nutrients

Review
Personalized Nutrition Approach in Food Allergy:
Is It Prime Time Yet?
Enza D’Auria 1, *, Mariette Abrahams 2 , GianVincenzo Zuccotti 1 and Carina Venter 3
1 Department of Pediatrics, Children’s Hospital V. Buzzi, University of Milan, Milan 20154, Italy;
gianvincenzo.zuccotti@unimi.it
2 Faculty of Social Sciences, University of Bradford, Bradford BD7 1DP, UK; mariette@marietteabrahams.com
3 Section of Allergy and Immunology, Children’s Hospital Colorado, University of Colorado,
Aurora, CO 80045, USA; carina.venter@childrenscolorado.org
* Correspondence: enza.dauria@unimi.it




Received: 27 December 2018; Accepted: 5 February 2019; Published: 9 February 2019


Abstract: The prevalence of food allergy appears to be steadily increasing in infants and young
children. One of the major challenges of modern clinical nutrition is the implementation of
individualized nutritional recommendations. The management of food allergy (FA) has seen major
changes in recent years. While strict allergen avoidance is still the key treatment principle, it is
increasingly clear that the avoidance diet should be tailored according to the patient FA phenotype.
Furthermore, new insights into the gut microbiome and immune system explain the rising interest in
tolerance induction and immunomodulation by microbiota-targeted dietary intervention. This review
article focuses on the nutritional management of IgE mediated food allergy, mainly focusing on
different aspects of the avoidance diet. A personalized approach to managing the food allergic
individual is becoming more feasible as we are learning more about diagnostic modalities and allergic
phenotypes. However, some unmet needs should be addressed to fully attain this goal.

Keywords: food allergy; avoidance diet; nutrition; personalized nutrition; phenotype; microbiome

1. Introduction
The true prevalence of food allergy is still unclear: a systematic review of challenge proven food
allergy (FA) prevalence in Europe estimates a very low prevalence of FA of 1% [1] compared to single
center studies reporting challenge proven prevalence figures of up to 10%. The latest paper on the
prevalence of food allergies in children in the USA reports the number of reported FA of 7.6% in
children [2] and 10.8% in adults [3].
A small number of foods, such as milk, egg, peanut, tree nuts, wheat, soy, fish, and shellfish,
are responsible of most of IgE mediated allergic reactions [4,5]. These reactions are induced by
allergenic proteins in the foods and are characterized by rapid onset (usually <2 h). These foods can
provoke severe reactions, especially tree nut and peanuts [5,6]. Clinical reactivity to carbohydrates in
mammalian meat is an exception—symptoms can be delayed for as long as 6 h [7].
The cornerstone of the management of FA still relies on avoiding the culprit food, since accidental
ingestion of the offending food may lead to symptoms including serious and potentially life-threatening
reactions, like anaphylaxis [8].
The management of food allergies has seen major transformations in the last decade. It is
increasingly clear that the avoidance diet should be tailored according to the patient FA phenotype [9].
Better characterization of FA phenotypes could help to personalize the dietary management of FA by
the degree of avoidance required.

Nutrients 2019, 11, 359; doi:10.3390/nu11020359 www.mdpi.com/journal/nutrients

Nutrients 2019, 11, 359 2 of 16

Furthermore, there is a greater focus seen on tolerance induction and immunomodulation

by microbiota-targeted dietary intervention to allow for greater control of allergies. In the era of
precision medicine, the field of precision nutrition involves tailored nutritional recommendations to
the individual. To plan personalized nutrition advice for patients with a food allergy, many factors
including clinical history, type of allergen, sensitization profiles, threshold level, dietary habits, food
preferences, physical activity, microbiome and genotype should all be considered.
In the field of food allergy, some of these factors are better-defined thanks to new diagnostic
molecular technologies [10]. Allergen-component resolved diagnostics (CRD) allows differentiating
between a true food allergy from pollen-food syndrome or clinically irrelevant sensitization. CRD
may predict the risk or severity of allergic reactions to specific food by identifying IgE to epitopes
within an allergen source. However, many other components necessary for dietary guidance are poorly
understood and need further investigation to be incorporated into clinical practice.
In this review, we will focus on the nutritional management of IgE mediated food allergy,
the avoidance diet, state of the art tools/therapies, and the remaining knowledge gap.

2. Making an Accurate Diagnosis: The First Step Required to Develop an Avoidance Diet
The first step in the diagnosis of a FA is to distinguish IgE-mediated from non–IgE-mediated
reactions. Most IgE caused reactions occur rapidly (minutes up to 2 h after ingestion) with the rare
exception [11]. Anaphylaxis is the most serious allergic reaction; it is rapid in onset, life-threatening,
and potentially fatal [12]. Different geographical locations show some differences in food allergen
triggers for anaphylaxis. A recent one from Spain suggested milk and eggs allergies are more severe
than nuts in their population [13].
Unlike IgE mediated, non IgE-mediated reactions are typically delayed from hours to weeks after
ingestion of the culprit food(s) [11].
A thourough clinical history is central in diagnosing FA. Components of this history should
ideally include food recalls, as well as timing, characteristics, and severity of symptoms. If the history
suggests an IgE mediated food allergy, skin prick tests (SPT) or food-specific IgE blood tests can be
used to confirm allergy diagnosis [5,14]. A positive test result does not confirm an IgE-mediated
allergic reaction, whereas a negative test, with rare exception, eliminates it [15].
In addition to the SPT and specific IgE tests, oral food challenges (OFC) and CRD are important
tools for allergy diagnosis. OFC remains the gold standard to confirm clinical reactivity, in most
cases [16,17]. Component-resolved diagnostics helps further define specific allergens and reduces
misdiagnosis due to cross-reactivity [18,19]. The usefulness of these tools can be explained through
the classic example—wheat allergy. Wheat allergy is often over diagnosed, due to the low specificity
of wheat IgE testing [20,21]. A patient with a grass pollen allergy may have elevated “wheat IgE
levels” while being wheat tolerant [22]. Therefore, both CRD and OFCs should be implemented in
children with an SPT or IgE positive wheat allergy. CRD increases the accuracy of wheat allergy
diagnosis by identifying the presence of specific IgE to omega-5 gliadin, the antibody highly specific
to wheat allergy [23]. Currently, oral provocation with wheat is the reference test for the diagnosis of
wheat/cereal allergy as it definitely shows if a child will tolerate wheat.
Additionally, profiling the specific IgE repertoire by CRD may help identify falsely diagnosed
allergies in highly polysensitized patients. This can be explained with the case of patients with allergen
extract positive but negative genuine components. In children with multiple sensitization to tree
nuts, including hazelnut, positive IgE extract but negative IgE genuine component are markers of
a probable cross-sensitization with grass pollen. These patients are very likely to be tolerant to hazelnut
in vivo [24]. CRD has become a useful tool for diagnosing FA, though the use of these tests varies
from country to country.; This technique has some limitations that should be considered. For instance,
the allergens are in a recombinant form and not always show the same IgE reactivity that natural
allergens. This is even more relevant in food allergy testing as the allergens used in the reagents
Nutrients 2019, 11, 359 3 of 16

are processed. Indeed, the oral food challenge (OFC) is the only effective method to confirm the FA
diagnosis, although the other preliminary diagnostic techniques could support the diagnosis.

3. Risk Assessment and Individual Threshold Level

In general, for IgE mediated-food allergy it is very important to identify patients who are likely to
have severe reactions from patients with mild to moderate ones. Unfortunately, as allergy severity
is multifactorial, this is difficult. Possible contributors to severe reactions are allergen bioavailability,
patient habits (e.g., Exercise [25]), and history of anaphylaxis—although many people who have
a history of only mild symptoms can develop anaphylaxis. Allergen-specific IgE levels and CRD may
assist in risk assessment as sensitization to some allergenic molecules is more likely to be related to
systemic rather than local reactions.
For instance, high levels of casein IgE has been shown to correlate with severe reactions, due to
accidental exposure, in cow’s milk allergic children [26]. Similarly, an association between specific IgE
to omega-5 gliadin component and severity of reactions during wheat challenge has been reported [21,
27]. In peanut allergic children, Eller and Bindslev–Jensen documented that symptom severity elicited
during challenge correlated significantly with the levels of Ara h 2 (r(s) 14 0.60, P < 0.0001) [28]. However,
patients with very low or undetectable sIgE may still experience severe allergic reactions [25,29].
The OFC allows us to ascertain information about individual threshold level can guide the
necessary level of food avoidance.
For instance, the challenge food for baked milk contains 1.3 g CM protein (equivalent to 40 mL
CM), and children who react during their CM OFC should avoid it completely due to their severe
phenotype [30].
Lieberman et al. showed that 66% of the patients with egg allergy undergoing baked egg OFC
tolerated baked egg and that most of the reactions were mild and treated with antihistamine alone,
regardless of sIgE and/or SPT. [31].
In our opinion, performing OFC with baked milk or egg in a controlled-setting has the potential
to greatly improve children’s quality of life [32].

