indeed soy) account for most of the allergic reactions.47
they appear to be the first steps of the atopic march, Characteristics common to major food allergens are
that initiates in infancy with food sensitization and that they are water-soluble glycoproteins, are 10 to 70
atopic dermatitis and continues with environmental kD in size, and are relatively stable to heat, acid, and
allergies and rhinitis and asthma development after 1- proteases. In addition, the presence of immunostimu-
2 years of age.36 latory factors in the food may also contribute to such
There has been a significant increase in the inci- sensitization. For example, the major glycoprotein al-
dence of food allergies including a rise of Emergency lergen from peanuts, Ara h 1 is not only very stable
Department visits for food allergic reactions.37,38 and resistant to heat! digestive enzyme degradation
Moreover peanut allergy prevalence in children in US but also acts as a TH2 adjuvant due to the expression
and England doubled in the last few years in identical of a glycan adduct.48 However, the biochemical char-
telephone surveys.26,39 The reasons for the increase acteristics of a food allergen cannot explain alone its
in food allergy prevalence are not known, but, the allergenicity, as only a minority of patient exposed to
short period of time over which the increase oc- it develop allergy. Indeed the natural consequence of
curred, suggests that environmental factors are more exposure to new foods is tolerance.
likely to be relevant than genetic factors as part of the Oral tolerance depends on an intact and immu-
hygiene hypothesis.40,41 It is likely that additional fac- nologically active gastrointestinal barrier. This bar-
tors play an important role such as methods of food rier includes the epithelial cells joined by tight junc-
preparation, increased use of antacids, and exposure tions and a thick mucus layer, as well as lumenal and
to medicinal creams containing food allergens.7,8 The brush border enzymes, bile salts, and extremes of
introduction of food later in the infant diet has been pH, which contribute to make antigens less immuno-
postulated to play a role in the increase of food al- genic. In addition, innate (natural killer cells, poly-
lergy.42 morphonuclear leukocytes, macrophages, epithelial
cells, and toll-like receptors) and adaptive immunity
PATHOGENESIS (intraepithelial and lamina propria lymphocytes,
Food allergy is an immunological reaction against a Peyers patches, IgA, and cytokines) provide an ac-
food allergen and is typically IgE mediated, not-IgE tive barrier to foreign antigens.49-53
mediated (i.e. cell mediated) or mixed IgE and not- As food allergy is more common in infants,49
IgE mediated. higher permeability of the intestinal mucosa in in-
IgE-mediated classic food allergic reactions are fants and early exposure to allergenic antigens have
those that are immediate, reproducible, and readily been proposed as a possible cause of sensitization in
diagnosed by detection of food-specific IgE. In food infant.49 However, it has been shown that the gastro-
allergic individuals the majority of acute allergic reac- intestinal mucosa reaches its maturity in terms of per-
tions to foods are due to the engagement of allergen meability at day 2-3 of life and the increased perme-
specific IgE antibody with its high-affinity receptor ability observed in some children with food allergy is
(FcRI), that is expressed on mast cells and baso- a consequence rather than a cause of the allergic in-
phils, and low affinity receptor (FcRII), which is pre- flammation.49,50,54,55 In contrast, early exposure to
sent on macrophages, monocyte, lymphocytes and foods might prevent the development of food allergy
platelets. When a specific antigen binds the IgE under some conditions. This is suggested by a recent
linked to the FcRI it determines a receptor cross- study that has shown that Israeli children, who fre-
linking and consequent release of mediators.6,8 Even quently consume a popular peanut snack beginning
if initially it was thought that mast cells were the prin- before age 1 year, have a 10-fold lower prevalence of
cipal effector cells in IgE-mediated acute reaction, fur- peanut allergy compared with children in the United
ther studies have shown that basophils play also a States and United Kingdom, where rarely peanuts are
major role in acute food allergy symptoms. Indeed pa- consumed before age of 12 months.42 Additional fac-

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Cianferoni A et al.

