Celiac disease is one of the most common autoimmune diseases, with an estimated prevalence of approximately 1% in various populations [1–3]. The disease is caused by an autoimmune response to gluten which leads to progressive villous atrophy in the small bowel, resulting in malabsorption. Gastrointestinal (GI) symptoms can be relatively nonspecific, such as diarrhea and abdominal pain. Systemic complications are common, and can include iron deficiency anemia and fatigue. Accurate recognition and diagnosis of celiac disease is important because implementation of a gluten-free diet can ameliorate many symptoms. If left untreated, celiac disease is associated with increased mortality in adult life from a range of causes, including autoimmune diseases and malignancy [4, 5].
For patients with an appropriate clinical history, diagnostic tools for the workup of celiac disease can be divided into three categories; serologic assays to measure celiac-associated autoantibodies, genetic assays to identify HLA-DQ2 or -DQ8, and duodenal biopsy to document the presence of villous atrophy. Although many groups have published guidelines on the diagnosis and management of celiac disease and the role of testing in this process [6, 7], surveys have found that there can be significant variation in adherence to these guidelines in different practice settings . While the exact steps of the algorithms can vary slightly depending upon the specific population being tested, most approaches recommend using serologic assays either prior to duodenal biopsy [9, 10] or concurrently with biopsy in cases with a strong clinical suspicion .
The most commonly-used serologic assays measure autoantibodies against tissue transglutaminase (tTG), deamidated gliadin (dGDN), and endomysial tissue (EMA). Antibodies against native gliadin are losing popularity because of inferior performance when compared to the newer dGDN assays [12, 13]. Although most assays measure IgA antibodies against these targets, IgG versions are also available for use in patients with IgA deficiency, a disorder commonly associated with celiac disease . The diagnostic characteristics of celiac serology tests have been well-described in many populations, and in general show analytical performance sufficient for use as a screening test [15–18]. tTG-IgA and EMA-IgA assays have shown the best diagnostic performance in most studies, with pooled sensitivities of 89- 90% and specificities of 98 – 99% in a recent systematic review of the literature . Recent studies have suggested that the use of serologic testing prior to endoscopy could potentially reduce the need for intestinal biopsy to diagnose celiac disease .
Given the high sensitivity and specificity of serologic testing, one would expect to find a fairly high diagnostic yield in duodenal biopsies for celiac disease. In a population with a disease prevalence of 1%, a test with the characteristics described above (90% Sn, 98% Sp) would have an expected positive predictive value (PPV) of roughly 47%. However, the historical experience at our institution has been that the majority of duodenal biopsies submitted for “rule out celiac” are histologically normal. In an effort to understand the causes for this discrepancy, we retrospectively examined the utilization of celiac serology in a cohort of patients who had been sent for duodenal biopsy.