The Watery Diarrhea-Colitis Syndrome

Abstract

Collagenous and lymphocytic/microscopic colitis represent a distinct histopathologic spectrum of findings, with occasional transition, observed in patients with normal or near-normal colonoscopic findings and chronic watery diarrhea (watery diarrhea- colitis syndrome). Biopsies are characterized by surface epithelial damage, an increased number of chronic inflamatory cells in the lamina propria, intraepithelial lymphocyto sis, intact crypt architecture, and in the cases of collagenous colitis, a thickened subepi thelial collagen layer (SCL). While their precise interrelationship is unclear, as their clinicopathologic similarities far outweigh their differences, it appears reasonable for pathologists and clinicians to consider them conceptually together as part of a syn drome of chronic watery diarrhea and colitis distinct from other forms of chronic inflammatory bowel disease. The etiology and pathogenesis of this syndrome are un clear. Colorectal surface epithelial damage appears to be for the most part responsible for the secretory diarrhea, while the thickened SCL appears to be a variable response to the surface epithelial damage. Why the thickened SCL occurs only in some cases, why it does not occur in other forms of colitis, and whether it functions as a diffusion barrier are unknown. The propensity of the watery diarrhea-colitis syndrome to pref erentially affect middle-aged and elderly women, an association with autoimmune disorders, and clinicopathologic similarities to celiac disease suggest that host immune factors are important. Other dietary factors, medications, or other agents may also play a role, and this is currently under investigation. Small bowel villous atrophy appears to account for the presence of steatorrhea noted in some reports. Definitive diagnosis is facilitated by the procurement of multiple, well-oriented biopsies, prefera bly extending at least into the proximal left colon. A thickened SCL occasionally can only be demonstrated in biopsies from the right colon. An appreciation of the normal variation found in colorectal biopsies and recognition of artifactual thickening of the subepithelial basement membrane in maloriented sections and in relation to bowel preparation will eliminate overdiagnosis of normal biopsies, while the absence of fea tures typical for other forms of inflammatory bowel disease facilitates differential diag nosis. Patients may respond dramatically to therapeutic intervention with drugs often used for ulcerative colitis and Crohn's disease, however, spontaneous remissions are well documented. A colitis-dysplasia-carcinoma sequence has not as yet been docu mented to occur in this patient population. In just over one decade the morphologic features of the watery diarrhea-colitis syndrome have come to be recognized. Hope fully, the next decade of observation and investigation will help to clarify the precise relationship between cases with and without a thickened SCL, as well as the etiology and pathogenesis of the secretory diarrhea. Int J Surg Pathol 1 (1): 65-82, 1993