4. Avoidance Diet: Towards Personalized Nutrition Advice

Managing food allergies and avoiding food allergic reactions involves an individualized approach
to food allergen avoidance while providing sufficient nutrition [33].
An avoidance diet is a complex undertaking that requires education about label reading, cooking,
preventing cross-contamination, and communicating information to family, caregivers, friends,
and restaurant personnel [34,35]. See Table 1

Table 1. Nutritional management according to risk assessment: What are the challenges?

Challenges of the Nutritional Management According to Risk Assessment

- local availability of food
- lack of understanding about foods to be avoided
- unexpected allergens in foods
- prepacked foods with inadequate allergen labeling
- defining “baked” milk and egg
- identify the “eliciting dose”
- risks of over restrictive diet
- potential long-term effects on health and quality of life

The standard information that should be provided to all patients includes advice on food labels
and relevant labeling laws, hidden allergens, and suitable replacement foods [36]. However, avoidance
advice should be individualized considering individual tolerances, cross-reactivity, and specific
allergens that drive the reaction. Allergies to novel allergens such as alpha-gal will also require
individualized avoidance advice.
Nutrients 2019, 11, 359 4 of 16

Individualized Allergen Avoidance

4.0.1. Milk and Egg

It is known that a large proportion of children with cow’s milk and egg allergies will be tolerant
to baked milk and egg irrespective of the age or population studied [37]. Baked milk or egg-containing
foods typically refer to muffins, but other forms such as cookies, waffles, and pancakes have also
been suggested. Baked cheese (pizza) has also been suggested for baked milk challenges [38–43].
No established guidelines to determine when to challenge have been established, so testing depends
on combination of history, sIgE, and skin test results. There is limited consensus about the exact time
and temperature of baking/cooking that is required, the need for a wheat/starch matrix, and where the
challenge/food reintroduction should be conducted, e.g., hospital/in-office vs. at home [44–46]. It is,
however, important to realize that some children who react to baked milk or baked egg may experience
severe symptoms, requiring epinephrine. [31,32,46]. Risk factors for severe reactions to baked foods
need further clarification but may include asthma requiring preventative treatment, multiple IgE
mediated food allergies, and a history of anaphylaxis. [45,47]. Baked milk and egg-containing foods
are successfully introduced at home in most children’s diets post a negative challenge with good
compliance; positively affecting the child’s food and texture repertoire [48]. However, as it is unclear if
continued and regular consumption of baked milk and egg-containing foods will speed up tolerance
to uncooked milk or egg [49,50], families should not be pressured about frequent intake unnecessarily.

4.0.2. Peanut, Tree Nuts, Seeds

Previously, patients with peanut or tree nut allergies were advised to avoid all nuts, due to the
risk of cross-reactivity or possible cross-contact/contamination. However, recent studies indicate
that clinical cross-reactivity may be as low as 30% [51]. For instance, walnuts and pecans are highly
cross-reactive with each other, but not with peanuts, hazelnuts or almonds Sensitization or clinical
allergy may develop after a period of unnecessarily exclusion [52]. The British Society for Allergy
and Clinical Immunology (BSACI) guidelines were the first food allergy management guidelines
to recommend active inclusion of tolerated nuts in diets of individuals with peanut or tree nut
allergy [53,54]. Peanuts are legumes, but allergy to other legumes is generally uncommon among
those with peanut allergy, though this does depend on geography and local diet [55,56]. Lupine, pea,
and soybean show some apparent cross-reactivity for patients who are highly allergic to peanut,
although it is very difficult to separate cross-reactivity from de novo sensitization. The risk of
cross-reaction may be higher for lupin than for other beans, particularly in Europe [57–59]. In the case
of lupine allergy, patients need to be informed about foods containing lupin which may include pies,
certain breads, and pastries.
Seeds are being used more often in commercial and gourmet foods—most commonly flaxseed,
sesame, sunflower, poppy, pumpkin, and mustard seeds [60]. Sesame and mustard seeds are among
the 14 most prevalent allergens in the EU, but not in the US [61]. In Europe, prevalence data
indicates sesame and mustard seed allergies are geographically disproportionate: high in some
areas (France and Spain), much lower in others (Germany and the Nordic countries) and unknown in
Eastern Europe [62]. Mustard and sesame seeds are often hidden in commercial foods, making
scrutiny of labels required at all times. Sesame seed allergy is not commonly seen outside of
Israel and Europe [63]. In addition to scrutiny of labels, children with sesame allergy should always
avoid sesame oil as it is cold/expeller pressed [64].

4.0.3. Fruit and Vegetable Allergies

Allergies to fruit and vegetables, in particular, require individualized advice as symptoms range
from milder symptoms triggered by pollen-food syndrome (PFS, secondary IgE mediated food allergy)
to more severe symptoms triggered by lipid transfer protein syndrome (LTP, primary IgE mediated
food allergy) [65]. It is important to differentiate between these two presentations of fruit and vegetable
Nutrients 2019, 11, 359 5 of 16

allergies as that will direct the dietary advice given. With PFS, cooked, canned, baked, microwaved
fruit and vegetables are allowed, whereas fruit/vegetable should be completely avoided in the case of
LTP allergies. The degree to which cross-reactive fruit and vegetables (including soy and nuts) should
be avoided requires careful diagnostic evaluation as blanket avoidance advice is not advocated [66–68].

4.0.4. Fish and Shellfish Allergy

It is important to distinguish between fish and shellfish (crustacean and mollusks) allergies. Fish
and shellfish allergies may co-exist [69] but the main allergens differ, and cross-reactivity between
fish and shellfish is unlikely. The main allergen in fish is β parvalbumin; in the case of shellfish,
the major allergen is tropomyosin [70]. Additionally, allergy to a certain fish or shellfish does not imply
allergies to all species in that particular group [71,72]. Subjects who suffer from fish allergy have only
about a 50% probability of being cross-reactive to another fish species. This is significantly lower than
those with shellfish allergies, who have up to a 75% chance of cross-reactivity [15]. In addition
to the allergens derived from fish themselves, fish contaminants, such as the parasite Anisakis,
can also cause allergic reactions, meaning Anisakis allergy can be falsely diagnosed as a fish allergy.
In particular, Anisakis allergy correlated to prevalence of parasitic infection in fish—for example,
in Spain and Southern Italy, there is a higher prevalence of Anisakis allergy due to moderately frequent
Anisakis infection. These allergic patients develop IgE against tropomyosin from Anisakis. As always,
sensitization depends in part on the consumption pattern of fish (cooked, undercooked or raw) and
the infection pattern of fish in the local region [73].

4.0.5. Alpha-Galactosidase
Alpha galactosidase (Alpha-gal) allergy is characterized by delayed (4 to 6 h after the ingestion)
hypersensitivity reactions to mammalian meats and is mediated by IgE antibodies to the oligosaccharide
galactose-alpha 1,3-galactose. It requires avoidance of mammalian meats and their organ meat. Some
individuals also need to avoid ice-cream, milk, and milk products but the degree of avoidance and foods
being avoided should be discussed with the allergist. This decision can be made based on past history of
reactions or tolerance [74,75]. Where the history is unclear, or the food has not been eaten in the past, an oral
food challenge can be conducted [76].

