Inflammatory Bowel Disease
Crohn disease (transmural, skip lesions, any GI segment) vs Ulcerative Colitis (mucosal, continuous, colon only). Distinguish from infectious colitis. Biologics have transformed management.
🔍 Overview
Crohn Disease vs Ulcerative Colitis
| Feature | Crohn Disease | Ulcerative Colitis |
|---|---|---|
| Location | Mouth to anus (terminal ileum most common) | Colon only -rectum always involved, extends proximally |
| Depth | Transmural → fistulas, strictures, abscesses | Mucosa/submucosa only |
| Pattern | Skip lesions, cobblestoning | Continuous, no skip lesions |
| Histology | Non-caseating granulomas | Crypt abscesses, pseudopolyps |
| Bloody diarrhea | Less common | Hallmark symptom |
| Smoking | Worsens disease | Protective (but don't recommend!) |
| Surgery | Not curative -disease recurs | Total colectomy is curative |
Toxic megacolon (colon dilation > 6 cm + systemic toxicity) is a life-threatening complication of both CD and UC. Requires surgical consultation, broad-spectrum antibiotics, and possible colectomy.
Severity Scoring, Truelove and Witts (UC)
| Parameter | Mild | Moderate | Severe |
|---|---|---|---|
| Bloody stools/day | < 4 | 4–6 | > 6 |
| Heart rate | Normal | ≤ 90 | > 90 |
| Temperature | Normal | ≤ 37.8°C | > 37.8°C |
| Hemoglobin | Normal | ≥ 10.5 g/dL | < 10.5 g/dL |
| ESR | ≤ 20 | 20–30 | > 30 |
Clinical Pearl: Truelove and Witts criteria are used at the bedside to determine if a UC flare requires IV steroids (severe) vs outpatient management (mild). A patient meeting severe criteria needs admission for IV methylprednisolone and GI consultation.
Crohn Disease Activity Index (CDAI), Concept
The CDAI is a composite score (0–600+) incorporating stool frequency, abdominal pain severity, general well-being, extraintestinal features, anti-diarrheal use, abdominal mass, hematocrit, and body weight. CDAI < 150 = remission; 150–220 = mild; 220–450 = moderate; > 450 = severe. Primarily used in clinical trials. At the bedside, use clinical judgment: stool frequency, CRP, nutritional status, and presence of complications (fistula, abscess) guide management decisions.
Mnemonic, B Symptoms of IBD Flare Requiring Admission
"FAST", Fever, Anemia, Six+ stools/day, Tachycardia. Any patient meeting these criteria should be admitted for IV steroids and GI consultation. Always rule out C. diff and CMV colitis before escalating immunosuppression.
🚨 Management
Step-Up Therapy
| Severity | UC Treatment | Crohn Treatment |
|---|---|---|
| Mild | Mesalamine (Asacol/Lialda) PO/PR | Mesalamine (limited evidence) or budesonide |
| Moderate | Oral steroids → thiopurines or biologics | Budesonide (Entocort) → thiopurines or biologics |
| Severe | IV steroids → Infliximab (Remicade) or cyclosporine | IV steroids → anti-TNF or vedolizumab |
| Perianal/Fistulizing | N/A | Anti-TNF (infliximab preferred) + antibiotics + surgical drainage |
Acute Severe UC Flare, Inpatient Management Algorithm
Acute Severe UC (Truelove-Witts severe): Admit → IV methylprednisolone 60 mg/day → assess response at Day 3. If no improvement (≥ 8 stools/day or 3–8 stools + CRP > 45): rescue therapy with infliximab or cyclosporine, or colectomy. Do NOT delay surgical consultation. Travis Criteria, 1996
- Day 0: Admit. Rule out C. diff (send toxin PCR), CMV colitis (if on immunosuppression, send CMV PCR). IV methylprednisolone 60 mg daily. DVT prophylaxis (UC flares are prothrombotic). NPO if toxic megacolon suspected.
- Day 1–3: Monitor stool frequency, CRP, abdominal exam. Flexible sigmoidoscopy (NOT full colonoscopy, perforation risk) to assess severity and rule out CMV.
- Day 3 assessment: Responding → transition to oral prednisone 40 mg, plan steroid taper + biologic initiation. NOT responding → infliximab 5 mg/kg (preferred) or IV cyclosporine 2 mg/kg/day. Surgical consultation for colectomy if refractory.
- Day 5–7: If rescue therapy failing → subtotal colectomy with end ileostomy is life-saving. Do not delay.
