What is the recommended inpatient treatment for a patient with a severe ulcerative colitis flare-up, including those with a history of Clostridioides difficile infection?

Inpatient Treatment for Ulcerative Colitis Flare-Ups

Immediate Management Upon Admission

All patients with acute severe ulcerative colitis (ASUC) should be admitted immediately and started on intravenous corticosteroids without delay, along with comprehensive baseline investigations including mandatory testing for Clostridioides difficile. 1

Diagnostic Criteria for Admission

Admit patients meeting modified Truelove and Witts criteria: 1

• >6 bloody stools per day PLUS at least one of:
  • Temperature >37.8°C
  • Heart rate >90 bpm
  • Hemoglobin <105 g/L
  • C-reactive protein >30 mg/L

Baseline Investigations (Perform Urgently)

Complete the following before or immediately upon admission: 1

• Blood tests: FBC, CRP, U&E, LFTs, magnesium
• Stool studies: Culture, microscopy, and C. difficile toxin assay (mandatory)
• Imaging: Abdominal X-ray or CT scan (CT preferred if perforation suspected)
• Flexible sigmoidoscopy: With biopsies for histology including CMV evaluation
• Pre-biologics screening: Consider on admission as nearly half will fail IV corticosteroids (hepatitis B/C, HIV, VZV, tuberculosis screening with chest X-ray and interferon-gamma release assay) 1

First-Line Treatment: Intravenous Corticosteroids

Start IV corticosteroids immediately without waiting for stool culture results: 1

Preferred regimen: 1

• Methylprednisolone 60-80 mg IV daily (preferred due to less hypokalaemia)
• OR Hydrocortisone 100 mg IV four times daily

Essential concurrent measures: 1

• Low molecular weight heparin for thromboprophylaxis
• Consider withholding 5-ASA medications
• Accurate stool chart recording frequency, consistency, and blood presence
• Daily senior gastroenterology review with FBC, U&E, CRP monitoring

Management of Clostridioides difficile Co-Infection

If C. difficile is diagnosed, treat immediately with oral vancomycin 500 mg four times daily for 10 days AND continue corticosteroids for the UC flare. 1, 2, 3

This is critical because: 2, 3

• C. difficile infection can complicate UC flares and worsen outcomes
• Treatment should not be delayed based on severity assessment
• Continue UC-directed therapy alongside C. difficile treatment

Day 3 Assessment: Determining Response to Steroids

On Day 3, assess response using stool frequency and CRP: 1

Criteria for Steroid Failure (Requiring Rescue Therapy):

• >8 bowel movements per day OR
• 3-8 bowel movements per day AND CRP >45 mg/L

If Steroid Failure Occurs:

1. Obtain urgent colorectal surgical review to determine if emergency colectomy required 1
2. Initiate rescue therapy if surgery not immediately indicated

Rescue Therapy Options (For Steroid-Refractory Disease)

Infliximab and cyclosporine are equally effective rescue agents, though infliximab is often preferred for ease of use and familiarity. 1, 4, 5

Infliximab Protocol: 1, 6

• 5 mg/kg IV at weeks 0,2, and 6
• Start azathioprine or mercaptopurine during hospitalization for synergistic effect
• Consider accelerated dosing (second dose 3-5 days after first) if insufficient response to initial 5 mg/kg dose 1
• Pneumocystis jirovecii prophylaxis required for patients on ≥20 mg prednisolone 1

Cyclosporine Protocol: 1

• 2 mg/kg/day IV for 1 week
• Convert to oral 3 mg/kg twice daily with target trough level 100-200 ng/mL
• Start azathioprine at day 7 in responders
• Continue until day 98

Important Considerations for Rescue Therapy:

• Both agents have equivalent efficacy (colectomy rates ~40% at 3 months) 1
• Choice depends on prior exposure, local expertise, and patient factors 4
• Cyclosporine increasingly used in infliximab-exposed patients 4

Monitoring During Hospitalization

Daily throughout stay: 1

• Senior gastroenterology review
• FBC, U&E, CRP
• Surgical review if: continued systemic toxicity, severe abdominal pain, edema with low albumin, or suspicion of toxic megacolon/perforation
• CT scan preferred over abdominal X-ray if severe complications suspected 1

Indications for Emergency Colectomy

Proceed to emergency colectomy if: 1, 7, 8

• Perforation of the colon
• Toxic megacolon refractory to medical therapy
• Severe colorectal bleeding
• Systemic inflammation with deteriorating clinical condition not responding to rescue therapy
• Failure of rescue therapy by day 7-14

Transition to Oral Therapy and Discharge

Switch to oral prednisolone 40 mg daily when: 1

• <4 bowel movements per day for 2 consecutive days
• No rectal bleeding

Discharge criteria: 1

• At least 24 hours stable on oral therapy without worsening
• If on infliximab: complete loading doses and arrange maintenance
• If on cyclosporine: discharge on oral formulation with appropriate monitoring
• Start or continue thiopurine therapy

Critical Pitfalls to Avoid

Do not delay corticosteroids while awaiting stool culture results - start treatment immediately upon admission 1

Do not use antimotility agents or opiates - these are contraindicated in ASUC and can precipitate toxic megacolon 2, 3, 9

Do not wait beyond day 3-5 to escalate therapy - delayed rescue therapy or colectomy increases morbidity and mortality 1, 5

Do not miss CMV colitis - obtain biopsies during flexible sigmoidoscopy for CMV evaluation; if positive, treat with IV ganciclovir 5 mg/kg twice daily for 3-5 days then oral valganciclovir 900 mg twice daily for 2-3 weeks 1

Do not forget thromboprophylaxis - ASUC patients have high VTE risk requiring LMWH 1