tors have been proposed as necessary to breach the T cell homing to target organs may explain why
oral tolerance. A temporary increase of permeability some food-allergic diseases are localized and not sys-
due to a infectious inflammatory process may in- temic as in the case of food-associated atopic dermati-
crease the absorption of allergenic antigens and favor tis or eosinophilic esophagitis. Indeed the CLA (cuta-
sensitization.50 Alternatively sensitization is facili- neous lymphocyte antigen) is upregulated in food-
tated, if the gastrointestinal barrier is bypassed by responsive T cells only in patients with food-
presentation of proteins via alternative routes, such as responsive atopic dermatitis.63 In eosinophilic esoph-
the respiratory tract or skin. In oral allergy syn- agitis a gene microarray analysis of esophageal tissue
drome, also known as pollen-food-related syndrome, has shown that the mRNA for eotaxin-3 was the most
oral tolerance is bypassed because sensitization oc- highly upregulated transcript in eosinophilic esoph-
curs through the respiratory route, due to cross reac- agitis tissue compared to healthy control esophagus
tivity between the pollen allergen and allergen con- and was correlated with tissue eosinophilia.64
tained in fruit (i.e. birch pollen protein Bet v 1 and the The non-IgE mediated food allergies represent the
a homologous apple protein, Mal d 1) that usually are minority of immunologic reactions to food and occur
well tolerated when ingested due to their instability in in the absence of demonstrable food-specific IgE anti-
presence of digestive enzymes.56 Data from murine body in the skin or serum. They are less well charac-
models demonstrate that epicutaneous application of terized, but typically are due to an acute or chronic in-
food proteins may result in very strong allergic sensi- flammation in the gastrointestinal tract, where
tization and TH2 inflammation.57 Indirect evidence in eosinophils and T cells seem to play a major
human of possible skin sensitization to food allergens role.8,43,44 For patients with food protein-induced en-
is a study, Lack et al.,58 where an increased risk of terocolitis, TNF- appears to have an important role.
peanut allergy in offspring was found to be related TNF- can be cultured in vitro from peripheral blood
with the use of infant skin creams containing peanut monocytes in infants with food-protein-induced en-
and not to maternal peanut ingestion during preg- terocolitis syndrome.65 Chung and colleagues also
nancy or lactation. found increased staining for TNF- in duodenal biop-
Oral tolerance may also be breached due a TH2- sies of infants with food-protein-induced enterocolitis
biasing dysregulation of the active immunological syndrome.66 For eosinophilic esophagitis, eosinophils
barrier that favors sensitization.49-53 Recent epidemi- and their growth and chemotactic factors play a key
ological studies identify potential environmental influ- role. Eotaxin-3 is upregulated 50X in the esophageal
ences that may promote such dysregulation, includ- tissue compared to controls with chronic esophagi-
ing reduced exposures to bacteria and infections (the tis.64 Also, IL-13 and IL-5 play a key role in the patho-
hygiene hypothesis), a rise in consumption of genesis in murine models67 and increased VCAM-1,
omega-6 and decreased consumption of omega-3 TGF- in the tissue samples leading to increased tis-
polyunsaturated fatty acids, reduced dietary antioxi- sue fibrosis.68
dants, and excess or deficiency of vitamin D.50,59,60 It Finally food allergy is at least in part genetically de-
has been proposed that the TH2-dysregulation is due termined. Peanut allergy, for example, is about ten-
to an altered equilibrium in the finely regulated rela- fold more likely to occur in a child with a sibling who
tionship between epithelial cells, antigen-presenting is peanut allergic compared to the general population
cells (dendritic cells), and regulatory T cells, that ulti- risk; however, specific genes have not been identi-
mately determine the type of T cell response that a fied.69 Similar for non-IgE-mediated food allergies,
food allergen elicits. Intestinal epithelial cells may act there is a large familial and ethnic difference with a
as nonprofessional antigen-presenting cells for T lym- predominance of Caucasian males with the disor-
phocytes as they express a class II major histocom- der.70-72
patibility complex (MHC), however they lack a sec-
ond signal, essential for T cell expansion after anti- DIAGNOSIS
gen presentation, suggesting their potential role in in- The patients history can be a powerful tool, espe-
duction of tolerance to food antigens.52 Several regu- cially if the patient and family are objective historians.
latory T cells have been found to be important for oral But the familys own perceptions and knowledge
tolerance: Th3 cells, a population of CD4+ cells that often influence history. Food allergy is clearly sus-
secrete transforming growth factor (TGF)-; Tr1 pected more often than it is found by accurate diag-
cells, cells that secrete IL-10; CD4+CD25+ regulatory nostic procedures and is confirmed by challenges in
T cells, that express the transcription factor FoxP3; less than 20% of the time. In general, the history can
CD8+ suppressor T cells; and gamma-delta T cells. be more helpful in IgE-mediated disorders, because
The role for regulatory T cells in food allergy comes these reactions occur so soon after food ingestion
from a family with severe food allergy carrying with a and because multiple target organs are affected. His-
FOXp3 mutation.61 Furthermore, increased levels of tory is harder for food-protein induced enterocolitis,
T regulatory cells have been reported to be associ- where symptoms occur hours later or days later in
ated with acquired tolerance to cows milk.62 eosinophilic esophagitis.

