Evaluation of 24-hour oesophageal pH monitoring in children with food allergy

Introduction

Food allergy is an important and frequent clinical problem, especially in the youngest children [1-3]. Similarly, gastroesophageal reflux disease is often seen in young children [4-6]. The relationships between these diseases have been described by many authors [7-14]. In our previous studies, the presence of gastroesophageal reflux was confirmed in 46.5% of children between 4 and 36 months of age with food allergy [15].

Reflux may be physiological, occurs rarely and is of short duration for example after exercise, less frequently during sleep. It is most commonly seen in newborns and infants born prematurely in the first few months of life due to immaturity of the anatomical-functional mechanisms protecting against backflow of gastric contents into the oesophagus [4, 10, 11, 16, 17]. Pathological reflux is characterized by increased frequency and intensity of episodes of acid regurgitation into the oesophagus and the occurrence of symptoms from other organs (gastroesophageal reflux disease). It occurs in children with an incidence of 1 : 100 to 1 : 300, according to different authors, and depends on age, coexisting diseases, and genetic, ethnic and racial factors [5, 7, 16, 18-20].

The pathomechanism of the formation of acid reflux may be primary, in which mechanisms of anti-reflux barrier are disturbed, or secondary, which is a clinical manifestation of other diseases, including food allergy [5, 7, 10, 11, 15, 16].

Twenty-four-hour oesophageal pH monitoring is widely regarded as the gold standard in diagnosis of gastroesophageal reflux. Evaluation of the recording allows differentiation of physiological from pathological reflux causing gastroesophageal reflux disease [6, 20-22]. However, it remains difficult to interpret the graphical recordings in order to determine the cause of pathological reflux. There is primary reflux resulting from insufficiency of the lower oesophageal sphincter and secondary reflux, which can be caused by various diseases including gastrointestinal disease, food allergy, metabolic diseases and neurological disorders. It can also occur after administration of certain drugs. It should be emphasized that the results of many authors concerning this problem are not fully unambiguous [9, 11, 12, 14, 15, 23, 24].

Aim The aim of the study was to analyse the record of 24

-h oesophageal pH monitoring in children with food allergy.

Material and methods

The retrospective analysis included 84 children with food allergy aged from 4 to 24 months. The control group consisted of 15 children at the same age diagnosed with gastroesophageal reflux, but without any features of allergic disease. All examined children were treated in the 2nd Department of Paediatrics and Allergology of the Polish Mother’s Memorial Hospital Research Institute in Lodz. Food allergy was diagnosed on the basis of the interview (clinical allergy symptoms and positive history of allergy in the family in some cases), positive food challenge test, and levels of serum concentration of allergen-specific antibodies (specific IgE) against cow's milk proteins. Concentrations  class 2 according to the 4-level classification of atopy confirmed IgE-mediated allergy [25].

All the children underwent 24-h oesophageal pH monitoring performed with Digitrapper Marc III (Synetics Medical, Sweden) using a probe with antimony electrodes calibrated prior to testing in a buffer solution at pH 7.01 and subsequently at pH 1.07.

The results were evaluated in accordance with the Sacre-Smits scale [26]. The parameters were assessed separately for the postprandial period (including the time of feeding with the next 2 h) and for the period between meals. The value of reflux ratio, number of reflux episodes, number of reflux episodes lasting longer than 5 min and duration of longest reflux were analysed.

The criteria of secondary reflux were fulfilled if the values of parameters mentioned above were higher in the period between meals than in the postprandial phase. Statistical analysis for the obtained data was applied.

Results

The analysis of results revealed in 67 (79.8%) of 84 examined children with food allergy elevated levels of allergen-specific antibodies against proteins of cow's milk ( class 2). These children were diagnosed as IgE-dependent allergic while the remaining 17 children were classified as IgE-independent allergic individuals (p < 0.05). Data from the medical interview showed positive family history for allergic disease in 61 children (72.6%).

