What is the best course of treatment for a patient with severe, refractory Crohn’s disease (CD) characterized by active ileocolonic inflammation, a complex high transsphincteric perianal fistula with large abscess, and profound malnutrition?

Management of Severe, Refractory Crohn's Disease with Complex Perianal Fistula and Malnutrition

This patient requires immediate surgical drainage of the perianal abscess with loose seton placement, temporary ileostomy for fecal diversion, aggressive nutritional support, followed by anti-TNF therapy (infliximab) combined with an immunomodulator once sepsis is controlled.

Immediate Emergency Management

Surgical Intervention for Perianal Sepsis

• Perform urgent surgical drainage of the perianal abscess under general anesthesia without wound packing 1.
• Do not actively search for or probe the fistula tract during initial abscess drainage, as this can create iatrogenic tracts and increase complexity 1.
• If an obvious fistula is present without probing, place a loose draining seton but do not lay open the fistula tract 1. The seton should be low-profile, made of soft material (such as silastic), avoiding bulky knots or firm suture material like nylon 1.
• Assess the rectum during abscess drainage to evaluate for proctitis, as this influences subsequent management 1.

Fecal Diversion

• Create a temporary diverting ileostomy given the severity of disease, profound malnutrition, and complex perianal sepsis 1. This patient has multiple risk factors for anastomotic complications (malnutrition, active inflammation, perianal sepsis), making primary anastomosis inappropriate in the emergency setting 1.
• The ileostomy allows control of luminal disease, promotes fistula healing by diverting fecal stream, and can be reversed once inflammation is controlled and nutritional status improves 1.

Perioperative Antibiotic Management

• Initiate broad-spectrum antibiotics covering gram-negative bacteria and anaerobes immediately 1. Appropriate regimens include:
  • Metronidazole combined with a fluoroquinolone (ciprofloxacin) or third-generation cephalosporin 1
  • Alternatively, piperacillin-tazobactam or ertapenem as single agents 2
• Continue antibiotics for 5-7 days post-drainage, adjusting based on culture results and clinical response 1.
• Monitor for clinical improvement within 3-5 days; if no improvement occurs, repeat imaging to assess adequacy of drainage 1.

Nutritional Support

• Initiate total parenteral nutrition (TPN) immediately given profound malnutrition and the emergency surgical context 1. TPN is mandatory in severely undernourished patients and is the mode of choice when emergency surgery is needed for complicated IBD 1.
• Continue TPN until enteral nutrition becomes feasible, typically after control of sepsis and improvement in clinical status 1.
• Nutritional optimization is critical before considering definitive fistula surgery or ileostomy reversal 1.

Medical Therapy After Sepsis Control

Anti-TNF Therapy with Immunomodulator Combination

• Initiate infliximab (5 mg/kg at weeks 0,2, and 6) once the abscess is adequately drained and sepsis is controlled 1. Infliximab is the most effective medical therapy for complex perianal fistulizing Crohn's disease 1.
• Combine infliximab with a thiopurine (azathioprine 1.5-2.5 mg/kg/day or 6-mercaptopurine 0.75-1.5 mg/kg/day) to enhance efficacy in complex fistulizing disease 1.
• The combination of anti-TNF with ciprofloxacin improves short-term outcomes and can be continued for several weeks 1.

Critical Timing Considerations

• Do not start anti-TNF therapy until the abscess is adequately drained, as immunosuppression in the presence of active sepsis increases risk of complications 1.
• If the patient was on steroids preoperatively, begin steroid withdrawal as soon as feasible post-operatively 1. Steroids should ideally be weaned over 4 weeks unless emergency surgery was required 1.

Maintenance Therapy and Long-Term Management

• Continue infliximab with thiopurine as maintenance therapy along with seton drainage 1. This combination approach (medical therapy plus seton) should be maintained long-term 1.
• Monitor clinical response by decreased fistula drainage, which is usually sufficient in routine practice 1.
• Consider MRI or endoscopic ultrasound at intervals to evaluate fistula tract inflammation and healing 1.

Seton Management

• The loose seton can remain in place long-term (median 33 weeks) and may be removed once optimal medical therapy achieves control 1. Up to 98% of setons can be successfully removed when used in combination with optimal medical therapy 1.
• Do not attempt definitive fistula closure surgery (advancement flap, LIFT, fistula plug) until proctitis is controlled, the patient is off steroids, nutritional status is optimized, and the fistula tract is well-defined 1.

Ileostomy Reversal Considerations

• Plan ileostomy reversal only after:
  • Control of luminal inflammation (documented endoscopically)
  • Significant improvement or closure of perianal fistula
  • Restoration of nutritional status
  • Stable maintenance on anti-TNF therapy for at least 3-6 months 1

Critical Pitfalls to Avoid

• Never probe aggressively for fistula tracts during emergency abscess drainage, as this creates iatrogenic complexity 1.
• Do not perform fistulotomy (laying open the fistula) in Crohn's disease, as this leads to poor healing and potential incontinence 1.
• Avoid starting immunosuppressive therapy before adequate drainage of sepsis 1.
• Do not attempt primary anastomosis in this setting with multiple risk factors (malnutrition, steroids, active inflammation, perianal sepsis) 1.
• Never attempt definitive fistula closure procedures (advancement flap, LIFT, plug) in the emergency setting or in the presence of active proctitis 1.

Refractory Disease Management

• If the patient fails to respond to infliximab plus thiopurine combination therapy, consider:
  • Switching to adalimumab 1
  • Maintaining the diverting ileostomy long-term 1
  • Proctectomy with permanent stoma as a last resort for truly refractory disease 1