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THE PRESENCE OF ANTIBODIES TO TISSUE TRANSGLUTAMINASE WITH A BIOPSY NEGATIVE FOR CELIAC DISEASE: A DIAGNOSTIC DILEMMA
C Tsien, K Waschke
Department of Gastroenterology, Montreal, QC
Clinicians are increasingly aware that celiac disease can present with a wide spectrum of symptoms, both intestinal and extraintestinal. With the widespread use of serologic tests to screen for asymptomatic or subclinical celiac disease, the clinician is faced more and more with the diagnostic dilemma of having a positive serology, but a negative duodenal biopsy.
The present report describes a middle-aged Italian woman with no significant family history who presented with long-standing crampy abdominal pain, bloating, loose stools, and a mild normocytic anemia. Her work-up revealed markedly elevated antibodies to tissue transglutaminase (tTG) on two separate occasions, and yet she had repeated normal upper endoscopies with duodenal biopsies showing normal mucosa. She had no antiendomysial antibodies (AEA), and HLA typing showed neither HLA DQ2 or DQ8. Her symptoms failed to improve on a gluten free diet.
We conducted a literature search using the MEDLINE (1950 to September 2007) and PubMed databases concerning the significance of anti-tTG antibodies despite a negative biopsy. While false positives account for some of these cases, certain authors have noted unusually high rates in select patient populations, such as those with chronic liver disease or chronic heart failure. Hypotheses range from cross-reactivity to the recombinant tTG, to hypergammaglobulinemia and a hyperactive immune response, to the ubiquitous expression of tTG in other organ systems (CNS, cardiovascular, etc). Thus, these populations could truly have antibodies to tTG without having celiac disease. We propose an algorithm that incorporates the above diagnoses. It also includes AEA screening and HLA typing, given their very high negative predictive values. A third possibility is that these patients have potential celiac disease, and are at risk of developing celiac disease at a later age. More research is needed concerning the frequency and methods of surveillance, as well as the clinical sequelae of untreated, asymptomatic celiac disease.