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Crohn Disease

Basics

  • Chronic, progressive inflammatory GI tract disorder; most common site terminal ileum (80%)
  • Hallmarks: transmural inflammation, fibrotic strictures, fistulas, fissures, abscesses, skip lesions, rectal sparing
  • Diverse presentations: ileitis, ileocolitis, isolated colitis

Epidemiology

  • Incidence: 3-20 per 100,000 person-years (North America), rising globally
  • Bimodal age: 15-30 years (peak), smaller second peak 50-80 years
  • Slight female predominance; increased incidence in northern climates
  • Prevalence: 247 per 100,000 persons

Etiology and Pathophysiology

  • Multifactorial: genetics, environment, microbial antigens, immune dysregulation causing inflammation and tissue injury
  • 15% have first-degree relative with IBD (3- to 30-fold increased risk)
  • Associated genetic syndromes: Turner, Hermansky-Pudlak, glycogen storage disease type 1b

Risk Factors

  • Cigarette smoking doubles risk; cessation reduces flares and relapses
  • Diet high in refined sugars, animal fat/protein, processed foods increases incidence

Commonly Associated Conditions

  • Extraintestinal manifestations:
  • Arthritis (20%), seronegative, may include ankylosing spondylitis, sacroiliitis (HLA-B27)
  • Skin disorders (10%): erythema nodosum, pyoderma gangrenosum, psoriasis
  • Ocular (5%): uveitis, iritis, episcleritis
  • Kidney stones, osteopenia, osteoporosis, hypocalcemia
  • Hypercoagulability: VTE prophylaxis essential during hospitalization
  • Gallstones, primary sclerosing cholangitis (5%)
  • Conditions linked to increased disease activity:
  • Peripheral arthropathy, episcleritis, oral aphthous ulcers, erythema nodosum
  • Complications:
  • GI bleed, toxic megacolon, bowel obstruction/perforation, peritonitis, malignancy
  • Intra-abdominal fistula, perianal disease

Diagnosis

History

  • Hallmarks: crampy abdominal pain ± bleeding, prolonged diarrhea, fatigue, weight loss, fever, perianal disease
  • Children: failure to thrive
  • Exacerbating factors: infection, smoking, NSAIDs, antibiotics, stress

Physical Exam

  • Signs of systemic inflammation/sepsis, malnutrition
  • Abdominal tenderness, distension, rebound, guarding, palpable mass
  • Perianal fistula, fissures, abscess
  • Skin: erythema nodosum, pyoderma gangrenosum, psoriasis

Differential Diagnosis

  • Acute abdomen: perforation, pancreatitis, appendicitis, diverticulitis, obstruction, stones, torsion
  • Chronic diarrhea with pain: UC, radiation colitis, infections, ischemia, microscopic colitis, celiac, malignancy
  • Wasting illness: malabsorption, malignancy

Diagnostic Tests and Interpretation

  • Labs: CBC, chemistries, LFTs, ESR, CRP, iron, B12, vitamin D, stool calprotectin
  • Stool studies: culture, C. difficile, ova/parasites if indicated
  • Imaging: KUB for toxic megacolon
  • Ileocolonoscopy with biopsy: highest sensitivity and specificity
  • Upper endoscopy if upper GI symptoms
  • Small bowel imaging: CT/MR enterography preferred over small bowel follow through; capsule endoscopy for small bowel visualization
  • Perianal disease: EUS or MRI pelvis, exam under anesthesia
  • Distinguishing CD vs UC:
  • CD: skip lesions, transmural, rectal sparing, granulomas, fistulas, RLQ pain, uncommon rectal bleeding
  • UC: continuous colonic involvement including rectum, LLQ pain, common rectal bleeding

Treatment

Disease Activity and Severity Assessment

  • Use Harvey Bradshaw Index or Crohn Disease Activity Index (CDAI)
  • Risk stratify for progressive disease: younger age, extensive disease, severe endoscopy, perianal disease, prior surgery, stricturing/penetrating behavior, EIMs

Mild to Moderate CD

  • Observation if asymptomatic and mild endoscopic disease
  • Steroids (budesonide, prednisone taper) for induction
  • No role for mesalamine or antibiotics
  • Maintenance: stop therapy or consider immunomodulator/biologic

Moderate to Severe CD

  • Induction: biologics preferred; short course steroids may be used for symptom relief
  • Maintenance: biologics ± immunomodulators
  • Immunomodulators: azathioprine, 6-MP (maintenance only), methotrexate (steroid-dependent)
  • Biologics:
  • Anti-TNF agents: infliximab, adalimumab, certolizumab pegol (induction and maintenance)
  • Gut-selective: vedolizumab
  • Anti-IL-12/23: ustekinumab
  • Anti-IL-23: risankizumab
  • JAK inhibitor: upadacitinib (post anti-TNF failure; monitor shingles risk)
  • Combination therapy reduces immunogenicity and improves efficacy

Additional Therapies

  • Oral lesions: topical corticosteroids or sucralfate
  • Gastroduodenal CD: PPIs, H2 blockers, sucralfate, anti-TNF therapy case reports

Surgery and Multidisciplinary Care

  • Collaboration between surgery, gastroenterology, nutrition, radiology, pathology

Admission/Inpatient

  • DVT prophylaxis essential

Ongoing Care

  • Monitor CBC, BMP, LFTs every 3-4 months
  • Monitor disease activity with CRP, calprotectin every 6 months
  • TPMT/NUDT15 genotyping before thiopurines; therapeutic drug monitoring for infliximab
  • Vaccinations: HPV, influenza, pneumococcal, meningococcal, hepatitis A/B, Tdap, varicella; avoid live vaccines on immunosuppressants
  • Shingles vaccine recommended for immunosuppressed ≥18 years
  • Colonoscopy with biopsies every 1-5 years after 8-10 years of colonic disease; annual in PSC patients
  • Annual pap smears and skin exams for immunocompromised
  • Bone health assessment and supplementation

Diet

  • Mediterranean diet recommended

Patient Education

  • CrohnsandColitisFoundation.org
  • IBDandMe.org

Clinical Pearls

  • Smoking doubles risk; cessation reduces flares and surgery
  • MRE preferred for luminal and extraluminal assessment without radiation
  • Test for TB and HBV before biologics
  • Screen for C. difficile in diarrhea
  • Hospitalized CD patients need DVT prophylaxis
  • Anti-TNF delays/prevents postoperative recurrence
  • Disease severity guides therapy more than activity

ICD10: - K50.0 Crohn’s disease of small intestine - K50.113 Crohn’s disease of large intestine with fistula - K50.011 Crohn’s disease of small intestine with rectal bleeding

Clinical Pearls: - Cigarette smoking doubles the risk of CD; cessation reduces flares and need for surgery. - MRE allows assessment of luminal and extraluminal disease without radiation exposure. - Assess TB and HBV prior to biologic therapy initiation. - Test for C. difficile infection when evaluating diarrhea in CD. - Hospitalized CD patients require DVT prophylaxis. - Anti-TNF therapy is effective in delaying or preventing postoperative recurrence. - Disease severity rather than disease activity should drive therapy decisions.