How should giant cell arteritis be diagnosed in a patient over 50 years old presenting with new‑onset temporal headache, scalp tenderness, jaw claudication, visual disturbances, fever and elevated inflammatory markers?

How to Diagnose Giant Cell Arteritis

In patients over 50 years old with new-onset temporal headache, scalp tenderness, jaw claudication, visual disturbances, fever, and elevated inflammatory markers, initiate high-dose oral prednisone (40–60 mg daily) immediately while arranging temporal artery biopsy within 2 weeks—do not delay treatment awaiting biopsy results, as untreated GCA carries a 14–50% risk of permanent, irreversible vision loss. 1

Clinical Diagnostic Criteria

Key Symptoms with Highest Diagnostic Value

The diagnosis of GCA relies on recognizing specific clinical patterns in patients over 50 years old:

• Jaw claudication is the most specific symptom (positive likelihood ratio 4.90), present in approximately 50% of patients, manifesting as pain during chewing that resolves with rest 2, 1
• Temporal artery thickening on palpation provides the highest diagnostic utility among physical signs (positive likelihood ratio 4.70) 2, 1
• Loss of temporal artery pulse yields a positive likelihood ratio of 3.25 2, 1
• Scalp tenderness (pain when combing hair or resting the head) has a positive likelihood ratio of 3.14 2, 1
• Limb claudication carries the highest positive likelihood ratio (6.01) and predicts severe ischemic complications 2, 1

Visual Symptoms Requiring Urgent Recognition

• Transient vision loss (amaurosis fugax) precedes permanent blindness in approximately 20% of patients and constitutes an urgent warning sign 1, 3
• Diplopia indicates cranial nerve ischemia 1, 3
• Anterior ischemic optic neuropathy occurs in 23.9% of cases (positive likelihood ratio 2.15) 1
• New-onset headache is present in 66–90% of biopsy-confirmed cases, though it has limited specificity 2, 1

Demographic Risk Factors

• Age over 50 years is mandatory; the disease almost never occurs below this threshold 1, 4
• Age over 70 years markedly increases pre-test probability (negative likelihood ratio 0.48 when absent) 2, 1
• Female predominance with a 2–3:1 ratio over men 1, 4
• Higher prevalence in populations of Northern European descent 1, 4

Laboratory Evaluation

Inflammatory Markers (Essential for Diagnosis)

Marker	Diagnostic Threshold	Likelihood Ratio	Clinical Interpretation
ESR	> 100 mm/h	LR+ = 3.11	Strongly supports GCA
ESR	< 40 mm/h	LR– = 0.18	Strongly argues against GCA
CRP	≥ 2.5 mg/dL	LR– = 0.38 if absent	Makes GCA unlikely when normal
Platelet count	> 400 × 10³/µL	LR+ = 3.75	Supports diagnosis

• Elevated ESR and CRP are present in more than 95% of cases at diagnosis, making normal inflammatory markers a strong argument against GCA 1, 5
• An ESR < 40 mm/h has a negative likelihood ratio of 0.18, effectively ruling out GCA in most cases 2, 1
• A CRP < 2.5 mg/dL has a negative likelihood ratio of 0.38, similarly making GCA unlikely 2, 1
• Rare cases (< 5%) can present with normal ESR and CRP; high clinical suspicion should still prompt biopsy or imaging 1

Temporal Artery Biopsy (Gold Standard)

Biopsy Technique and Timing

• Obtain a specimen of at least 1 cm length to minimize false-negative results from skip lesions, which occur in approximately 10% of cases 1, 6
• Perform biopsy within 2 weeks of initiating glucocorticoids; histopathologic changes remain detectable for 1–2 weeks after treatment begins 1, 6
• Begin with unilateral biopsy; proceed to contralateral biopsy only if the first is negative and clinical suspicion remains high 1
• The procedure must be performed by an experienced surgeon and interpreted by an experienced pathologist 1

Histopathologic Features

• Arterial wall thickening with luminal narrowing 1
• Mononuclear inflammatory infiltrates invading the media layer 1, 7
• Multinucleated giant cells in the media (may be absent in some cases) 1, 7
• Occasional necrosis of the arterial wall 1

