What is Crohn's disease?

Crohn's Disease: Definition and Clinical Overview

Crohn's disease is a chronic inflammatory bowel disease characterized by transmural inflammation that can affect any part of the gastrointestinal tract from mouth to anus, causing significant morbidity, mortality, and impaired quality of life when not adequately controlled. 1

Disease Characteristics

Pathophysiology and Etiology

• Results from a complex interplay between:
  • Genetic susceptibility
  • Environmental factors
  • Altered gut microbiota
  • Dysregulated immune responses 1

Epidemiology

• Prevalence: Approximately 145-157 per 100,000 people in developed countries 1
• Up to one-third of patients are diagnosed before age 21 1
• Increasing incidence worldwide 1

Clinical Presentation

• Common symptoms:
  • Abdominal pain (often right lower quadrant)
  • Chronic diarrhea (may be bloody)
  • Weight loss
  • Fatigue
  • Fever (in some cases) 1
• Severe disease may present with:
  • ≥10 loose stools/day
  • Daily abdominal pain
  • Anorectal symptoms (pain, urgency, incontinence)
  • Significant impact on activities of daily living 1

Disease Classification

Montreal Classification

Crohn's disease is categorized into several phenotypes:

1. Inflammatory (non-stricturing, non-penetrating)
2. Stricturing (causing narrowing of the intestinal lumen)
3. Penetrating (forming fistulas)
4. Perianal disease 1

Anatomical Distribution

• Can affect the entire GI tract
• Most commonly affects terminal ileum and colon
• Upper GI involvement (esophagus, stomach, duodenum) occurs in 30-75% of patients 2
• Skip lesions (areas of inflammation with normal mucosa in between) are characteristic 3

Diagnosis

Diagnostic Approach

• Laboratory assessment:

  • Inflammatory markers: CRP, ESR, fecal calprotectin
  • Complete blood count (anemia common)
  • Liver function tests
  • Stool studies to rule out infection 4

• Endoscopy:

  • Ileocolonoscopy with biopsies is the gold standard
  • Reveals ulcerations, skip lesions, cobblestone appearance
  • Upper endoscopy may show specific findings:
    • Bamboo-joint-like appearance in gastric cardia
    • Notch-like appearance in duodenum 2

• Imaging:

  • MR enterography (MRE) is preferred first-line imaging for small bowel
  • Detects transmural inflammation and extraluminal complications
  • CT may be used in acute settings but has radiation exposure
  • Ultrasound useful in some settings 4

Disease Activity Assessment

• Combines symptoms, biomarkers, endoscopy, and imaging
• Crohn's Disease Activity Index (CDAI):
  • Remission: <150
  • Mild-moderate: 150-220
  • Moderate-severe: 220-450
  • Severe: >450 1
• Fecal calprotectin >150 mg/g indicates active inflammation 4

Complications

• Intestinal complications:

  • Strictures leading to obstruction
  • Fistulas (enterocutaneous, rectovaginal, perianal)
  • Abscesses
  • Perforation
  • Colorectal cancer risk

• Extraintestinal manifestations:

  • Arthritis/arthralgia
  • Skin manifestations (erythema nodosum, pyoderma gangrenosum)
  • Eye inflammation (uveitis, episcleritis)
  • Primary sclerosing cholangitis
  • Ankylosing spondylitis 3

Disease Course and Prognosis

• Chronic relapsing-remitting course
• Historically, 20% of patients hospitalized annually
• Surgery rates: 24% within 1 year, 36% by 5 years, 47% by 10 years
• Recent improvements in outcomes due to:
  • Earlier diagnosis
  • Increasing use of biologics
  • Treat-to-target approaches
  • Better endoscopic management 1

Treatment Approach

Treatment Goals

• Induce and maintain clinical remission
• Achieve mucosal healing
• Prevent complications (surgery, hospitalization)
• Improve quality of life 1

Medication Options

1. Conventional therapies:

   • Corticosteroids (for induction only)
   • Immunomodulators (thiopurines, methotrexate)
   • 5-ASA compounds (limited efficacy)

2. Biologic therapies:

   • Anti-TNF agents (infliximab, adalimumab, certolizumab)
   • Anti-integrin agents (vedolizumab)
   • Anti-IL-12/23 (ustekinumab) 1, 5, 6

Treatment Selection

• Based on disease severity, location, behavior, and prior treatments
• For moderate-severe disease:
  • Anti-TNF therapy often first-line biologic
  • Combination with immunomodulator may improve outcomes
  • Alternative biologics for primary non-response or loss of response 1

Surgical Management

• Required in many patients despite optimal medical therapy
• Not curative - recurrence common
• Indications: strictures, fistulas, abscesses, perforation, refractory disease 7

Monitoring

• Regular assessment of:
  • Clinical symptoms
  • Inflammatory markers (CRP, fecal calprotectin)
  • Endoscopic evaluation
  • Cross-sectional imaging when appropriate 1
• Treat-to-target approach with objective measures of inflammation 1

Common Pitfalls in Management

• Relying solely on symptoms for disease assessment (symptoms may not correlate with inflammation)
• Failing to rule out infections before escalating immunosuppression
• Overuse of CT scans in young patients (radiation exposure)
• Assuming normal CRP rules out active disease
• Premature use of opioids for pain management 4

Crohn's disease requires a comprehensive approach to diagnosis, monitoring, and treatment, with the goal of preventing disease progression and improving quality of life through tight control of inflammation.