1. An interesting case of a 42 year old woman with diarrhea Christie Seibert, MD July 28, 2004

2. No financial support.

3. HPI Roberta is a 42 yo woman with a 3 mo h/o diarrhea (“explosive and watery”) Roberta is a 42 yo woman with a 3 mo h/o diarrhea (“explosive and watery”) Usually ~2-3 stools/day but once had 7-8 in an hour, prompting an UC visit (2 mo prior) Usually ~2-3 stools/day but once had 7-8 in an hour, prompting an UC visit (2 mo prior) Often “explosions” follow meals Often “explosions” follow meals No nocturnal stools No nocturnal stools Has mild pain in lower abd w/ bloating Has mild pain in lower abd w/ bloating 1-2 Immodium D helped a bit 1-2 Immodium D helped a bit No personal h/o bowel problems No personal h/o bowel problems

4. Other History PMH: DJD of hips, on chronic NSAIDS (sulindac). Otherwise healthy. PMH: DJD of hips, on chronic NSAIDS (sulindac). Otherwise healthy. SH: no recent travel, camping. Office manager. No ill contacts. SH: no recent travel, camping. Office manager. No ill contacts. FH: nothing remarkable FH: nothing remarkable ROS: feels well except for occ nausea, no weight loss ROS: feels well except for occ nausea, no weight loss

5. Exam Not febrile. Normotensive. Not febrile. Normotensive. Abdomen soft, with minimal tenderness in RLQ with deep palpation. No HSM. NL bowel sounds. Abdomen soft, with minimal tenderness in RLQ with deep palpation. No HSM. NL bowel sounds. Guiaic negative. Guiaic negative.

6. Lab evaluation UC (after 1 mo of sxs): UC (after 1 mo of sxs): –Giardia and Cryptosporidium neg –TSH and CBC normal This visit (after 3 mo of sxs): This visit (after 3 mo of sxs): –Fecal leukocytes neg What now???

7. Differential Diagnosis IBS IBS IBD IBD Lactose intolerance Lactose intolerance Factitious diarrhea (laxative abuse) Factitious diarrhea (laxative abuse) Malabsorption Malabsorption Hyperthyroidism Hyperthyroidism Chronic infection (parasites) Chronic infection (parasites)

8. Colonoscopy with biopsy

9. Learning Objectives Define microscopic colitis including subtypes Define microscopic colitis including subtypes Describe pathophysiology and possible drug associations Describe pathophysiology and possible drug associations Delineate clinical features Delineate clinical features Describe treatments, including an expert opinion treatment algorithm Describe treatments, including an expert opinion treatment algorithm

10. Microscopic Colitis Chronic, watery diarrhea Chronic, watery diarrhea Essentially normal endoscopy Essentially normal endoscopy Inflammation on colonic biopsy (no mucosal ulcerations) Inflammation on colonic biopsy (no mucosal ulcerations)

11. 2 major subsets of Microscopic Colitis Lymphocytic colitis Lymphocytic colitis Collagenous colitis Collagenous colitis

12. Epidemiology Prevalence of 10-16 cases/100,000 people Prevalence of 10-16 cases/100,000 people At referral centers, this accounts for approx 10% of patients scoped for chronic diarrhea. At referral centers, this accounts for approx 10% of patients scoped for chronic diarrhea. Typically presents in 6 th -7 th decade Typically presents in 6 th -7 th decade Female: male ratio as high as 20:1 for collagenous type Female: male ratio as high as 20:1 for collagenous type

13. Pathophysiology Unknown Unknown ??NSAIDs, simvastatin, lansoprazole, ticlopidine (mainly case reports and case control studies) ??NSAIDs, simvastatin, lansoprazole, ticlopidine (mainly case reports and case control studies) Association with celiac disease Association with celiac disease –Up to 1/3 of pts with celiac disease will have MC on colonic biopsy –10% of MC pts will have celiac ds

