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Introduction
We report the case of a 56 year old male with severe, recurrent pouchitis refractory to antibiotics that was successfully treated with a probiotic, VSL #3.
Case History
This patient has a past history of chronic ulcerative colitis since 1977. In the fall of 1989, he was hospitalized with severe colitis complicated by acute pulmonary embolus. Recurrent rectal bleeding, anemia and diarrhea lead to frequent hospitalization for intravenous steroids, blood transfusions and an ultimate recommendation for colectomy. In the Spring of 1990, the patient underwent proctocolectomy, with simultaneous ileo-pouch anal anastamosis (IPAA) and diverting ileostomy. Pathology examination of the colectomy specimen was consistent with pancolitis with numerous foci of adenomatous dysplastic changes. There were no granulomas or skip areas suggestive of Crohn’s disease in the removed colon. Diverting ileostomy was closed about 4 months later. Within 3 months of this surgery, the patient experienced fecal continence and control of about 6 soft and “mush-like” bowel movements per day. All colitis and anticoagulation medications were discontinued.
The patient had no problems related to the IPAA and bowel habits remained stable with good continence for 15 yrs. In the Fall of 2005, the patient experienced abdominal bloating, distention, and diarrhea greater than 12 movements per day. Endoscopic examination revealed pouchitis. Treatment with metranidozole for two weeks, resolved symptoms and bowel habits returned to baseline. Six month later, the patient was hospitalized with a massive pulmonary embolus. A hypercoagulable state was confirmed by detection of low protein C and S levels and chronic anticoagulation initiated. Over the ensuing 12 months, he experienced recurrent pouchitis and severe transfusion requiring hematochezia. Upper endoscopy, small bowel contrast radiography (SBFT), abdominal and pelvic CT scan, celiac antibody test, and pouch endoscopy with biopsy confirmed that the source of symptoms was pouchitis, Figures 1 & 2. Treatment for relapsing pouchitis consisted of a total of 6 alternating courses of metranidozole and ciprofloxacin over 12 months. Careful review of previous and current histology did not show evidence of Crohn’s disease, ischemia, or opportunistic infection of the pouch. The patient was informed of treatment options to include indefinite cycling of antibiotics, probiotics and surgical take down of the IPAA with placement of an ileostomy. He chose the probiotic option and was treated with VSL#3(VSL Pharmaceuticals, Fort Lauderdale, Florida), two packets in water twice daily. Within a week, bowel movements decrease to 6-8/day, hematochezia stopped and abdominal bloating and distention resolved. Pouch endoscopy after 2 months of probiotic treatment showed resolution of mucosal ulceration and bleeding, Figure 3. Probiotic, VSL#3, dose was decreased one packet per day, and pouchitis reoccurred. The patient was then treated with a prolonged 2 month course of ciprofloxacin, followed by continuous probiotic VSL#3 at 2 packets twice daily. He is now without pouchitis symptoms or rectal bleeding for 4 months.
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Figure 1 |
Figure 2 |
Figure 3 |
Discussion
The lifetime risk for chronic ulcerative colitis patients to require colectomy is about 20%.1,2 Since Pemberton’s report in 1987, on safety and efficacy of IPAA the continent anal pouch procedure has become the preferred “Quality of life” option for proctocolectomy patients versus ilesotomy. Unfortunately, pouchitis has been shown to occur at a rate of 1% per year post operatively.4 The exact cause of pouchitis is not know, but has been suggested to be caused by dysbiosis of the natural intestinal flora.5 Usually high counts of anaerobic bacteria and clostridium species predominate in IPAA patients with pouchitis.5,6,7
There are rare case reports of Clostridium difficle enteritis in the ileoanal pouch and no cases of bacterial enteric pathogens causing pouchitis.8 Stool testing for C. difficile toxin is reasonable, especially if the endoscopic findings suggest pseudomebranes. Otherwise stool testing is usually of no utility. Flexible endoscopy of the pouch is helpful in examining for changes suggestive of Crohn’s disease, CMV pouchitis, ischemic bowel or anastamostic stricture.1,2 Biopsy of the pouch even when macroscopically normal is recommended as it may identify a specific etiology. Pelvic MRI, retrograde or per oral contrast X-ray of the small bowel and pouch may be helpful in defining the anatomy and specific cause of pouch dysfunction. Endoscopic appearance of pouchitis can be variable and Shinozaki, et al,9 have proposed and endoscopic pouch activity index.
Clinical experience has demonstrated that most patients with pouchitis treated with metranidozole or ciprofloxacin experience clinical improvement within 1-2 days.9 A recent comparative trial between ciprofloxacin (1000 mg/day) and metranidozole (20 mg/kg/d) showed greater improvement in the pouch disease activity index (PDAI) and significantly lower side effects (0 vs. 33%) in the ciprofloxacin group.10 Rifaximin is a new, nonabsorbable antibiotic with immunomodulatory functions on the gut. Preliminary results indicate that rifaximin, may be beneficial in Crohn’s disease, ulcerative colitis and refractory pouchitis.11
The evaluation of probiotics in a variety of intestinal ailments has been prolific in the last decade.13 Immunologic basis for probiotic actions have been examined in both animal models and human clinical trials. Sandborn has proposed that probiotics, like VSL#3, may promote cytoprotection of the pouch mucosa through bacterial-enterocyte signaling and a reduction in lipopolysaccharide (LPS)-induced mucosal secretion of tumor necrosis factor (TNF-a) and interferon (INF-?).14 Others have suggested, that probiotics “crowd out” bacterial flora that promote a Th-2 inflammatory response.5,13,15 These and other mechanisms are likely to be responsible for the beneficial effect of probiotics among a variety of intestinal disorders to include irritable bowel syndrome, ulcerative colitis, clostridium difficile colitis.
Recent studies have demonstrated that altering pouch bacterial contents with probiotic bacteria can be effective therapeutic strategy.15,16 In randomized placebo controlled trials by Gionchetti, et al, the probiotic, VSL#3 has been shown to be effective in treatment of chronic pouchitis and in primary prevention after IPAA.17 With the onset of pouchitis highest within the first 6 post operative months among ulcerative colitis patients with concomitant primary sclerosing cholangitis, some have suggested primary prevention with probiotics for this high risk group.2,9
Conclusions:
Pouchitis is a common long term complication of IPAA, estimated to occur in up to 20%. As illustrated in our patient, when antibiotic treatment of pouchitis is unsuccessful, the probiotic, VSL#3 seems to be an effective alternative.
References
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15. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis a double-blind, placebo-controlled trial. Gastroenterology 2000; 119:305–309.
16. Mimura T, Rizzello F, Helwig U, et al. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 2004;53:108–114.
17. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy a double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202–1209.
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