Dyspepsia
Encyclopedia
Dyspepsia also known as upset stomach or indigestion, refers to a condition of impaired digestion
. It is a medical condition characterized by chronic or recurrent pain
in the upper abdomen
, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating
, belching, nausea
, or heartburn
. Dyspepsia is a common problem, and is frequently due to gastroesophageal reflux disease
(GERD) or gastritis
, but in a small minority may be the first symptom of peptic ulcer disease (an ulcer of the stomach or duodenum
) and occasionally cancer
. Hence, unexplained newly-onset dyspepsia in people over 55 or the presence of other alarming symptoms may require further investigations.
Functional dyspepsia (previously called nonulcer dyspepsia) is dyspepsia "without evidence of an organic disease that is likely to explain the symptoms". Functional dyspepsia is estimated to affect about 15% of the general population in western countries.
. Pain worsened by exertion and associated with nausea
and perspiration may also indicate angina
.
Occasionally dyspeptic symptoms are caused by medication, such as calcium antagonists (used for angina
or high blood pressure
), nitrates (used for angina), theophylline
(used for chronic lung disease), bisphosphonate
s, corticosteroid
s and non-steroidal anti-inflammatory drug
s (NSAIDs, used as painkillers).
The presence of gastrointestinal bleeding
(vomit containing blood), difficulty swallowing
, loss of appetite, unintentional weight loss, abdominal swelling and persistent vomiting
are suggestive of peptic ulcer disease or malignancy, and would necessitate urgent investigations.
People under the age of 55 years with no alarm features do not need endoscopy but are considered for investigation for peptic ulcer disease caused by Helicobacter pylori
infection
. Investigation for H. pylori infection is usually performed when there is a moderate to high prevalence of this infection in the local community or the person with dyspepsia has other risk factors for H. pylori infection, related for example to ethnicity or immigration from a high-prevalence area. If infection is confirmed it can usually be eradicated by medication.
Medication-related dyspepsia is usually related to non-steroidal anti-inflammatory drug
s (NSAIDs) and can be complicated by bleeding or ulceration with perforation of stomach wall.
, prokinetic agents, and antiflatulent
s. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy.
Antacids and sucralfate
were found to be no better than placebo in a literature review. H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction), but only a marginal benefit in good quality trials. Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia. They have been shown in a meta-analysis to produce a relative risk reduction of up to 50%, but the studies evaluated to come to this conclusion used the drug cisapride
which has since been removed from the market (now only available as an investigational agent) due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit. Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects. Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride. So, with the somewhat recent advent of the proton pump inhibitor (PPI) class of medications, the question of whether these new agents are superior to traditional therapy has arisen.
A 2002 systemic review of herbal products found that several herbs, including peppermint
and caraway
, have anti-dyspeptic effects for non-ulcer dyspepsia with "encouraging safety profiles". A 2004 meta-analysis, pooling data from three double-blind placebo-controlled studies
, found the multiple herbal extract Iberogast
to be significantly more effective than placebo (p value = .001) at treating patients with functional dyspepsia through the targeting of multiple dyspeptic pathologies. This German-made phytopharmaceutical was found to be equivalent to cisapride and significantly superior to metoclopramide at reducing the symptoms of functional dyspepsia over a four week period. Retrospective surveillance of 40,961 children (12 years and under) found no serious side-effects. Red pepper powder has also found to be promising. Ginger
and related products made therefrom have been shown to have some positive alleviation of symptoms, in particular for motion sickness and pregnancy-related nausea
Currently, PPIs are, depending on the specific drug, FDA indicated for erosive esophagitis
, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome
, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. There are, however, evidence-based guidelines and literature that evaluate the use of PPIs for this indication. A helpful chart summarizing the major trials is available from the functional dyspepsia guidelines published in the World Journal of Gastroenterology in 2006.
The CADET study was the first to compare a PPI (omeprazole 20 mg daily) to both an H2-RA (ranitidine 150 mg BID) as well as a prokinetic agent (cisapride 20 mg BID) alongside placebo. The study evaluated these agents in patients at 4 weeks and 6 months and noted that omeprazole had a significantly better response at 6 months (31%) than cisapride (13%) or placebo (14%) (p = .001) while it was just above the cutoff for being statistically significantly better than ranitidine (21%) (p = .053). Omeprazole also showed a significant increase in quality of life scores over the other agents and placebo in all but one category measured (p = .01 to .05).
The ENCORE study, which was a follow-up of patients from the OPERA study, showed responders to omeprazole therapy had fewer clinic visits than non-responders (1.5 vs 2.0) over a three month period (p < .001).
review found that treating H. pylori did have a small effect in improving nonulcer dyspepsia symptoms.
Digestion
Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....
. It is a medical condition characterized by chronic or recurrent pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
in the upper abdomen
Abdomen
In vertebrates such as mammals the abdomen constitutes the part of the body between the thorax and pelvis. The region enclosed by the abdomen is termed the abdominal cavity...
