3.3 Inflammatory Bowel Disease

Intestinal and colorectal disorders tested on the ABIM examination encompass inflammatory bowel disease, malabsorptive enteropathies, functional bowel disorders, diverticular disease, and evidence-based colorectal cancer screening.

1. Inflammatory Bowel Disease (IBD)

Crohn Disease vs. Ulcerative Colitis

Extraintestinal Manifestations (EIMs)

• Activity Parallels Luminal Bowel Inflammation:
  • Erythema Nodosum: Tender, red, subcutaneous nodules on pretibial surfaces (correlates with flare; resolves with IBD control).
  • Peripheral Arthritis (Type 1 Pauciarticular): Asymmetric, large joint involvement (<5 joints; resolves with IBD control).
  • Episcleritis: Scleral injection, burning, and irritation without vision loss.
  • Aphthous Stomatitis: Painful oral mucosal ulcers.
• Activity Independent of Luminal Bowel Inflammation:
  • Pyoderma Gangrenosum: Violaceous, undermined, necrotizing cutaneous ulcers with ragged borders (most common on shins). Critical clinical rule: Do NOT surgically debride due to pathergy (worsening of ulcer); treat with systemic corticosteroids or anti-TNF therapy (Infliximab).
  • Ankylosing Spondylitis & Sacroiliitis: Strongly associated with HLA-B27; causes chronic inflammatory lower back pain and morning stiffness; progresses independently of IBD.
  • Uveitis: Deep ocular pain, photophobia, headache, and blurred vision; requires immediate ophthalmology evaluation and topical/systemic steroids.
  • Primary Sclerosing Cholangitis (PSC): Autoimmune cholestatic destruction of intra/extrahepatic bile ducts; 70–80% of PSC patients have coexisting UC. Progresses independently of colectomy.
• Metabolic & Malabsorptive Complications (Predominantly Crohn Disease):
  • Nephrolithiasis (Calcium Oxalate Stones): Terminal ileal inflammation/resection impairs bile acid resorption, leading to unabsorbed luminal fatty acids that bind calcium. Free unchelated oxalate is hyperabsorbed in the colon, producing enteric hyperoxaluria and calcium oxalate kidney stones.
  • Gallstones (Cholesterol Stones): Interruption of the enterohepatic circulation of bile salts causes bile to become supersaturated with cholesterol.
  • Macrocytic Anemia: Vitamin B12 deficiency due to terminal ileal disease/resection.

Toxic Megacolon Crisis Management

Toxic Megacolon is a life-threatening, non-obstructive colonic dilatation (transverse colon diameter $>6\text{ cm}$ on abdominal radiograph/CT) accompanied by systemic toxicity.

• Jalan Diagnostic Criteria: Radiographic colonic dilation $>6\text{ cm}$ PLUS at least 3 of:
  1. Fever $>38.6^\circ\text{C}$ ($>101.5^\circ\text{F}$)
  2. Tachycardia $>120\text{ bpm}$
  3. Leukocytosis $>10,500/\mu\text{L}$ with left shift
  4. Anemia
  • PLUS at least 1 sign of systemic toxicity: Dehydration, altered mental status, electrolyte abnormalities, or hypotension.
• Emergency Management Protocol:
  1. Complete bowel rest (NPO) and Nasogastric (NG) tube decompression.
  2. Aggressive IV fluid resuscitation and correction of hypokalemia/hypomagnesemia (hypokalemia worsens colonic atony).
  3. Discontinue all antimotility agents (narcotics, anticholinergics, loperamide, diphenoxylate-atropine).
  4. Initiate IV Broad-Spectrum Antibiotics (e.g., Ceftriaxone + Metronidazole or Piperacillin-tazobactam) to prevent sepsis from bacterial translocation.
  5. Initiate High-Dose IV Corticosteroids (Methylprednisolone 60 mg IV daily or Hydrocortisone 100 mg IV q8h).
  6. Urgent Colorectal Surgery Consultation: If no clinical improvement within 24 to 72 hours, or if peritonitis, colonic perforation, or worsening necrosis develops, immediate Subtotal Colectomy with End Ileostomy is mandatory.