Biologics Comparison Table
| Drug | Mechanism | Approved For | Key Pearls |
|---|---|---|---|
| Infliximab (Remicade) | Anti-TNF-alpha (chimeric mAb) | UC + Crohn | Preferred for fistulizing Crohn + acute severe UC. IV infusion. ACT 1/ACT 2, 2005 |
| Adalimumab (Humira) | Anti-TNF-alpha (fully human mAb) | UC + Crohn | SC injection, convenient for outpatient. Less immunogenic than infliximab. CLASSIC I, 2006 |
| Vedolizumab (Entyvio) | Anti-α4β7 integrin (gut-selective) | UC + Crohn | Lower systemic infection risk, does NOT increase TB/opportunistic infection risk. Slower onset (8–14 weeks). Preferred if infection concerns. GEMINI 1, 2013 |
| Ustekinumab (Stelara) | Anti-IL-12/23 (p40 subunit) | Crohn (UC emerging) | IV induction → SC maintenance. Good safety profile. Consider after anti-TNF failure. UNITI-1/UNITI-2, 2016 |
| Tofacitinib (Xeljanz) | JAK inhibitor (small molecule) | UC only | Oral, no infusions. Rapid onset. Risk: VTE, herpes zoster. Avoid in patients with VTE risk factors. OCTAVE, 2017 |
Choosing a Biologic: Anti-TNF is first-line for most moderate-severe IBD and fistulizing Crohn. Vedolizumab preferred if TB/infection risk is high (gut-selective mechanism). Ustekinumab for anti-TNF failures. Tofacitinib is oral and fast-acting but limited to UC with VTE monitoring required.
Extraintestinal Manifestations
- MSK: Peripheral arthritis (follows disease activity), sacroiliitis/ankylosing spondylitis (independent)
- Skin: Erythema nodosum (follows activity), pyoderma gangrenosum (independent)
- Eyes: Uveitis, episcleritis
- Hepatobiliary: Primary sclerosing cholangitis (strong UC association)
🧪 Workup
- Colonoscopy with biopsies -gold standard for diagnosis
- CT enterography/MR enterography -small bowel involvement (Crohn)
- Stool studies -C. diff, cultures, O&P (rule out infectious mimics)
- CRP, ESR -inflammation markers
- Fecal calprotectin -non-invasive marker of intestinal inflammation
- CBC (anemia), albumin, iron studies
- pANCA (UC ~70%) vs ASCA (Crohn ~60%)
💊 Medications
| Drug | Dose | Class | Key Notes |
|---|---|---|---|
| Mesalamine (Asacol) | 2.4–4.8 g/day PO | 5-ASA | UC first-line mild disease. Minimal role in Crohn. |
| Budesonide (Entocort) | 9 mg daily × 8 wk taper | Steroid | Ileal/right colon Crohn. Less systemic effects than prednisone. |
| Azathioprine (Imuran) | 2–2.5 mg/kg/day | Thiopurine | Steroid-sparing. Check TPMT before starting. Risk: lymphoma, pancreatitis. |
| Infliximab (Remicade) | 5 mg/kg IV wk 0,2,6 then q8wk | Anti-TNF | Moderate-severe IBD. Screen for TB/Hep B before starting. |
| Vedolizumab (Entyvio) | 300 mg IV q8wk | Anti-integrin | Gut-selective. Lower infection risk than anti-TNF. |
| Ustekinumab (Stelara) | Induction IV → 90 mg SC q8wk | Anti-IL12/23 | Moderate-severe Crohn. Growing UC evidence. |
📋 On Rounds
Pimp Questions
How do you distinguish Crohn from UC on colonoscopy?
Crohn: Skip lesions (patchy inflammation), cobblestone mucosa, aphthous ulcers, deep linear ulcers, strictures. Can involve terminal ileum. Histology: non-caseating granulomas (found in ~30%). UC: Continuous inflammation starting at rectum extending proximally, loss of vascular pattern, pseudopolyps, friability. Histology: crypt abscesses, crypt architectural distortion.
What must you screen for before starting anti-TNF therapy?
(1) Tuberculosis -QuantiFERON Gold or PPD (anti-TNF reactivates latent TB). (2) Hepatitis B -HBsAg, anti-HBc, anti-HBs (risk of fulminant reactivation). (3) Hepatitis C. (4) Age-appropriate cancer screening. (5) Vaccination status (give live vaccines BEFORE starting, not after).
What is PSC and which IBD is it associated with?
