Agnieszka Kosmowska, Krystyna Mowszet, Barbara Iwańczak

ORIGINAL PAPERS
Adv Clin Exp Med 2006, 15, 3, 445–451
ISSN 1230−025X
© Copyright by Silesian Piasts
University of Medicine in Wrocław
AGNIESZKA KOSMOWSKA, KRYSTYNA MOWSZET, BARBARA IWAŃCZAK
Assessment of the Frequency of Food Allergy
in Children with Gastroesophageal Reflux Disease
Ocena częstości występowania alergii pokarmowej
u dzieci z chorobą refluksową przełyku
Department of Pediatrics, Gastroenterology, and Nutrition, Silesian Piasts University of Medicine in Wrocław,
Poland
Abstract
Background. Food allergy may be a cause of pathological gastroesophageal reflux. A 24−hour esophageal pH tra−
cing pattern typical for food allergy was described in the literature.
Objectives. The assessment of the frequency of food allergy in children under 3 years of age with gastroesopha−
geal reflux disease.
Material and Methods. The analysis comprised a group of 28 children (11 girls and 17 boys) aged 3–36 months
(average: 12.6 months) in whom gastroesophageal reflux disease was diagnosed based on clinical symptoms and
24−hour esophageal pH−metry. Patient medical history, family history, physical examination, immunological tests
(total serum IgE, blood eosinophilia, skin prick tests with native food allergens), and trials of elimination and pro−
vocation with food allergens (lasting 3–6 months) were the grounds for diagnosis.
Results. In the analyzed group of children with gastroesophageal reflux disease, food allergy was recognized in 12
patients (42.8%). Allergy to cow’s milk, egg yolk, and egg white were the most frequent.
Conclusions. Based on presented studies it can be concluded that in the group of children aged 3–36 months with
gastroesophageal reflux disease, food allergy was observed significantly more frequently (42.8%) than in the gene−
ral population (2–4%). In 25% of the children a biphasic pattern of the esophageal pH tracing typical for food al−
lergy was observed (Adv Clin Exp Med 2006, 15, 3, 445–451).
Key words: food allergy, gastroesophageal reflux disease, children.
Streszczenie
Wprowadzenie. Alergia pokarmowa może powodować częstsze występowanie patologicznego refluksu żołądko−
wo−przełykowego. W piśmiennictwie przedstawiono również charakterystyczny zapis 24−godzinnej pH−metrii
u części dzieci chorych na alergię pokarmową.
Cel pracy. Ocena częstości występowania alergii pokarmowej u dzieci do lat 3 z rozpoznaną chorobą refluksową
przełyku.
Materiał i metody. Badaniami objęto grupę 28 dzieci (11 dziewczynek i 17 chłopców) w wieku 3–36 miesięcy
(średnia wieku: 12,6 miesiąca), u których na podstawie objawów klinicznych i 24−godzinnej pH−metrii przełyku
rozpoznano chorobę refluksową. Podstawą do rozpoznania alergii pokarmowej był wywiad zarówno osobniczy, jak
i rodzinny, badanie przedmiotowe, wyniki badań alergologicznych: eozynofilia w rozmazie krwi obwodowej, cał−
kowitego stężenia IgE w surowicy krwi, a u dzieci powyżej 5. m.ż. – punktowe testy skórne z natywnymi alerge−
nami pokarmowymi (pod uwagę brano 6–12 alergenów) oraz wyniki próby eliminacji i prowokacji pokarmowej
(3–6 miesięcy).
Wyniki. W analizowanej grupie dzieci z rozpoznaną chorobą refluksową przełyku alergię pokarmową (na białka
mleka krowiego, żółtko i białko jaja) rozpoznano u 12 pacjentów (42,8%). Najczęściej rozpoznawano alergię na
białka mleka krowiego, żółtko i białko jaja.
Wniosek. Na podstawie przeprowadzonych badań stwierdzono, że w grupie dzieci 3–36 miesięcy z rozpoznaną
chorobą refluksową przełyku znacznie częściej (42.8%) rozpoznano alergię pokarmową niż w populacji ogólnej
(2–4%). U 3/12 dzieci stwierdzono dwufazowy zapis pH−metryczny charakterystyczny dla alergii pokarmowej
(Adv Clin Exp Med 2006, 15, 3, 445–451).
