Can a patient with Crohn's disease have a normal colonoscopy and still experience recurrent perianal fistulas?

Crohn's Disease with Normal Colonoscopy and Recurrent Perianal Fistulas

Yes, it is possible for a patient to have Crohn's disease with a normal colonoscopy and recurrent perianal fistulas as the only manifestation. This presentation represents a distinct subset of Crohn's disease that can be challenging to diagnose and manage.

Epidemiology and Presentation

Perianal fistulas occur in approximately 14-38% of patients with Crohn's disease 1. Notably:

• Perianal fistulas can precede or appear simultaneously with the diagnosis of intestinal Crohn's disease in 36-81% of patients who develop perianal disease 1
• A small proportion of patients with Crohn's disease may persist in having only isolated perianal involvement 1
• The risk of developing perianal fistulas varies by disease location:
  • 12% in ileal disease
  • 15% in ileocolonic disease
  • 41% in colonic disease with rectal sparing
  • 92% in colonic disease with rectal involvement 1

Diagnostic Considerations

When encountering a patient with recurrent perianal fistulas and normal colonoscopy findings, consider:

1. Cross-sectional imaging: MRI enterography or CT enterography should be performed to evaluate for small bowel involvement that may be beyond the reach of colonoscopy 1

   • MRI is preferred in young patients and those with known perianal fistulas 1
   • Figure 10 in the consensus recommendations shows cases where normal terminal ileum was observed on colonoscopy, but proximal small bowel inflammation was detected on cross-sectional imaging 1

2. Comprehensive perianal assessment:

   • Contrast-enhanced pelvic MRI is considered the initial procedure for assessment of perianal fistulizing Crohn's disease 1
   • Examination under anesthesia (EUA) is considered the gold standard for evaluating perianal fistulas 1
   • Endoscopic anorectal ultrasound is a good alternative if rectal stenosis is excluded 1

3. Classification of fistulas:

   • Simple fistulas: low (superficial or low intersphincteric or low transsphincteric), single external opening, no pain/fluctuation, no rectovaginal fistula, no anorectal stricture 1
   • Complex fistulas: high (high intersphincteric, high transsphincteric, extrasphincteric, or suprasphincteric), may have multiple external openings, associated with pain/abscess/rectovaginal fistula/anorectal stricture 1

Management Approach

For patients with recurrent perianal fistulas and normal colonoscopy:

1. Initial management:

   • Seton placement for drainage of fistulas, particularly complex ones 1, 2
   • Antibiotics (metronidazole 750-1500 mg/day or ciprofloxacin 1000 mg/day) for up to 3-4 months 1

2. Medical therapy:

   • Infliximab is strongly recommended for patients with perianal fistulizing Crohn's disease 2
   • Higher infliximab trough levels (>10 μg/mL) may be beneficial specifically for perianal fistulizing disease 2
   • Consider combination therapy with an immunomodulator (azathioprine/6-mercaptopurine) to reduce immunogenicity and improve outcomes 2

3. Surgical options:

   • For simple fistulas: fistulotomy may be considered 1
   • For complex fistulas: seton placement followed by medical treatment (preferably anti-TNF) 1
   • In refractory cases: defunctioning ileostomy can be offered 1
   • For severe refractory cases: proctectomy may be necessary 1

Monitoring and Prognosis

Despite optimal management, outcomes can be challenging:

• In a multicenter case series of isolated complex perianal fistulas, despite surgical and/or medical management, active symptomatic fistulas persisted in 58% of patients at follow-up (median 5.5 years) 3
• Symptom remission was achieved in only 21%, and complete fistula closure in 21% 3
• Regular assessment of fistula drainage, inflammatory markers, and clinical symptoms is essential 2

Important Caveats

1. Disease progression: Isolated perianal fistulas may represent an early presentation of Crohn's disease that could later manifest with intestinal involvement 3

2. Cancer risk: Long-standing perianal Crohn's disease carries a risk of malignancy, necessitating monitoring 1

3. Diagnostic challenges: Distinguishing between isolated cryptoglandular fistulas and Crohn's disease with isolated perianal manifestation can be difficult 3

4. Treatment resistance: Perianal fistulas in Crohn's disease often require multiple surgical interventions and have high recurrence rates 4

In summary, while uncommon, Crohn's disease can present with normal colonoscopy findings and recurrent perianal fistulas as the only manifestation. This presentation requires thorough evaluation with cross-sectional imaging and perianal assessment, followed by a combined medical-surgical approach to management.