creation date: 2025-11-13 15:26
tags: Pathologies
Ulcerative Colitis
Background
Definitions
Ulcerative colitis (UC) is one of the two major disorders comprising inflammatory bowel disease (IBD), the other being Crohn’s disease.
UC is an idiopathic inflammatory condition resulting in diffuse friability and superficial erosions, characteristically involving the mucosa and submucosa of the rectum and the colon, extending proximally as disease extent increases.
UC is the most common cause of IBD worldwide.
Etiology and Pathogenesis
Causes of UC is unknown but there appears to be a primary genetic component.
The pathogenesis of UC first involves a defect in the epithelial barrier. The defect affects the colonic mucin and possibly tight junctions, leading to an intake of luminal antigens. Immune response which may include atypical Th cell response against epithelial cells. There is a particularly disproportionate increase in IgG1 antibodies in UC patients. Inflammation leads to leukocyte recruitment into the mucosal tissue.
Enteric microflora also play a role in the pathogenesis and severity of inflammation. Disease is likely in part a result of homeostatic imbalance between enteric microflora and host mucosal immunity.
Clinical Presentation
Signs & Symptoms
The primary symptoms is diarrhea with or without blood. Bowel movements are frequent and small in volume.
Associated symptoms include:
- Colicky abdominal pain
- Urgency
- Tenesmus
- Incontinence
Systemic symptoms may include:
- Fever
- Fatigue
- Weight loss
- Dyspnea/palpitations due to anemia secondary to iron deficiency
Physical findings include:
- Abdominal tenderness
- Fever
- Hypotension
- Tachycardia
- Pallor
- Evidence of blood on DRE
Extra-intestinal manifestations include:
- Arthritis/arthopathy (non-destructive peripheral arthritis and ankylosing sponylitis)
- Uveitis and episcleritis or other eye manifestations
- Skin changes (eg. erythema nodosum, pyoderma ganrenosum)
- Hepatobiliary (primary sclerosing cholangitis, fatty liver, autoimmune liver disease)
- Venous and arterial thromboembolism
- Pulmonary inflammation
History & Physical Exam
The onset of symptoms are typically gradual, progressing over several weeks. A prodrome of self-limited rectal bleeding may occur.
Patients may report attacks of bloody diarrhea lasting weeks to month. With treatment, disease course typically consist of intermittent exacerbations with long periods of symptomatic remission.
History should elicit extent of symptoms and extra-intestinal manifestations. Assessment of complications of severe bleeding, fulminant colitis and toxic megacolon and perforation.
History can also rule out alternative causes of colitis including travel history and STI risk. History of abdo-pelvis radiation and NSAID use should be sought.
Diagnosis
Criteria
Diagnosis requires:
- Presence of chronic diarrhea for >4 weeks
- Evidence of active inflammation on endoscopy
- Chronic changes on biopsy
- Exclusion of other causes of colitis
Disease activity can be classified by severity:
Mild
- ≤4 stools per day with or without small amounts of blood
- Mild symptoms with no systemic toxicity
- Normal CRP and ESR
Moderate - 4-6 loose, bloody stools per day
- Mild anemia and non-severe abdominal pain
- No or minimal systemic toxicity
Severe - ≥6 loose, bloody stools per day
- Severe cramps and evidence of systemic toxicity (fever, tachycardia, anemia, elevated inflammatory markers)
Work-up
Laboratory studies
Blood test can be used to assess severity of disease:
- CBC
- Electrolytes
- Albumin
- ESR or CRP
Stool studies should be used to rule out alternative etiology:
- C. difficile PCR
- Routine cultures (Salmonella, Shigella, Campylobacter, Yesinia)
- Shina-like toxin-producing E. coli (O157:H7)
- Ova and parasite microscopy
- Giardia stool antigen test
STI testing may be warranted if suspected.
Endoscopy and biopsy
Endoscopic findings are nonspecific. Ileocolonoscopy can evaluate the extent of colonic disease and investigate for inflammation suggestive of Crohn’s disease. For patients with high risk of toxic megacolon (eg. hospitalized patients), a sigmoidoscopy is sufficient. Findings include:
- Loss of vascular markings due to mucosal engorgement
- Granularity of mucosa
- Petechiae
- Exudates
- Edema
- Erosions
- Touch friability
- Spontaneous bleeding
Biopsy of colon obtained during endoscopy are used to establish the chronicity of inflammation and exclude alternative diagnoses. Findings suggestive of UC include:
- Crypt abscesses
- Crypt branching
- Shortening and disarray
- Crypt atrophy
- Epithelial cell abnormalities (eg. mucin depletion, Paneth cell metaplasia)
- Lamina propria cellularity
- Basal plasmacytosis
- Basal lymphoid aggregates
- Lamina propria eosinophils
Differential
Other causes of chronic diarrhea include:
- Crohn’s disease
- Infectious colitis
- Radiation colitis
- Diversion colitis
- Solitary rectal ulcer syndrome
Red Flags / Complications
Major acute complication includes:
- Toxic megacolon (lack of motility results in massive dilation of the colon, increasing risk of perforation)
Chronic complications include:
- Strictures
- Dysplasia
- Colorectal adenocarcinoma especially >10 years (needs surveillance colonoscopy at higher frequency)
Management
Low-risk mild-to-moderate disease
Patients with the following features are at a lower risk of long-term sequelae:
- Mild or moderate symptoms with no systemic toxicity
- Lack of severe endoscopic findings
- Normal or mild elevation in CRP, ESR, and/or fecal calprotectin levels
- No extraintestinal manifestations
- Diagnosis at age >40 years
- Normal albumin
Induction
Initial phase of treatment is to achieve endoscopic and clinical remission with consideration of histologic improvement.
In most patients:
- 5-aminosalicylic acid (5-ASA) (eg. Mesalamine)
- Consider induction course of oral or topical glucocorticoids
Maintenance
In patients with the following, maintenance therapy is generally required:
- Ulcerative proctitis with >1 disease flare per year
- Ulcerative protosigmoiditis
- Ulcerative colitis proximal to sigmoid colon (eg. left-sided colitis, extensive colitis)
Maintenance regimens typically involve continuing mesalamine (eg. nightly suppository).
In patients without the above features, maintenance therapy is not necessary as remissions are often long-term and relapses are quickly resolved with topical 5-ASA.
Note: smoking
Smoking is protective against UC but is a risk factor for Crohn’s disease and colon cancer.
Moderate-to-severe disease
Patients are considered at elevated risk if they have any of the following features:
- Extensive colitis
- Deep colonic ulcers
- Age <40
- Elevated CRP and/or ESR
- Glucocorticoid requirement to maintain remission
- History of hospitalization for UC
- Co-existing infection
Induction
Several specific regimens are available based on risk factors:
- Anti-TNF with or without immunomodulator
- Vedolizumab (anti-integrin antibody) - preferred if risk for infection or malignancy
Maintenance
Long-term use of induction agent is typical to maintain remission.
In-patient management
For severe disease needing hospitalization, goals of treatment are:
- Achieve hemodynamic stability
- Reduce symptoms
- Long term clinical remission
Briefly, management may include:
- Monitoring
- Fluids and electrolyte repletion
- VTE prophylaxis
- Nutritional management
- Blood transfusion if severely anemic or hemodynamically unstable
- Antibiotics (not routine)
Initial therapies generally consist of:
- Systemic glucocorticoids
- Topical glucocorticoids
Further escalation of therapy may include:
- Infliximab
- Surgery for complications