Słowa kluczowe: alergia pokarmowa, choroba refluksowa przełyku, dzieci.
446
Gastroesophageal reflux disease (GERD)
comprises a number of clinical symptoms that are
triggered by a pathological retrograde movement
of acidic content from the stomach to the esopha−
gus [1, 3]. Pathological gastroesophageal reflux is
associated with dysfunction of the lower esopha−
geal sphincter, disturbances in esophageal clearance,
and delayed gastric emptying [2]. Two types of pa−
thological gastroesophageal reflux can be distin−
guished: primary and secondary. Primary reflux is
related to anatomical and functional disturbances
in esophageal motility, while secondary esophage−
al reflux develops in the course of other systemic
diseases, such as metabolic and neurological dis−
eases, which are associated with a reduced muscu−
lar tone, food allergy, and the use of certain drugs
(methylxanthines, calcium channel blockers, and
others) [3–5, 7, 10].
Many authors emphasize the more frequent
coexistence of pathological gastroesophageal re−
flux with food allergy in children younger than
three years old. In infancy, this frequency can re−
ach 40%. There is a pathogenetic cause−and−effect
relationship between these conditions. The main
allergen responsible for the observed symptoms is
cow’s milk protein [7–10].
Among the clinical symptoms of GERD in
small children are regurgitation, vomiting, lack of
thriving, disturbances in growth, recurrent infec−
tions of the upper and lower respiratory tract,
anxiety, irritability, disturbed sleep, fetor ex ore,
and episodes of coughing and apnea. These symp−
toms and findings are frequently similar to those
of food allergy [12]. Therefore it is difficult to dis−
tinguish between primary gastroesophageal reflux
and reflux secondary to food allergy when taking
into account only the clinical picture. Chronic rhi−
nitis, atopic dermatitis, and diarrhea are more fre−
quently observed in children with coexisting food
allergy and gastroesophageal reflux [5–7, 15].
Analysis of the graphical pattern of esophage−
al pH−metry helps to discriminate between gastro−
esophageal reflux secondary to food allergy and
primary gastroesophageal reflux. In allergy to
cow’s milk protein, both isolated and associated
with gastroesophageal reflux, a provocation by
milk formula causes a rapid increase in esophage−
al pH with a subsequent gradual decrease till the
next feeding; in primary gastroesophageal reflux,
such a pattern, strictly correlated with meals, is not
observed [5–10, 12, 15, 16].
The diagnosis of gastroesophageal reflux se−
condary to food allergy is particularly important in
the choice of treatment method. The basic method
in the treatment of gastroesophageal reflux secon−
dary to food allergy is the introduction of elimina−
tion diets: formulas based on casein hydrolysates
A. KOSMOWSKA, K. MOWSZET, B. IWAŃCZAK
and whey proteins, hypoallergic diets, and anti−al−
lergic drugs.
The objective of the present study was to esti−
mate the frequency of food allergy in children
under three years of age with gastroesophageal re−
flux disease.
Material and Methods
The analysis comprised a group of 28 children
younger than three years old (range: 3–36 months,
average: 12.6 months) in whom, based on medical
history, physical examination, and clinical observa−
tion, an indication for 24−hour esophageal pH−metry
was established and GERD was diagnosed. The
group consisted of 11 girls (39.28%) and 17 boys
(60.72%). Twenty−four−hour esophageal pH−metry
was performed using a two−channel antimonic elec−
trode. The tip of the probe was positioned in the eso−
phagus according to the Strobel rule (at 87% of the
distance between the anterior nostrils and lower eso−
phageal sphincter). Pathological acid reflux was
diagnosed based on the total number of acid reflux
episodes (≥ 50), the number of acid reflux episodes
lasting more than 5 minutes (≥ 2), and the percentage
of the time of exposure of the gastric mucosa to a pH
below 4 (in infants ≥ 5% of the entire duration of the
investigation and in older children ≥ 3.4%) [17].
