What is the role of fecal calprotectin in a pediatric patient with a history of diarrhea and possible STEC-HUS (Shiga toxin-producing Escherichia coli-Hemolytic Uremic Syndrome)?

What is Fecal Calprotectin and Its Role in Pediatric STEC-HUS

Fecal calprotectin is a calcium- and zinc-binding protein released in large quantities by neutrophils during intestinal inflammation, but it has no established role in the diagnosis or management of STEC-HUS in pediatric patients. 1

Definition and Biological Basis

Fecal calprotectin is a protein derived from the cytoplasm of neutrophils that migrates into gastrointestinal tissue during inflammatory processes. 2, 3 It is extremely stable in feces, making it practical for laboratory measurement. 4 The protein has direct antimicrobial functions and plays a role in regulating the innate immune response. 3

Established Clinical Applications

Fecal calprotectin is primarily used to differentiate inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS) and to monitor disease activity in established IBD. 1

Diagnostic Thresholds in IBD

• Normal levels are defined as <50 μg/g stool 1
• Values >150 μg/g have 71% sensitivity and 69% specificity for detecting moderate to severe endoscopic inflammation in ulcerative colitis 1
• Values >250 μg/g improve specificity to 73% with 67% sensitivity 1
• The British Society of Gastroenterology recommends using thresholds between 100-250 μg/g to trigger colonoscopy, as this improves positive predictive value with minimal reduction in negative predictive value 1

Limited Role in Acute Infectious Diarrhea

The Infectious Diseases Society of America explicitly states there are insufficient data to make a recommendation on the value of fecal calprotectin measurement in people with acute infectious diarrhea. 1, 5

Why Calprotectin is Not Useful in Acute Infectious Diarrhea

• Calprotectin is elevated in both infectious gastroenteritis and IBD, making it unable to discriminate between these conditions 1
• Some studies suggest higher calprotectin levels may indicate bacterial etiologies of diarrhea, but other studies have found no diagnostic value 1
• The evidence is limited and conflicting 1

No Role in STEC-HUS Diagnosis or Management

For pediatric patients with suspected or confirmed STEC-HUS, fecal calprotectin measurement is not recommended and provides no clinical utility. 1

Appropriate Diagnostic Approach for STEC-HUS

Instead of calprotectin, the following tests are recommended:

• Frequent monitoring of hemoglobin, platelet counts, electrolytes, blood urea nitrogen, and creatinine to detect early manifestations of HUS (strong recommendation, high-quality evidence) 1
• Examination of peripheral blood smear for red blood cell fragmentation when HUS is suspected (strong recommendation, high-quality evidence) 1
• Stool culture and Shiga toxin testing to identify STEC 1
• Serologic tests may be considered for postdiarrheal HUS if stool culture did not yield a Shiga toxin-producing organism (weak recommendation, low-quality evidence) 1

Important Caveats About Calprotectin Testing

Factors That Elevate Calprotectin Without IBD

• NSAID use within the past 6 weeks significantly elevates calprotectin through direct mucosal injury 5, 6
• Colorectal neoplasia elevates calprotectin and must be excluded 6
• Untreated celiac disease causes intestinal inflammation that elevates calprotectin 6
• Local bleeding from hemorrhoids can cause false elevations 6

Technical Considerations

• Use the first stool passed in the morning for sampling 5
• Samples should be stored for no more than 3 days at room temperature before analysis 5, 6
• Different calprotectin assays are not interchangeable, and the same assay should be used for serial measurements in a given patient 1
• There is substantial within-stool and within-day variation in measurements 1

Clinical Context for Your Pediatric Patient

In a pediatric patient with diarrhea and possible STEC-HUS, focus diagnostic efforts on identifying STEC through stool culture and Shiga toxin testing, and monitor for HUS development through serial blood counts and renal function tests rather than measuring fecal calprotectin. 1 Calprotectin will likely be elevated due to the infectious colitis but provides no actionable information for diagnosis or management of STEC-HUS. 1