Timing of initial symptom onset during milk and wheat challenges: A retrospective study.

BACKGROUND: Allergic reactions to milk appear sooner than those to hen's eggs, irrespective of the total dose of the oral food challenges (OFCs) and type of matrices. The reported median times for the first symptom occurrence are 20-30 min with milk and 50-60 min with eggs. However, allergic reactions due to wheat have not yet been fully investigated. METHODS: This study retrospectively collected data from OFC for milk and wheat conducted at Sagamihara National Hospital and Sendai Medical Center from 2009 to 2023. The time from the start of the OFC to the onset of symptoms was compared between children with cow's milk and wheat allergy. RESULTS: Twenty-five and 13 children reacted to single-dose OFCs with milk products equivalent to 25 mL of raw cow's milk or 15 g of udon noodles, respectively. The median ages of patients with positive challenges were 1.4 and 2.8 years for milk and wheat, respectively, and the median times for the first symptom occurrence were 20 min and 53 min, respectively (p = .006). CONCLUSION: This multicenter study was the first to examine the time of symptom appearance during single-medium-dose milk and wheat challenges. Allergic reactions to wheat appear later than those for milk during OFC. For multiadministration OFC for wheat, the dosing interval should be longer than 60 min. Our findings can help improve the safety of OFCs.

Allergic reactions to milk appear sooner than reactions to hen's eggs: a retrospective study.

BACKGROUND: Oral food challenge test doses are recommended to be performed at least 20 min apart; however, the times of symptom provocation from the start of the oral food challenge have never been compared between different foods. In this study, the durations from the start of the oral food challenge to symptom development in children with egg or milk allergy were compared. METHODS: Thirty-eight and 74 children who had previously passed oral food challenges to 96 g of yogurt and pumpkin cake containing » whole egg underwent oral food challenges with 200 mL raw cow's milk and 1 whole scrambled egg, respectively; of these, 15/38 and 33/74 children had a reaction. RESULTS: The median ages of patients with a positive challenge were 5.8 and 5.1 years for milk and eggs, respectively. The median times for the first symptom occurrence were 20 min (range, 5-55 min) and 50 min (5-480 min), respectively (p = 0.009). The first symptoms developed within 30, 60, and 90 min in 12/15 (80 %), 15/15 (100 %), and 15/15 (100 %) children with milk allergies, and in 10/33 (30.3 %), 20/33 (60.6 %), and 26/33 (78.8 %) children with egg allergies, respectively. The median times of peak symptoms were 50 min (10-210 min) and 120 min (30-560 min) (p = 0.001), and those of symptom disappearance were 90 min (30-240 min) and 180 min (80-700 min) for milk and eggs (p = 0.002), respectively. DISCUSSION: Based on the results of our study, symptoms developed within 30 min for only a subset of patients for eggs, and may even take upwards of 60 min to develop. The times of symptom disappearance were 90 min and 180 min for milk and eggs, respectively, indicating that egg-allergic patients should be observed for a longer period time than milk-allergic patients. CONCLUSIONS: Allergic reactions induced by milk appeared and disappeared sooner than those induced by eggs.

Erratum: Butter Tolerance in Children Allergic to Cow's Milk.

[This corrects the article DOI: 10.4168/aair.2015.7.2.186.].

Does Terminating the Avoidance of Cow's Milk Lead to Growth in Height.

BACKGROUND: Cow's milk allergy is known to result in decreased body height; accordingly, the aim of this study was to investigate whether termination of milk avoidance leads to an increase in body height. METHODS: Between 2010 and 2011, 253 children with food allergies who were ≥2 years of age visited our outpatient department; 195 had height data available from approximately 1 year after their initial food allergy diagnosis and were included in the study. The height standard deviation scores (HtSDs) were calculated using data from the 2000 Japanese National Physical Growth Survey Report for Infants and Children, and changes in height were then retrospectively evaluated using clinical records. RESULTS: The mean age of the 195 patients was 5.8 ± 3.0 years. The mean HtSDs increased significantly from -0.19 ± 0.99 at diagnosis to -0.12 ± 1.02 (p = 0.025) 1 year later for all children. The HtSDs of 110 cases had increased, but the HtSDs of 85 cases had decreased 1 year after the initial diagnosis. The only significant factor related to increased HtSD was tolerated milk allergy 1 year after the initial diagnosis (p = 0.004). CONCLUSIONS: Terminating the avoidance of cow's milk might lead to growth in height, although a prospective study with a larger sample size is needed to confirm these results.

