Crohn’s Disease

Epidemiology ₍₁₎

• Incidence: 1.3 to 5.3 per 100,000 individuals
• Bimodal age distribution: 1st peak: Ages 15-25, 2nd peak: Ages 50-80

Symptoms

• Diarrhea +/- blood
• Colicky abdominal pain
• Urgency, tenesmus (constant feeling of needing to pass stools despite emptiness)
• Systemic symptoms (fever, fatigue, weight loss)

Diagnosis

• Rule out other diseases
  • Amebiasis (travel history)
  • C. diff (prior antibiotic use, C. diff toxin screen)
  • Proctitis (sexual history)
  • Colonic ischemia (atherosclerotic disease, CTA),
  • Radiation/NSAID colitis (history)
  • CMV colitis (history of immunosuppression)
  • Salmonella/shigella/campylobacter/yersinia (routine stool cultures)
• Laboratory findings
  • Anemia
  • ESR, CRP elevations
  • Fecal calprotectin (+): This is a protein found largely in neutrophils, its presence in the stool is sensitive for Inflammatory Bowel Disease (but not Crohn’s Disease in particular). This test also lacks specificity. ₍₂₎
  • Low Iron, Vitamin D, or Vitamin B12 (due to poor absorption)
• Colonoscopy
  • Findings: “Cobblestone” appearance of the mucosa. Lesions may be discontinuous, or “skip”, instead of being continuous as they are seen in Ulcerative Colitis
• Biopsy
  • Transmural inflammation
  • Non-caseating granulomas in 13-36% of cases ₍₃₎

Management

• Mild-moderate Disease (Superficial ulcers, limited extent of disease)
  • Remission:
    • Budesonide (high first-pass metabolism in the liver limits systemic side effects)
    • PO glucocorticoids (alternatively, sulfasalazine)
      • Attempt to taper off. If unable, consider moving to management for moderate-severe disease
  • Maintenance:
    • If remission achieved by glucocorticoid, taper off, observe with repeat colonoscopy
    • If remission required treatment with below therapies, continue those as maintenance therapy
• Moderate-severe Disease (Deep ulcers, diffuse disease, perianal involvement)
  • TNF-α inhibitors (i.e. infliximab, adalimumab, and certolizumab)
    • Need tuberculosis and HBV screening prior to initiation of therapy
  • Immunomodulator [Thiopurines (i.e. azathioprine, or its metabolite, 6-mercaptopurine), or methotrexate]
    • Check Thiopurine Methyltransferase (TPMT) activity before initiating thiopurines. Decreased activity may lead to an increased risk of thiopurine-induced myelosuppression ₍₄₎
    • Attempt discontinuation within 1-2 years post-remission if colonoscopy confirms subsided inflammation. May continue TNF-α inhibitor
  • For remission/induction, may use either of the above options in isolation or in combination. May also use glucocorticoids initially as a bridge to these other therapies
• American Gastroenterological Association (AGA) recommends a screening colonoscopy at MAXIMUM 8 years after diagnosis. After that, next screening colonoscopy as early as 1-2 years later if the disease is diffuse or if the left colon is involved ₍₅₎

Complications

• Intestinal
  • Colon cancer associated with Crohn’s Disease with >1/3 colonic involvement
  • Bleeding/Anemia
  • Fistulas (Enteroenteric, enterovesicular, enterovaginal, enterocutaneous)
  • Abscess
  • Malabsorption -> Mineral and vitamin deficiencies (especially fat-soluble vitamins)
• Extraintestinal
  • Arthritis
  • Ankylosing Spondylitis
  • Erythema nodosum
  • Pyoderma gangrenosum (though much more frequently associated with Ulcerative Colitis)
  • Primary Sclerosing Cholangitis (though much more frequently associated with Ulcerative Colitis)
  • Uveitis

References

1. AL;, S. (n.d.). Epidemiology of Crohn’s Disease. Retrieved January 16, 2021, from https://pubmed.ncbi.nlm.nih.gov/3745850/
2. Pathirana, W., Chubb, S., Gillett, M., & Vasikaran, S. (2018, August). Faecal Calprotectin. Retrieved December 28, 2020, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370282/
3. Park JB;Yang SK;Myung SJ;Byeon JS;Lee YJ;Lee GH;Jung HY;Hong WS;Kim JH;Min YI;. (n.d.). [Clinical characteristics at diagnosis and course of Korean patients with Crohn’s disease]. Retrieved January 16, 2021, from https://pubmed.ncbi.nlm.nih.gov/14745246/
4. Nguyen, C., Mendes, M., & Ma, J. (2011, May 15). Thiopurine methyltransferase (TPMT) genotyping to predict myelosuppression risk. Retrieved January 16, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3094768/
5. Lee, J., & Lee, K. (2016, July). Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease. Retrieved January 16, 2021, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977735/#b15-ce-2016-090