|
|
|
The common types of peptic ulcer are duodenal ulcers and gastric (stomach) ulcers. Until recently, the cause was unknown, and was thought to be a result of too much acid, smoking, alcohol, stress or bad diet. While it is true that any of these things may bring on a bout of pain from an ulcer, or slow its healing (particularly cigarette smoking), it is unlikely that they cause the ulcer in the first place.
In recent years much new information has become available about the cause of ulcers. There is now no doubt that most duodenal and gastric (stomach) ulcers are caused by a chronic infection of the stomach with a bacterium (germ) known as Helicobacter pylori . The other common cause of ulcers is anti-inflammatory drugs, commonly used for arthritis and back pain. Both causes may exist together. If the stomach is infected with Helicobacter and you are taking anti-inflammatory drugs, the risk of developing an ulcer is quite high.
Some patients with ulcers have no symptoms at all. Commonly, burning pain in the upper part of the abdomen is felt at various times, for example when hungry, an hour or so after a meal or in the early hours of the morning. Occasionally, if the ulcer is bleeding, the faeces will turn pitch black, and if this ever occurs, urgent medical attention should be sought. (Other common causes of black motions are iron tablets or DeNol tablets). The most common cause of indigestion, (discomfort or pain after a meal) is not an ulcer, as many people think, but is actually a different condition known as reflux oesophagitis. Many people who were thought to have had an ulcer in the past, have actually had reflux oesophagitis, sometimes also known as "hiatus hernia". Typically this condition produces "heartburn", excessive burping, a sour taste in the throat from refluxed stomach juice and is often worse when a person is lying down. It may be difficult to distinguish between an ulcer and reflux oesophagitis from the symptoms alone, and occasionally both conditions co-exist. Some drugs (e.g. Tagamet, Zantac, Pepcidine, Amfamox, Tazac, Losec, Zoton, Somac, Pariet, Nexium ) are effective in relieving pain from either an ulcer or reflux oesophagitis. Modern techniques of investigation, especially gastroscopy, make it easy to distinguish between the two conditions.
|
Apart from causing gastric and duodenal ulcers, this bacterium even more often causes inflammation of the lining of the stomach, known as gastritis. Moreover, people with Helicobacter gastritis frequently feel, and are, quite well. Some patients develop symptoms identical to an ulcer, without an actual ulcer being present. In the past, when barium meal x-ray had revealed no sign of an ulcer, the problem was often labelled "nervous dyspepsia", and was thought to be a psychological disorder. Whereas there are some true cases of nervous dyspepsia, most of these patients have either Helicobacter gastritis or reflux oesophagitis . Accordingly, barium meal X-rays are now used much less commonly. Other common symptoms of Helicobacter gastritis include nausea, an uncomfortable bloated sensation of the upper abdomen and halitosis (bad breath). The germ can be eradicated, although it can be quite stubborn - a combination of drugs is therefore most effective. Eradicating the germ dramatically reduces the risk of another ulcer forming in the future, once it has been healed. Recurrence of Helicobacter pylori in the stomach, following successful treatment, is rare. However, incomplete eradication of the Helicobacter germ occurs in about 10% of cases. There is now no doubt that long term Helicobacter gastritis may result in stomach cancer, and is probably the major cause of this disease world-wide. However, the risk in any individual is small, and it is likely that stomach cancer occurs in no more than about 1-2% of patients with long-standing untreated Helicobacter gastritis . Stomach cancer in Australia is now only one quarter as common as it was in the early part of the century, probably because of a lower incidence of Helicobacter gastritis within the community. The reason for this is probably related to safer water and food supplies. In underdeveloped countries, up to 80% of people have Helicobacter gastritis , and in these communities the incidence of stomach cancer is much higher than it now is in Australia.