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Food Allergy

Tabl
e 1 95% Pr
edi
ct
iveval
uesf
orpr
ickski
ntestandspeci
fi
cIgE
Food Spec
if
icI
gE(
kU/
L) WhealSi
ze
Egg 7(>2yr)(78) 13mm(
108)
Egg 2(<2yr)(109) 6mm(
109)
Egg 17.
5(notprevi
ousex
pos
edt
oeggs
)(110) 5mm(
110)
Peanut 15(111) 8mm(
111)
Peanut 15(78) 8mm(
112)
Mil
k 32(78) 12.
5mm(
108)
Mil
k Nonef
ound(77) 6mm(
112)
Soy,Wheat None(77,78)

Thus a systematic review of the patients diet is a dicting 95%77,78 or even 50% predictive values79 on
highly useful first step. Important historical consid- food challenges (Table 1). However, similar to prick
erations include the following: 1.) Is the reaction re- skin test, the predictive values changes for the food,
producible? Does it occur each time the food is in- age of the patient or the history of previous reaction.
gested? If not, it is an unlikely trigger. 2.) What is the Predictive values can only be developed for milk, egg,
time frame for the reaction? Immediate hypersensitiv- peanut, tree nuts, sesame seed and fish. 95% predic-
ity reactions generally occur rapidly, often within tive values can not be developed for soy and wheat.
minutes and virtually always within 2 hours.73 The younger patients have a lower cut-off value for
Mixed and T-cell mediated reactions have a charac- 95% predictive value, while no previous exposure to
teristically delayed onset. Therefore patients with the food or clear history has a higher predictive value
FPIEC typically begin to have symptoms later than 1 (Table 1).
hours after ingestion. Additional clinical history For non-IgE-mediated disorders, fewer laboratory
elements can be helpful. Timing of the first and last diagnostic tools exist. Atopy patch test have been
occurrences can reveal whether sensitivity is increas- used for eosinophilic esophagitis, food protein in-
ing or waning. These considerations together with duced enterocolitis and atopic dermatitis.80-84 Com-
the quantity necessary to trigger a reaction are help- pared to prick skin test, atopy patch test is more spe-
ful for planning diagnostic challenge procedures as cific, but less sensitive.81,85-87 The negative predictive
well. Occasionally, the history can be complicated by value is close to 90% except for milk, where it is close
the fact that trace amounts of foods may occur in cer- to 60%. Therefore, atopy patch test can be provide
tain products. guidance but not absolute for dietary advice for non-
IgE mediated food allergy. Eosinophils in the blood
LABORATORY STUDIES or stool may point to an ongoing enteropathy, but
Immediate hypersensitivity skin tests (prick skin these findings are certainly nonspecific. Serum levels
tests) examine for the presence of food protein spe- of allergen-specific IgG are not helpful. Endoscopy
cific IgE. In general, skin tests have positive predic- followed by examination of biopsy specimens are the
tive accuracies of about 50%; but their negative pre- most important tools in non-IgE-mediated disorders
dictive values are in excess of 95%.74 The larger the and critical for the diagnosis of eosinophilic esophagi-
size of wheal on skin test, the more likely a patient tis. Challenges are needed to identify specific food
will react to the food74-76 (Table 1). The size of the triggers in all cases.
wheal or flare on skin test unfortunately does not pre- There are no tests that indicate the severity or
dict the severity of the reaction. Furthermore, the age what patients are at high risk for severe allergic reac-
of the patient, previous exposure! reactions to the tion or anaphylaxis.73 However, recent work by Vadas
food and the type of food changes the predictive and colleagues examining patients with experienced
value for a wheal size. In general, the younger the fatal and nonfatal peanut-induced anaphylaxis com-
age, the smaller the skin test needs to be positive pre- pared to normal controls, patients with food allergy
dictive value; a negative skin test for IgE-mediated and patients with mild peanut reactions. The patients
problems is very helpful as false negative reactions with peanut anaphylaxis had elevated platelet-
are rare. activating factor (PAF) and decreased PAF acetylhy-
An alternative method to detect food protein spe- drolase suggesting failure of PAF acetylhydrolase to
cific IgE is by in vitro methods, (FEIA-CAP or RAST inactivate PAF contributes to anaphylaxis.88
test). Some investigators may prefer to use in vitro
testing when there is persistent dermatographism ORAL FOOD CHALLENGES
(rare), severe eczema, or when families are reluctant Often an elimination diet provides diagnostic informa-
either to discontinue H1 blockers. Similar to prick tion as well as symptomatic relief. If not, it is possible
skin tests, a cut-off value can be developed for pre- that not all responsible foods have been eliminated

