How do peptic ulcers present?
Peptic ulcers tend to present in one of two ways, either with gastric symptoms or they can be asymptomatic. The main symptoms of peptic ulcers are:
- Upper abdominal pain or discomfort (stomach ulcers tend to hurt shortly after eating whereas duodenal ulcers tend to hurt several hours later)
- Haematemesis – vomiting blood
- Melaena – black tarry stool due to altered blood that has been partially digested (frank blood in stool is usually due to lower gastrointestinal bleeding)
It is now accepted that H. pylori causes up to 75% of peptic ulcers in Europe and the USA, but this wasn’t always the case. Back in the 1980s it was thought that spicy food, alcohol, stressful lifestyles and non-steroidal anti-inflammatory drugs (NSAIDs) were the main causes. NSAIDs are still responsible for about 25% of peptic ulcers but the other causes have been replaced with H. pylori following the work of two Australian doctors in the early 1980s; Dr John Warren and Dr Barry Marshall.
How was the association between H. pylori and peptic ulcers discovered?
Dr John Warren and Dr Barry Marshall are credited as showing that H. pylori caused peptic ulcers. They had shown the presence of this bacterium (similar to Campylobacter species) in patients with gastritis but had failed to demonstrate that transmitting the bacterium to another host lead to the new host developing disease. This led to the medical profession being sceptical about the association of H. pylori with peptic ulcers which must have been very frustrating for Dr Warren and Dr Marshall.
In 1982 Dr Marshall decided to prove the association between H. pylori and ulcers by deliberately ingesting a culture of the bacterium. Within a week he had developed nausea and vomiting and terrible halitosis (bad breath) which apparently his mother complained about a lot. An endoscopy at this time showed severe gastritis (inflammation of the stomach). In order to try and show that H. pylori caused peptic ulcers Dr Marshall tried to tough out his symptoms but by 2 weeks enough was enough and he started to take antibiotics to try and eliminate the bacterium. A repeat endoscopy at this time failed to show any ulcers.
The experiment could be described as foolhardy as in natural exposure to H. pylori no one swallows such a large amount of bacteria in pure culture and so the risks were high. However, I suspect that there are people out there who think the ends justified the means… maybe…but not me…I prefer flavoured yogurt for breakfast! Personally I find it curious how this experiment is hailed as the discovery of the link between peptic ulcers and H. pylori, when in fact the experiment actually only showed a link to gastritis; Dr Marshall never actually developed ulcers. Whatever your views about this experiment it is now famous and Dr Warren and Dr Marshall were awarded a Nobel Prize for medicine in 2005 for their work on peptic ulcer disease. Maybe I should change my breakfast to live yoghurt and look for other associations?
How can H. pylori survive in the stomach?
The stomach is a pretty hostile place; very few bacteria can survive there because of the acid produced. H. pylori has an advantage in that not only can it physically attach to the gastric mucosa but it also produces vast quantities of urease. The urease breaks down urea in the stomach mucosa to produce ammonia and water and the alkaline ammonia neutralises gastric acid around the bacterium thereby protecting it. H. pylori is also motile and able to swim into the mucus lining the stomach which also helps to protect it from the stomach contents.
How is peptic ulcer disease managed?
When I was at medical school in the early 1990s most peptic ulcers presented with severe gastrointestinal bleeding and patients needed urgent surgical treatment to stop them dying, either over-sewing of the ulcer or gastrectomy to remove the bleeding part of the stomach. It was major surgery and patients took a long time to recover.
Nowadays early management of H. pylori infection is simpler and safer and I suspect that many general surgeons are no longer that familiar with the operations to treat ulcer disease in an emergency.
How is H. pylori infection diagnosed?
Patients with symptoms of gastritis (who do not get better with lifestyle changes or antacids), peptic ulcers and patients about to embark on prolonged courses of treatment with NSAIDs should be tested for H. pylori.
The two most commonly available tests are the stool antigen test (SAT) and the urease breath test (UBT).
The SAT looks for the presence of the actual bacterium H. pylori in faeces. This enzyme immunoassay has few false positives but does have a false negative rate of about 10-15%.
The UBT is based on the ability of H. pylori to split urea to produce CO2 and ammonia. In the test the patient is given urea labelled with carbon 13 to drink (non-radioactive and a different type of carbon from that which normally occurs in nature carbon 14). When H. pylori breaks down the labelled urea the CO2 produced and breathed out by the patient has carbon 13 not carbon 14 and this can be detected by mass spectrometry of the air the patient breaths out into a machine. The specificity is very high, 95-100%, and therefore false positives are very rare.
