Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory bowel disease characterized by continuous mucosal inflammation and ulceration of the colon and rectum, typically presenting with bloody diarrhea and abdominal pain.

Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease (IBD) characterised by diffuse, continuous mucosal inflammation limited to the colon ^[1]^[2]. The name itself tells you the disease:

"Ulcerative" → ulcer-forming (Latin ulcus = sore/wound)
"Colitis" → inflammation of the colon (Greek kolon = large intestine + -itis = inflammation)

Key defining features that separate UC from Crohn's disease (CD):

Feature	UC	CD
Distribution	Colon & rectum, continuous	Any part of GI tract, skip lesions
Depth	Mucosal / submucosal	Full thickness (transmural)
Fistula	Never	Common (intestinal / perianal)
Benign stricture	Rare	Common
Perianal disease	Rare	Up to 40%
Rectal sparing	No (almost always involves rectum)	Yes (rectal sparing)

^[1]^[3]

The inflammation most commonly begins in the rectum and extends proximally in a continuous fashion — there are no "skip lesions" ^[2]. Occasionally, patients with pancolitis may develop backwash ileitis (mild ileal inflammation from reflux of colonic contents through an incompetent ileocaecal valve), but this should not be confused with true small bowel Crohn's disease.

Indeterminate colitis accounts for 10-15% of patients with IBD who fail to be classified between UC and CD ^[1]^[2]. This can be due to inadequate tissue biopsy or a truly indeterminate form of disease. Surgical treatment for these patients is similar to UC ^[2].

Key Distinction

Think of UC as a "paint roller" — it paints the colon continuously from the rectum upward. Crohn's is a "spray can" — it splatters patches anywhere from mouth to anus, and goes deep through the wall.

2. Epidemiology

3. Risk Factors and Protective Factors

Category	Risk Factor	Explanation
Drug history	NSAIDs	NSAIDs inhibit COX → reduce protective prostaglandins in gut mucosa → impaired mucosal defence → flare of colitis. They also shift arachidonic acid metabolism toward leukotrienes (pro-inflammatory)
Family history	IBD in first-degree relative	Polygenic susceptibility; however less family clustering in East Asia ^[1]
Medical history	Infectious gastroenteritis in prior 1 year	Post-infectious dysbiosis may trigger immune dysregulation in genetically susceptible individuals ^[2]
Disease-specific	Primary sclerosing cholangitis	Bidirectional association — PSC is strongly associated with UC. Majority of patients with PSC have underlying UC; only ~5% of UC patients have PSC ^[2]^[4]
Other	Early age of disease onset, male sex (for CRC risk)	Earlier onset = longer cumulative inflammatory burden ^[1]

Category	Protective Factor	Explanation
Surgical history	Prior appendicectomy	Protective for UC (but is a risk factor for CD). The appendix is a lymphoid organ rich in immune cells that may prime mucosal immune responses; removing it may reduce the likelihood of the aberrant Th2-driven immune response seen in UC
Social history	Smoking	Protective for UC but a risk factor for CD ^[2]. Nicotine increases colonic mucus production, decreases pro-inflammatory cytokines (IL-1, IL-8), and improves mucosal blood flow — these protect the colonic mucosa. Patients who quit smoking are at increased risk of developing UC or experiencing flares

Classic Exam Pitfall

Students often confuse which IBD is associated with smoking. Remember:

Smoking PROTECTS against UC (think: nicotine patches were once trialled as UC therapy)
Smoking WORSENS CD (doubles the risk of flare and surgery)
Appendicectomy PROTECTS against UC but is a risk factor for CD

These are reversed between the two diseases.

4. Anatomy and Function (Relevant to UC)

5. Etiology and Pathophysiology

UC is an immune-mediated disease arising from a complex interplay of:

Genetic susceptibility
Environmental triggers
Gut microbiome dysbiosis
Dysregulated mucosal immune response

Factor	Role
Westernised diet (high fat, high sugar, low fibre)	Alters gut microbiome composition; reduces short-chain fatty acid (SCFA) production (butyrate is the primary fuel for colonocytes)
Urbanisation/improved hygiene	Hygiene hypothesis: less childhood microbial exposure → inadequate training of immune tolerance → aberrant immune response to commensal bacteria
Antibiotics in early life	Disrupt developing microbiome
NSAIDs	Directly damage mucosal barrier; divert arachidonic acid to leukotriene pathway
Stress	Activates the hypothalamic-pituitary-adrenal axis → increases gut permeability and inflammatory cytokines
Prior GI infection	Post-infectious dysbiosis → immune priming → loss of tolerance to commensals ^[2]

6. Classification

The Montreal classification is the standard phenotypic classification for UC ^[2]:

Code	Classification	Description	HK Prevalence
E1	Proctitis	Involvement limited to the rectum (distal to the rectosigmoid junction, ~15 cm)	Part of proctosigmoiditis group
E2	Left-sided UC (distal UC)	Involvement extending up to the splenic flexure	~32% in HK
E3	Extensive UC (pancolitis)	Involvement extending proximal to the splenic flexure	~33.5% in HK

^[2]

From Felix's notes, the HK distribution uses a slightly different subdivision ^[2]:

Proctitis = rectum only
Proctosigmoiditis (34.5%) = rectum + sigmoid
Distal UC (32%) = rectum + sigmoid + colon up to splenic flexure (= Montreal E2)
Pancolitis (33.5%) = beyond splenic flexure (= Montreal E3)
Backwash ileitis = ileal involvement (in the setting of pancolitis)

This is the classic bedside severity assessment for UC — used in clinical practice to determine need for admission and treatment intensity ^[2]:

Parameter	Mild	Moderate	Severe
Bloody stools per day	< 4	≥ 4	≥ 6
Pulse	< 90 bpm	≤ 90 bpm	> 90 bpm
Temperature	< 37.5°C	≤ 37.8°C	> 37.8°C
Haemoglobin	> 11.5 g/dL	≥ 10.5 g/dL	< 10.5 g/dL
ESR	< 20 mm/h	< 30 mm/h	> 30 mm/h
CRP	Normal	≤ 30 mg/L	> 30 mg/L

Interpretation: Immediate admission is warranted in severe disease ^[2].

How to Remember Truelove and Witts' Severe Criteria

"6-90-37.8-10.5-30-30":

≥ 6 bloody stools/day
Pulse > 90 bpm
Temp > 37.8°C
Hb < 10.5 g/dL
ESR > 30 mm/h
CRP > 30 mg/L

If ANY one systemic criterion (pulse, temp, Hb, ESR, CRP) is met along with ≥ 6 bloody stools/day → severe UC → admit immediately.

6.3 Comparison Between Crohn's Disease and Ulcerative Colitis

This is an extremely high-yield comparison table for exams:

Feature	Crohn's Disease	Ulcerative Colitis
Haematochezia	Rare	Common
Passage of mucus or pus	Rare	Common
Abdominal mass	Sometimes	Rare
Upper GIT involvement	✓	✗
Small bowel involvement	✓	✗
Large bowel involvement	✓	✓
Rectal involvement	✓ (usually spared)	✓ (almost always involved)
Perianal involvement	✓	✗
Small bowel obstruction	Common	Rare
Large bowel obstruction	Common	Rare

Feature	CD	UC
ASCA (Anti-Saccharomyces cerevisiae antibodies)	Common	Rare
pANCA (perinuclear anti-neutrophil cytoplasmic antibodies)	Rare	Common

Feature	CD	UC
Pattern of involvement	Focal, patchy	Diffuse, continuous
Depth of inflammation	Transmural	Mucosal and submucosal
Granulomas	✓ (MUST exclude TB)	✗
Goblet cells	Preserved (✓)	Depleted (✗)
Distorted crypt architecture	✓	✓
Cryptitis and crypt abscess	✓	✓

^[2]

Feature	CD	UC
Skip lesions	✓	✗
Ulcers	Solitary, deep, and focal	Shallow
Fistula formation	✓	✗
Abscess formation	✓	✗
Stricture	✓	✗ (rare; if present → suspect malignancy)
Pseudopolyps	✗	✓

^[2]

Why No Fistulae in UC?

Fistulae are abnormal tracts connecting two epithelial surfaces. They require transmural inflammation to burrow through the entire bowel wall. Since UC is limited to the mucosa and submucosa, the inflammation never reaches deep enough to create fistulae. This is a fundamental architectural difference from CD.

Pseudopolyps — What Are They?

Pseudopolyps (inflammatory polyps) are islands of regenerating mucosa surrounded by areas of mucosal ulceration and denudation. They are NOT true neoplastic polyps, but they indicate severe previous inflammation. They are characteristic of UC because the widespread, continuous shallow ulceration creates this "island" pattern. Pseudopolyps are a risk factor for IBD-associated CRC ^[1].

7. Clinical Features

7.1 Symptoms (with Pathophysiological Basis)

Clinical features are related to inflammatory damage in the GIT ^[1]:

Symptom	Description	Pathophysiological Basis
Bloody diarrhoea (haematochezia)	The central feature of UC ^[2]. Passage of blood and/or mucus mixed with stool.	Inflamed, friable, ulcerated rectal and colonic mucosa bleeds easily. The mucosal surface is denuded and superficial vessels are exposed. Mucus production increases as a failed attempt at mucosal protection but also reflects goblet cell dysfunction.
Diarrhoea	Prolonged, fluctuating course. Stools are frequent, small-volume ^[2].	1) Excessive fluid secretion — inflammatory mediators (prostaglandins, histamine) stimulate Cl⁻ secretion from crypt cells → water follows osmotically. 2) Impaired fluid reabsorption — damaged colonic mucosa cannot absorb water and electrolytes normally. 3) The inflamed, non-compliant rectum loses its reservoir function → cannot store stool → frequent small-volume stools.
Tenesmus	Painful straining with a sensation of incomplete evacuation	Inflammation of the rectal wall irritates stretch receptors and pelvic floor nerves, creating a constant sensation of "needing to go" even when the rectum is empty.
Urgency and incontinence	Sudden, irresistible need to defecate; may result in faecal incontinence	The inflamed rectum loses compliance (becomes stiff and fibrotic) → reduced distensibility → even small volumes of stool trigger the defecation reflex. The internal anal sphincter may also be affected by inflammation.
Constipation	UC limited to the rectum (proctitis) may paradoxically present with constipation ^[1]	When only the rectum is inflamed, the proximal colon compensates by increased water absorption, leading to hard, infrequent stools proximal to the inflammation. The rectum itself produces mucus and blood but may not have enough volume to trigger normal defecation. This is a classic exam pitfall!
Abdominal cramps and pain	Colicky abdominal pain ^[1]^[2], typically in the left lower quadrant (where the sigmoid/descending colon lies)	Spasm of the inflamed colonic smooth muscle. Prostaglandins and leukotrienes released by inflammatory cells directly stimulate smooth muscle contraction and activate visceral pain afferents.
Rectal bleeding with bowel movement	Pain or rectal bleeding with bowel movement ^[1]	Direct mucosal ulceration and friability; passage of stool mechanically disrupts the fragile, inflamed mucosa

Constipation in Proctitis

A common mistake is to think UC always presents with diarrhoea. In proctitis (E1), the patient may present with constipation because only the rectum is inflamed. The proximal colon overcompensates by absorbing more water. The patient may pass formed stools but with blood and mucus. Don't be fooled on the exam!