|
(used commonly for arthritis and back pain) This is another common cause of gastric (stomach) and duodenal ulcers. A 60 Minutes TV programme highlighted this, and has made many people very frightened indeed. In fact, only a small minority of people taking these drugs ever develops an ulcer. There are large numbers of these drugs on the market, and they include:
Newer anti-inflamatory drugs (Celebrex, Vioxx) known as Cox II inhibitors are probably less likely to cause ulcers. Drugs commonly used in gout include Zyloprim and Colchicine and these do not cause ulcers. Paracetamol ( Panadol, Dymadon ) is much less likely than any of the others above to result in ulcer problems. Aspirin should be strictly avoided in patients with known, suspected or past ulcers, as not only can it result in a flare-up, but can also result in troublesome bleeding from the ulcer. Although the anti-inflammatory drugs listed above may also cause bleeding (by inhibiting the ability of the blood to clot), this effect is not as great as with aspirin . If there is no past history of an ulcer, and you do not have symptoms suggestive of an ulcer, then there is no reason to cease anti-inflammatory drugs. If you are taking anti-inflammatory tablets for arthritis, in addition to aspirin (even ˝ tablet a day, which is often used to "thin the blood") it is essential you are checked for the possibility of Helicobacter gastritis. This does not necessarily mean an endoscopy (gastroscopy), as it is easy to check for the presence of Helicobacter with a blood test or breath test - if in any doubt, discuss with your doctor.
Poor diet does not cause ulcers. In particular, acidic foods such as tomatoes and pineapple do not cause ulcers. Some foods will result in pain if an ulcer is already present, and obviously these foods should be avoided. Otherwise, there is no point in adhering to an "ulcer diet" or any other form of diet, in the hope that this will help the ulcer to get better.
This form of peptic ulcer is so named because it occurs in the stomach, rather than the duodenum. One reason that gastric ulcers are treated with more caution is that very rarely, stomach cancers may look like a simple benign gastric ulcer in the early stages. For this reason, when a gastric ulcer is seen at gastroscopy, a biopsy is taken to make sure there are no cancer cells present. Cancer in this situation is uncommon, but to be on the safe side, it is recommended that all patients with a gastric ulcer have a second gastroscopy about six weeks later to make sure it has healed. If not, another biopsy is taken. Duodenal ulcers never progress to cancer and there is usually no need for a second gastroscopy or biopsy, unless the pain persists despite treatment.
|
Effective acid-supressing drugs have been available, the best known examples of which are the "H2-antagonist" drug Zantac (ranitidine), and the"PPI" drug, Losec (omeprazole). H2A drugs are strong acid supressors, and PPI's are extremely potent. There are many H2A's and PPI's made by various companies and they are all virtually identical in their effects. These drugs are equally effective in relieving pain from reflux oesophagitis and peptic ulcer, but unfortunately have to be taken for life for permanent relief. Better alternatives exist in both conditions.
Most people who have used these will agree that relief of pain is very rapid and satisfying. These drugs work by reducing the acid present in the stomach. Without acid, ulcers will heal, although too much acid is not the primary cause, as was previously thought. Unfortunately, this means that to keep the ulcer healed, these drugs must be taken indefinitely. Nobody wants to be on life-long treatment, and the cost of the tablets can be enormous. A better approach is to eradicate the germ when it is present, and if possible, to stop using ulcer-causing anti-inflammatory drugs if these are the culprits. Anti-inflammatory drugs may be taken in suppository form, and even when used by this method, they can still cause ulcer problems, although probably to a lesser extent than the tablets. It is hardly ever necessary for anyone to be on life-long treatment for an ulcer . If you smoke, it is important that you stop, as ulcer healing is delayed by smoking.