Primary Sclerosing Cholangitis -progressive fibrosis and stricturing of intra/extrahepatic bile ducts. Strongly associated with UC (~70-80% of PSC patients have UC). Diagnosed by MRCP (beading of bile ducts). Increases risk of cholangiocarcinoma. UC + PSC patients have even higher colorectal cancer risk.
A UC patient on azathioprine presents with a flare. What infection must you rule out before escalating immunosuppression?
You must rule out C. difficile (send stool toxin PCR) and CMV colitis (send CMV PCR and request CMV immunohistochemistry on biopsy). Both mimic IBD flares and will worsen with increased immunosuppression. C. diff is extremely common in IBD patients (even without prior antibiotics). CMV colitis occurs in immunosuppressed patients and requires IV ganciclovir, not steroids. Always test before escalating therapy.
Why is vedolizumab considered safer than anti-TNF agents in terms of infection risk?
Vedolizumab targets the α4β7 integrin, which is selectively expressed on gut-homing lymphocytes. This blocks lymphocyte trafficking to the GI tract specifically, without systemic immunosuppression. Unlike anti-TNF agents, vedolizumab does not increase the risk of TB reactivation, opportunistic infections, or systemic infections. Preferred in patients with prior serious infections, latent TB concerns, or elderly patients.
What are the criteria for toxic megacolon and how do you manage it?
Toxic megacolon = radiographic colonic dilation > 6 cm (transverse colon) or cecum > 9 cm PLUS systemic toxicity (fever > 38.6, HR > 120, WBC > 10.5K, or altered mental status). Management: (1) NPO + NG decompression. (2) IV fluids + electrolyte correction. (3) IV broad-spectrum antibiotics. (4) IV methylprednisolone.
What is the role of TPMT testing before starting azathioprine?
TPMT (thiopurine methyltransferase) metabolizes azathioprine/6-MP. ~10% are heterozygous (intermediate activity) and 0.3% are homozygous deficient. Deficient patients accumulate toxic 6-thioguanine nucleotides causing severe myelosuppression. Check TPMT genotype/phenotype before the first dose. Homozygous deficient = absolute contraindication. Heterozygous = start at 50% dose with close CBC monitoring.
When should you consider surgery for Crohn disease?
Surgery in Crohn is not curative (recurs in ~50% within 5 years), reserved for complications: (1) Obstruction/stricture unresponsive to medical therapy. (2) Abscess not drainable percutaneously. (3) Fistula refractory to anti-TNF + surgical drainage. (4) Perforation. (5) Dysplasia/cancer on surveillance. Post-surgical prophylaxis with metronidazole or anti-TNF reduces recurrence. POCER, 2015
How does UC increase colorectal cancer risk and what is the surveillance strategy?
UC-associated CRC follows the inflammation-dysplasia-carcinoma sequence. Risk factors: duration > 8 years, pancolitis, concurrent PSC, family history, persistent inflammation. Surveillance: colonoscopy at 8 years after onset, then every 1-3 years with chromoendoscopy + random biopsies. PSC patients: annual colonoscopy from diagnosis. 5-ASA may be chemoprotective.
Clinical Examples
📋 Case 1, Acute Severe UC Flare
Patient: 34F with known UC (pancolitis, on mesalamine) presents with 3 days of worsening bloody diarrhea (10-12/day), cramping, fever 38.9°C, HR 112.
Labs: WBC 14.2, Hgb 9.8, CRP 62, albumin 2.4, K 3.1. C. diff PCR negative.
Assessment: Meets Truelove-Witts severe criteria. KUB: no toxic megacolon.
Management:
- Admit. IV methylprednisolone 60 mg/day. DVT prophylaxis. Correct K.
- Flexible sigmoidoscopy day 1-2 for severity + CMV biopsy.
- Day 3: 8+ stools/day, CRP 55 → Travis criteria met for steroid failure.
- Rescue therapy: infliximab 5 mg/kg. Surgical consultation placed.
- Responded by day 5. Oral prednisone taper + infliximab maintenance initiated.
Teaching Point: Day-3 reassessment with Travis criteria is critical. Delayed rescue therapy increases colectomy and mortality risk.
📋 Case 2, Crohn with Perianal Fistula
Patient: 26M with ileal Crohn (on azathioprine), 2 weeks of perianal pain, swelling, purulent drainage. 4-5 loose stools/day, 8 lb weight loss.
Exam: External fistula at 5 o'clock with purulent discharge. Fluctuant area = undrained abscess.
Imaging: MRI pelvis: complex perianal fistula + intersphincteric abscess (2.3 cm).
