What is the recommended diagnostic work‑up and treatment approach for a patient presenting with colitis?

Diagnostic Work-Up and Treatment Approach for Colitis

For a patient presenting with colitis, immediately obtain blood tests (CBC, CRP, albumin, liver function), stool cultures including Clostridioides difficile toxin assay, and perform flexible sigmoidoscopy with biopsies to confirm diagnosis and exclude infectious causes before initiating treatment. 1

Initial Diagnostic Evaluation

Laboratory Assessment

• Complete blood count, CRP, albumin, and liver function tests are essential at presentation to assess disease severity and systemic inflammation 1
• Faecal calprotectin has excellent sensitivity for diagnosing inflammatory bowel disease, though specificity is limited by infections and medications 1
• Stool samples must be sent for culture and C. difficile toxin assay to exclude infectious causes, as infection occurs in 38% of cases presenting with acute bloody diarrhea 1, 2
• Patients with appropriate travel history require stool microscopy for parasitic infections 1

Endoscopic Evaluation

Flexible sigmoidoscopy with biopsies is the cornerstone of diagnosis and should be performed before starting treatment 1, 2. This approach:

• Confirms active colitis and excludes mimics such as CMV colitis, rectal prolapse, malignancy, or irritable bowel syndrome 1, 2
• Approximately 95% of patients have inflammation visible in the left colon, making sigmoidoscopy adequate for diagnosis 1
• Full colonoscopy is NOT recommended in acute severe colitis due to perforation risk, particularly in patients on corticosteroids 1, 2

Critical pitfall: Always obtain biopsies from multiple sites to determine the full extent of inflammation, as macroscopic appearance underestimates disease extent compared to histology 1, 2

Imaging Studies

• Plain abdominal radiograph should be performed in acute severe colitis to exclude colonic dilatation (≥5.5 cm) and estimate disease extent 1
• CT or ultrasound may be used to define disease extent and complications in acute presentations 1
• Cross-sectional imaging has limited diagnostic utility for colitis itself (sensitivity 53-85%, specificity 75-78%) and is primarily useful for ruling out complications when pain, fever, or bleeding predominate 1

Classification and Prognostic Assessment

Disease Extent Classification

Disease extent must be defined as it determines treatment approach, cancer surveillance, and prognosis 1:

• Proctitis: Rectal involvement only (5% 10-year colectomy rate) 1
• Left-sided colitis: Up to splenic flexure (8% 10-year colectomy rate) 1
• Extensive colitis: Beyond splenic flexure (19% 10-year colectomy rate) 1

Important consideration: Disease extent can change over time—up to 50% of patients with proctitis or proctosigmoiditis develop more extensive disease, and classification should always reflect maximal extent 1

Severity Assessment

Acute severe colitis (by Truelove and Witts' criteria) requires immediate hospital admission 1. The British Society of Gastroenterology defines this as:

• Stool frequency >6/day with blood
• Plus systemic toxicity (fever, tachycardia, anemia, or elevated ESR)

Treatment Algorithm

Mild to Moderate Disease

• Proctitis: Topical therapy with suppositories as first-line 1
• Left-sided colitis: Topical therapy with enemas as first-line 1
• Extensive colitis: Oral therapy (often combined with topical) 1
• 5-aminosalicylates (oral and rectal) are typically first-line for mild to moderate disease 3

Critical pitfall: Discontinuation of maintenance therapy is a common cause of relapse—approximately 50% of patients relapse annually after stopping treatment 1, 4

Acute Severe Colitis Management

Hospitalized patients require:

• High-dose intravenous corticosteroids (methylprednisolone 30 mg every 12 hours or hydrocortisone 100 mg 6-hourly) 1
• Daily assessment with blood tests and clinical scoring 1
• Flexible sigmoidoscopy to confirm diagnosis and exclude CMV infection, particularly in steroid-refractory cases 1

For steroid non-responders (after ≥3 days):

• Rescue therapy with intravenous infliximab or ciclosporin should be initiated 1
• Patients not responding within 7 days of rescue therapy, or those with complications (toxic megacolon, severe hemorrhage, perforation), require subtotal colectomy and ileostomy 1
• Early surgical referral is critical—delay in surgery increases perioperative morbidity and mortality 1

Maintenance Therapy

• Patients responding to IV corticosteroids should be transitioned to purine analogues or advanced medical therapy 1
• For moderate to severe disease, options include thiopurines, anti-TNF biologics, anti-integrin agents, and JAK inhibitors 3
• Patients achieving prolonged remission with immunomodulators/advanced therapies can discontinue 5-ASA 1

Special Considerations

Infection Exclusion

Never attribute symptoms to inflammatory bowel disease flare without excluding infection first 4, 2. This is particularly critical for:

• C. difficile (can mimic or coexist with IBD) 1, 4
• CMV (especially in steroid-refractory cases requiring biopsy with immunohistochemistry or PCR) 2

Monitoring and Surveillance

• Multimodal monitoring using clinical, biochemical, imaging, and endoscopic parameters is recommended 1
• Endoscopic remission predicts better long-term outcomes and lower colectomy rates 1, 4
• Cancer surveillance colonoscopy is required for left-sided and extensive colitis but not for isolated proctitis 1

Immune Checkpoint Inhibitor Colitis

For patients on cancer immunotherapy presenting with colitis:

• Stool lactoferrin or calprotectin can stratify patients for endoscopy (90% sensitivity for histologic inflammation) 1
• Flexible sigmoidoscopy is often adequate as 95% have left colon involvement 1
• Treatment escalates from corticosteroids to infliximab or vedolizumab for refractory cases 1