Symptom	Pathophysiological Basis
Fever	Pro-inflammatory cytokines (IL-1, IL-6, TNF-α) act on the hypothalamic thermoregulatory centre to raise the set point. Also consider secondary causes: perforation with peritonitis or superimposed C. difficile infection ^[2]
Fatigue	Multifactorial: anaemia of chronic disease (hepcidin-mediated iron sequestration), iron deficiency anaemia (chronic blood loss), malnutrition, cytokine-driven sickness behaviour (TNF-α, IL-6 directly cause fatigue via CNS effects), and sleep disturbance from nocturnal symptoms
Anorexia	Circulating inflammatory cytokines (TNF-α → also called "cachectin") suppress appetite centres in the hypothalamus
Weight loss	Result of malabsorption, decreased oral intake ^[2]. In UC specifically: reduced food intake (patients avoid eating to avoid triggering symptoms), increased metabolic demand from chronic inflammation, and protein-losing enteropathy through the denuded mucosa

Symptom	Pathophysiological Basis
Pallor, dyspnoea, palpitations, fatigue ^[2]	Chronic blood loss from the ulcerated colonic mucosa leads to iron deficiency anaemia. Additionally, anaemia of chronic disease (ACD) occurs because IL-6 stimulates hepatic hepcidin production → hepcidin blocks ferroportin → iron is trapped in macrophages and enterocytes → functional iron deficiency even if stores are adequate. Reduced oxygen-carrying capacity → compensatory tachycardia (palpitations) and increased respiratory rate (dyspnoea)

Symptom

Pathophysiological Basis

Pallor, dyspnoea, palpitations, fatigue ^[2]

Chronic blood loss from the ulcerated colonic mucosa leads to iron deficiency anaemia. Additionally, anaemia of chronic disease (ACD) occurs because IL-6 stimulates hepatic hepcidin production → hepcidin blocks ferroportin → iron is trapped in macrophages and enterocytes → functional iron deficiency even if stores are adequate. Reduced oxygen-carrying capacity → compensatory tachycardia (palpitations) and increased respiratory rate (dyspnoea)

7.2 Signs (with Pathophysiological Basis)

Sign	Pathophysiological Basis
Pallor	Anaemia from chronic blood loss + ACD (see above)
Tachycardia	Compensatory response to anaemia and/or dehydration; if > 90 bpm → suggests severe disease (Truelove and Witts)
Fever	Systemic inflammatory response; > 37.8°C = severe disease
Dehydration (dry mucous membranes, reduced skin turgor, sunken eyes)	Chronic diarrhoea → fluid and electrolyte losses
Cachexia / weight loss	Chronic inflammation, malnutrition, protein-losing enteropathy
Clubbing	Rare in UC (more common in CD). Mechanism poorly understood; may relate to chronic hypoxia, circulating vasodilators (VEGF, PDGF), or inflammatory mediators causing connective tissue proliferation in nail beds

Sign	Pathophysiological Basis
Left lower quadrant tenderness	The sigmoid and descending colon (most commonly affected in left-sided UC) are tender due to active mucosal and submucosal inflammation
Diffuse abdominal tenderness	In extensive colitis/pancolitis
Abdominal distension	If toxic megacolon develops (non-obstructive dilatation due to inflammation extending into the muscularis propria → loss of smooth muscle tone → colonic atony)
Absence of palpable mass	Unlike CD, UC rarely produces a palpable mass because there is no transmural inflammation, no mesenteric thickening, and no fistula/abscess formation
Rebound tenderness / guarding	Suggests perforation with peritonitis — a surgical emergency

Finding	Significance
Blood / mucus on the glove	Confirms rectal bleeding; the rectal mucosa is friable
Tenderness	Active proctitis
No perianal disease (fissures, fistulae, skin tags)	Perianal disease is characteristic of CD, NOT UC. If perianal disease is found in a patient labelled as "UC," reconsider the diagnosis

7.3 Extraintestinal Manifestations (EIMs)

Extraintestinal manifestations are present in up to 25–40% of IBD patients globally, though fewer EIMs are seen in East Asian populations ^[1]. They can be divided into those that correlate with disease activity and those that are independent.

Key EIMs from lecture slides ^[1]:

Musculoskeletal: peripheral or axial arthropathy
Cutaneous: erythema nodosum, pyoderma gangrenosum
Ocular: scleritis, uveitis
Primary sclerosing cholangitis (PSC)

These flare when the colitis flares and improve when the colitis is treated:

System	Manifestation	Pathophysiology
Musculoskeletal	Peripheral arthropathy (type 1: large joint, pauciarticular, asymmetric)	Circulating immune complexes and cross-reactive antibodies (molecular mimicry between gut bacterial antigens and joint synovial antigens) deposit in joints → synovitis
Dermatological	Erythema nodosum (tender, red nodules on anterior shins)	Immune complex–mediated panniculitis (inflammation of subcutaneous fat). The anterior shin is affected because it is a watershed area with poor blood supply → immune complexes deposit here
Ocular	Episcleritis (painless, red eye without vision loss)	Immune complex deposition in the episcleral vessels

These may occur even when colitis is in remission:

System	Manifestation	Pathophysiology
Musculoskeletal	Axial arthropathy (ankylosing spondylitis, sacroiliitis) — associated with HLA-B27	Molecular mimicry; shared antigens between gut bacteria and spinal entheses. The HLA-B27 molecule may present cross-reactive peptides to cytotoxic T cells
Musculoskeletal	Osteoporosis / osteomalacia	Chronic corticosteroid use, chronic inflammation (cytokines increase osteoclast activity via RANKL), malabsorption of calcium and vitamin D
Dermatological	Pyoderma gangrenosum (deep, painful, violaceous ulcers with undermined edges, typically on lower limbs) — more common in UC than CD ^[2]	Neutrophilic dermatosis; aberrant neutrophil chemotaxis and function. The pathergy phenomenon (worsening at sites of trauma) is characteristic
Ocular	Uveitis (painful, red eye with photophobia and blurred vision) / Scleritis / Iritis	T cell–mediated inflammation of the uveal tract; may share antigens with colonic epithelium
Hepatobiliary	Primary sclerosing cholangitis (PSC)	Chronic progressive inflammation and fibrosis of intrahepatic and extrahepatic bile ducts. Mechanism: aberrant homing of gut-primed T lymphocytes to the liver via the portal circulation (gut-liver axis). These T cells recognise cross-reactive antigens on biliary epithelium. Strong association with UC — majority of PSC patients have UC, but only ~5% of UC patients develop PSC ^[2]^[4]
Hepatobiliary	Fatty liver / autoimmune liver disease	Chronic inflammation, malnutrition, drug effects (corticosteroids, methotrexate)
Vascular	Arterial and venous thromboembolism (DVT, PE, portal/mesenteric vein thrombosis)	IBD is a prothrombotic state: inflammatory cytokines increase tissue factor expression, increase fibrinogen, decrease protein C/S, increase platelet activation, and promote endothelial dysfunction. Risk is 2–3× that of the general population
Urogenital	Renal stones (calcium oxalate)	Fat malabsorption → free fatty acids bind calcium → calcium is unavailable to bind oxalate in the gut → increased free oxalate is absorbed and excreted by the kidney → oxalate stones. (More common in CD with ileal disease, but can occur in extensive UC)
Haematological	Autoimmune haemolytic anaemia	Autoantibodies against RBC antigens; part of the generalised immune dysregulation
Endocrine	Vitamin B12 deficiency	Relevant mainly in CD with terminal ileal disease/resection. In UC, can occur with backwash ileitis or from secondary bacterial overgrowth
GI	Colorectal cancer	Chronic inflammation → oxidative DNA damage → dysplasia → carcinoma sequence. Risk factors include: disease duration, extent of colitis, severity of inflammation, PSC, pseudopolyps, strictures, family history of CRC ^[1]

CRC Risk Factors in IBD

Risk factors for IBD-associated colorectal neoplasia (from lecture slides ^[1]):

Patient-Specific Factors:

Primary sclerosing cholangitis
History of colorectal neoplasia
Family history of CRC in first-degree relative
Smoking (+)
Early age of disease onset (+)
Male sex (+)

Disease-Specific Factors:

Disease duration
Disease extent
Cumulative inflammatory burden
Active inflammation endoscopically or histologically

Endoscopic Features:

Stricture (UC, longer disease duration, proximal location, symptoms)
Shortened tubular colon
Pseudopolyps

Feature	UC	CD
Diarrhoea	Bloody, frequent, small-volume	May or may not be bloody; larger-volume if small bowel involved
Abdominal pain	LLQ, colicky, relieved by defecation	RLQ (ileal), may be obstructive
Rectal bleeding	Almost always present	Variable
Perianal disease	Absent	Common (fissures, fistulae, abscesses, skin tags)
Abdominal mass	Rare	RLQ mass (inflamed ileum/mesentery)
Mouth ulcers	Uncommon	Common (aphthous ulcers)
Malnutrition	Less common (colon mainly)	More common (small bowel malabsorption)

Clinical Feature	Pathophysiology
Bloody diarrhoea	Friable, ulcerated mucosa + impaired water absorption + increased secretion
Tenesmus	Rectal inflammation irritating stretch receptors
Urgency	Reduced rectal compliance from fibrosis/inflammation
Constipation (proctitis)	Proximal colonic compensation + impaired rectal function
Pseudopolyps	Mucosal regeneration islands between areas of shallow ulceration
No fistulae	Inflammation confined to mucosa/submucosa (not transmural)
No granulomas	Th2-driven atypical immune response (not the Th1 granulomatous response of CD)
pANCA positivity	Autoantibodies against neutrophil myeloperoxidase — reflects the autoimmune component
PSC association	Aberrant gut-primed lymphocyte homing to biliary epithelium
Thromboembolism	Prothrombotic state from systemic inflammation
Pyoderma gangrenosum	Neutrophilic dermatosis; aberrant neutrophil function
CRC risk	Chronic inflammation → oxidative DNA damage → dysplasia-carcinoma sequence

High Yield Summary

Definition: UC = chronic, relapsing IBD with diffuse, continuous mucosal/submucosal inflammation limited to the colon, almost always starting from the rectum and extending proximally.

Epidemiology: Peak age 30s–70s; M = F; rising incidence in Hong Kong (Westernisation); roughly equal thirds of proctosigmoiditis/distal UC/pancolitis in HK.

Risk Factors: NSAIDs, family history of IBD, prior GI infection. Protective: Smoking, appendicectomy (opposite to CD!).

Pathophysiology: Genetic susceptibility + environmental triggers → microbiome dysbiosis → epithelial barrier breach → atypical Th2 immune response → mucosal/submucosal inflammation → crypt abscesses, goblet cell depletion, shallow ulceration.

Classification: Montreal E1/E2/E3. Severity by Modified Truelove & Witts (severe = ≥ 6 bloody stools/day + any systemic feature).

Cardinal symptom: Bloody diarrhoea (+ mucus, tenesmus, urgency). Proctitis may present with constipation.

Key differences from CD: No skip lesions, no transmural disease, no fistulae, no granulomas, no perianal disease, shallow ulcers, pseudopolyps. pANCA+ (not ASCA+).

EIMs: Peripheral arthropathy, erythema nodosum, episcleritis (correlate with activity). PSC, ankylosing spondylitis, pyoderma gangrenosum, uveitis (independent of activity).

CRC risk: Increased with longer duration, greater extent, PSC, active inflammation, pseudopolyps, strictures, family history.

Active Recall - Ulcerative Colitis (Definition, Epidemiology, Etiology, Classification, Clinical Features)

Differential Diagnosis of Ulcerative Colitis

9.2 Key Differentials — Detailed Breakdown

This is the single most important differential because both are IBD, share overlapping features, and roughly 10% of cases fail to be classified between UC and CD (indeterminate colitis) ^[1]^[2].

Why it can mimic UC: Both can present with bloody diarrhoea, abdominal pain, weight loss, and extraintestinal manifestations. When CD is limited to the colon (colonic CD, ~32% of CD cases ^[2]), the clinical picture can be virtually indistinguishable from UC.