Butter Tolerance in Children Allergic to Cow's Milk.

We performed an oral food challenge (OFC) with 10 g of butter (equivalent of 2.9 mL cow's milk) and 25-mL heated cow's milk for 68 children with cow's milk-allergy. Thirty-eight children reacted only to heated cow's milk. Twenty-four children reacted to neither heated milk nor butter. Thirty-eight (86.4%) of 44 patients with positive results to the OFC for heated milk could safely tolerate butter. It is highly likely that even children with cow's milk-allergy who show positive results to an OFC for heated milk can consume butter. The milk-specific IgE value indicative of a negative predictive value of over 95% was 17.8 kUA/L, and patients with low milk-specific IgE values may be able to safely consume butter. Including butter in the diets of patients with milk-allergy after a butter challenge may improve quality of life.

[The effects of great East Japan earthquake on patients with food allergy in Miyagi Prefecture].

BACKGROUND: Although many food-allergic children experienced the Great East Japan Earthquake, little was known about the effects of the disaster on them. METHODS: Using a questionnaire survey, we studied 194 patients with food allergy in Miyagi Prefecture, who were hospitalized for the oral food challenge test after the earthquake. This survey consists of items related to the damage to home, means of gathering information, lack of allergen-free foods, exacerbation of atopic dermatitis or bronchial asthma, etc. RESULTS: At the earthquake, most of the patients lived around Sendai city. Lifeline disruptions, communication breakdown, and goods shortage occurred in almost all family. Immediately after the earthquake, it was difficult to continue the food elimination diet. Asthmatic attack occurred in 14% of food-allergic children with bronchial asthma. Exacerbation of eczema was seen in 60% of food-allergic patients with atopic dermatitis. Almost all guardians of atopic dermatitis children think that it was because the shower was unavailable after the earthquake. CONCLUSION: It is necessary to supply food-allergic patients with the specific food elimination diet, and atopic dermatitis patients with the shower facilities as soon as possible after the natural disaster occurs.

Non-Helicobacter bacterial flora rarely develops in the gastric mucosal layer of children.

Non-Helicobacter bacteria can be cultured from the gastric mucosa in adults but in children, there are no studies about such microflora. The purpose of this study, therefore, was to clarify whether gastric biota develops in children. In 10 children and 10 adults or elderly (5 H. pylori-infected and 5 uninfected in each group), biopsy specimens of the gastric antrum and corpus and gastric juice were studied for bacterial examinations and the data were compared between both age groups in relation to H. pylori status and luminal pH. Bacterial genera and species were analyzed using both culture and real-time polymerase chain reaction (PCR) with the 52 genus- and species-specific primer sets. Non-Helicobacter bacteria in the mucosa were cultured from all adult patients, whereas microorganisms were cultured in only one child (p < .001). Gastric pH was lower in children (median, 1.4) than in adults (median, 2.6) (p < .005). The grade of endoscopic gastric atrophy was moderate or severe in 8 adults, but absent or mild in all 10 children. Among adults, there was a significant positive correlation between gastric pH and total bacterial counts of both the mucosa and juice. These data indicate that impaired gastric acid secretion associated with long-term H. pylori infection enables non-Helicobacter bacteria to colonize in the human stomach. Such microorganisms rarely colonize in the gastric mucosa in children regardless of H. pylori status.

Association between gastric atrophy and Helicobacter pylori infection in Japanese children: a retrospective multicenter study.

The purpose of this study was to determine whether Helicobacter pylori infection and mucosal inflammation result in gastric atrophy in Japanese children. A total of 196 patients ages 1-16 years were retrospectively studied: 131 patients were infected with H. pylori and 65 patients were uninfected. Antral (n = 196) and corpus biopsy specimens (n = 70) were investigated based on the Updated Sydney system. In both the antrum and corpus, H. pylori-infected patients showed significantly higher degrees of inflammation and activity of gastritis, compared with noninfected patients. The prevalence of grade 2 or 3 atrophy in the antrum was 10.7% in H. pylori-infected patients and 0% in the noninfected patients (P < .01) and in corpus 4.3% and 0%, respectively (P = .20). The frequency of intestinal metaplasia in the 2 study groups was 4.6% and 4.6% in the antrum and 0% and 4.2% in the corpus, respectively. Among H. pylori-infected patients, the antrum showed significantly higher degrees of H. pylori density, inflammation and activity of gastritis, and atrophy than the corpus. In the antrum, atrophy was significantly correlated with activity, whereas in the corpus, atrophy correlated with H. pylori density, inflammation, and activity. H. pylori-induced gastric inflammation can cause atrophy in Japanese children, predominantly in the antrum. It remains to be determined whether H. pylori-infected children with gastric atrophy are at increased risk for gastric cancer.

