Inflammatory Bowel Disease - IBD

Inflammatory bowel disease (IBD) represents a spectrum of chronic disorders affecting the gastrointestinal tract; Crohn disease (CD) and ulcerative colitis (UC) are the major disorders. When a definite diagnosis of CD or UC cannot be made following colectomy, the disease is referred to as indeterminate colitis (IC). The term inflammatory bowel disease unclassified (IBDU) can be used to reflect clinical and endoscopic evidence of IBD with no small bowel involvement, no histological evidence in favor of CD or UC, and no infection.

  • Diagnosis
  • Screening
  • Monitoring
  • Pharmacogenetics
  • Background
  • Pediatrics
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

Laboratory Testing

  • Nonspecific initial testing
    • CBC – microcytic anemia and thrombocytosis are most common abnormalities
    • C-reactive protein (CRP)
      • Preferred test to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) (Choosing Wisely: 20 Things Physicians and Patients Should Question, 2017; American Society for Clinical Pathology)
        • Elevated CRP differentiates IBD from IBS
        • Normal CRP does not rule out IBD
          • Low specificity for IBD
          • Sensitivity is variable and dependent on disease (ulcerative colitis [UC] versus Crohn disease [CD])
        • If CRP not available, order erythrocyte sedimentation rate (ESR)
    • Fecal lactoferrin
      • Released from polymorphonuclear leukocyte granules during active mucosal inflammation
      • Negative result does not rule out IBD
      • Positive result suggests infection or IBD
    • Albumin – may be decreased
    • Stool evaluation – rule out infectious etiologies
      • Clostridium difficile toxin B gene (tcdB) by polymerase chain reaction (PCR) – if risk factors are present
      • Parasitic analysis (PCR testing recommended) – only if appropriate history
        • Cryptosporidium hominis, C. parvum
        • Cyclospora cayetanensis
        • Dientamoeba fragilis
        • Entamoeba histolytica
        • Giardia lamblia/intestinalis/duodenalis
      • Stool culture – only if appropriate exposure history or risk factors
        • Vibrio
        • Yersinia
        • Campylobacter
    • Normal test results for CBC, albumin, or biomarkers should not prevent a full evaluation for IBD if clinical suspicion for disease is strong
  • Fecal calprotectin – marker of gut inflammation with good sensitivity (Langhorst, 2008)
    • May assist in differentiating IBD from functional disorders of the intestinal tract, such as IBS (Langhorst, 2008)
    • May avoid unnecessary endoscopies (van Rheenen, 2010)
    • Negative result and low pretest probability of disease may be sufficient to rule out a diagnosis of IBD (Yang, 2014)
    • Positive result warrants further testing to definitively diagnose IBD
    • Superior to CRP, ESR, anti-Saccharomyces cerevisiae antibodies (ASCA), and perinuclear atypical antineutrophilic cytoplasmic antibodies (ANCA) tests (von Roon, 2007; Henderson, 2012)
  • Serologic testing for specific antibodies
    • May be useful in supporting a diagnosis and classification of IBD, especially in indeterminate colitis
    • Marker testing cannot be used as the sole means of definitive diagnosis of IBD – lacks sensitivity, specificity (American College of Gastroenterology [ACG], 2009)
    • >20 serologic markers are currently identified for IBD, with variable diagnostic performance
    • Negative results do not rule out IBD – tests have low sensitivities for UD and CD
    • Classic markers that are widely available include the following
      • ASCA
        • ASCA IgG antibodies – found in 60-70% of CD and 10-15% of UC patients
        • ASCA IgA antibodies – found in 35% of CD and <1% of UC patients
        • Detection of ASCA IgG and IgA antibodies in the same serum specimen is highly specific for CD
      • ​ANCA
        • CD – 5-15%
        • UC – 60-80%
      • Antiglycan antibodies (Crohn diagnostic panel)
        • May be useful in predicting disease phenotype in confirmed CD patients
        • Panel consists of 4 glycan antibody tests
          • Saccharomyces cerevisiae antibody (ASCA) IgG
          • Laminaribioside carbohydrate antibody (ALCA), IgG
          • Mannobioside carbohydrate antibody (AMCA), IgG
          • Chitobioside carbohydrate antibody (ACCA), IgA
        • Presence of ≥2 markers has a specificity of  ≥95% for CD with a 1.7 elevated relative risk for abdominal surgery compared to seronegative patients with CD
    • Other markers – anti-I2 IgA, anti-flagellin (Cbir1)
    • No role for HLA-B27 testing in IBD – most useful in patients symptomatic for ankylosing spondylitis


