FISTULIZING CROHN’S DISEASE
• • • • Crohn’s disease first described in 1932 o 6 of 14 original patients with fistulas Most common site for fistula: sigmoid colon, cecum 60-70% of patients with fistulas need surgery Incidence: o 20-40% of patients with Crohn’s develop fistulas o 17% entero-enteric o 85% perianal Population based study: o 35% incidenceof fistulas in patients with Crohn’s disease o 20% of patients with Crohn’s have perianal fistulas o 5-10% of patients with Crohn’s have entero-enteric fistulas Cumulative incidence: o 33% after 10 years o 50% after 20 years Recurrent fistulas uncommon, 66% only 1 episode
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Etiology: • Transmural inflammatory process penetrates into adjacent organs • Fistulas usually coexist with or are preceded by an abscess - similar pathophysiology • 2 types 1. internal: o terminate into adjacent organs or mesentery (enteroenteric, enterovesical, ileocolic, gastrocolic rectovaginal) 2. external: o terminate on the surface (enterocutaneous, parastomal, perianal) Presentation: • Often asymptomatic • Most represent more aggressive disease • Often occur after surgery • Ileosigmoid fistula o initial symptoms are often obstructive o after fistula develops the patient often becomes asymptomatic • External fistulas: o Usually present with local pain, drainage, abscess formation • Internalfistulas: o Often asymptomatic and are therefore unrecognized o Major fistula, such as gastro-colic: presents with symptoms of short gut o Minor fistulas such as ileo-cecal and ileo-ileal: usually asymptomatic
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Repeat procedures are more common in patients with fistulizing disease o In a study of 101 patients, there was a statistically significant difference: Mean interval between 1st and 2nd surgery: 1.7 years in patients with fistulas vs. 13 years in patients without fistulas Treatment: 1. Define anatomy of fistula 2. Drain any associated sepsis 3. Eradicate fistulous tract 4. Prevent recurrence 5. Preserve sphincter function in perianal Medical Management: No placebo-controlled trials for internal fistula • Mesalamine/sulfasalazine: o No specific study of effect on fistulas o Induction of remission and maintenance • Corticosteroids o Induction of remission o Not efficacious for fistula o 2 uncontrolled trials increased surgery / increased mortality • Antibiotics: Cipro/Flagyl • Immunomodulators o 6 Mercaptopurine /Azathioprine: AZA non-enzymmatically converted to 6MP Present: 1 controlled study perianal efficacious in clinical response, complete fistula healing lower corticosteriod dose, 3m Pichney 1992: literature review, 3/3 gastro-colic responded Wheeler 1998: entero-vesical 18/31 responded, 12/31 maintained o Methotrexate: Induce remission in Crohn's disease, 4-8 weeks response time o Cyclosporine A: 1/4 randomized placebo-controlled studies induction of remission No data for fistula closure o Tacrolimus Inhibit transcription of interleukin 2 in T-helper lymphocytes Studies ongoing o Infliximab Chimeric monoclonal antibody directed against TNF-alpha Crohn's: TNF-alpha in stool, serum, and intestinal tissue Mucosal cells: secretion of TNF -alpha, failure to release enhanced soluble TNF receptors by mononuclear cells in the lamina propria Present 1999: 94 patients 10% abdominal, 90% perianal Endpoint: ♦ Primary = decrease >50% in number of open fistula ♦ Secondary = closure of all open fistula ♦ Tertiary = nonresponse 68% 5 mg/kg, 56% 10 mg/kg primary endpoint; 26% placebo 55% 5 mg/kg, 38% 10 mg/kg secondary endpoint; 13% placebo mean duration to closure 3 months
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Poritz 2002: 26 patients with fistula 9 perianal, 6 entero-cutaneous, 4 peristomal, 4 intra-abdominal, 3 rectovaginal 69% partial/complete response; 31% no response ♦ 23% complete, maintained 6.5 months ♦ 46% partial closure: 6 stable, 6 increased symptoms ♦ 54% to surgery: 9 persistent fistula, 9 abscess, 3 stenosis ♦ 15-35% nonresponse rate ♦ 60% adverse reaction Sands 2004 NEJM Multicentcr, double-blind randomized placebo controlled trial 306 adults with Crohn's and abdominal or perianal fistula >3 months Time loss of response shorter in placebo group: 40 weeks vs 14 weeks (p=.009) Week 54: ♦ 19% in placebo complete absence ♦ 36% in maintenance group Initial response rate to infliximab, increased sustained Surgical: • External o Spontaneous: rare, 4/1500, 3 coloumbilical, 1 ileum to linea alba o Postoperative: ileocutaneous, colocutaneous, through previous scar Early (< 1 week ) anastomotic breakdown Late (after 7-10 days) recurrent Crohn's disease, anastomotic leak Fecal diversion and/or resection of fistula and anastomosis o Peri-ileostomy: excess tension on sutures between abdominal wall fascia and serosa Early ( < 1 week) anastomotic breakdown Late: recurrent Crohn’s disease, primary resection or medical treatment Relocation of stoma if abscess/infection • Internal o Enteroenteric: ileo-colic most common (ileo-cecal, ileo-sigmoid) o Symptoms: obstructive, septic o Relative indications for surgery o Resection of ileum and fistula repair (closure nondiseased organ) o Natural course: Broe 1982 24 patients with internal fistula 10 surgery within 1 year 8 surgery 10 years intractable disease 6 no surgery, only radiographic • Severity of illness o Acutely ill, abscess, toxicity: surgery, medical maintenance o Minimal symptoms: medical therapy with antibiotics o No symptoms: unclear if treatment alters course Stefanie Schluender, M.D. April 22, 2004 94