Gastric epithelial cell turnover and mucosal protection in Japanese children with Helicobacter pylori infection.

BACKGROUND: In adults, epithelial cell proliferation and apoptosis of the gastric mucosa are induced by Helicobacter pylori infection and are associated with gastric atrophy or gastric carcinoma. In children, there are few studies about such epithelial changes. To elucidate the role of H. pylori infection in gastric mucosal inflammation, we immunohistochemically examined gastric mucosa of Japanese children. METHODS: Biopsy specimens obtained from the gastric antrum and corpus of H. pylori-infected (n = 13) and noninfected children (n = 15) were studied for immunolocalization of Ki-67, single-strand DNA, manganese superoxide dismutase (Mn-SOD), and CD68, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling. In 10 patients with successful eradication, pre- and posttreatment results were compared. RESULTS: In both gastric antrum and corpus, neutrophil and mononuclear cell infiltration, epithelial cell proliferation, and apoptosis significantly increased in H. pylori-infected patients, predominantly in the antrum. In the antrum of H. pylori-infected patients, there was positive correlation between the degrees of neutrophil infiltration and cell proliferation (P < 0.05) or apoptosis (P < 0.05). H. pylori eradication improved mucosal inflammation, cell proliferation (P < 0.001), and apoptosis (P < 0.01) in the antrum. Mn-SOD immunoreactivity and CD68-positive macrophages in the antrum, which significantly increased in H. pylori-infected patients, decreased after the eradication. CONCLUSIONS: H. pylori infection induced gastric mucosal inflammation and epithelial cell turnover in children. Moreover, gastric mucosal defense mechanism against H. pylori infection was activated. H. pylori eradication in childhood might prevent the accumulation of gastric epithelial cell damage.

Helicobacter heilmannii infection in a child after successful eradication of Helicobacter pylori: case report and review of literature.

An 11-year-old boy with Helicobacter pylori-associated duodenal ulcer was successfully treated with a combination of lansoprazole, amoxicillin, and clarithromycin. Endoscopy and gastric biopsies were repeated 2 and 12 months later, showing ulcer healing and eradication of H. pylori. However, a 3-year follow-up study demonstrated H. heilmannii in the antral mucosa based on its characteristic morphology and positive urease test and negative culture. The patient had no contact with domestic animals such as cats and dogs. A 7-day course with lansoprazole, amoxicillin, and clarithromycin was performed again, resulting in successful eradication of the organism. Pediatric cases with H. heilmannii infection reported are reviewed.

Comparison between the 13C-urea breath test and stool antigen test for the diagnosis of childhood Helicobacter pylori infection.

BACKGROUND: As noninvasive tests for Helicobacter pylori infection, the 13C-urea breath test (UBT) and stool antigen test have been widely used. In children, however, there are few studies reporting which test shows superior performance. The purpose of this study was to compare the 13C-UBT and stool antigen test for their accuracy in diagnosing H. pylori infection in children. METHODS: A total of 123 Japanese children, ages 2 to 17 years (mean, 12 years) who underwent gastric biopsies for H. pylori infection were studied. The diagnoses included gastritis (n = 55), gastric ulcer (n = 5), duodenal ulcer (n = 20), iron-deficiency anemia (n = 7), and other conditions (n = 36). The cutoff value of the 13C-UBT was defined to be 3.5 per thousand. The stool antigen test was performed using the HpSA enzyme-linked immunosorbent assay (ELISA) (Premier Platinum HpSA). In 16 patients who received eradication therapy, the 13C-UBT and HpSA were repeated 2 months after treatment. RESULTS: Based on biopsy tests, 60 children were infected with H. pylori and 63 children were not. For the 13C-UBT, the sensitivity, specificity, and accuracy were 95.0% (95% confidence interval [CI], 86.1%-99.0%), 98.4% (95% CI, 91.5%-100%), and 96.4% (95% CI, 93.6%-99.9%), respectively. For the HpSA, the sensitivity, specificity, and accuracy were 98.3% (95% CI, 90.8%-100%), 98.4% (95% CI, 91.2%-100%), and 98.3% (95% CI, 96.0%-100%), respectively. There were no significant differences between the performance of these two tests. In the assessment of H. pylori eradication, the results of 13C-UBT and HpSA agreed with those of biopsy tests. CONCLUSIONS: The 13C-UBT and the HpSA are equally accurate for the diagnosis of active H. pylori infection in Japanese children.