How to distinguish from UC:

Feature	Favours CD	Favours UC
Distribution	Skip lesions, rectal sparing	Continuous from rectum proximally
Depth	Full thickness (transmural)	Mucosal/submucosal
Fistulae	Common (intestinal/perianal)	Never
Perianal disease	Up to 40%	Rare
Benign stricture	Common	Rare (suspect malignancy if present)
Granulomas on biopsy	Present (must exclude TB)	Absent
Goblet cells	Preserved	Depleted
Ulcers	Deep, focal, cobblestone	Shallow, diffuse
Pseudopolyps	Rare	Present
Serological markers	ASCA positive	pANCA positive
Small bowel involvement	Yes (especially terminal ileum)	No (except backwash ileitis)
Upper GI involvement	Yes (mouth to anus)	No
Smoking	Risk factor (worsens disease)	Protective
Appendicectomy	Risk factor	Protective

^[1]^[2]^[3]

When to Think Indeterminate Colitis

If a patient has colonic-only IBD with features of BOTH UC and CD — e.g., continuous colitis with some deep ulcers, or diffuse colitis with a few skip areas — the label "indeterminate colitis" is applied. This occurs in ~10% of IBD patients ^[1]. The practical point is that surgical management follows UC protocols (i.e., proctocolectomy with ileal pouch-anal anastomosis is still an option, though pouch failure rates are slightly higher).

Why it can mimic UC: IBS presents with chronic abdominal pain and altered bowel habits ^[2], which overlaps with mild UC.

Why it is NOT UC — first principles reasoning:

IBS is a functional disorder — there is no organic pathology, no mucosal inflammation, no ulceration
IBS does NOT cause:
- Bloody stools (if a patient has blood in the stool, it is NOT IBS until proven otherwise)
- Raised inflammatory markers (CRP, ESR, faecal calprotectin are all normal)
- Weight loss, anaemia, fever, or nocturnal symptoms
- Abnormal endoscopy or histology

Key distinguishing features:

Feature	IBS	UC
PR bleeding	Absent	Present (hallmark)
Faecal calprotectin	Normal ( < 50 μg/g)	Elevated
CRP/ESR	Normal	Elevated
Endoscopy	Normal	Mucosal inflammation, ulceration, pseudopolyps
Nocturnal symptoms	Absent (functional pain does not wake patients)	Present (severe UC causes nocturnal diarrhoea)
Rome IV criteria	Meets criteria for functional disorder	Does not meet criteria

Clinical pearl: Faecal calprotectin is the best non-invasive test to distinguish IBD from IBS. It is a neutrophil-derived protein (60% of neutrophil cytosol) and is the most sensitive marker of intestinal inflammation in IBD ^[5]. A normal faecal calprotectin essentially excludes active IBD and points toward IBS.

Infection including E. coli, Salmonella, Shigella, Campylobacter, Yersinia, and amoebiasis should be excluded with stool studies ^[2]. C. difficile infection should be considered particularly in patients treated with antibiotics ^[2].

Why infectious colitis can mimic UC: Acute infectious colitis can produce identical symptoms — bloody diarrhoea, abdominal cramps, tenesmus, fever. On endoscopy, some infections (e.g., Shigella, E. histolytica) can cause diffuse colonic inflammation with shallow ulceration that looks exactly like UC.

Why the distinction is critical: Treating infectious colitis with immunosuppression (steroids, azathioprine) would worsen the infection catastrophically. Conversely, treating UC with antibiotics alone would not control the underlying immune-mediated process.

How to distinguish:

Feature	Infectious Colitis	UC
Onset	Acute (days to 1–2 weeks)	Chronic, insidious (weeks to months)
Duration	Usually self-limiting ( < 4–6 weeks)	Chronic, relapsing-remitting
Travel history	Often positive (endemic areas for amoebiasis, Salmonella, etc.)	Not relevant
Antibiotic use	Recent antibiotics → C. difficile ^[2]	Not a trigger (though antibiotics can worsen UC)
Stool culture / PCR	Positive for pathogen	Negative
Histology	Acute inflammation, no chronic architectural changes	Chronic architectural changes (crypt distortion, branching, goblet cell depletion)
Sexual history	Neisseria gonorrhoeae and HSV are associated with proctitis ^[2]	Not relevant

Specific pathogens to consider:

Pathogen	Key Features	Why It Mimics UC
C. difficile	Antibiotic-associated pseudomembranous colitis ^[2]; produces toxin A (enterotoxin) and toxin B (cytotoxin); pseudomembranes on endoscopy	Can cause diffuse colitis with bloody diarrhoea. Can also superinfect existing UC (always check C. diff toxin in UC flares!)
Salmonella / Shigella / Campylobacter	Acute dysentery with bloody stools, fever	Self-limiting; stool culture positive
E. coli O157:H7	Produces Shiga toxin → haemorrhagic colitis, HUS	Bloody diarrhoea, abdominal cramps
Entamoeba histolytica	Travel to endemic areas (South/Southeast Asia, Africa) ^[2]; flask-shaped ulcers on biopsy	Chronic bloody diarrhoea; can cause amoebic liver abscess
Yersinia enterocolitica	Terminal ileitis (mimics CD more than UC); sometimes misdiagnosed as acute appendicitis ^[6]	RLQ pain, diarrhoea
Mycobacterium tuberculosis	Must exclude enteric TB (especially in Hong Kong!) ^[3]; caseating granulomas, ileocaecal involvement	Can cause chronic colitis with granulomas (mimics CD more than UC)
CMV	Immunocompromised patients; can reactivate in patients on immunosuppression for UC	Can cause colitis with deep ulcers, may complicate existing UC (steroid-refractory UC should be tested for CMV)

^[2]^[5]^[6]

Must Exclude Infections Before Starting Immunosuppression

Every patient presenting with a first episode of colitis MUST have stool studies (microscopy for ova and parasites, culture, C. difficile toxin PCR) before immunosuppressive therapy is started. In Hong Kong specifically, TB testing is mandatory — TB can mimic IBD and immunosuppression in the setting of undiagnosed TB is life-threatening. Hepatitis serology and HIV testing should also be performed ^[5].

Why it can mimic UC: Ischaemic colitis presents with rapid onset of abdominal pain, haematochezia or bloody diarrhoea ^[4]. On endoscopy, the mucosa may appear oedematous, friable, and ulcerated — resembling UC.

Why it is NOT UC — first principles reasoning:

Ischaemic colitis results from inadequate blood supply to the colon (usually from low-flow states or atherosclerotic disease), NOT from immune-mediated mucosal inflammation
It characteristically affects watershed areas (splenic flexure and rectosigmoid junction) — these are the boundaries between the SMA and IMA territories, and between the IMA and internal iliac arteries
The pattern is segmental (not continuous from rectum) and spares the rectum (dual blood supply from IMA and internal iliac artery protects it) — this is the opposite of UC which STARTS at the rectum

Key distinguishing features:

Feature	Ischaemic Colitis	UC
Onset	Acute, sudden	Gradual, insidious
Risk factors	Advanced age, hypertension, DM, dehydration, laxative use, haemodialysis, OCP, AF, atherosclerotic disease ^[4]	Younger patients, family history of IBD
Distribution	Segmental, watershed areas; rectum usually spared	Continuous from rectum
CT findings	Segmental colonic wall thickening, "thumbprinting" (submucosal oedema/haemorrhage)	Continuous colonic wall thickening, loss of haustral pattern
Endoscopy	Segmental with sharp demarcation ("line of demarcation"), bluish/dusky mucosa	Continuous erythema, friability, shallow ulcers, pseudopolyps
Chronicity	Usually self-limiting (resolves in 1–2 weeks); can stricture	Chronic, relapsing

From the lecture slides, the causes of PR bleeding should be systematically categorised ^[9]:

Anatomical Location	Causes
Anal	Haemorrhoids; Anal fissures; Cancer
Colorectal	Cancer; Rectal ulcers; Diverticular bleeding; Angiodysplasia; Inflammatory bowel disease; Radiation proctitis; Ischaemic bowel; Infective colitis; Post-polypectomy bleeding
Small bowel	Meckel's diverticulum; Angiodysplasia, haemangioma; Small bowel tumour; Small bowel ulcer (NSAID-related); Crohn's disease; Aortoenteric fistula
Upper GI bleeding	Massive UGIB can present as haematochezia

^[9]

The systematic approach involves asking four key questions:

Question	What to Consider
1. Is this organic or functional?	IBS (functional) vs. IBD/infection/cancer (organic). Faecal calprotectin is the best discriminator.
2. If organic, is this infectious?	Always exclude infection FIRST: stool culture, C. diff toxin, ova & parasites, TB testing. Sexual history for STI-associated proctitis. Travel history for amoebiasis.
3. If non-infectious, is this IBD?	UC vs. CD vs. indeterminate colitis. Use clinical, endoscopic, histological, and serological features.
4. If non-IBD, what else?	Ischaemic colitis (elderly, vascular risk factors, segmental). Radiation colitis (prior radiation). Drug-induced (NSAIDs). CRC (mass on colonoscopy). SRUS (straining history, characteristic histology). Diverticular disease.

The essential investigations to request during the differential diagnosis workup include ^[2]^[5]:

Stool examination: culture, C. difficile toxin, calprotectin
Blood tests: CBP, CRP, ESR, albumin, ferritin
Serological markers: pANCA (UC), ASCA (CD)
Hepatitis serology, HIV, TB testing
Colonoscopy with biopsies (gold standard)

High Yield Summary — Differential Diagnosis of UC

Crohn's disease — most important differential; distinguish by distribution (skip lesions, rectal sparing), depth (transmural), complications (fistulae, perianal disease, strictures), and serology (ASCA+ vs. pANCA+). ~10% are indeterminate.
IBS — functional, no blood, no raised inflammatory markers, normal faecal calprotectin and endoscopy.
Infectious colitis — MUST exclude before starting immunosuppression. Stool studies mandatory. C. difficile in antibiotic users; amoebiasis in travellers; TB in Hong Kong. STI proctitis (gonorrhoea, HSV) in MSM.
Ischaemic colitis — elderly, vascular risk factors, acute onset, segmental distribution at watershed areas, rectal sparing.
Radiation colitis — history of pelvic/abdominal radiation; telangiectasias on endoscopy.
Drug-induced colitis — temporal relationship with NSAIDs; resolves on cessation.
SRUS — straining history; fibromuscular obliteration on histology.
CRC — always consider; strictures in UC are malignant until proven otherwise.
Diverticular disease — older patients, painless massive bleeding (diverticular bleed) or pain + fever + leucocytosis (diverticulitis).

