Does C-reactive protein (CRP) increase in Nonsteroidal Anti-Inflammatory Drug (NSAID) colitis?

C-Reactive Protein Elevation in NSAID Colitis

Yes, C-reactive protein (CRP) does increase in NSAID colitis, though the elevation is typically less pronounced than in other forms of inflammatory bowel disease such as Crohn's disease.

Relationship Between CRP and NSAID Colitis

NSAID colitis is a form of drug-induced colitis that results from the use of non-steroidal anti-inflammatory drugs. According to current evidence:

• CRP serves as an acute-phase protein produced by hepatocytes in response to inflammatory cytokines (IL-6, TNF-alpha, IL-1beta) 1
• In colitis generally, CRP levels correlate with inflammation, but with important distinctions between different types of colitis

CRP Elevation Patterns in Different Types of Colitis

1. NSAID Colitis and Ulcerative Colitis:

   • CRP increases are typically modest in NSAID colitis, similar to the pattern seen in ulcerative colitis 2
   • CRP is a less reliable marker of inflammation in ulcerative colitis compared to Crohn's disease, except in cases of severe, extensive colitis 1
   • Median CRP values in ulcerative colitis by severity 3:
     • Mild disease: 0 mg/L (range 0-15 mg/L)
     • Moderate disease: 3 mg/L (range 0-29 mg/L)
     • Severe disease: 12 mg/L (range 2-33 mg/L)

2. Comparison with Crohn's Disease:

   • CRP elevations are significantly higher in Crohn's disease than in ulcerative colitis across all severity categories 3
   • CRP is a more sensitive (98.6% vs 71.4%) and specific (95% vs 84.6%) activity index in Crohn's disease than in ulcerative colitis 4

Clinical Utility of CRP in NSAID Colitis

The European Consensus on Diagnosis and Management of Ulcerative Colitis notes that NSAIDs may exacerbate inflammatory bowel disease 2. When evaluating a patient with suspected NSAID colitis:

• CRP should be measured as part of the initial laboratory workup 2
• CRP broadly correlates with clinical severity in colitis, with the exception of proctitis 2
• A normal CRP does not rule out NSAID colitis, especially if mild or localized 2

Monitoring Considerations

When using CRP to monitor NSAID colitis:

• CRP levels >10 mg/L may indicate more severe inflammation 2
• Fecal calprotectin has a significant relationship with CRP (r=0.57; p<0.001) in patients with colitis and may be a more sensitive marker of intestinal inflammation 5
• CRP should be interpreted in conjunction with clinical symptoms and other inflammatory markers 2

Practical Approach to CRP Testing in Suspected NSAID Colitis

1. Initial Assessment:

   • Measure CRP as part of initial laboratory evaluation
   • Consider fecal calprotectin as a complementary test (more sensitive for intestinal inflammation)
   • Document NSAID usage (type, dose, duration)

2. Interpretation:

   • Mild elevation or normal CRP does not exclude NSAID colitis
   • Higher CRP levels (>10 mg/L) suggest more severe inflammation
   • Compare with baseline CRP if available

3. Monitoring:

   • Serial CRP measurements can help track disease activity
   • Normalization of previously elevated CRP may suggest improvement
   • Persistent elevation despite NSAID discontinuation suggests alternative or additional pathology

Important Caveats

• CRP is not specific to intestinal inflammation and can be elevated due to various inflammatory conditions 6
• CRP should be used as an additional tool that aids clinical observation but cannot replace comprehensive evaluation 1
• In patients with mild NSAID colitis, CRP may remain within normal range despite endoscopic evidence of inflammation 2

Remember that while CRP can be helpful in assessing NSAID colitis, its sensitivity is lower than in Crohn's disease, and normal values do not exclude the diagnosis, especially in milder cases.