The results of 24-h oesophageal pH monitoring evaluation confirmed gastroesophageal reflux disease (GERD) in 29 children (34.5%) with allergy to proteins of cow’s milk. Among them there were 11 boys and 18 girls. The remaining 55 children with allergy were negative for reflux disease in 24-h pH-metry. In this group, unlike in children with coexisting gastroesophageal reflux, boys prevailed over girls (34/21). Similarly, the comparison group was also dominated by boys (9/6). The outcomes of evaluated parameters of 24-h oesophageal pH monitoring in children with and without food allergy are shown in Table I. It was found that parameters such as number and duration of reflux episodes were significantly increased in the period between meals in relation to the postprandial period. However, the reflux ratio showed no significant difference between study periods, and the number of reflux episodes longer than 5 min was correct in both groups (study and control). It should be emphasized that the number of reflux episodes was higher for children with coexistent allergy. Mean values of evaluated parameters in children with allergy and children without allergic disease are shown in Table II. In addition, a detailed graphical analysis of the 24-h oesophageal pH monitoring recordings was performed, showing large difficulties of interpretation. These resulted from the fact that analysed results were not fully unambiguous. For each child the severity of reflux in both analysed periods – postprandial and between meals – was compared. The analysis showed some differences. Among children with food allergy, in 12 children (41.4%) reflux was more intense in the period between meals and thus more similar to reflux secondary to allergy, while the remaining 17 children had reflux of primary character with higher intensity during the postprandial period. On the other hand, among children with reflux without allergy in 9 patients (60.0%) the results of oesophageal pH monitoring were characteristic for primary gastroesophageal reflux and in 6 patients (40.0%) for secondary reflux. Graphical records and examples are shown in Figures 1 and 2. The prevalence of primary and secondary reflux in both groups is shown in Figure 3. It shows that the frequency was similar in both groups.

Discussion

Food allergy in infants and young children most often is caused by IgE-dependent mechanisms [8, 10, 27]. Similarly, among our patients there was a high percentage of children (79.8%) with IgE-dependent allergy confirmed by a positive result of food challenge, and the presence of elevated serum levels of allergen-specific antibodies to cow's milk proteins. The allergy has great importance in the pathogenesis of gastroesophageal reflux, because food allergen adversely affects the mucous membrane of the oesophagus and promotes formation or increases the course of pathological reflux [8, 11, 28].

Many authors emphasize frequent and simultaneous occurrence of food allergy and gastroesophageal reflux [8-10, 12, 15, 17, 24]. Reflux may also be a clinical manifestation of allergy [10, 29]. Among our subjects about one third of children (34.5%) had both of these diseases. It should be noted that the incidence is similar to that observed by other authors, according to which it varies from 30% to 46% [10, 12, 15, 23, 24, 30]. The diagnosis of gastroesophageal reflux disease was confirmed by positive 24-h oesophageal pH monitoring, which is a reliable test in the diagnosis of gastroesophageal reflux [5, 6, 15, 21-24]. Analysis of the results showed differences in graphical recording of oesophageal pH monitoring in both the postprandial and between meals periods. It was found that there was a significantly higher number of reflux episodes in children with GER and allergy than in children with GER but without the allergy. These findings are compatible with the study results of Funkowicz et al. [9].

In the literature the need for differentiation between primary and secondary reflux is extensively emphasized, as it is important for the therapeutic procedure [9, 10, 12, 15, 30]. Therefore, like many other researchers we made an attempt of differential diagnosis on the basis of the graphical record of 24-h oesophageal pH monitoring. It should be noted, however, that this analysis is difficult and the observations of researchers are various. Cavatatio et al. [12] and Iacono et al. [13] observed that in children with allergy and gastroesophageal reflux the record varies depending on the cause. These authors found out that in primary reflux pH drops below four are irregular and of various duration. On the other hand, in secondary reflux there is a rapid increase of pH after the consumed meal with slow reduction to the next meal. Other investigators did not confirm these findings [9, 30-32]. In our study the record was typical of primary reflux in 17 children. However, in 12 subjects the recording with features of secondary reflux dependent on allergy aroused some doubts; it was intensified during the period between meals but this record was not fully phasic.

It seems therefore that this diversity of records should be analysed together with clinical symptoms and in allergic children with results of immunological and allergological tests, which is in accordance with the views of other authors [22, 23, 30].

Furthermore, demonstrating a similar prevalence of GER with features of secondary reflux in children with food allergy (12/29) and in the comparison group (6/15) indicates that the record of oesophageal pH monitoring cannot be the basis for the diagnosis of gastroesophageal reflux secondary to allergy to cow’s milk. These observations are consistent with those of other authors [9, 10, 15, 30, 31].

Conclusions

1. Twenty-four-hour oesophageal pH monitoring is helpful, but it cannot be the sole diagnostic criterion in the diagnosis of gastroesophageal reflux dependent on food allergy.

2. The diagnosis of gastroesophageal reflux dependent on allergy should be based on the results of oesophageal pH monitoring as well as allergological and immunologic tests.

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