Upper gastrointestinal symptoms (recurrent upper abdominal pain, discomfort, burning, bloating, early satiety, nausea, and belching) that may reflect dyspepsia are not disease specific and remain limited in the differentiation of organic and functional gastrointestinal disorders. Reflux symptoms (retrosternal burning or regurgitation) and lower gastrointestinal symptoms (periumbilical pain, constipation, and diarrhea) may be mistaken for dyspepsia.
For differentiation of organic dyspepsia (OD) and functional dyspepsia (FD) in the adult population based on the severity of dyspeptic symptoms, certain scales have been developed (1–4); however, none has been shown to be 100% reliable or valid (3). To date, no generally recognized dyspepsia symptom scale has been developed for the pediatric population. The results of the pediatric dyspepsia symptom scale that is in development has lower reliability and validity rates than those of the scale for the adult population (5,6). Although there are sufficient data on the justification of the endoscopy procedure according to scores in adults, which is a cost-effective method, the data on the same issue have remained limited for the pediatric population (7). The present study aimed to determine the symptom scores of the children with upper gastrointestinal system complaints that indicate organic pathologies in light of the answers provided for the questions in the dyspepsia questionnaire, which was applied the day before the endoscopy procedure. Thereby, patients with OD that requires upper gastrointestinal system endoscopy (UGE) can be determined and separated from patients with FD; thus, unnecessary endoscopy procedures may be avoided.
PATIENTS AND METHODS
Between September 2007 and September 2008, 176 dyspeptic children who presented to pediatric gastroenterology outpatient clinics of the Baskent University medical faculty with either continuous or intermittent complaints of the upper gastrointestinal system for at least 3 months were enrolled. Age, sex, body mass index (BMI), medication (nonsteroid anti-inflammatory drugs and antacids) history in the last month, and nutritional habits (acidic drinks, tea or coffee, and/or fastfood consumption) of the subjects were recorded.
Patients with a history of organic or systemic disease, diagnosis of peptic ulcer or gastroesophageal reflux, and Helicobacter pylori infection, neurological diseases, alarm symptoms (dysphagia, persistent vomiting, dysphonia, sudden loss of weight, fever, history of jaundice, hematemesis, and melena); a high level of amylase-lipase or aminotranspherases; and parasite, Giardia antigen, or occult blood in the stool, history of antibiotics or antisecretory drug use for dyspeptic complaints in the last month, and patients who had been treated in other centers for similar complaints were not included in the study.
The patients with more pronounced complaints of defecation or those whose symptoms were alleviated after defecation were also excluded. Children younger than 10 years old were not included in the study because they would not be able to provide accurate answers to the questions on the dyspepsia questionnaire.
At the time of presentation, the symptoms of 24 patients suggested gastroesophageal reflux. Esophageal 24-hour pH monitoring was performed, and 15 patients with reflux were excluded from the study. Thus, the study was performed on 161 patients.
One day before the UGE procedure, all of the patients were provided a questionnaire and asked to respond the questions on the Likert dyspepsia scale. The endoscopist was blinded to patients' responses on the questionnaire. In measuring the severity of specific gastrointestinal symptoms, the 5-point Likert dyspepsia severity scale (1: no complaints at all, 2: little, 3: moderate, 4: quite a lot, and 5: I have serious complaints that significantly affect my daily school-home life, and I feel the need to rest) was used, and in measuring the incidence of the symptoms, the 5-score Likert dyspepsia incidence scale (1: no complaints, 2 [mild]: <2 times in a week, 3 [moderate]: 3 to 4 times in a week, 4 [severe]: intermittent in every day, and 5 [very severe]: many times per day) were used (1) (Table 1).