, upper abdominal fullness and feeling full earlier than expected when eating. It can be accompanied by bloating
Bloating
Bloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Symptoms:The most common...
, belching, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, or heartburn
Heartburn
Heartburn, also known as pyrosis or acid indigestion is a burning sensation in the chest, just behind the breastbone or in the epigastrium...
. Dyspepsia is a common problem, and is frequently due to gastroesophageal reflux disease
Gastroesophageal reflux disease
Gastroesophageal reflux disease , gastro-oesophageal reflux disease , gastric reflux disease, or acid reflux disease is chronic symptoms or mucosal damage caused by stomach acid coming up from the stomach into the esophagus...
(GERD) or gastritis
Gastritis
Gastritis is an inflammation of the lining of the stomach, and has many possible causes. The main acute causes are excessive alcohol consumption or prolonged use of nonsteroidal anti-inflammatory drugs such as aspirin or ibuprofen. Sometimes gastritis develops after major surgery, traumatic...
, but in a small minority may be the first symptom of peptic ulcer disease (an ulcer of the stomach or duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
) and occasionally cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Hence, unexplained newly-onset dyspepsia in people over 55 or the presence of other alarming symptoms may require further investigations.
Functional dyspepsia (previously called nonulcer dyspepsia) is dyspepsia "without evidence of an organic disease that is likely to explain the symptoms". Functional dyspepsia is estimated to affect about 15% of the general population in western countries.
Signs and symptoms
The characteristic symptoms of dyspepsia are upper abdominal pain, bloating, fullness and tenderness on palpationPalpation
Palpation is used as part of a physical examination in which an object is felt to determine its size, shape, firmness, or location...
. Pain worsened by exertion and associated with nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and perspiration may also indicate angina
Angina
Angina pectoris, commonly known as angina, is chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries . Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries...
.
Occasionally dyspeptic symptoms are caused by medication, such as calcium antagonists (used for angina
Angina
Angina pectoris, commonly known as angina, is chest pain due to ischemia of the heart muscle, generally due to obstruction or spasm of the coronary arteries . Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries...
or high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
), nitrates (used for angina), theophylline
Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. Because of its numerous side-effects, the drug is now rarely administered for clinical use. As a member of the xanthine family, it...
(used for chronic lung disease), bisphosphonate
Bisphosphonate
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases...
s, corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s and non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s (NSAIDs, used as painkillers).
The presence of gastrointestinal bleeding
Gastrointestinal bleeding
Gastrointestinal bleeding or gastrointestinal hemorrhage describes every form of hemorrhage in the gastrointestinal tract, from the pharynx to the rectum. It has diverse causes, and a medical history, as well as physical examination, generally distinguishes between the main forms...
(vomit containing blood), difficulty swallowing
Dysphagia
Dysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
, loss of appetite, unintentional weight loss, abdominal swelling and persistent vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
are suggestive of peptic ulcer disease or malignancy, and would necessitate urgent investigations.
Diagnosis
People under 55 years, without alarm symptoms, can be treated without investigation. People over 55 years with recent onset dyspepsia or those with alarm symptoms should be urgently investigated by upper gastrointestinal endoscopy. This will rule out peptic ulcer disease, medication-related ulceration, malignancy and other rarer causes.People under the age of 55 years with no alarm features do not need endoscopy but are considered for investigation for peptic ulcer disease caused by Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
. Investigation for H. pylori infection is usually performed when there is a moderate to high prevalence of this infection in the local community or the person with dyspepsia has other risk factors for H. pylori infection, related for example to ethnicity or immigration from a high-prevalence area. If infection is confirmed it can usually be eradicated by medication.
Medication-related dyspepsia is usually related to non-steroidal anti-inflammatory drug
Non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s (NSAIDs) and can be complicated by bleeding or ulceration with perforation of stomach wall.
Treatment
Functional and undifferentiated dyspepsia have similar treatments. Decisions around the use of drug therapy are difficult because trials included heartburn in the definition of dyspepsia. This led to the results favoring proton pump inhibitors (PPIs), which are effective for the treatment of heartburn. Traditional therapies used for this diagnosis include lifestyle modification, antacids, H2-receptor antagonists (H2-RAs)H2-receptor antagonist
The H2 receptor antagonists are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective ...
, prokinetic agents, and antiflatulent
Antiflatulent
An antiflatulent agent is a drug used for the alleviation or prevention of excessive intestinal gas, i.e., flatulence.- Preventing gas :* Enzymes - Enzyme-based dietary supplements break down indigestible substances and prevent these substances from reaching the large intestine intact -- where...
s. It has been noted that one of the most frustrating aspects of treating functional dyspepsia is that these traditional agents have been shown to have little or no efficacy.