Active Recall - Differential Diagnosis of Ulcerative Colitis

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (pp. 2, 6, 9, 11) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections: overview, etiology, clinical manifestation, differential diagnosis, diagnosis) ^[3] Senior notes: felixlai.md (Inflammatory bowel disease — Crohn's disease sections: comparison table, histological features) ^[4] Senior notes: felixlai.md (Diverticular disease section: differential diagnosis including ischaemic colitis) ^[5] Lecture slides: Inflammatory bowel disease.pdf (p. 11 — Diagnosis: laboratory tests, faecal calprotectin) ^[6] Lecture slides: GC 195. Lower and diffuse abdominal pain RLQ problems; pelvic inflammatory disease; peritonitis and abdominal emergencies.pdf (p. 20 — Ileitis causes) ^[7] Senior notes: maxim.md (LGIB DDx table — colorectal carcinoma features) ^[8] Senior notes: maxim.md (Diverticular disease section) ^[9] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (p. 8 — Causes of PR bleeding)

Diagnostic Criteria, Diagnostic Algorithm & Investigations for Ulcerative Colitis

Patient history should cover ^[5]:

Domain	Key Questions	Rationale
Bowel symptoms	Onset, duration, frequency, blood/mucus, urgency, tenesmus, nocturnal symptoms	Characterise the presentation; nocturnal symptoms suggest organic disease (not IBS)
Medications	NSAIDs (trigger flare/mimic UC); antibiotics (C. difficile risk) ^[2]	Must exclude drug-induced colitis and superimposed C. diff
Surgery	Prior appendicectomy (protective for UC; risk factor for CD)	Alters pretest probability
Drug history	Current medications, immunosuppression, biologics	Baseline before starting therapy; drug interactions
Immunisation status	Hep B, varicella, influenza, pneumococcal, COVID-19	Must assess before starting immunosuppression ^[5] — live vaccines contraindicated on biologics/thiopurines
Sexual history	Neisseria gonorrhoeae and HSV are associated with proctitis ^[2]	STI proctitis can mimic UC proctitis, especially in MSM
Travel history	Areas endemic for parasitic infection such as amoebiasis ^[2]	Amoebic colitis mimics UC
Family history	IBD in first-degree relatives	Increases pretest probability

Physical examination should include ^[5]:

Examination	Findings	Significance
General examination	Pallor, vital signs (fever, hypotension, tachycardia) ^[2]	Assess severity (Truelove & Witts); tachycardia + fever = severe
Abdomen	Tenderness (LLQ for left-sided UC; diffuse for pancolitis), distension (toxic megacolon), peritonism (perforation)	Localise disease; detect complications
Perianal region	Skin tags, fissures, fistulae, abscess, PR exam ^[5]	If perianal disease is found → strongly consider CD instead of UC (perianal disease is rare in UC)
Extraintestinal inspections	Mouth (aphthous ulcers), eyes (episcleritis, uveitis), skin (erythema nodosum, pyoderma gangrenosum), joints (arthropathy) ^[5]	Screen for EIMs; oral ulcers more suggestive of CD
Digital rectal examination	Blood/mucus on glove, rectal tenderness ^[2]	Confirms rectal involvement; assesses for rectal mass

10.5 Investigation Modalities — Detailed Breakdown

Blood tests: CBP, CRP, ESR, albumin, ferritin ^[5]

Test	Expected Findings in UC	Pathophysiological Basis / Interpretation
CBP (Complete Blood Picture) with differentials	Anaemia (may be microcytic from iron deficiency or normocytic from chronic disease); leucocytosis (active inflammation or infection); thrombocytosis (reactive) ^[2]	Iron deficiency anaemia: chronic blood loss from friable ulcerated mucosa → depleted iron stores → low MCV, low ferritin, low serum iron, high TIBC. Anaemia of chronic disease: IL-6 → hepcidin → iron sequestration → low serum iron but normal/high ferritin. Autoimmune haemolytic anaemia: rare EIM, Coombs-positive ^[2]
CRP (C-reactive protein)	Elevated in active disease; CRP in Crohn disease is typically higher than in ulcerative colitis ^[2]. CRP monitoring under therapy is useful to document efficacy of anti-inflammatory treatment ^[2]	CRP is an acute-phase reactant produced by the liver in response to IL-6. In UC, the CRP rise is often modest (because inflammation is mucosal, not transmural), so a normal CRP does NOT exclude active UC. However, a significantly elevated CRP ( > 30 mg/L) in UC = severe disease (Truelove & Witts) and suggests deep/extensive inflammation
ESR (Erythrocyte Sedimentation Rate)	Elevated ( > 30 mm/h = severe)	ESR rises with increased fibrinogen and immunoglobulins in chronic inflammation. Less specific than CRP but included in Truelove & Witts criteria. Slow to rise and slow to fall — better reflects chronic disease activity
Albumin	Hypoalbuminemia ^[2]	Malabsorption and protein-losing enteropathy ^[2] — inflamed, denuded colonic mucosa leaks albumin into the lumen. Also: decreased hepatic synthesis due to chronic inflammation (negative acute-phase reactant) and reduced oral intake. Low albumin is a marker of disease severity and nutritional status
Ferritin	May be low (iron deficiency) or normal/elevated (acute-phase reactant in active inflammation)	Ferritin is both an iron storage marker AND an acute-phase reactant. In active UC, it can be misleadingly normal even with true iron deficiency. Always interpret with transferrin saturation and TIBC
Electrolyte profile	Hypokalaemia ^[2]	Chronic diarrhoea → loss of K⁺ in stool (colonic secretion is K⁺-rich). Can also lose bicarbonate → non-anion gap metabolic acidosis
RFT	Usually normal; assess baseline before starting nephrotoxic drugs (e.g., ciclosporin, 5-ASA can rarely cause interstitial nephritis)	Baseline renal function important for drug dosing
LFT	May show cholestatic pattern if concurrent PSC; elevated ALP/GGT	Screen for PSC; also baseline before azathioprine/methotrexate
Serum iron and vitamin B12 level	Low iron (chronic blood loss); vitamin B12 deficiency (rare in UC, more relevant in CD with ileal disease/resection) ^[2]	Iron deficiency from chronic GI blood loss; B12 deficiency relevant if backwash ileitis or post-surgical short bowel

Serological markers from lecture slides and notes ^[2]^[5]:

Marker	Association	Sensitivity/Specificity	Interpretation
pANCA (Perinuclear antineutrophil cytoplasmic antibodies)	Common in UC ^[2]^[5]	Sensitivity ~60–70% for UC; specificity ~85%	pANCA targets myeloperoxidase in neutrophil perinuclear granules. Positive pANCA supports UC diagnosis, but ~30–40% of UC patients are pANCA-negative, so a negative result does NOT exclude UC
ASCA (Anti-Saccharomyces cerevisiae antibodies)	Common in CD ^[2]^[5]	Sensitivity ~60% for CD; specificity ~85%	ASCA targets mannose epitopes in the yeast S. cerevisiae cell wall — these share structural similarity with microbial antigens in CD. ASCA-positive + pANCA-negative strongly favours CD
Anti-OmpC antibody	Potential serological marker for IBD ^[2]	Research stage	Targets outer membrane porin C of E. coli; reflects loss of immune tolerance to commensal bacteria

Serological Markers Are Supportive, Not Diagnostic

pANCA and ASCA help differentiate UC from CD in indeterminate cases but are NOT diagnostic on their own. They have imperfect sensitivity and specificity. The combination of pANCA+/ASCA− favours UC, while pANCA−/ASCA+ favours CD. But endoscopy + histology remain the gold standard.

Stool examination: culture, Cl. difficile toxin, calprotectin ^[5]

Test	Target	Rationale
Stool culture	Escherichia coli O157:H7, Salmonella, Shigella, Yersinia, Campylobacter ^[2]	Must exclude bacterial infection before immunosuppression
Microscopy	Ova, parasites ^[2]	Exclude amoebiasis (Entamoeba histolytica), Giardia, Cryptosporidium
Antigen detection	E. coli O157:H7, Entamoeba, Cryptosporidium, Giardia ^[2]	More sensitive than microscopy for certain parasites
PCR	C. difficile toxin A (enterotoxin) and B (cytotoxin) ^[2]; Shiga toxin	C. diff is critical to exclude — can cause initial presentation mimicking UC, or can superinfect existing UC causing a flare refractory to standard therapy
Faecal calprotectin	Intestinal inflammation (non-specific)	Neutrophil-derived protein, 60% of neutrophil cytosol ^[5]. Most sensitive marker of intestinal inflammation in IBD ^[5]. Well correlated with endoscopic disease activity ^[5]. Predicts disease relapse and postoperative relapse ^[5]. Normal value ( < 50 μg/g) essentially excludes active IBD. Values > 150–250 μg/g strongly suggest mucosal inflammation. Used for: (1) screening (IBD vs IBS), (2) monitoring treatment response, (3) predicting relapse

Why is faecal calprotectin so useful? From first principles: when neutrophils infiltrate the inflamed intestinal wall (as happens in UC with cryptitis and crypt abscesses), they release their cytoplasmic contents into the lumen. Calprotectin constitutes 60% of the neutrophil cytoplasm. It is resistant to degradation by intestinal proteases, so it survives transit through the GI tract and can be measured in stool. The more mucosal inflammation there is, the more neutrophils infiltrate, and the higher the faecal calprotectin. This is why it correlates so well with endoscopic disease activity.

Hepatitis serology, HIV, TB testing ^[5]

Test	Rationale
Hepatitis B surface antigen + anti-HBc	Immunosuppression (steroids, thiopurines, biologics) can cause HBV reactivation → fulminant hepatitis. Must know HBV status before treatment. If positive → antiviral prophylaxis
Hepatitis C antibody	Baseline screening; potential hepatotoxicity of immunosuppressants
HIV testing	Immunosuppression in undiagnosed HIV is dangerous; also, HIV-associated enteropathy can mimic IBD
TB testing (IGRA / Mantoux + CXR)	MUST do AFB smear and culture with sensitivity testing to rule out enteric TB ^[2]. Anti-TNF biologics reactivate latent TB → disseminated TB → death. TB ileocolitis mimics CD. In Hong Kong (intermediate TB burden), this is mandatory before starting biologics

Hong Kong Context — TB Screening Is Mandatory

Hong Kong has an intermediate burden of TB. AFB smear and culture with sensitivity testing must be done to rule out enteric TB ^[2]. This is non-negotiable before starting immunosuppression, especially anti-TNF agents. Enteric TB can cause granulomatous inflammation that mimics CD, and giving anti-TNF to a patient with undiagnosed TB is potentially fatal.

Modality	Indication	Key Findings	Interpretation
CXR	Indicated in patients presenting with fever or if perforation is suspected ^[2]	Free gas under diaphragm (pneumoperitoneum)	If free air → perforation → surgical emergency. Also baseline for TB screening (pulmonary TB)
AXR (Abdominal X-ray)	Indicated to evaluate for colonic calibre ^[2]	Dilated colon, mucosal oedema ("thumb-printing"), loss of haustral markings, "lead pipe" colon (chronic UC)	Toxic megacolon: total or segmental non-obstructive dilatation of colon ≥ 6 cm or caecum > 9 cm with systemic toxicity ^[2]. AXR is the first-line investigation for suspected toxic megacolon. Also look for small bowel dilatation (ileus)
CT abdomen/pelvis	Not first-line for UC diagnosis, but useful for complications (abscess, perforation, toxic megacolon) or when colonoscopy is contraindicated	Colonic wall thickening, pericolonic fat stranding, "accordion sign" (alternating contrast and oedematous mucosa), complications	Helps differentiate UC complications from other surgical emergencies. Also useful in the acute setting when colonoscopy is unsafe
MR enterography (MRE) or CT enterography (CTE)	Small bowel assessment — mainly for CD ^[5]	Not typically needed in UC (no small bowel involvement); used if backwash ileitis vs. CD ileal disease is uncertain	MRE is preferred over CTE in young patients (no ionising radiation) ^[5]. If ileal disease is prominent, consider reclassifying as CD

F. Endoscopy — The Gold Standard

Imaging and endoscopy ^[5]:

Modality	When to Use	Key Features
Colonoscopy	Colonic assessment in UC/CD ^[5]. Standard investigation for suspected UC. Allows full visualisation of colon + terminal ileum + tissue biopsy	The definitive diagnostic investigation for UC
Sigmoidoscopy	For severe active disease ^[5]. Used when full colonoscopy is too risky (risk of perforation in severe/fulminant colitis or toxic megacolon)	Safer in acute severe UC — avoids the need for full bowel prep and avoids manipulating a severely inflamed, dilated colon. Sufficient to confirm diagnosis (since UC always involves the rectum) and obtain biopsies

Why colonoscopy and not just sigmoidoscopy?