5. Nutritional Impact of Food Allergies: Growth and Nutrient Intake

There is rising concern that children with FA have an insufficient nutrient intake or nutrient
imbalance leading to adverse health implications. Data published over the past few years indicates
that children with food allergies (IgE, non-IgE, and mixed presentations of IgE and non-IgE)
show growth impairment, both in weight and length. They are often underweight [77], and in
the case of chronic malnutrition, they become stunted, e.g., a child who is too short for his/her
age [78,79]. However, excessive weight gain has also been reported in children with food allergies,
but poorly researched [77,80,81]. A recent international survey conducted by Meyer et al. [82] included
430 patients from twelve allergy centers world-wide. The pooled data indicated that 6% were
underweight, 9% stunted, 5% undernourished, and 3–5% were overweight. In this study, growth
impairments varied by allergy profile. Children with cow’s milk allergy (CMA) had a lower weight
for age z-score, as a result of acute malnutrition or “wasting”; children with mixed IgE and non-IgE
mediated FA were stunted, and children with only non-IgE FA were underweight with lower body
mass index (BMI). Very different growth patterns were observed between children from different
countries. Atopic comorbidities did not affect growth.
Avoidance diets required for FA management place children at risk for potential inadequate
nutrition. In this regard, a number of studies have investigated the nutritional adequacy of elimination
diets. However, most of them have been conducted in young children aged six months to four years.
Children with food allergies (IgE, non-IgE, and mixed presentations of IgE and non-IgE) are also at
higher risk of insufficient intake of protein, calories, vitamins, and minerals [83–87]. The micronutrients
Nutrients 2019, 11, 359 6 of 16

implicated are iodine, calcium, and vitamin D, especially in children with CMA [83,88,89]. However,
it has been shown that children with cow’s milk allergies or multiple food allergies are able to
achieve similar mean intakes of nutrients as healthy children when receiving nutrition counselling and
substitution of nutritionally equivalent foods [78,83,90–92].
Limited data exist on dietary intake in teenagers and adults with food allergies, with contrasting
results [93,94]. One study reports, higher intakes of calcium, iron, folate, and vitamin E have been
demonstrated in participants >20 years with food allergy [44]. Conversely, lower intakes of calcium
and phosphorous have been reported in young adults with CMA, with one study reporting that 27%
were at risk of osteoporosis [48]. Maslin et al. showed no significant difference between these two
groups and control groups with the intake of calcium. Iron, copper, zinc, selenium, and iodine were
below the Recommended National Intakes (RNI) for both groups and their controls [94]. There are
currently no data on BMI status on adults with IgE mediated food allergy. These factors need to be
considered when providing nutrition advice to children and adults with food allergies. Although
information on healthy eating is important, consideration to vitamin and mineral supplementation in
hypoallergenic formulas in the case of children should be given [84,95]. Nutritional counselling and
monitoring growth and development are crucial in the management of FA, as the avoidance diet may
affect the well-being of FA patients (see Table 2).

Table 2. Effect of avoidance diet on patients.

Effect of Avoidance Diet

- poor growth
- micronutrient deficiencies
- altered taste perception
- long term effects on food preferences and choices
- reduced quality of life

6. Food Behaviour and Preferences

In children with FA, the development of their food habits and preferences takes place in the context
of their chronic condition. Since parents have the main responsibility for the dietary management of
their child’s food allergies [96], their parenting style and the way they interact with the child during
feedings both have an effect on a child’s food habits [97]. A child’s food allergies add a burden to
parents [98]. Food refusal has also been shown to occur in toddlers with food allergies [99] and more
specifically eosinophilic gastrointestinal disease [100]. Additionally, a study on children aged 5 to
14 years in France showed that children who have outgrown their food allergies are more reluctant to
try new foods than their siblings [101]. Food neophobia and refusal could result from unnecessarily
high dietary restrictions that parents place on their children due to increased anxiety and fear of an
allergic reaction [102]. The long-term effects of avoidance diet on food behavior and preferences needs
further investigation.
Food choice behavioral problems have been documented in older children or adults with food
allergies. Teenagers with food allergies, strive to eat the same foods as their peers, often leading to
risk taking behavior. However, they reported reluctance to try new foods when away from home.
In contrast to the non-food allergic teens, those with food allergies felt that parental control over food
intake was to protect them [103].
Adults with FA felt that their allergies limited them from the pleasure of eating and they often
found it difficult to find safe foods. They also felt that the need to be constantly organized to have safe
foods available was a burden [104].

7. Microbiota-Diet and Genetic Factors: A Complex and Still Unknown Interplay

FA is thought to be the result of a disruption of mucosal immunological tolerance, due to dietary
factors, gut microbiota, and interactions between them [105]. Different bacterial taxa may be associated
Nutrients 2019, 11, 359 7 of 16

with different food allergy subphenotyes. Differences in gut microbiome have been observed in subjects
with tree-nut allergy in respect to those with cow’s milk allergy [106,107]. The observed differences
may however be influenced by age, population, sex and diet. Furthermore, recent data indicate that
for cow’s milk allergy, the microbiome differs between those children who are sensitized vs. not
sensitized [108], those with clinical allergy vs. those with no allergy [109], and those who develop
tolerance vs. those who do not [110]. Overall, these findings suggest the possibility to manipulate the
gut microbiota with preventive or therapeutic purposes.
Data in pediatric studies indicate that certain pre and probiotics tested may address dysbiosis [111]
and may even induce tolerance development [112]. More clinical trials regarding the use of pre and
probiotics in the management of food allergies are needed before clinical recommendations can be made.
These studies should also consider genetic background and age in their design. Another important
issue to be considered is that the gut microbiome composition and diversity can be modulated by host
genetic profiling [113]. A host’s genetic composition is able to modulate their gut microbiota, which is
another paramount area of study [114].
Whether diet diversity may improve dysbiosis and microbial diversity in those with food allergies
remains to be seen [115].
Further studies need to investigate the complex interplay between the host genetic components
and environmental factors, including the microbiota and diet, in the pathogenesis and expression of
food allergy that is still largely unknown.

8. The Technology Revolution in FA Management

Increasingly, personalized devices to aid in allergen detection have been invented, and the industry
has grown rapidly over the last decade [116]. These technologies have resulted both from increased
demand for transparency of product information and scientific advancements. [117]. The rapid drop
in the price of personalised nutrition devices has resulted in mass accessibility [118]. Deciphering food
labels is a difficult task and for those with allergies, a daily chore that if done incorrectly, can lead to
negative and possibly fatal outcomes [119,120].
New digital technologies have started to appear on the market that attempts to address the
daily challenges families face when choosing products for a child with allergies. For a full review
of technologies involved in portable allergy products, we refer readers to the comprehensive article
by Ross, G.M.S [121]. There have been a number of technology services advising about potential
risks related to food composition. For concerned consumers, having instant access to information can
remove the guesswork and can potentially save time. However, there are no validated, personalized
systems for testing individual meals for specific food source products. It is also noteworthy that
sometimes component recipes change and accuracy as well of lack of clinical validation of these
products are issues frequently raised.
With such rapid advances in the scientific and technology industry, it is, however, important
to have comprehensive communication between consumer advocates, the food industry, and the
clinicians to help improve avoidance of allergens by technical fixes, while being fully aware of the
limitations and current lack of validation of these products in a variety of matrices or in foods with
multiple ingredients (see Figure 1). What is clear, is that management of allergies will require the
intervention of a specialist multidisciplinary team with registered dietitians playing a key role in
supporting families while staying abreast of new technologies [122].
Some examples of products currently available on the market, outlining their pros, cons and
future considerations, are listed below (Table 3).
Nutrients 2019, 11, 359 8 of 16

Table 3. Personalized nutrition offering for Food allergies.

Currently Available
Description Pros Cons Future directions
Resources or Tools

• These app scanners provide quick

SmartwithfoodTM , SpoonguruTM , results that are easy to understand • The app only reports on a limited number
FoodmaestroTM , WhiskTM . These apps • Apps should increase the number of
and can always be on hand. of allergens.
are available free to consumers. Through allergens they have
• They can provide peace of mind as a • The app is not a medical device and,
barcode scanning, image recognition, information about.
Apps second line. therefore, cannot replace a medical
natural language processing and • New products could ideally be
• The platforms rely on food professional’s advice; consumers should
machine learning technology, consumers developed based on the popularity
manufacturers to provide accurate always ask questions and always check
can obtain instant information whether a of scanned products.
product information in terms of the food label.
product contains allergens. their recipes.