14. Clinical Features Non-bloody chronic watery diarrhea (secretory) Non-bloody chronic watery diarrhea (secretory) Intermittent (85%) vs continuous (13%) vs single episode (2%) Intermittent (85%) vs continuous (13%) vs single episode (2%) Can be insidious or sudden Can be insidious or sudden Usually 4-10 stools/day Usually 4-10 stools/day 27% nocturnal diarrhea 27% nocturnal diarrhea Assoc with abd pain, mild weight loss Assoc with abd pain, mild weight loss May include oligoarthritis May include oligoarthritis Fecal WBCs may be present in up to 50% Fecal WBCs may be present in up to 50%

15. Treatment RCT (14 pts) given 3 chewable bismuth tabs TID vs placebo for 8 wks (Fine 1999) RCT (14 pts) given 3 chewable bismuth tabs TID vs placebo for 8 wks (Fine 1999) –Sig decrease in fecal freq/weight –Benefits lasted 1-8 mo in 9 pts after stopping therapy RCT (20 pts) given Budesonide (9mg/6mg/3mg) vs placebo for 8 weeks (Baert 2002) RCT (20 pts) given Budesonide (9mg/6mg/3mg) vs placebo for 8 weeks (Baert 2002) –Clinical response in 100% of steroid pts vs 20% of placebo –8 of 10 pts with response relapsed within 8 weeks RCT (51 pts) given Budesonide (9mg/d) vs placebo for 6 wks (Mielhke 2002) RCT (51 pts) given Budesonide (9mg/d) vs placebo for 6 wks (Mielhke 2002) –Clinical response in 77% of steroid pts vs 12% of placebo

16. Other Treatments (Response rates from retrospective studies) Antidiarrheal agents 73% Antidiarrheal agents 73% Sulfasalazine42% Sulfasalazine42% Mesalamine45% Mesalamine45% Cholestyramine65% Cholestyramine65% Azathioprine/6-MP20% Azathioprine/6-MP20%

17. Expert Opinion Treatment Algorithm First, stop NSAIDS, other drugs First, stop NSAIDS, other drugs 1 st line: antidiarrheal agents 1 st line: antidiarrheal agents 2 nd line: Bismuth 2-3 chew tabs TID 2 nd line: Bismuth 2-3 chew tabs TID 3 rd line: 3 rd line: –Sulfasalazine –Mesalamine –Cholestyramine Then: steroids Then: steroids

18. References Pardi D. Microscopic Colitis. Mayo Clin Pro. 2003;78(5):614-7. Pardi D. Microscopic Colitis. Mayo Clin Pro. 2003;78(5):614-7. Bonderup Ok et al. Budesonide treatment of collagenous colitis: a randomised, double blind placebo controlled trial with morphometric analysis. Gut. 2003;52(2):1248-51. Bonderup Ok et al. Budesonide treatment of collagenous colitis: a randomised, double blind placebo controlled trial with morphometric analysis. Gut. 2003;52(2):1248-51. Mielhkle et al. Budesonide treatment for microscopic colitis: a randmised, double blind, placebo-controlled, multicenter trial. Gastroenterology. 2002;123(4):978- 84. Mielhkle et al. Budesonide treatment for microscopic colitis: a randmised, double blind, placebo-controlled, multicenter trial. Gastroenterology. 2002;123(4):978- 84. Fine K et al. Randomised, double-blind, placebo- controlled trail of bismuth subsalicylate for microscopic colitis. Gastroenterology 1999;116:A880. Fine K et al. Randomised, double-blind, placebo- controlled trail of bismuth subsalicylate for microscopic colitis. Gastroenterology 1999;116:A880. Dietrich CF, Kaspary W. Lymphocytic and collagenous colitis. UptoDate.com. Accessed 6/29/04. Dietrich CF, Kaspary W. Lymphocytic and collagenous colitis. UptoDate.com. Accessed 6/29/04.