Toxicology 93"(1994) 77-83

IOXICI]IOGY
ELSEVIER

Role of new allergens and of allergens

consumption in the increased incidence
of food sensitizations in France *

Fran~oise Andr6 *a, Claude Andr6 a'b, Lise Colin a,

Florina Cacaraci b, Sylvie Cavagna a
aLaboratoire d'lmmunopathologie Digestive, INSERM, Pavilion IG,
Centre Hospitalier Lyon-Sud, 69310 Pierre B~nite, France
bStallergbnes S.A., 7 All~e des Platanes, 94264 Fresnes Cedex, France

Received 5 November 1993; accepted 25 February 1994

Abstract

Food allergy is a group of distinct clinico-pathological entities that have an immunological

basis in common, and in which an abnormal or exaggerated immunological response to a spe-
cific food leads to disease. Some clinical pictures involving multiple organ system (anaphyl-
axis) are potentially fatal. The data on the incidence, prevalence, mortality rate and food
products involved in food-induced anaphylaxis and the evolution of food sensitization com-
pared with changes in eating habits are not very reliable. In the present study we analysed,
over a period of 9 years (1984-1992), a group of 580 patients with pathological reactions to
foods, 60 of which presented severe, near-fatal reactions. We sought the etiologic components
and food sensitization in comparison with the principal tendencies of food consumption in
France. Food products most frequently incriminated in anaphylactic reactions are not of a
primary nutritional importance: celery (30%), crustaceans (17%), fish (13%), peanuts (12%),
mango (6%), mustard (3%), but they are often hidden allergens in commercial foods. The sen-
sitization to food products in the group of 580 patients reveals, in decreasing order of frequen-
cy: wheat (39%), peanuts (37%), crab (34%), celery (30%), soy (30%). Compared with previous
data, the frequency of sensitization to different foods has changed; for instance, the sensitiza-
tions to wheat, soy, peanuts, celery, mustard, rice, are definitely increasing. The increased con-
sumption and more attentive clinical research may be the reasons for this evolution. For
products such as egg and pork, the data are stable and parallel with consumption, whilst for
other products like milk and other dairy products, the increased consumption is accompanied
by a decrease of the incidence of sensitization. The reactivity to some allergens may be affected
by the way of preparing the food.

*Presented at the Second Summer School in lmmunotoxicology, Beaune, France, 13-15 October
1993.
*Corresponding author.

0300-483X/94/$07.00 © 1994 Elsevier Science Ireland Ltd. All rights reserved

SSDI 0300-483X(94)02878-X
78 F. AndrO et al. / Toxicology 93 (1994) 77-83

Keywords: Food sensitization; Food allergens; Anaphylaxis; Food consumption; Epide-

miology

1. Introduction

The digestive tract of man has a remarkable capacity to adapt to different patterns
of eating as well as to the enormous variety of foods which are consumed. Regula-
tory mechanisms exist for the induction and suppression of immunological reactions
to the antigens of ingested food (Andr6 et al., 1974, 1975; Richman et al., 1978; La-
font et al., 1982) and an abnormal immune response to food antigens is defined as
food allergy. A cause-and-effect relationship between specific antibodies and/or im-
munocompetent cells on the one hand, and clinical symptoms on the other hand, is
required for the diagnosis of food allergy. In many cases of clinical reactions to food,
an immunological mechanism will not be demonstrable and in these cases the term
'intolerance' is preferable and the concept of pseudo-allergy is more or less
synonymous with intolerance. The term intolerance should be further elaborated,
not only by describing its signs and provoking products, but also by speculating on
the operative mechanism that might be involved. Thus, reference can be made to
food intolerance due to non-IgE mediated mast cell degranulation or to biogenic
amine loads contained in food.
Food products may be food allergens, that trigger a pathological reaction through
an immunological mechanism, or they may be constituents capable of provoking a
reaction without involvement of the immune system: food allergy and food in-
tolerance, respectively. The manifestations ascribed to food hypersensitivity enclose
a wide spectrum, although it is not known why the manifestations of food allergy
and intolerance differ between individuals since the same food allergen may cause
quite different complaints in different patients.
A wide range of symptoms have been described:

• gastrointestinal symptoms: vomiting, diarrhoea, abdominal pain (colic),

malabsorptive disorders;
• respiratory manifestations: rhinitis, asthma;
• cutaneous manifestation: urticaria, oedema, pruritis, atopic dermatitis; and
• anaphylaxis (shock).