• Costs can be prohibitive.

• These scanners are small, provide • It is not a medical device and, therefore,
quick results that are easy consultation with a healthcare
to understand. professional is still required.
Scanners such as TellspecTM , ScioscanTM • They can provide peace of mind as a • Concerns have been raised about the
• These tools need to be
and NimaTM are handheld, mobile second line. accuracy in detecting allergens (Popping
clinically validated
Food scanners devices that use hyperspectral or imaging • These products may provide some et al., 2017).
• These tools need to comply with
technology to analyse nutritional reassurance once standard allergen • Scanners work best with homogenous
medical devices regulation
information and detect allergens. avoidance advice has been followed solid products. For example, testing may
but should NOT be used instead of be highly inaccurate in foods with
advice provided by the allergist multiple ingredients or high-fat matrices.
or dietitian. • It is not clear who holds the data on
these products.

• A mobile and attractive device that

Such as Allergy AmuletTM is a device • It is not a medical device • Needs to be clinically validated.
provides instant results.
that is worn as a necklace and works by • It is important the consumers read labels • In the future, potentially sensors or
Wearable devices • These products may provide some
inserting strips into food, available and ask about ingredients to the dietitian. implants could detect from a
reassurance once standard allergen
in 2019. • Have not been validated for accuracy nanoparticle of food.
avoidance advice has been followed.

• Technology is still expensive.

Is the new technology which enables • Some allergens can be removed.
• Current lack of understanding of
DNA of food (and humans) to be edited. • It is not clear how differentiating the long-term impact of eating
This means that new foods and products Consumers with allergies will have a wider appropriately altered foods from native gene-edited foods.
CRISPR food sources. For some allergenic sources,
can be developed where the culprit variety of foods to eat • Extensive public education will
allergen’s DNA has been edited without such as wheat, the genetic complexity of
be required.
the devastating effects. the crop is unlikely to allow simple
genetic knockout of allergenic genes.
Nutrients 2019, 11, 359 9 of 16

Figure 1. Nutrition approach: unmet needs.

9. Conclusions
A personalized approach to managing the food allergic individual is becoming more feasible
as we are learning more about diagnostic modalities and allergic phenotypes. The availability
of specialized foods and technology are increasing which also enables the clinicians to provide
personalized advice. A multidisciplinary team approach, including a dietitian, is crucial to provide
individualized recommendations to patients.

Author Contributions: E.D. and C.V contributed to the conception and design of the review, drafting the review;
M.A. contributed in the review drafting; G.V.Z. and C.V. contributed to revise the manuscript. All the authors
approved the manuscript for publication.
Funding: This research received no external funding
Acknowledgments: We would like to acknowledge Miriam Ben Abdallah for editing the paper.
Conflicts of Interest: The authors declare no conflict of interests.
Nutrients 2019, 11, 359 10 of 16

References
1. Nwaru, B.I.; Hickstein, L.; Panesar, S.S.; Muraro, A.; Werfel, T.; Cardona, V.; Dubois, A.E.; Halken, S.;
Hoffmann-Sommergruber, K.; Poulsen, L.K.; et al. EAACI Food Allergy and Anaphylaxis Guidelines Group.
The epidemiology of food allergy in Europe: A systematic review and meta-analysis. Allergy 2014, 69, 62–75.
[CrossRef]
2. Gupta, R.S.; Warren, C.M.; Smith, B.M.; Blumenstock, J.A.; Jiang, J.; Davis, M.M.; Nadeau, K.C. The Public
Health Impact of Parent-Reported Childhood Food Allergies in the United States. Pediatrics 2018, 142,
e20181235. [CrossRef] [PubMed]
3. Osborne, N.J.; Koplin, J.J.; Martin, P.E.; Gurrin, L.C.; Lowe, A.J.; Matheson, M.C.; Ponsonby, A.L.;
Wake, M.; Tang, M.L.; Dharmage, S.C.; et al. HealthNuts Investigators. Prevalence of challenge-proven
IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants.
J. Allergy ClinImmunol. 2011, 127, e1–e2. [CrossRef] [PubMed]
4. Chafen, J.J.; Newberry, S.J.; Riedl, M.A.; Bravata, D.M.; Maglione, M.; Suttorp, M.J.; Sundaram, V.; Paige, N.M.;
Towfigh, A.; Hulley, B.J.; et al. Diagnosing and managing common food allergies: A systematic review.
JAMA 2010, 303, 1848–1856. [CrossRef] [PubMed]
5. Boyce, J.A.; Assa’ad, A.; Burks, A.W.; Jones, S.M.; Sampson, H.A.; Wood, R.A.; Plaut, M.; Cooper, S.F.;
Fenton, M.J.; Arshad, S.H.; et al. NIAID-sponsored expert panel. Guidelines for the diagnosis
and management of food allergy in the United States: Report of the NIAID-sponsored expert panel.
J. Allergy ClinImmunol. 2010, 126, S1–S58. [CrossRef] [PubMed]
6. Gupta, R.S.; Springston, E.E.; Warrier, M.R.; Smith, B.; Kumar, R.; Pongracic, J.; Holl, J.L. The prevalence,
severity, and distribution of childhood food allergy in the United States. Pediatrics 2011, 128, e9–e17.
[CrossRef] [PubMed]
7. Commins, S.P.; Satinover, S.M.; Hosen, J.; Mozena, J.; Borish, L.; Lewis, B.D.; Woodfolk, J.A.;
Platts-Mills, T.A.E. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients
with IgE antibodies specific for galactose-alpha-1,3-galactose. J. Allergy ClinImmunol. 2009, 123, 426–433.
[CrossRef] [PubMed]
8. Sova, C.; Feuling, M.B.; Baumler, M.; Gleason, L.; Tam, J.S.; Zafra, H.; Goday, P.S. Systematic review of
nutrient intake and growth in children with multiple IgE-mediated food allergies. Nutr. Clin. Pract. 2013, 28,
669–675. [CrossRef] [PubMed]
9. Deschildre, A.; Lejeune, S.; Cap, M.; Flammarion, S.; Jouannic, L.; Amat, F.; Just, J. Food allergy phenotypes:
The key to personalized therapy. ClinExp Allergy 2017, 47, 1125–1137. [CrossRef] [PubMed]
10. Matricardi, P.M.; Kleine-tebbe, J.; Hoffmann, H.J.; Valenta, R.; Hilger, C.; Hofmaier, S.; Aalberse, R.C.;
Agache, I.; Asero, R.; Ballmer-Weber, B.; et al. EAACI Molecular Allergology User’s Guide.
Pediatr. Allergy Immunol. 2016, 27, 1–250. [CrossRef]
11. Sampson, H.A.; Aceves, S.; Bock, S.A.; James, J.; Jones, S.; Lang, D.; Nadeau, K.; Nowak-Wegrzyn, A.;
Oppenheimer, J.; Perry, T.T.; et al. Food allergy: A practice parameter update-2014. J. Allergy Clin. Immunol.
2014, 134, 1016–1025. [CrossRef] [PubMed]
12. Muraro, A.; Roberts, G.; Worm, M.; Bilo, M.B.; Brockow, K.; Fernandez-Rivas, M.; Santos, A.F.; Zolkipli, Z.Q.;
Bellou, A.; Bindslev-Jensen, C.; et al. Anaphylaxis: Guidelines from the European Academy of Allergy and
Clinical Immunology. Allergy 2014, 69, 1026–1045. [CrossRef] [PubMed]
13. Benedé, S.; Garrido-Arandia, M.; Martín-Pedraza, L.; Bueno, C.; Díaz-Perales, A.; Villalba, M. Multifactorial
modulation of food-induced anaphylaxis. Front. Immunol. 2017, 8, 552. [CrossRef]
14. Centre for Clinical Practice at NICE (UK). Food Allergy in Children and Young People: Diagnosis and Assessment
of Food Allergy in Children and Young People in Primary Care and Community Settings; National Institute for
Health and Clinical Excellence: London, UK, 2011.
15. Sicherer, S.H.; Sampson, H.A. Food allergy. J. Allergy Clin. Immunol. 2010, 125, S116–S125. [CrossRef]
[PubMed]
16. Petersen, T.H.; Mortz, C.G.; Bindslev-jensen, C.; Eller, E. Cow’s milk allergic children-Can component-
resolved diagnostics predict duration and severity? Pediatr. Allergy Immunol. 2018, 29, 194–199. [CrossRef]
[PubMed]
17. Sicherer, S.H.; Sampson, H.A. Food allergy: A review and update on epidemiology, pathogenesis, diagnosis,
prevention, and management. J. Allergy ClinImmunol. 2018, 141, 41–58. [CrossRef] [PubMed]
Nutrients 2019, 11, 359 11 of 16