Colonoscopy allows you to see the full extent of disease (needed for Montreal classification E1/E2/E3, which determines treatment and surveillance strategy)
Allows ileal intubation to assess for backwash ileitis or ileal disease that might suggest CD
Biopsy should be taken from the left and right colon and rectum even if normal in appearance to assess for microscopic inflammation ^[2] — this is critical because treated UC may have patchy healing, and microscopic disease may exist without macroscopic changes

Contraindications to colonoscopy in UC context ^[10]:

Known or suspected perforation
Acute diverticulitis
Fulminant colitis (use sigmoidoscopy instead)

Feature	Description	Pathophysiological Basis
Uniform and continuous lesions	Disease starts at rectum and extends proximally without skip areas ^[2]	Continuous mucosal immune activation spreading retrograde from the rectum
Hyperaemic mucosa	Red, engorged mucosal surface	Mucosal engorgement — inflammatory mediators (histamine, prostaglandins, NO) cause vasodilation of mucosal and submucosal vessels ^[2]
Diffuse granularity of mucosa	Mucosa has a sandpaper-like, granular texture instead of smooth, glistening surface	Loss of the normal smooth mucosal surface due to widespread superficial oedema and inflammatory cell infiltration
Erosion, oedema, and exudates	Superficial mucosal breaks with mucopurulent exudate ^[2]	Neutrophil-mediated destruction of surface epithelium; exudate = fibrin, neutrophils, necrotic debris
Touch friability, petechiae, and bleeding	Mucosa bleeds on light contact with the endoscope ^[2]	The inflamed mucosa is so fragile (loss of epithelial integrity + dilated submucosal vessels close to the surface) that minimal mechanical trauma causes bleeding
Shallow ulceration	Ulcers are superficial, not deep ^[2]	Inflammation is limited to mucosa/submucosa — ulcers do not penetrate the muscularis propria (unlike the deep, transmural ulcers of CD)
Pseudopolyps	Hypertrophied masses of mucous membrane resembling polyps ^[2]	Islands of regenerating/hypertrophied mucosa projecting above surrounding denuded, ulcerated mucosa. Indicate prior severe inflammation. NOT neoplastic, but are a risk factor for IBD-associated CRC ^[1]
Loss of normal vascular pattern	Normal submucosal vascular pattern is obscured	Mucosal oedema and inflammatory infiltrate obscure the delicate submucosal vessels normally visible through transparent healthy mucosa
Loss of haustral folds	"Lead pipe" colon on imaging; featureless colon on endoscopy	Chronic inflammation → fibrosis of the submucosa → loss of the semilunar folds (haustra) that normally give the colon its segmented appearance. This is a sign of long-standing, burnt-out disease

The Mayo endoscopic subscore is widely used to grade endoscopic severity:

Score	Findings	Description
0	Normal or inactive	No inflammation
1	Mild	Erythema, decreased vascular pattern, mild friability
2	Moderate	Marked erythema, absent vascular pattern, friability, erosions
3	Severe	Spontaneous bleeding, ulceration

This score is important because it correlates with treatment decisions and is used as an endpoint in clinical trials for UC therapeutics.

Histological findings in UC ^[2]:

Feature	Description	Significance
Mucosal and submucosal (superficial) inflammation	Inflammatory infiltrate (neutrophils, lymphocytes, plasma cells) confined to the mucosa and submucosa	Distinguishes UC from CD (which is transmural) ^[2]
Diffuse, continuous involvement	Inflammation involves the entire biopsy uniformly, without patchy or skip areas	Distinguishes from CD (focal, patchy) ^[2]
Cryptitis	Neutrophil infiltration into crypt epithelium	Active inflammation — neutrophils migrating from the lamina propria into the crypt lumen
Crypt abscesses	Collections of neutrophils within the crypt lumen	The crypt lumen fills with neutrophils, forming a microabscess. Shared with CD but more prominent in UC
Crypt architectural distortion	Crypt branching, shortening, and disarray ^[2]	A hallmark of chronicity — repeated cycles of destruction and regeneration lead to irregular crypt arrangement. Normal crypts are parallel, evenly spaced, and extend from muscularis mucosae to surface. Distorted crypts are branched, irregular, shortened
Goblet cell depletion	Reduced numbers of mucin-secreting goblet cells	Chronic inflammatory destruction of goblet cells → reduced mucus production → impaired mucosal barrier. In CD, goblet cells are NOT depleted ^[2] — this is a key distinguishing feature
Granulomas	Rare in UC ^[2]	If granulomas are found, consider CD (where they are common) or TB (caseating granulomas). Non-caseating granulomas in a colitis specimen should prompt reclassification to CD or "indeterminate colitis"
Basal plasmacytosis	Plasma cells at the base of the mucosa (between crypt bases and muscularis mucosae)	An early and sensitive marker of IBD chronicity — normally, the crypt bases are free of plasma cells. Their presence indicates chronic immune activation
Paneth cell metaplasia	Paneth cells appearing in the left colon (they are normally found only in the small bowel and right colon)	A marker of chronic mucosal injury and regeneration — the colonic epithelium undergoes metaplastic change in response to persistent inflammation

Key Histological Features — UC vs CD

UC histology = "Diffuse, superficial, and depleted"

Diffuse continuous involvement
Superficial (mucosal/submucosal) inflammation
Goblet cell depletion
Crypt distortion with abscesses
NO granulomas

CD histology = "Patchy, deep, and granulomatous"

Focal patchy involvement
Transmural inflammation
Goblet cells preserved
Non-caseating granulomas (MUST exclude TB)

From lecture slides ^[5]:

Modality	Primary Role	Relevance to UC
Small bowel capsule endoscopy (SBCE)	Small bowel assessment in CD	NOT standard in UC (no small bowel disease). May be used if considering reclassification to CD
Single or double balloon enteroscopy	Small bowel assessment in CD	Deep small bowel visualisation; rarely needed in UC
OGD	Foregut symptoms in CD	UC does not involve the upper GI tract. If upper GI symptoms are present, consider CD
MRI anal canal	Perianal assessment in CD	UC does not cause perianal disease. If perianal pathology is found → reconsider CD

^[5]

Montreal phenotypic classification — according to extent of inflammation observed at colonoscopy ^[2]. This influences treatment modality and timing of starting surveillance and its frequency ^[2].

Code	Classification	Description	Approximate HK Prevalence
E1	Proctitis	Involvement limited to rectum	~34.5% (proctosigmoiditis group)
E2	Left-sided UC (distal UC)	Involvement extending up to the splenic flexure	~32%
E3	Extensive UC (pancolitis)	Involvement extending proximal to the splenic flexure	~33.5%

^[2]

UC distribution from lecture slides ^[5]: Pancolitis: Entire colon 18%; Left colitis: Up to the left flexure 28%; Proctitis: Rectosigmoid 54%

HK vs Global Distribution Difference

Note the difference between global and HK data. Globally, proctitis is the most common form at ~54% ^[5], whereas in HK the distribution is roughly equal thirds ^[2]. This may reflect differences in when patients present (HK patients may present later with more extensive disease) or population genetics. Know both sets of numbers for exams.

Why does extent matter?

Treatment: Proctitis (E1) can often be managed with topical (rectal) 5-ASA alone; left-sided (E2) may need combined oral + rectal; pancolitis (E3) always needs systemic therapy
CRC surveillance timing: More extensive disease = earlier and more frequent surveillance colonoscopies
Prognosis: Pancolitis has higher rates of hospitalisation, colectomy, and CRC risk

This is not a diagnostic criterion per se, but is integral to the initial workup because it determines immediate management (outpatient vs. admission, oral vs. IV therapy):

Parameter	Mild	Moderate	Severe
Bloody stools/day	< 4	≥ 4	≥ 6
Pulse	< 90 bpm	≤ 90 bpm	> 90 bpm
Temperature	< 37.5°C	≤ 37.8°C	> 37.8°C
Haemoglobin	> 11.5 g/dL	≥ 10.5 g/dL	< 10.5 g/dL
ESR	< 20 mm/h	< 30 mm/h	> 30 mm/h
CRP	Normal	≤ 30 mg/L	> 30 mg/L

Interpretation: Immediate admission warranted in severe disease ^[2].

Why these particular parameters?

Bloody stools/day → directly reflects the extent and severity of mucosal ulceration and bleeding
Pulse and temperature → systemic inflammatory response; tachycardia also reflects hypovolaemia from blood/fluid loss
Haemoglobin → chronic blood loss severity
ESR/CRP → magnitude of the systemic inflammatory response

To make a diagnosis of UC, you need:

Step	Requirement	Test
1	Compatible clinical features	History + examination
2	Evidence of mucosal inflammation	Faecal calprotectin (screening); colonoscopy (definitive)
3	Characteristic endoscopic pattern	Continuous, rectal involvement, shallow ulcers, pseudopolyps, friability
4	Confirmatory histology	Mucosal/submucosal inflammation, crypt distortion, goblet cell depletion, no granulomas
5	Exclusion of infections	Stool studies (culture, C. diff, O&P), TB testing, Hep B/C, HIV
6	Exclusion of other mimics	Clinical context + endoscopy + histology to exclude ischaemic, radiation, drug-induced colitis, CRC
7	Classification	Montreal extent (E1/E2/E3) + severity (Truelove & Witts)

When to reconsider the diagnosis: If the patient develops features atypical for UC (perianal disease, small bowel strictures, non-caseating granulomas on biopsy, poor response to standard UC therapy), reclassify as CD or indeterminate colitis. Up to 10% of patients are reclassified over time.

High Yield Summary — Diagnosis of UC

No single diagnostic criterion — UC is diagnosed by combining clinical features + endoscopy + histology + exclusion of infections.

Focused history: Bowel symptoms, drug history (NSAIDs, antibiotics), sexual history (STI proctitis), travel history (amoebiasis), family history, immunisation status.

Examination: General (pallor, fever, tachycardia) + abdomen + perianal (MUST check — perianal disease = think CD) + EIM screen (mouth, eyes, skin, joints).

Key blood tests: CBP, CRP, ESR, albumin, ferritin, pANCA (UC) vs ASCA (CD). Hepatitis serology, HIV, TB testing before immunosuppression.

Key stool tests: Culture, C. difficile toxin PCR, ova & parasites, faecal calprotectin (most sensitive non-invasive marker of intestinal inflammation; neutrophil-derived; correlates with endoscopic activity; predicts relapse).

Endoscopy: Colonoscopy = gold standard. Use flexible sigmoidoscopy in acute severe UC (safer). Biopsy from left colon, right colon, and rectum even if normal-appearing. MUST do AFB smear and culture to exclude enteric TB.

Endoscopic findings: Continuous from rectum; hyperaemia; granularity; friability; shallow ulcers; pseudopolyps; loss of vascular pattern.

Histological findings: Mucosal/submucosal inflammation; diffuse continuous; crypt distortion and abscesses; goblet cell depletion; NO granulomas.

Radiology: AXR for toxic megacolon (≥ 6 cm or caecum > 9 cm); CXR if perforation suspected.

Classify: Montreal E1/E2/E3 (determines treatment + surveillance). Severity by Modified Truelove & Witts (determines admission + treatment intensity).

Active Recall - Diagnosis of Ulcerative Colitis

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p. 52 — IBD-associated CRC risk factors) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections: overview, diagnosis, biochemical tests, radiological tests, endoscopic findings, histological findings) ^[5] Lecture slides: Inflammatory bowel disease.pdf (pp. 7, 10, 11, 12 — Diagnosis: patient history, physical examination, laboratory tests, faecal calprotectin, imaging and endoscopy, UC distribution) ^[10] Senior notes: felixlai.md (Colonoscopy section — indications and contraindications)

Management of Ulcerative Colitis

11.3 Medical Treatment — Drug-by-Drug Breakdown

The cornerstone of UC therapy — the first drug you reach for in mild-to-moderate disease ^[2].

Name breakdown: "5-amino" = the active amine group; "salicylate" = derived from salicylic acid (related to aspirin). These are anti-inflammatory agents that act locally on the colonic mucosa.

Initial therapy in patients with mild to moderate UC who do not have systemic symptoms based on its relative safety to other drugs ^[2].