False negatives can occur with both tests if the patient is taking antibiotics which might suppress the bacterium or if they are on antacids. Patients undergoing a SAT or UBT should ideally be off antibiotics and antacids for 4 weeks prior to the test.
Patients who have either a positive SAT or UBT should be treated with “triple therapy” to eradicate H. pylori (see below).
Patients who have gastritis or peptic ulcers diagnosed during an endoscopy can have a urease test performed on a biopsy specimen. The principle is the same as for the UBT but rather than testing for carbon 13 labelled CO2, the test only has to look for the ability of the bacterium to split urea and cause a change in pH. The most commonly used test is the CLOtest (Campylobacter-Like Organism test). Yes really this is its name; clearly they were struggling and ran out of fancy test names!
NB In the past, a blood test to detect antibodies to H. pylori was one of the main investigations available in the UK but this is no longer routinely performed as it cannot tell the difference between current and past infection.
How is H. pylori treated?
The treatment of H. pylori is known as “triple therapy” as it normally consists of three oral drugs, usually an anti-acid drug (e.g. a proton pump inhibitor, PPI) plus two antibiotics.
PPI e.g. Lansoprazole 30mg BD
PLUS Amoxicillin 1g BD
PLUS Clarithromycin 500mg BD
(if 1st line contraindicated)
PPI e.g. Lansoprazole 30mg BD
PLUS Clarithromycin 500mg BD
PLUS Metronidazole 400mg BD
First line treatment is effective in over 85% of patients therefore at present there is no recommendation in the UK to routinely undertake follow up testing for cure. However if symptoms persist, or multiple regimens of antibiotics are required, then repeat testing with SAT or UBT should be performed. In addition a different treatment regimen should be tried as well as considering whether to perform an endoscopy to look for other pathology.
Alternative treatment regimens for H. pylori treatment and eradication may include combinations of a PPI and TWO of the following antibiotics:
- Tetracycline hydrochloride 500mg QDS
- Doxycycline 100mg BD
- Levofloxacin 250mg BD
- Rifabutin 150mg BD
Duration: 7 days UNLESS using as 3rd line treatment in which case use for 10 days.
The guideline listed in the references at the end of this blog gives further treatment regimens for patients who fail therapy for H. pylori.
It is likely that there will be a recommendation in the near future to confirm cures with repeat testing 4-6 weeks after stopping treatment as the incidence of treatment failure due to resistance is increasing.
If patients fail two treatment regimens then endoscopy should be performed to take samples to culture H. pylori and test it for antibiotic resistance. Culture is difficult and requires specialist laboratory media. Endoscopists should send biopsy samples placed in Dent’s media to the microbiology laboratory who will forward them to the Reference Laboratory. It takes 1-2 weeks to get the result back. The Endoscopist needs to inform the laboratory in advance of the procedure as most laboratories do not stock Dent’s media and have to order it in specifically for when a patient is undergoing a biopsy; the laboratory need about two weeks warning for this!! In an emergency samples can be sent in normal saline but this is not as good and the success of these cultures are lower.
If culture and sensitivity is performed then treatment regimens can be tailored to include TWO antibiotics to which the bacterium has been shown to be sensitive giving a much better chance of successful eradication. In this case 10 days of antibiotics are usually given.
The main complications of gastritis and peptic ulcer disease caused by H. pylori are:
- Bleeding (5-20%)
- Perforation (5-10%)
- Gastric malignancy – chronic gastritis can predispose to cancer
These rates are those for patients who have peptic ulcers, but in my experience I don’t see many of these patients anymore as I expect many patients with H. pylori are treated before they get peptic ulcers and therefore the overall incidence of complications in the total population has fallen.
So the Microbiologist replied to their colleague advising them to stop any PPIs or antibiotics the patient was on and wait until the laboratory has ordered some Dent’s media before performing the endoscopy and biopsy. The Microbiologist also suggested that as the patient had already failed 1st and 2nd line regimens, it would be sensible to wait for the results of the culture and sensitivity before treating if the patient remained stable. If the patient was too unwell to wait then to treat with a combination of a PPI and Doxycycline PLUS Levofloxacin for 10 days (neither of which the patient had had before). The results from the biopsy confirmed sensitivity to Doxycycline and Levofloxacin as well as resistance to Amoxicillin, Clarithromycin and Metronidazole (1st and 2nd line regimens). The patient improved and follow up testing at six weeks confirmed eradication of the Helicopter pylon… I mean Helicobacter pylori…
NB Who knew…there is a helicopter pylon! It supports the rotor head of a helicopter… but it certainly doesn’t cause peptic ulcers.