  • Gold standard for diagnosis (ACG, 2010; European Consensus, 2012)
    • CD – presence of sarcoid-like granulomas, lymphoid hyperplasia, ileal inflammation
    • UC – cryptitis, crypt abscesses, mucin depletion, crypt atrophy, Paneth cell metaplasias

Imaging Studies

  • MRI or CT enterography/enteroclysis
  • Double-contrast barium enema – use only when endoscopy is unavailable
    • CD – ileum, terminal ileum, ileocecal valve, and cecum
    • UC – ileum is usually spared

Other Testing

  • Endoscopy – gold standard when combined with histology
    • Wireless capsule endoscopy for detecting lesions in small bowel
      • May be most helpful in patients with continued symptoms after surgery for UC


  • Use any available panel that includes ASCA, ALCA, AMCA, ACCA
  • Positive result for ≥2 markers is associated with poor prognosis in CD

Differential Diagnosis

  • Colorectal cancer (CRC) screening – highly recommended for patients with ulcerative colitis because of an increased risk for CRC
  • Fecal lactoferrin
    • Released from polymorphonuclear leukocyte granules during active mucosal inflammation
    • May be useful as a marker in inflammatory bowel disease (IBD) for monitoring disease severity
      • Correlates with disease activity
    • May be used for monitoring IBD activity and predicting relapse
      • Sensitivity and specificity higher in Crohn disease (CD)
  • Fecal calprotectin
    • Released from neutrophils during active inflammatory episodes
    • Concentration is proportionately related to degree of inflammation
      • Gastrointestinal bleeding does not proportionally increase calprotectin, but will increase values if >100 mL/day of bleeding
    • May be useful in monitoring disease severity and in predicting relapse (Stragier, 2013)
      • Better for ulcerative colitis (UC) than CD (Stragier, 2013)
  • C-reactive protein (CRP)
    • Decreased values correlate with improvement in disease (Stragier, 2013)
  • ​Infliximab and adalimumab activity and neutralizing antidrug antibody (ADA)
    • Infliximab and adalimumab are tumor necrosis factor (TNF)-α inhibitor drugs used for the treatment of patients with chronic inflammatory and autoimmune diseases, including CD and UC
    • Up to 50-60% of patients with CD treated with TNF antagonists experience treatment failures
    • Immunogenicity of TNF antagonist drugs and development of ADAs are major causes of secondary treatment failure (loss of clinical response during treatment after initial favorable response and improvement of clinical symptoms)
    • Increasing evidence, including clinical trials, support the favorable cost-benefit of laboratory test-guided management of patients with treatment failure
    • Monitoring serum levels of TNF-α antagonists and detecting neutralizing ADAs can be used to adjust treatment according to the patient’s individual needs
      • TNF-α activity and neutralizing antibody assays measure the ability of the drug to inhibit TNF-α function and detect the presence of function neutralizing ADAs, which are major contributors to treatment failure
  • Thiopurine drugs – may be used in treating inflammatory bowel disease
    • Thiopurine prodrugs are metabolized via thiopurine methyltransferase (TPMT) enzymatic activity
    • Deficiency of TPMT predicts hematopoietic toxicity after thiopurine treatment
    • Testing to determine activity level may be helpful in dosing thiopurine drugs and may help avert bone marrow suppression
      • For deficient activity, dose reduction of 80-90% may be required
      • For intermediate activity, dose reduction of 20-50% may be required
    • Genotype for the TPMT gene cannot be inferred from TPMT activity (phenotype)
    • TPMT phenotype testing does not replace need for clinical monitoring of patients treated with thiopurine drugs
      • Phenotype testing should not be requested for patients currently treated with thiopurine drugs; results will be falsely low
      • Current TPMT phenotype may not reflect future TPMT phenotype, particularly in patients who received blood transfusions within 30-60 days of testing