Using the Likert dyspepsia scale, the severity and incidence of the most common 8 dyspeptic symptoms (epigastric pain, upper abdominal discomfort, retrosternal pyrosis, sour-bitter taste, halitosis, belching, nausea, and early satiety) were investigated. For each symptom, total score (incidence × severity of a provided symptom) were calculated (1). Furthermore, dyspepsia-associated quality of life (any absence from school because of the symptoms, participation in social activities such as playing games and sightseeing) and other features of the abdominal pain (awakening at night because of epigastric pain, pain before meals, whether the pain resolved by taking antiacid medication or on eating, and a sense of pyrosis in the stomach) were queried.
UGE was performed on all of the patients included in the study, and gastric antrum biopsy specimens were obtained for histological evaluation and the rapid urease test. In the biopsy specimens, the same pathologist evaluated the presence and the severity of inflammatory changes. Based on the density of the inflammatory cells in the lamina propria and glandular epithelium, the severity of gastritis was histologically classified using Sydney scoring (0 = none, 1 = mild, 2 = moderate, 3 = severe). Presence of mononuclear cells was considered as chronic inflammation, and presence of polymorphonuclear leukocytes was considered as acute-active inflammation. Presence or absence of H pylori was noted.
OD and FD differentiation was based on endoscopic appearance combined with histopathological findings of the gastric antrum. The patients whose endoscopy findings were normal but had moderate or severe chronic antral gastritis histologically were enrolled in the OD group. The patients whose endoscopy evaluation revealed erosive esophagitis, erosive duodenitis, and peptic ulcer were also enrolled in the OD group even if their antral histology results were normal or showed mild inflammation (8). The patients whose endoscopic findings were normal or showed mild esophageal, gastric, and duodenal mucosal hyperemia or mild antral gastritis histologically were enrolled in the FD group (9).
The patients who had gastric mucosal erythema were classified according to their histological findings based on biopsy specimen evaluations of the lesion or the antrum. These patients were classified in the OD group if histological findings indicated moderate to severe gastric inflammation and in the FD group if the histological findings indicated mild gastric inflammation (8,9).
The presence of H pylori was investigated with 2 tests (urease and gastric histopathology). For negative urease test and positive histopathology, it was considered presence of H pylori infection.
Age, sex, BMI, medication history, nutritional habits, and quality of life related to dyspepsia of the patients in the 2 groups were compared, and the relation among the severity, incidence, and total scores of each dyspepsia symptom and endoscopic and histological evaluation results were studied.
The parents of all of the patients were provided a consent form and were asked to read and sign it. The study protocol was approved by the Baskent University ethics committee.
The normal distributions of continuous variables were evaluated with the Shapiro-Wilk test. The weight and the BMI variables had a normal distribution, and the group variations were homogenous. Thus, for these variables, the differences in the mean values for dyspepsia and sex were evaluated through 2 factorial variance analyses. The age variable did not show a normal distribution according to sex, and thus theMann-Whitney U test was used for comparison. The differences between the groups for total score variables were evaluated with the Mann-Whitney U test. In the analysis of 2-way tables, depending on the incidence and the count of the cells in the table, the Pearson chi-square test, likelihood ratio, or Fisher exact test were used. The binary logistic regression analysis was used in the investigation of the risk factors, and the receiver operating characteristic (ROC) analysis was used in the determination of the differential values. The results were expressed as n (%) for categorical variables and as mean ± SD, median value, and minimum–maximum value for constant variables. P < 0.05 was considered statistically significant. In the analysis of the datasets, SPSS 17.0 (SSPS, Inc, Chicago, IL) was used.
When endoscopic and gastric histopathology findings were combined, 100 (62%) of 161 dyspeptic patients were classified in the OD group and 61 (38%) were classified in the FD group. The demographic characteristics of the patients are shown in Table 2. No statistically significant differences were determined among age, sex, and BMI in patients with OD and FD. Also, we did not observe any relation among medication history, poor nutritional habits, and type of dyspepsia. The UGE and histopathological findings from the gastric antrum of the patients are provided in Table 3.
