DYSPEPSIA

EPIDEMIOLOGY:

Published figures for the prevalence of dyspepsia vary from 20% to 40%, of which perhaps only a quarter can be attributed to peptic ulcer disease.⁽¹⁾ There is a lack of data regarding prevalence of dyspepsia in Pakistan.

PATHOPHYSIOLOGY:

Approximately 25 percent of patients with dyspepsia have an underlying organic cause. However, up to 75 percent of patients have functional (idiopathic or nonulcer) dyspepsia with no underlying cause on diagnostic evaluation.^(2-4)

Dyspepsia secondary to organic disease — Although there are several organic causes for dyspepsia, the main causes are peptic ulcer disease, gastroesophageal reflux, gastric malignancy, and nonsteroidal anti-inflammatory drug (NSAID)-induced dyspepsia.

Peptic ulcer disease — Upper abdominal pain or discomfort is the most prominent symptom in patients with peptic ulcers. Although discomfort from ulcers is usually centered in the epigastrium, it may occasionally localize to the right or left upper quadrants.⁽⁵⁾ While the pain may radiate to the back, back pain as the primary symptom is atypical of peptic ulcer disease.

While classic symptoms of duodenal ulcer occur when acid is secreted in the absence of a food buffer (i.e. two to five hours after meals or on an empty stomach), peptic ulcers can be associated with food-provoked symptoms. Thus, pain related to the timing of a meal cannot accurately distinguish a duodenal ulcer from a gastric ulcer.

Peptic ulcers can also be associated with postprandial belching, epigastric fullness, early satiation, fatty food intolerance, nausea, and occasional vomiting.

GASTROESOPHAGEAL REFLUX — The most common symptoms of gastro esophageal reflux disease (GERD) are retrosternal burning pain and regurgitation.⁽⁶⁾ GERD should be suspected when these symptoms accompany dyspepsia and are the predominant complaints ⁽⁷⁾.

GASTROESOPHAGEAL MALIGNANCY — Gastroesophageal malignancy is an uncommon cause of chronic dyspepsia in the Western hemisphere but the incidence is higher in patients of Asian, Hispanic, or Afro-Caribbean extraction. The incidence of malignancy also increases with age. When present, abdominal pain tends to be epigastric, vague and mild early in the disease but more severe and constant as the disease progresses. In addition, other symptoms and signs typically evolve with disease progression (e.g. anemia, fatigue, weight loss).

BILIARY PAIN — Classic biliary pain is characterized by episodic acute and severe upper abdominal pain, usually in the epigastrium or right upper quadrant. It is not colicky. The pain typically lasts for at least one hour and may persist for several hours. The pain may radiate to the back or scapula, and is often associated with restlessness, sweating, or vomiting. Episodes are typically separated by weeks to months and patients are completely pain free between attacks.

DRUG-INDUCED DYSPEPSIA — NSAIDs and COX-2 selective inhibitors can cause dyspepsia even in the absence of peptic ulcer disease.

Several other drugs have been implicated as causes of dyspepsia. However, data to support the role of these medications in drug induced dyspepsia are limited. These medications include calcium channel blockers, methylxanthines, alendronate, orlistat, potassium supplements, acarbose and certain antibiotics, including erythromycin.^(8,9)

OTHER CAUSES — Celiac disease and chronic pancreatitis may rarely present with dyspepsia alone. Other rare causes for dyspepsia include infiltrative diseases of the stomach (e.g. eosinophilic gastritis, Crohn disease, sarcoidosis), diabetic radiculopathy, metabolic disturbances (e.g. hypercalcemia, heavy metal toxicity), hepatoma, steatohepatitis, celiac artery compression syndrome, superior mesenteric artery syndrome, and intestinal angina

FUNCTIONAL DYSPEPSIA — Functional (idiopathic or nonulcer) dyspepsia is defined as the presence of one or more of the following: postprandial fullness, early satiation, epigastric pain or burning, and no evidence of structural disease to explain the symptoms.⁽¹⁰⁾ These criteria should be fulfilled for the last three months with symptom onset at least six months before diagnosis.

A diagnosis of functional dyspepsia can therefore only be established after exclusion of other causes of dyspepsia.⁽¹¹⁾

SIGN AND SYMPTOMS:

The primary symptoms of dyspepsia are

• Upper abdominal pain or discomfort
• Belching
• Nausea
• Vomiting
• Abdominal bloating
• Feeling full after eating only a small amount of food (early satiety) and
• Abdominal distention (swelling).

The symptoms most often are provoked by eating.

