What is ulcerative colitis?

What is Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory bowel disease characterized by continuous mucosal inflammation that begins in the rectum and extends proximally through the colon in a confluent pattern, presenting classically with bloody diarrhea, urgency, and tenesmus. 1

Disease Definition and Pathophysiology

Ulcerative colitis represents a chronic idiopathic inflammatory disorder limited to the colonic mucosa, affecting approximately 240,000 people in the UK and exceeding 400 per 100,000 in North America. 1, 2 The disease results from dysregulated immune responses to intraluminal antigens in genetically susceptible individuals, with environmental triggers (infection, drugs, or other agents) precipitating disease onset. 1, 3

The etiology remains unknown, though the genetic component is present with mutations in genes like CARD15/NOD2 (Chr 16), OCTN1 and 2 (Chr 5), and DLG5 (Chr 10) identified in inflammatory bowel disease. 1 Interestingly, smoking decreases the risk of UC through unknown mechanisms, unlike Crohn's disease where it increases risk. 1

Cardinal Clinical Features

The hallmark symptom is bloody diarrhea, accompanied by colicky abdominal pain, urgency, and tenesmus. 1 The disease follows a relapsing-remitting course, with approximately 50% of patients experiencing a relapse in any given year. 1

Key clinical characteristics include:

• Continuous, confluent inflammation starting at the anal verge and extending proximally with clear demarcation between inflamed and normal mucosa 1
• Rectal bleeding with or without mucus, fecal urgency, and variable abdominal pain often relieved by defecation 4, 5
• Approximately 20% of patients experience acute severe flares requiring hospitalization, which remains a potentially life-threatening condition 1, 6

Disease Extent Classification

The Montreal/Paris classification system defines three main categories:

• E1 (Proctitis): Limited to the rectum 1
• E2 (Left-sided colitis): Extends to the splenic flexure 1
• E3 (Extensive colitis/Pancolitis): Extends proximal to the splenic flexure or hepatic flexure 1, 7

Pancolitis affects 20-40% of UC patients and carries the worst prognosis with a 19% 10-year colectomy rate and highest colorectal cancer risk. 7

Diagnostic Approach

Diagnosis requires clinical suspicion supported by endoscopic findings (continuous inflammation from rectum), typical histological features on biopsy, and negative stool examinations for infectious agents. 1

Essential diagnostic elements include:

• Ileocolonoscopy with biopsies from at least five sites around the colon including rectum and ileum 1, 4
• Endoscopic features: mucosal friability, spontaneous bleeding, ulcerations, loss of vascular pattern, and granularity 1, 4
• Histopathology showing basal plasmacytosis (earliest diagnostic feature), crypt architectural distortion, mucosal atrophy, and diffuse transmucosal inflammatory infiltrate 1
• Exclusion of infectious causes including C. difficile and Cytomegalovirus 1, 8

Initial Investigations

Initial workup should include full blood count, electrolytes, liver and renal function, iron studies, vitamin D level, C-reactive protein, and fecal calprotectin. 1 CRP above 10 mg/L after a year of extensive colitis predicts increased surgical risk. 1

Fecal calprotectin is the most sensitive neutrophil-derived protein marker for intestinal inflammation, valuable for selecting patients for diagnostic investigation and assessing disease severity. 1

Disease Course and Prognosis

With modern management, UC shows only slight excess mortality in the first two years after diagnosis, with little subsequent difference from the general population. 1 However, life expectancy remains approximately 5 years shorter than people without UC (80.5 years for females, 76.7 years for males). 2

Critical prognostic factors:

• Overall, 20-30% of patients with pancolitis require colectomy 1
• Within 5 years of diagnosis, approximately 20% are hospitalized and 7% undergo colectomy 2
• After 20 years of disease duration, colorectal cancer risk is 4.5%, with a 1.7-fold higher risk compared to the general population 2
• Approximately 90% of patients are fully capable of work after the first year 1

Extraintestinal Manifestations

Approximately 27% of patients develop extraintestinal manifestations, with inflammatory arthropathies and primary sclerosing cholangitis being the most common and clinically important. 2, 3 These may include joint pain/swelling, skin lesions, eye inflammation, and liver problems. 8

Common Diagnostic Pitfalls

A gold standard for UC diagnosis does not exist—it requires the combination of clinical, laboratory, imaging, and endoscopic parameters including histopathology. 1 Repeat endoscopy with histopathological review after an interval may be necessary if diagnostic doubt remains. 1

In early stage disease, only 20% of patients show crypt distortion within 2 weeks of first symptoms, making distinction from infectious colitis challenging. 1 Preserved crypt architecture does not rule out UC at early stages. 1

Classification should always remain as the maximal extent ever documented, even if inflammation regresses over time, as up to 10% of patients with initial proctitis ultimately develop extensive colitis or pancolitis. 7