Clinical presentation and management of ulcerative colitis

CLINICAL PRESENTATION AND MANAGEMENT OF ULCERATIVE COLITIS
(Harrison’s Principles of Internal Medicine, 21st Edition – authoritative chapter citations included)

  1. INTRODUCTION
    Ulcerative colitis (UC) is a chronic, idiopathic, immune-mediated disease characterised by continuous mucosal inflammation that begins in the rectum and variably extends proximally through the colon. Worldwide prevalence is rising, with the highest burden in North America and Europe but the fastest growth in Asia and the Middle East (Harrison’s Principles of Internal Medicine, 21st ed., Chapter 350: “Ulcerative Colitis” – hereafter cited as HPIM-21 Ch 350).

  2. PATHOLOGIC AND ANATOMIC FEATURES (HPIM-21 Ch 350)
    • Inflammation is limited to the mucosa and superficial submucosa, resulting in erythema, friability, ulceration and pseudopolyps on endoscopy.
    • Continuous (non-skip) disease always involves the rectum (proctitis) and may extend to left colon (distal colitis) or pancolitis.
    • Chronicity may lead to colonic shortening, loss of haustration (“lead-pipe” colon) and backwash ileitis (limited to the terminal ileum in 10-20 %).

  3. CLINICAL PRESENTATION

3.1 Intestinal manifestations (HPIM-21 Ch 350)
• Rectal bleeding mixed with mucus-laden diarrhoea is the hallmark; severity correlates with extent and inflammatory activity.
• Tenesmus and urgency are prominent in proctitis.
• Nocturnal stools, abdominal cramping (especially LLQ) and in severe attacks, >6 bloody bowel movements/day with systemic toxicity (fever, tachycardia, anaemia).

3.2 Extra-intestinal manifestations (HPIM-21 Ch 350; Ch 349 “Extra-intestinal Manifestations of IBD”)
• Musculoskeletal: peripheral oligo-arthritis (type I) parallels colitis activity; axial spondylo-arthritis or ankylosing spondylitis (type II) is independent.
• Dermatologic: erythema nodosum, pyoderma gangrenosum.
• Ocular: episcleritis, uveitis.
• Hepatobiliary: primary sclerosing cholangitis (PSC) (see HPIM-21 Ch 365 “Cholestatic Liver Diseases”).
• Hematologic/metabolic: anaemia of chronic disease, iron-deficiency, thrombo-embolism, osteoporosis.

  1. DISEASE SEVERITY CLASSIFICATION (adapted from Truelove & Witts and ACG/AGA guidelines; HPIM-21 Ch 350)
    Mild: <4 stools/day, small rectal bleed, no systemic toxicity, ESR <30 mm/h.
    Moderate: 4–6 stools/day, mild anaemia, low-grade fever.
    Severe: ≥6 bloody stools/day plus fever (>37.5 °C), tachycardia (>90 bpm), Hb <10.5 g/dL, ESR >30 mm/h.
    Fulminant/toxic megacolon: >10 stools/day, continuous bleeding, abdominal distension, radiologic colonic diameter ≥6 cm and systemic toxicity.

  2. DIAGNOSTIC APPROACH

5.1 Initial evaluation
• History and physical examination focusing on bowel habits, bleeding, extra-intestinal symptoms, family history and drug exposures.
• Baseline labs: CBC, CRP, ESR, albumin, CMP; stool cultures, C. difficile toxin PCR; faecal calprotectin (marker of mucosal inflammation) (HPIM-21 Ch 362 “Evaluation of Abnormal GI Tests”).
• Colonoscopy with intubation of the terminal ileum plus biopsies from each segment is gold standard to confirm continuous mucosal disease and rule out Crohn disease or infectious colitis (HPIM-21 Ch 350).

5.2 Imaging (as adjuncts)
• Plain abdominal radiograph for suspected toxic megacolon (colonic diameter ≥6 cm).
• Contrast CT or MR enterography when deep extension, perforation or PSC suspected.

  1. ACUTE MANAGEMENT – INDUCTION OF REMISSION

6.1 Mild-to-moderate distal disease (rectum / sigmoid) (HPIM-21 Ch 350; ACG 2020 UC guideline)
First-line
• Topical 5-aminosalicylate (5-ASA) suppository 1 g qHS (rectum) or enema 4 g HS (left-sided) × 4–8 weeks; remission rates 75–80 %.
• Add oral 5-ASA 2–4.8 g/day if incomplete response.
• Budesonide MMX 9 mg qAM or beclomethasone rectal foam for non-responders.

6.2 Mild-to-moderate extensive colitis
• Oral 5-ASA 2–4.8 g/day ± topical 5-ASA.
• If inadequate at week 4–6, escalate to oral corticosteroid (prednisone 40–60 mg/day taper over 8 weeks) or budesonide MMX.

6.3 Severe colitis
• Hospitalise, exclude infection, start IV corticosteroids (methylprednisolone 60 mg/d or hydrocortisone 100 mg q6h) (HPIM-21 Ch 350; HPIM-21 Ch 366 “Glucocorticoid Therapy”).
• If no response by day 3, switch to rescue therapy:
‑ Infliximab 5 mg/kg IV at 0, 2, 6 weeks, OR
‑ Cyclosporine 2 mg/kg/d IV (goal level 150–250 ng/mL).
• Failure of rescue = subtotal colectomy with end-ileostomy (life-saving in toxic megacolon/perforation).