  • Incidence in U.S. (CDC, 2015)
    • CD – 3-15/100,000
    • UC – 2-14/100,000
  • Sex
    • CD – M<F
    • UC – M:F, equal
  • Ethnicity
    • Highest in Caucasians and Ashkenazi Jews
    • Lowest in African Americans, Asians, and Hispanics

Risk Factors

  • Increased risk
    • Medications (eg, NSAIDs)
    • Infections (eg, Salmonella typhi, Campylobacter jejuni)
  • Genetics
    • CD – first-degree relatives have 10- to 15-fold increased risk (Laass, 2014)


  • 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 (so-called “strip” lesions)
  • UC
    • Ulcers and inflammation in top layers of colon and rectal lining
    • Symmetrical
    • Uninterrupted inflammation from the rectum proximally

Clinical Presentation

  • CD – ileocolitis, abdominal pain, fever, diarrhea (less prominent than in UC)
  • UC – bloody diarrhea, rectal bleeding, abdominal pain
  • Extraintestinal manifestations – up to 35% of IBD cases
    • Dermatologic
      • Erythema nodosum
      • Pyoderma gangrenosum
      • Sweet syndrome – acute febrile neutrophilic dermatosis
    • Musculoskeletal
      • Arthritis – large joints, often asymmetric
      • Ankylosing spondylitis, sacroiliitis
    • Ophthalmologic
      • Uveitis/iritis
      • Episcleritis
      • Optic neuritis
    • Gastrointestinal
    • Genitourinary
  • Complications
    • CD – fistulas, abscesses
    • UC – massive hemorrhage, toxic megacolon, marked increase in incidence of colon cancer

Clinical Background


  • Prevalence – 10-25% of inflammatory bowel disease (IBD) cases diagnosed during childhood
    • Steady increase in incidence over past four decades
  • Sex
    • M>F (male predominance is less than in adult-onset disease)

Clinical Presentation

  • Childhood-onset disease typically has more severe phenotype characterized by extensive intestinal involvement with rapid, early progression
  • Most patients present before adolescence
    • <5 years – isolated colonic disease common
    • 6-17 years – small bowel disease and extensive disease more common
  • Crohn disease (CD) more common than ulcerative colitis (UC)
  • Often nonspecific initial presentation – anemia, fever, growth failure


Indications for Testing

Laboratory Testing

  • Nonspecific initial testing
    • C-reactive protein (CRP)
      • 25% of children with mild IBD have normal CRP
    • Refer to Diagnosis section
  • Fecal calprotectin
    • Sensitivity/specificity – higher in children
    • Refer to Diagnosis section
  • Serologic testing
    • Fewer studies in children
    • Refer to Diagnosis section


  • Refer to Diagnosis section

Other Testing

  •  Endoscopy – gold standard when combined with histology


  • Refer to Monitoring section
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.

Calprotectin, Fecal 0092303
Method: Quantitative Enzyme-Linked Immunosorbent Assay


Test is not specific or diagnostic for IBD

Presence of infections, inflammatory disorders, GI bleeding, and colorectal cancer may elevate levels of calprotectin

Does not differentiate ulcerative colitis (UC) from Crohn disease (CD)

Results may fluctuate as disease activity fluctuates; GI bleeding results in increased CALPRO

False negatives are more common in children and teenagers than adults

Lactoferrin, Fecal by ELISA 0061164
Method: Qualitative Enzyme-Linked Immunosorbent Assay


Positive results suggest the presence of the inflammatory bowel pathologies; however, other intestinal ailments, including GI infections and colorectal cancer, can result in elevated lactoferrin

Negative result does not exclude the presence of intestinal inflammation

Inflammatory Bowel Disease Differentiation Panel 2013270
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody

Crohn Disease Prognostic Panel 2001613
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay


