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

Management 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 should still be initiated, followed by temporal artery biopsy and additional diagnostic imaging to confirm the diagnosis.

Diagnostic Approach for GCA with Normal Inflammatory Markers

Initial Evaluation

• Despite normal ESR and CRP, GCA remains a clinical diagnosis that requires prompt treatment
• Normal inflammatory markers occur in approximately 4-15% of GCA cases with normal ESR, and in about 0.8% of cases with both normal ESR and CRP 1
• Clinical suspicion should guide management decisions regardless of laboratory values

Diagnostic Testing Algorithm

1. Temporal Artery Biopsy:

   • Remains the gold standard for diagnosis even with normal inflammatory markers 2
   • Obtain a long-segment temporal artery biopsy (>1 cm) to increase diagnostic yield 2
   • Perform biopsy within 2 weeks of starting glucocorticoids 2
   • Initially perform unilateral biopsy, but consider bilateral if symptoms are not clearly localized 2

2. Additional Testing:

   • Evaluate complete blood count for thrombocytosis, which can be a stronger predictor of positive biopsy than ESR 3
   • Consider neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as supportive markers 3
   • For patients with negative temporal artery biopsy, obtain noninvasive vascular imaging of large vessels 2

Treatment Approach

Initial Treatment

• Begin high-dose glucocorticoids immediately upon clinical suspicion, even with normal inflammatory markers 4
  • For patients without visual symptoms: Oral prednisone 40-60 mg/day 4
  • For patients with threatened vision loss: IV pulse methylprednisolone (250mg-1g every 6-8 hours for 3 days) 4

Combination Therapy

• Add tocilizumab 162mg subcutaneously weekly to the glucocorticoid regimen 4, 5

  • Tocilizumab has shown superior outcomes in achieving sustained remission (56% vs 14% with glucocorticoids alone) 5
  • Reduces cumulative glucocorticoid dose requirements 5

• Consider aspirin for antiplatelet effect, especially with critical involvement of vertebral or carotid arteries 4

Glucocorticoid Tapering

• Maintain initial high-dose for one month, then gradually taper 4
• Aim to reach 10-15 mg/day by 3 months, and ≤5 mg/day by 1 year 4
• Typical treatment duration is 1-2 years 4

Monitoring and Follow-up

Disease Activity Assessment

• Do not rely solely on ESR and CRP for monitoring, as they may remain normal throughout the disease course 6, 7
• Focus on clinical symptoms and signs of active disease 4
• Obtain noninvasive vascular imaging to evaluate large vessel involvement 2

Relapse Management

• For relapses with cranial ischemic symptoms, increase glucocorticoid dose and ensure tocilizumab is being used 4
• Consider adding a non-glucocorticoid immunosuppressive drug (methotrexate, leflunomide) for relapses while on moderate-to-high-dose glucocorticoids 4

Important Caveats

• Never delay treatment while awaiting biopsy results or due to normal inflammatory markers 4, 7
• Do not exclude GCA diagnosis based solely on normal ESR and CRP 6, 7
• Patients with normal inflammatory markers may still present with typical GCA symptoms and risk permanent vision loss if treatment is delayed 7
• Patients with normal ESR/CRP may have different clinical presentations, with more polymyalgia rheumatica symptoms and fewer constitutional symptoms, anemia, and thrombocytosis 6

Remember that GCA is an ophthalmological emergency, and treatment should never be delayed due to normal inflammatory markers when clinical suspicion is high.