18. D’auria, E.; Mameli, C.; Piras, C.; Cococcioni, L.; Urbani, A.; Zuccotti, G.V.; Roncada, P. Precision medicine
in cow’s milk allergy: Proteomics perspectives from allergens to patients. J. Proteomics 2018, 188, 173–180.
[CrossRef]
19. Mirnezami, R.; Nicholson, J.; Darzi, A. Preparing for precision medicine. N. Engl. J. Med. 2012, 366, 489–491.
[CrossRef]
20. Venter, C.; Maslin, K.; Arshad, S.H.; Patil, V.; Grundy, J.; Glasbey, G.; Twiselton, R.; Dean, T. Very low
prevalence of IgE mediated wheat allergy and high levels of cross-sensitisation between grass and wheat in
a UK birth cohort. Clin. Transl. Allergy 2016, 6, 22. [CrossRef]
21. Nilsson, N.; Sjölander, S.; Baar, A.; Berthold, M.; Pahr, S.; Vrtala, S.; Valenta, R.; Morita, E.; Hedlin, G.;
Borres, M.P.; et al. Wheat allergy in children evaluated with challenge and IgE antibodies to wheat
components. Pediatr. Allergy Immunol. 2015, 26, 119–125. [CrossRef]
22. Constantin, C.; Quirce, S.; Poorafshar, M.; Touraev, A.; Niggemann, B.; Mari, A.; Ebner, C.; Akerström, H.;
Heberle-Bors, E.; Nystrand, M.; et al. Micro-arrayed wheat seed and grass pollen allergens for
component-resolved diagnosis. Allergy 2009, 64, 1030–1037. [CrossRef] [PubMed]
23. Palosuo, K.; Varjonen, E.; Kekki, O.M.; Klemola, T.; Kalkkinen, N.; Alenius, H.; Reunala, T. Wheat omega-5
gliadin is a major allergen in children with immediate allergy to ingested wheat. J. Allergy ClinImmunol.
2001, 108, 634–638. [CrossRef] [PubMed]
24. Beyer, K.; Grabenhenrich, L.; Härtl, M.; Beder, A.; Kalb, B.; Ziegert, M.; Finger, A.; Harandi, N.; Schlags, R.;
Gappa, M.; et al. Predictive values of component-specific IgE for the outcome of peanut and hazelnut food
challenges in children. Allergy 2015, 70, 90–98. [CrossRef] [PubMed]
25. Turner, P.J.; Baumert, J.L.; Beyer, K.; Boyle, R.J.; Chan, C.H.; Clark, A.T.; Crevel, R.W.; DunnGalvin, A.;
Fernández-Rivas, M.; Gowland, M.H.; et al. Can we identify patients at risk of life-threatening allergic
reactions to food? Allergy 2016, 71, 1241–1255. [CrossRef] [PubMed]
26. Boyano-martínez, T.; García-ara, C.; Pedrosa, M.; Díaz-pena, J.M.; Quirce, S. Accidental allergic reactions in
children allergic to cow’s milk proteins. J. Allergy ClinImmunol. 2009, 123, 883–888. [CrossRef] [PubMed]
27. Ito, K.; Futamura, M.; Borres, M.P.; Takaoka, Y.; Dahlstrom, J.; Sakamoto, T.; Tanaka, A.; Kohno, K.; Matsuo, H.;
Morita, E. IgE antibodies to omega-5 gliadin associate with immediate symptoms on oral wheat challenge in
Japanese children. Allergy 2008, 63, 1536–1542. [CrossRef] [PubMed]
28. Eller, E.; Bindslev-jensen, C. Clinical value of component-resolved diagnostics in peanut-allergic patients.
Allergy 2013, 68, 190–194. [CrossRef]
29. Perry, T.T.; Matsui, E.C.; Conover-walker, M.K.; Wood, R.A. The relationship of allergen-specific IgE levels
and oral food challenge outcome. J. Allergy ClinImmunol. 2004, 114, 144–149. [CrossRef]
30. Yanagida, N.; Okada, Y.; Sato, S.; Ebisawa, M. New approach for food allergy management using low-dose
oral food challenges and low-dose oral immunotherapies. Allergol. Int. 2016, 65, 135–140. [CrossRef]
31. Lieberman, J.A.; Huang, F.R.; Sampson, H.A.; Nowak-w˛egrzyn, A. Outcomes of 100 consecutive open,
baked-egg oral food challenges in the allergy office. J. Allergy ClinImmunol. 2012, 129, 1682–1684. [CrossRef]
32. Nowak-Wegrzyn, A.; Bloom, K.A.; Sicherer, S.H.; Shreffler, W.G.; Noone, S.; Wanich, N.; Sampson, H.A.
Tolerance to extensively heated milk in children with cow’s milk allergy. J. Allergy ClinImmunol. 2008, 122,
342–347. [CrossRef] [PubMed]
33. Venter, C.; Groetch, M.; Netting, M.; Meyer, R. A patient-specific approach to develop an exclusion diet to
manage food allergy in infants and children. Clin. Exp. Allergy 2018, 48, 121–137. [CrossRef] [PubMed]
34. Kim, J.S.; Sicherer, S.H. Living with food allergy: Allergen avoidance. Pediatr. Clin. North Am 2011, 58,
459–470. [CrossRef] [PubMed]
35. Muñoz-furlong, A. Daily coping strategies for patients and their families. Pediatrics 2003, 111, 1654–1661.
[PubMed]
36. Venter, C.; Meyer, R. Session 1: Allergic disease: The challenges of managing food hypersensitivity.
Proc. Nutr. Soc. 2010, 69, 11–24. [CrossRef] [PubMed]
37. Savage, J.; Sicherer, S.; Wood, R. The natural history of food allergy. J. Allergy Clin. Immunol. Pract. 2016, 4,
196–203. [CrossRef] [PubMed]
38. Leonard, S.A.; Caubet, J.C.; Kim, J.S.; Groetch, M.; Nowak-Wegrzyn, A. Baked milk- and egg-containing
diet in the management of milk and egg allergy. J. Allergy Clin. Immunol. Pract. 2015, 3, 13–23. [CrossRef]
[PubMed]
Nutrients 2019, 11, 359 12 of 16

