Gastroenterology & Internal Medicine
Ulcerative colitis - Hemorrhagic rectocolitis
Ulcerative colitis (UC) - also known as ulcerative colitis (UC) - is a chronic inflammatory bowel disease (IBD) characterized by diffuse, continuous, non-granulomatous mucosal and submucosal inflammation of the colon and rectum. Unlike Crohn's disease (which can affect any segment of the digestive tract from mouth to anus, both segmentally and transmurally), ulcerative colitis always extends contiguously from the rectum to the proximal colon, never extending beyond the ileocecal valve except in cases of reflux ileitis. It is one of the chronic inflammatory bowel diseases (IBD), along with Crohn's disease and unclassified colitis (IBD-I). Its prevalence in Canada is among the highest in the world - around 230-260 cases per 100,000 inhabitants, representing one of the highest overall prevalences along with Scandinavian countries and the UK. In Quebec, an estimated 30,000-40,000 people live with ulcerative colitis. Incidence has been rising steadily since the 1990s, particularly in emerging countries (India, China, Brazil), suggesting the decisive involvement of environmental factors (Western-style diet, antibiotics, disturbance of the intestinal microbiota) in its pathogenesis. The disease typically evolves through inflammatory flare-ups interspersed with periods of remission of variable duration - 50-% of patients experience a flare-up per year. Without effective disease-modifying therapy, 15-20 % of patients will require total colectomy during their lifetime. Ulcerative colitis is also associated with an increased risk of colorectal cancer - of the order of 2 % at 10 years, 8 % at 20 years and 18 % at 30 years of evolution for pancolitis - justifying regular colonoscopic surveillance.
Pathophysiology
- Mucosal immune dysregulation: ulcerative colitis results from an inappropriate innate and adaptive immune response against commensal intestinal microbiota in genetically predisposed subjects; dendritic cells and macrophages in the colonic mucosa abnormally recognize commensal bacterial antigens → activation of the NF-κB pathway → production of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) → recruitment of neutrophils and Th2/Th17 lymphocytes to the mucosa → formation of abscessed crypts and mucosal ulcerations ; Th2 response (IL-5, IL-13) predominates in UC - unlike Crohn's disease (Th1/Th17)
- Genetic factors: over 200 susceptibility loci identified in IBD, including around thirty specific to UC; genes involved: HLA-DRB1, IL-10, JAK2 (JAK-STAT pathway - target of JAK inhibitors), ECM1, CDH1 (E-cadherin - epithelial barrier integrity); concordance in monozygotic twins of 15-20 % (vs. 50-60 % in Crohn's disease) - underlining the predominance of environmental factors in UC
- Environmental factors : tobacco - paradoxical protective factor in UC (reduced risk by 40 % and severity) - smoking cessation can trigger or worsen UC (nicotine reduces intestinal permeability and modifies mucosal cytokines); appendectomy before age 20 for true appendicitis - protective effect (-70 % risk of UC); NSAIDs - can trigger or exacerbate flare-ups; antibiotics in early childhood - disruption of intestinal microbiota → dysbiosis
- Damage to the mucosal barrier: alteration of the mucus layer (deficient MUC2 mucins), weakened inter-enterocyte tight junctions → increased intestinal permeability → bacterial translocation → maintenance of inflammation; characteristic mucosal ulcerations with cryptic abscess formation (accumulation of neutrophils in Lieberkühn's crypts) are the histological consequence of this intense mucosal inflammation
Classification of ulcerative colitis according to extent (Montreal)
| Stadium | Scope | Therapeutic implications |
|---|---|---|
| E1 | Isolated proctitis - limited to rectum (< 15 cm from anal margin) | First-line topical rectal treatment (mesalazine suppositories or enemas); systemic treatment if topical treatment fails or is not possible |
| E2 | Left colitis - up to the splenic angle (left angle of the transverse colon) | Topical mesalazine (enema) + oral mesalazine; oral corticosteroids for moderate to severe flare-ups |
| E3 | Pancolitis - beyond the splenic angle - affects the transverse, ascending colon and/or cecum | Full-dose oral mesalazine (4 g/day) ± topical; biotherapy more often required; highest risk of colorectal cancer - intensified colonoscopic surveillance |
Clinical signs and activity score (Mayo score)
- Cardinal symptoms: bloody diarrhea (hematochezia) - an almost constant sign (90-95 % of attacks) - bright red blood mixed with stool or on paper; frequent defecatory urgency (tenesmus) and false stool - a sign of rectal involvement; crampy or colicky lower abdominal pain relieved by defecation; increased number of stools (from 3-5 to > 10 stools/day in severe forms).