In part of the studied patients (15 children,
53.8%) in whom previous medical history (e.g. se−
vere persistent vomiting) could indicate an anato−
mical defect, a contrast X−ray study of the upper
gastrointestinal tract was performed.
The following factors were analyzed in the
children: physical development using the percentile
charts of Palczewska, clinical manifestations ac−
companying GERD, results of allergic and immu−
nological studies, and selected laboratory tests.
Allergy was diagnosed on the basis of the pa−
tient’s medical history, family history, physical
examination, laboratory tests, i.e. eosinophil count,
total serum IgE, and, additionally in children older
than 5 months, allergic skin prick test with native
food allergens (6–12 of the most common food al−
lergens were taken into consideration), and long−
term monitoring of elimination of suspected food
products and provocation trials (lasting 3 to 6
months).
Statistical analysis was performed using the χ2
test, where p < 0.05 was regarded as significant.
Results
The study group of 28 children with patholo−
gical gastroesophageal reflux included 18 infants
(64.29%) and 10 children aged 13 to 36 months
Assessment of the Frequency of Food Allergy in Children with Gastroesophageal Reflux Disease
447
Fig. 1. pH−metric record in food allergy co−existing gastroesophageal reflux disease in child of the investigated group
Ryc. 1. Zapis pH−metryczny w chorobie refluksowej przełyku współistniejącej z alergią pokarmową u dziecka z gru−
py badanej
Fig. 2. pH−metric record in gastroesophageal reflux disease in child of the investigated group (primary reflux)
Ryc. 2. Zapis pH−metryczny w chorobie refluksowej przełyku u dziecka z grupy badanej (refluks pierwotny)
(35.71%). There were more boys (60.7%) in the
studied group of children. In all the children, pa−
thological acidic gastroesophageal reflux was diag−
nosed based on a 24−hour pH−metric tracing. In
12 children (7 infants and 5 older children) food
allergy was recognized. A biphasic pH−metric tra−
cing typical for food allergy was observed in 3 ca−
ses (Fig. 1). In the remaining cases, such a strict
correlation of pH tracing with meals was not obse−
rved (Fig. 2).
Anatomical developmental abnormalities of
the esophagus, stomach, and duodenum were ex−
cluded by contrast X−ray study of the upper intesti−
nal tract.
In the studied group of children the following
symptoms were the most frequent clinical manife−
stations: regurgitation in 78.57% (22 children), vo−
miting in 64.28% (18 children), lack of thriving in
42.85% (12 children), and atopic dermatitis in
32.14% (9 children). Additionally, in the medical
histories of 32.14% of the children (9 children) an
increased frequency of recurrent bronchitis and
pneumonia was reported, and in 25.0% (7 chil−
dren) a chronic cough. Two children (7.15%) were
under allergologist care due to diagnosed bron−
chial asthma. Malnutrition (body mass below the
3rd percentile) was observed in about one third of
described patients (35.7%). According to parents,
448
A. KOSMOWSKA, K. MOWSZET, B. IWAŃCZAK
among the most disturbing symptoms were anxie−
ty (17.85%, 5 cases), disturbed sleep (17.85%,
5 children), and recurrent otitis media (7.15%,
2 children). Recurrent diarrhea was observed in
5 patients (17.85%) (Table 1).
The frequency of the symptoms listed above
was similar in children with and without food al−
lergy. With the exception of atopic dermatitis,
which was more frequent in children with food al−
lergy, there were no statistically significant diffe−
rences (Table 1).
Family history of allergy was reported in 6 ca−
ses (21.42%), polinosis in parents or siblings and
cow’s milk allergy in siblings being the most fre−
quent.
