Dyspepsia

Dyspepsia (from the Greek "δυς-" (Dys-), meaning hard or difficult, and "πέψη" (Pepse), meaning digestion) is chronic or recurrent pain or discomfort centered in the upper abdomen Discomfort, in this context, includes mild pain, upper abdominal fullness and feeling full earlier than expected with eating. It can be accompanied by bloating, belching, nausea or heartburn. It may be called indigestion. Heartburn is excluded from the definition of dyspesia in ICD 10, as it usually has a different cause and management pathway. When a patient has dyspepsia, but underlying disease is found, the patient is said to have non-ulcer dyspepsia or functional dyspepsia or idopathic dyspepsia.

Classification

Dyspepsia has been proposed to have symptomatic subgroups:

• ulcerlike - "Pain centered in the upper abdomen is the predominant (most bothersome) symptom."
• dysmotilitylike - "An unpleasant or troublesome non-painful sensation (discomfort) centered in the upper abdomen is the predominant symptom; this sensation may be characterized by or associated with upper abdominal fullness, early satiety, bloating, or nausea."
• refluxlike
• nonspecific

However, there is not a strong correlation of symptom type and measures of abnormal motility or hypersensitivity.

A cluster analysis identified 4 groups, the first two are associated with delayed gastric emptying and the second two are associated with gastric hypersensitivity:

• Factor 1 - "characterized by nausea, vomiting, early satiety, and weight loss...associated with delayed emptying...younger age, female sex, and sickness behavior"
• Factor 2 - "characterized by postprandial fullness and bloating...associated with delayed emptying"
• Factor 3 - "characterized by pain symptoms and associated with gastric hypersensitivity and several psychosocial dimensions including medically unexplained symptoms and health-related quality of life dimensions".
• Factor 4 - "characterized by belching, is also associated with hypersensitivity, but is unrelated to psychosocial dimensions."

Cause/etiology

Some cases are caused by medications such as calcium antagonists, nitrates, theophyllines, bisphosphonates, corticosteroids and non-steroidal anti-inflammatory drugs [NSAIDs]).

Several studies provide prevalences of underlying causes based on findings at esophagogastroduodenoscopy (EGD).

Findings in various populations

	Patients referred to gastroenterologists for dyspesia	Primary care patients with dyspepsia	Volunteers with dyspepsia	Volunteers without dyspepsia	Volunteers without dyspepsia	Referred patients in China
Normal
Macroscopically normal by EGD	60%	54%	73%	82%	66%
Histologically normal by biopsy at EGD					35%
Esophagus
Macroscopic esophagitis by EGD	14%	12%	13%	9%	22% (included Grades 1 & 2)
Hiatal hernia >2 cm by UGI	40%				26%
Hiatal hernia by EGD		3%			3%
Stomach/duodenum
Peptic ulcer disease (PUD)	20%	8%	9%	4%	4%
Gastritis/duodenitis	14%	20%	5% (erosions required)	5% (erosions required)	9-16%
Other
Malignancy	3%	0%	0.4%	0.5%	0%	4%

Non-ulcer dyspepsia (NUD)

Rome criteria

Nonulcer dyspepsia exists (functional dyspepsia) when esophagogastroduodenoscopy and other tests have excluded other diseases and the patient has the following Rome II criteria: At least 12 weeks, which need not be consecutive, within the preceding 12 months of:

1. Persistent or recurrent dyspepsia (pain or discomfort centered in the upper abdomen); and
2. No evidence of organic disease (including at upper endoscopy) that is likely to explain the symptoms; and
3. No evidence that dyspepsia is exclusively relieved by defecation or associated with the onset of a change in stool frequency or stool form (i.e., not irritable bowel).

Possible causes of NUD

The implied lack of organic disease may actually be incorrect as there may be physiological abnormalities that are too subtle for commonly used tests. For example, some patients may have gastric motor function or visceral sensitivity.

