Inflammatory Bowel Disease - IBD

Diagnostic Algorithm

Clinical Background

Inflammatory bowel disease (IBD) represents a spectrum of chronic disorders affecting the gastrointestinal tract of which Crohn disease (CD) and ulcerative colitis (UC) are the major entities. In some cases referred to as indeterminate colitis (IC) if a definite diagnosis of CD or UC cannot be made following colectomy. Recently, inflammatory bowel disease, type unclassified (IBDU), was coined to reflect clinical and endoscopic evidence for IBD of the colon with no small bowel involvement, no histological evidence in favor of CD or UC and no infection.

Epidemiology

• Incidence
  • UC – 1/1000
  • CD – 0.8/1000
• Age
  • Initial peak – 15-30 years (most common peak)
  • Second peak – >60 years
• Sex
  • CD – M>F, 1.8:1
  • UC – M:F, equal
• Ethnicity – highest incidence in Jews, lowest in Blacks and Hispanics

Risk Factors

• Genetics
  • CD – first-degree relatives have 4-20 times increased risk   

Pathophysiology

• Inappropriate and persistent activation of the immune system against normal intestinal flora

  • CD

    • Typically involves ileum 
    • May affect any part of digestive tract
    • Extends deep into affected tissues
    • Asymmetrical and segmental with areas of both healthy and diseased tissue
  • UC
    • Ulcers and inflammation in top layers of lining of colon and rectum
    • Symmetrical
    • Uninterrupted from the rectum proximally

Clinical Presentation

• CD – ileocolitis, abdominal pain, fever
• UC – diarrhea, rectal bleeding, abdominal pain
• Extraintestinal manifestations (in up to 35% of patients with IBD)
  • Dermatologic
    • Erythema nodosum – 15% CD and 10% UC
    • Pyoderma gangrenosum – <1% CD and 5-10% UC
    • Sweet syndrome
  • Musculoskeletal
    • Arthritis – 10-15% of all IBD patients; large joints, often asymmetric
    • Ankylosing spondylitis – 10% of all IBD patients
  • Ophthalmologic
    • Uveitis/iritis – 10% of all IBD patients
    • Episcleritis
  • Gastrointestinal
    • Hepatic steatosis – 50% of all IBD patients
    • Primary sclerosing cholangitis (PSC) – 1-5% of all IBD patients; however, 50-75% of all PSC patients have IBD
    • Cholelithiasis
  • Genitourinary
    • Ureteral obstruction and fistulae – <5% of all patients
    • Nephrolithiasis – 10-20% CD
    • Metabolic bone disease
• Complications
  • CD – fistulas, abscesses
  • UC – massive hemorrhage, toxic megacolon, marked increased incidence of colon cancer

Treatment

• Early treatment may delay complications
• Goal of treatment is remission
• Colorectal cancer screening is highly recommended because of an increased risk of colon cancer in UC

Diagnosis

• Indications for testing – diarrhea, bloody stools
• Laboratory testing
  • Initial testing – sedimentation rate (ESR) or C-reactive protein (CRP), stool evaluation (ova and parasite stool culture, Clostridium difficile toxin assay) to rule out infectious etiology, CBC
    • Elevated ESR or CRP differentiates IBD from inflammatory bowel syndrome (IBS)
  • Serologic markers may be useful in supporting a diagnosis and classification of IBD, especially in indeterminate colitis; these markers are not recommended as standalone testing to diagnose IBD
    • More than 20 serologic markers with variable clinical utilities exist
    • The most studied serologic markers include:
      • ANCA – usually atypical pANCA staining
      • ASCA IgG and IgA antibodies
      • Subtypes differentiation as listed in the table below

        Patient Statistics for Inflammatory Bowel Disease Subtypes
        Test	Crohn Disease	Ulcerative Colitis
        Saccharomyces cerevisiae antibodies (ASCA) IgG, IgA	60-70%	10-15%
        Atypical pANCA IgG	5-15%	60-80%
        Omp IgA*	50%	<10% (Nikolaus 2007)
        *Omp IgA may detect ASCA seronegative CD patients with antibodies to other colonic microbial antigens. The presence and level of immune responses to microbial antigens have been associated with more aggressive disease phenotypes in children with CD.

• Histology
  • Presence of sarcoid-like granulomas suggests CD
• Endoscopy – gold standard when combined with histology
• Imaging studies
  • CT scan
  • Double-contrast barium enema – use only when endoscopy is not available

Differential Diagnosis

• Inflammatory bowel syndrome (IBS)
• Colorectal cancer
• Ischemic colitis
• Infectious diarrhea
• Celiac disease
• Diverticulitis
• Collagenous colitis
• Drug-induced enteropathy

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Inflammatory Bowel Disease Differentiation Profile 0050567 Method: Enzyme-Linked Immunosorbent Assay/Indirect Fluorescent Antibody
Lactoferrin, Fecal by ELISA 0061164 Method: Enzyme-Linked Immunosorbent Assay
Outer Membrane Protein (OMP) IgA 0051384 Method: Enzyme-Linked Immunosorbent Assay

Guidelines

General References

References from the ARUP Institute for Clinical and Experimental Pathology®