What is the appropriate management for a 67-year-old systemically well patient with elevated faecal calprotectin, normal blood results, and a normal Faecal Immunochemical Test (FIT)?

Management of Markedly Elevated Faecal Calprotectin (1700 μg/g) in a Systemically Well 67-Year-Old Patient

This patient requires urgent colonoscopy with terminal ileum intubation to evaluate for inflammatory bowel disease (IBD), despite the normal FIT test, as a calprotectin level of 1700 μg/g indicates severe intestinal inflammation that demands endoscopic assessment and tissue diagnosis. 1

Rationale for Urgent Endoscopic Evaluation

• A calprotectin level >250 μg/g strongly suggests active inflammatory disease requiring immediate investigation, and this patient's level of 1700 μg/g is nearly 7-fold higher than this threshold, indicating severe intestinal inflammation 2, 1

• The normal FIT test does not exclude IBD or other significant organic pathology, as FIT is designed to detect colorectal cancer and has limited sensitivity for inflammatory conditions 2, 3

• In patients with calprotectin >150 μg/g and any symptoms (even mild), the false positive rate is only 4.6%, meaning 95.4% of such patients have true moderate-to-severe endoscopic inflammation 2, 1

• Age ≥50 years increases the likelihood of organic pathology, including IBD, colorectal neoplasia, and other inflammatory conditions that require endoscopic diagnosis 3, 4

Specific Pre-Endoscopy Workup

Before colonoscopy, obtain the following:

• Stool cultures and C. difficile testing to exclude infectious causes, as enteric infections can markedly elevate calprotectin 2, 1

• Complete blood count, CRP, ESR, and comprehensive metabolic panel to assess for systemic inflammation, anemia, and renal function 1

• Medication review: Document any NSAID, aspirin, or proton pump inhibitor use in the past 6 weeks, as these can elevate calprotectin (though rarely to this degree) 5, 4

• Coeliac serology if not previously performed, as this should be excluded in chronic diarrhea evaluation 2

Endoscopic Approach

• Complete colonoscopy with terminal ileum intubation is mandatory (not just flexible sigmoidoscopy) to assess full disease extent and differentiate between ulcerative colitis and Crohn's disease 1

• Obtain multiple biopsies from all colonic segments and terminal ileum, even from normal-appearing mucosa, as histology is essential for definitive diagnosis 1

• If Crohn's disease is suspected based on colonoscopy findings, arrange cross-sectional imaging (MR enterography or CT enterography) to evaluate small bowel involvement 1

Critical Clinical Considerations

Why FIT Negativity Doesn't Change Management

• FIT is optimized for detecting colorectal cancer (sensitivity 0.99 for cancer) but has poor sensitivity for inflammatory conditions 2

• Calprotectin is superior to FIT for detecting IBD and organic inflammatory pathology in symptomatic patients 3

• The combination of markedly elevated calprotectin (1700 μg/g) with normal FIT actually increases the likelihood of IBD rather than malignancy 3

Age-Related Factors

• Patients ≥50 years with elevated calprotectin have higher rates of organic pathology compared to younger patients, though the sensitivity for IBD remains high (93.8%) 3

• The positive predictive value of elevated calprotectin is lower in older adults (12.8% for IBD) due to higher rates of other conditions (diverticular disease, ischemic colitis, medication effects), but a level of 1700 μg/g far exceeds typical elevations from these causes 3, 4

Common Pitfalls to Avoid

• Do not repeat calprotectin testing or adopt a "watch and wait" approach with levels this high—this indicates active disease requiring immediate investigation 2, 1

• Do not assume the patient is "well" based on lack of systemic symptoms alone—IBD can present with isolated intestinal inflammation without fever, weight loss, or laboratory abnormalities 2, 1

• Do not delay endoscopy for empiric treatment trials—tissue diagnosis is essential before initiating immunosuppressive therapy 1

• Do not rely on the normal FIT to exclude significant pathology—calprotectin is the more relevant biomarker for inflammatory conditions 2, 3

Expected Diagnostic Outcomes

• At this calprotectin level, the likelihood of finding endoscopic inflammation approaches 95% 2, 1

• Possible diagnoses include: moderate-to-severe ulcerative colitis, Crohn's disease, microscopic colitis (though typically lower calprotectin), ischemic colitis, or less commonly, colorectal neoplasia with associated inflammation 2, 6

• If colonoscopy is entirely normal macroscopically, histology may still reveal microscopic inflammation, and consideration should be given to small bowel imaging or capsule endoscopy 1

Post-Endoscopy Management Framework

• If IBD is confirmed, treatment intensity should match disease severity, with calprotectin levels >250 μg/g typically requiring immunomodulator or biologic therapy rather than aminosalicylates alone 2, 1

• Repeat calprotectin at 2-4 months after treatment initiation to assess biochemical response, with target <150 μg/g indicating adequate treatment response 1

• Perform follow-up endoscopy at 6-12 months to confirm mucosal healing, as calprotectin normalization correlates with but does not guarantee endoscopic remission 2, 1