Etiology and Clinical Implications of Collagenous Sprue: A Single Institution Experience
E Vakiani, C Arguelles, M Mansukhani, P Green, G Bhagat. Columbia University, New York, NY
Background: Collagenous sprue (CS) is considered one of the causes of refractory sprue. The etiology of CS is controversial and this entity has been associated with poor clinical outcomes. We thus retrospectively analyzed cases of CS diagnosed at our institution.
Design: Patients were identified through a search of our departmental archives between 1999 and 2008. Small bowel biopsies were assessed for histologic variables including subepithelial collagen and degree of villous atrophy. The thickness of collagen deposition was measured on trichrome stained sections and classified as mild (10-14 m), moderate (15-20 m) or marked (>20 m). Stains for CD3 and CD8 and PCR for T cell receptor gene rearrangement were performed in all cases. Flow cytometry analysis was performed in a subset. Clinical data including serologies and response to gluten free diet (GFD) and immunomodulator therapy (IMRx) were obtained from the treating physicians.
Results: Twenty one patients with CS were identified (18F, 3 M, age range 25-80 yrs, median 63 yrs). Twenty patients (95%) had positive serologies for celiac disease. One patient was diagnosed with autoimmune enteropathy. Ten patients (48%) had an atypical (non-diarrhea predominant) presentation. Small bowel biopsies from 19 patients were available for assessment of collagen thickness, which varied from mild (n=9) to moderate (n=6) to marked (n=4). The degree of villous atrophy was total (n=12) or subtotal (n=7). An increase in CD3+CD8- intraepithelial lymphocytes was observed in 42% (8/19) of the biopsies, and flow cytometry, where performed, showed an expansion of T cells. PCR analysis showed minor clones in 4/19 (21%) cases. The degree of subepithelial fibrosis did not correlate with the presence of clonal T cell expansions. Follow-up biopsies, available in 10 patients showed a reduction in subepithelial collagen in 6 patients, while persistent T cell clones were seen in 2 patients. Clinically, 6/21 (29%) patients responded to GFD and all patients (n=8) receiving IMRx showed a response. None of the 4 patients with marked fibrosis responded to GFD. There was no progression to lymphoma and all patients are currently alive (4.1 yrs mean follow-up time; range 0.3-9.5 yrs).
Conclusions: The vast majority of patients in our series of CS had celiac disease. Most cases had total villous atrophy with polyclonal T cell infiltrates. A response to GFD was seen, although in a minority of patients. Even though most patients required IMRx for symptom control, CS was not associated with a dismal prognosis as reported previously.
Monday, March 9, 2009 11:00 AM
Platform Session: Section C, Monday Morning