What test should be ordered to assess gut inflammation in a patient with a history of Ankylosing Spondylitis, currently on Cimzia (certolizumab pegol), and previous significant gut inflammation, presenting with bloody stools, abdominal cramps, diarrhea, fatigue, and weight loss?

Testing for Gut Inflammation in a Patient with Ankylosing Spondylitis on Cimzia

Order a repeat fecal calprotectin test immediately, along with CRP, complete blood count, and stool cultures to exclude infection, then proceed to colonoscopy with biopsies given the alarm features and high pretest probability of active IBD. 1

Immediate Laboratory Testing

Priority Tests

• Fecal calprotectin is the most sensitive non-invasive marker for intestinal inflammation and should be repeated to confirm the previous elevation 1, 2
• C-reactive protein (CRP) with a cutoff of 5 mg/L to assess inflammatory activity 1, 2
• Complete blood count to detect anemia, leukocytosis, and thrombocytosis that accompany active disease 2
• Stool cultures and Clostridium difficile toxin testing are mandatory to exclude infectious causes, particularly given the patient is on immunosuppression 1, 2

Important Caveat About Calprotectin in This Population

• Patients with ankylosing spondylitis can have subclinical gut inflammation unrelated to IBD, which may cause false positive calprotectin elevations 1, 3
• Two elevated calprotectin measurements taken 15-20 days apart are needed to establish clinical relevance in patients with spondyloarthritis 1
• NSAIDs can falsely elevate calprotectin, though this patient's symptoms suggest true inflammation 1, 4

Interpretation of Results and Next Steps

If Calprotectin >250 μg/g and/or CRP >5 mg/L

• Proceed directly to colonoscopy with biopsies given the moderate to severe symptoms (bloody stools, weight loss, 4-month duration) which represent high pretest probability for active inflammation 1, 4
• The AGA guidelines specifically recommend endoscopic assessment rather than empiric treatment adjustment in patients with moderate to severe symptoms and elevated biomarkers 1
• Do not delay endoscopy based on biomarker results alone when alarm features are present (bloody stools, weight loss) 1, 4

If Calprotectin 100-250 μg/g

• This intermediate range still warrants colonoscopy given the alarm features of bloody stools and weight loss 1, 4
• The British Society of Gastroenterology recommends urgent gastroenterology referral for levels >250 μg/g, but alarm features override this threshold 1, 4

If Calprotectin <100 μg/g with Normal CRP

• This would be unusual given the symptoms, but if present, still proceed to endoscopy because bloody stools are an alarm feature requiring cancer pathway evaluation 1, 4
• Normal biomarkers do not exclude active IBD, particularly in ulcerative colitis where CRP may not elevate 1, 2

Why Endoscopy is Essential in This Case

The combination of bloody stools, weight loss, and 4-month symptom duration constitutes alarm features that mandate endoscopic evaluation regardless of biomarker results. 1, 4

• Fecal calprotectin is not sensitive enough to exclude colorectal cancer or advanced adenoma 1
• The patient has known previous gut inflammation, making IBD diagnosis more likely 1
• Diagnosis of IBD requires combination of clinical history, endoscopic findings, and histology—no single gold standard test exists 1, 2
• Distinguishing between Crohn's disease, ulcerative colitis, and unclassified IBD requires endoscopic and histological evaluation per ECCO criteria 1

Additional Considerations

Cimzia (Certolizumab Pegol) Context

• Certolizumab is approved for both ankylosing spondylitis and Crohn's disease, making it an appropriate choice if IBD is confirmed 1, 5
• However, the development of new GI symptoms on anti-TNF therapy requires investigation, as this could represent treatment failure, paradoxical inflammation, or infection 1

Supplementary Tests to Consider

• Serum albumin to assess nutritional status and inflammation severity 2
• Liver enzymes to evaluate hepatobiliary involvement 2
• Iron studies (ferritin, transferrin saturation) given likely iron deficiency anemia from chronic blood loss 2

Common Pitfall to Avoid

Do not rely solely on biomarkers to make treatment decisions in symptomatic patients with alarm features. 1 The AGA explicitly recommends against empiric treatment adjustment based on elevated biomarkers alone without endoscopic confirmation, and alarm features (bloody stools, weight loss) always require direct visualization regardless of biomarker levels. 1, 4