How do you differentiate infection from inflammation in a patient with vasculitis?

Differentiating Infection from Inflammation in Vasculitis

The most effective approach to differentiate infection from inflammation in vasculitis patients is through a structured clinical assessment combined with targeted laboratory testing, imaging studies, and when appropriate, tissue biopsy, as infection can mimic disease flares and inappropriate immunosuppression in the setting of infection can be fatal. 1

Clinical Assessment and Initial Evaluation

• Perform a structured clinical examination at each visit to detect new organ involvement, which may develop at any time during the disease course 2
• Evaluate for signs of infection including fever, localized pain/swelling, purulent discharge, or specific organ-related symptoms 2
• Assess for vasculitis-specific manifestations that may help differentiate from infection, such as new-onset purpura, mononeuritis multiplex, or glomerulonephritis 3
• Consider that both infection and vasculitis flare can present with elevated inflammatory markers, making differentiation challenging 1

Laboratory Testing

• Obtain basic laboratory tests including complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) 3
• Perform urinalysis with microscopic examination to assess for active sediment suggesting glomerulonephritis versus infection 3
• Test for ANCA (including indirect immunofluorescence and ELISA) when appropriate, as rising titers may suggest active vasculitis rather than infection 2
• Collect appropriate cultures (blood, urine, sputum, etc.) based on clinical presentation before initiating or intensifying immunosuppression 2

Imaging Studies

• Consider appropriate imaging based on symptoms:
  • Chest imaging for pulmonary symptoms to differentiate between pulmonary hemorrhage, vasculitic nodules, and pneumonia 2
  • MRI/CT for neurological symptoms to distinguish CNS vasculitis from infectious encephalitis 2
  • Vascular imaging (ultrasound, MRA, CTA) may help identify vessel wall inflammation in large vessel vasculitis versus other causes 2

Tissue Biopsy

• A positive biopsy is strongly supportive of active vasculitis and should be performed when feasible to assist in differentiating from infection 2
• Kidney biopsy can be particularly helpful in distinguishing active disease from damage or alternative diagnoses including infection 2
• Histopathological findings such as fibrinoid necrosis or pauci-immune glomerulonephritis support active vasculitis rather than infection 2

Specific Diagnostic Challenges

• In patients with ANCA-associated vasculitis, differentiation between disease activity and infection is particularly challenging as both can present with similar clinical features 2
• Patients with vasculitis on immunosuppressive therapy are at increased risk of opportunistic infections that may mimic disease flares 2
• Infection can sometimes trigger a vasculitis flare, making both conditions present simultaneously 3

Practical Approach to Differentiation

1. High suspicion for infection:

   • Presence of localized symptoms with purulence
   • Positive cultures or specific infectious markers
   • Response to empiric antibiotics
   • Lack of typical vasculitis manifestations 2, 1

2. High suspicion for vasculitis flare:

   • Multisystem involvement typical of the patient's known vasculitis pattern
   • Rising ANCA titers in previously ANCA-positive patients
   • Characteristic imaging findings (e.g., vessel wall enhancement)
   • Positive biopsy findings 2

3. Indeterminate cases:

   • Consider empiric antibiotic coverage while awaiting culture results
   • Low threshold for biopsy of affected tissues
   • Close monitoring of response to initial therapy
   • Multidisciplinary consultation with infectious disease specialists 2, 3

Management Considerations

• Patients with vasculitis should be managed in collaboration with, or at centers with specific vasculitis expertise to ensure accurate differentiation between infection and disease activity 2
• In cases where infection cannot be ruled out but vasculitis activity is strongly suspected, consider empiric antimicrobial coverage while initiating or continuing immunosuppression 3
• For patients with confirmed infection, treat the underlying infectious etiology appropriately before increasing immunosuppression 2
• Regular screening for treatment-related adverse effects and comorbidities, including infection, should be performed in all patients with vasculitis 2

Common Pitfalls to Avoid

• Failing to obtain appropriate cultures before escalating immunosuppression 3
• Misinterpreting elevated inflammatory markers as disease activity without excluding infection 1
• Overlooking the possibility of concurrent infection and vasculitis activity 2
• Delaying appropriate treatment while waiting for all test results in rapidly deteriorating patients 3
• Not considering opportunistic infections in immunosuppressed patients (e.g., Pneumocystis jirovecii, cytomegalovirus, tuberculosis) 2