Inflammatory bowel diseases (IBD)

Summary

Inflammatory bowel disease (IBD) is a group of chronic, relapsing inflammatory disorders of the GI tract caused by an abnormal immune response to gut flora in genetically susceptible individuals.

• Two main subtypes: Crohn disease (CD) and ulcerative colitis (UC).
• Classic presentation: recurrent bloody diarrhea, abdominal pain, weight loss, and fever.
• Diagnosis is confirmed by endoscopy + biopsy.
• Treated with anti-inflammatory drugs (mesalamine, azathioprine, 6-MP, anti-TNF); flares treated with steroids.
• Surgery is curative in UC, but reserved for complications in CD.

Definition

• IBD = chronic, relapsing inflammation of the bowel due to an abnormal immune response to enteric flora.
• Subclassified into two main entities:
  • Crohn disease (CD) – any part of the GI tract (mouth to anus); transmural inflammation.
  • Ulcerative colitis (UC) – limited to colon/rectum; mucosal & submucosal only.
• Both are idiopathic, present with diarrhea, abdominal pain, weight loss, and bleeding.

Epidemiology

• Peak onset: adolescence and young adulthood.
• In pediatric IBD: ~4% present before age 5, ~18% before age 10.
• Sex differences:
  • Girls → more likely to develop Crohn disease.
  • Boys → more likely to develop ulcerative colitis.
• More common in Caucasians, especially Ashkenazi Jews.

Etiology and Risk Factors

The exact cause of IBD is unknown. It results from an interaction between genetics + environment + immune dysregulation in a susceptible host.

• Genetic susceptibility – NOD2/CARD15 mutations associated with CD; positive family history is the strongest risk factor.
• Environmental triggers:
  • Smoking (↑ CD, ↓ UC).
  • Hygiene hypothesis.
  • Enteric microorganisms / altered microbiome.
  • Diet, NSAIDs, stress.
• Immune response: abnormal T-cell activation against normal gut flora → chronic inflammation.

Crohn Disease vs Ulcerative Colitis

The two IBD subtypes share many features but differ in location, depth, and complications. Compare them side-by-side using the IBD subtype characteristics reference table.

Pathology

The hallmark histological and gross findings are the highest-yield distinguishing features.

Crohn Disease

• Transmural inflammation with noncaseating granulomas (pathognomonic).
• Knife-like fissuring ulcers extending through all bowel layers.
• Cobblestoning, creeping fat, serpiginous ulcers on gross specimen.
• Skip lesions — areas of normal mucosa between diseased segments.

Ulcerative Colitis

• Mucosal + submucosal inflammation only (does not penetrate deeper layers).
• Crypt abscesses (neutrophils within crypts) — characteristic finding.
• Pseudopolyps, friable mucosa, loss of haustra ("lead-pipe colon").
• Inflammation is continuous starting at the rectum and extending proximally.

Clinical Features

Shared Symptoms

• Chronic diarrhea, crampy abdominal pain.
• Weight loss, low-grade fever, fatigue.
• GI bleeding (more typical of UC).

Crohn Disease

• Insidious onset of abdominal pain (often RLQ), non-bloody diarrhea, weight loss.
• Palpable RLQ mass (transmural inflammation of terminal ileum).
• Perianal disease: skin tags, fissures, fistulas, abscesses.
• Oral ulcers (aphthous), malabsorption (B12, fat → steatorrhea).

Ulcerative Colitis

• Bloody diarrhea with mucus and tenesmus.
• LLQ pain, urgency, low-grade fever.
• No perianal/oral disease and no fistulas.

Extraintestinal Manifestations (both CD & UC)

• Eye: episcleritis, scleritis, uveitis.
• Skin: erythema nodosum, pyoderma gangrenosum.
• Joints: peripheral arthritis, ankylosing spondylitis, sacroiliitis.
• Liver: primary sclerosing cholangitis (PSC) — strongly linked to UC.
• Renal: calcium oxalate stones (enteric hyperoxaluria) — typical of CD.
• Biliary: cholesterol gallstones in CD (bile acid malabsorption).

Diagnosis

Initial Workup

• Labs: leukocytosis, iron-deficiency anemia, ↑ ESR/CRP, ↓ albumin.
• Stool studies: fecal calprotectin/lactoferrin (↑); exclude infection (C. difficile, ova/parasites).
• Antibodies (supportive, not diagnostic):
  • p-ANCA → ulcerative colitis.
  • ASCA (anti-Saccharomyces cerevisiae) → Crohn disease.

Confirmatory Test

• Endoscopy + biopsy is the gold standard.
  • Colonoscopy with ileoscopy for suspected CD.
  • Flexible sigmoidoscopy/colonoscopy for UC.

Imaging

• CT/MR enterography in CD: terminal ileum wall thickening, "string sign" (luminal narrowing), strictures, fistulas, abscesses.
• Avoid colonoscopy in acute severe colitis (risk of perforation/toxic megacolon) — use abdominal X-ray.

Differential Diagnosis

• Infectious gastroenteritis – acute, self-limited; stool cultures positive (Salmonella, Shigella, Campylobacter, Yersinia, E. coli O157:H7).
• C. difficile colitis – recent antibiotic use; toxin assay positive.
• Celiac disease (sprue) – chronic diarrhea, weight loss; anti-tTG IgG/IgA positive; duodenal biopsy shows villous atrophy.
• Diverticulitis – older patient, LLQ pain, fever; CT shows inflamed diverticula.
• Irritable bowel syndrome (IBS) – no weight loss, no bleeding, normal labs and endoscopy.
• Intestinal TB – mimics Crohn (ileocecal involvement); biopsy shows caseating granulomas.
• Ischemic colitis – elderly patient, "watershed" areas (splenic flexure), bloody diarrhea.