Multicenter comparison of rapid lateral flow stool antigen immunoassay and stool antigen enzyme immunoassay for the diagnosis of Helicobacter pylori infection in children.

BACKGROUND AND AIM: The stool antigen enzyme immunoassay (EIA) methods are widely used for diagnosing Helicobacter pylori infection. Recently, a novel, rapid stool antigen test, the lateral flow immunoassay (LFI) method, has been developed. The primary purpose of this study was to compare the EIA method with the LFI method for the diagnosis of H. pylori infection in children. MATERIALS AND METHODS: Stool specimens from children being evaluated for H. pylori infection were also examined using the LFI (ImmunoCard STAT! HpSA) and EIA methods (Premier Platinum HpSA). The sensitivity, specificity and accuracy of the test were based on the 13C-labeled urea breath test. RESULTS: One hundred and eighty-two children and adolescents, 3-17 years of age (mean 9.2 years), were studied. In addition, 29 patients who received eradication therapy were re-evaluated 2 or 3 months post-treatment. The 13C-labeled urea breath test was positive in 64 patients (35.2%). The sensitivity, specificity and accuracy of the LFI method were 90.6% (95% CI = 80.7-96.5%), 95.8% (92.1-99.4%), and 94.0% (90.5-97.4%), respectively and for the EIA method, sensitivity, specificity and accuracy were 96.8% (95% CI, 89.0-99.6%) and 99.2% (97.5-100%), and 98.3% (96.5-100%), respectively. There were no significant differences in results among the age groups 3-5, 6-10 and 11-17 years. As for the assessment of H. pylori eradication, the results of the LFI and EIA methods agreed with those of 13C-urea breath test in 27/29 and 29/29 patients, respectively. CONCLUSIONS: The LFI stool antigen method showed a good sensitivity, specificity and accuracy for diagnosing H. pylori infection in children. This novel method may be useful in clinical practice as an office-based test because it is rapid, reliable and easy to perform.

Effect of Helicobacter pylori infection on gastric acid secretion and meal-stimulated serum gastrin in children.

BACKGROUND: Comparative studies of gastric acid secretion in children related to Helicobacter pylori infection are lacking. The purpose of this study was to compare acid secretion and meal-stimulated gastrin in relation to H. pylori infection among pediatric patients. MATERIALS AND METHODS: Thirty-six children aged 10-17 years (17 with H. pylori infection) undergoing diagnostic endoscopy participated in the study. Diagnoses included gastritis only (n = 23), duodenal ulcer (n = 5) and normal histology (n = 8). Gastric acid output was studied using the endoscopic gastric secretion test before and 2-3 months after H. pylori eradication. Meal-stimulated serum gastrin response was assessed before and 12 months after eradication. RESULTS: H. pylori gastritis was typically antrum-predominant. Acid secretion was greater in H. pylori-positive patients with duodenal ulcer than in gastritis-only patients or controls [mean +/- standard error (SE): 6.56 +/- 1.4, 3.11 +/- 0.4 and 2.65 +/- 0.2 mEq/10 minutes, respectively; p <.001]. Stimulated acid secretion was higher in H. pylori-positive boys than girls (5.0 +/- 0.8 vs. 2.51 +/- 0.4 mEq/10 minutes, respectively; p <.05). Stimulated acid secretion pre- and post-H. pylori eradication was similar (5.47 +/- 0.8 vs. 4.67 +/- 0.9 mEq/10 minutes, respectively; p =.21). Increased basal and meal-stimulated gastrin release reversed following H. pylori eradication (e.g. basal from 134 to 46 pg/ml, p <.001 and peak from 544 to 133 pg/ml, p <.05). CONCLUSIONS: H. pylori infection in children is associated with a marked but reversible increase in meal-stimulated serum gastrin release. Gastric acid hypersecretion in duodenal ulcer remains after H. pylori eradication, suggesting that the host factor plays a critical role in outcome of the infection.

