Ulcerative Colitis

Chronic relapsing-remitting inflammatory bowel disease characterized by continuous mucosal inflammation limited to the colon, always involving the rectum and extending proximally in a continuous (non-skip) pattern: distinguishes from Crohn's disease (transmural, skip lesions, can affect any part of GI tract).

Etiology multifactorial: genetic susceptibility, dysregulated mucosal immune response to gut microbiota, environmental triggers.

Classified by extent (Montreal classification):

• Proctitis: limited to rectum

• Left-sided colitis: extends to splenic flexure

• Extensive colitis (pancolitis): extends beyond splenic flexure, may involve entire colon

Classified by severity (Truelove and Witts criteria commonly used): mild, moderate, severe: based on stool frequency, blood, systemic symptoms, inflammatory markers.

• Bloody diarrhea (hallmark feature); frequency correlates with disease extent/severity

• Urgency, tenesmus (especially with rectal involvement/proctitis)

• Abdominal pain/cramping, typically left-sided or lower abdominal

• Mucus discharge

• Systemic symptoms in moderate-severe disease: fever, malaise, weight loss, tachycardia

• Severe/fulminant colitis (Truelove-Witts severe): ≥6 bloody stools/day PLUS ≥1 systemic feature: fever >37.8°C, HR >90, Hb <10.5g/dL, ESR >30 ; medical emergency, risk of toxic megacolon

• Toxic megacolon (life-threatening complication): colonic dilation (>6cm on imaging), systemic toxicity, risk of perforation ; requires urgent surgical involvement

• Extraintestinal manifestations (can parallel or run independent of colitis activity):

• Joint: peripheral arthritis (parallels disease activity), axial arthropathy/ankylosing spondylitis (independent course)

• Skin: erythema nodosum (parallels activity), pyoderma gangrenosum (independent course)

• Eye: episcleritis, uveitis

• Hepatobiliary: primary sclerosing cholangitis (PSC) ; important association, increases colorectal cancer risk further, independent of colitis activity, screen with LFTs

• Increased risk of venous thromboembolism during flares (hypercoagulable state)

• Colonoscopy with biopsy: gold standard: continuous inflammation from rectum extending proximally, loss of vascular pattern, granularity, friability, ulceration; biopsy confirms crypt architecture distortion, crypt abscesses, basal plasmacytosis (chronic inflammation pattern distinguishing from acute infectious colitis)

• Flexible sigmoidoscopy: preferred in acute severe flare (avoid full colonoscopy : perforation risk in severely inflamed/toxic colon)

• Stool studies: essential to exclude infectious colitis (stool culture, C. difficile toxin, ova/parasites) before/alongside diagnosis; infection can also trigger flares in established UC

• Fecal calprotectin: elevated, useful marker of intestinal inflammation, helps distinguish IBD from functional bowel disease, and monitors disease activity/response to treatment

• Bloods: FBC (anemia, thrombocytosis), CRP/ESR (correlate with activity, though can be normal in mild/limited disease), U&E, LFTs (screen for PSC), iron studies (chronic blood loss anemia)

• Imaging: abdominal X-ray in acute severe colitis (assess for toxic megacolon, colonic dilation), CT if complications suspected (perforation, abscess)

• Differentiating UC from Crohn's: continuous vs. skip lesions, rectal sparing more typical of Crohn's, transmural (Crohn's) vs. mucosal (UC) inflammation, fistulae/strictures more typical of Crohn's, ANCA (more UC-associated) vs. ASCA (more Crohn's-associated) serology can support but not definitively distinguish

Differentials: Crohn's disease, infectious colitis (bacterial ;Salmonella, Shigella, Campylobacter, E. coli, C. difficile; parasitic; amoebic colitis, important to exclude especially in endemic areas as steroids would worsen amoebic disease), ischemic colitis, radiation colitis, microscopic colitis, colorectal malignancy.

Induction of remission (by severity and extent):

• Mild-moderate proctitis/left-sided disease: topical (rectal) 5-ASA (mesalazine suppository/enema) first-line; superior to oral 5-ASA alone for distal disease; combine with oral 5-ASA if inadequate response to topical alone

• Mild-moderate extensive colitis: oral 5-ASA (mesalazine 2-4.8g/day) ± topical 5-ASA; if inadequate response, add oral corticosteroid (prednisolone 40mg od, tapering course over 6-8 weeks)

• Moderate-severe disease not responding to 5-ASA/steroids: oral corticosteroids; if steroid-refractory or steroid-dependent, escalate to biologics or thiopurines

• Severe/fulminant colitis (hospitalized, emergency management):

IV corticosteroids: hydrocortisone 100mg qds or methylprednisolone 60mg od

VTE prophylaxis (hypercoagulable state; do NOT withhold despite bloody diarrhea, risk of VTE outweighs bleeding risk with prophylactic dosing)

Daily monitoring: stool frequency/blood, vital signs, abdominal exam (peritonism, distension), inflammatory markers, abdominal X-ray if deteriorating (toxic megacolon surveillance)

• Day 3 reassessment (Oxford/Travis criteria): if stool frequency >8/day or CRP >45 + stool frequency 3-8/day at day 3 despite IV steroids;high likelihood of colectomy need, escalate to rescue therapy:

IV ciclosporin, or

Infliximab (anti-TNF); both effective rescue options, choice based on local expertise/patient factors

Surgical consultation early in severe flares; colectomy (subtotal colectomy with ileostomy, definitive proctocolectomy later) if rescue medical therapy fails, toxic megacolon develops, or perforation/hemorrhage occurs; should not be delayed once medical therapy failure is clear, given mortality risk of delayed surgery in fulminant colitis

Maintenance of remission:

• Oral ± topical 5-ASA; mainstay for mild-moderate disease, continued long-term (also has chemopreventive effect reducing colorectal cancer risk)

• Thiopurines (azathioprine, mercaptopurine); for steroid-dependent disease or those needing more than 5-ASA; check TPMT activity/genotype before starting (risk of severe myelosuppression in deficient patients); monitor FBC/LFTs regularly

• Biologics for moderate-severe or refractory disease: anti-TNF (infliximab, adalimumab, golimumab), anti-integrin (vedolizumab, gut-selective), anti-IL-12/23 (ustekinumab)

• JAK inhibitors: tofacitinib, upadacitinib; oral option for moderate-severe disease, carries similar boxed warnings as in RA (VTE, cardiovascular, malignancy risk in appropriate risk groups)

• Avoid long-term corticosteroids for maintenance (toxicity); steroid-sparing strategy is a treatment goal

Colorectal cancer surveillance: increased risk with disease duration (>8-10 years), extensive colitis, PSC association, family history; surveillance colonoscopy with biopsies per interval guidelines (typically starting 8-10 years post-diagnosis, more frequent with PSC or high-risk features).

Nutrition: address deficiencies (iron, B12/folate if extensive disease, vitamin D), dietitian input during flares; no strong evidence for specific exclusion diets in UC (unlike some evidence in Crohn's for enteral nutrition).

Referral: gastroenterology for all diagnosed/suspected IBD; surgical involvement early in severe/fulminant colitis or complications; ongoing MDT (multidisciplinary team) management for complex/refractory disease.