Which laboratory and imaging studies should be ordered for the workup of suspected giant cell arteritis?

Diagnostic Workup for Giant Cell Arteritis

Order ESR and CRP immediately, start high-dose prednisone 40–60 mg daily without waiting for results, and arrange temporal artery biopsy within 2 weeks—never delay treatment while awaiting diagnostic confirmation because untreated GCA carries a 14–50% risk of permanent vision loss. 1, 2

Immediate Laboratory Tests

Essential Inflammatory Markers

• Erythrocyte sedimentation rate (ESR): An ESR >100 mm/h has a positive likelihood ratio of 3.11 for GCA, while ESR <40 mm/h strongly argues against the diagnosis (negative likelihood ratio 0.18). 1, 2, 3
• C-reactive protein (CRP): CRP ≥2.5 mg/dL supports the diagnosis; CRP <2.5 mg/dL makes GCA unlikely (negative likelihood ratio 0.38). 1, 2, 3
• Complete blood count with platelets: Platelet count >400 × 10³/μL has a positive likelihood ratio of 3.75 for GCA. 1, 2, 3
• Hemoglobin: Anemia is present in 87% of GCA patients, though it has limited specificity. 2

Additional Baseline Tests

• Complete metabolic panel, hemoglobin A1C, fasting lipid panel, prothrombin time, and partial thromboplastin time are reasonable for cardiovascular risk stratification and pre-treatment assessment. 1

Histopathologic Confirmation

Temporal Artery Biopsy (Gold Standard)

• Obtain a specimen ≥1 cm in length to minimize false-negative results from skip lesions, which occur in approximately 10% of cases. 1, 2, 3
• Perform within 2 weeks of starting glucocorticoids: Histopathologic changes remain detectable for 1–2 weeks after treatment initiation, allowing biopsy after therapy has begun. 1, 2
• Start with unilateral biopsy: Proceed to contralateral biopsy only if the first is negative and clinical suspicion remains high. 1, 3
• Ensure experienced surgeon and pathologist: Proper technique and interpretation are critical for diagnostic accuracy. 1, 2
• Typical findings include arterial wall thickening, luminal narrowing, mononuclear inflammatory infiltrates in the media, and occasional multinucleated giant cells. 1, 2

Vascular Imaging Studies

First-Line Imaging for Cranial GCA

• Temporal and axillary artery ultrasound: Shows characteristic "halo sign" (circumferential wall thickening) with 88% sensitivity and 97% specificity when performed by experienced operators. 1, 4
• Ultrasound is non-invasive, readily available, and can be performed at bedside without radiation exposure. 4

Large Vessel Assessment (Baseline in All Newly Diagnosed Patients)

• MR angiography or CT angiography of neck, chest, abdomen, and pelvis to detect extracranial large vessel involvement, aneurysms, and stenoses. 1, 2, 4
• FDG-PET (combined with low-dose CT): Preferred modality for detecting large vessel inflammation in the aorta and major branches, showing increased tracer uptake in inflamed arterial walls. 4
• Large vessel involvement is much more common than previously recognized and may require adjusted monitoring. 5, 6

When to Obtain Additional Imaging

• If temporal artery biopsy is negative but clinical suspicion remains high, obtain noninvasive vascular imaging of large vessels to identify extracranial GCA. 1, 4, 3
• Imaging should never delay glucocorticoid initiation, particularly with visual symptoms or jaw claudication. 4

Cardiovascular and Neurologic Evaluation

Cardiac Assessment

• Electrocardiography should be performed as soon as possible after presentation. 1
• Echocardiography (at least transthoracic) is reasonable when no cause is identified by other workup elements, especially in patients with retinal artery occlusion. 1

Neurovascular Imaging

• Brain MRI with diffusion-weighted imaging (DWI) is the preferred modality within 24 hours of symptom onset for patients with visual or neurologic symptoms; if unavailable, obtain head CT. 1
• Noninvasive imaging of cervicocephalic vessels (MRA, CTA, or carotid ultrasound/transcranial Doppler) should be performed routinely for patients with suspected vascular transient monocular vision loss or retinal artery occlusion. 1

Critical Clinical Examination Findings to Document

Physical Examination

• Temporal artery palpation: Thickening (LR+ 4.70), loss of pulse (LR+ 3.25), or tenderness are highly suggestive findings. 2, 4, 3
• Four-extremity blood pressures: Measure to detect large vessel disease and limb claudication. 1, 2
• Scalp tenderness: Has a positive likelihood ratio of 3.14. 2, 3
• Ophthalmologic evaluation: Assess for anterior ischemic optic neuropathy, cranial nerve palsies, or central retinal artery occlusion. 2

Key Clinical Predictors

• Jaw claudication (LR+ 4.90) is the most specific cranial symptom, present in ~50% of patients. 2, 3
• Limb claudication has the highest positive likelihood ratio (6.01) and predicts severe ischemic complications. 2, 3
• New-onset headache is present in 66–90% of biopsy-confirmed cases but has limited specificity. 2

Common Pitfalls to Avoid

• Never delay glucocorticoid therapy while awaiting biopsy or imaging results—irreversible vision loss can occur within hours to days. 1, 2
• Do not obtain biopsy specimens <1 cm: Skip lesions lead to false-negative results in 10% of cases. 1, 2
• Do not dismiss GCA with normal inflammatory markers: Although rare (<5% of cases), GCA can present with normal ESR and CRP; high clinical suspicion should still prompt biopsy or imaging. 2
• Do not rely solely on ACR 1990 classification criteria for bedside diagnosis—they are intended for research classification, not clinical decision-making. 2
• Do not overlook large vessel GCA: Patients may present with constitutional symptoms alone, limb claudication, or polymyalgia rheumatica without typical temporal headache. 3, 6