The results of the endoscopy findings were that 117 (72.6%) of 161 dyspeptic patients were diagnosed as having antral gastritis. Of these, 74 (63%) had erythematous, 39 (33.3%) had nodular, and 4 (3.7%) had erosive gastritis appearance. Eleven patients (7%) were diagnosed as having duodenal ulcer.
It was observed in the endoscopic findings of 100 patients with OD that 75 (75%) patients had antral gastritis, 7 (7%) patients had antral gastritis and duodenitis, 5 (5%) patients had antral gastritis and erosive esophagitis, and 11 (11%) patients had duodenal ulcer. In 2 (2%) patients in the OD group, normal endoscopic findings were determined; however, in their antrum histology, chronic active gastritis was observed. For this reason, these patients were included in the OD group.
We observed normal UGE findings in 18 (29%) of the 61 patients in the FD group. Antral gastritis was diagnosed in 42 (69%) patients, and in 1 (2%) patient antral gastritis and duodenitis was determined. Overall, the UGE findings of 20 (12.4%) of 161 dyspeptic patients were reported to be normal.
Among the 100 patients with OD, histological findings indicated that 5 (5%) patients had normal antral histology, 10 (10%) patients had mild chronic gastritis, 31 (31%) patients had moderate to severe chronic gastritis, and 54 (54%) patients had chronic active gastritis.
Among the 61 patients with FD, normal gastric antrum was diagnosed in the histology findings of 42 (69%) patients, and 19 (31%) patients in this group had mild chronic gastritis.
Overall, in 85 (53%) of 161 dyspeptic patients, chronic active gastritis and moderate to severe chronic gastritis were determined histologically. Among the 161 patients, 29 (18%) patients had mild chronic gastritis and gastric antrum histology was normal in 47 (29%) patients.
Association Between Dyspepsia Scores and Dyspepsia Type (Organic or Functional Dyspepsia)
The following observations were noted: In 153 (95%) patients, epigastric pain; in 147 (91.3%) patients, discomfort in the upper abdomen; in 27 (16.8%) patients, retrosternal pyrosis; in 59 (36.6%) patients, sour-bitter taste; in 67 (42%) patients, halitosis; in 70 (43.5%) patients, belching; in 102 (63.4%) patients, nausea; and in 112 (69.5%) patients, early satiety.
Of 93 patients who had an epigastric pain severity of Likert 4 and 5, 65 (70%) patients were in the OD group and 28 (30%) patients were in the FD group (P = 0.042); however, of 68 patients who had an epigastric pain severity of Likert 1 to 3, 33 (48.5%) patients were in the OD group and 35 (51.5%) were in the FD group (P > 0.05). Although mild epigastric pain could not differentiate dyspepsia type, having severe epigastric pain indicated OD in our patients.
Of 97 patients with an epigastric pain incidence score of 4 and 5, 67 (69%) patients were in the OD group and 30 (31%) were in the FD group (P = 0.028). Of 64 patients with an epigastric pain incidence score of Likert 1 to 3, 31 (48%) patients were in the OD and 33 (52%) patients were in the FD group (P > 0.05). Although high incidence (at least once per day) of epigastric pain indicated OD, a pain incidence of 3 to 4 times in ≤1 week did not differentiate the OD or the FD groups. No significant relation was found between the severity, incidence, and total scores of other dyspeptic symptoms and dyspepsia type (P > 0.05).
Evaluation with the ROC analysis of 8 dyspepsia total scores, including epigastric pain, yielded no cutoff value of the total scores for differentiation of OD and FD (Table 4). Furthermore, in the binary logistic regression analysis, it was determined that in differentiating dyspepsia types, 2 to 8 combinations of total scores of various symptoms did not produce a significant regression formula, and this method could not differentiate OD and FD (P < 0.5–0.6).
The mean total score values of all of the dyspeptic symptoms were compared for differentiation of OD and FD (Table 4). Finally, no significant relation was found between the mean total score values of all dyspeptic symptoms and dyspepsia type (P > 0.05) (Table 5).