- Clinical Mayo score (0-9): stool frequency (0 = normal, 1 = 1-2 more than normal, 2 = 3-4 more, 3 = > 4 more) + blood in stool (0 = absent, 1 = traces, 2 = obvious blood, 3 = majority blood) + physician's overall assessment (0-3); score 0-2 = remission; 3-5 = mild activity; 6-9 = moderate to severe; endoscopic Mayo score (0-3 depending on mucosal aspect) is used to assess mucosal healing (current therapeutic objective)
- Truelove and Witts score - severe acute colitis (indication for hospitalization): more than 6 bloody stools per day + at least one of the following criteria: fever > 37.8°C, tachycardia > 90/min, anemia (hemoglobin 30 mm/h or CRP > 30 mg/L; this picture requires hospitalization for IV corticosteroid therapy and monitoring of response within 3 to 5 days (Oxford criteria - risk of emergency colectomy if non-responder).
- Extra-intestinal manifestations (present in 25-40 % of patients): articular (peripheral arthritis of large joints - correlates with intestinal disease activity; axial spondylarthropathy - independent of activity); cutaneous (erythema nodosum - parallels disease; pyoderma gangrenosum - independent, specific immunosuppressive treatment); ocular (episcleritis - correlates with activity; anterior uveitis - independent); hepatobiliary (primary sclerosing cholangitis - PSC - affecting 5-8 % of patients with extensive UC : progressive fibrous narrowing of the bile ducts, increased risk of cholangiocarcinoma and colorectal cancer)
Diagnosis
- Colonoscopy with staged biopsies: reference examination - direct visualization of mucosa (erythema, loss of vascular network, granularity, ulcerations, pseudopolyps, friability on contact, spontaneous bleeding); multiple staged biopsies (rectum + sigmoid colon + left colon + transverse colon + right colon + terminal ileum) - histology : diffuse inflammation of the mucosa and submucosa, cryptids and cryptic abscesses (accumulation of neutrophils in Lieberkühn crypts), architectural distortion of crypts, depletion of caliciform cells; colonoscopy is contraindicated in severe acute colitis (risk of perforation) - short flexible rectosigmoidoscopy is preferred in this context
- Biological workup: CBC (iron-deficiency or inflammatory anemia, reactive thrombocytosis), CRP and VS (markers of inflammatory activity), albumin (undernutrition), creatinine and electrolytes, liver workup (PSC), fecal calprotectin (marker of intestinal inflammation - normal value 250 µg/g → active mucosal inflammation - useful for screening, follow-up and distinction with IBS); coprocultures and search for Clostridioides difficile (A/B toxin) before any immunosuppressive treatment - to rule out a triggering infection
- Imaging: barium enema or abdominal CT scan (severe acute colitis with suspected toxic megacolon); pelvic MRI (if perineal involvement to be distinguished from Crohn's disease); intestinal ultrasound (splitting of the colonic wall - non-irradiating alternative to CT scan for follow-up).
- Serum biomarkers: perinuclear ANCA (pANCA) positive in 60-70 % of UC vs 10-15 % of Crohn's disease - useful for orienting the differential diagnosis between IBD; ASCA (antiSaccharomyces cerevisiae) positive in Crohn's disease but rarely in UC - ANCA+/ASCA- combination suggestive of UC
Treatment according to severity and extent
| Clinical situation | Recommended treatment (ECCO Guidelines 2022) |
|---|---|
| Mild to moderate proctitis (E1) | Mesalazine (5-ASA) suppositories 1 g/night - first-line treatment; if unsuccessful: mesalazine enemas 1-4 g/evening; topical corticoids (budesonide rectal foam) as an alternative; oral mesalazine 2-4 g/day in combination if insufficient response to topical alone. |
| Mild to moderate left colitis (E2) or mild pancolitis (E3) | Oral mesalazine 3-4 g/day (MMX gastro-resistant tablets) + topical mesalazine (enema 4 g/night) - the combination is superior to the oral route alone (ASCEND study); objective: clinical and endoscopic remission (mucosal healing - endoscopic Mayo score 0-1); long-term maintenance with mesalazine 2-2.4 g/day (reduces the risk of relapse and colorectal cancer). |
| Moderate to severe flare-up (Mayo score 6-9) | Oral corticosteroid therapy: prednisone 40-60 mg/day for 2-4 weeks, tapering off over 8-12 weeks (do not use as maintenance therapy - frequent corticosteroid dependence); budesonide MMX 9 mg/day - alternative with less systemic effects for moderate colitis; thiopurines (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day) as maintenance therapy if corticosteroid-dependent (> 2 relapses/year requiring corticosteroids). |