Medical Pharmacotherapy for IBD

Step-Up Approach: 5-ASA (UC) ➔ Corticosteroids (Induction Only) ➔ Immunomodulators / Biologics / Small Molecules (Maintenance)

1. 5-Aminosalicylates (5-ASAs):
   • Oral Mesalamine (2.4–4.8 g/day) and Topical Mesalamine (rectal suppository 1 g daily for proctitis; rectal enema 4 g daily for left-sided colitis). First-line for induction and maintenance of mild-to-moderate UC. (Minimal to no efficacy in Crohn disease).
   • Sulfasalazine: Requires supplemental Folic Acid (1 mg daily) due to inhibition of dihydrofolate reductase.
2. Corticosteroids:
   • Oral Prednisone (40–60 mg daily), IV Methylprednisolone (60 mg daily), or Oral Budesonide (9 mg daily; ileocecal-release for mild-to-moderate ileal/right-colon CD, or Budesonide MMX for UC). Budesonide has extensive first-pass hepatic metabolism (~90%), resulting in fewer systemic glucocorticoid side effects.
   • Core ABIM Rule: Corticosteroids are used for INDUCTION OF REMISSION ONLY. They must NEVER be used for maintenance therapy due to lack of mucosal healing and high risks of osteoporosis, avascular necrosis, cataracts, and opportunistic infections.
3. Immunomodulators (Thiopurines):
   • Azathioprine (2.0–2.5 mg/kg/day) and 6-Mercaptopurine (6-MP) (1.0–1.5 mg/kg/day).
   • Mandatory Pre-Treatment Testing: Measure Thiopurine Methyltransferase (TPMT) and NUDT15 enzymatic activity or genotype. Patients with homozygous deficiency accumulate cytotoxic 6-thioguanine nucleotides (6-TGN), causing fatal bone marrow aplasia and severe leukopenia.
   • Adverse effects: Pancreatitis (dose-independent), hepatotoxicity, myelosuppression, and increased long-term risk of non-Hodgkin lymphoma and non-melanoma skin cancer.
4. Biologics & Targeted Small Molecules:
   • Anti-TNF Agents: Infliximab (IV), Adalimumab (SQ), Golimumab (SQ), Certolizumab pegol (SQ). First-line for moderate-to-severe IBD.
   • Anti-Integrin: Vedolizumab (monoclonal antibody targeting $\alpha_4\beta_7$ integrin, blocking leukocyte homing selectively to the gut mucosa; gut-specific mechanism with lower risk of systemic immunosuppression/infections).
   • Anti-IL-12/23 & Anti-IL-23: Ustekinumab (targets p40 subunit of IL-12 and IL-23), Risankizumab, and Mirikizumab (targets p19 subunit of IL-23).
   • JAK Inhibitors (Oral): Tofacitinib, Upadacitinib (indicated for moderate-to-severe UC and CD; black box warnings for major adverse cardiovascular events [MACE], thrombosis, and serious infections; administer recombinant zoster vaccine prior to initiation).
   • S1P Receptor Modulator (Oral): Ozanimod (sphingosine-1-phosphate receptor modulator; requires baseline EKG to rule out conduction abnormalities and baseline ophthalmologic exam to rule out macular edema).
   • Mandatory Pre-Biologic Screening: All patients initiating anti-TNF or advanced biologic/small molecule therapies must be screened for Latent Tuberculosis (Interferon-Gamma Release Assay [IGRA] / T-Spot or TST + Chest Radiograph) and Hepatitis B (HBsAg, Anti-HBc total, Anti-HBs).

Colorectal Cancer Surveillance in IBD

• Initiation of Surveillance: Perform high-definition colonoscopy with chromoendoscopy (using methylene blue or indigo carmine dye spray with targeted biopsies) starting 8 years after the onset of symptoms in patients with pancolitis or left-sided colitis (disease extending proximal to the rectum).
• Special Exception for Concomitant PSC: In patients with coexisting Primary Sclerosing Cholangitis (PSC), surveillance colonoscopy must begin immediately at the time of PSC diagnosis, regardless of IBD disease duration.
• Surveillance Frequency: Repeat colonoscopy every 1 to 2 years thereafter.