M1215
The Differential Diagnosis of Persisting Villous Atrophy: There Is More Than Refractory Celiac Disease
Wieke H Verbeek¹, B. Mary E. von Blomberg², Chris J Mulder¹, Marco W Schreurs²
1. Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands, 2. Pathology, VU University Medical Center, Amsterdam, Netherlands

Background: Refractory Celiac Disease (RCD) is characterized by persisting mucosal pathology in spite of a strict gluten free diet (GFD). The first step in the diagnosis of RCD is to reconsider the initial CD diagnosis. Furthermore, other causes of villous atrophy require exclusion, among which adult autoimmune enteropathy (AIE). The latter is an entity reported primarily in infancy, resulting in protracted diarrhea and is characterized by small intestinal villous atrophy and the presence of circulating enterocyte autoantibodies. Aim: To investigate whether AIE patients, or other patients showing persisting villous atrophy, are erroneously diagnosed as RCD type I. Methods: Sera from patients initially diagnosed as, and those suspected for RCD, were included based on: 1) persisting villous atrophy despite a strict GFD, 2) initial CD diagnosis doubtful (e.g. no positive serology and/or HLA-DQ2/8 negative). A total of 20 sera were screened for the presence of enterocyte autoantibodies using an indirect immunofluorescence test on cryosections of normal human duodenum. Results: Three out of 20 sera analyzed, showed clear antibody reactivity against the duodenal epithelial layer. One patient showed strong IgA and IgG staining of enterocyte-cytoplasm and -brushborder, respectively, characteristic for AIE. A second patient showed only moderate IgA staining of enterocytes. Furthermore, the third patient showed strong IgG staining of the extracellular martix of enterocytes. The latter “chicken-wire” staining pattern is characteristic for auto-immune pemphigus. Conclusions: Our results indicate that some cases of persisting villous atrophy are not associated with RCD. These cases should be considered candidates for AIE or other intestinal auto-immune phenomena, including a pemphigus-like intestinal disorder. Correct identification of such patients is pivotal, in view of different treatment regimens. We propose routine screening for the presence of enterocyte auto-antibodies is included in the diagnostic work-up for RCD.