Topical 5-ASA is the first-line treatment in mild to moderate UC in those who are willing to use rectal therapy including suppositories or enemas ^[2].

Property	Detail
Mechanism of action	Anti-inflammatory effect ^[2] — 5-ASA inhibits the NF-κB pathway, scavenges reactive oxygen species, inhibits lipoxygenase and cyclooxygenase locally, and reduces neutrophil chemotaxis. It acts topically on the mucosa — this is why rectal formulations work so well in distal disease
Clinical role	Induction agent AND maintenance agent ^[2] — unlike steroids, 5-ASA is effective for BOTH induction and maintenance
Route of administration	Mesalamine: Oral / Enema / Suppository ^[2]; Sulfasalazine: Oral ^[2]
Dosage	Mesalamine: 2–4.8 g/day oral; rectal: 1 g suppository (proctitis) or 4 g enema (left-sided); Sulfasalazine: 3–6 g/day oral

Choosing the route by disease extent:

Extent	Preferred Route	Why?
E1 (Proctitis)	Suppository (e.g., mesalamine 1 g OD–BD)	The suppository reaches and coats the rectal mucosa directly. Oral 5-ASA is released too proximally and does not reach the rectum in adequate concentration
E2 (Left-sided)	Enema (e.g., mesalamine 4 g) ± oral 5-ASA	Enema fluid distributes up to the splenic flexure. Combination with oral is more effective than either alone
E3 (Pancolitis)	Oral 5-ASA + topical (enema/suppository)	Oral formulations are designed to release 5-ASA throughout the colon. Adding topical therapy boosts rectal/distal drug levels. Combination therapy is more effective in inducing remission ^[2]

Key formulations and differences:

Drug	Key Feature	Notes
Mesalamine (Pentasa / Asacol)	Pure 5-ASA in pH-dependent or time-dependent release coating	Nephrotoxicity is the key adverse effect ^[2] (interstitial nephritis — monitor creatinine annually). Pentasa releases 5-ASA throughout the small bowel + colon; Asacol releases in the terminal ileum and colon (pH > 7)
Sulfasalazine	5-ASA linked to sulfapyridine via an azo bond; colonic bacteria cleave the bond to release 5-ASA	Adverse effects: Nausea, headache, fever, agranulocytosis, pancreatitis, SJS ^[2]. Associated with "sulfa" allergy and pregnancy complications including kernicterus (crosses placenta) and neural tube defect (inhibits absorption and metabolism of folic acid) ^[2]. Requires folic acid supplementation if used in pregnancy

Why Sulfasalazine Is Less Preferred Than Mesalamine

Sulfasalazine requires colonic bacteria to cleave the azo bond and release active 5-ASA. The sulfapyridine carrier molecule is responsible for most of the side effects (nausea, headache, rash, agranulocytosis, male infertility via oligospermia). Mesalamine formulations bypass the need for a sulfapyridine carrier, delivering pure 5-ASA with fewer systemic side effects. However, sulfasalazine is cheaper and may have additional benefit for IBD-related joint disease (the sulfapyridine component has DMARD-like properties).

The second-line agents for induction — used when 5-ASA fails or for moderate-severe disease ^[2].

Critical concept: Steroids are for induction ONLY — they are NOT maintenance agents.

Calcium and vitamin D supplements required for osteoprotective effect if prescribed for more than 12 weeks ^[2].

Clinical role = Induction agent (Induction of remission). Ineffective in maintenance of remission and NOT used for long-term ^[2].

Property	Detail
Mechanism of action	Glucocorticoids suppress the immune system broadly: inhibit NF-κB → reduce pro-inflammatory cytokines (TNF-α, IL-1, IL-6); inhibit phospholipase A₂ → reduce prostaglandin and leukotriene synthesis; reduce neutrophil migration; induce lymphocyte apoptosis. They are potent anti-inflammatory agents but have extensive systemic side effects
Why NOT for maintenance?	Chronic steroid use causes: osteoporosis, adrenal suppression, diabetes, cataracts, infection risk, Cushingoid features, avascular necrosis. The risk-benefit ratio is unacceptable for long-term use. Also, studies show steroids do NOT prevent relapse once stopped
Dosing	Prednisolone: 40 mg/day initially, reducing by 5 mg/week. Budesonide 9 mg/day — has extensive first-pass hepatic metabolism → fewer systemic side effects but also less potent. Budesonide MMX (multi-matrix) formulation specifically designed for colonic release in UC
IV formulation (severe UC)	Hydrocortisone 100 mg IV QDS or methylprednisolone 60 mg/day IV ^[2]^[11]

Steroid-dependent vs. steroid-refractory:

Term	Definition	Action
Steroid-dependent	Relapse when steroids are tapered below a certain dose, or relapse within 3 months of stopping	Escalate to thiopurines (AZA/6-MP) as steroid-sparing maintenance
Steroid-refractory	No response to adequate dose of IV steroids within 3–5 days	Escalate to rescue therapy (infliximab or cyclosporin) or surgery

These are the steroid-sparing maintenance agents — the drugs that keep patients in remission and allow steroids to be withdrawn ^[2].

Property	Detail
Drugs	Azathioprine (AZA) / 6-Mercaptopurine (6-MP) ^[2]
Mechanism of action	AZA is a prodrug → converted to 6-MP → metabolised to 6-thioguanine nucleotides (6-TGN), which are purine analogues that incorporate into DNA → inhibit DNA synthesis → suppress rapidly dividing lymphocytes. This is why they are "immunomodulators" — they modulate the adaptive immune response by killing proliferating T and B cells
Clinical role	Maintenance agent. Steroid-sparing. Slow onset: takes 8–12 weeks to reach full effect (because you need to accumulate enough 6-TGN to suppress lymphocyte proliferation). This means steroids must be used as a "bridge" during the lag period
Key pre-treatment test	TPMT (thiopurine methyltransferase) genotype/phenotype: TPMT is an enzyme that inactivates 6-MP. ~10% of people have intermediate TPMT activity and ~0.3% have absent TPMT → these patients accumulate toxic levels of 6-TGN → severe myelosuppression. Must check TPMT before starting
Adverse effects	Bone marrow suppression (leucopenia, pancytopenia), hepatotoxicity, pancreatitis (idiosyncratic, 3–5%), nausea, increased infection risk, slightly increased lymphoma risk
Monitoring	Regular FBC (every 1–3 months), LFT, 6-TGN levels (therapeutic drug monitoring)

Methotrexate is NOT effective in UC unlike in Crohn's disease ^[2] — this is an important exam point.

Why Does Methotrexate Work in CD But Not UC?

The exact reason is not fully understood, but it likely relates to the different immunological profiles. CD is driven by Th1/Th17 pathways, where methotrexate's folate antagonism and adenosine-mediated anti-inflammatory effects are particularly effective. UC is driven by an atypical Th2/NKT cell pathway that is less responsive to methotrexate's mechanism. Pragmatically: just remember that methotrexate has no proven efficacy in UC — don't use it.

Rescue therapy agents: Cyclosporin and Tacrolimus ^[2].

Property	Detail
Drugs	Cyclosporin / Tacrolimus ^[2]
Mechanism of action	Calcineurin inhibitors block the calcineurin-NFAT pathway in T cells: calcineurin is a phosphatase that activates NFAT (nuclear factor of activated T cells) → NFAT enters the nucleus → transcribes IL-2 (the key T cell growth factor). By blocking calcineurin, these drugs prevent IL-2 production → suppress T cell proliferation and activation. This is a rapid-acting immunosuppressive mechanism (unlike thiopurines which take weeks)
Clinical role	Rescue therapy in acute severe UC that is refractory to IV steroids ^[2]. Acts as a "bridge" to thiopurine maintenance (because thiopurines take 8–12 weeks to kick in)
Dosing	Cyclosporin: 2–4 mg/kg/day IV initially, then convert to oral; target trough level 150–300 ng/mL. Tacrolimus: oral or IV, target trough level 10–15 ng/mL (induction)
Contraindications	Renal impairment (nephrotoxic), uncontrolled hypertension, hypocholesterolaemia ( < 3.0 mmol/L → increased seizure risk with cyclosporin), active infection
Adverse effects	Nephrotoxicity, hypertension, tremor, seizures (cyclosporin — especially with low cholesterol/Mg²⁺), gingival hyperplasia, hirsutism (cyclosporin), diabetes (tacrolimus), opportunistic infections

The big guns — used for moderate-severe UC refractory to conventional therapy ^[2].

Name breakdown: "Anti-TNF" = antibodies against Tumour Necrosis Factor-alpha, a key pro-inflammatory cytokine. "Infliximab" = inf(usion) + -ximab (chimeric monoclonal antibody); "Adalimumab" = ada(ptive) + -mumab (fully human monoclonal antibody).

Indicated in patients with refractory disease to 5-ASA, immunomodulators, and steroids ^[2].

MUST screen for TB with CXR / QuantiFERON-TB Gold + HBV infection with HBsAg ^[2]:

Requires TB prophylaxis with isoniazid or rifampicin ^[2]
Requires HBV prophylaxis with entecavir ^[2]

Property	Infliximab (Remicade)	Adalimumab (Humira)
Type	Chimeric anti-TNF antibody (mouse/human) ^[2]	Humanised anti-TNF antibody ^[2]
Route	IV infusion	SC injection
Induction	IV 5 mg/kg at weeks 0, 2, 6 ^[2]	SC 160 mg at week 0, 80 mg at week 2 ^[2]
Maintenance	IV 5 mg/kg every 8 weeks ^[2]	SC 40 mg every 2 weeks ^[2]
Onset	Response quicker and better ^[2]	Response slower and less effective ^[2]
Key advantage	1st line biologic ^[2]; faster onset; preferred for acute severe UC as rescue	Can be self-administered at home

Do not stop anti-TNFα easily unless there is deep remission of at least 18 months with normal blood and endoscopic parameters ^[2].

Contraindications ^[2]:

Latent untreated or active TB
Lymphoma
Heart failure of NYHA Class III–IV (TNF-α has compensatory effects in heart failure; blocking it worsens cardiac function)
Demyelinating disease (Multiple sclerosis) (anti-TNF can worsen or trigger CNS demyelination)
Optic neuritis

Adverse effects ^[2]:

Reactivation of infection (e.g., TB/HBV) — TNF-α is critical for granuloma formation and containment of intracellular pathogens; blocking it allows dormant mycobacteria to reactivate
Lymphoma — small absolute increase in risk (especially hepatosplenic T-cell lymphoma when combined with thiopurines in young males)
Non-melanoma skin cancer
Infusion reactions (infliximab — chimeric antibody → can trigger anti-drug antibodies)
Paradoxical psoriasis

Pre-Biologic Screening Checklist

Before starting ANY biologic (anti-TNF, vedolizumab, ustekinumab, JAK inhibitor):

TB: CXR + IGRA/QuantiFERON. If latent TB → isoniazid prophylaxis for ≥ 4 weeks before starting biologic
HBV: HBsAg + anti-HBc. If positive → entecavir prophylaxis
HCV, HIV: Screen
Varicella: Check immunity; vaccinate if non-immune (BEFORE starting, as live vaccines are contraindicated on biologics)
Assess for active infections, heart failure, demyelinating disease

These are increasingly used in UC and are high-yield for 2025/2026 exams:

Drug	Class	Mechanism	Role in UC
Vedolizumab (Entyvio)	Anti-integrin (α4β7)	Blocks the α4β7 integrin on gut-homing lymphocytes → prevents them from binding to MAdCAM-1 on intestinal endothelium → stops lymphocyte trafficking to the gut. "Gut-selective" immunosuppression — does not suppress systemic immunity	Moderate-severe UC; induction and maintenance. Preferred in patients where infection risk is a concern (gut-selective, not systemic)
Ustekinumab (Stelara)	Anti-IL-12/23 (p40 subunit)	Blocks the shared p40 subunit of IL-12 and IL-23 → suppresses Th1 (IL-12) and Th17 (IL-23) pathways	Approved for moderate-severe UC; induction (IV) then maintenance (SC)
Tofacitinib (Xeljanz)	JAK inhibitor (JAK1/3)	Blocks Janus kinase (JAK) signalling → inhibits the JAK-STAT pathway → reduces signalling of multiple cytokines (IL-2, IL-6, IL-12, IL-23, IFN-γ). An oral small molecule (not a biologic antibody)	Moderate-severe UC; oral tablet. Advantages: rapid onset, oral route. Risks: herpes zoster, VTE, cardiovascular events, lipid elevation
Ozanimod (Zeposia)	S1P receptor modulator	Blocks sphingosine-1-phosphate (S1P) receptors → traps lymphocytes in lymph nodes → prevents their migration to the inflamed colon	Moderate-severe UC; oral tablet. Requires cardiac monitoring at initiation (bradycardia risk)

Antibiotics have MINIMAL role in treatment of active disease in UC ^[2].

