What is the recommended treatment for Giant Cell Arteritis (GCA) with normal Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)?

Treatment of Giant Cell Arteritis with Normal ESR and CRP

For patients with suspected Giant Cell Arteritis (GCA) with normal ESR and CRP, immediate treatment with high-dose glucocorticoids is still strongly recommended, as normal inflammatory markers do not rule out the diagnosis. 1

Diagnostic Approach for GCA with Normal Inflammatory Markers

Despite normal ESR and CRP, GCA remains a possibility when clinical symptoms are present. The diagnostic approach should include:

• Temporal artery biopsy is the gold standard for diagnosis 2

  • Obtain a unilateral long-segment temporal artery biopsy (>1 cm) within 2 weeks of starting treatment 2
  • Bilateral biopsies may be appropriate if symptoms aren't clearly localized to one side 2

• Noninvasive vascular imaging to evaluate large vessel involvement 2

  • Particularly important when temporal artery biopsy is negative 2
  • Options include CT angiography, MR angiography, PET scan, or vascular ultrasound 2

• Clinical assessment remains crucial when inflammatory markers are normal 3

  • Look for headache, scalp tenderness, jaw claudication, visual disturbances, and constitutional symptoms
  • Presence of typical symptoms should prompt treatment regardless of normal lab values 3

Treatment Algorithm for GCA with Normal ESR and CRP

1. Initial Treatment:

   • Begin high-dose oral glucocorticoids (prednisone 1 mg/kg/day up to 80 mg) immediately upon clinical suspicion 2, 1
   • For patients with threatened vision loss: IV pulse glucocorticoids (methylprednisolone 500-1000 mg/day for 3-5 days) 2, 1
   • Do not delay treatment while awaiting biopsy results 1

2. Combination Therapy:

   • Add tocilizumab 162mg subcutaneously weekly to the glucocorticoid regimen 2, 1
   • Consider aspirin for patients with critical involvement of vertebral or carotid arteries 2, 1

3. Maintenance and Tapering:

   • Maintain initial high-dose prednisone for one month 1
   • Taper to 10-15 mg/day by 3 months 1
   • Further taper to ≤5 mg/day by 1 year 1
   • Total treatment duration typically 1-2 years 1

Monitoring and Relapse Management

• Regular clinical monitoring for disease activity is strongly recommended 2

  • Do not rely solely on inflammatory markers, as they may remain normal despite active disease 3, 4
  • Monitor for visual deterioration, particularly in the first week of treatment 1

• For relapses with cranial ischemic symptoms:

  • Increase glucocorticoid dose and ensure tocilizumab is being used 2, 1
  • Consider adding a non-glucocorticoid immunosuppressive agent (e.g., methotrexate) if relapse occurs on moderate-to-high dose glucocorticoids 2

Important Considerations and Pitfalls

• Do not dismiss GCA diagnosis based solely on normal inflammatory markers 3

  • Studies have confirmed that GCA with typical symptoms and biopsy-proven disease can occur with normal ESR and CRP 3
  • The sensitivity of ESR alone ranges from 76-86%, while CRP sensitivity is 97.5% 4
  • Combined ESR and CRP testing provides 99% sensitivity, but false negatives still occur in 0.8% of cases 4

• Avoid rapid glucocorticoid tapering without glucocorticoid-sparing therapy 1

  • Relapses are common (34-75% of patients) during tapering 1
  • During relapses, ESR may be normal in 48% of cases and CRP in 56% 5

• Monitor for treatment-related adverse effects 1

  • Glucocorticoid-related adverse effects occur in 86% of patients 1
  • Monitor for tocilizumab-related effects including neutropenia, elevated liver enzymes, and lipid abnormalities 1
  • Consider bone protection therapy to prevent glucocorticoid-induced osteoporosis 1

The evidence clearly demonstrates that normal inflammatory markers do not exclude GCA, and treatment decisions should be based primarily on clinical presentation rather than laboratory values alone when GCA is suspected.