What is the treatment for a patient with a biopsy showing an ulcer bed and necroinflammatory exudate, indicative of active ulcerative colitis?

Treatment of Active Ulcerative Colitis with Ulcer Bed and Necroinflammatory Exudate

A biopsy showing ulcer bed with necroinflammatory exudate indicates severe active ulcerative colitis requiring immediate escalation to advanced therapy, with consideration for hospitalization and intravenous corticosteroids if the patient has systemic symptoms. 1

Understanding the Histopathologic Findings

The presence of an ulcer bed with necroinflammatory exudate represents severe active inflammation with epithelial damage and neutrophilic infiltration 1. This finding indicates:

• High disease activity with surface epithelium damage, mucin depletion, and acute inflammatory cell infiltrate 1
• Substantial risk of relapse even if symptoms temporarily improve, as these histological features predict poor outcomes 1
• Need for CMV exclusion - testing for cytomegalovirus should be performed on biopsies with prominent granulation tissue derived from large ulcers, particularly if the patient is on or being considered for immunosuppressive therapy 1

Immediate Clinical Assessment

Before initiating treatment, determine disease severity through:

• Stool frequency, rectal bleeding severity, and presence of systemic symptoms (fever, tachycardia) 1
• Laboratory markers: Complete blood count, CRP, albumin, and electrolytes 2
• Fecal calprotectin if not already obtained - levels >150 mg/g confirm active inflammation 1
• Exclude infectious triggers: Stool cultures including Clostridium difficile toxin assay 1

Treatment Algorithm Based on Clinical Severity

For Moderate-to-Severe Disease Without Hospitalization Criteria

Initiate advanced therapy immediately rather than attempting conventional therapy escalation 2, 3:

• First-line biologic options: Infliximab 5 mg/kg IV at weeks 0,2, and 6, or other TNF antagonists (adalimumab), vedolizumab, ustekinumab, or JAK inhibitors (tofacitinib, upadacitinib) 2, 3
• Combination therapy is superior: Combine TNF antagonists with thiopurines (azathioprine 1.5-2.5 mg/kg/day) or methotrexate rather than using biologic monotherapy 2
• Bridge with oral corticosteroids if needed: Prednisolone 40 mg daily tapered over 8 weeks, but only as a bridge to advanced therapy 2

For Acute Severe Colitis (≥6 bloody stools/day + systemic toxicity)

Hospitalize immediately and initiate IV corticosteroids 2:

• IV methylprednisolone 40-60 mg/day (or hydrocortisone 100 mg four times daily) 2
• Supportive care: IV fluid and electrolyte replacement with potassium supplementation ≥60 mmol/day, low-molecular-weight heparin for thromboprophylaxis (rectal bleeding is NOT a contraindication) 2
• Daily monitoring: Stool frequency, vital signs, complete blood count, CRP, albumin, electrolytes 2
• Unprepared flexible sigmoidoscopy to assess severity and exclude CMV colitis 2

Assess response at day 3-5 2:

• Predictors of steroid failure: >8 stools/day OR 3-8 stools/day with CRP >45 mg/L on day 3 2
• If inadequate response by day 3-5: Initiate rescue therapy with infliximab 5 mg/kg IV or ciclosporin 2 mg/kg/day IV 2
• Maximum IV steroid duration: 7-10 days - prolonged courses offer no benefit and increase toxicity 2

Surgical Consultation

Involve surgery early - surgical consultation should begin from admission for acute severe colitis 2. Indications for colectomy include:

• Failure of rescue therapy after 4-7 days 2
• Toxic megacolon without improvement after 24-48 hours 2
• Perforation or massive hemorrhage 2
• Subtotal colectomy with ileostomy is the procedure of choice in emergency settings 2

Critical Pitfalls to Avoid

Do not delay advanced therapy - histological features of ulcer bed with necroinflammatory exudate predict high relapse risk, making conventional 5-ASA therapy insufficient 1. The pathology report should indicate high disease activity requiring aggressive treatment 1.

Do not miss CMV reactivation - in patients with severe colitis refractory to immunosuppressive therapy, CMV testing is mandatory, as reactivation occurs in 10-56.7% of UC patients and increases morbidity 1. Immunohistochemistry or quantitative PCR are more sensitive than H&E staining 1.

Avoid anti-diarrheal medications in severe disease to prevent toxic megacolon 2.

Monitoring Treatment Response

• Clinical response within 2 weeks for corticosteroid therapy 2
• Endoscopic reassessment at 8-12 weeks for biologics to confirm mucosal healing 1, 2
• Target histological remission - resolution of neutrophils and crypt architectural distortion, though some chronic changes may persist 1
• Serial fecal calprotectin at 3-6 month intervals to detect early flares, targeting <50 μg/g for mucosal healing 4