Crohn Disease

Detailed Overview

Crohn disease typically involves the terminal ileum and right colon, sparing the rectum (unlike Ulcerative Colitis). The transmural nature of the inflammation leads to strictures, fistulas, and abscesses. It follows a relapsing and remitting course. Treatment focuses on inducing and maintaining remission using immunosuppressants and biologics to prevent permanent bowel damage.

Epidemiology & Demographics

Incidence is highest in North America and Europe. Bimodal age distribution: peak onset between 15-30 years, and a second smaller peak at 60-70 years. Slightly more common in females.

Etiological Mechanism

Complex interplay of genetic susceptibility (NOD2 mutations), environmental triggers, and an exaggerated mucosal immune response to normal gut flora.

Primary Causes

Idiopathic autoimmune response.

• Smoking: The strongest modifiable risk factor. Smoking doubles the risk, exacerbates symptoms, and increases the need for surgery.
• Genetics: NOD2/CARD15 mutations on chromosome 16 impair gut innate immunity.

Defective gut barrier function allows luminal luminal bacteria to invade the lamina propria. Macrophages and dendritic cells mount a massive Th1/Th17 mediated immune response, releasing TNF-alpha and IFN-gamma. This results in transmural inflammation (all layers: mucosa, submucosa, muscularis, serosa). The deep ulcerations coalesce to form cobblestoning. Healing leads to collagen deposition and strictures (fibrosis). Transmural fissures can burrow through the gut wall, forming fistulas to adjacent organs or skin.

Characteristic Clinical Presentation

• Abdominal Pain: Typically crampy, non-radiating pain localized to the right lower quadrant (RLQ) due to terminal ileitis.
• Chronic Diarrhea: Prolonged, usually non-bloody diarrhea (unless the colon is heavily involved).
• Perianal Disease: Painful skin tags, fissures, and perianal abscesses/drainage.

Physical Examination Signs

• RLQ Mass
• Apthous Ulcers
• Erythema Nodosum

• Bowel Obstruction: Most common complication requiring surgery, caused by fibrotic strictures in the small bowel.
• Fistulas: Abnormal connections between organs; e.g., enterovesical fistula leading to pneumaturia (air in urine) and recurrent UTIs.

Diagnostic Criteria & Guidelines

Combination of clinical presentation, endoscopic findings of skip lesions/cobblestoning, and biopsy showing transmural inflammation with non-caseating granulomas.

Differential Diagnosis

• Ulcerative Colitis (continuous, rectum involved, mucosal only, bloody diarrhea)
• Appendicitis (acute RLQ pain)
• Intestinal Tuberculosis (also causes caseating granulomas in terminal ileum)

Laboratory Tests & Biomarkers

• Fecal Calprotectin: Significantly elevated (>200 mcg/g); highly sensitive marker for active gut inflammation.
• Anti-Saccharomyces cerevisiae antibodies (ASCA): Positive in 60% of Crohn patients (pANCA is usually negative, unlike UC).
• Vitamin B12: Decreased (<200 pg/mL) due to destruction of the terminal ileum where B12 is absorbed.

Imaging Modalities & Findings

• CT Enterography:
• Colonoscopy:

• Inflammatory
  Mucosal ulceration and edema causing diarrhea and pain.
• Fibrostenotic
  Chronic scarring leads to fixed bowel strictures and recurrent bowel obstruction.
• Fistulizing
  Transmural tracts connect bowel to skin (enterocutaneous), bladder (enterovesical), or vagina (enterovaginal).

Second-Line & Adjunctive Therapy

Immunomodulators like Azathioprine (2.0-2.5 mg/kg daily) or Methotrexate to maintain remission if biologics fail. Alternative biologics: Vedolizumab (anti-integrin) or Ustekinumab (anti-IL-12/23).

Surgical & Procedural Management

Unlike UC, surgery is NOT curative. Resection is reserved for complications (strictures, fistulas, abscesses, refractory bleeding). Ileocecectomy is the most common procedure. Strictureplasty preserves bowel length.

Recommended Lifestyle Changes

• Absolute smoking cessation.
• Enteral nutrition therapy or low-residue diet during acute flares.

Patient Counseling & Advice

Emphasize that surgery does not cure Crohn disease, as it often recurs at the anastomosis site. Medication adherence is critical to prevent short bowel syndrome from multiple surgeries.

Follow-Up & Monitoring Schedule

Fecal calprotectin every 6 months to check for subclinical inflammation. Colonoscopy 1 year after starting biologics to confirm mucosal healing. Surveillance colonoscopy for cancer starts 8 years after disease onset.

Preventive Strategies

No primary prevention. Avoid NSAIDs, which can trigger severe disease flares.

Chronic, lifelong disease. >70% will require at least one surgery in their lifetime. Life expectancy is slightly reduced compared to the general population.