39. Leonard, S.A.; Nowak-Wegrzyn, A.H. Baked milk and egg diets for milk and egg allergy management.
Immunol. Allergy Clin. North Am 2016, 36, 147–159. [CrossRef]
40. Leonard, S.A.; Sampson, H.A.; Sicherer, S.H.; Noone, S.; Moshier, E.L.; Godbold, J.; Nowak-Wegrzyn, A.
Dietary baked egg accelerates resolution of egg allergy in children. J. Allergy Clin. Immunol. 2012, 130,
473–480. [CrossRef]
41. MiceliSopo, S.; Greco, M.; Cuomo, B.; Bianchi, A.; Liotti, L.; Monaco, S.; DelloIacono, I. Matrix effect on
baked egg tolerance in children with IgE-mediated hen’s egg allergy. Pediatr. Allergy Immunol. 2016, 27,
465–470. [CrossRef]
42. MiceliSopo, S.; Greco, M.; Monaco, S.; Bianchi, A.; Cuomo, B.; Liotti, L.; Iacono, I.D. Matrix effect on baked
milk tolerance in children with IgE cow milk allergy. Allergol. Immunopathol. 2016, 44, 517–523. [CrossRef]
[PubMed]
43. Kim, J.S.; Nowak-Wegrzyn, A.; Sicherer, S.H.; Noone, S.; Moshier, E.L.; Sampson, H.A. Dietary baked milk
accelerates the resolution of cow’s milk allergy in children. J. Allergy Clin. Immunol. 2011, 128, 125–131.
[CrossRef] [PubMed]
44. Dupont, C. How to reintroduce cow’s milk? Pediatr. Allergy Immunol. 2013, 24, 627–632. [CrossRef] [PubMed]
45. Luyt, D.; Ball, H.; Makwana, N.; Green, M.R.; Bravin, K.; Nasser, S.M.; Clark, A.T. Standards of Care
Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). BSACI guideline
for the diagnosis and management of cow’s milk allergy. Clin. Exp. Allergy 2014, 44, 642–672. [CrossRef]
[PubMed]
46. Athanasopoulou, P.; Deligianni, E.; Dean, T.; Dewey, A.; Venter, C. Use of baked milk challenges and milk
ladders in clinical practice: A worldwide survey of healthcare professionals. Clin. Exp. Allergy 2017, 47,
430–434. [CrossRef] [PubMed]
47. Mehr, S.; Turner, P.J.; Joshi, P.; Wong, M.; Campbell, D.E. Safety and clinical predictors of reacting to
extensively heated cow’s milk challenge in cow’s milk-allergic children. Ann. Allergy Asthma. Immunol. 2014,
113, 425–429. [CrossRef] [PubMed]
48. Lee, E.; Mehr, S.; Turner, P.J.; Joshi, P.; Campbell, D.E. Adherence to extensively heated egg and cow’s milk
after successful oral food challenge. J. Allergy Clin. Immunol. Pract. 2015, 3, 125–127. [CrossRef]
49. Netting, M.; Gold, M.; Quinn, P.; El-Merhibi, A.; Penttila, I.; Makrides, M. Randomised controlled trial of
a baked egg intervention in young children allergic to raw egg but not baked egg. World Allergy Organ. J.
2017, 10, 22. [CrossRef]
50. Lambert, R.; Grimshaw, K.E.C.; Ellis, B.; Jaitly, J.; Roberts, G. Evidence that eating baked egg or milk
influences egg or milk allergy resolution: A systematic review. Clin. Exp. Allergy 2017, 47, 829–837.
[CrossRef]
51. Couch, C.; Franxman, T.; Greenhawt, M. Characteristics of tree nut challenges in tree nut allergic and tree
nut sensitized individuals. Ann. Allergy Asthma. Immunol. 2017, 118, 591–596. [CrossRef]
52. Elizur, A.; Bollyky, J.B.; Block, W.M. Elimination diet and the development of multiple tree-nut allergies.
Pediatr. Res. 2017, 82, 671. [CrossRef]
53. Stiefel, G.; Anagnostou, K.; Boyle, R.K.; Brathwaite, N.; Ewan, P.; Fox, A.T.; Huber, P.; Luyt, D.;
Till, S.J.; Venter, C. BSACI guideline for the diagnosis and management of peanut and tree nut allergy.
Clin. Exp. Allergy 2017, 47, 719–739. [CrossRef] [PubMed]
54. Eigenmann, P.A.; Lack, G.; Mazon, A.; Nieto, A.; Haddad, D.; Brough, H.A.; Caubet, J.C. Managing nut
allergy: A remaining clinical challenge. J. Allergy Clin. Immunol. Pract. 2017, 5, 296–300. [CrossRef]
55. Pascual, C.Y.; Fernandez-Crespo, J.; Sanchez-Pastor, S.; Padial, M.A.; Diaz-Pena, J.M.; Martin-Munoz, F.;
Martin-Esteban, M. Allergy to lentils in Mediterranean pediatric patients. J. Allergy Clin. Immunol. 1999, 103,
154–158. [CrossRef]
56. Martinez San Ireneo, M.; Ibanez, M.D.; Sanchez, J.J.; Carnes, J.; Fernandez-Caldas, E. Clinical features of
legume allergy in children from a Mediterranean area. Ann. Allergy Asthma. Immunol. 2008, 101, 179–184.
[CrossRef]
57. Moneret-Vautrin, D.A.; Guerin, L.; Kanny, G.; Flabbee, J.; Fremont, S.; Morisset, M. Cross-allergenicity of
peanut and lupine: The risk of lupine allergy in patients allergic to peanuts. J. Allergy Clin. Immunol. 1999,
104, 883–888. [CrossRef]
Nutrients 2019, 11, 359 13 of 16

58. Fiocchi, A.; Sarratud, P.; Terracciano, L.; Vacca, E.; Bernardini, R.; Fuggetta, D.; Ballabio, C.; Duranti, M.;
Magni, C.; Restani, P. Assessment of the tolerance to lupine-enriched pasta in peanut-allergic children.
Clin. Exp. Allergy 2009, 39, 1045–1051. [CrossRef] [PubMed]
59. Peeters, K.A.; Koppelman, S.J.; Penninks, A.H.; Lebens, A.; Bruijnzeel-Koomen, C.A.; Hefle, S.L.; Taylor, S.L.;
van Hoffen, E.; Knulst, A.C. Clinical relevance of sensitization to lupine in peanut-sensitized adults. Allergy
2009, 64, 549–555. [CrossRef]
60. Patel, A.; Bahna, S.L. Hypersensitivities to sesame and other common edible seeds. Allergy 2016, 71,
1405–1413. [CrossRef] [PubMed]
61. Allen, K.J.; Turner, P.J.; Pawankar, R.; Taylor, S.; Sicherer, S.; Lack, G.; Rosario, N.; Ebisawa, M.; Wong, G.;
Mills, E.N.C; et al. Precautionary labelling of foods for allergen content: Are we ready for a global framework?
World Allergy Organ. J. 2014, 7, 10. [CrossRef]
62. Moonesinghe, H.; Kilburn, S.; Mackenzie, H.; Venter, C.; Lee, K.; Dean, T. The prevalence of “novel” food
allergens worldwide: a systematic review. Clin. Transl. Allergy 2015, 5, 9. [CrossRef]
63. Adatia, A.; Clarke, A.E.; Yanishevsky, Y.; Ben-Shoshan, M. Sesame allergy: Current perspectives.
J. Asthma. Allergy 2017, 10, 141–151. [CrossRef] [PubMed]
64. Efsa Panel on Dietetic Products NaA. Scientific Opinion on Dietary Reference Values for fats, including
saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids,
and cholesterol. EFSA J. 2010, 8, 1461–1568.
65. Fernandez-Rivas, M. Fruit and vegetable allergy. Chem. Immunol. Allergy 2015, 101, 162–170. [PubMed]
66. Goikoetxea, M.J.; D’Amelio, C.M.; Martinez-Aranguren, R.; Gamboa, P.; Garcia, B.E.; Gomez, F.; Fernandez, J.;
Bartra, J.; Parra, A.; Alvarado, M.I.; et al. Is microarray analysis really useful and sufficient to diagnose nut
allergy in the mediterranean area? J. Investig. Allergol. Clin. Immunol. 2016, 26, 31–39. [PubMed]
67. Gomez, F.; Aranda, A.; Campo, P.; Diaz-Perales, A.; Blanca-Lopez, N.; Perkins, J.; Garrido, M.; Blanca, M.;
Mayorga, C.; Torres, M.J. High prevalence of lipid transfer protein sensitization in apple allergic patients
with systemic symptoms. PLoS One 2014, 9, e107304. [CrossRef] [PubMed]
68. Haroun-Diaz, E.; Azofra, J.; Gonzalez-Mancebo, E.; de Las Heras, M.; Pastor-Vargas, C.; Esteban, V.;
Villalba, M.; Diaz-Perales, A.; Cuesta-Herranz, J.I. Nut allergy in two different areas of Spain: Differences in
clinical and molecular pattern. Nutrients 2017, 9, 909. [CrossRef]
69. Moonesinghe, H.; Mackenzie, H.; Venter, C.; Kilburn, S.; Turner, P.; Weir, K.; Dean, T. Prevalence of fish and
shellfish allergy: A systematic review. Ann. Allergy Asthma. Immunol. 2016, 117, 264–272. [CrossRef]
70. Faber, M.A.; Pascal, M.; El Kharbouchi, O.; Sabato, V.; Hagendorens, M.M.; Decuyper, I.; Bridts, C.H.;
Ebo, D.G. Shellfish allergens: Tropomyosin and beyond. Allergy 2017, 72, 842–848. [CrossRef]
71. Sharp, M.F.; Lopata, A.L. Fish allergy: In review. Clin. Rev. Allergy Immunol. 2014, 46, 258–271. [CrossRef]
72. Stephen, J.N.; Sharp, M.F.; Ruethers, T.; Taki, A.; Campbell, D.E.; Lopata, A.L. Allergenicity of bony and
cartilaginous fish—Molecular and immunological properties. Clin. Exp. Allergy 2017, 47, 300–312. [CrossRef]
[PubMed]
73. Lopata, A.L.; Lehrer, S.B. New insights into seafood allergy. Curr. Opin. Allergy Clin. Immunol. 2009, 9,
270–277. [CrossRef] [PubMed]
74. Scott, P. Commins invited commentary: Alpha-gal allergy: Tip of the iceberg to a pivotal immune response.
Curr. Allergy Asthma. Rep. 2016, 16, 61.
75. Mullins, R.J.; James, H.; Platts-Mills, T.A.; Commins, S. Relationship between red meat allergy and
sensitization to gelatin and galactose-α-1,3-galactose. J. Allergy Clin. Immunol. 2012, 129, 1334–1342.
[CrossRef] [PubMed]
76. Steinke, J.W.; Platts-Mills, T.A.; Commins, S.P. The alpha-gal story: Lessons learned from connecting the
dots. J. Allergy Clin. Immunol. 2015, 135, 589–596. [CrossRef] [PubMed]
77. Meyer, R.; De Koker, C.; Dziubak, R.; Skrapac, A.K.; Godwin, H.; Reeve, K.; Chebar-Lozinsky, A.; Shah, N. A
practical approach to vitamin and mineral supplementation in food allergic children. Clin. Transl. Allergy
2015, 5, 11. [CrossRef] [PubMed]
78. Flammarion, S.; Santos, C.; Guimber, D.; Jouannic, L.; Thumerelle, C.; Gottrand, F.; Deschildre, A. Diet and
nutritional status of children with food allergies. Pediatr. Allergy Immunol. 2011, 22, 161–165. [CrossRef]
79. Vieira, M.C.; Morais, M.B.; Spolidoro, J.V.; Toporovski, M.S.; Cardoso, A.L.; Araujo, G.T.; Nudelman, V.;
Fonseca, M.C. A survey on clinical presentation and nutritional status of infants with suspected cow’ milk
allergy. BMC Pediatr. 2010, 10, 25. [CrossRef]
Nutrients 2019, 11, 359 14 of 16

