April 1997
MIAMI BEACH, Fla. — Pediatricians need to change their thinking from "no acid, no ulcer to no acid, no Helicobacter pylori," according to William J. Byrne, MD, clinical professor of pediatrics, University of California/San Francisco in Oakland, Calif.
"The three factors that contribute to the etiology of peptic ulcer disease in children or adults are nonsteroidal anti-inflammatory drugs, acid and H. pylori" said Byrne. "Up to 95% of duodenal ulcer patients are H. pylori positive, and 65% of gastric ulcer patients are H. pylori positive," Byrne said at the recent Annual Pediatric Postgraduate Course, sponsored here by Miami Children's Hospital. Byrne is also medical director/senior vice president for medical affairs, Children's Hospital in Oakland.
H. pylori is a gram-negative bacteria that colonizes only in gastric mucosa or gastric-type epithelium. It is spiral shaped, has four to six flagelli at one pole and has come to survive in the acidic environment of the stomach. "H. pylori has only recently begun to be appreciated as the cause of disease, but the organism itself is not new," said Byrne. Spiral shaped organisms were first recognized at the turn of the century in human stomachs, and were seen in the stomachs of animals as far back as 1890. But it really wasn't until the pioneering work of Warren and Marshall in 1983 that a connection between H. pylori and gastritis was made. The whole field of gastroenterology in terms of peptic ulcer disease changed after that.
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H. pylori is so widespread it has become the most common infection in humans. It has been found in every country in which it has been sought, according to Byrne. "However, the infection rates in both children and adults are much higher in the developing worlds than they are in the industrialized countries," he said.
"There are certain factors that are important in terms of infection rates. We do know that lower economic status correlates with an increased infection rate, and also crowded living conditions. We should start to think about children with abdominal pain in this population as possibly being H. pylori positive."
Because H. pylori is so incredibly common, Byrne said it is only natural to wonder why more infection isn't seen? An estimated 10% to 25% of individuals infected with H. pylori will eventually develop symptomatic disease. "We don't know or understand why some patients develop symptomatic disease and others do not," said Byrne. "Perhaps it has to do with different phenotypes or there may be some individual host factors that still have to be elucidated," he said.
How does this organism survive in the hostile environment of the stomach? "H. pylori produces urease, which may neutralize acid and allow the organism to survive in this acid environment," explained Byrne. "It is a very motile organism, so it furrows its way down to the mucosa and there it comes in contact with the gastric epithelium, where it secretes adenosine and actually fits on to the gastric epithelium."
How does an organism that lives in the gastric epithelium cause a duodenal ulcer? The proposed mechanics, according to Byrne, go something like this: H. pylori colonizes in the gastric epithelium and because of this colonization there is an increased load of acid, which develops a metaplasmia in the duodenum; the duodenum reverts back to a slightly more permanent epithelium and the H. pylori then moves into the duodenum where they produce an inflammatory response and ultimately a duodenal ulcer evolves.
Serology and breath tests are two ways to diagnose H. pylori. Other options include a lack-of-urease test, "which allows you to actually see the bacteria," according to Byrne, "or you can culture the organism."
Although serology is available, there are still several problems that need to be overcome. "One is that it does not tell you whether or not you've actually eradicated the infection," said Byrne, "so while the test will tell you if someone has been exposed, it won't tell you whether the infection is active, and you cannot determine whether you've eradicated the organism."
Byrne has high hopes for a breath test. "The one test that I hope will become available because it is very sensitive and very specific is a breath test," said Byrne. "It is non-invasive in the sense that it does not require endoscopy. It just requires a sample of the person's breath." The test is used with carbon 13 or carbon 14 isotopes, which the patient ingests usually in capsule form.
"If H. pylori is present, the urease splits the urea into radioactive CO2. This is an easy way of determining if a patient is infected and after you have treated them, whether or not you have successfully eradicated the infection. Hopefully this will soon be more readily available," said Byrne.
The proof that H. pylori needs to be treated is that children with duodenal ulcers who are not treated for H. pylori have a 55% relapse rate; while children with duodenal ulcers who are treated for H. pylori have a less than 3% relapse rate. "Clearly when you are treating a patient with a documented duodenal ulcer, you not only want to decrease acid secretion, but you have got to get rid of the bug," said Byrne.
Byrne recommended a three-drug combination for a course of six to eight weeks. Omeprazole (Prilosec, Astra Merck) with amoxicillin and clarithromycin (Biaxin, Abbott) offers a 90% to 95% eradication rate. "If the symptoms exist, do a serology for H. pylori. If the bug is not eradicated after one course of the triple therapy, I would suggest that you treat the patient for a second course.
"If after the second course, the child remains symptomatic, you should refer to a pediatric gastroenterologist who will probably do an upper endoscopy," said Byrne.
A vaccine for H. pylori is under development because of its worldwide prevalence. "We're looking at developing a vaccine," said Byrne, "which hopefully will not only be prophylactic, but will also actually have some therapeutic value."
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