No statistically significant relations were found between missing school days, inability to participate in activities such as playing games and sightseeing, and OD and FD (P > 0.05). However, significant relations were determined between abdominal pain causing awakening at night, abdominal pain when hungry, and relief in symptoms on taking antacid drugs or on eating and OD (respectively, P = 0.001, P = 0.001, and P = 0.015) (Table 6).
Comparisons of Patients for Severity of Antral Gastric Inflammation
In comparisons of 85 (53%) patients whose histopathological evaluations revealed marked antral gastric inflammation (chronic active gastritis and moderate to severe chronic gastritis) and 76 (47%) patients whose histopathological evaluations showed mild chronic gastritis or normal findings, no statistically significant differences were found for age, sex, BMI, and nutritional habits (P > 0.05). No significant relation was determined between the severity of antral gastric inflammation and the severity, incidence, and total scores of 8 dyspeptic symptoms, missing school days, inability to participate in social activities, response to antacids, abdominal pain when hungry, and pyrosis (P > 0.05).
Awakening at night because of abdominal pain was more common in the group of patients with marked gastric inflammation (chronic active gastritis and moderate to severe chronic gastritis) (P = 0.02). In 38 (44%) of the 86 (54%) patients with abdominal pain–related awakening at night, and in 16 (21%) of the 75 (46%) patients with no abdominal pain, marked gastric inflammation was determined.
Comparisons of the Patients Infected and Uninfected With H pylori
H pylori infection was diagnosed in 82 patients (51%). In the comparisons of the patients infected or uninfected with H pylori, no statistically significant differences were found for age, sex, BMI, and nutritional habits (P > 0.05). No differences were determined between H pylori–positive and H pylori–negative groups in terms of the severity, incidence, and total scores of 8 dyspeptic symptoms, missing school, inability to participate in social activities, response to antacids, abdominal pain when hungry, and pyrosis (P > 0.05).
Recently, FD was defined in the adult Rome III criteria as the presence of ≥1 dyspepsia symptoms (bothersome postprandial fullness, early satiation, epigastric pain, and epigastric burning) that are considered to originate from the gastroduodenal region in the absence of any organic, systemic, or metabolic disease, last at least 3 months, and show no evidence of structural disease (7). The committee recommended 2 conditions: postprandial distress syndrome and epigastric pain syndrome under the umbrella of functional dyspepsia. According to the pediatric Rome III consensus report, FD is defined as persistent or recurrent pain or discomfort above the umbilicus not relieved by defecation or not associated with the onset of a change in stool frequency or form. There should be no evidence of an inflammatory, anatomic, metabolic, or neoplastic process that could explain the subject's symptoms (7,8). The pediatric definition is somewhat different from the adult FD definition. The adult FD definition included epigastric burning, postprandial fullness, and early satiation terms. Symptoms such as nausea and belching are also not included in both adult and pediatric FD definitions; however, children may experience these unlabeled symptoms. The term “discomfort” in the pediatric Rome III definition is unspecified and may include indefinable symptoms reported by the child such as nausea, belching, and pyrosis. For this reason, we included these symptoms indicating upper gastrointestinal discomfort in our Likert dyspepsia questionnaire that was given to children.
Dyspepsia prevalence among school-age children ranges between 3.5% and 27% (10,11). Miele et al (12), in their survey of 9660 children at an age range of 1 month to 12 years, have diagnosed 194 (2%) children with FGSD and determined FD prevalence as 0.27%. The diagnosis of FD is one of the most common diagnoses among FGSDs. Walker et al (13) diagnosed 15.9% of 78 children at an age range of 4 to 17 years who had FGSD with FD. In our study, based on both endoscopic and histopathological findings of the dyspeptic patients, 62% were classified in the OD group and 38% were classified in the FD group. Accordingly, the rate of the patients who were diagnosed with OD was higher.