Non-ulcer dyspepsia, when of acute onset, may be due to gastric dysmotor dysfunction following gastrointestinal infections.

H. pylori

The role of H. pylori is not clear.

Association with other diseases

Psychiatric diagnoses

Psychiatric diagnoses are more prevalent among patients with normal endoscopies than abnormal endoscopies.

Irritable bowel

There is much overlap among patients with non-ulcer dyspepsia and irritable bowel syndrome.

Celiac disease

Using historical controls, non-ulcer dyspepsia has been found to associate with celiac disease.

Diagnosis

History and physical examination

The history and physical examination cannot reliably detect when organic disease underlies dypspepsia.

Alarm features or red flags that may indicate serious underlying diseases are:

• Age older than 55 years with new-onset dyspepsia
• Family history of upper gastrointestinal cancer
• Unintended weight loss
• Gastrointestinal bleeding
• Progressive dysphagia
• Odynophagia
• Unexplained iron-deficiency anemia
• Persistent vomiting
• Palpable mass or lymphadenopathy
• Jaundice

Although the value of these findings is hard to establish, one study found that the best predictions of abnormal investigations were:

• History of an previous ulcer
• Age 50 or more
• Pain better with food or milk (presumably identifies duodenal pathology)
• Pain occurs < one hour after eating (presumably identifies gastric pathology)

Regarding gastric cancer, helpful findings are anemia and persistence of symptoms.

Identifying a psychiatric disorder may reduce the chance than a serious organic disorder is present.

On physical examination, pallor of conjunctiva, nail-bed or palmar crease, or the absence of nail-bed blanching are predictive of significant anemia (hemoglobin less than 12 gm/dl).

Laboratory tests

Complete blood count

One study found that by using "H. pylori serology and a hemoglobin reading in the evaluation of dyspeptic patients under 45 years of age, the need for endoscopy can be reduced by 55%."

In adults, 60% of patients with iron deficiency anemia may have underlying gastrointestinal disorders leading to chronic blood loss.

H. pylori testing

Clinical practice guidelines by the American Gastroenterological Association state "H. pylori testing is optimally performed by a ¹³C-urea breath test or stool antigen test."

Several studies indicate the need to test dyspeptic patients for H. pylori. One study found that by using "H. pylori serology and a hemoglobin reading in the evaluation of dyspeptic patients under 45 years of age, the need for endoscopy can be reduced by 55%."

A randomized controlled trial found that among patients without alarm symptoms, the cost of breath testing all patients is offset by the reduction in endoscopy.

The accuracy of the breath test for detecting peptic ulcer disease is:

• sensitivity 93%
• specificity 60%

False negative tests

Testing should be delayed for 2 weeks after stopping PPI use to avoid false negative breath test or a stool antigen test.

Impact of testing

In summary, test and treat may reduce symptoms at two months with no improvement at one year.

"While early endoscopy offered some advantages 'Test and treat' was the most cost-effective strategy" according to a randomized controlled trial. In this trial, the relative benefit ratio of Helicobacter pylori serum testing for improvement at 2 months was 1.2 and, the relative benefit increase was 23.7%. In populations similar to those in this study which had a rate of benefit as measured by the improvement at 2 months of 59% without treatment, the number needed to treat is 7. There were no differences at 12 months.

"Test and treat and acid suppression are equally cost effective in the initial management of dyspepsia" according to a randomized controlled trial. In this trial, the relative benefit ratio of Helicobacter pylori breath testing for no dyspepsia at one year was 1.1 and, the relative benefit increase was 5.9%. In populations similar to those in this study which had a rate of benefit as measured by the no dyspepsia at one year of 17% without treatment, the number needed to treat is 100.

Other tests

Blood tests for celiac disease.

Radiology

UGI as historic significance as good before EGD.