DIAGNOSTIC TESTS:

The approach to and extent of diagnostic evaluation of a patient with dyspepsia is based on the presence or absence of alarm features, patient age, and the local prevalence of Helicobacter pylori (H. pylori) infection.⁽¹²⁾

Patients with gastroesophageal reflux disease (GERD) and nonsteroidal anti-inflammatory drug (NSAID) induced dyspepsia should be treated with an empiric trial of proton pump inhibitors (PPI) for eight weeks and NSAIDs should be discontinued.

Further evaluation should be pursued if these patients continue to have symptoms after eight weeks of PPI therapy or earlier if they have alarm features

PATIENT WITH ALARM FEATURES OR AGE ≥55 YEARS:

EARLY UPPER ENDOSCOPY: Upper endoscopy should be performed for the evaluation of new onset dyspepsia in patients with alarm features or those age ≥55 years. Upper endoscopy provides a gold standard for establishing a specific cause in patients with upper abdominal pain. Biopsies of the stomach should be obtained to rule out H. pylori. Patients with H. pylori should receive eradication therapy in addition to treatment based on the underlying diagnosis.

Multiple studies have evaluated the yield of upper endoscopy in patients with dyspepsia. A meta-analysis of nine studies with 5389 patients found that the most prevalent findings in patients with dyspepsia were erosive esophagitis and peptic ulcer disease (pooled prevalence 6 and 8 percent, respectively).⁽¹³⁾

The diagnostic yield of upper endoscopy increases with age.^(14,15) In the absence of alarm features, early endoscopy (within two weeks) in patients of age ≥55 years is performed. These recommendations are largely consistent with the American Gastroenterological Association (AGA) and American College of Gastroenterology (ACG) guidelines.^(16,17,18) However, the optimal age cut-off for endoscopic evaluation in patients with dyspepsia (without alarm features) is controversial and is supported by limited evidence that suggests that the risk of malignancy in most United States populations prior to 55 years is low.

Guidelines also suggest that the age cutoff may vary between countries, depending upon the prevalence of gastric cancer.⁽¹⁹⁾ The AGA guidelines suggest that it may be reasonable in some populations in developed nations to consider the age of 60 or 65 years as the threshold age at which endoscopy should be offered to all new dyspeptic patients and an age cutoff of 45 or 50 years may be more appropriate for United States patients of Asian, Hispanic, or Afro-Caribbean extraction or in populations with a high incidence of gastric cancer in young individuals. A European consensus statement recommends endoscopy in adults older than 45 years old who present with persistent dyspepsia. These recommendations highlight the fact that diagnostic evaluation of the patient with dyspepsia need to be individualized based on symptoms, age, ethnic background, family history, and nationality.

If the upper endoscopy is normal, patients with alarm features or persistent symptoms of dyspepsia should undergo further evaluation to exclude other etiologies. However, most patients with a normal upper endoscopy and routine laboratory tests have functional dyspepsia.

Patient without alarm features and age <55 years — The two main strategies in patients <55 years without alarm features are to test and treat for H. pylori and to provide empiric antisecretory therapy. The efficacy of the H. pylori test and treat strategy varies based on whether it is employed in primary or secondary care settings and the local prevalence of H. pylori. ^(20,21)

Patients <55 years of age without alarm features should be tested and treated for H. pylori if the local prevalence of H. pylori is >10 percent.⁽²²⁾ Empiric treatment with a proton pump inhibitor (PPI) should be recommended in areas with prevalence <5 percent.

In areas with a prevalence of 5 to 10 percent, the strategies of test and treat H. pylori or empiric PPI therapy may be equivalent in terms of dyspepsia resolution, patient satisfaction, and cost.⁽¹⁶⁾ It is therefore reasonable for clinicians to use clinical judgment in deciding upon noninvasive H. pylori testing or an empiric trial of a PPI. The decision should include consideration of the patient's age, past history, nonsteroidal anti-inflammatory drug use, comorbidities, symptom duration, risk factors for gastric or esophageal malignancy and H. pylori infection, availability and cost of diagnostic testing, and patient preference.

TEST FOR HELICOBACTER PYLORI: The rationale for H. pylori testing in patients with dyspepsia is based upon the recognition of H. pylori as an etiologic factor in peptic ulcer disease. Testing for H. pylori should be performed with a urea breath test or stool antigen assay. Serologic testing should not be used due to their low positive predictive value.⁽²³⁾

Patients who test positive for an infection with H. pylori should undergo treatment with eradication therapy. Most dyspeptic patients who are H. pylori positive and who are treated with appropriate antibiotic therapy persist with dyspeptic symptoms; the number needed to treat to successfully relieve dyspeptic symptoms is estimated at 1 in 14.

