Dyspepsia

Dyspepsia describes pain or discomfort in the upper abdomen. It has been defined variously by a number of expert groups:

• Prior to 1991, dyspepsia included patients with symptoms of heartburn and acid reflux.¹

• The Rome I definition defined patients with sole reflux symptoms as having gastro-oesophageal reflux disease (GORD) - also seen as 'GERD'.

• These criteria were extended to exclude patients with predominant reflux symptoms and symptoms suggestive of irritable bowel syndrome (IBS).²

Incidence

Prescribing on ulcer healing drugs varies from year to year but there is a general increasing trend. One study of proton pump inhibitor (PPI) prescribing in UK general practice showed a steady increase from 1990-2014.³

• About 40% of adults have dyspepsia each year. Approximately 25% of people with dyspepsia will consult their GP.⁴

• There is evidence of inappropriate (not per guidelines) PPI prescribing by GPs and hospital doctors.⁵

Presentation⁶

• Epigastric discomfort

• Fullness or bloating

• Excessive flatus

• Nausea

• Fatty food intolerance

Always ask about family history and medication use.

In one study of endoscopic findings, patients with dyspeptic symptoms were found to have:⁷

• Peptic ulcer disease (13%).

• GORD (18%).

• Functional dyspepsia ( 66%).

Older patients are more likely to have serious disease.

Investigations^{8 9}

• Always check for abdominal mass.

• Consider taking FBC to demonstrate another alarm feature - eg, iron-deficiency anaemia.

• Test for Helicobacter pylori.

Referral for endoscopy⁹

Routine endoscopic investigation of dyspeptic patients is not necessary but should be considered in patients over the age of 55 in whom:

Differential diagnosis¹⁰

• Peptic ulcer.

• Functional (non-ulcer) dyspepsia.

• IBS.

• Atypical GORD.

• Biliary pain - eg, gallstones.

• Achalasia.

• Medication-induced dyspepsia.

• Aerophagia.

• Oesophageal spasm.

• Oesophageal cancer or stomach cancer.

Exclude abdominal mass and other causes of abdominal pain.

Evidence-based management

Urgent specialist referral - two-week rule

For patients without alarm features and with previous investigations for dyspepsia⁹

It is possible to treat on the basis that a similar pathology has recurred, although refer to a specialist if the patient is unresponsive to treatment or the diagnosis is in doubt.

• If there has been a peptic ulcer previously and no evidence of H. pylori eradication, prescribe H. pylori eradication therapy if the test is positive. See the separate Helicobacter Pylori article for details.

• If peptic ulcer has been excluded (functional or non-ulcer dyspepsia), H. pylori eradication (after a positive test) may relieve symptoms.

• For people with GORD, offer a full-dose PPI, as detailed in the NICE guidance, for four to eight weeks.¹¹

• Where there is no initial response to a PPI (and recent endoscopy has shown GORD), offer H₂-receptor antagonist (H₂RA).

• Prokinetic agents are no longer recommended. However, several new-generation prokinetics such as acotiamide are emerging. Acotiamide has received approval for use in Japan and is currently being evaluated in Europe.¹²

• Some patients may require prolonged high doses of PPI and may ultimately be candidates for anti-reflux surgery. This is often carried out laparoscopically. A 2015 Cochrane review concluded there was considerable uncertainty in the balance of benefits versus harms compared to long-term medical treatment with a PPI.¹³ The risk versus benefits of both approaches need to be discussed with individuals on a case by case basis.

• If there has been oesophagitis previously, prescribe a PPI.

• If symptoms recur after initial treatment, offer the lowest-dose PPI that will control symptoms.

• If severe oesophagitis has been diagnosed on endoscopy:

  • A full-dose PPI should be given for eight weeks (taking into account preference and clinical circumstances - eg, tolerability to PPIs, underlying health conditions and possible interactions with other drugs).

  • Switch to another full-dose PPI or high-dose PPI if initial treatment fails.¹¹

  • Offer a full-dose PPI long-term as maintenance treatment.

For the uninvestigated patient without alarm features⁹

The NICE guideline suggests the following steps:

• Review medications: possible drug causes of dyspepsia include NSAIDs, steroids, calcium antagonists, nitrates, theophyllines and bisphosphonates. Reduce or stop if possible.

• Offer lifestyle advice, ie stopping smoking, more regular meals, ceasing excessive alcohol consumption.

• Antacids are cheap, simple and may be all that is required for relief of occasional symptoms. Most antacids contain a mixture of aluminium hydroxide that tends to cause constipation and magnesium hydroxide that tends to cause diarrhoea. The balance between the two cannot be assured and there may be disturbance of bowel function. If a large amount of antacid is being consumed, consider acid suppression.

• Try either of the following. The alternative choice can be tried if symptoms persist or return:
  

  • Test for H. pylori (carbon-13 urea breath test, stool antigen or laboratory serology) and eradicate if positive.

  • Empirical acid suppression (with PPI) - full dose for one month.

Where there has been a satisfactory response at any of the steps above, reassure and return to self-care.

If the patient responds to a PPI but then relapses, consider low-dose or intermittent treatment.

Where patients show an inadequate response to treatment, consider other diagnoses (eg, gallstones) and/or referral to a specialist.

Pharmacological issues¹⁴

• Adverse reactions to PPIs and H₂RAs are usually rare and mild but severe problems can arise:
  

  • Rare but not serious problems may include taste disturbance, peripheral oedema, photosensitivity, fever, arthralgia, myalgia and sweating.

  • Serious problems include liver dysfunction, hypersensitivity reactions (including urticaria, angio-oedema, bronchospasm, anaphylaxis), depression, interstitial nephritis, blood disorders (including leukopenia, leukocytosis, pancytopenia, thrombocytopenia) and skin reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous eruption).

• Many of the drugs used in the management of peptic ulcer disease carry a warning that they should not be used in pregnancy or whilst breastfeeding:
  

  • This is usually because of lack of information about safety in pregnancy rather than evidence of adverse effects in pregnancy.

  • However, misoprostol - a prostaglandin analogue - should be avoided in pregnancy as it may cause abortion.

• PPIs are metabolised mostly in the liver. In liver disease, dose adjustment may be required for omeprazole, pantoprazole and esomeprazole. There are no data on the use of rabeprazole in people with severe hepatic impairment, so the manufacturer advises caution.

• The long-term safety of PPIs has been subject to debate. Emerging evidence from multiple observational studies suggests long-term use of PPIs is associated with a higher risk of gastric cancer development. This does not mean that PPIs should be universally banned from long-term use, rather that they should be tailored to the individual's risk-benefit profile. The risk is likely limited to individuals with current or past history of H. pylori infection, particularly those with underlying precancerous gastric lesions. Patients in genuine need - eg, those with Barrett's oesophagus or high risk of upper GI bleeding - should not be denied the benefits of long-term PPI therapy. Further prospective research is needed.¹⁵

• Omeprazole and esomeprazole may interfere with warfarin monitoring.

Monitoring¹⁶

Patients should be reviewed at the end of a course of treatment, especially H. pylori eradication, to confirm a satisfactory outcome. The criteria to be used to measure satisfactory patient outcome are subject to controversy, and instruments to determine clinical endpoints are evolving.

If simple acid suppression is given, the patient should be reviewed after one or two months to ascertain that the end is being achieved and there are no warning signs such as weight loss to suggest malignancy.