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Cianferoni A et al.

(not all detected in diagnostic work-up, hidden ingre- allergy in England.42 However, this can not account
dients, or sufficient allergen is contained in hy- for the increased rate of sesame seed allergy in Is-
poallergenic casein hydrolysate formula in milk- rael, which is also introduced early into the diet.89
sensitive patient). Elemental diets (Neocate, EleCare) The only dietary measure which has been shown to
may also be helpful as these avoid all protein aller- be important in well conduced longitudinal studies is
gens. If the elimination diet is successful, food chal- the introduction formulas and solid foods into infants
lenges are indicated to confirm the diagnosis and diet before 4-6 months of age diets.90,91 Therefore,
clarify the individual food triggers. For gastrointesti- the American Academy of Pediatrics no longer rec-
nal disorders, biopsy after elimination (normaliza- ommends food avoidance during pregnancy and has
tion) and then after reintroduction (inflammatory re- no specific recommendation on food reintroduction
sponse) can help identify responsible food triggers. beside breast feeding and no solids until 4 months of
Oral food challenges are the key to establishing age.92
the identity of specific food triggers. Most rigorous New studies of alternate routes of allergen admini-
method is double-blinded and placebo controlled stration are in progress.93 In a recent study, sublin-
(DBPC), but single blind (patient) and open chal- gual immunotherapy with hazelnut was successful in
lenges can be performed. The least time intensive reducing symptoms in 23 adults with hazelnut al-
procedure is the open challenge. If endpoints are spe- lergy.94,95 About 50% of the patients in the active
cifically defined and documented, this procedure is group reached maximum doses (20 g), while only 9%
satisfactory for diagnostic purposes.76 DBPC chal- in the placebo group reached the maximum doses.
lenges are indicated when the endpoints are subjec- This data indicates a tolerance to hazelnut after sub-
tive complaints (bias is possible) or there are specific lingual immunotherapy is possible as assessed by
research objectives. double-blind, placebo-controlled food challenge.
Using a standardized oral immunotherapy (OIT)
FOOD ALLERGY THERAPY protocol for treatment of various food allergies, Patri-
The only proven therapy is food elimination. How- arca et al.96,97 reported that 83% of food-allergic sub-
ever, many families find it is difficult to read labels as jects completing the protocol could subsequently tol-
many foods have multiple ways to call an ingredient erate the food to which they were previously allergic.
(for example, casein, whey and lactoalbumin for The most common food allergy in their cohort was
milk). Therefore, governments enacted labeling laws. milk, followed by egg and fish. In comparison to age-
For example, in Japan, labeling of food for common matched food allergic controls, subjects receiving
allergies by Ministry of Health, Labour and Welfare OIT demonstrated a significant decrease in food-
(2001) mandate labeling for 5 food (milk, egg, pea- specific IgE and an increase in specific IgG4.96,97
nut, wheat and buckwheat) with Ministerial Ordi- Meglio and colleagues employed an OIT protocol in
nance No.23 of 2001 and recommended labeling for children with proven IgE-mediated sensitivity to
19 more foods (abalone, squid, salmon roe, shrimp! milk.98,99 In 6 months, 15 of 21 children were fully de-
prawn, orange, crab, kiwifruit, beef, tree nuts, sensitized; 3 children were partially so. Even the par-
salmon, mackerel, soybeans, chicken, pork, Matsu- tial desensitization dramatically reduced the risk of
take mushrooms, peaches, yams, apples and gelatin). severe reactions after accidental or unnoticed inges-
The United States enacted FALPCA in 2005 to help tion of cows milk at low quantities. At 4-5 years of
with reading labels to prevent accidental exposure to follow-up, 14! 20 children totally (n = 13, 65%) or par-
foods for 8 most common food allergens (milk, egg, tially (n = 1, 5%) tolerated cows milk. Also, Burks and
peanuts, tree nuts, fish, shellfish, soy, and wheat). All colleagues used another OIT protocol to successfully
patients at risk for anaphylaxis must be trained to desensitize 7 children with egg allergy and confirmed
identify early symptoms and be prepared to treat ap- with DBPC food challenge.100 Egg-specific IgG con-
propriately. Auto-injectable epinephrine is essential centrations increased significantly similar to Patriarca
together with education to help identify avoidable 96,97 suggests that this might be a marker for develop-