The results of selected laboratory tests are pre−
sented in Table 2. Anemia was the most frequently
observed disturbance and was diagnosed in
42.85% (12 children); in 8 cases (28.57%) it was
accompanied by a decreased iron level. Eosinophi−
lia was observed in 17.85% of cases. In 14.28%
(4 children) total serum IgE was elevated, in
22.14% (9 children) the skin prick test with native
food allergens was positive, most frequently with
cow’s milk protein (5 children, 29.41%), egg yolk
(4 children, 23.52%), and egg white (3 children,
17.64%). Increased total IgE and positive skin
prick tests were observed exclusively in children
with food allergy, with the difference in frequency
on the border of significance and significant, res−
pectively. A trial of cow’s milk allergen elimina−
tion for three to six months followed by provoca−
tion with allergen was positive in 12 children
(42.85%). Clinical observation and the tests de−
scribed above confirmed food allergy in 12 chil−
dren (42.85%), with a prevalence of boys (9 vs. 3).
Table 1. Clinical symptoms accompanying GERD
Tabela 1. Objawy kliniczne towarzyszące GERD
Clinical symptoms
(Objawy kliniczne)
Total
(Ogółem)
n = 28
a (%)
Children
with GERD
– without food
allergy
(Dzieci z GERD
bez alergii
pokarmowej)
n = 16
b (%)
Children with
GERD and
food allergy
(Dzieci z GERD
i alergią
pokarmową)
n = 12
c (%)
Statistic
significance
(Istotność
statystyczna)
(b−c)
Regurgitation
(Ulewania)
22 (78.57)
12 (75)
10 (83.3)
ns.
Vomiting
(Wymioty)
18 (64.28)
11 (68.75)
7 (58.3)
ns.
Anorexia
(Brak łaknienia)
12 (42.85)
5 (31.25)
7 (58.3)
ns.
Malnutrition
(Niedożywienie)
10 (35.7)
4 (25)
6 (50)
ns.
Atopic dermatits
(Zmiany skórne typu a.z.s.)
9 (32.14)
0 (0)
9 (75)
0.001
Recurrent bronchitis and pneumonia
(Nawracające zapalenia oskrzeli i płuc)
9 (32.14)
4 (25)
5 (41.6)
ns.
Chronic cough
(Przewlekły kaszel)
7 (25)
4 (25)
3 (25)
ns.
Irritability
(Rozdrażnienie)
5 (17.85)
2 (12.5)
3 (25)
ns.
Sleeping disturbances
(Niespokojny sen)
5 (17.85)
3 (18.75)
2 (16.6)
ns.
Recurrent diarrhoea
(Nawracające biegunki)
5 (17.85)
1 (6.25)
4 (33.3)
ns.
Otitis media
(Zapalenia ucha środkowego)
2 (7.14)
1 (6.25)
1 (8.3)
ns.
Astma oskrzelowa
(Bronchial asthma)
2 (7.14)
1 (6.25)
1 (8.3)
ns.
Nieżyt nosa
(Rhinitis)
2 (7.14)
0 (0)
2 (16.6)
ns.
449
Assessment of the Frequency of Food Allergy in Children with Gastroesophageal Reflux Disease
Tabela 2. Abnormal results of selected diagnostic investigations
Table 2. Wybrane nieprawidłowości w badaniach dodatkowych
Abnormal results
(Nieprawidłowe wyniki)
Total
(Ogółem)
n = 28
a (%)
Children
with GERD
– without food
allergy
(Dzieci z GERD
bez alergii
pokarmowej)
n = 16
b (%)
Children with
GERD and
food allergy
(Dzieci z GERD
i alergią
pokarmową)
n = 12
c (%)
Statistic
significance
(Istotność
statystyczna)
(b−c)
Anaemia
(Niedokrwistość)
12 (42.85)
7 (43.75)
5 (41.66)
ns.
Sideropenia
(Sideropenia)
8 (28.57)
4 (25)
4 (33.3)
ns.
Eosinophilia
(Eozynofilia)
5 (17.85)
1 (6.25)
4 (33.3)
ns.
Increased total IgE blood concentration
(Podwyższone stężenie IgE całk. w surowicy)
4 (14.28)
0 (0)
4 (33.3)
0.0513
Positive skin prick tests results
(Dodatnie testy skórne z natywnymi
alergenami pokarmowymi)*
9/17 (52.94)
0/5 (0)
9/12 (75)
0.0045
* skin prick tests were carried out in 17 children.