[The prospects of vaccination against H. pylori infection].

H. pylori causes numerous gastroduodenal diseases including malignancies. Although eradication of H. pylori using antibiotics is clinically performed, it is sometimes unsuccessful because of resistant bacteria and patient non-compliance with treatment. Therefore prophylactic and therapeutic vaccination against H. pylori infection is necessary for clinical use but it is still under study. H. pylori is widely believed to be transmitted in childhood. If long and chronic H. pylori infection causes gastric cancer, vaccination should be targeted at children for the prophylaxis of cancer. Systemic immunization with aluminum hydroxide which has been already proved to be safe for human child, deserve attention.

Evaluation of therapeutic efficacy of adjuvant Helicobacter pylori whole cell sonicate in mice with chronic H. pylori infection.

Successful prophylactic administration of Helicobacter pylori whole cell sonicate (WCS) plus complete Freund's adjuvant (CFA) or aluminum hydroxide (ALM) against subsequent H. pylori infection was reported recently. Here we tested the effect of WCS plus TiterMax Gold (TMX) or ALM in mice with chronic H. pylori infection. Mice with chronic (18 weeks) H. pylori infection were injected intraperitoneally with H. pylori (Sydney strain) WCS plus ALM or TMX once weekly for three times. The number of colonizing H. pylori in the stomach, IgG1 and IgG2a levels, and local inflammatory status were determined after therapeutic immunization. H. pylori specific IgG1, but not IgG2a, was significantly induced in mice immunized with H. pylori WCS plus TMX or ALM. Immunization did not result in reduction of bacterial count or recruiting inflammatory cells to the stomach. Adjuvant H. pylori WCS resulted in induction of CD4+ Th2 cell-mediated immunity although it did not reduce bacterial density in mice with chronic H. pylori infection. Our results implied that CD4+ Th1 cell-mediated immunity, rather than Th2 cell dominant immunity, might play a role in reducing the number of bacteria in chronic H. pylori infection.

Diagnostic accuracy of the 13C-urea breath test for childhood Helicobacter pylori infection: a multicenter Japanese study.

OBJECTIVES: In adults, the 13C-urea breath test (UBT) has been widely used as a noninvasive test of Helicobacter pylori infection because of its high sensitivity and specificity. However, this test is less well established in pediatric practice. The optimum cutoff value and test protocol of the 13C-UBT remains to be established in the pediatric population. The primary purpose of this study was to evaluate diagnostic accuracy of the 13C-UBT for children and to determine its optimum cutoff value. METHODS: A total of 220 Japanese children aged 2-16 yr (mean = 11.9) who underwent upper GI endoscopy and gastric biopsies were finally studied. Endoscopic diagnoses included gastritis (n = 131), gastric ulcer (n = 15), duodenal ulcer (n = 72), and combined ulcer (n = 2). H. pylori infection status was confirmed by biopsy tests including histology, urease test, and culture. With the 13C-UBT, breath samples were obtained at baseline and at 20 min after ingestion of 13C-urea without a test meal and were analyzed by isotope ratio mass spectrometry. Based on biopsy tests, a cutoff value was determined using a receiver operating characteristic curve. In 26 children (seven children infected and 19 noninfected), paired breath samples were also measured by nondispersive infrared spectometry (NDIRS). RESULTS: Biopsy tests demonstrated that 89 children (40%) were infected with H. pylori and 131 children were not infected. There were no statistical differences in mean delta 13C values at 20 min between male and female H. pylori-infected and noninfected patients. A receiver operating characteristic analysis defined the best cutoff value as 3.5 per thousand. The overall sensitivity and specificity at a cutoff value of 3.5 per thousand were 97.8% (95% CI = 92.1-99.7%) and 98.5% (95% CI = 96.4-100%), respectively: high sensitivity and specificity were demonstrated in all three age groups (< or =5, 6-10, and > or = 11 yr). There was a close correlation between the values with isotope ratio mass spectrometry and NDIRS methods (r = 0.998, p < 0.001). CONCLUSIONS: The 13C-UBT with a cutoff value of 3.5 per thousand is an accurate diagnostic method for active H. pylori infection. The test with the NDIRS method is inexpensive and might be widely applied in clinical practice.