Most diseases of the gastrointestinal tract can be directly visualized by endoscopy or from a histopathologic review of a biopsy obtained during the endoscopic procedure. In addition, many gastrointestinal tract disorders can be identified with various imaging studies. This accessibility of lesions for direct examination and biopsy has limited the need for clinical laboratory tests in identifying most gastrointestinal disorders. However, because imaging studies are often expensive, and endoscopic procedures are both expensive and invasive, there is a clinical need for laboratory tests to aid in the diagnosis and management of persons with a number of gastrointestinal disorders. Infectious diseases involving the gastrointestinal tract are numerous, and are discussed in Chapter 5. The clinical laboratory plays an important role in identifying pathogenic microorganisms of the gastrointestinal tract.

The clinical laboratory also plays a role in the evaluation of dyspepsia (abdominal discomfort caused by acid), and/or ulcer disease, particularly that induced by Helicobacter pylori infection; in the recognition and monitoring of celiac sprue; and in the detection and genetic profiling of colon cancer. Laboratory tests for these disorders are presented in this chapter.

Description

According to the American Gastroenterological Association (AGA), dyspepsia is defined as chronic or recurrent pain or discomfort centered in the upper abdomen. Other conditions (particularly reflux of acid into the esophagus, referred to as gastroesophageal reflux disease [GERD]) can also cause abdominal discomfort, and it is often difficult to specifically characterize the type and location of discomfort. About 10% of those in the United States with upper abdominal symptoms are found to have peptic ulcers, with a wide range between different countries. Other causes include gastritis related to use of nonsteroidal anti-inflammatory agents, and “functional dyspepsia,” in which no obvious pathology is present in the stomach.

The major cause of peptic ulcer disease is infection with H. pylori. The infection is most likely to occur in childhood, especially if the children are living in low socioeconomic conditions. In developed countries, H. pylori infection prevalence increases with age. Not all patients with H. pylori infection develop ulcer disease, as many suffer from dyspepsia without ulcers. The infection initially produces an acute gastritis that lasts 1 to 4 weeks. Once infected, however, chronic active gastritis occurs in the majority of individuals and may lead to more serious outcomes. Especially when infected in early childhood, individuals are at risk for the development of multifocal atrophic gastritis and over time, subsequently, have an increased risk for gastric adenocarcinoma.

Diagnosis

The evaluation of individuals with dyspepsia depends on age and the severity of symptoms. According to guidelines, direct visualization of the upper gastrointestinal tract by endoscopy is the preferred initial step in persons over age 55 years, or in younger patients who have a family history of gastric cancer or who also have more worrisome symptoms such as weight loss, difficulty swallowing food, recurrent vomiting, or gastrointestinal bleeding. In younger patients without these symptoms, the recommended approach is to test for the presence of active H. pylori infection and treat infected individuals. Those without evidence of infection are treated with drugs that inhibit acid production. Persons who do not respond to these treatments should then have an endoscopy.

Laboratory tests for H. pylori can be separated into those that identify exposure and those that detect active infection (Table 15–1). Because H. pylori is able to split urea (it is a urease-positive organism), its presence can be detected by ability of the individual to metabolize urea. The urea breath test (UBT) involves ingestion of a food product containing urea labeled with a small amount of radioactive carbon. If urease activity is present, the urea will be split into ammonia and carbon dioxide. The amount of radioactive carbon dioxide in the breath correlates with urease activity. The UBT has a high accuracy, and its performance is simple. Use of drugs that suppress acid production may cause falsely negative UBTs.

H. pylori has a unique surface antigen that can be detected in the stool of infected individuals, but not in those with inactive infection. Stool antigen testing with kits using monoclonal antibodies to the antigen is sensitive and specific. These kits have a high accuracy, for both initial diagnosis of H. pylori and posttreatment follow-up testing. Both the UBT and the stool antigen test can be used to evaluate the success of antibiotic treatment for H. pylori. Successful treatment should lead to loss of stool antigen (after several weeks) and the loss of urease activity in the stomach.

Serologic tests for IgG antibodies to H. pylori indicate past or current infection. They have a sensitivity and a specificity of only about 85% to 90%, and have largely been replaced by tests that directly identify the organism. Serology is the only test not affected by reduction of bacterial load in the stomach, and, therefore, serologic testing for H. pylori is not subject to false-negative results when bacterial load reduction occurs. Unlike the stool antigen and urease tests, serologic tests remain positive for years after successful treatment, and because of that they are of no use to monitor the effects of treatment.