80. Fleischer, D.M.; Conover-Walker, M.K.; Christie, L.; Burks, A.W.; Wood, R.A. Peanut allergy: Recurrence and
its management. J. Allergy Clin. Immunol. 2004, 114, 1195–1201. [CrossRef]
81. De Swert, L.F.A.; Gadisseur, R.; Sjolander, S.; Raes, M.; Leus, J.; Van Hoeyveld, E. Secondary soy allergy in
children with birch pollen allergy may cause both chronic and acute symptoms. Pediat. Allerg. Imm.UK 2012,
23, 118–124. [CrossRef]
82. Meyer, R.M.; Vieira, M.C.; Chong, K.W.; Chatchatee, P.; Vlieg-Boerstra, B.J.; Groetch, M.; Dominguez-Ortega, G.;
Heath, S.; Lang, S.; Archibald-Durham, L.; et al. International survey on growth indices and impacting factors in
children with food allergies. J. Hum. Nutr. Diet. 2018, in press. [CrossRef] [PubMed]
83. Christie, L.; Hine, R.J.; Parker, J.G.; Burks, W. Food allergies in children affect nutrient intake and growth.
J. Am. Diet. Assoc. 2002, 102, 1648–1651. [CrossRef]
84. Meyer, R.; De Koker, C.; Dziubak, R.; Godwin, H.; Dominguez-Ortega, G.; Shah, N. Dietary elimination
of children with food protein induced gastrointestinal allergy—Micronutrient adequacy with and without
a hypoallergenic formula? Clin. Transl. Allergy 2014, 4, 31. [CrossRef] [PubMed]
85. Toyran, M.; Kaymak, M.; Vezir, E.; Harmanci, K.; Kaya, A.; Ginis, T.; Kose, G.; Kocabas, C.N. Trace element
levels in children with atopic dermatitis. J. Investig. Allergol. Clin. Immunol. 2012, 22, 341–344. [PubMed]
86. Noimark, L.; Cox, H.E. Nutritional problems related to food allergy in childhood. Pediatr. Allergy Immunol.
2008, 19, 188–195. [CrossRef] [PubMed]
87. Ojuawo, A.; Lindley, K.J.; Milla, P.J. Serum zinc, selenium and copper concentration in children with allergic
colitis. East. Afr. Med. J. 1996, 73, 236–238. [PubMed]
88. Foong, R.X.; Meyer, R.; Dziubak, R.; Lozinsky, A.C.; Godwin, H.; Reeve, K.; Hussain, S.T.; Nourzaie, R.;
Shah, N. Establishing the prevalence of low vitamin D in non-immunoglobulin-E mediated gastrointestinal
food allergic children in a tertiary centre. World Allergy Organ. J. 2017, 10, 4. [CrossRef]
89. Thomassen, R.A.; Kvammen, J.A.; Eskerud, M.B.; Juliusson, P.B.; Henriksen, C.; Rugtveit, J. Iodine status
and growth in 0-2-year-old infants with cow’s milk protein allergy. J. Pediatr. Gastroenterol. Nutr. 2016, 64,
806–811. [CrossRef]
90. D’Auria, E.; Fabiano, V.; Bertoli, S.; Bedogni, G.; Bosetti, A.; Pendezza, E.; Sartorio, M.U.A.; Leone, A.;
Spadafranca, A.; Borsani, B.; et al. Growth Pattern, resting energy expenditure, and nutrient intake of
children with food allergies. Nutrients 2019, 11, 212. [CrossRef]
91. Seppo, L.; Korpela, R.; Lönnerdal, B.; Metsäniitty, L.; Juntunen-Backman, K.; Klemola, T.; Paganus, A.;
Vanto, T. A follow-up study of nutrient intake, nutritional status, and growth in infants with cow milk
allergy fed either a soy formula or an extensively hydrolyzed whey formula. Am. J. Clin. Nutr. 2005, 82,
140–145. [CrossRef]
92. BerniCanani, R.; Leone, L.; D’auria, E.; Riva, E.; Nocerino, R.; Ruotolo, S.; Terrin, G.; Cosenza, L.;
Di Costanzo, M.; Passariello, A.; et al. The effects of dietary counseling on children with food allergy:
A prospective, multicenter intervention study. J. Acad. Nutr. Diet. 2014, 114, 1432–1439. [CrossRef] [PubMed]
93. Goldberg, M.R.; Nachshon, L.; Sinai, T.; Epstein-Rigbi, N.; Oren, Y.; Eisenberg, E.; Katz, Y.; Elizur, A. Risk
factors for reduced bone mineral density measurements in milk-allergic patients. Pediatr. Allergy Immunol.
2018, 29, 850–856. [CrossRef] [PubMed]
94. Maslin, K.; Venter, C.; Mackenzie, H.; Vlieg-boerstra, B.; Dean, T.; Sommer, I. Comparison of nutrient intake
in adolescents and adults with and without food allergies. J. Hum. Nutr. Diet. 2018, 31, 209–217. [CrossRef]
[PubMed]
95. Giovannini, M.; D’auria, E.; Caffarelli, C.; Verduci, E.; Barberi, S.; Indinnimeo, L.; Iacono, I.D.; Martelli, A.;
Riva, E.; Bernardini, R. Nutritional management and follow up of infants and children with food allergy:
Italian Society of Pediatric Nutrition/Italian Society of Pediatric Allergy and Immunology Task Force
Position Statement. Ital. J. Pediatr. 2014, 40, 1. [CrossRef] [PubMed]
96. Mandell, D.; Curtis, R.; Gold, M.; Hardie, S. Anaphylaxis: How do you live with it? Health. Soc. Work 2005,
30, 325–335. [CrossRef]
97. Sommer, I.; Chisholm, V.; Mackenzie, H.; Venter, C.; Dean, T. Relationship between maternal and child
behaviors in pediatric food allergy–an exploratory study. Ann. Allergy. Asthma. Immunol. 2016, 116, 78–80.
[CrossRef]
98. Komulainen, K. Parental burden in families with a young food-allergic child. Child. Care Pract. 2010, 16,
287–302. [CrossRef]
Nutrients 2019, 11, 359 15 of 16

