What labs should be checked for a Crohn's disease flare?

Laboratory Tests for Crohn's Disease Flare

When evaluating a suspected Crohn's disease flare, obtain a complete blood count, comprehensive metabolic panel (including liver enzymes, albumin, and renal function), iron studies, C-reactive protein, and fecal calprotectin, while simultaneously excluding infectious triggers with stool cultures and C. difficile toxin testing. 1, 2

Essential Laboratory Panel

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
• Erythrocyte sedimentation rate (ESR) provides complementary inflammatory assessment, though it is less sensitive than CRP 1, 2
• CRP >5 mg/L in symptomatic patients with moderate to severe symptoms suggests endoscopic activity, though approximately 20% of patients with active Crohn's disease may have normal CRP levels 3, 1

Complete Blood Count

• Complete blood count with differential is essential to assess for anemia (from chronic inflammation or blood loss), leukocytosis (indicating active inflammation), and thrombocytosis (a common finding in active disease) 3, 1, 2
• Hemoglobin, hematocrit, and platelet count correlate with disease activity and should be monitored 4

Nutritional and Metabolic Assessment

• Serum albumin and pre-albumin assess nutritional status and degree of inflammation, with hypoalbuminemia indicating active disease 3, 1, 2
• Comprehensive metabolic panel including electrolytes (to identify imbalances from diarrhea), liver enzymes (to evaluate hepatobiliary involvement and medication toxicity), and renal function (creatinine and urea) is mandatory 3, 1, 2
• Iron studies (serum iron, total iron-binding capacity, transferrin saturation, ferritin) are necessary to evaluate for iron deficiency anemia, which is common in Crohn's disease 3, 1, 2

Stool Studies (Critical to Exclude Infectious Triggers)

• Stool cultures are mandatory to exclude bacterial pathogens in all patients with suspected flares 1, 2
• C. difficile toxin testing is necessary in every suspected flare, as C. difficile infection can precipitate or mimic flares and is associated with higher mortality 1, 2
• Fecal calprotectin correlates better with endoscopic inflammation than CRP or white blood cell count and is the most sensitive non-invasive marker for intestinal inflammation 3, 1, 2, 5

Interpretation of Key Biomarkers

Fecal Calprotectin Thresholds

• Fecal calprotectin <150 mg/g effectively rules out active inflammation in asymptomatic patients, with a sensitivity of 81% and specificity of 72% 1
• Fecal calprotectin >250 mg/g suggests endoscopically active disease, though confirmation with endoscopy is recommended before treatment escalation 1
• Fecal calprotectin is increased in over 95% of patients with active IBD and reliably differentiates IBD from irritable bowel syndrome 5

Combined Biomarker Strategy

• The combination of elevated CRP and fecal calprotectin provides the most reliable assessment of inflammatory activity 1
• In symptomatic patients with moderate to severe symptoms, elevated fecal calprotectin or CRP suggests endoscopic activity 1
• In asymptomatic patients, fecal calprotectin <150 mg/g and normal CRP (<5 mg/L) reliably rule out active inflammation, avoiding unnecessary endoscopy 1

Critical Pitfalls and Caveats

When Biomarkers Are Insufficient

• Biomarkers alone are insufficient in mildly symptomatic patients—neither normal nor elevated biomarkers accurately determine endoscopic activity in this setting 1
• Discordance between symptoms and biomarkers merits endoscopic evaluation for confirmation 1
• Normal CRP does not exclude active Crohn's disease, as some patients may have endoscopically active disease without CRP elevation 3, 1, 2

Specificity Limitations

• Fecal calprotectin lacks specificity to distinguish IBD from other causes of inflammation including infections and medication effects 2
• Fecal calprotectin and lactoferrin may be normal in patients with clinically and endoscopically active Crohn's disease, particularly with isolated ileal disease 3

Monitoring Frequency During Flares

Perform the complete laboratory panel (CBC, liver profile, albumin, iron studies, renal function, CRP, fecal calprotectin) every 3-12 months as part of global disease assessment, with more frequent monitoring during active flares or when adjusting therapy 3, 1