Inflammatory bowel syndrome
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Here is a comprehensive overview of Inflammatory Bowel Disease (IBD).
Inflammatory Bowel Disease (IBD)
IBD is a chronic, relapsing-remitting inflammatory condition of the gastrointestinal tract. It comprises two main subtypes — Crohn's disease (CD) and Ulcerative colitis (UC) — plus a less common category, indeterminate colitis, used when histology doesn't clearly distinguish the two.
Epidemiology & Etiology
IBD results from a dysregulated immune response in a genetically susceptible host, triggered by environmental and microbial factors. Key contributors:
- Genetics: >200 susceptibility loci identified; NOD2 mutations are the strongest known risk factor for CD
- Microbiome: Dysbiosis with reduced microbial diversity
- Environmental triggers: Western diet, smoking (protective in UC, harmful in CD), appendectomy (protective in UC), NSAIDs, antibiotics
- Peak onset: CD — ages 15–30 (with a second peak in the 7th decade); UC — ages 20–40
Key Distinguishing Features
| Feature | Crohn's Disease | Ulcerative Colitis |
|---|---|---|
| GI extent | Esophagus to anus ("mouth to anus") | Colon only |
| Pattern | Skip lesions (discontinuous) | Continuous, starting from rectum |
| Depth | Transmural (all bowel layers) | Mucosal/submucosal only |
| Ulceration | Discrete, aphthous → cobblestoning | Continuous, diffuse erythema |
| Fistulas/strictures | Common | Rare |
| Perianal disease | Common (20–40%) | Absent |
| Rectal involvement | ~60% | Always (hallmark) |
| Granulomas | Noncaseating (pathognomonic if present) | Absent |
(Goldman-Cecil Medicine, Table 127-1)
Clinical Manifestations
Crohn's Disease
The terminal ileum is affected in ~70% of patients. Presentations:
- Ileocolonic (most common, 40%): RLQ pain, diarrhea, weight loss, hematochezia
- Ileal only (30%): Obstructive symptoms — distension, nausea, cramping
- Perianal (up to 30%): Fistulas, abscesses, fissures, skin tags with pain and discharge
- Upper GI (<5%): Dysphagia, odynophagia, heartburn
- Fistulas (enterocutaneous, rectovaginal, enterovesicular) occur in 20–40% of patients
Ulcerative Colitis
- Hematochezia, bloody diarrhea, tenesmus, urgency, excessive mucus production
- In proctitis/proctosigmoiditis: paradoxical constipation with difficulty defecating
- Severe/extensive disease: weight loss, fever, hypoalbuminemia, peripheral edema
- At diagnosis: ~14–37% have pancolitis; ~44–49% have proctosigmoiditis
Extraintestinal Manifestations
| System | Manifestations |
|---|---|
| Musculoskeletal | Peripheral arthritis/arthralgia, ankylosing spondylitis, sacroiliitis (10–20%) |
| Dermatologic | Erythema nodosum (10–15%), pyoderma gangrenosum (1–2%) |
| Ocular | Uveitis, episcleritis (5–15%) |
| Hepatobiliary | Primary sclerosing cholangitis (2–7.5% of IBD; 70–80% of PSC patients have underlying IBD) |
| Renal | Calcium oxalate stones (fat malabsorption in CD), uric acid stones |
(Goldman-Cecil Medicine, Table 127-2)
Diagnosis
Endoscopy + biopsy is the cornerstone. Key findings:
- Crohn's: Aphthous ulcers early → deep linear/serpiginous ulcers → cobblestoning; skip areas; possible small bowel or upper GI involvement. Noncaseating granulomas on biopsy (rarely seen on endoscopic samples, but pathognomonic)
- UC: Diffuse mucosal erythema starting at the rectum → granular, edematous mucosa → friability → ulceration; continuous proximal spread; pseudopolyps in long-standing disease
- Histology (UC): Crypt distortion, lymphocytic infiltrate, crypt abscesses
- Imaging: CT/MR enterography for small bowel involvement in CD; can show mural thickening, "comb sign" (engorged mesenteric vessels), fat stranding
Treatment
Step-Up Approach
| Tier | Agents | Use |
|---|---|---|
| Aminosalicylates (5-ASA) | Mesalamine, sulfasalazine | Mild–moderate UC; maintenance |
| Corticosteroids | Prednisone, budesonide | Induction of remission (not maintenance) |
| Immunomodulators | Azathioprine, 6-MP, methotrexate | Maintenance; steroid-sparing |
| Anti-TNF-α biologics | Infliximab, adalimumab, certolizumab (CD), golimumab (UC) | Moderate–severe disease; fistulizing CD |
| Anti-integrins | Vedolizumab | Gut-selective; moderate–severe UC & CD |
| IL-12/23 inhibitors | Ustekinumab | Moderate–severe CD (also UC) |
| JAK inhibitors | Tofacitinib, upadacitinib | Moderate–severe UC |
Anti-TNF Biologics (key pharmacology)
- Infliximab (IV): 5 mg/kg at 0, 2, 6 weeks → every 8 weeks maintenance; chimeric (25% mouse/75% human); t½ ~8–10 days
- Adalimumab (SC): 160 mg → 80 mg at wk 2 → 40 mg every 2 weeks; fully humanized; t½ ~2 weeks
- Certolizumab pegol (SC): PEGylated Fab fragment; 400 mg at 0, 2, 4 weeks → every 4 weeks
- Golimumab (SC): For UC; fully humanized; t½ ~14 days
- Major adverse effect: serious infections (including TB reactivation — screen before initiation); risk of lymphoma with long-term use
(Goodman & Gilman's Pharmacological Basis of Therapeutics)
Surgery
- UC: Colectomy is curative — indicated for refractory disease, toxic megacolon, dysplasia/cancer
- CD: Not curative; surgery for strictures, fistulas, abscesses, or medically refractory disease; bowel-preserving resection preferred
Complications & Cancer Risk
- Colorectal cancer (CRC): Risk begins after ~7 years of UC; rises ~10% per decade, reaching 15–34% at 30 years. Risk correlates with disease extent and duration. CD also increases CRC risk 4–20×
- Toxic megacolon: Severe, life-threatening complication primarily in UC
- Dysplasia surveillance: Colonoscopy every 1–2 years after 8–10 years of pancolitis
- Osteoporosis: From chronic corticosteroid use and malabsorption
- Thromboembolism: IBD is a prothrombotic state — increased DVT/PE risk during flares
Recent Evidence
A 2024 AGA network meta-analysis (PMID 39425738) synthesized comparative efficacy of advanced therapies for moderate-to-severe UC, supporting individualized biologic and small-molecule selection. The BSG IBD Guideline 2025 incorporates the latest network meta-analysis data on induction and maintenance agents for both CD and UC.
Sources: Goldman-Cecil Medicine 26e, Ch. 127 | Goodman & Gilman's Pharmacological Basis of Therapeutics, Ch. 55 | Sleisenger & Fordtran's Gastrointestinal and Liver Disease
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