What laboratory tests should be checked in a Crohn's disease (CD) workup?

Laboratory Tests for Crohn's Disease Workup

A comprehensive laboratory panel should be obtained at initial Crohn's disease workup, including complete blood count, inflammatory markers (CRP and ESR), comprehensive metabolic panel with liver enzymes, albumin, renal function, iron studies, vitamin B12, and fecal calprotectin, along with stool cultures and Clostridium difficile toxin testing to exclude infectious causes. 1

Essential Blood Tests

Complete Blood Count with Differential

• Hemoglobin and hematocrit to assess for anemia, which is common in Crohn's disease due to chronic inflammation, blood loss, or nutritional deficiencies 1, 2
• Leukocyte count to evaluate for leukocytosis, though this correlates poorly with disease activity 1, 3
• Platelet count to detect thrombocytosis, which often accompanies active inflammation 1

Inflammatory Markers

• C-reactive protein (CRP) is the preferred inflammatory marker as it is more sensitive than ESR and correlates better with endoscopic disease activity in Crohn's disease 1, 2, 4
• Erythrocyte sedimentation rate (ESR) provides complementary inflammatory assessment, though it is less sensitive than CRP 1, 2
• Important caveat: Approximately 20% of patients with active Crohn's disease may have normal CRP levels, so normal inflammatory markers do not exclude active disease 1

Metabolic and Nutritional Assessment

• Comprehensive metabolic panel including serum electrolytes to assess for imbalances from diarrhea or malabsorption 1, 2
• Liver enzymes (ALT, AST, alkaline phosphatase, bilirubin) to establish baseline and detect hepatobiliary complications or medication effects 1
• Serum albumin and pre-albumin to assess nutritional status and degree of inflammation 1, 2
• Renal function (creatinine, BUN) to establish baseline before initiating medications 1

Additional Nutritional Markers

• Iron studies (serum iron, ferritin, total iron-binding capacity) to evaluate for iron deficiency anemia 1, 2
• Vitamin B12 level as terminal ileal disease commonly causes B12 deficiency 1
• Folate level to assess nutritional status 4
• Vitamin D level to evaluate for deficiency, which is common in inflammatory bowel disease 4

Stool Studies

Fecal Biomarkers

• Fecal calprotectin is highly valuable for differentiating inflammatory bowel disease from irritable bowel syndrome, with pooled sensitivity of 93-95% and specificity of 91-96% for diagnosing IBD 1
• A cutoff of 100 μg/g provides greater diagnostic precision than 50 μg/g 1
• Fecal calprotectin correlates better with endoscopic inflammation than CRP or white blood cell count 2
• Fecal lactoferrin can also be assessed as an alternative marker of intestinal inflammation 1

Infectious Workup

• Stool cultures are mandatory to exclude bacterial pathogens such as Salmonella, Shigella, Campylobacter, and Yersinia 1, 2
• Clostridium difficile toxin testing is essential to rule out this infectious trigger, which can precipitate or mimic Crohn's disease flares 1, 2
• Blood cultures if systemic infection is suspected 1

Genetic Testing Considerations

Genetic testing should NOT be used for diagnosing Crohn's disease in routine clinical practice. 5

• NOD2/CARD15 testing lacks adequate sensitivity and specificity for diagnosis 5
• More than 250 IBD-associated genetic variants have been identified, but they do not allow diagnosis of IBD 5
• Limited exception: Genetic testing may be considered in very early onset inflammatory bowel disease, patients with family history suggesting Mendelian inheritance, or severe refractory disease 5
• Pharmacogenomic testing: TPMT (thiopurine methyltransferase) polymorphism testing is recommended before initiating azathioprine therapy 5

Clinical Context and Interpretation

At Initial Diagnosis

All four assessment modalities should be used where resources allow: symptom assessment, endoscopic evaluation, laboratory markers, and cross-sectional imaging to establish baseline values for future comparison 1

Key Pitfalls to Avoid

• Do not rely solely on inflammatory markers for diagnosis: Normal CRP and ESR can be observed in up to 28% of children with Crohn's disease at diagnosis 6
• Biomarkers alone are insufficient in mildly symptomatic patients: Neither normal nor elevated biomarkers accurately determine endoscopic activity in this setting 2
• Discordance between symptoms and biomarkers merits endoscopic evaluation for confirmation 2
• CRP correlates better with Crohn's disease than ulcerative colitis: This distinction is important when differentiating between the two conditions 1, 2

Diagnostic Accuracy Considerations

The combination of elevated CRP and fecal calprotectin provides the most reliable assessment of inflammatory activity 2. However, no single laboratory test serves as a gold standard for Crohn's disease diagnosis—the diagnosis requires a combination of clinical, biochemical, endoscopic, radiological, and histological investigations 1, 5.