Can Calprotectin Be Slightly Elevated in Post-Infectious IBS?
Yes, calprotectin can be slightly elevated in patients with post-infectious IBS, with approximately 33% showing low-level elevation (T1 positive, <15 μg/g), which is significantly more frequent than in non-post-infectious IBS patients (9.8%). 1
Understanding the Inflammatory Component
Post-infectious IBS represents a distinct subgroup where low-grade intestinal inflammation persists after an acute gastroenteritis episode. The key findings include:
Post-infectious IBS patients demonstrate higher rates of positive calprotectin tests compared to non-post-infectious IBS, though the elevations remain in the low range (T1: <15 μg/g) rather than the moderate (T2: 15-60 μg/g) or high ranges (T3: >60 μg/g) seen in inflammatory bowel disease 1
None of the IBS patients in controlled studies had calprotectin levels reaching T2 or T3 ranges, which helps distinguish functional disorders from true IBD 1
Among IBD patients in clinical remission who also meet Rome II criteria for IBS-like symptoms, calprotectin levels tend to be elevated, particularly in Crohn's disease patients, suggesting occult inflammation rather than pure functional symptoms 2
Clinical Interpretation Framework
The British Society of Gastroenterology provides clear thresholds for interpretation in primary care settings:
Calprotectin <100 μg/g suggests IBS is likely and patients can be managed in primary care without gastroenterology referral 3
Calprotectin 100-250 μg/g represents an intermediate zone requiring either repeat testing or routine gastroenterology referral based on clinical suspicion 3
Calprotectin >250 μg/g strongly suggests active inflammatory disease and warrants urgent gastroenterology referral 3
Practical Considerations for Post-Infectious IBS
When evaluating a patient with suspected post-infectious IBS:
Recent NSAID use (within 6 weeks) can falsely elevate calprotectin and should be excluded before interpretation 3, 4
In acute diarrhea settings, calprotectin will not discriminate between IBD and gastroenteritis, making stool culture and/or endoscopy the appropriate diagnostic investigations 4
The first morning stool should be used for sampling, stored no more than 3 days at room temperature before analysis to ensure accuracy 3
Distinguishing True IBD from Post-Infectious IBS
The diagnostic utility of calprotectin lies in its negative predictive value:
Calprotectin has 91.1% sensitivity and 86.7% specificity for differentiating IBD from IBS, with an area under the ROC curve of 0.959 5
Mean calprotectin levels in IBD patients (445.68±237.35 μg/g) are dramatically higher than in IBS patients (39.16±17.31 μg/g), providing clear separation between these conditions 5
Calprotectin correlates well with histological inflammation detected by colonoscopy and successfully predicts relapses in IBD patients 6
When to Pursue Further Investigation
Despite slight elevation in post-infectious IBS, certain clinical scenarios demand endoscopic evaluation:
Alarm features (rectal bleeding, abdominal pain with weight loss, iron-deficiency anemia) require cancer pathway referral regardless of calprotectin level, as calprotectin is not sensitive enough to exclude colorectal cancer 3, 7
Patients with moderate to severe symptoms and calprotectin >150 μg/g should undergo endoscopic assessment rather than empiric treatment, as this represents intermediate pretest probability for active inflammation 3, 8
Repeat calprotectin measurement after 2-3 weeks may be valuable, as 53% of patients with initially elevated levels (≥100 μg/g) show reduction on repeat testing 4
Clinical Bottom Line
Post-infectious IBS can present with mildly elevated calprotectin reflecting residual low-grade inflammation, but these elevations remain substantially lower than those seen in active IBD. The key is recognizing that **slight elevations (<100 μg/g) support the diagnosis of post-infectious IBS rather than contradicting it**, while levels consistently >150 μg/g should prompt consideration of alternative diagnoses including occult IBD 1, 2. This noninvasive marker helps distinguish patients requiring intensified follow-up from those who can be managed conservatively in primary care 2.