Property	Detail
Indications	Septic complications of IBD such as fulminant colitis ^[2]; pouchitis post-IPAA
Drugs	Ciprofloxacin / Metronidazole ^[2]
Why minimal role in active UC?	UC is an immune-mediated disease, not an infectious one. Unlike CD (where antibiotics help via treating microperforation, bacterial overgrowth, and perianal sepsis), the mucosal inflammation of UC is not driven by a specific pathogen

Severity	Setting	Induction	Maintenance	Escalation
Mild	Outpatient	Topical 5-ASA (suppository/enema) ± oral 5-ASA	Continue 5-ASA (same route)	If refractory → add oral 5-ASA → oral steroids
Moderate	Outpatient	Oral 5-ASA + topical 5-ASA; add oral prednisolone (40 mg/day) if inadequate response	5-ASA ± thiopurine (AZA/6-MP) if steroid-dependent	If steroid-refractory → biologics
Severe	Admit	IV hydrocortisone (100 mg QDS) ± VTE prophylaxis, fluid resuscitation, exclude C. diff/CMV	Bridge to thiopurine/biologic maintenance	If no response by Day 3 → rescue (infliximab/cyclosporin). If no response by Day 4–7 → surgery ^[2]

^[2]^[11]

Emergency surgery is needed in 20% of UC patients and 5–10% of Crohn's colitis patients ^[11].

Criteria (ECCO/ACG guidelines): ≥ 6 bloody stools/day + at least one of: Fever (37.8°C), tachycardia, anaemia ( < 10.5 g/dL), raised CRP ^[11].

Day-by-day management:

Day	Action
Day 0 (Admission)	Assess severity (Truelove & Witts). Bloods (FBC, CRP, albumin, electrolytes). Stool for C. diff toxin + culture. AXR (check colonic calibre — exclude toxic megacolon). CT abdomen and pelvis if perforation suspected ^[11]. Start IV hydrocortisone 100 mg QDS. IV fluids. VTE prophylaxis (LMWH — IBD is a prothrombotic state). Nutritional support. Stop anticholinergics/opioids (increase toxic megacolon risk)
Day 1–2	Monitor stool frequency, vital signs, bloods daily. Continue IV steroids
Day 3	Assess response. Risk for colectomy (without 2nd line therapy): 24h stool frequency > 8; or stool frequency 3–8 + CRP > 45 mg/L → colectomy risk = 85% ^[11]. If no response → initiate RESCUE THERAPY
Day 3–5	Rescue: Infliximab 5 mg/kg IV (preferred) or Cyclosporin IV ^[2]^[11]. Also consider flexible sigmoidoscopy to exclude CMV colitis (which mimics steroid-refractory UC; treat with ganciclovir if positive)
Day 5–7+	If response to rescue → bridge to maintenance (thiopurine + infliximab or vedolizumab). If no response to rescue by Day 4–7 → SURGERY ^[2]

Predictors of colectomy ^[2]:

BO > 12/day on Day 2 of IV steroid → Colectomy = 55%
BO > 8/day or BO 3–8/day + CRP > 45 on Day 3 of IV steroid → Colectomy = 85%
(Stool frequency × 0.14 × CRP) on Day 3 of IV steroid ≥ 8 → Colectomy = 75%
Colonic dilatation > 5.5 cm → Colectomy = 75%
Ileus with ≥ 3 small bowel loops of gas → Colectomy = 73%
High CRP, low albumin and pH, ESR > 75, temp > 38°C on admission → 5–9× risk ^[2]

The Day 3 Decision

Day 3 of IV steroids is the critical decision point in acute severe UC. If the patient has not responded (still ≥ 6 bloody stools + systemic features), you MUST escalate to rescue therapy immediately — do NOT continue IV steroids for another week hoping for improvement. Delay in escalation increases perforation risk and mortality. The Travis/Oxford criteria (stool frequency × 0.14 × CRP ≥ 8) is a validated predictor that should trigger urgent surgical consultation.

11.6 Surgical Treatment

Surgery is usually not indicated in UC but is potentially curative ^[2]. This is a crucial distinction from CD (where surgery is NOT curative and should be avoided as long as possible).

Scenario	Procedure	Rationale
Emergency (acutely ill)	3-stage: Total abdominal colectomy + end ileostomy ^[2]^[11]	Rectum left in situ because it is an extraperitoneal organ and resection takes too long in a critically ill patient ^[2]. Foley catheter used to decompress rectum for 3–4 days ^[2]. Rectum left untouched; 2nd stage operation when patient is stable ^[11]
Stage 2 (recovery)	Completion proctectomy + IPAA ^[2]^[11] with diverting loop ileostomy	Done after patient recovers and steroids withdrawn (steroids impair anastomotic healing)
Stage 3	Reversal of diverting loop ileostomy ^[2]	Final step — restores intestinal continuity
Elective (stable patient)	2-stage: Total proctocolectomy + IPAA + diverting loop ileostomy ^[2]	IPAA in J-configuration ^[2]. Standard of care — avoids long-term stoma. Followed by reversal of loop ileostomy later
Poor sphincter function	Total proctocolectomy + permanent end ileostomy ^[8]	If anal sphincter is incompetent, IPAA is futile (patient would be incontinent). Permanent stoma is needed
Female wanting to maintain fertility	Total colectomy + ileorectal anastomosis (IRA) ^[8]	Avoids pelvic adhesions and thus infertility ^[8]. Disadvantage: diseased rectum remains → risk of rectal disease recurrence → needs ongoing surveillance

Why is IPAA the standard of care?

The "J-pouch" (ileo-pouch-anal anastomosis) creates a neorectum from the terminal ileum, folded into a J-shape and anastomosed to the anal canal
Allows the patient to defecate per anum without a permanent stoma
Mean stool frequency: ~6/day (acceptable for most patients)
Maintains continence in most patients with intact sphincters

Complications of IPAA ^[2]^[8]:

Pouchitis — most common complication (~50% lifetime risk); presents with increased stool frequency, urgency, bloody stool, fever. Treated with metronidazole and ciprofloxacin ^[2]
Pouch-vaginal / perineal fistula ^[2]
Anastomotic stricture ^[2]
Anastomotic dehiscence with sepsis ^[2]
Sexual dysfunction / infertility ^[2] (pelvic dissection can damage autonomic nerves — hypogastric and pelvic splanchnic nerves)
Pelvic nerve damage: impotence ^[8]
Pouch dysfunction: increased faecal frequency, urgency, incontinence ^[8]

Surgery Is Curative in UC — But Not in CD

This is a fundamental difference. In UC, all the disease is in the colon and rectum. Removing the entire colon and rectum (total proctocolectomy) removes ALL diseased tissue → cure. In CD, disease can recur anywhere in the GI tract even after resection — so surgery is never curative and should be minimised.

Long-standing UC carries an increased risk of colorectal cancer through the inflammation → dysplasia → carcinoma sequence ^[1]^[2].

AGA Guidelines (2010) ^[12]:

Surveillance colonoscopy started at a maximum 8 years after UC or Crohn's colitis ^[12]
Optimal surveillance interval not clearly defined:
- Left-sided or extensive colitis: within 1–2 years after initial screening colonoscopy ^[12]
- After two negative examinations, every 1–3 years ^[12]
- Individualised (presence of other risk factors) ^[12]
Primary sclerosing cholangitis: yearly ^[12] (PSC dramatically increases CRC risk)
Ulcerative proctitis: NOT considered at increased risk ^[12]
Ideally, surveillance colonoscopy should be performed when disease is in remission ^[12]

BSG Guidelines (2010) ^[13] — risk-stratified surveillance:

Risk Category	Surveillance Interval	Criteria
Lower risk	Every 5 years	Extensive or left-sided colitis without active inflammation; Crohn's colitis < 50% involvement
Intermediate risk	Every 3 years	Extensive or left-sided colitis with mild inflammation; FHx of CRC > 50; pseudopolyps
Higher risk	Every year	Extensive or left-sided colitis with moderate-severe inflammation; stricture or dysplasia in past 5 years; FHx of CRC < 50

Surveillance methods ^[2]:

Chromoendoscopy — highest yield for dysplasia detection; involves topical application of methylene blue or indigo carmine to enhance mucosal irregularities and facilitate targeted biopsies ^[2]
High-definition white light colonoscopy — alternative with high diagnostic yield; preferred when chromoendoscopy yield is decreased or mucosa poorly visualised (inadequate prep, active inflammation, pseudopolyps, strictures) ^[2]
Narrow band imaging (NBI) — does NOT enhance dysplasia detection ^[2]

Management of dysplasia ^[14]:

Endoscopically visible dysplasia:
- Polypoid → polypectomy ^[14]
- Non-polypoid → endoscopic resection if complete resection is possible ^[14]
- Surgery should be considered if not endoscopically feasible ^[14]
Endoscopically invisible dysplasia:
- Associated with high rate of CRC ^[14]
- Referred to an experienced endoscopist ^[14]
- If LGD or no dysplasia → 5% LGD changed to HGD or CRC → surveillance or surgery? ^[14]
- If invisible HGD or multifocal LGD, surgery should be offered ^[14]

Step	Drug Class	Examples	Role	Key Points
1	5-ASA	Mesalamine, sulfasalazine	Induction + maintenance	First-line for mild-moderate; topical preferred for distal disease
2	Corticosteroids	Prednisolone, budesonide MMX, hydrocortisone IV	Induction ONLY	Not for maintenance; taper once remission achieved
3	Thiopurines	AZA, 6-MP	Maintenance (steroid-sparing)	Slow onset (8–12 weeks); check TPMT first; methotrexate NOT effective in UC
4	Biologics	Infliximab, adalimumab, vedolizumab, ustekinumab	Induction + maintenance	Screen for TB/HBV; contraindicated in active TB, NYHA III–IV HF, MS
5	Small molecules	Tofacitinib, ozanimod	Induction + maintenance	Oral; rapid onset; newer agents
Rescue	Calcineurin inhibitors / Anti-TNF	Cyclosporin, infliximab	Acute severe UC refractory to IV steroids	Bridge to maintenance; surgery if fails by Day 4–7
Surgery	—	Total colectomy / proctocolectomy + IPAA	Curative	Emergency: 3-stage; Elective: 2-stage; complications include pouchitis

High Yield Summary — Management of UC

Principles: Induce and maintain remission; treatment determined by extent (E1/E2/E3) and severity (Truelove & Witts).

Mild-moderate: 5-ASA first-line (topical for distal, oral + topical for extensive). Combination > monotherapy. If fails → oral steroids.

Moderate-severe outpatient: Oral steroids for induction → thiopurines (AZA/6-MP) for steroid-sparing maintenance. If steroid-refractory/dependent → biologics.

