The histologic spectrum and clinical outcome of refractory and unclassified sprue

The vast majority of patients with celiac disease respond to a gluten-free diet; yet, a small number of refractory patients do not respond and have pe rsistent malabsorption and residual mucosal abnormalities of the small inte stine. The histologic features of refractory/unclassified sprue have been p ublished as case reports,often without long-term follow up, and no clear hi stologic picture has emerged. We present the results of a long-term study o f the clinical and histologic features of 10 patients with refractory/uncla ssified sprue. The histologic features of small bowel biopsies in this grou p of patients were compared with those of 10 patients with responsive celia c disease and with 10 patients without malabsorption who had normal duodena l biopsies. Five of the 10 refractory patients ultimately developed collage nous sprue as a distinct histologic marker of refractory disease. Additiona l distinctive findings found in small bowel biopsies in the refractory grou p were subcryptal chronic inflammation (10 of 10) and marked mucosal thinni ng in three patients. Other nonspecific findings included acute inflammatio n and gastric metaplasia. One patient with collagenous sprue developed a B- cell lymphoma of the ileum. and in general collagenous sprue was associated with a poor prognosis. Two of five patients died whereas two others requir e total parenteral nutrition for survival. Pathologists evaluating small bo wel biopsies in the setting of malabsorption should be aware of the subtle histologic changes described here that may portend a refractory course.