Delta Sem (6) - GIT Lecture (7) - IBD (1)

Crohn's Disease Definition

• Chronic inflammatory condition can affect any part of the GIT, but most frequently affects the terminal ileum

Crohn's Disease Epidemiology

• Slightly more common in females
• Peak onset is between 20-40 years old, with a second smaller peak in older adults

Crohn's Disease Aetiology & Pathogenesis

• Tissue inflammation is caused by an abnormal immune response against bacterial antigens in the lumen of the GIT
• Strong genetic component, with high concordance among monozygotic twins
• Diet and smoking play a role

Crohn's Disease Pathology

• Disease distribution is as follows:
  • 40% affects the terminal ileum and caecum
  • 20% affects the colon only, 30% affects the ileum and colon
  • 10% affects any part of the GIT, perianal disease, mouth, oesophagus and stomach
• Hallmark: focal intestinal inflammation
• Disease is discontinuous, causing skip lesions (unlike UC, which is continuous)
• Early lesions include aphthous ulcers
• Non-caseating granulomas are present in up to 70% of cases
• Inflammation is transmural, which leads to large ulcers, sinus tracks, fissures and fistulae
• Healing leads to extensive fibrosis, which leads to stricture formation

Crohn's Disease Symptoms

• Abdominal pain, diarrhea, weight loss, anorexia, and fever occur
• Growth retardation is common in children
• Anemia occurs in 30%, mainly due to iron deficiency, vitamin B12 deficiency in ileal disease or folate deficiency in proximal small bowel disease
• Small bowel obstruction can occur due to strictures
• Colonic Crohn's disease may present with bloody diarrhea
• Gastroduodenal Crohn's disease can present as Helicobacter-negative peptic ulcer disease

Crohn's Disease Behaviour

• Intestinal affection may be inflammatory, stricturing or penetrating

Crohn's Disease Extra-intestinal manifestations

• Arthropathy including sacroilitis particularly affects the large joints
• Association with ankylosing spondylitis in patients with HLA-B27
• Metabolic bone disease (osteopenia)
• Venous and arterial thromboembolic disease results from hospitalization, immobility, malnutrition, and increased platelet count and clotting factors
• Skin manifestations include pyoderma gangrenosum, and erythema nodosum
• Ocular manifestations appear as scleritis, episcleritis and anterior uveitis
• Gallstones
• Fatty liver, autoimmune hepatitis and primary sclerosing cholangitis can occur
• Renal oxalate stones appear

Crohn's Disease Laboratory Investigations

• CBC may show anemia, increased WBC and platelet count
• Serum iron, B12 and folate levels may be decreased
• LFTs: Low serum albumin and high CRP
• Calcium, magnesium and zinc levels may be low
• Stool tests: Stool culture and sensitivity, Clostridioides difficile toxin, to exclude infectious colitis
• Elevated fecal calprotectin or lactoferrin can differentiate between IBD and IBS
• Immunological markers: antibodies to Saccharomyces cervisiae (ASCA) can be found in up to 50% of cases, but found less often in Ulcerative Colitis
• p-ANCA is found in 70% of UC but only 15% of Crohn's patients

Crohn's Disease Imaging

• Colonoscopy is the gold standard for diagnosing colonic and terminal ileal disease and can take mucosal biopsies
• Video capsule endoscopy can visualize all parts of the GIT, detecting lesions not visible in other imaging
• Barium follow-through: was the standard method for evaluating the small bowel, showing a "string sign", but is largely replaced by US, CT, and MRI
• Small bowel US detects thickened terminal ileum walls, abscesses, and fistulae
• CT enterography is useful in evaluating small bowel disease
• MRI enterography is better than CT for detecting strictures

Crohn's Disease Treatment

• Corticosteroids can rapidly induce remission, but are not for long-term therapy
  • Budesonide is almost as effective as prednisolone, but with fewer side effects
• Azathioprine or methotrexate are widely used in patients with active CD who fail to taper steroids and require several weeks for action
• Aminosalicylates: Mesalazine treats colonic disease
• Anti-TNF α antibodies:
  • Infliximab IV infusions
  • Adalimumab SC
• Anti-integrin therapy: Vedolizumab
• Anti-IL-12/IL-23 therapy: Ustekinumab is approved
• Other novel oral therapies: Tofacitinib selective JAK inhibitors given orally
• Antibiotics:
  • Metronidazole heals perianal fistulae
  • Ciprofloxacin is also used in treating complications with good effect
• Nutritional therapy helps to correct nutritional deficiencies
  • Elemental diets induce remission
• Surgery is indicated in:
  • Intra-abdominal masses
  • Fistulae
  • Fibrotic strictures with obstruction
  • Toxic megacolon
  • Hemorrhage
  • Cancer

Comparison of Crohn's Disease versus Ulcerative Colitis

• Site of origin:
  • Crohn's Disease: Terminal ileum
  • Ulcerative Colitis: Rectum
• Pattern of progression:
  • Crohn's Disease: "Skip" lesions/irregular
  • Ulcerative Colitis: Proximally contiguous
• Thickness of inflammation:
  • Crohn's Disease: Transmural
  • Ulcerative Colitis: Submucosa or mucosa
• Symptoms:
  • Crohn's Disease: Crampy abdominal pain
  • Ulcerative Colitis: Bloody diarrhea
• Complications:
  • Crohn's Disease: Fistulas, abscess, obstruction
  • Ulcerative Colitis: Hemorrhage, toxic megacolon
• Radiographic findings:
  • Crohn's Disease: String sign on barium X-ray
  • Ulcerative Colitis: Lead pipe colon on barium X-ray
• Risk of Colon Cancer:
  • Crohn's Disease: Slight increase
  • Ulcerative Colitis: Marked increase
• Surgery
  • Crohn's Disease: For complications such as stricture
  • Ulcerative Colitis: Curative