UPPER ENDOSCOPY — Endoscopic evaluation of patients with dyspepsia without alarm features provides a very small additional benefit over a strategy to test and treat for H. pylori and is unlikely to be cost-effective. It is therefore reserved for patients with persistent symptoms despite antisecretory therapy and H. pylori testing / treatment.

One of the most comprehensive systematic reviews included 17 controlled trials that involved comparison of 20 variations in the treatment strategies.⁽²⁴⁾ Initial endoscopy was associated with a small reduction in the risk of recurrent dyspeptic symptoms compared with a strategy of initial empiric treatment. H. pylori testing with endoscopy for a positive result increased costs but did not improve symptoms. H. pylori testing followed by eradication appeared to be as effective as initial endoscopy, but reduced costs by decreasing the proportion of patients that ultimately required an endoscopy.

TREATMENT OPTIONS:

PHARMACOLOGICAL OPTIONS:

Patients with dyspepsia should be tested and treated for H. pylori if the local prevalence of H. pylori is >10 percent.

TRIPLE THERAPY:⁽²⁵⁾

Triple therapy for Helicobacter pylori infection consists of the following:

1. Proton pump inhibitor (PPI) (omeprazole 20 mg BID, lansoprazole 30 mg BID, esomeprazole 40 mg QD, pantoprazole 40 mg QD, rabeprazole 20 mg BID)⁽²⁶⁾plus
2. Clarithromycin 500 mg BID⁽²⁶⁾(first-line) or metronidazole 500 mg BID (when clarithromycin resistance increasing)⁽²⁷⁾  plus
3. Amoxicillin 1000 mg BID⁽²⁶⁾or metronidazole (if not used above)

Duration options are as follows (each duration below yields good outcomes of around 80% and is associated with similar risks because of good tolerance):

• 14 days (deemed the most prudent recommendation based on a meta-analysis of 7 studies and confirmed by a large Italian randomized single-center trial)⁽²⁶⁾
• 7 days (no significant difference from 14 days based on a prospective randomized comparative trial in Nairobi)
• 10 days [also showed high cure rates with metronidazole 500 mg TID and high-dose esomeprazole (40 mg BID) based on a pilot study)]⁽²⁷⁾

TREATMENT FOR HELICOBACTER PYLORI:  Patients who have continued symptoms after successful eradication of H. pylori should be treated with antisecretory therapy with a proton pump inhibitor for four to eight weeks.^(16,28) However, some patients may continue to have symptoms of dyspepsia and may require additional evaluation.

ANTISECRETORY THERAPY — Empiric antisecretory therapy without H. pylori testing / treatment should be recommended in areas of very low prevalence for H. pylori (<5 percent) and may also be considered in areas with prevalence of 5 to 10 percent). Proton pump inhibitor therapy is more effective in relieving symptoms of dyspepsia as compared with H2 antagonists.^(29,30)

ANTACIDS: Antacids are often used in combination with viscous lidocaine to treat dyspepsia, evidence of their efficacy is lacking

PROTON PUMP INHIBITORS — PPIs appear to be moderately effective in the treatment of some patients with functional dyspepsia

H2 RECEPTOR ANTAGONISTS — Patients with functional dyspepsia are more likely to respond to H2 receptor antagonists (H2RA) than to placebo.

ANTIDEPRESSANTS — Central mechanisms may contribute to functional dyspepsia either through increased upper gastrointestinal sensitivity or through other mechanisms. Tricyclic antidepressants should be considered in patients with functional dyspepsia and persistent symptoms despite PPI therapy for eight weeks. There is no current evidence to support the use of selective serotonin reuptake inhibitors in patients with functional dyspepsia.

ANTINOCICEPTIVE AGENTS — It is hypothesized that antinociceptive agents may impact the central processing of pain, thereby decreasing visceral hypersensitivity that has been associated with functional dyspepsia. Carbamazepine, tramadol, or pregabalin can be considered in patients who fail a four-week trial of prokinetic agents and in patients who cannot tolerate prokinetics.

PROKINETIC AGENTS — The possible relationship between nonulcer dyspepsia and abnormal gastric emptying provided the rationale for treatment trials of prokinetic agents.

Itopride is a dopamine D2 antagonist with acetylcholinesterase inhibitory activity that has prokinetic effects and probably also modulates gastric accommodation and hypersensitivity.

GUIDELINES:

Treatment for dyspepsia is based on guidelines from the prestigious societies such as NICE.

To review the NICE guidelines, click on the below link:

https://www.nice.org.uk/guidance/cg184/documents/dyspepsiagord-nice-guideline2

LONG TERM MONITORING 

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.⁽³¹⁾

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