Hyams et al (10) classified 38% of 56 dyspeptic children in the OD group according to the UGE findings only. The most common endoscopic findings of OD were erosive esophagitis/gastritis/duodenitis, peptic ulcer, and cancer (10). Antral nodularity may be added to these findings. Ozcay et al (14) reported that the antral nodular gastritis rate detected 64.7% in H pylori–infected children. In a meta-analysis of 18 studies, 1871 children with recurrent abdominal pain were evaluated through UGE and biopsy (15). In this meta-analysis, endoscopic findings other than ulcer-erosion have been considered nonspecific endoscopic findings. In addition, many endoscopic findings such as erythema, pallor, and increased or reduced vascularity have been considered nondiagnostic (16).
The histopathological evaluations of the antrum biopsy specimens of our dyspeptic patients indicated normal findings in 29% and mucosal inflammation of various degrees in 71%. The endoscopic and histological findings of dyspeptic and nondyspeptic adults were compared in an earlier study, and only 11.4% of nondyspeptic group had normal endoscopic and histological findings (17). The authors could not establish an association between dyspeptic symptoms and gastric and duodenal inflammation (17). The literature contains few studies on the histopathological findings of dyspeptic children. The antrum histology of 69% of our patients with FD was normal, whereas 31% had mild chronic gastritis. In their study of the esophagus, antrum, and duodenum biopsy of 88 children with FD, Schurman et al (18) reported mild esophagitis in 21%, mild to moderate chronic gastritis in 44%, and mild to moderate duodenitis (increased lymphocyte and plasma cells, no villous loss) in 25%. However, they observed no findings of severe inflammation in any of their patients. It was reported that in patients with FD, mild to moderate mucosal inflammation may be noted (18). In the meta-analysis of 18 studies involving UGE and biopsy evaluations in children with recurrent abdominal pain, histologically nonspecific gastrointestinal inflammation was noted in 23% to 93%, and H pylori infection was determined in 2% to 63% of the patients (15). It has been emphasized that mucosal erythema-inflammation cannot be considered an endoscopic finding, and nonspecific histological gastrointestinal inflammatory lesions do not require treatment because of their unknown prognostic value. Furthermore, it has been reported that asymptomatic individuals may also have gastrointestinal inflammation histologically (19).
We based our study on both endoscopic and histological findings of the antrum mucosa. Antral mucosa samples were obtained because of the high rate of H pylori infection in Turkey. In 85% of our patients with OD and in more than half (53%) of all of the dyspeptic patients in our study, marked antral mucosal inflammation (moderate to severe chronic gastritis/chronic active gastritis) was noted. One of the etiologies for these findings may be the H pylori infection determined in 51% of our patients because histopathologically, in 94% of the H pylori–infected patients, marked mucosal inflammation was detected.
In our study, the 5-point Likert scale was used in determining the severity and incidence of gastrointestinal system complaints of dyspeptic children. The Likert scale is used in measuring the severity and incidence of the symptoms of various diseases. Caplan et al (5) used the Likert scale in the diagnosis of FGSD in 315 children 10 to 18 years of age. In addition, the 5-point Likert scale is used in determining the severity of respiratory difficulties in children with asthma, and the 7-point Likert scale is used in determining the incidence of coughing attacks in children with nighttime coughing (20,21).