Positive results may indicate an aggressive disease; however, negative results do not rule out aggressive disease

Thiopurine Methyltransferase, RBC 0092066
Method: Enzymatic/Quantitative Liquid Chromatography-Tandem Mass Spectrometry


Does not replace clinical monitoring

TPMT inhibitors may contribute to falsely low test results

TPMT activity should be assessed prior to treatment with thiopurine drugs

TPMT testing – blood transfusion within 30 days will reflect donor status

Thiopurine Methyltransferase (TPMT) Genotyping, 4 Variants 2012233
Method: Polymerase Chain Reaction/Fluorescence Monitoring


Only targeted TPMT allele variants will be detected by this panel

Diagnostic errors can occur due to rare sequence variations

Genotyping in patients who have received allogenic stem cell/bone marrow transplant will reflect donor status

Genotyping cannot distinguish the *1/*3A genotype from the *3B/*3C genotype

Thiopurine drug metabolism and risk for toxicity may be affected by genetic and nongenetic factors that are not evaluated by this test

Test does not assess for TPMT allele variants associated with ultra-high enzyme activity

Genotyping does not replace the need for therapeutic drug monitoring or clinical observation

Infliximab and Infliximab-dyyb Activity and Neutralizing Antibody 2008320
Method: Cell Culture/Quantitative Chemiluminescent Immunoassay/ Semi-Quantitative Chemiluminescent Immunoassay

Infliximab and Infliximab-dyyb with Reflex to Antibody 2013612
Method: Cell Culture/Quantitative Chemiluminescent Immunoassay/ Semi-Quantitative Chemiluminescent Immunoassay

Adalimumab Activity and Neutralizing Antibody 2011248
Method: Cell Culture/Quantitative Chemiluminescent Immunoassay/ Semi-Quantitative Chemiluminescent Immunoassay

Adalimumab Activity with Reflex to Antibody 2013605
Method: Cell Culture/Quantitative Chemiluminescent Immunoassay/ Semi-Quantitative Chemiluminescent Immunoassay


Choosing Wisely. An initiative of the ABIM Foundation. [Accessed: Nov 2017]

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Kornbluth A, Sachar DB, Practice Parameters Committee of the American College of Gastroenterology. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010; 105(3): 501-23; quiz 524. PubMed

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition, Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA. Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis Foundation of America. J Pediatr Gastroenterol Nutr. 2007; 44(5): 653-74. PubMed

General References

Beniwal P, Harrell L. The status of diagnostic markers for inflammatory bowel disease. Curr Gastroenterol Rep. 2010; 12(6): 479-84. PubMed

Bossuyt X. Serologic markers in inflammatory bowel disease. Clin Chem. 2006; 52(2): 171-81. PubMed

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Feuerstein JD, Cheifetz AS. Ulcerative colitis: epidemiology, diagnosis, and management. Mayo Clin Proc. 2014; 89(11): 1553-63. PubMed

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Henderson P, Casey A, Lawrence SJ, Kennedy NA, Kingstone K, Rogers P, Gillett PM, Wilson DC. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease. Am J Gastroenterol. 2012; 107(6): 941-9. PubMed

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Jones J, Loftus EV, Panaccione R, Chen L, Peterson S, McConnell J, Baudhuin L, Hanson K, Feagan BG, Harmsen SW, Zinsmeister AR, Helou E, Sandborn WJ. Relationships between disease activity and serum and fecal biomarkers in patients with Crohn's disease. Clin Gastroenterol Hepatol. 2008; 6(11): 1218-24. PubMed

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References from the ARUP Institute for Clinical and Experimental Pathology®

Jaskowski TD, Litwin CM, Hill HR. Analysis of serum antibodies in patients suspected of having inflammatory bowel disease. Clin Vaccine Immunol. 2006; 13(6): 655-60. PubMed

Lazar-Molnar E, Delgado JC. Immunogenicity Assessment of Tumor Necrosis Factor Antagonists in the Clinical Laboratory. Clin Chem. 2016; 62(9): 1186-98. PubMed

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Medical Reviewers

Last Update: December 2017