What are the next steps for a patient with elevated fecal calprotectin levels, indicating gastrointestinal inflammation?

From the Guidelines

A fecal calprotectin level of 100 μg/g indicates mild intestinal inflammation that warrants further investigation, and the next steps should include a referral to a gastroenterologist for evaluation, as this level falls in a gray zone that could represent either inflammatory bowel disease (IBD) or other conditions. The gastroenterologist will likely recommend colonoscopy with biopsies to directly visualize the intestinal mucosa and obtain tissue samples for definitive diagnosis, as suggested by the AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis 1. While awaiting specialist consultation, symptomatic treatment may include loperamide 2mg as needed for diarrhea (maximum 8mg daily) and acetaminophen for pain (up to 3000mg daily in divided doses). Dietary modifications such as avoiding spicy foods, caffeine, and alcohol may help reduce symptoms. It's essential to note that fecal calprotectin is a marker of neutrophil migration into the intestinal mucosa, and levels between 50-150 μg/g represent a diagnostic uncertainty zone, as stated in the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults 1. The patient should be monitored for worsening symptoms such as persistent diarrhea, blood in stool, weight loss, or abdominal pain, which would warrant more urgent evaluation. Repeat testing in 4-6 weeks may be helpful if symptoms are mild and stable to assess trend.

Some key points to consider:

• Fecal calprotectin is a useful surrogate marker of inflammatory activity in IBD, as stated in the British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults 1.
• A calprotectin cut-off of 50 μg/g had the best sensitivity (90.6%) to detect endoscopically active disease, with specificity performing best (78.2%) at levels >100 μg/g, as reported in a recent meta-analysis 1.
• The AGA suggests using fecal calprotectin >150 mg/g, elevated fecal lactoferrin, or elevated CRP to rule in active inflammation and inform treatment adjustment and avoid routine endoscopic assessment of disease activity in patients with symptomatically active UC, as stated in the AGA clinical practice guideline on the role of biomarkers for the management of ulcerative colitis 1.
• In patients with CD with mild symptoms and elevated biomarkers of inflammation (fecal calprotectin >150 mg/g, CRP >5 mg/L), the AGA suggests endoscopic assessment of disease activity rather than empiric treatment adjustment, as recommended in the AGA clinical practice guideline on the role of biomarkers for the management of Crohn's disease 1.

From the Research

Fecal Calprotectin Results and Next Steps

• A fecal calprotectin level of 100 µg/g indicates a possible inflammation, and further testing may be required to confirm the presence of inflammation 2.
• According to the guidelines, when fecal calprotectin levels are between 100 µg/g to 250 µg/g, inflammation is possible, and further testing, such as colonoscopy, is required to confirm inflammation 2.
• Fecal calprotectin is a useful surrogate marker of gastrointestinal inflammation and can be used to distinguish between inflammatory bowel disease (IBD) and non-organic disease in symptomatic patients 3, 4, 5.
• Elevated fecal calprotectin levels in patients in clinical remission are associated with an increased risk of disease relapse within 12 months of follow-up 3.
• The measurement of fecal calprotectin can be used to monitor intestinal inflammation and evaluate therapeutic responses, providing evidence of relapse or mucosal healing 4, 5.

Considerations for Interpretation

• Fecal calprotectin levels can be affected by various factors, including age, medication, and day-to-day variation 4.
• Laboratories should be mindful of the characteristics of their own assay and factors that may affect results 4.
• Interpretation of fecal calprotectin concentrations must always take into account the clinical history and symptoms specific to each patient 5.

Management Strategies

• When fecal calprotectin levels are <50 µg/g to 100 µg/g, quiescent disease is likely, and therapy should be continued 2.
• When fecal calprotectin levels are >250 µg/g, active inflammation is likely, and strategies to control inflammation should be initiated 2.
• Fecal calprotectin can be a useful tool to assist in the management of patients with IBD, providing evidence of relapse or mucosal healing to enable therapy to be intensified or reduced 3, 4, 2.