What is the approach to screen for inflammatory diseases?

Screening for Inflammatory Diseases: A Comprehensive Approach

The optimal approach to screening for inflammatory diseases requires a multi-marker panel assessment, with C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) serving as first-line tests, supplemented by disease-specific biomarkers based on clinical presentation. 1

Initial Screening Tests

First-Line Laboratory Tests

• High-sensitivity C-reactive protein (hs-CRP)

  • More responsive to acute inflammation
  • Sensitivity: 73%, specificity: 78% for distinguishing organic from functional disease 1
  • Cutpoints for cardiovascular risk assessment: 2
    • Low risk: <1.0 mg/L
    • Average risk: 1.0-3.0 mg/L
    • High risk: >3.0 mg/L

• Erythrocyte sedimentation rate (ESR)

  • Better reflects chronic inflammatory states
  • Sensitivity: 54-78%, specificity: 46-95% for distinguishing organic from functional disease 1

• Complete blood count (CBC)

  • Assess for leukocytosis, anemia, and thrombocytosis which may indicate inflammation 1

Interpretation of Combined Results

CRP	ESR	Interpretation
Elevated	Normal	Acute inflammation
Normal	Elevated	Chronic inflammation or non-inflammatory factors
Elevated	Elevated	Active inflammation [1]

Disease-Specific Screening Approaches

Rheumatic Diseases

1. Initial screening panel:

   • ESR and CRP (mandatory)
   • Complete blood count
   • Liver and kidney function tests 2

2. For suspected interstitial lung disease (ILD) in rheumatic diseases:

   • Baseline pulmonary function tests (PFTs), including spirometry and DLCO
   • Chest radiography
   • High-resolution computed tomography (HRCT) for patients with symptoms or risk factors 2

3. For Sjögren syndrome patients:

   • Annual PFTs and chest radiograph for those with risk factors
   • HRCT if signs/symptoms appear or PFTs are abnormal 2

4. For idiopathic inflammatory myopathies:

   • Clinical assessment
   • Autoantibody profile (anti-MDA5, anti-synthetase antibodies)
   • Chest radiograph
   • PFTs with spirometry, DLCO, and respiratory pressures evaluation 2

Inflammatory Bowel Disease (IBD)

1. Mandatory laboratory tests:

   • ESR and CRP
   • Complete blood count
   • Liver and kidney function tests
   • Serum albumin 1

2. Specific IBD markers:

   • Fecal calprotectin
     • <50 mg/g: High sensitivity (88%) for ruling out inflammation
     • <150 mg/g: Recommended to rule out active inflammation

     • 250 mg/g: Higher specificity (74%) for active inflammation 1

3. Additional testing:

   • Stool cultures to rule out infectious causes
   • Ileocolonoscopy with biopsies (gold standard) 1

Cardiovascular Disease Risk Assessment

1. Recommended approach:

   • Calculate traditional risk factors first
   • Consider hs-CRP testing for patients at intermediate risk (10-20% 10-year risk)
   • Two hs-CRP measurements, averaged, optimally 2 weeks apart 2

2. Important considerations:

   • If hs-CRP >10 mg/L, search for obvious source of infection or inflammation
   • Discard result >10 mg/L and remeasure in 2 weeks 2

Neuroinflammatory Conditions

1. Key principle:

   • A single inflammatory marker is insufficient to describe complex biological cascades
   • Multiple markers with similar or distinct functions should be measured simultaneously 2

2. For Alzheimer's disease and neuroinflammation:

   • Multiple CSF inflammatory markers should be assessed to capture the complexity of neuroinflammatory processes 2

Screening in Special Populations

Patients on Immunosuppressive Therapy

For patients with inflammatory bowel disease on immunosuppression, additional screening includes: 2

• Hepatitis B and C virus serologies
• Epstein-Barr virus serology
• HIV serology (with appropriate counseling)
• Tuberculosis screening:
  • Clinical risk assessment
  • Chest radiograph
  • Tuberculin skin test and/or interferon gamma release assay

Pediatric Considerations

• In early-onset IBD (under 5 years of age), underlying immune deficiencies should be highly suspected 2
• Special vaccination considerations are needed for immunosuppressed children 2

Pitfalls and Limitations

1. Non-specificity of markers:

   • Inflammatory markers are not specific for any particular disease
   • Elevated levels can occur in various conditions including infections, malignancies, and autoimmune disorders 2, 1

2. False positives and negatives:

   • Obesity, smoking, and hormone replacement therapy can elevate hs-CRP 2
   • Normal inflammatory markers do not rule out inflammatory disease 1

3. Interpretation challenges:

   • A single inflammatory marker is insufficient to characterize immune function or dysfunction 2
   • Context matters - age, comorbidities, and medications can affect marker levels 2

4. Timing considerations:

   • Markers have different temporal profiles through aging and disease 2
   • CRP rises and falls more quickly than ESR during acute inflammation 1

Practical Algorithm for Screening

1. Step 1: Assess clinical presentation and risk factors for specific inflammatory diseases
2. Step 2: Order first-line tests (CRP, ESR, CBC)
3. Step 3: Based on results and clinical suspicion, order disease-specific markers:
   • Rheumatic diseases: Autoantibodies, imaging
   • IBD: Fecal calprotectin, endoscopy
   • Cardiovascular risk: Repeat hs-CRP
   • Neuroinflammation: CSF inflammatory panel
4. Step 4: Interpret results in clinical context and proceed with appropriate diagnostic workup

By following this structured approach to inflammatory marker testing, clinicians can effectively screen for inflammatory diseases while avoiding unnecessary testing and ensuring timely diagnosis and treatment.