| Severe acute colitis - hospitalization (Truelove and Witts) | Methylprednisolone IV 60 mg/day (or hydrocortisone 400 mg/day) continuous infusion; assessment of response at 72h (Oxford criteria - fecal output, CRP, clinical score); if non-responder at 72-96h → salvage therapy: infliximab 5 mg/kg IV (single bolus before colectomy decision) or ciclosporin IV 2 mg/kg/day (response rate 60-80 % but temporary response); emergency total colectomy if toxic megacolon (> 6 cm), perforation, refractory massive bleeding or non-response to salvage therapy within 4-7 days |
| Moderate to severe colitis refractory to immunosuppressants/biotherapies | Anti-TNF-alpha: infliximab IV (5 mg/kg at S0, S2, S6 then every 8 weeks) or adalimumab SC (160 mg/80 mg/40 mg) - remission rate 30-40 % at 1 year; anti-integrin: vedolizumab IV (300 mg at S0, S2, S6 then every 8 weeks) - intestine-selective action, less systemic infectious risk (GEMINI 1); anti-IL-12/23: ustekinumab SC (single IV induction dose then SC every 8-12 weeks) - CU approved in 2019; JAK inhibitors: tofacitinib 10 mg 2×/day (OCTAVE Induction) - rapid response (week 8), useful in case of injection refusal or failure to biologics; filgotinib and upadacitinib - JAK1-selective, approved in Europe and Canada; ozanimod (S1P agonist) - new mechanism approved Health Canada 2023 |
| Surgery (colectomy) | Indications: severe refractory acute colitis (emergency), toxic megacolon or perforation, high-grade dysplasia or colorectal cancer on colitis, disease refractory to all lines of medical treatment; procedure of choice: total proctocolectomy with ileo-anal anastomosis (J-shaped ileal reservoir - Kock's pouch) - preserves anal continence; definitive ileostomy if reservoir impossible or elderly/fragile patient. |
ℹ️
Visit fecal calprotectin is a very useful marker of intestinal inflammation for monitoring ulcerative colitis - it is measured on a stool sample and reflects actual mucosal inflammatory activity (independent of symptoms). A calprotectin > >). 80 % if calprotectin > 500 µg/g).
Colorectal cancer surveillance and prevention
- Increased risk of colorectal cancer: duration of disease progression (> 8-10 years → regular colonoscopic surveillance), extent of colitis (pancolitis > left colitis > proctitis), severity of chronic inflammation (persistent inflammation → p53 mutations, chromosomal instability), associated CSP (risk multiplied by 4-5), first-degree family history of CRC
- Recommended colonoscopic surveillance (ECCO 2022): chromoendoscopy (staining with methylene blue or indigo carmine + directed biopsies of suspicious lesions) recommended to improve detection of flat dysplasia - superior to systematic 4-quadrant biopsy; frequency: every 1 year if associated PSC, pancolitis with chronic active inflammation or previous low-grade dysplasia; every 2-3 years if pancolitis in remission; every 3-5 years if left colitis; no systematic surveillance if isolated proctitis (risk of CRC not increased)
- Mesalazine as chemoprophylaxis: prolonged use of maintenance mesalazine reduces the risk of colorectal cancer by 40-75 % in meta-analyses - mucosal anti-inflammatory and pro-apoptotic mechanism on dysplastic epithelial cells; additional argument for maintaining long-term maintenance treatment even in deep remission
- Vaccinations recommended for patients on immunosuppressive therapy: pneumococcal vaccine (PCV13 + PPSV23), annual influenza vaccine (inactivated), VZV vaccine (zoster - live attenuated: to be administered BEFORE the start of immunosuppressive therapy or at a later date), HPV vaccine if < 45 years of age.
Severe acute colitis - toxic megacolon - absolute emergency
Dial 911 or go immediately to the emergency room if you present with: more than 6 bloody stools per day accompanied by fever (> 38°C), rapid pulse, diffuse and intense abdominal pain or progressive abdominal distension - this may correspond to severe acute colitis or toxic megacolon (colon dilatation > 6 cm), potentially life-threatening complications requiring emergency hospitalization, IV corticosteroid therapy and possibly emergency surgery. Do not take NSAIDs (ibuprofen, naproxen) during a flare-up of ulcerative colitis - these drugs can trigger or aggravate severe colitis.
Consult at Clinique Omicron
Clinique Omicron's physicians assess symptoms suggestive of ulcerative colitis (chronic bloody diarrhea, defecatory emergencies), prescribe the initial diagnostic work-up (fecal calprotectin, blood tests, referral for colonoscopy), adjust disease-modifying treatments (mesalazine, thiopurines), monitor relapses and initiate reimbursement procedures for biotherapies (RAMQ). Consultations are available at our points of service in Quebec, as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for information purposes only and does not replace the advice of a qualified healthcare professional. Ulcerative colitis is a chronic disease requiring regular medical follow-up by a gastroenterologist.
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