99. Fortunato, J.E.; Scheimann, A.O. Protein-energy malnutrition and feeding refusal secondary to food allergies.
Clin. Pediatr. 2008, 47, 496–499. [CrossRef]
100. Mukkada, V.A.; Haas, A.; Maune, N.C.; Capocelli, K.E.; Henry, M.; Gilman, N.; Petersburg, S.; Moore, W.;
Lovell, M.A.; Fleischer, D.M.; et al. Feeding dysfunction in children with eosinophilic gastrointestinal
diseases. Pediatrics 2010, 126, e672–e677. [CrossRef]
101. Rigal, N.; Reiter, F.; Morice, C.; De boissieu, D.; Dupont, C. Food allergy in the child: An exploratory study
on the impact of the elimination diet on food neophobia. Arch. Pediatr. 2005, 12, 1714–1720. [CrossRef]
102. Ng, I.E.; Turner, P.J.; Kemp, A.S.; Campbell, D.E. Parental perceptions and dietary adherence in children
with seafood allergy. Pediatr. Allergy Immunol. 2011, 22, 720–728. [CrossRef] [PubMed]
103. Sommer, I.; Mackenzie, H.; Venter, C.; Dean, T. An exploratory investigation of food choice behavior of
teenagers with and without food allergies. Ann. Allergy Asthma Immunol. 2014, 112, 446–452. [CrossRef]
[PubMed]
104. Sommer, I.; Mackenzie, H.; Venter, C.; Dean, T. Factors influencing food choices of food-allergic consumers:
Findings from focus groups. Allergy 2012, 67, 1319–1322. [CrossRef]
105. Berin, M.C.; Sampson, H.A. Mucosal immunology of food allergy. Curr. Biol. 2013, 23, 389–400. [CrossRef]
106. Hua, X.; Goedert, J.J.; Pu, A.; Yu, G.; Shi, J. Allergy associations with the adult fecal microbiota: Analysis of
the American Gut Project. E. Bio. Med. 2016, 3, 172–179. [CrossRef] [PubMed]
107. Berni, C.R.; Sangwan, N.; Stefka, A.T.; Nocerino, R.; Paparo, L.; Aitoro, R.; Calignano, A.; Khan, A.A.;
Gilbert, J.A.; Nagler, C.R. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing
bacterial strains in food allergic infants. ISME J. 2016, 10, 742–750. [CrossRef] [PubMed]
108. Azad, M.B.; Konya, T.; Guttman, D.S.; Field, C.J.; Sears, M.R.; HayGlass, K.T.; Mandhane, P.J.; Turvey, S.E.;
Subbarao, P.; Becker, A.B.; et al. CHILD Study Investigators. Infant gut microbiota and food sensitization:
Associations in the first year of life. Clin. Exp. Allergy 2015, 45, 632–643. [CrossRef] [PubMed]
109. Dong, P.; Feng, J.J.; Yan, D.Y.; Lyu, Y.J.; Xu, X. Early-life gut microbiome and cow’s milk allergy—
A prospective case—Control 6-month follow-up study. Saudi. J. BiolSci. 2018, 25, 875–880. [CrossRef]
110. Bunyavanich, S.; Shen, N.; Grishin, A.; Wood, R.; Burks, W.; Dawson, P.; Jones, S.M.; Leung, D.Y.M.; Sampson, H.;
Sicherer, S. Early-life gut microbiome composition and milk allergy resolution. J. Allergy ClinImmunol. 2016, 138,
1122–1130. [CrossRef]
111. Candy, D.C.A.; Van Ampting, M.T.J.; Oude Nijhuis, M.M.; Wopereis, H.; Butt, A.M.; Peroni, D.G.;
Vandenplas, Y.; Fox, A.T.; Shah, N.; West, C.E.; et al. A synbiotic-containing amino-acid-based formula
improves gut microbiota in non-IgE-mediated allergic infants. Pediatr. Res. 2018, 83, 677–686. [CrossRef]
112. BerniCanani, R.; Nocerino, R.; Terrin, G.; Coruzzo, A.; Cosenza, L.; Leone, L.; Troncone, R. Effect
of Lactobacillus GG on tolerance acquisition in infants with cow’s milk allergy: A randomized trial.
J. Allergy ClinImmunol. 2012, 129, 580–582. [CrossRef] [PubMed]
113. Ridaura, V.K.; Faith, J.J.; Rey, F.E.; Cheng, J.; Alexis, E.; Kau, A.L.; Griffin, N.W.; Lombard, V.; Henrissat, B.;
Bain, J.R.; et al. Cultured gut microbiota from twins discordant for obesity modulate adiposity and metabolic
phenotypes in mice. Science 2014, 341, 1241214. [CrossRef] [PubMed]
114. Bonder, M.J.; Kurilshikov, A.; Tigchelaar, E.F.; Mujagic, Z.; Imhann, F.; Vila, A.V.; Deelen, P.; Vatanen, T.;
Schirmer, M.; Smeekens, S.P.; et al. The effect of host genetics on the gut microbiome. Nat. Genet. 2016, 48,
1407–1412. [CrossRef] [PubMed]
115. Claesson, M.J.; Jeffery, I.B.; Conde, S.; Power, S.E.; O’Connor, E.M.; Cusack, S.; Harris, H.M.; Coakley, M.;
Lakshminarayanan, B.; O’Sullivan, O.; et al. Gut microbiota composition correlates with diet and health in
the elderly. Nature 2012, 488, 178–184. [CrossRef] [PubMed]
116. Ronteltap, A.; Van trijp, H.; Berezowska, A.; Goossens, J. Nutrigenomics-based personalised nutritional
advice: In search of a business model? Genes Nutr. 2013, 8, 153–163. [CrossRef] [PubMed]
117. Ordovas, J.M.; Ferguson, L.R.; Tai, E.S.; Mathers, J.C. Personalised nutrition and health. BMJ 2018, 361, 2173.
[CrossRef] [PubMed]
118. Van ommen, B.; Van den broek, T.; De hoogh, I.; van Erk, M.; van Someren, E.; Rouhani-Rankouhi, T.;
Anthony, J.C.; Hogenelst, K.; Pasman, W.; Boorsma, A.; et al. Systems biology of personalized nutrition.
Nutr. Rev. 2017, 75, 579–599. [CrossRef]
119. Miller, L.M.; Cassady, D.L. The effects of nutrition knowledge on food label use. A review of the literature.
Appetite 2015, 92, 207–216. [CrossRef]
Nutrients 2019, 11, 359 16 of 16

120. Bahri, R.; Custovic, A.; Korosec, P.; Tsoumani, M.; Barron, M.; Wu, J.; Sayers, R.; Weimann, A.;
Ruiz-Garcia, M.; Patel, N.; et al. Mast cell activation test in the diagnosis of allergic disease and anaphylaxis.
J. Allergy ClinImmunol. 2018, 142, 485–496. [CrossRef]
121. Ross, G.M.S.; Bremer, M.G.E.G.; Nielen, M.W.F. Consumer-friendly food allergen detection: Moving towards
smartphone-based immunoassays. Anal. Bioanal.Chem. 2018, 410, 5353–5371. [CrossRef]
122. Abrahams, M.; Frewer, L.J.; Bryant, E.; Stewart-Knox, B. Perceptions and experiences of early-adopting
registered dietitians in integrating nutrigenomics into practice. Br. Food J. 2018, 120, 763–776. [CrossRef]

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