Antacids and sucralfate
Sucralfate
Sucralfate is a cytoprotective agent, an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Brand names include Sucramal in Italy; Carafate in U.S.A.; Pepsigard, Sucral, Sucrafil, Hapifate in India; Sutra or Musin in parts of South-East Asia; Sulcrate...
were found to be no better than placebo in a literature review. H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction), but only a marginal benefit in good quality trials. Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia. They have been shown in a meta-analysis to produce a relative risk reduction of up to 50%, but the studies evaluated to come to this conclusion used the drug cisapride
Cisapride
Cisapride is a gastroprokinetic agent, a drug which increases motility in the upper gastrointestinal tract. It acts directly as a serotonin 5-HT4 receptor agonist and indirectly as a parasympathomimetic. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous...
which has since been removed from the market (now only available as an investigational agent) due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit. Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects. Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride. So, with the somewhat recent advent of the proton pump inhibitor (PPI) class of medications, the question of whether these new agents are superior to traditional therapy has arisen.
A 2002 systemic review of herbal products found that several herbs, including peppermint
Peppermint
Peppermint is a hybrid mint, a cross between the watermint and spearmint . The plant, indigenous to Europe, is now widespread in cultivation throughout all regions of the world...
and caraway
Caraway
Caraway also known as meridian fennel, or Persian cumin is a biennial plant in the family Apiaceae, native to western Asia, Europe and Northern Africa....
, have anti-dyspeptic effects for non-ulcer dyspepsia with "encouraging safety profiles". A 2004 meta-analysis, pooling data from three double-blind placebo-controlled studies
Placebo-controlled studies
A Placebo-controlled study is a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect...
, found the multiple herbal extract Iberogast
Iberogast
Iberogast, also known as STW 5, is a prokinetic liquid formulation of nine herbs indicated for Irritable Bowel Syndrome and dyspepsia. A proprietary blend, it was developed in Germany in 1961 and is available in other countries...
to be significantly more effective than placebo (p value = .001) at treating patients with functional dyspepsia through the targeting of multiple dyspeptic pathologies. This German-made phytopharmaceutical was found to be equivalent to cisapride and significantly superior to metoclopramide at reducing the symptoms of functional dyspepsia over a four week period. Retrospective surveillance of 40,961 children (12 years and under) found no serious side-effects. Red pepper powder has also found to be promising. Ginger
Ginger
Ginger is the rhizome of the plant Zingiber officinale, consumed as a delicacy, medicine, or spice. It lends its name to its genus and family . Other notable members of this plant family are turmeric, cardamom, and galangal....
and related products made therefrom have been shown to have some positive alleviation of symptoms, in particular for motion sickness and pregnancy-related nausea
Currently, PPIs are, depending on the specific drug, FDA indicated for erosive esophagitis
Esophagitis
Esophagitis is inflammation of the esophagus. It may be acute or chronic. The acute esophagitis can be catarrhal or phlegmonous, whereas the chronic esophagitis may be hypertrophic or atrophic.-Infectious:...
, gastroesophageal reflux disease (GERD), Zollinger-Ellison syndrome
Zollinger-Ellison syndrome
Zollinger–Ellison syndrome is a triad of gastric acid hypersecretion, severe peptic ulceration, and non-beta cell islet tumor of pancreas . In this syndrome increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. Often the cause is a tumor of...
, eradication of H. pylori, duodenal and gastric ulcers, and NSAID-induced ulcer healing and prevention, but not functional dyspepsia. There are, however, evidence-based guidelines and literature that evaluate the use of PPIs for this indication. A helpful chart summarizing the major trials is available from the functional dyspepsia guidelines published in the World Journal of Gastroenterology in 2006.
The CADET study was the first to compare a PPI (omeprazole 20 mg daily) to both an H2-RA (ranitidine 150 mg BID) as well as a prokinetic agent (cisapride 20 mg BID) alongside placebo. The study evaluated these agents in patients at 4 weeks and 6 months and noted that omeprazole had a significantly better response at 6 months (31%) than cisapride (13%) or placebo (14%) (p = .001) while it was just above the cutoff for being statistically significantly better than ranitidine (21%) (p = .053). Omeprazole also showed a significant increase in quality of life scores over the other agents and placebo in all but one category measured (p = .01 to .05).
The ENCORE study, which was a follow-up of patients from the OPERA study, showed responders to omeprazole therapy had fewer clinic visits than non-responders (1.5 vs 2.0) over a three month period (p < .001).
H. pylori connection
The relationship between H. pylori and functional dyspepsia has been controversial, with several trials finding a benefit and others finding no benefit; a 2003 Cochrane CollaborationCochrane Collaboration
The Cochrane Collaboration is a group of over 28,000 volunteers in more than 100 countries who review the effects of health care interventions tested in biomedical randomized controlled trials. A few more recent reviews have also studied the results of non-randomized, observational studies...
review found that treating H. pylori did have a small effect in improving nonulcer dyspepsia symptoms.