Gastrointestinal: Collagenous Sprue

Abstract

A 66-year-old woman with no past medical history presented for further evaluation of chronic diarrhea. Five months previously, she had a sudden-onset of watery, large volume stools that occurred four to six times per day. After one month of persistent symptoms, she underwent an upper endoscopy which revealed the small bowel mucosa to be diffusely abnormal with mucosal granularity, scalloping, and a fine mosaic mucosal pattern with cobblestoning and whitish villi (Figure 1). Small bowel biopsies showed villous atrophy and increased intraepithelial lymphocytes with a mixed population of lymphocytes, plasma cells, and eosinophils (Figure 2). Serologic testing for celiac disease with both IgA and IgG tissue transglutaminase antibodies was negative. Human leukocyte antigen (HLA) haplotype testing showed positivity for HLA DQ2 and HLA DQ8. A presumptive diagnosis of serologically negative celiac disease was made and she was initiated on and compliant with a gluten-free diet for two months without any improvement in diarrhea. Because of persistent symptoms, she was referred for further evaluation. On further review of the small bowel biopsy, in addition to villous atrophy and increased intraepithelial lymphocytes, there was thickening (>10 micrometer) of the subepithelial collagen band (Figure 2, arrow); findings diagnostic of collagenous sprue. In most malabsorptive disorders, histopathologic examination of the small bowel biopsy is not diagnostic as there is a limited spectrum of mucosal response to injury. However, in some cases there may be specific histologic features present that may be diagnostic. The malabsorptive disorders with diagnostic histologic features include: Whipple's disease, abetalipoproteinemia, intestinal lymphangiectasia, giardiasis, lymphoma, autoimmune enteropathy, and collagenous sprue. Collagenous sprue is a clinicopathological entity characterized by chronic diarrhea and malabsorption with the histological findings of subepithelial collagen deposition and villous atrophy of the small intestinal mucosa. The only histologic feature that differentiates it from celiac disease is the thickened subepithelial collagen band. Weinstein et al. introduced the term ‘collagenous sprue’ in a report in the New England Journal of Medicine in 1970 in which they described an individual with malabsorption who was initially thought to have celiac disease but failed to respond to a gluten-free diet (GFD). Traditional thinking is that collagenous sprue is a complication of celiac disease. However, many patients with collagenous sprue have no evidence of celiac disease and collagenous sprue may represent the final result of a mucosal insult other than gluten sensitivity. The etiology of collagenous sprue is unknown but immune-mediated mechanisms are likely given initial responses to immunosuppressive therapy. Regardless of the etiology, collagenous sprue is thought to portend a poor prognosis with severe morbidity and mortality. Our patient was started on budesonide 9 mg daily and after three days had a complete resolution of diarrhea. The budesonide was subsequently tapered with a recurrence of diarrhea at budesonide 3 mg daily. She has been maintained on budesonide 6 mg daily without adverse sequelae. Clinical improvement on a GFD is an important component of diagnosing celiac disease. Lack of response to a GFD should raise the possibility of alternative diagnoses and small bowel biopsies should then be reviewed by an expert pathologist to exclude other diagnoses. Duodenal intraepithelial lymphocytosis and villous atrophy may occur in other small bowel disorders including collagenous sprue. Contributed by