Since the mid 1980's, surgery for ulcers has been very rarely necessary unless there is an emergency situation such as uncontrolled bleeding or perforation. Even major bleeding (usually associated with the use of NSAID-drugs including aspirin) or perforation (usually presenting as an instant severe upper abdominal pain) can be managed without open abdominal surgery in most cases. Now that the cause of most ulcers is apparent, removal of the cause usually results in permanent healing of the ulcer. Remember, an ulcer is not a life-long sentence, and the vast majority can be healed within six weeks of treatment.
|
|
|
Clarithromycin-based triple therapies have been accepted as the best treatments for curing Helicobacter pylori infection. Clarithromycin has several qualities that justify this choice, such as good diffusion in the gastric mucosa not greatly affected by the low pH. However, the widespread use of this drug during the last 10 years has led to the development of resistant H. pylori strains.
The mechanism of this resistance is well known. There are two positions on the sequence of the 23S RNA gene at which mutations occur. These mutations modify the spatial structure of the ribosome and prevent macrolide binding. This straightforward mechanism explains why resistance is easily detected in the laboratory, and why it has a progressive but limited spread.
In fact, mutations are only transferred vertically to bacterial descendants, rather than horizontally, as is the case with resistance factors carried by plasmids. In addition, the spread of H. pylori itself is limited essentially to the immediate family of index cases. For these reasons, the level of resistance to macrolides, including clarithromycin, is in the range of 0–20% in adults throughout the world, and parallels the use of macrolides. To cite an example in Europe, France, which has the highest rate of macrolide consumption, also has the highest rate of H. pylori resistance to clarithromycin. The rate of resistance in children can be even higher than in adults, and can reach 30–40%. It is now clear that macrolide resistance is the best factor for predicting the failure of clarithromycin-based regimens. The predictiveness is so good that the value of a pragmatic approach for treatment can be questioned when the resistance level reaches 20%. In these circumstances, performing antimicrobial susceptibility testing would be a more rational approach. This is in line with the development of tests that provide very accurate results within a few hours after biopsy sampling—compared to several days using the standard culture and antibiogram testing. This test is based on real-time polymerase chain reaction (PCR) testing and an analysis of the melting curve obtained. Another method, which even avoids the need for PCR testing, has also been proposed—the fluorescent in-situ hybridization (FISH) method.
Another drug used to treat H. pylori to which resistance may develop is metronidazole. However, the situation with this agent is not as clear as for macrolides. An oxygen-insensitive nitroreductase, encoded by rdxA, is claimed to be the enzyme responsible for metronidazole reduction, which is the necessary step occurring inside the cell for a compound to be active on the DNA. Point mutations on rdxA have also been associated with this resistance. However, it seems that this enzyme does not explain the whole picture. Other enzymes such as FrxA seem to be part of the process, although it is not possible at this stage to determine whether they have a direct or indirect action. The consequence is that molecular detection of this type of resistance is not possible, in addition to the fact that the standard methods produce discordant and sometimes even unreproducible results for a given method.
With regard to the prevalence of metronidazole resistance, there is a clear-cut difference between tropical and temperate countries. In tropical countries, metronidazole is widely used to treat parasitic infections, and H. pylori resistance may reach 80–90%. In temperate countries, the prevalence is in the range of 10–50%, and may be due to the use of this drug for gynecological and dental infections. Fortunately, the clinical impact is not as dramatic as that for clarithromycin resistance; most large studies and meta-analyses indicate a reduction in treatment efficacy of about 20% in the case of metronidazole resistance.
In addition to macrolide and metronidazole resistance, it is noteworthy that a few strains resistant to amoxicillin have also been described. The mechanism seems to involve the penicillin-binding proteins, but no in-depth studies have been performed. H. pylori has also developed resistance to quinolones and rifamycins through mutation. Cases of resistance to tetracycline are exceptional, but possible.
Since the introduction of the first antibiotics in the 1940s, bacteria have always succeeded in surviving by developing resistance, which has been combatted by producing new antibiotics. It is logical that H. pylori has also developed resistance mechanisms, and that the prevalence of resistance is on the increase. Unfortunately, it seems that we have given up on this race, as there are no new antibiotics in the pipeline. We will therefore need to prepare ourselves for a difficult period in which careful use of the antibiotics currently available is warranted.