Acute severe UC (admit): IV hydrocortisone × 3 days → if no response → rescue therapy (infliximab or cyclosporin) → if no response by Day 4–7 → surgery.

Key predictors of colectomy: Stool freq > 8/day; stool freq 3–8 + CRP > 45; Travis index ≥ 8; colonic dilatation > 5.5 cm.

Biologics: Must screen TB (CXR + IGRA) + HBV (HBsAg). Contraindicated: active TB, lymphoma, NYHA III–IV HF, MS, optic neuritis.

Surgery is CURATIVE in UC. Emergency: 3-stage (colectomy + end ileostomy → completion proctectomy + IPAA → reversal of ileostomy). Elective: 2-stage (proctocolectomy + IPAA + loop ileostomy → reversal). Pouchitis is the most common complication (Rx: metronidazole + ciprofloxacin).

Methotrexate is NOT effective in UC. Antibiotics have MINIMAL role except for septic complications and pouchitis.

CRC surveillance: Start at 8 years for pancolitis. Chromoendoscopy is best for dysplasia detection. PSC → yearly surveillance. Proctitis → no increased risk.

Active Recall - Management of Ulcerative Colitis

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p. 52 — IBD-associated CRC risk factors) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis sections: treatment, surgical treatment, complications, prevention) ^[8] Senior notes: maxim.md (Inflammatory bowel disease: surgical indications; Surgical procedures for UC; Surgical procedures for CD) ^[11] Lecture slides: Inflammatory bowel disease.pdf (pp. 18, 19, 20 — Surgical indications, emergency surgery, colectomy) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p. 56 — AGA guideline 2010 for CRC surveillance) ^[13] Lecture slides: Inflammatory bowel disease.pdf (p. 57 — BSG guideline 2010 for risk-stratified surveillance) ^[14] Lecture slides: Inflammatory bowel disease.pdf (p. 55 — Management of dysplasia)

Complications of Ulcerative Colitis

The complications of UC can be organised into three categories:

Local / intestinal complications — arising directly from the colonic disease
Extraintestinal manifestations (covered in the Clinical Features section; cross-referenced here)
Treatment-related complications — arising from medical or surgical therapy

This section focuses primarily on the local/intestinal complications and surgical complications, as they are the most clinically actionable and highest-yield for examinations.

12.1 Local / Intestinal Complications

What it is: The most feared acute complication of UC — a true surgical emergency.

Definition ^[2]:

Total or segmental non-obstructive dilatation of the colon ≥ 6 cm or caecum > 9 cm AND the presence of systemic toxicity

Name breakdown: "Toxic" = systemic toxicity (sepsis-like state); "mega" = large (Greek megas); "colon" = the large bowel. So the name literally tells you: a dangerously dilated, toxic colon.

Pathophysiology (from first principles):

Clinical presentation ^[2]:

Fever, tachycardia, hypotension, dehydration
Electrolyte disturbances (hypokalaemia worsens colonic atony — a vicious cycle)
Anaemia, hypoalbuminaemia
Mental changes (encephalopathy from sepsis/metabolic derangement)
Physical examination: abdominal distension, reduced/absent bowel sounds, diffuse tenderness, ± peritonism (if perforation has occurred)

Diagnosis ^[2]:

Diagnosis is made by plain AXR
- Dilated colon ≥ 6 cm (transverse colon measured) or caecum > 9 cm
- Loss of haustral markings
- "Thumb-printing" sign (submucosal oedema/haemorrhage causing scalloped indentations along the colonic wall)
- Impending perforation: thumb-printing sign ^[8]

Management ^[2]:

Bowel rest and total parenteral nutrition (TPN)
Fluid and electrolyte replacement — aggressively correct hypokalaemia (K⁺ depletion worsens colonic atony)
Corticosteroids (IV hydrocortisone)
Stop all medications that reduce colonic motility — opioids, anticholinergics, loperamide, and codeine must be immediately discontinued as they worsen dilatation
Nasogastric tube decompression + frequent position changes (rolling the patient) to help redistribute intraluminal gas
Serial AXR (every 12–24 hours) to monitor colonic calibre
Surgical intervention (emergency total abdominal colectomy + end ileostomy) if:
- Failure of toxic dilatation to respond to 48 hours of therapy ^[11]
- Deterioration despite optimal treatment ^[11]
- Signs of perforation or peritonitis
- Progressive dilatation on serial AXR

Why Stop Opioids and Anticholinergics in Toxic Megacolon?

Opioids bind μ-receptors on myenteric plexus neurons → reduce acetylcholine release → decreased peristalsis → colonic atony → WORSENS dilatation. Anticholinergics directly block the muscarinic receptors needed for smooth muscle contraction. Both drug classes can precipitate or worsen toxic megacolon and must be stopped immediately.

This is the most important long-term complication of UC.

CRC in IBD patients is preceded by dysplasia ^[16]. Incidence of CRC in IBD: 18% after 30 years of colitis ^[16].

Pathophysiology — the Inflammation-Dysplasia-Carcinoma Sequence:

This is distinct from the sporadic adenoma → carcinoma sequence in non-IBD CRC. In IBD-CRC:

The "field effect" of chronic diffuse inflammation means dysplasia can arise anywhere in the colon (not just in a single polyp)
Dysplasia may be flat (invisible endoscopically) rather than polypoid — making detection much harder
The risk is cumulative — longer disease duration = greater cumulative inflammatory burden = more DNA damage

Risk factors for IBD-associated colorectal neoplasia ^[1]:

Category	Risk Factors
Patient-specific	Primary sclerosing cholangitis; history of colorectal neoplasia; family history of CRC in first-degree relative; smoking (+); early age of disease onset (+); male sex (+)
Disease-specific	Disease duration; disease extent; cumulative inflammatory burden; active inflammation endoscopically or histologically
Endoscopic features	Stricture (UC, longer disease duration, proximal location, symptoms); shortened tubular colon; pseudopolyps

^[1]

Why PSC is the strongest risk factor: PSC is associated with a 4-fold increase in CRC risk in UC patients, independent of disease duration or extent. The mechanism is thought to involve altered bile acid metabolism — PSC causes cholestasis and changes the bile acid pool, with secondary bile acids (e.g., deoxycholic acid) being directly genotoxic to colonic epithelium.

CRC Surveillance (covered in detail in the Management section; key points summarised here):

AGA Guidelines ^[12]:

Started at a maximum 8 years after UC or Crohn's colitis
Left-sided or extensive colitis: within 1–2 years after initial screening colonoscopy
After two negative examinations, every 1–3 years
PSC: yearly
Ulcerative proctitis: NOT considered at increased risk
Ideally performed when disease is in remission

BSG Guidelines — risk-stratified ^[13]:

Lower risk → Every 5 years	Intermediate risk → Every 3 years	Higher risk → Every year
Extensive/left-sided colitis without active inflammation; Crohn's colitis < 50% involvement	Extensive/left-sided colitis with mild inflammation; FHx CRC > 50; pseudopolyps	Extensive/left-sided colitis with moderate-severe inflammation; stricture or dysplasia in past 5 years; FHx CRC < 50

Surgery (proctocolectomy + IPAA) is curative for UC but carries its own set of complications ^[2]^[8]:

Complication	Mechanism	Presentation
Pouch-vaginal / perineal fistula ^[2]	Anastomotic leak or localised sepsis tracking to an adjacent structure	Passage of faecal material or air through the vagina; perineal discharge
Anastomotic stricture ^[2]	Fibrosis at the pouch-anal anastomotic site	Progressive difficulty evacuating the pouch; increased straining; narrowed calibre of stool; can be treated with endoscopic balloon dilatation
Anastomotic dehiscence with sepsis ^[2]	Breakdown of the surgical anastomosis → faecal leak into the pelvis	Pelvic sepsis — fever, abdominal/pelvic pain, raised WCC/CRP; may require drainage ± defunctioning ileostomy

These were covered in detail in the Clinical Features section. A brief high-yield summary of the key EIM-complications:

System	Complication	Key Points
Hepatobiliary	Primary sclerosing cholangitis (PSC)	Strong association with UC; majority of PSC patients have underlying UC; only 5% of UC patients develop PSC ^[4]. Leads to cholestasis → liver failure → cholangiocarcinoma. Dramatically increases CRC risk → annual surveillance colonoscopy ^[12]
Vascular	Arterial and venous thromboembolism	IBD is a prothrombotic state (2–3× risk). DVT, PE, portal/mesenteric vein thrombosis. Must give VTE prophylaxis during hospitalisation and flares
Dermatological	Pyoderma gangrenosum (more common in UC)	Deep painful ulcers with undermined, violaceous edges; pathergy phenomenon. Treat underlying UC + wound care + immunosuppression. Does NOT always correlate with disease activity
Musculoskeletal	Osteoporosis / Osteomalacia	Chronic steroid use + chronic inflammation → increased bone resorption. Calcium + vitamin D supplementation mandatory if steroids > 12 weeks
Haematological	Iron deficiency anaemia / Anaemia of chronic disease	Most common systemic complication; from chronic GI blood loss + hepcidin-mediated iron sequestration

High Yield Summary — Complications of UC

Stricture: Rare in UC (unlike CD). Must be considered malignant until proven otherwise by endoscopy with biopsy.

Fulminant colitis: > 10 stools/day + continuous bleeding + toxic symptoms. High risk of toxic megacolon. Immediate admission, IV steroids, surgical standby.

Toxic megacolon: Colon ≥ 6 cm or caecum > 9 cm + systemic toxicity. Diagnosed on AXR. Stop opioids/anticholinergics. Bowel rest + TPN + IV fluids + steroids. Surgery if no response to 48 hours therapy.

Perforation: Usually consequence of toxic megacolon. Associated with high mortality. Surgical emergency.

Severe haemorrhage: 6–10% need emergency colectomy. Indication for emergency surgery if uncontrolled.

CRC: Incidence 18% after 30 years. Inflammation → dysplasia → carcinoma sequence. Risk factors: PSC, disease duration, extent, cumulative inflammation, pseudopolyps, strictures, FHx CRC. Surveillance starts at 8 years; PSC = yearly; proctitis = not at increased risk. Chromoendoscopy has highest dysplasia detection yield.

Post-IPAA: Pouchitis (~50%; Rx metronidazole/ciprofloxacin), anastomotic stricture, pouch-vaginal fistula, dehiscence, sexual dysfunction/infertility. Female fertility preserved by IRA instead of IPAA.

Prognostic indicators: Age < 16 at diagnosis → more aggressive course. Older age at diagnosis → lower colectomy risk.

Active Recall - Complications of Ulcerative Colitis

References

^[1] Lecture slides: Inflammatory bowel disease.pdf (p. 52 — IBD-associated CRC risk factors) ^[2] Senior notes: felixlai.md (Inflammatory bowel disease — Ulcerative colitis: complications, surgical treatment, prevention/CRC screening) ^[4] Senior notes: felixlai.md (Primary sclerosing cholangitis section) ^[8] Senior notes: maxim.md (Inflammatory bowel disease: surgical indications; Surgical procedures for UC) ^[11] Lecture slides: Inflammatory bowel disease.pdf (pp. 18, 19, 20, 21 — Surgical indications, emergency surgery, colectomy, surgical options) ^[12] Lecture slides: Inflammatory bowel disease.pdf (p. 56 — AGA guideline 2010 for CRC surveillance) ^[13] Lecture slides: Inflammatory bowel disease.pdf (p. 57 — BSG guideline 2010 for risk-stratified surveillance) ^[15] Lecture slides: GC 186. Lower and diffuse abdominal painfresh blood in stool.pdf (p. 11 — IBD and PR bleeding) ^[16] Lecture slides: Inflammatory bowel disease.pdf (p. 51 — IBD-associated CRC, colitis-dysplasia-carcinoma sequence, 18% incidence after 30 years)