Anaphylaxis is an acute, and in principle life-threatening, immunological

generalized reaction that results from sudden mast cell degranulation with mediators
release. Mast cell degranulation on a non-immunological basis is called anaphyla-
toi'd reaction. The failure to recognize the severity of these reactions and to adminis-
ter epinephrine promptly increases the risk of a fatal outcome. The data on the
incidence, prevalence or mortality rate for food-induced anaphylaxis are not very
reliable. Fatal food-induced anaphylaxis is rarely reported although Yunginger et al.
(1988) described seven cases of fatal post-prandial anaphylaxis and Sampson et al.
(1992) reported six children and adolescents who died of anaphylactic reactions to
 F. Andr~ et al. / Toxicology 93 (1994) 77-83 79

food and seven others who experienced near-fatal anaphylactic reactions. The foods
most frequently incriminated as a trigger of anaphylaxis were: peanuts (eight cases),
nuts (six cases), pecan (one), crab (one), fish (one), egg (one) and milk (one). How-
ever, recently the spectrum has become wider with, for instance, two cases of
anaphylactic reactions set off by the ingestion of a small amount of mustard sauce
(Montreal et al., 1992), and a case of anaphylaxis caused by banana (Savonius and
Kanerva, 1993) was also reported, completing the picture of severe reactions to food.
It may be noted that the foods which are the most implicated in food-induced ana-
phylaxis are not part of everyday food, but the low number of reports in the medical
literature does not permit general conclusions with regard to food products that are
involved in severe reactions and the evolution of food sensitization compared with
changes in eating habits. In the present study we analysed, over a period of 9 years
(1984-1992), a group of 580 patients with pathological reactions to food, comparing
the evolution of food sensitization with the main tendencies of food consumption
in France.
In a group of 60 of these patients who presented severe reactions to foods, at-
tempts were made to determine the most frequently involved food products in ana-
phylaxis.

2. Patients and methods

Over a period of 9 years (1984-1992), 580 patients, 480 adults and 100 children,
with a mean age of 30 (range, 1-83), 290 females and 290 males, were investigated
for food allergy in the same clinical department and proved to have both food sensi-
tization and food allergy to at least one substance by an oral provocation test, except
in those with anaphylaxis. The clinic pictures included urticaria (in 254 cases), atopic
dermatitis (172), asthma and/or rhinitis (54), anaphylaxis (60), and irritable bowel
syndrome (40).
In the group of 60 patients with severe reactions to food, consisting of 41 women
and 19 men aged between 15 and 83 years with a mean age of 34, 52 experienced
anaphylactic shocks (two with cardiac arrest), six had angioedema (one needing tra-
cheal intubation and another tracheotomy) and two severe bronchospasms that
needed mechanical ventilation.
In order to identify the sensitizations, a clinical history was completed for all of
the patients. Skin tests were made with the prick test technique in all the patients
to whom antihistaminic drugs had not been administered. The tests were made on
the volar part of the forearm by using Stallerpoint needles and the following solu-
tions: (i) glycerol food extracts; (ii) glycerol solvent for the negative reference solu-
tion; and (iii) codein phosphate at 9% for the positive reference solution (Stallerg6nes
S.A., Fresnes, France). Sometimes tests were also made with fresh food extracts by
the method prick by prick. Skin tests were considered as positive if the diameter of
the weal was at least 5 mm and 3 mm larger than that of the negative reference test.
Tests were made systematically for egg, cow milk, wheat, soy, peanut, orange, crab,
fish, celery, tomato, pork, and baker's yeast. The other foods tested depended o n
each individual's clinical history.
80 F. Andrd et al. / Toxicology 93 (1994) 77-83

Specific IgE were assayed on a plasma sample by the radioimmunological method

(RAST, Pharmacia, Uppsala, Sweden) following the producer's instructions. The
following tests were made systematically: peanut, wheat, celery, crab, cow milk pro-
teins, egg white, onion, orange, parsley, fish, pork, soy, and tomato. The remaining
specific IgE tests were made on the basis of each individual's clinical history.
The evolution of sensitization to food products was compared with statistical
data, obtained from the French Institut National de la Statistique et des Etudes
Economiques, on the evolution of food products consumption over the same period
(Abramovici, 1992).

3. Results

In the group of 60 cases with severe reactions to food, the most frequently im-
plicated products were: celery (30%), crustaceans (17%), fish (13%), peanuts (12%),
mango (7%), mustard (3%). The detailed results are shown in Table 1.
The only food sensitizations that were taken into account in the 580 patients were
those identified by the presence of plasma IgEs. Indeed, the reactivity of skin tests
clearly proved to be too weak: for instance, in the same patients the positivity was
only 25% for wheat and soy, 24% for peanut, 37% for crab, 29% for celery and 26%
for cow milk proteins.
The sensitization to food products in the group of 580 patients reveals, in decreas-
ing order of frequency: wheat (39%), peanuts (37%), crab (34%), celery (30%), soy
(30%); the detailed results are shown in Table 2. Over the 1984-1992-period there

Table 1
Food Involved in anaphylactic reactions, Lyon - - 1984-1992

Food Incidence frequency

Celery 18
Crab 10
Fish
Peanut
Mango
Mustard
Soy
Lychee
Kiwi
Cow milk
Egg
Almond
Coconut
White bean
Ewe milk
Avocado
Beef
Orange
Camomile
 F. Andr~ et al. / Toxicology 93 (1994) 77-83 81