Management:
- Step 1: EUA with abscess I&D + seton placement.
- Step 2: Cipro 500 BID + metronidazole 500 TID (bridge to biologic).
- Step 3: Infliximab initiated (preferred for fistulizing Crohn). ACCENT II, 2004
- Azathioprine continued (combination reduces immunogenicity). Seton removed at 3 months.
Teaching Point: Always drain abscess BEFORE biologics. Combined medical-surgical approach is standard for fistulizing Crohn.
📋 Case 3, Toxic Megacolon
Patient: 58F with UC on IV steroids for 4 days. Overnight: abdominal distention, absent bowel sounds, fever 39.4°C, HR 128, BP 92/58, AMS.
Labs: WBC 22K, lactate 3.8, K 2.9, Hgb 7.4.
Imaging: KUB: transverse colon 8.5 cm. No free air.
Assessment: Toxic megacolon, dilation > 6 cm + systemic toxicity.
Management:
- NPO, NG tube, aggressive IVF, correct K. IV pip-tazo. Continue IV steroids.
- Avoid: opioids, anticholinergics, loperamide, colonoscopy.
- Emergent surgical consult. Serial abdominal exams + KUB q12h.
- No improvement 24h → subtotal colectomy with end ileostomy.
Teaching Point: Mortality 20-30% with perforation. Do NOT delay surgery. Intern role: serial exams, trend WBC/lactate, escalate immediately.
⚡ Summary
Crohn or UC
Crohn: transmural, skip lesions, anywhere from mouth to anus, with strictures, fistulas and perianal disease, and granulomas on biopsy. UC: mucosal only, continuous from the rectum proximally, colon only, with no fistulas. Smoking worsens Crohn but is protective in UC, which is one of the few clean epidemiologic dividers between them.
Exclude Infection Before Immunosuppressing
Always rule out C. difficile and CMV colitis before escalating immunosuppression in a flare. Both mimic and both are made dramatically worse by steroids and biologics. CMV in particular hides inside a steroid-refractory UC flare, so a patient who is not responding by day 3 needs the question asked again, with biopsies.
Grade the UC Flare at the Bedside
Truelove and Witts decides admission versus outpatient care. FAST: Fever, Anemia, Six or more stools a day, Tachycardia. Plus raised ESR or CRP and bloody stools. Meeting severe criteria means admit for IV steroids and GI consultation, not a prednisone prescription and a clinic follow-up.
Acute Severe UC Runs on a Day-3 Clock
Admit, give IV methylprednisolone 60 mg daily, and formally assess response on day 3. No improvement, defined as 8 or more stools a day, or 3 to 8 stools with CRP above 45, means rescue therapy now with infliximab or cyclosporine, or colectomy. Prolonging failed steroids is what turns a rescuable flare into an emergency colectomy, and the risk of perforation rises with every extra day.
Toxic Megacolon Is a Surgical Problem
Colonic dilation above 6 cm with systemic toxicity. Get surgery involved, give broad-spectrum antibiotics, stop antidiarrheals, anticholinergics and opioids, which all precipitate it, and be prepared for colectomy. Serial abdominal films and examinations, since the diagnosis is made by watching the trend.
Step-Up Therapy, With the Right Agent
Mesalamine works in UC and is largely ineffective in Crohn. Steroids induce remission but never maintain it, so a patient who cannot come off them needs a maintenance agent, not another course. Thiopurines and methotrexate for maintenance, checking TPMT before azathioprine. Biologics for moderate to severe disease, and increasingly early in high-risk Crohn rather than after everything else has failed.
Choosing a Biologic Is About the Patient, Not the Drug
Anti-TNF is first line for most moderate to severe disease and is the choice for fistulizing Crohn. Vedolizumab when infection or TB risk is high, because it is gut-selective and not systemically immunosuppressing. Ustekinumab after anti-TNF failure. Tofacitinib is oral and works fast in UC, with cardiovascular and thrombotic warnings. Screen for latent TB and hepatitis B before any anti-TNF.
Remember What Happens Outside the Gut
Extraintestinal manifestations that track bowel activity: peripheral arthritis, erythema nodosum, episcleritis. Those that do not: ankylosing spondylitis, primary sclerosing cholangitis, pyoderma gangrenosum, uveitis. PSC in particular is independent of colitis activity and raises colorectal cancer risk enough to need annual colonoscopy. Colorectal cancer surveillance starts 8 years after diagnosis in extensive colitis, and every patient needs bone health, vitamin D, iron and vaccination attention.
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