What are the key aspects of ulcerative colitis that a medical student needs to know?

Ulcerative Colitis: Essential Knowledge for Medical Students

Definition and Pathophysiology

Ulcerative colitis is a chronic inflammatory bowel disease causing continuous mucosal inflammation of the colon that begins in the rectum and extends proximally in a continuous fashion, characterized by a relapsing-remitting course. 1

• UC is limited to the mucosa (does not extend transmurally like Crohn's disease) 1
• The precise etiology remains unknown, preventing curative medical therapy 1
• Key risk factors include genetics, environmental factors, autoimmunity, and gut microbiota 2
• UC has a bimodal age distribution with peaks in the 2nd-3rd decades and again between 50-80 years 2

Epidemiology

• Overall incidence: 1.2-20.3 cases per 100,000 persons/year 2
• Overall prevalence: 7.6-245 cases per 100,000 persons 2
• More common than Crohn's disease worldwide 2
• Incidence has increased globally, especially in developing nations 3
• First-degree relatives have significantly increased risk (IRR: 4.08) 4

Clinical Presentation

The classic presentation includes bloody diarrhea with or without mucus, rectal urgency, tenesmus, and variable abdominal pain often relieved by defecation. 2

Core Symptoms to Document:

• Stool frequency, consistency, and presence of rectal bleeding 4
• Urgency, tenesmus, abdominal pain, incontinence, and nocturnal diarrhea 4
• Fever, weight loss, and fatigue (severity indicators) 4

Physical Examination Findings:

• Mild to moderate disease: Often unremarkable except blood on rectal examination 5
• Severe disease: Fever, tachycardia, weight loss, abdominal tenderness, distension, reduced bowel sounds 5

Extra-intestinal Manifestations:

• Joint pain/swelling, skin lesions, eye inflammation, liver problems 4

Disease Classification

By Extent (determines treatment and surveillance):

• Proctitis: Limited to rectum 1
• Left-sided colitis: Extends to splenic flexure 1
• Extensive colitis: Extends proximal to splenic flexure 1

Disease extent influences treatment modality (topical vs. oral therapy) and determines cancer surveillance frequency. 1

• Proximal extension occurs in 20-50% of patients over time 1
• Extensive colitis carries highest CRC risk; proctitis has risk similar to general population 1

By Severity (Mayo Score):

Component	0	1	2	3
Stool frequency	Normal	1-2/day > normal	3-4/day > normal	5/day > normal
Rectal bleeding	None	Streaks	Obvious	Mostly blood
Mucosa	Normal	Mild friability	Moderate friability	Spontaneous bleeding
Physician assessment	Normal	Mild	Moderate	Severe

1

Remission is defined as stool frequency ≤3/day, no rectal bleeding, and normal mucosa at endoscopy. 1

Diagnostic Approach

There is no single gold standard test; diagnosis requires combination of clinical history, laboratory tests, endoscopy with histopathology, and exclusion of infectious causes. 5

Essential History Elements:

• Symptom timeline: onset, duration, pattern, progression 4
• Recent travel and infectious exposures 4
• Medication history (especially antibiotics, NSAIDs) 4
• Smoking status (current smoking protective; former smoking increases risk 70%) 4
• Family history of IBD or colorectal cancer 4
• Previous appendectomy (may be protective if before adulthood) 4
• Sexual behavior (relevant for infectious differential) 4

Laboratory Evaluation:

• Must obtain: CBC, electrolytes, liver/renal function, iron studies, vitamin D, CRP, fecal calprotectin 5
• Immunization status assessment 5
• Stool specimens mandatory to exclude infectious causes, particularly C. difficile 5
• Severe disease: elevated CRP typically associated with elevated ESR, anemia, hypoalbuminemia (predictive for colectomy risk) 5

Endoscopic Evaluation:

Ileocolonoscopy with biopsy is essential for definitive diagnosis. 5

Obtain minimum of two biopsies from at least five sites around the colon (including rectum) and ileum. 1, 6

Endoscopic Features:

• Continuous, confluent colonic involvement beginning at anal verge, extending proximally 6
• Clear demarcation between inflamed and normal mucosa (transition occurs abruptly within millimeters) 6
• Rectal involvement is characteristic 6
• Severe disease: mucosal friability, spontaneous bleeding, ulcerations 6
• Loss of normal vascular pattern, granularity, erosions 2

In acute severe colitis, perform flexible sigmoidoscopy rather than full colonoscopy to confirm diagnosis and exclude infection. 5

Histopathological Features:

