In a patient over 50 with typical symptoms of temporal (giant‑cell) arteritis but a normal erythrocyte sedimentation rate, does this exclude the diagnosis and how should it be treated?

Temporal Arteritis with Normal ESR

Direct Answer

A normal ESR does not exclude giant cell arteritis (GCA), and high-dose glucocorticoids (prednisone 40–60 mg daily) must be started immediately based on clinical suspicion alone, without waiting for confirmatory testing. 1

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Why Normal ESR Does Not Rule Out GCA

Although elevated inflammatory markers (ESR >40 mm/h and CRP ≥2.5 mg/dL) are present in >95% of GCA cases at diagnosis, approximately 4–5% of biopsy-proven GCA patients present with both normal ESR and normal CRP. 1, 2

Diagnostic Performance of Inflammatory Markers

• ESR <40 mm/h has a negative likelihood ratio of only 0.18, meaning it substantially reduces—but does not eliminate—the probability of GCA 1
• CRP <2.5 mg/dL has a negative likelihood ratio of 0.38 1
• When both ESR and CRP are normal, the odds ratio for positive temporal artery biopsy drops to 0.49, but GCA remains possible 2
• CRP is more sensitive than ESR for detecting GCA (86.9% vs 84.1% sensitivity), so a normal CRP is more reassuring than a normal ESR alone 2

Clinical Profile of GCA with Normal Inflammatory Markers

Patients with biopsy-proven GCA and normal ESR/CRP more commonly present with:

• Polymyalgia rheumatica symptoms (shoulder and pelvic girdle pain/stiffness) 2
• Fewer constitutional symptoms (less fever, weight loss, fatigue) 2
• Less anemia and thrombocytosis on complete blood count 2

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When to Treat Despite Normal ESR

Initiate high-dose prednisone 40–60 mg daily immediately if the patient has:

• Age >50 years (mandatory demographic criterion) 1
• New-onset localized headache (present in 66–90% of biopsy-confirmed cases) 1
• Jaw claudication (pain with chewing that resolves with rest; positive likelihood ratio 4.90—the most specific symptom) 1
• Scalp tenderness (positive likelihood ratio 3.14) 1
• Temporal artery abnormalities on palpation (thickening [LR+ 4.70], absent pulse [LR+ 3.25], or tenderness) 1
• Visual disturbances (transient vision loss, diplopia, blurred vision—occur in 20% before permanent blindness) 1
• Limb claudication (positive likelihood ratio 6.01; predicts severe ischemic complications) 1

The risk of permanent, irreversible vision loss in untreated GCA is 14–50%, and blindness can occur within hours to days. 1 This catastrophic outcome mandates immediate treatment based on clinical suspicion, regardless of inflammatory markers.

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Immediate Management Algorithm

Step 1: Start Glucocorticoids Without Delay

• For patients WITHOUT visual symptoms:
  Oral prednisone 40–60 mg daily (or 1 mg/kg/day, maximum 60 mg) as a single morning dose 1, 3

• For patients WITH visual symptoms or threatened vision loss:
  Intravenous methylprednisolone 500–1000 mg daily for 3 consecutive days, then transition to oral prednisone 40–60 mg daily 1, 3

• Do not delay treatment while awaiting temporal artery biopsy, imaging, or specialist consultation 1

Step 2: Arrange Temporal Artery Biopsy Within 2 Weeks

• Obtain a specimen ≥1 cm in length to minimize false-negative results from skip lesions (present in ~10% of cases) 1
• Biopsy remains diagnostic for 1–2 weeks after starting glucocorticoids, so treatment should never be postponed 1
• If the first biopsy is negative but clinical suspicion remains high, proceed to contralateral biopsy 1

Step 3: Obtain Baseline Vascular Imaging

• MR or CT angiography of the neck, chest, abdomen, and pelvis to detect extracranial large-vessel involvement 1
• Temporal artery ultrasound (if experienced operators available) showing "halo sign" has 88% sensitivity and 97% specificity 1

Step 4: Add Tocilizumab as First-Line Adjunctive Therapy

• Tocilizumab 162 mg subcutaneously weekly should be initiated at diagnosis to reduce cumulative glucocorticoid exposure and prevent relapses 1, 3
• Methotrexate may be used as an alternative steroid-sparing agent when tocilizumab is contraindicated 1, 3

Step 5: Initiate Bone Protection

• Calcium, vitamin D, and bisphosphonates (unless contraindicated) for all patients on long-term glucocorticoids 1

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Glucocorticoid Tapering Strategy

• Maintain initial high dose (40–60 mg daily) for 1 month until symptoms resolve and inflammatory markers normalize 1, 3
• Target 15–20 mg/day by 2–3 months 3
• Target 10–15 mg/day by 3 months 1
• Target ≤5 mg/day by 12 months if disease is controlled 1, 3
• Guide tapering by clinical symptoms and ESR/CRP, not by a rigid calendar 1, 3
• Total treatment duration is typically 1–2 years; relapses occur in 34–75% of patients during tapering 3

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Critical Pitfalls to Avoid

• Never delay glucocorticoid initiation while awaiting biopsy or imaging; irreversible vision loss can occur within hours 1, 4, 5
• Do not rely solely on ESR to exclude GCA; documented cases of biopsy-proven GCA with normal ESR exist 6, 4, 5
• Do not obtain biopsy specimens <1 cm; skip lesions cause false-negative results in ~10% of cases 1
• Do not use alternate-day glucocorticoid dosing; daily dosing is required 3
• Do not rely on isolated ESR/CRP elevations to guide treatment escalation; clinical assessment takes priority 3

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Case Examples from the Literature

• A 68-year-old man developed biopsy-proven bilateral GCA with complete vision loss in one eye, presenting with CRP 29 mg/L but ESR 4 mm/h (normal) 6
• An elderly woman with visual changes had a delayed diagnosis because of normal ESR, resulting in substantial morbidity 4
• A patient with biopsy-proven GCA and normal ESR subsequently developed devastating CNS complications due to delayed treatment 5

These cases underscore that clinical suspicion must override laboratory values when evaluating for GCA.