Vascular Imaging (Alternative or Adjunctive to Biopsy)

Temporal Artery Ultrasound

• The "halo sign" (circumferential wall thickening) has 88% sensitivity and 97% specificity when performed by experienced operators 1
• This non-invasive modality can support diagnosis when biopsy is unavailable or negative 1, 6

Large-Vessel Imaging

• MR angiography or CT angiography of the neck, chest, abdomen, and pelvis should be obtained at baseline in all newly diagnosed patients to detect extracranial large-vessel involvement 1
• FDG-PET imaging can show increased tracer uptake in affected arterial walls 1
• If temporal artery biopsy is negative but clinical suspicion persists, obtain non-invasive large-vessel imaging to identify extracranial GCA 1

Immediate Management Algorithm

Step 1: Recognize High-Risk Clinical Pattern

In any patient over 50 years old presenting with:

• New-onset temporal headache, OR
• Jaw claudication, OR
• Visual disturbances (transient vision loss, diplopia, blurred vision), OR
• Scalp tenderness with palpable temporal artery abnormalities

AND elevated inflammatory markers (ESR > 40 mm/h or CRP ≥ 2.5 mg/dL)

Step 2: Initiate Treatment Immediately

• For patients WITHOUT visual symptoms: Start high-dose oral prednisone 40–60 mg daily immediately, without waiting for biopsy confirmation 1, 6
• For patients WITH visual symptoms or threatened vision loss: Administer IV methylprednisolone 500–1000 mg daily for 3 consecutive days, then transition to high-dose oral prednisone 40–60 mg daily 1, 3
• Do not delay glucocorticoid therapy while awaiting biopsy or imaging results; irreversible vision loss can occur within hours to days 1, 3

Step 3: Arrange Diagnostic Confirmation

• Schedule temporal artery biopsy within 2 weeks of starting glucocorticoids 1
• Obtain baseline MR or CT angiography of neck, chest, abdomen, and pelvis to assess large-vessel involvement 1
• Measure blood pressure in all four extremities to detect large-vessel disease 1

Step 4: Add Adjunctive Therapy

• Initiate tocilizumab (IL-6 receptor antagonist) at diagnosis for all GCA patients to reduce cumulative glucocorticoid exposure and prevent relapses 1, 3
• Prescribe low-dose aspirin 75–150 mg daily to reduce cardiovascular and cerebrovascular ischemic events 1, 3

Critical Diagnostic Pitfalls to Avoid

• Never delay glucocorticoid initiation while awaiting temporal artery biopsy or imaging; untreated GCA carries a 14–50% risk of permanent vision loss 1, 3
• Never obtain biopsy specimens shorter than 1 cm; skip lesions cause false-negative results in approximately 10% of cases 1
• Do not rely solely on the 1990 ACR classification criteria for clinical diagnosis; they are intended for research classification, not bedside decision-making 1
• Do not dismiss GCA in patients with normal ESR or CRP if clinical suspicion is high; rare cases (< 5%) present with normal inflammatory markers 1
• Do not use moderate-dose glucocorticoids (≈ 30 mg daily) as initial therapy; the risk of vision loss is too high 3

Monitoring and Follow-Up

• Perform comprehensive ophthalmologic evaluation in all patients with visual symptoms to assess for anterior ischemic optic neuropathy and cranial nerve palsies 3
• Monitor clinical symptoms (headache, jaw claudication, visual changes) and inflammatory markers (ESR, CRP) at each visit to guide treatment adjustments 1
• Conduct periodic vascular imaging in patients with known large-vessel involvement to surveil for aneurysms or stenoses 1

Special Diagnostic Considerations

Respiratory Manifestations

• Chronic dry, harsh, non-productive cough occurs in fewer than 10% of GCA patients and may be the sole presenting feature 7
• In patients over 50 years with unexplained chronic cough and elevated inflammatory markers, evaluate for GCA 7
• The cough typically resolves dramatically within days to weeks of starting high-dose prednisone 7

Large-Vessel GCA

• Large-vessel involvement often lacks cranial symptoms and carries a higher relapse rate compared with cranial-limited disease 1
• Baseline imaging of the aorta and its branches is essential to detect aneurysms, stenoses, and establish a reference for future monitoring 1