Early Disease:

• Basal plasmacytosis is the earliest diagnostic feature with highest predictive value 1, 6
• Only 20% show crypt distortion within 2 weeks of first symptoms 6
• Preserved crypt architecture does NOT rule out early UC 6
• Major differential: infectious colitis (shows preserved crypt architecture with acute inflammation) 6
• Repeat biopsies after interval may be necessary for definitive diagnosis 6

Established Disease:

Diagnosis based on combination of:

• Widespread crypt architectural distortion and mucosal atrophy 1, 6
• Diffuse transmucosal inflammatory infiltrate with basal plasmacytosis 1, 6
• Active inflammation causing cryptitis and crypt abscesses 1, 6
• Decreasing gradient of inflammation from distal to proximal 1, 6

Quiescent Disease:

• Lack of active inflammation (no mucosal neutrophils) 1, 6
• Persistent architectural damage: crypt distortion, atrophy, Paneth cell metaplasia 1, 6
• Disappearance of basal plasmacytosis 1, 6

Critical Pitfall: Histological healing is distinct from endoscopic mucosal healing—histological inflammation may persist despite endoscopic remission and is associated with adverse outcomes. 1, 6

Imaging Studies:

• Abdominal X-ray, CT, or ultrasound help define extent and complications 5
• CT hallmark: mural thickening (mean 8mm vs. normal 2-3mm) 2
• CT is preferred initial study for acute abdominal symptoms 2

Biopsy Handling:

• Accompany with clinical information: endoscopic findings, disease duration, current treatment 1, 6
• Fix immediately in buffered formalin before transport 1, 6

Treatment Principles

Goals: improve quality of life, achieve steroid-free remission, minimize cancer risk. 2

Treatment by Disease Extent and Severity:

Proctitis:

• First-line: Topical 5-ASA (suppositories) 2, 7

Left-sided or Extensive Disease (Mild-Moderate):

• Combination of oral and topical 5-ASA ± corticosteroids 2, 7

Severe Disease:

• Requires hospitalization 2, 7
• Intravenous corticosteroids 2, 7
• If refractory: calcineurin inhibitors (cyclosporine, tacrolimus) OR TNF-α antibodies (infliximab) 2, 7
• Immunomodulators (azathioprine, 6-mercaptopurine) 7

Moderate-Severe Disease (Additional Options):

• Thiopurines 8
• Biological agents targeting TNF and integrins 8
• Small-molecule Janus kinase inhibitors 8

Maintenance Therapy:

• After remission induction, continue appropriate medications to maintain steroid-free remission 2, 7

Emergency Surgery Indications:

• Refractory toxic megacolon 2, 7
• Colonic perforation 2, 7
• Severe continuous colorectal bleeding 2, 7
• Up to 15% of patients require surgery due to medical therapy failure or dysplasia development 8

Monitoring and Follow-up

Response determined by combination of clinical parameters, endoscopy, and laboratory markers (CRP, fecal calprotectin). 5

• Assess mucosal healing endoscopically or by fecal calprotectin 3-6 months after treatment initiation in clinical responders 5
• Mucosal healing associated with reduced colectomy risk and lower inflammation at 5 years 5
• Absence of histological acute inflammatory infiltrate predicts quiescent disease course 1

Cancer Surveillance

Patients with extensive colitis have highest CRC risk; left-sided colitis carries intermediate risk approaching extensive colitis with longer disease duration. 1

• Long disease duration and chronic active disease increase CRC risk 9
• Risk may be lower with long-lasting mucosal healing 9
• Surveillance colonoscopy required for left-sided and extensive colitis 1
• Proctitis does not require surveillance (risk similar to general population) 1
• Histology may show greater extent than endoscopy—biopsies necessary for full extent determination and risk stratification 1

Critical Pitfalls and Caveats

Always exclude infectious causes before confirming UC diagnosis, particularly C. difficile and CMV. 5, 4

• Microbial testing recommended in colitis relapse 5
• Disease extent can change: up to 50% with proctitis/proctosigmoiditis develop more extensive disease over time 5
• Treatment may alter classical distribution pattern—awareness crucial to avoid misdiagnosis 1
• Repeat endoscopy with histopathology may be necessary if diagnostic doubt remains 5
• Consider differential diagnoses: IBS, infectious colitis, medication side effects, colorectal cancer 4
• Close gastroenterologist-surgeon collaboration mandatory to avoid delaying surgery when needed 7
• Optimize vaccinations and screen for colon cancer, skin cancer, bone loss, depression 8