What is the appropriate work‑up and management for a patient with an elevated fecal calprotectin of 167 µg/g?

Management of Fecal Calprotectin 167 µg/g

A fecal calprotectin of 167 µg/g falls in the intermediate range (100–250 µg/g) and requires gastroenterology referral for colonoscopy, with urgency determined by symptom severity: urgent referral within 1–2 weeks for moderate-to-severe symptoms (rectal bleeding, significant abdominal pain, weight loss, frequent diarrhea), or routine referral within 2–4 weeks for mild or minimal symptoms. 1

Interpretation of This Calprotectin Level

• At 167 µg/g, this level indicates probable intestinal inflammation requiring further investigation, as values >150 µg/g have 71% sensitivity and 69% specificity for moderate-to-severe endoscopic disease. 2

• The false-positive rate varies dramatically by symptom severity: only 4.6% in patients with moderate-to-severe symptoms (meaning 95.4% truly have inflammation), 15.5% with mild symptoms, and 22.4% in asymptomatic patients. 1

• This level cannot reliably exclude inflammatory bowel disease even if symptoms are mild, as the false-negative rate at <150 µg/g is 8.5%. 3

Baseline Testing Before or Concurrent with Referral

Complete the following workup immediately:

• Complete blood count to assess for anemia (suggesting chronic blood loss) and thrombocytosis (indicating active inflammation). 1

• C-reactive protein (CRP) as a complementary inflammatory marker, though recognize that 20% of active Crohn's disease patients have normal CRP. 1

• Comprehensive metabolic panel to evaluate for dehydration and electrolyte abnormalities from diarrhea. 1

• Celiac serology (tissue transglutaminase antibodies) to exclude celiac disease as an alternative diagnosis. 1

• Stool culture including C. difficile testing to exclude infectious causes, as acute gastroenteritis can markedly elevate calprotectin. 1, 4

Critical Caveat: NSAID Use

• Recent NSAID use within the past 6 weeks can cause false-positive elevation of fecal calprotectin. 1, 4

• If the patient has used NSAIDs recently, repeat calprotectin testing after at least 6 weeks of NSAID cessation before proceeding to colonoscopy, unless alarm features are present. 1

Urgency of Gastroenterology Referral

Urgent Referral (1–2 weeks) if:

• Moderate-to-severe symptoms including rectal bleeding with abdominal pain, significant weight loss, frequent diarrhea (>4 bowel movements daily), or nocturnal symptoms. 1

• Any alarm features such as iron-deficiency anemia, palpable abdominal or rectal mass, unexplained anal ulceration, or change in bowel habit in patients >40 years old—these mandate suspected cancer pathway referral regardless of calprotectin level. 1

Routine Referral (2–4 weeks) if:

• Mild or minimal symptoms without alarm features. 1

• Consider repeat calprotectin testing in 2–3 weeks if symptoms are very mild and clinical suspicion for IBD is low, to differentiate persistent from transient elevation. 1

• If repeat testing normalizes to <100 µg/g and symptoms align with irritable bowel syndrome, manage as functional bowel disorder without colonoscopy. 1

Endoscopic Evaluation

When colonoscopy is performed:

• Complete ileocolonoscopy with terminal ileum intubation is required to assess full disease extent. 1

• Multiple biopsies from both inflamed and normal-appearing mucosa are essential to establish histologic diagnosis and differentiate Crohn's disease from ulcerative colitis. 1

• If Crohn's disease is suspected based on clinical features, consider cross-sectional imaging (MR or CT enterography) to evaluate small bowel involvement and complications such as strictures or fistulas. 1

Alternative Diagnoses to Consider

Elevated calprotectin is not specific for IBD and can occur in:

• Infectious gastroenteritis (hence the importance of stool cultures). 1, 5

• Colorectal cancer or advanced adenomas (though calprotectin is not sensitive enough to exclude malignancy). 1, 4

• Microscopic colitis (requires biopsies even from normal-appearing mucosa). 1

• Diverticular disease with inflammation. 6

• Local bleeding from hemorrhoids (can cause false elevation). 4

Post-Diagnosis Management Framework

If IBD is confirmed:

• Treatment intensity should match disease severity: calprotectin >250 µg/g typically requires immunomodulator or biologic therapy rather than aminosalicylates alone. 1

• Repeat calprotectin at 2–4 months after treatment initiation, targeting <150 µg/g as evidence of adequate therapeutic response. 1, 3

• Follow-up colonoscopy at 6–12 months to confirm mucosal healing, as calprotectin normalization correlates with but does not guarantee endoscopic remission. 1

• Serial calprotectin monitoring every 3–6 months in established IBD patients facilitates early detection of impending flares. 1

Common Pitfall to Avoid

Do not empirically adjust IBD treatment based on this calprotectin level without endoscopic confirmation of diagnosis in a treatment-naïve patient. 1 While patients with known IBD and moderate-to-severe symptoms can have treatment adjusted based on calprotectin >150 µg/g, establishing the initial diagnosis requires endoscopy with biopsies. 3