Treatment

The goals of therapy are to induce remission during a flare and then maintain remission long-term. Choice of agent depends on disease severity, location, and subtype (UC vs. CD).

Medical therapy

• Mesalamine (5-ASA) derivatives are the standard therapy — first-line for mild–moderate disease, especially ulcerative colitis. Includes mesalamine and sulfasalazine; given orally for extensive disease or as suppository/enema for distal UC.
• Acute exacerbations are treated with high-dose corticosteroids — oral prednisone for moderate flares, IV hydrocortisone or methylprednisolone for severe flares. Budesonide is preferred for ileal Crohn's (first-pass hepatic metabolism → fewer systemic effects). Never used for maintenance.
• Immunomodulators (azathioprine, 6-mercaptopurine, methotrexate) — steroid-sparing maintenance agents. Check TPMT activity before starting azathioprine to avoid life-threatening myelosuppression.
• Biologics for moderate–severe or refractory disease — anti-TNF (infliximab, adalimumab), anti-integrin (vedolizumab), anti-IL-12/23 (ustekinumab).
• Antibiotics (metronidazole, ciprofloxacin) — useful for perianal Crohn's and fistulizing disease.

Surgical therapy

• Surgery is curative in ulcerative colitis — total proctocolectomy removes the diseased organ entirely. Indicated for refractory disease, dysplasia/cancer, or toxic megacolon.
• Surgery in Crohn's disease is reserved for complications — fistulae, strictures, abscesses, obstruction, or perforation. Limited bowel-sparing resection only; disease inevitably recurs at the anastomosis, so surgery is not curative.

Complications

IBD complications fall into three buckets — those shared between Crohn and UC, those that are Crohn-specific (driven by transmural inflammation and terminal-ileum disease), and those that are UC-specific (driven by mucosal, continuous colonic inflammation).

Shared (CD and UC)

• Colorectal cancer — risk rises after ~8–10 years of colonic involvement. Risk factors: longer duration, greater extent of colitis, PSC, family history. Surveillance colonoscopy every 1–2 years with random biopsies; use the IBD colonoscopy surveillance guidelines.
• GI bleeding and anemia (iron deficiency from chronic blood loss; B12 deficiency in Crohn with ileal disease).
• Malnutrition and weight loss (especially in Crohn with extensive small-bowel disease).
• Bowel perforation (more common with severe colitis or toxic megacolon).
• Venous thromboembolism (VTE) — IBD is a hypercoagulable state during flares (DVT/PE risk ↑).

Crohn-specific complications

Driven by transmural inflammation that tunnels through all layers of the bowel wall, plus terminal ileum dysfunction.

• Fistulas — abnormal tracts between bowel and adjacent structures from transmural inflammation:
  • Enterocutaneous (bowel contents draining to skin)
  • Enteroenteric (bowel-to-bowel)
  • Enterovesical (recurrent UTIs, pneumaturia, fecaluria)
  • Rectovaginal (stool from vagina)
  • Perianal — see the perianal/anorectal fistula reference.
• Strictures → small bowel obstruction (SBO): crampy abdominal pain, vomiting, obstipation, dilated loops with air–fluid levels.

  

  Link to the full SBO reference table for workup and management.
• Abscesses — intra-abdominal or perianal pus collections; drain + antibiotics + treat underlying disease.
• Terminal ileum disease/resection consequences:
  • Cholesterol gallstones (↓ bile acid pool → cholesterol-supersaturated bile).
  • Calcium-oxalate kidney stones (fat malabsorption → calcium binds fat → free oxalate absorbed → hyperoxaluria).
  • Vitamin B12 deficiency (terminal ileum is the only B12 absorption site) → macrocytic anemia, neuropathy.
  • Fat-soluble vitamin deficiencies (A, D, E, K) from bile-acid loss and steatorrhea.
• Perianal disease — skin tags, fissures, fistulas, abscesses. Very characteristic of Crohn.

UC-specific complications

Driven by continuous mucosal inflammation of the colon.

• Toxic megacolon — surgical emergency; severe colitis paralyzes the colonic smooth muscle.

  

  Full workup/management in the toxic megacolon reference table.
• Primary sclerosing cholangitis (PSC) — chronic inflammation/fibrosis of intra- and extra-hepatic bile ducts.
  • MRCP: "beaded" bile ducts (alternating strictures and dilations).
  • Labs: ↑ alkaline phosphatase; p-ANCA positive.
  • Complications: recurrent cholangitis, cholangiocarcinoma, and a further ↑ in colorectal cancer risk. Open the PSC reference table for full features.
• Higher cumulative colorectal cancer risk than CD (entire colon continuously inflamed).
• Severe hemorrhage from diffuse mucosal ulceration.
• Perforation — usually in the context of toxic megacolon or severe fulminant colitis.

Mnemonics

Key Points for Exams

• Crohn ≠ Ulcerative colitis: transmural + skip + granuloma vs. continuous + mucosal + crypt abscess.
• Bloody diarrhea → think UC first.
• RLQ pain + perianal disease + fistula → think Crohn.
• p-ANCA = UC; ASCA = Crohn.
• Smoking: protects UC, worsens Crohn.
• Endoscopy + biopsy = gold standard diagnosis.
• Steroids for flares, never for maintenance.
• Anti-TNF (infliximab, adalimumab): screen for TB + HBV first.
• Total colectomy curative in UC; surgery in CD is for complications only.
• Colon cancer surveillance begins 8–10 years after diagnosis (colonic involvement).
• PSC + UC association is a classic exam pearl.
• Toxic megacolon = no colonoscopy; consider urgent colectomy.