What are the symptoms and treatment options for ulcerative colitis?

Ulcerative Colitis: Symptoms and Treatment

Primary Symptoms

Rectal bleeding is the most important symptom in ulcerative colitis, followed by urgency and stool frequency/diarrhea. 1 These symptoms form the core clinical presentation that distinguishes active disease from remission.

Cardinal Gastrointestinal Symptoms

• Rectal bleeding ranges from streaks of blood in stool to frank bleeding, and was ranked as the most important symptom by expert consensus 1
• Urgency to pass stools significantly impacts quality of life, with 72% of patients reporting this as having a large impact on their daily functioning 1
• Increased stool frequency/diarrhea typically presents as 3-4 stools per day above baseline in moderate disease, and >5 stools per day in severe disease 1
• Abdominal pain occurs in 56% of patients and is often cramping in nature, located in the lower abdomen 1
• Tenesmus (painful straining with bowel movements) is a characteristic symptom that should be specifically assessed 1

Systemic and Extraintestinal Symptoms

• Fatigue is experienced by 83% of patients with UC and was rated as having a large impact on quality of life by 59% of patients 1, 2
• Sleep disturbance should be assessed using a numerical scale (such as PROMIS Sleep Disturbance Item Bank), as it significantly impacts disease control 1
• Joint pain is the most important extraintestinal manifestation, followed by uveitis and skin symptoms 1
• Fever may indicate severe inflammation or superimposed infection and requires immediate evaluation 2

Critical Pitfall in Symptom Assessment

Patients and gastroenterologists have significant discrepancies in acceptable symptom thresholds for remission. Patients expect complete absence of symptoms (no bleeding, no urgency, no increased stool frequency), while gastroenterologists often accept mild symptoms occurring occasionally (<2 days per week) 1. This gap must be addressed when setting treatment targets.

Severity Classification

Mild Disease

• 1-2 stools per day above normal 1
• Streaks of blood in stool 1
• Mild mucosal friability on endoscopy 1

Moderate Disease

• 3-4 stools per day above normal 1
• Obvious blood in stool 1
• Moderate friability with some ulceration 1

Severe Disease

• ≥5 stools per day above normal 1
• Mostly blood in stool 1
• Spontaneous bleeding and deep ulceration on endoscopy 1
• Requires hospitalization with monitoring of vital signs four times daily 3

Treatment Algorithm

Mild to Moderate Disease (First-Line)

5-aminosalicylic acid (5-ASA) is the first-line therapy for induction and maintenance of remission in mild to moderate ulcerative colitis. 4

• For proctitis: Use topical 5-ASA suppositories or enemas as primary therapy 5
• For more extensive disease: Combine oral 5-ASA (2.4-4.8g daily) with topical 5-ASA for superior efficacy 5, 6
• Oral corticosteroids may be added as a bridge to induce remission, but should not be used for maintenance 5, 4

Moderate to Severe Disease (Advanced Therapies)

For patients with inadequate response to 5-ASA or corticosteroids, biologic therapies or small molecule inhibitors are indicated. 4

Biologic Options (in order of evidence strength):

• Anti-TNF agents (infliximab, adalimumab, golimumab): Proven efficacy for achieving mucosal healing 7
  • Infliximab dosing: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 8
  • Consider dose escalation to 10 mg/kg if initial response is lost 8
• Anti-integrin therapy (vedolizumab): Targets gut-specific inflammation 4, 7
• Anti-IL-12/23 therapy (ustekinumab): Alternative for refractory cases 4

Small Molecule Options:

• JAK inhibitors (tofacitinib): Oral therapy with response rates of 30-60% 4
• S1P modulators (ozanimod): Newer oral alternative 4

Acute Severe Ulcerative Colitis (ASUC)

Intravenous corticosteroids are first-line therapy for acute severe UC, with rescue therapy required if no response after 3-5 days. 3, 9

Immediate Management:

• Hospitalize with joint gastroenterology and colorectal surgery management 3
• IV corticosteroids: Hydrocortisone 400 mg/day or methylprednisolone 60 mg/day 3
• Supportive care: IV fluids, electrolyte replacement, subcutaneous heparin for thromboprophylaxis 3
• Rule out infection: Always obtain stool cultures for C. difficile, bacterial pathogens, and consider CMV testing 3, 9
• Monitor CBC, CRP, albumin every 24-48 hours 3

Rescue Therapy (Day 3-5 if inadequate response):

• Infliximab 5 mg/kg IV 3, 8, 9
• Cyclosporine as alternative rescue agent 3, 9
• Urgent colectomy if medical rescue fails or fulminant colitis develops (25-30% of severe flares require surgery) 3

Critical Treatment Pitfalls

• Never use NSAIDs in UC patients, as they significantly exacerbate colonic inflammation and increase ulcer recurrence risk 1, 2
• Always exclude infection before escalating therapy, as superimposed bacterial or viral infections account for a significant proportion of flares 3
• Do not delay colectomy in patients with refractory toxic megacolon, perforation, or continuous severe bleeding 5, 9
• Avoid full colonoscopy in acute severe colitis due to perforation risk; flexible sigmoidoscopy is sufficient 1

Monitoring and Treatment Targets

Comprehensive disease control should include both symptom resolution and objective measures of inflammation. 1

• Biomarkers: Fecal calprotectin >150 mg/g or elevated CRP indicate moderate to severe endoscopic inflammation and guide treatment escalation 3
• Endoscopic remission: Target complete mucosal healing, defined as normal-appearing mucosa without friability or ulceration 1, 7
• Histologic remission: Emerging as preferred endpoint, as histologic inflammation predicts relapse even with endoscopic healing 7
• Surveillance colonoscopy: Required at 8 years from diagnosis for dysplasia screening, given 4.5% risk of colorectal cancer after 20 years 4

Long-Term Outcomes

• Approximately 20% of patients require hospitalization within 5 years of diagnosis 4
• 7% undergo colectomy within 5 years 4
• Life expectancy is reduced by approximately 5 years compared to the general population (80.5 years for females, 76.7 years for males) 4
• Mucosal healing significantly reduces risk of clinical relapse, hospitalization, surgery, and colorectal cancer 7