* testy skórne wykonano u 17 dzieci.
n – number.
n – liczba badanych.
ns. – not significant.
ns. – nieistotny.
Discussion
The coexistence of GERD with food allergy in
children under 3 years old is a frequent phenome−
non. As shown in present study, food allergy is ob−
served in 42.85% of children with pathological ga−
stroesophageal reflux (in 38.89% of the infants
and 50% of the children aged 13–36 months). Ac−
cording to Iacono et al. [14], who conducted a stu−
dy on infants, food allergy was diagnosed in
41.8% of children with pathological gastroesopha−
geal reflux. Semeniuk et al. [16] found cow’s milk
allergy in 43% of children aged 2–15 months with
gastroesophageal reflux. Janiszewska and Czer−
wionka−Szaflarska [12] studied a large group of
children aged 1–16 years (excluding infants) with
diagnosed acidic gastresophageal reflux based on
24−hour esophageal pH−metry and in 48% of the
cases found IgE−dependent food allergy.
The frequency of gastroesophageal reflux in
children with diagnosed food allergy is also simi−
lar: 30–40% according to Semeniuk et al. [6] and
46.5% according to Kamer et al. [4]. The results
obtained in present study resemble those of other
authors.
Graphical analysis of the pH−metric recording
in most cases allows for the distinction between
primary and secondary pathological gastroesopha−
geal reflux. In described material the authors obse−
rved a typical biphasic pattern, which correlated
with feeding in about 25% of the children with
food allergy. In the remaining cases the pH−metric
pattern was different, which suggests primary ga−
stroesophageal reflux coexisting with food allergy.
Attention was first drawn to the typical pattern of
the esophageal pH tracing in children with coexi−
sting food allergy and pathological gastroesopha−
geal reflux by Iacono et al. [14] and Cavataio et al.
[5, 15]. It should be emphasized that the clinical
pictures of food allergy and gastroesophageal re−
flux disease in the group of the youngest children
is similar (regurgitation, vomiting, recurrent respi−
ratory tract infections, unsatisfying body mass in−
crease). Diarrhea and rhinitis were slightly more
frequently observed in children with coexisting
food allergy and GERD than in isolated pathologi−
cal gastroesophageal reflux (the difference not stati−
stically significant). Atopic dermatitis was statisti−
cally significantly more frequent in the first group.
The obtained results are of great practical va−
lue. The recognition of an allergic background of
GERD permits effective therapy. The therapeutic
methods used in the treatment of primary gastroe−
sophageal reflux, i.e. positional therapy, increased
450
A. KOSMOWSKA, K. MOWSZET, B. IWAŃCZAK
density of formulas, prokinetic drugs, and proton
pump inhibitors, applied to secondary gastroeso−
phageal reflux caused by food allergy do not yield
improvement. The most important stage in the
treatment of the latter condition should be the in−
troduction of elimination diet and, in some cases,
anti−allergic drugs.
In described group of children with GERD co−
existing with food allergy the authors observed
subsiding or at least significant alleviation of clini−
cal symptoms after the introduction of elimination
diet, anti−allergic drugs and, in some cases, proki−
netics.
Based on the study described above, it can be
concluded that in the group of children aged 3–36
months with GERD, food allergy was observed
significantly more frequently (42.8%) than in the
general population (2–4%). In 25% of the children
a biphasic pattern of the esophageal pH tracing, ty−
pical for food allergy, was observed.
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Assessment of the Frequency of Food Allergy in Children with Gastroesophageal Reflux Disease
Address for correspondence:
Agnieszka Kosmowska
Katedra i Klinika Pediatrii, Gastroenterologii i Żywienia AM
ul. M. Skłodowskiej−Curie 50/52
50−369 Wrocław
Poland
Tel.: +48 071 32 00 803
e−mail: [email protected]
Conflict of interest: None declared.
Received: 17.11.2005
Revised: 17.01.2006
Accepted: 17.02.2006
Praca wpłynęła do Redakcji: 17.11.2005 r.
Po recenzji: 17.01.2006 r.
Zaakceptowano do druku: 17.02.2006 r.
451