Inflammatory Bowel Disease: Crohn vs Ulcerative Colitis
A boards-focused deep dive contrasting Crohn disease and ulcerative colitis across pathophysiology, presentation, diagnosis, and management—packed with vignette buzzwords, endoscopy/imaging/lab findings, and next-best-step decisions for STEP 1 and STEP 2 CK.
Overview & Pathophysiology
Inflammatory bowel disease (IBD) comprises two chronic, relapsing-remitting disorders driven by a dysregulated mucosal immune response to gut flora in a genetically susceptible host: Crohn disease (CD) and ulcerative colitis (UC).
Crohn disease can involve any part of the GI tract, mouth to anus—classically the terminal ileum—with skip lesions and transmural inflammation (linked to NOD2/CARD15 variants; Th1/Th17-driven). Its transmural nature explains the hallmark complications: fistulae, abscesses, and strictures.
Ulcerative colitis is confined to the colon, begins in the rectum, and spreads proximally and continuously, with inflammation limited to the mucosa and submucosa.
A favorite boards twist: smoking worsens Crohn but is protective in UC (UC is a disease of nonsmokers/ex-smokers). Both have a first incidence peak around ages 15–35, share extraintestinal manifestations, and require exclusion of infection (C. difficile, enteric pathogens) before diagnosis.
- Crohn = transmural + skip lesions + terminal ileum; UC = mucosal + continuous + rectum always involved
- NOD2/CARD15 = strongest genetic link to Crohn (impaired bacterial sensing)
- Smoking is harmful in Crohn, protective in UC; appendectomy (for true appendicitis, especially before age 20) also lowers UC risk
- Serologies: ASCA → Crohn; atypical p-ANCA → UC (supportive, not diagnostic)
- Fecal calprotectin ↑ = mucosal inflammation; helps distinguish IBD from IBS and tracks activity
- Extraintestinal (both): anterior uveitis/episcleritis, erythema nodosum, pyoderma gangrenosum, peripheral (large-joint) arthritis, ankylosing spondylitis/sacroiliitis
- Primary sclerosing cholangitis (PSC) pairs strongly with UC ('beaded' ducts; ↑ cholangiocarcinoma + colorectal cancer risk)
- Track bowel activity: erythema nodosum, peripheral arthritis, episcleritis, oral aphthae. Run independent of activity: PSC, ankylosing spondylitis/sacroiliitis, anterior uveitis
- Crohn malabsorption (terminal ileum): B12 deficiency and bile-salt loss → cholesterol gallstones + enteric hyperoxaluria → calcium-oxalate kidney stones
Crohn Disease vs Ulcerative Colitis
| Feature | Crohn Disease | Ulcerative Colitis |
|---|---|---|
| Location | Mouth→anus; terminal ileum; rectum often spared | Colon only; rectum always, extends proximally |
| Pattern / depth | Skip lesions, transmural | Continuous, mucosa/submucosa |
| Histology | Non-caseating granulomas (~30%) | Crypt abscesses, crypt distortion; no granulomas |
| Endoscopy | Cobblestoning, aphthous/linear ulcers | Friable mucosa, pseudopolyps, lost haustra |
| Imaging / gross | String sign (Kantor); creeping fat/fibrofatty proliferation; fistula/stricture on enterography | 'Lead-pipe' colon on barium (loss of haustra) |
| Stool | Non-bloody diarrhea | Bloody diarrhea, tenesmus |
| Key complications | Fistula, stricture, abscess, B12 deficiency | Toxic megacolon, perforation |
| Smoking | Worsens | Protective |
| Serology | ASCA+ | atypical p-ANCA+ |
| Surgery | Not curative (recurs at anastomosis) | Colectomy is curative |
Vignette: A 24-year-old woman has 4 months of crampy right-lower-quadrant pain and non-bloody diarrhea with a 9-kg weight loss. Exam shows perianal skin tags/fistula and an oral aphthous ulcer. Labs: iron-deficiency anemia, low B12, ↑ CRP, ↑ fecal calprotectin. Ileocolonoscopy reveals cobblestoned mucosa and skip lesions in the terminal ileum; biopsy shows non-caseating granulomas.
Diagnosis: Crohn disease (terminal ileitis).
Next best step: MR (or CT) enterography to map small-bowel extent and detect fistula/stricture/abscess before therapy. Induce remission (ileocecal disease → oral budesonide; moderate–severe → corticosteroids ± anti-TNF), then maintain with an immunomodulator/biologic—not chronic steroids. Counsel smoking cessation.
Board trap: RLQ pain in a young patient mimics appendicitis; skip lesions + granulomas + perianal disease point to Crohn. Non-caseating granulomas distinguish it from caseating TB.
