CHICAGO — When testing patients for celiac disease, physicians can no longer rely on a single paradigm for both overtly symptomatic patients and asymptomatic but genetically at-risk patients, according to Dr. Edwin Liu.
These two categories of patients require different approaches, said Dr. Liu, who spoke at a meeting on celiac disease sponsored by the American Gastroenterological Association.
Most symptomatic patients need only one antibody test, transglutaminase IgA (IgA-TGA) and an IgA antibody level to assess for celiac disease. But genetically at-risk patients may need multiple tests over time to screen for the presence of celiac autoimmunity and to determine if a biopsy is needed. Patients considered at risk for celiac disease include first-degree relatives of those with celiac disease or type 1 diabetes, and patients with type 1 diabetes.
The patient with classic symptoms and an abnormal TGA result usually can be biopsied immediately with a greater than 90% likelihood that intestinal lesions will be found, but TGA predicts disease in only about 75% of asymptomatic patients at genetic risk.
Patients with very elevated blood TGA levels are more likely to have more severe intestinal injury, so “in screening those at genetic risk, we have to understand our own lab tests well,” Dr. Liu said in an interview. Therefore, in deciding when to perform a biopsy, physicians should interpret tests in a quantitative fashion. This interpretation should consider changes in TGA values over time, because a single positive result may not provide enough information to make a decision to proceed with biopsy.
“In the case of a symptomatic person, [a single positive result] is probably okay, because you are looking for the presence or absence of disease. However, in the case of a person who's at risk for celiac disease, multiple tests over time may be needed due to the potential for disease. In addition, “we really need to understand what is a very high level,” he said, “because higher TGA levels are more likely to lead to findings of intestinal lesions.”
Complicating this diagnostic picture is the wide variability of currently available IgA-TGA assays, said Dr. Liu of the Barbara Davis Center for Childhood Diabetes and the section of gastroenterology, hepatology, and nutrition at the Children's Hospital and the University of Colorado at Denver. The definition of what constitutes a high TGA value differs depending on the laboratory and the assay used.
Asymptomatic individuals may need to be tested several times before deciding whether to proceed with biopsy. This is because a biopsy done too soon could produce normal histologic findings that suggest the absence of disease, but these normal findings do not necessarily rule out the possibility that disease will develop, Dr. Liu said.
He cited an example of the patient with type 1 diabetes who has an abnormal TGA and whose small intestinal biopsy is normal. The finding is not necessarily a “false positive” TGA level, but could be caused instead by the underlying biology of celiac disease. “If we biopsy patients too early they may not have had time to develop intestinal lesions,” he said. “If we believe that the paradigm for most autoimmunity also applies to celiac disease—that autoantibodies precede the development of actual disease—then performing intestinal biopsy in the early stages of autoimmunity might lead to findings of normal histology.”
Although some clinicians prefer to perform a biopsy at the first sign of abnormality on TGA because they do not want to miss a case of disease, Dr. Liu said the approach to diagnosis at his institution differs somewhat. “We don't want to biopsy more than once,” he said, adding that this strategy is viable because “the kids we follow are in the medical system, so we can afford to be patient and try to determine the optimal time for biopsy” with serial serologic tests.