Our results indicated that of the dyspeptic complaints, the severity, incidence, and total scores of epigastric pain were significantly related to dyspepsia type. We found that OD was indicated on the Likert scale only when the severity and incidence of epigastric pain were 4 and 5 (severe and very severe). Nearly 70% of the patients with severity and incidence scores of 4 and 5 for epigastric pain were in the OD group. In addition to the use of the Likert scale, the patients were asked some questions to be responded to as “present or not present.” Among these, abdominal pain awakening at night, abdominal pain when hungry, antacid use, and relief of symptoms after meals and OD were significantly related. Including these items, the 5-point Likert scale can be more helpful for evaluating dyspeptic children. To investigate the nature of the relation between epigastric pain and OD, the relation between H pylori infection and epigastric pain was evaluated. However, the severity and incidence of epigastric pain in H pylori–infected patients were not high. This finding suggests that the severity of epigastric pain in H pylori–infected patients varies, and by considering the severity of the pain only, the diagnosis of H pylori infection cannot be made. Various results have been obtained in the studies on the relation between pain severity and H pylori infection. In some studies, a significant relation between H pylori infection and epigastric pain has been shown. For example, in the study by Ozcay et al (14), epigastric pain (68%) was the most common symptom in 102 children with H pylori infection, and after eradication treatment, 75.7% of dyspeptic symptoms partially or completely resolved. In some studies, however, no relations have been determined between H pylori and epigastric pain (22,23). In our study, 95% of our patients experienced epigastric pain. In our study, unlike in the above-mentioned studies, the presence of epigastric pain, its severity, and its incidence were also investigated. We concluded that OD and FD could not be differentiated based on the severity and incidence of epigastric pain.
In the present study, the incidence rates of abdominal pain awakening at night, abdominal pain when hungry, relief of symptoms after antacid use and meals were higher in the OD group than in the FD group. Furthermore, in H pylori–infected patients, the incidence rates of abdominal pain awakening at night and abdominal pain when hungry were significantly higher than in the uninfected patients. Thus, abdominal pain when hungry and abdominal pain awakening at night were thought to be associated with OD and H pylori infection. Similar to our findings, Giacomo et al (11) studied the relation between dyspeptic symptoms and H pylori infection and found a significantly higher incidence rate of severe abdominal pain awakening at night in the H pylori–infected group. H pylori was not found to have any effects on the severity or the incidence of epigastric pain, upper abdominal discomfort, retrosternal pyrosis, sour-bitter taste, halitosis, belching, nausea, and early satiety.
Among the children participating in the study, it was observed that 22.4% of the children were involved in activities such as withdrawal from social life and 16.8% of the children were involved in activities such as absence from school because of severity of gastric pain. However, these were not indicative of OD. Parallel to our study, Hyams et al (10) compared 56 dyspeptic children with or without gastrointestinal mucosal inflammation and found no significant differences for attendance at school.
Comparisons of the patients in our study with marked antral inflammation (53%) and normal to mild inflammation (47%) for the severity and incidence of dyspeptic symptoms showed no significant differences. In those with marked inflammation, the incidence rate of abdominal pain awakening at night was higher. In contrast, a relation was found in 251 adult patients between abdominal pain when hungry and antrum inflammation (24). In the same study, significant improvement was noted in the severity of inflammation and symptoms after H pylori–eradication treatment. The literature contains no such comparative studies in children.
In the present study, the severity and incidence of symptoms in dyspeptic patients were measured to determine whether a cutoff value that indicates OD could be established. Each dyspeptic symptom or combinations of symptoms were measured and thus, a differentiation of FD patients from OD patients was aimed at. Another aim was to develop an objective scale to persuade the patients to be classified in the OD group and for their parents to allow the endoscopy procedure. However, no threshold value of symptom score was determined that would differentiate OD and FD in dyspeptic children before the endoscopy procedure. Various combinations of each symptom score with others did not differentiate dyspepsia types.
In conclusion, endoscopic and histological findings were concomitantly evaluated in the present study and the patients were classified into the OD or the FD groups according to the criteria defined. Furthermore, the study also aimed to determine whether the Likert dyspepsia scale was useful in differentiating OD and FD and whether the use of the endoscopy procedure was indicated according to the scores obtained from the dyspepsia scale. To the best of our knowledge, our study is the first in the pediatric age group in this field. No significant cutoff value of dyspepsia symptom score for differentiation of OD and FD was determined, and the clinical value of the endoscopy procedure according to scores of the dyspepsia scale in the differentiation of OD and FD could not be shown.
Redesigning the Likert scale used in the present study, applying this scale on a higher number of dyspeptic patients, and using a different definition of OD/FD defined in our study may contribute to future studies of similar design.
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