What is the next step in management for a patient with recurrent symptoms of bloating, fever, and blood and mucus in stool, with normal C-Reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR), and Hemoglobin (Hb) within normal limits, after initial improvement with treatment?

Recurrent Inflammatory Bowel Disease: Proceed to Endoscopy

In a patient with recurrent symptoms of bloating, fever, blood, and mucus after initial improvement, proceed directly to colonoscopy with biopsies to assess disease activity and guide treatment escalation, as normal CRP and ESR do not reliably exclude active endoscopic inflammation in this clinical context. 1

Why Endoscopy is Mandatory

• Normal inflammatory markers are unreliable in symptomatic patients: CRP has only 49% sensitivity for detecting endoscopically active IBD, meaning it misses active inflammation in over half of cases 2
• The AGA explicitly recommends endoscopic assessment when patients have moderate to severe symptoms (blood and mucus qualify as moderate symptoms) even with normal biomarkers, rather than empiric treatment adjustment 1
• Normal CRP is particularly uninformative in ulcerative colitis, where active inflammation frequently occurs without CRP elevation 1, 3

Fecal Biomarkers Should Be Obtained Before Endoscopy

• Measure fecal calprotectin and fecal lactoferrin before proceeding to colonoscopy, as these have 88% and 82% sensitivity respectively for detecting endoscopic inflammation—far superior to CRP 2
• If fecal calprotectin is >150 mg/g or fecal lactoferrin is elevated, this confirms the need for endoscopy and treatment adjustment 1
• Even if fecal markers are normal, the presence of blood and mucus mandates endoscopic evaluation given the high false-negative rate of all biomarkers in symptomatic patients 1, 4

Rule Out Infection First

• Obtain stool cultures for bacterial pathogens, C. difficile toxin PCR, and ova/parasites before attributing symptoms to IBD relapse 1
• C. difficile infection occurs more frequently in IBD patients and can mimic disease flare with blood, mucus, fever, and abdominal symptoms 5
• Blood cultures are indicated given the presence of fever 1

Endoscopic Evaluation Strategy

• Perform complete colonoscopy with intubation of terminal ileum to assess disease extent and severity 1
• Obtain multiple biopsies from both inflamed and normal-appearing mucosa, as microscopic inflammation may be present despite normal endoscopic appearance 6
• Document Mayo Endoscopic Score (for UC) or Simple Endoscopic Score (for CD) to guide treatment decisions 1

Treatment Escalation Based on Findings

• If moderate to severe endoscopic activity is confirmed, escalate therapy immediately rather than continuing current regimen 1
• For patients on 5-ASA or immunomodulators alone, advance to biologic therapy (anti-TNF agents like infliximab 5 mg/kg at weeks 0,2,6, then every 8 weeks) 7
• For patients already on biologics who have lost response, consider dose intensification (e.g., infliximab 10 mg/kg) or switch to alternative mechanism of action 1, 7

Common Pitfalls to Avoid

• Do not rely on normal CRP/ESR to rule out active disease: These markers have poor sensitivity, particularly in ulcerative colitis where up to 50% of patients with active inflammation have normal CRP 1, 2, 3
• Do not empirically escalate treatment without endoscopic confirmation in patients with only mild symptoms, but blood and mucus constitute moderate symptoms requiring direct visualization 1
• Do not delay endoscopy for repeat biomarker testing in 3-6 months: This strategy applies only to asymptomatic patients with elevated biomarkers, not symptomatic patients with alarm features 1

Hemoglobin of 14.7 g/dL Considerations

• The normal hemoglobin suggests either recent onset of bleeding, intermittent blood loss, or localized disease without significant chronic blood loss 1
• This does not exclude significant mucosal inflammation and should not delay endoscopic evaluation 8