Indigestion

Indigestion, also known as dyspepsia, is a condition of impaired digestion.^[1] Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain.^[2] People may also experience feeling full earlier than expected when eating.^[3] Dyspepsia is a common problem and is frequently caused by gastroesophageal reflux disease (GERD) or gastritis.^[4] In a small minority it 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.^[5]

Functional indigestion (previously called nonulcer dyspepsia)^[6] is indigestion "without evidence of an organic disease that is likely to explain the symptoms".^[7] Functional indigestion is estimated to affect about 15% of the general population in western countries.^[6]

Signs and symptoms

In most cases, the clinical history is of limited use in distinguishing between organic causes and functional dyspepsia. A large systematic review of the literature was recently performed to evaluate the effectiveness of diagnosing organic dyspepsia by clinical opinion versus computer models in patients referred for upper endoscopy. The computer models were based on patient demographics, risk factors, historical items,and symptoms. The study showed that neither clinical impression nor computer models were able to adequately distinguish organic from functional disease.^[8]

In a recent study, patients with peptic ulcer disease were compared with patients with functional dyspepsia in an age and sex-matched study. Although the functional dyspepsia group reported more upper abdominal fullness, nausea, and overall greater distress and anxiety, almost all the same symptoms were seen in both groups. Therefore, it is the clinician’s challenging task to separate patients who may have an organic disorder, and thus warrant further diagnostic testing, from patients who have functional dyspepsia, who are given empiric symptomatic treatment.The workup should be targeted to identify or rule out specific causes. Traditionally, people at high-risk have been identified by “alarm” features. However, the utility of these features in identifying the presence of upper cancer of the esophagus or stomach has been debated. A meta analysis looking at the sensitivity and specificity of alarm features found a range of 0–83% and 40–98%, respectively. However, there was high heterogeneity between studies.^[9]

The physical examination may elicit abdominal tenderness, but this finding is nonspecific. A positive Carnett sign, or focal tenderness that increases with abdominal wall contraction and palpation, suggests an etiology involving the abdominal wall musculature. Cutaneous dermatomal distribution of pain may suggest a thoracic polyradiculopathy. Thump tenderness over the right upper quadrant may suggest chronic cholecystitis.^[10]

Cause

Non-ulcer indigestion

In about 50-70% of patients with dyspepsia, no definite organic cause can be determined. In this case, dyspepsia is referred to as non-ulcer dyspepsia and its diagnosis is established by the presence of epigastralgia for at least 6 months, in the absence of any other cause explaining the symptoms.

Post-infectious

Gastroenteritis increases the risk of developing chronic dyspepsia. Post infectious dyspepsia is the term given when dyspepsia occurs after an acute gastroenteritis infection. It is believed that the underlying causes of post-infectious IBS and post-infectious dyspepsia may be similar and represent different aspects of the same pathophysiology.^[11]

Functional

This is the most common cause of chronic dyspepsia. More than 70% of people have no obvious organic cause for their symptoms after evaluation. Symptoms may arise from a complex interaction of increased visceral afferent sensitivity, gastric delayed emptying (gastroparesis) or impaired accommodation to food. Anxiety is also associated with functional dyspepsia. In some people, it appears before the onset of gut symptoms; in other cases, anxiety develops after onset of the disorder, which suggests that a gut-driven brain disorder may be a possible cause. Although benign, these symptoms may be chronic and difficult to treat.^[12]

Diseases of the gastrointestinal tract

When dyspepsia can be attributed to a specific cause, the majority of cases concern gastroesophageal reflux disease (GERD) and peptic ulcer disease. Less common causes include gastritis, gastric cancer, esophageal cancer, coeliac disease, food allergy, inflammatory bowel disease, chronic intestinal ischemia and gastroparesis.

Liver and pancreas diseases

These include cholelithiasis, chronic pancreatitis and pancreatic cancer.

