When should treatment be started for colitis based on clinical symptoms, endoscopic findings, or laboratory markers of active inflammation?

When to Treat Colitis

Start treatment for colitis immediately when patients present with typical symptoms of bloody diarrhea, increased stool frequency, or abdominal pain, combined with elevated inflammatory biomarkers (fecal calprotectin >150 mg/g or CRP >5 mg/L), without waiting for endoscopic confirmation in moderate-to-severe cases. 1, 2

Treatment Initiation Based on Symptom Severity

Mild Symptoms

• Patients with mild symptoms (minimal rectal bleeding, stool frequency slightly increased) and elevated biomarkers (fecal calprotectin >150 mg/g, CRP >5 mg/L) should undergo endoscopic assessment before empiric treatment adjustment. 1
• This approach prevents overtreatment, as approximately 20-35% of symptomatic patients may actually be in endoscopic remission. 1
• Start oral and rectal 5-aminosalicylates for confirmed mild-to-moderate ulcerative colitis after endoscopic documentation. 3, 4

Moderate-to-Severe Symptoms

• Patients with moderate-to-severe symptoms (frequent rectal bleeding with RBS 2-3, significant stool frequency increase with SFS 2-3) and elevated fecal calprotectin can be treated empirically without routine endoscopy. 1
• In this high pretest probability scenario (85% prevalence of endoscopic inflammation), elevated biomarkers have only 5.4% false-positive rates, making treatment adjustment safe without endoscopic confirmation. 1
• Initiate treatment immediately with oral mesalamine 2.4-4.8 g daily for ulcerative colitis or corticosteroids for more severe presentations. 3, 4

Severe Acute Colitis

• Start intravenous corticosteroids immediately in severe acute ulcerative colitis (high stool frequency, systemic signs, anemia, markedly elevated CRP) without awaiting complete infection workup. 5
• Perform urgent flexible sigmoidoscopy with biopsies including CMV testing, but do not delay corticosteroid administration. 5
• Stool cultures and Clostridioides difficile testing should be sent but should not delay treatment initiation. 5

Biomarker-Guided Treatment Decisions

When Symptoms and Biomarkers Align

• Symptomatic patients with persistently elevated biomarkers (fecal calprotectin >150 mg/g) after initial treatment likely have ongoing inflammation and warrant treatment adjustment without endoscopy. 1
• This approach is supported by moderate-quality evidence showing 14% absolute improvement in achieving clinical and endoscopic remission at 12 months with biomarker-guided treatment. 1

When Symptoms and Biomarkers Diverge

• Symptomatic patients with normal biomarkers (fecal calprotectin <150 mg/g, CRP <5 mg/L) require endoscopic assessment before treatment adjustment. 1
• Normal CRP has a 26.4% false-negative rate, meaning a significant proportion of symptomatic patients with normal CRP actually have endoscopic activity. 1
• Asymptomatic patients with elevated biomarkers should undergo endoscopic confirmation before treatment escalation. 1

Distinguishing Colitis Types Before Treatment

Ulcerative Colitis vs. Diverticulitis

• Ulcerative colitis presents with bloody diarrhea with mucus, urgency, and tenesmus, occurring in up to 90% of flares, typically in younger patients with chronic relapsing symptoms. 2
• Diverticulitis presents with acute-onset severe left lower quadrant pain, fever, and leukocytosis over days, typically in patients over 40 years. 2
• Obtain CT abdomen/pelvis with IV contrast for suspected diverticulitis; check fecal calprotectin for suspected ulcerative colitis. 2

Treatment Escalation Strategy

Initial Therapy Failure

• Patients not responding to 5-aminosalicylates with persistent symptoms and elevated biomarkers should be escalated to thiopurines, biologics (TNF-α antagonists, IL-12/23 inhibitors), or JAK inhibitors. 6, 4
• Complete pre-biologic screening (tuberculosis, hepatitis B/C, HIV, VZV serology) before initiating advanced therapies. 5

Monitoring During Treatment

• Perform interval biomarker assessment every 3 months in symptomatically active patients to guide treatment adjustments. 1
• This biomarker-plus-symptom strategy is superior to symptom-based evaluation alone, with a relative risk of 1.61 for achieving clinical and endoscopic remission. 1

Critical Pitfalls to Avoid

• Do not delay treatment in severe colitis waiting for endoscopy or complete infection workup. 5
• Do not rely on symptoms alone for treatment decisions, as 20-35% of symptomatic patients may be in endoscopic remission. 1
• Do not assume normal CRP excludes active disease; up to 26% of patients with active inflammation have normal CRP. 1
• Do not treat mild symptoms with elevated biomarkers empirically; endoscopic assessment prevents overtreatment. 1
• Do not omit tuberculosis screening before biologics, even in low-risk patients, as reactivation can be fatal. 5