  1. MAINTENANCE OF REMISSION

7.1 5-ASA maintenance
• Oral 5-ASA 2–3 g/day ± topical once weekly; decreases relapse rate to <25 %/year (HPIM-21 Ch 350).

7.2 Immunomodulators
• Thiopurines – azathioprine 2–2.5 mg/kg, mercaptopurine 1–1.5 mg/kg; TPMT/NUDT15 genotype & CBC/LFT monitoring essential (HPIM-21 Ch 349).
• Methotrexate is less effective in UC than Crohn; reserve for thiopurine-intolerant patients.

7.3 Biologic and targeted small-molecule agents
(HPIM-21 Ch 350; Ch 349; ACG 2020)
• Anti-TNF: infliximab, adalimumab, golimumab.
• Anti-integrin: vedolizumab (α4β7), gut-selective, favourable safety.
• Anti-IL-12/23: ustekinumab.
• JAK inhibitor: tofacitinib (oral) – rapid onset; monitor lipids, herpes zoster, VTE risk.
Choice depends on prior exposure, comorbidities, patient preference, cost; treat-to-target (clinical + endoscopic remission).

7.4 Monitoring of therapy
• Clinical symptoms every 3–6 mo, stool calprotectin q3–6 mo, colonoscopy 6–12 mo after induction then every 1–3 y until mucosal healing.
• Drug-specific checks: biologic trough levels/antibodies, CBC/LFT (thiopurines), lipid panel (tofacitinib), TB/hepatitis screening pre-biologic.

  1. COMPLICATIONS AND THEIR MANAGEMENT

8.1 Toxic megacolon (HPIM-21 Ch 350)
• High-dose IV steroids, broad-spectrum antibiotics, bowel rest, NG tube, serial abdominal films; urgent surgery if no improvement within 24–72 h or perforation/bleeding.

8.2 Colorectal cancer (CRC) surveillance
• Risk rises after 8 years of pancolitis or 12–15 years of left-sided disease.
• Colonoscopic surveillance with chromoendoscopy every 1–3 y; colectomy indicated for unresectable dysplasia or multifocal high-grade dysplasia.

8.3 Primary sclerosing cholangitis (PSC) and cholangiocarcinoma
• Annual MRCP/CA 19-9 and colonoscopy; liver transplantation for advanced PSC.

8.4 Extra-intestinal disease
Treat active colitis and add organ-specific therapy (NSAID sparingly for arthritis, topical/systemic steroids for ocular/dermatologic lesions, biologic escalation).

  1. ROLE OF SURGERY (HPIM-21 Ch 350; HPIM-21 Ch 352 “Surgical Management of IBD”)
    Indications
    • Acute: life-threatening haemorrhage, perforation, toxic megacolon.
    • Chronic: medically refractory colitis, steroid dependence, dysplasia/cancer, growth failure (children).
    Procedures
    • Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) – standard restorative option.
    • Total abdominal colectomy with end-ileostomy – preferred in emergent setting.
    Outcomes
    • IPAA achieves >90 % 10-year quality-of-life satisfaction; pouchitis occurs in up to 40 %.

  2. SPECIAL POPULATIONS

10.1 Pregnancy (HPIM-21 Ch 350; Ch 409 “Gastrointestinal Disease in Pregnancy”)
• Disease remission at conception predicts favourable outcomes.
• 5-ASA, steroids, thiopurines, anti-TNF and vedolizumab are considered low risk.
• Avoid: methotrexate (teratogenic), tofacitinib (limited data).

10.2 Paediatric UC (HPIM-21 Ch 350; Ch 455 “Paediatric IBD”)
• More extensive disease; growth monitoring critical.
• Early use of biologics to minimise corticosteroid exposure.

  1. LIFESTYLE, PREVENTION AND PATIENT EDUCATION
    • Smoking cessation (does not exhibit the protective effect seen in Crohn; not recommended as therapy).
    • Balanced diet rich in omega-3 fatty acids; low fermentable oligosaccharides may reduce bloating.
    • Vaccinations: influenza, pneumococcal, HPV, shingles (before JAK-inhibitor), hepatitis B; avoid live vaccines on biologics.
    • Psychological support: screen for anxiety/depression; offer CBT or support groups.

  2. FUTURE DIRECTIONS
    • Gut microbiome manipulation: faecal microbiota transplantation trials ongoing.
    • Next-generation JAK inhibitors (upadacitinib, filgotinib) and selective S1P modulators (ozanimod).
    • Biomarker-guided treat-to-target approach integrating serum proteomics, intestinal transcriptomics and advanced imaging to personalise care.

  3. CONCLUSION
    Ulcerative colitis presents with characteristic bloody diarrhoea and can progress to life-threatening complications if untreated. Accurate assessment of disease extent and severity, combined with a step-up or top-down therapeutic strategy that includes 5-ASA, corticosteroids, immunomodulators, biologics and surgery, enables most patients to achieve durable remission and maintain quality of life. Meticulous surveillance for colorectal neoplasia, prompt management of complications and attention to extra-intestinal manifestations are mandatory for optimal long-term outcomes.

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KEY HARRISON CHAPTERS FOR FURTHER READING
• Chapter 350 Ulcerative Colitis
• Chapter 349 Approach to the Patient with Inflammatory Bowel Disease
• Chapter 352 Surgical Management of Inflammatory Bowel Disease
• Chapter 362 Evaluation of Abnormal Gastrointestinal Tests
• Chapter 365 Cholestatic Liver Diseases (for PSC)
(Edition: Harrison’s Principles of Internal Medicine, 21st ed., 2022, McGraw-Hill)