What is the appropriate workup and treatment for a patient presenting with symptoms suggestive of colitis, including abdominal pain, diarrhea, and possibly blood in the stool?

Workup for Colitis

Begin with stool evaluation to rule out infectious causes—specifically Clostridioides difficile, ova and parasites, and viral pathogens—as this is the critical first step before initiating any immunosuppressive therapy. 1

Initial Clinical Assessment

Establish Baseline and Severity Grading

• Document the patient's baseline bowel habits and quantify the increase in stool frequency above baseline 1
• Grade 1: <4 additional bowel movements/day without colitis symptoms (cramping, urgency, blood/mucus, fever) 1
• Grade 2: 4-6 additional bowel movements/day with mild/moderate colitis symptoms limiting instrumental activities 1
• Grade 3: >6 additional bowel movements/day with severe symptoms, hemodynamic instability, or requiring hospitalization 1
• Grade 4: Life-threatening complications including ischemic bowel, perforation, or toxic megacolon 1

Critical Red Flags Requiring Urgent Evaluation

• Blood or mucus in stool suggests infectious colitis, inflammatory bowel disease, or ischemic colitis and mandates immediate workup 1, 2
• Hemodynamic instability (tachycardia, hypotension) indicates severe disease requiring urgent intervention 2
• Peritoneal signs (rebound tenderness, guarding) suggest bowel necrosis or perforation 2
• Abdominal pain out of proportion to examination findings raises concern for mesenteric ischemia 2

Laboratory Workup

Stool Studies (Essential for All Patients with Grade ≥2 or Blood in Stool)

• Infectious workup: C. difficile toxin, bacterial culture (Salmonella, Shigella, Campylobacter), ova and parasites, viral pathogens 1
• For Grade 1 diarrhea without colitis symptoms, defer stool testing until symptoms persist beyond 2-3 days of conservative treatment or worsen 1
• Multiplex PCR testing is preferred over traditional stool cultures for rapid pathogen identification 3, 4

Inflammatory Markers

• Fecal calprotectin: Quantitative measure of inflammation; high levels correlate with ulceration and predict need for aggressive therapy 1, 2
• Fecal lactoferrin: Qualitative biomarker with 70% sensitivity for endoscopic inflammation and 90% sensitivity for histologic inflammation; use to stratify urgency of endoscopy 1, 2

Blood Tests

• Complete blood count, comprehensive metabolic panel, and lactate level 1, 2
• Lactic acidosis indicates transmural ischemia and bowel necrosis 2
• Evaluate for electrolyte abnormalities and anemia requiring correction 2

Imaging Studies

CT Abdomen/Pelvis with IV Contrast

• Indicated for Grade ≥2 colitis to assess for complications and rule out alternative diagnoses 1
• Identifies bowel wall thickening (mean 8mm in colitis vs. 2-3mm normal), mesenteric vessel engorgement, and fluid-filled colonic distention 1, 2
• Essential for detecting life-threatening complications: perforation, abscess, toxic megacolon, or ischemic bowel 1, 2
• CT angiography is first-line imaging for suspected ischemic colitis 2

Endoscopic Evaluation

Colonoscopy or Flexible Sigmoidoscopy with Biopsy

• Strongly consider for all Grade ≥2 colitis to establish etiology and guide treatment 1
• Prioritize early endoscopy (≤7 days from symptom onset) as this reduces symptom duration (19 vs. 47 days) and steroid treatment duration (49 vs. 74 days) 1
• Patients with positive fecal lactoferrin or calprotectin should undergo endoscopy, as these markers predict need for aggressive therapy 1
• Biopsy findings showing ulceration predict steroid-refractory disease requiring early biologic therapy (infliximab or vedolizumab) 1

Histologic Findings Guide Management

• Ulcerative colitis: Continuous inflammation, crypt architectural distortion, decreased crypt density, heavy diffuse transmucosal inflammation without granulomas 5, 6
• Infectious colitis: Mixed inflammatory infiltrates with neutrophils, lymphocytes, plasma cells, and eosinophils 1
• Ischemic colitis: More diffuse inflammatory changes than classic inflammatory bowel disease 1, 2

Special Considerations

Exclude Other Causes of GI Bleeding

• Patients with blood in stool require evaluation for peptic ulcer disease, malignant bleeding, diverticulosis, angiodysplasia, hemorrhoids, and ischemia 1

Risk Stratification for Ischemic Colitis

• Age >60 years, low-flow states, shock (especially cardiogenic), and vasoconstrictor medications (cocaine, ergots, vasopressin, norepinephrine, NSAIDs) increase risk 2
• Test for CMV in addition to standard infectious workup 2

Immunotherapy-Related Colitis Context

• If patient is on immune checkpoint inhibitors, recognize that symptoms typically develop 6-8 weeks after starting treatment 1
• Higher rates occur with CTLA-4 blockade (30-40%) and combination PD-1/PD-L1 plus CTLA-4 therapy 1

Common Pitfalls to Avoid

• Do not delay stool studies in patients with blood/mucus in stool, fever, or other colitis symptoms—infectious workup must be completed before initiating immunosuppressive therapy 1
• Do not rely solely on symptom grade to predict endoscopic severity; fecal markers and endoscopy provide more accurate assessment 1
• Do not defer endoscopy in Grade ≥2 colitis, as early endoscopy significantly improves outcomes 1
• Do not miss ischemic colitis in elderly patients or those with cardiovascular risk factors—maintain high suspicion and obtain CT angiography 2