Esophagogastroduodenoscopy (EGD)

Direct visualization by esophagogastroduodenoscopy(EGD) is very sensitive for peptic ulcer disease, but may not detect all possible underlying causes of dyspepsia. For example, gastroesophageal reflux disease that does not cause macroscopic esophagitis will be missed by esophagogastroduodenoscopy.

For patients with positive Helicobacter pylori tests, obtaining endoscopy may be reasonable alternative to empiric antibiotics though less well studied. This strategy allows identification of patients with GERD and also may reduce discontinuing antibiotics due to drug-related side effects and adverse reactionss.

For patients with negative Helicobacter pylori testing, endoscopy is not needed if they are less than 45 years old and without alarm symptoms.

Diagnostic strategy

Many randomized controlled trials have compared empiric treatment (either for Helicobacter pylori or acid suppression), routine Helicobacter pylori testing, and routine esophagogastroduodenoscopy (EGD). These are summarized in a meta-analysis by the Cochrane Collaboration. Additional trials have been published since the review by the Cochrane.

Treatment

Clinical practice guidelines by the American Gastroenterological Association address treatment.

The type of dyspepsia, motility versus acid, may weakly predict which medicine will reduce symptoms.

Reassurance

Regarding the treatment of non-ulcer dyspepsia, the value of simple reassurance is suggested by the response to placebo ranging from 40% to 70%.

Acid suppression

A meta-analysis of randomized controlled trials by the Cochrane Collaboration concluded "there is evidence that anti-secretory therapy may be effective in NUD" with a number needed to treat for PPIs of 10. Subsequent randomized controlled trials have had conflicting results reporting both benefit and no benefit. Stepping up therapy may be better than stepping down therapy.

As needed use of histamine H2 antagonists may be effective.

Prokinetic drugs

Prokinetic drugs include:

• Serotonin-3 (5-HT3) receptor agonists (cisapride, mosapride)
• Dopamine receptor antagonists (domperidone, metoclopramide, itopride)
• Opiate agonists (trimebutine). Trimebutine also has antiserotonergic activity.

The Cochrane Collaboration concluded "trials evaluating prokinetic therapy are difficult to interpret as the...[positive] result could have been due to publication bias.". More recently, a randomized controlled trial of itopride found that 100 mg three times per day benefited 17% of patients (number needed to treat is 6).

Tricylic antidepressants

A meta-analysis found that patients needed to be treated to improve 1 patient (number needed to treat is 3).

Eradication of H. pylori

In order to treat underlying peptic ulcer, clinical practice guidelines by the American Gastroenterological Association recommend:

• "Patients 55 years of age or younger without alarm features should receive Helicobacter pylori test and treat followed by acid suppression if symptoms remain"

The Cochrane Collaboration concluded "small but statistically significant effect in H. pylori positive non-ulcer dyspepsia. The number needed to treat was 14. An economic model suggests this modest benefit may still be cost-effective but more research is needed." A more recent randomized controlled trial did not find a difference.

The effect of eradication seems related to the presence of gastritis. Patients with antral predominant gastritis are more likely to improve whereas patients with corpus-predominant gastritis are less likely to improve. This may be due to antral erosions being due to hyperacidity the is corrected by treatment whereas corpus erosions are hypoacidic and treating this may increase the ability of the stomach to produce acid. Another study found that patients with gastritis or erosions were less likely to respond, but this study did not separate patients with antral versus corpus erosions.

Psychological interventions

It is unclear if any form of psychological interventions is beneficial

Prevention

Users of nonsteroidal anti-inflammatory (NSAID) medications

Patients with a history of bleeding ulcer have a 26% rate of ulcers with NSAIDs. Patients with H. pylori have 2.5 risk of an ulcer on NSAIDs.

For patients starting long-term NSAIDs, screening for H. pylori with a breath test among patients with prior ulcer or dyspepsia and treating positive patients reduced subsequent rate of ulcers.

For patients who must take NSAIDs, proton pump inhibitors may be effective in preventing dyspepsia.

Asymptomatic adults

Community screening for H. pylori may be beneficial.