Food or drug intolerance

Acute, self-limited dyspepsia may be caused by overeating, eating too quickly, eating high-fat foods, eating during stressful situations, or drinking too much alcohol or coffee. Many medications cause dyspepsia, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), antibiotics (metronidazole, macrolides), diabetes drugs (metformin, Alpha-glucosidase inhibitor, amylin analogs, GLP-1 receptor antagonists), antihypertensive medications (angiotensin converting enzyme [ACE] inhibitors, Angiotensin II receptor antagonist), cholesterol-lowering agents (niacin, fibrates), neuropsychiatric medications (cholinesterase inhibitors [donepezil, rivastigmine]), SSRIs (fluoxetine, sertraline), serotonin-norepinephrine-reuptake inhibitors (venlafaxine, duloxetine), Parkinson drugs (Dopamine agonist, monoamine oxidase [MAO]-B inhibitors), corticosteroids, estrogens, digoxin, iron, and opioids.^[13]

Helicobacter pylori infection

The role of Helicobacter pylori in functional dyspepsia is controversial, and no clear causal relationship has been established. This is true for both the symptom profile and pathophysiology of functional dyspepsia. Although some epidemiologic studies have suggested an association between H. pylori infection and functional dyspepsia, others have not. The discrepancy may stem in part from differences in methodology and lack of adequate consideration of confounding factors such as past history of peptic ulcer disease and socioeconomic status.^[14] Controlled trials disagree about whether or not H. pylori eradication is beneficial in functional dyspepsia, with roughly half of the trials showing improvement and the other half no improvement. In a recent multicenter U.S. trial that randomized 240 patients to treatment or placebo, and followed patients for 12 months, 28% of treated patients versus 23% of those receiving placebo reported relief of symptoms at the 12-month follow-up. Similarly, recent European trials have not shown significant differences in symptoms after H. pylori eradication as compared with controls. Systematic reviews of eradication have been conducted, with varying results. A systematic review in the Annals of Internal Medicine suggested no statistically significant effect, with an odds ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.89–1.89; P = 0.18). Still, no effect was seen after adjusting for heterogeneity and for cure of H. pylori. In contrast, a Cochrane review found a small but statistically significant effect in curing symptoms (H. pylori cure vs placebo, 36% vs 30%, respectively).^[15][16]

Systemic diseases

There are a number of systemic diseases that may involve dyspepsia, including coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, and chronic renal disease.

Pathophysiology

Psychosomatic and cognitive factors are important in the evaluation of patients with chronic dyspepsia. The psychiatric hypothesis holds that the symptoms of dyspepsia may be due to depression, increased anxiety, or a somatization disorder. Epidemiological studies suggest there is an association between functional dyspepsia and psychological disorders. Symptoms of neurosis, anxiety, hypochondriasis, and depression are more common in patients being evaluated for unexplained gastrointestinal complaints than in healthy controls. Comparisons of functional and organic dyspepsia have demonstrated that patients with functional dyspepsia are less likely to have decreased stress or anxiety at 1-year follow-up after being reassured of having no serious disease. This suggests that functional dyspepsia symptoms are long-lasting, compared with those of organic dyspepsia, and that the emotional ties are strong.^[17]

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.^[5]

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 NSAIDs and can be complicated by bleeding or ulceration with perforation of stomach wall.

Treatment

Functional and undifferentiated dyspepsia have similar treatments. Drug therapy decisions 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), prokinetic agents, and antiflatulents. 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.^[18]

Acid suppression

Antacids and sucralfate were found to be no better than placebo in a literature review.^[19] H2-RAs have been shown to have marked benefit in poor quality trials (30% relative risk reduction^[19]), but only a marginal benefit in good quality trials.^[18] Prokinetic agents would empirically seem to work well since delayed gastric emptying is considered a major pathophysiological mechanism in functional dyspepsia.^[18] 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)^[20] due to serious adverse events such as torsades, and publication bias has been cited as a potential partial explanation for such a high benefit.^[19] Modern prokinetic agents such as metoclopramide, erythromycin and tegaserod have little or no established efficacy and often result in substantial side effects.^[19] Simethicone has been found to be of some value, as one trial suggests potential benefit over placebo and another shows equivalence with cisapride.^[19] 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.

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.^[18]

Alternative medicine

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".^[21] A 2004 meta-analysis of the multiple herbal extract Iberogast found it to be more effective than placebo in people with functional dyspepsia.^[22]

Etymology

The word dyspepsia is from the Greek δυσ- dys-, "bad" or "difficult", and πέψις pepsis "digestion".

See also

• Functional bowel disorder

References

Look up indigestion in Wiktionary, the free dictionary.