risks. ment of tolerance.

FUTURE THERAPIES CHINESE HERBAL THERAPIES


One alternative approach to prevent food allergies Recent work by Li has suggested the unique combi-
was to delay the introduction, promote breast feeding nation of herbs Zhi Fu Zi (Radix Lateralis Aconiti Car-
or remove the allergen from the mothers diet during michaeli Praeparata) and Xi Xin (Herba Asari),could
pregnancy. Overall, these therapeutic options have also help with the induction of tolerance.101,102 These
not been successful. In fact, the recent study by Lack herbs have been successful in murine models of pea-
and colleagues suggest that the delayed introduction nut allergy and anaphylaxis. All placebo-treated mice
of peanut in the England can account for the in- developed severe anaphylactic signs, increased
creased food allergy compared to genetically plasma histamine levels, and marked vascular leak-
matched control group in Israel with 10 fold peanut age. In contrast, no sign of anaphylactic reactions was

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Food Allergy

observed in actively-treated mice.101,102 But, this ther- 11. Venter C, Pereira B, Grundy J et al. Incidence of paren-
apy has not been tried in any clinical trials in humans. tally reported and clinically diagnosed food hypersensitiv-
Other potential therapies including anti-IgE antibod- ity in the first year of life. J Allergy Clin Immunol 2006;
117:1118-24.
ies, cytokine!anticytokine therapies, and novel immu-
12. Venter C, Pereira B, Grundy J, Clayton CB, Arshad SH,
notherapies utilizing engineered proteins.103 For ex- Dean T. Prevalence of sensitization reported and objec-
ample, development of non-allergic protein can pre- tively assessed food hypersensitivity amongst six-year-old
vent binding to IgE and anaphylaxis, but allow bind- children: a population-based study. Pediatr Allergy Immu-
ing to T cells and induce tolerance. Hypoallergenic nol 2006;17:356-63.
proteins have been made for peanut,104 fish,105 and 13. Venter C, Pereira B, Voigt K et al. Prevalence and cumu-
others. This model has been successful in a murine lative incidence of food hypersensitivity in the first 3
years of life. Allergy 2008;63:354-9.
peanut model with decreased anaphylaxis.106 Ad-
14. Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence
vances in the understanding of anaphylaxis may also
of seafood allergy in the United States determined by a
lead to new therapies for food allergy. The finding by random telephone survey. J Allergy Clin Immunol 2004;
Vadas and colleagues of elevated PAF levels in pa- 114:159-65.
tients with peanut anaphylaxis suggesting the impor- 15. Pereira B, Venter C, Grundy J, Clayton CB, Arshad SH,
tance of the PAF pathway.88 They continued their Dean T. Prevalence of sensitization to food allergens, re-
work and have now found that blockade of PAF path- ported adverse reaction to foods, food avoidance, and
food hypersensitivity among teenagers. J Allergy Clin Im-
way can also prevent anaphylaxis in a murine
munol 2005;116:884-92.
model.107 16. Yocum MW, Butterfield JH, Klein JS, Volcheck GW,
Schroeder DR, Silverstein MD. Epidemiology of anaphy-
CONCLUSION
laxis in Olmsted County: A population-based study. J Al-
Food allergies are a common pediatric condition af- lergy Clin Immunol 1999;104 (Pt 1):452-6.
fecting 4-6% of the US population. Food allergies are 17. Bock SA, Munoz-Furlong A, Sampson HA. Fatalities due
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