A A A A A A
II ~ ~ II

~4
II

,.D

@
e~

,.~ 0 0 @
o
a~
82 F. Andr6 et al. / Toxicology 93 (1994) 77-83

was an increase in frequency for allergens such as wheat, soy, yeast, onion, garlic,
rice, rye and mustard. The frequency is relatively stable for peanuts, crab, shrimp,
celery, fish, orange, egg, pork, hazel nut and apple, and there was a gradual decrease
in frequency for milk, potato, carrot and strawberry. For comparison, the changes
in the consumption of food products (Abramovici, 1992) are shown in Table 2.
There was a gradual decrease in the consumption of bread, but a significant increase
for cereals (20%), a gradual increase for milk but a significant increase for dairy pro-
duce (> 40%), a significant increase for rice (> 50%), for seasoning sauces (> 55%),
for tinned, canned, bottled, deep-frozen foods ( > 40%), fish ( > 18%), fresh fruits and
vegetables (> 18%). Eggs, beef and pork consumption were stable but potato con-
sumption decreased.

4. Discussion

It may be noted that better modern diagnosis and greater skill of physicians con-
tribute significantly to the increase of food sensitization. However, the present study
clearly shows that the incidence of food sensitization is increasing regularly. This ob-
servation is consistent with the observation of a general increase of atopy in other
countries like Japan (Nakagomi et al., 1994). As far as food sensitization is con-
cerned, symptoms caused by an allergy to fruits and vegetables have been also
reported more frequently in Italy (Ortolani et al., 1993). The number of patients
reported by these authors was also very high with 706 observations, and anaphylaxis
present in 2%.
The data collected in the 580 patients from the present study show clearly that the
sensitivity of skin-prick tests, averaging at best 25%, is too low to be considered as
satisfactory in an epidemiological study; this report relies on plasma specific IgE
determination only. Methodological limitations of the present study should be men-
tioned: a possible development of the sensitivity of the RAST assay over the con-
cerned period, restrictive research on food sensitization as a function of clinical
history,and changes in the medical approach to food allergy by physicians.
As in the other studies mentioned (Yunginger et al., 1988; Montreal et al., 1992;
Sampson et al., 1992; Savonius and Kanerva, 1993), the food products frequently
involved in. anaphylaxis are not of primary nutritional importance. Some have a high
frequency of sensitization (peanuts, celery, crustaceans, fish), whilst others are less
frequent, but all may be masked in many preparations. A real problem is how to
avoid hidden allergens in commercial foods, as most dramatic accidents occurred
after dining away from home or by unknowingly ingesting the foods responsible for
the reactions.
The sensitization to food products in the whole group of patients of the present
study reveals the increase in frequency to allergens such as wheat, soy, yeast, onion,
tomato, garlic, rice, rye, white beans, orange and mustard. In comparison with pre-
vious data on the frequency of sensitization to different food products in France
(Moneret-Vautrin and Andre, 1983) there are notable differences. For instance, the
sensitization to peanuts (4%), wheat (4%), celery (7%), and mustard (1%) increased
significantly and other products like rice and soy, which were not mentioned in these
data, appear to be important allergenic products.
 F. Andr~ et al. / Toxicology 93 (1994) 77-83 83

Increased c o n s u m p t i o n a n d a more attentive clinical e x a m i n a t i o n may be reasons

for this evolution. F o r example, sensitization to rice followed the increase of rice
c o n s u m p t i o n , sensitization to wheat parallels c o n s u m p t i o n of cereals in spite of the
decrease in bread c o n s u m p t i o n . Despite an increased c o n s u m p t i o n , one may observe
a stable but already high frequency of sensitization to peanuts (37%), crab (34%),
celery (30%).
Surprisingly, a significant increase in dairy produce c o n s u m p t i o n corresponds to
a stable or slow rate of decrease of sensitization to milk a n d some allergens may be
affected by the m e t h o d of preparing the food.
Patterns of cross allergenicity may also interfere in drawing up the clinical picture.
Cross allergenicity a m o n g celery - - c u c u m b e r - - carrot - - watermelon a n d between
p e a n u t - - soy - - garden peas - - haricot beans or between hazelnut - - rye grain - -
sesame seeds - - kiwis - - p o p p y seeds has d e m o n s t r a t e d by possession of c o m m o n
allergenic structures. However, the differing developments of sensitization to peanut
(which remains stable) a n d soy (which increases) or the sensitization to tomato
(which increases) a n d potato (which decreases), although belonging to the same veg-
etable family, prove that cross allergenicity is n o t a d e t e r m i n a n t factor. The fact that
specific IgEs were assayed systematically or not systematically in the 580 patients did
not modify the conclusions.
Essentially, the present tendency of sensitization, of a c o n t i n u o u s increase, follows
the changes in eating habits.

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