Vignette: A 28-year-old man with 2 years of ulcerative colitis presents with >10 bloody stools/day, fever 38.9°C, HR 120, and a distended, tender abdomen. Plain abdominal X-ray shows the transverse colon dilated to 7 cm.
Diagnosis: Toxic megacolon complicating acute severe UC (colonic dilation >6 cm + systemic toxicity).
Next best step (management bundle):
- NPO, IV fluids/electrolyte correction, consider NG decompression
- IV corticosteroids (+ broad-spectrum antibiotics if perforation/sepsis suspected)
- Stop opioids, anticholinergics, and antidiarrheals (they precipitate it)
- Test for C. difficile; obtain early surgical consult
- No improvement in 48–72 h → total colectomy
Avoid colonoscopy and barium enema (perforation risk). Severe UC without megacolon that fails IV steroids at day 3–5 → rescue infliximab or cyclosporine; refractory disease → colectomy (curative).
- Ileocolonoscopy with biopsy = gold standard for both; always exclude infection first (C. difficile, stool cultures/O&P)
- Crohn: skip lesions, cobblestoning, linear/aphthous ulcers, transmural inflammation, non-caseating granulomas (~30%, specific but not sensitive); creeping fat is a gross/enterographic finding
- UC: continuous friable mucosa from the rectum, pseudopolyps, crypt abscesses, crypt distortion; backwash ileitis possible in pancolitis
- Small-bowel Crohn: CT/MR enterography (best for fistula/stricture/abscess); barium string sign of Kantor
- UC barium: 'lead-pipe' colon (loss of haustra)
- Labs: ↑ ESR/CRP, anemia, hypoalbuminemia; fecal calprotectin/lactoferrin for activity; ASCA (CD) vs atypical p-ANCA (UC)
- Severe flare / toxic megacolon: colonoscopy and barium are contraindicated (perforation)
- UC, mild–moderate: 5-ASA (mesalamine) first line—topical/rectal for proctitis/left-sided, oral for extensive; oral+rectal combo improves remission
- UC, moderate–severe/refractory: anti-TNF (infliximab), vedolizumab, ustekinumab, or a JAK inhibitor (tofacitinib/upadacitinib); steroids only to induce, never to maintain
- Acute severe UC: hospitalize → IV steroids; day 3–5 nonresponse → rescue infliximab or cyclosporine; failure → colectomy (curative)
- Crohn: 5-ASA largely ineffective; ileocecal flare → budesonide; moderate–severe → steroids to induce, then immunomodulator (azathioprine/6-MP/MTX) ± biologic; top-down biologics for high-risk/fistulizing disease
- Crohn surgery treats obstruction, fistula, abscess, refractory disease but is NOT curative (recurs at anastomosis)—resect conservatively (short-gut risk)
- Perianal fistulizing Crohn: pelvic MRI + exam under anesthesia; anti-TNF ± seton; add metronidazole/cipro if abscess/infection
- Always: smoking cessation (Crohn), VTE prophylaxis during flares, vaccinate before immunosuppression
- Crohn: enteroenteric/enterovesical/perianal fistulae, abscess, fibrotic strictures → obstruction; B12 deficiency (terminal ileum); bile-salt malabsorption → cholesterol gallstones; enteric hyperoxaluria → calcium-oxalate kidney stones; fat-soluble vitamin deficiency
- UC: toxic megacolon, fulminant colitis, perforation, massive hemorrhage
- Colorectal cancer: risk rises with duration (>8–10 yr), extent (pancolitis), and coexisting PSC; UC classically emphasized, but extensive colonic Crohn carries comparable risk
- Surveillance colonoscopy: begin ~8 years after diagnosis of extensive/left-sided colitis, then every 1–3 years with targeted + random biopsies
- PSC + IBD: start surveillance at PSC diagnosis and continue annually (highest CRC risk)
- IBD neoplasia is often flat and multifocal → chromoendoscopy; confirmed high-grade dysplasia → colectomy
- The C's of Crohn: Cobblestoning, Creeping fat, Cancer risk, and 'it Can be anywhere, mouth-to-anus'—with non-caseating granulomas
- UC = 'You See' the mucosa only (superficial, mucosa/submucosa) and it always starts low (rectum first, then continuous/proximal)
- Smoking: Crohn is worsened by it; UC is the ex-smoker's disease (protective)
- Serology: ASCA → Crohn; atypical p-ANCA → UC
- Imaging: String sign (Kantor) = Crohn; 'lead-pipe' colon = UC
- PSC pairs with UC (p-ANCA–positive; screen for cholangiocarcinoma + colorectal cancer)
- Toxic megacolon → think UC; stop anti-motility/opioid agents and avoid colonoscopy/barium
Reminder: caseating granulomas point to TB (and fungal infection), not Crohn. Crohn granulomas are non-caseating—a feature it shares with sarcoidosis, the classic non-caseating distractor.
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