What is the role of stool calprotectin in assessing gastrointestinal involvement in children with Henoch-Schönlein Purpura (HSP)?

Fecal Calprotectin as a Diagnostic and Monitoring Tool for Gastrointestinal Involvement in Pediatric HSP

Fecal calprotectin is a highly useful non-invasive biomarker for identifying gastrointestinal involvement in children with Henoch-Schönlein Purpura (HSP), with a cut-off value of 69-264.5 μg/g (mg/kg) demonstrating excellent sensitivity (93.1%) and specificity (87.5%) for detecting GI manifestations. 1, 2

Diagnostic Performance and Cut-off Values

The optimal cut-off value for identifying GI involvement in pediatric HSP is 69.10 mg/kg, with children having fecal calprotectin >50 mg/kg showing significantly more frequent GI involvement (77.8% vs. 20.8%) and more severe GI symptoms. 1

• A higher cut-off of 264.5 μg/g provides 93.1% sensitivity and 87.5% specificity for early diagnosis of abdominal-type HSP, with diagnostic performance superior to traditional inflammatory markers like white blood cell count 2
• Fecal calprotectin levels are significantly elevated in the acute phase of HSP with GI involvement (median 379.9 ± 399.8 mg/kg) compared to HSP without GI involvement (77.4 ± 97.6 mg/kg) 1
• The sensitivity of fecal calprotectin exceeds that of C-reactive protein and WBC count for early detection of abdominal HSP 2

Clinical Utility for Severity Assessment

Fecal calprotectin levels correlate directly with the severity of GI symptoms, including abdominal pain duration, HSP clinical score, and abdominal pain severity. 1

• Children with fecal calprotectin >50 mg/kg demonstrate significantly longer abdominal pain duration and higher clinical severity scores 1
• Fecal calprotectin levels are significantly higher in patients with lower GI tract involvement (from terminal ileum) compared to upper GI tract involvement (581.8 ± 510.1 mg/kg vs. 214.67 ± 150.5 mg/kg), with a cut-off value of 277.5 mg/kg distinguishing lower tract involvement 1
• This anatomic distinction is clinically important because lower GI involvement may indicate more severe disease requiring closer monitoring for complications like intussusception or Meckel's diverticulum bleeding 3

Monitoring Treatment Response

Fecal calprotectin levels decrease progressively during treatment, with normalization typically occurring within 7 days of appropriate therapy, making it an excellent marker for monitoring disease activity. 2

• Median fecal calprotectin levels in the acute phase (3053 μg/g) and at 3 days post-treatment (2778.3 μg/g) are significantly elevated compared to controls (102.5 μg/g), but approach normal levels by day 7 of treatment 2
• Serial fecal calprotectin measurements can guide treatment decisions and identify patients requiring escalation to immunosuppressive therapy beyond corticosteroids 2

Comparison to Other Biomarkers

While D-dimer and fibrin degradation products (FDP) correlate with overall HSP disease activity, fecal calprotectin is specifically superior for detecting and monitoring GI tract involvement. 4

• D-dimer (r=0.371) and FDP (r=0.369) show stronger correlation with total clinical scores than inflammatory markers like WBC count (r=0.241) or CRP (r=0.260) 4
• However, fecal calprotectin provides direct assessment of intestinal inflammation rather than systemic coagulation activation 1, 2
• Patients with GI symptoms have significantly elevated ANC, CRP, D-dimer, and FDP levels, but fecal calprotectin offers the most specific assessment of mucosal inflammation 4

Practical Implementation Algorithm

For children presenting with HSP, measure fecal calprotectin at initial presentation to stratify risk for GI complications:

1. Fecal calprotectin <50 mg/kg: Low risk for significant GI involvement; manage with symptomatic care and close observation 1

2. Fecal calprotectin 50-264.5 mg/kg: Moderate risk; initiate corticosteroids and monitor closely for development of severe GI symptoms (intense pain, bleeding, protein-losing enteropathy) 1, 2

3. Fecal calprotectin >264.5 mg/kg: High risk for severe GI involvement; strongly consider early corticosteroid therapy and prepare for potential need for second-line immunomodulatory therapy (such as intravenous immunoglobulins) if steroid-refractory 2, 5

4. Fecal calprotectin >277.5 mg/kg: Suspect lower GI tract involvement; maintain heightened vigilance for complications like intussusception, ileal bleeding, or Meckel's diverticulum involvement that may require surgical intervention 1, 3

Important Clinical Caveats

Children under 2 years require higher fecal calprotectin thresholds due to wider normal ranges in young children, though HSP typically affects older children (median age 5.5 years in severe cases). 6, 5

• Fecal calprotectin should be measured using the first morning stool sample and analyzed within 3 days at room temperature to ensure accuracy 7
• NSAID use within the past 6 weeks can falsely elevate fecal calprotectin levels and should be documented 7, 8
• Serial measurements (at presentation, day 3, and day 7) provide the most comprehensive assessment of treatment response and disease trajectory 2
• Persistent elevation of fecal calprotectin despite 7 days of corticosteroid therapy should prompt consideration of steroid-refractory disease requiring escalation to intravenous immunoglobulins or other immunomodulatory agents 2, 5

Limitations and Context

Fecal calprotectin is not specific to HSP and can be elevated in other pediatric inflammatory conditions including inflammatory bowel disease, infectious gastroenteritis, and celiac disease. 7, 8

• The clinical context of HSP (purpuric rash, joint involvement, typical age group) distinguishes it from IBD, but infectious gastroenteritis should be excluded with stool cultures 9, 8
• Unlike IBD where fecal calprotectin guides long-term management decisions, in HSP it primarily serves as an early diagnostic and short-term monitoring tool during the acute phase 6, 1, 2