What is the diagnosis and treatment for a patient with symptoms suggestive of atypical Giant Cell Arteritis (GCA)?

Atypical GCA or Something Else?

If you suspect atypical GCA based on clinical presentation, immediately initiate high-dose glucocorticoids (40-60 mg/day prednisone) while simultaneously pursuing rapid diagnostic confirmation through temporal artery biopsy and/or vascular imaging within 24 hours. 1

Recognizing Atypical GCA Presentations

The diagnosis becomes challenging when classic cranial symptoms are absent. Consider GCA even without typical temporal headache if the patient presents with:

High-Yield Atypical Features

• Limb claudication (positive LR 6.01) - the strongest predictor of GCA 1
• Constitutional symptoms alone - weight loss >2 kg, low-grade fever, fatigue, night sweats 1
• Large vessel involvement - bruits (particularly axillary), reduced pulses, blood pressure asymmetry in upper limbs 1
• Polymyalgia rheumatica symptoms without cranial features 1
• Unexplained stroke or cerebral ischemia in patients >50 years 1

Classic Features That May Be Present

• Jaw claudication (positive LR 4.90) 1
• Temporal artery abnormalities - thickening (positive LR 4.70), loss of pulse (positive LR 3.25), or tenderness (positive LR 3.14) 1

Critical Laboratory Assessment

Obtain these tests immediately to stratify risk:

• ESR and CRP - both are essential as they provide complementary information 2
  • ESR >100 mm/h has positive LR 3.11 1
  • Normal ESR (<40 mm/h) argues strongly against GCA (negative LR 0.18) 1
  • Normal CRP (<2.5 mg/dL) argues strongly against GCA (negative LR 0.38) 1
• Platelet count - thrombocytosis >400 × 10³/μL supports GCA (positive LR 3.75) 1
• Age consideration - absence of age >70 years decreases likelihood (negative LR 0.48) 1

Critical pitfall: No single feature confirms or excludes GCA - you must combine multiple clinical and laboratory findings 1, 2

Immediate Treatment Decision Algorithm

WITH Visual Symptoms or Threatened Vision Loss

1. Start IV pulse glucocorticoids immediately before any diagnostic testing 1
2. Urgent ophthalmology consultation to exclude other causes of visual disturbance 1
3. Proceed with diagnostic workup (do not delay treatment) 1

Rationale: Delaying glucocorticoid therapy when visual loss is present is the strongest risk factor for permanent blindness 1

WITHOUT Visual Symptoms

1. Start high-dose oral glucocorticoids (40-60 mg/day prednisone) if clinical suspicion is reasonable based on combination of features 1
2. Arrange fast-track referral to specialized center for diagnostic workup within 24 hours 1
3. Pre-emptive therapy should only be given for a short period and should not delay early referral 1

Important caveat: There is no consensus on whether all suspected GCA cases without visual symptoms require pre-emptive glucocorticoids, but evidence supports rapid treatment to reduce permanent visual impairment 1

Diagnostic Confirmation Strategy

Temporal Artery Biopsy (Preferred in US)

• Obtain within 2 weeks of starting glucocorticoids to maximize histopathologic detection 1, 3
• Long-segment biopsy >1 cm (not <1 cm) due to focal, segmental nature of disease 1, 3
• Initial unilateral biopsy is sufficient; proceed to contralateral if negative and suspicion remains high 1
• Histopathologic changes can be detected even weeks after glucocorticoid initiation 1

When Temporal Artery Biopsy is Negative

If biopsy is negative but clinical suspicion remains high, obtain noninvasive vascular imaging of large vessels (CT angiography, MR angiography, or PET/CT) with clinical reassessment 1

Baseline Large Vessel Imaging

For all newly diagnosed GCA patients, obtain noninvasive vascular imaging to evaluate large vessel involvement, which may identify extracranial disease and establish baseline for monitoring complications like aneurysms and stenoses 1

Alternative Diagnoses to Consider

When evaluating atypical presentations, actively exclude:

• Other causes of sudden visual disturbance - requires ophthalmologic evaluation 1
• Cerebral ischemia from other etiologies - requires neurologic evaluation 1
• Takayasu arteritis if patient presents with limb claudication, hypertension, pulse inequality, or is younger 1

Key distinguishing features for Takayasu arteritis: New onset/worsening limb claudication, hypertension (>140/90 mmHg), new loss of pulses, pulse inequality, severe abdominal pain, or younger age 1

Treatment Optimization

Initial Glucocorticoid Regimen

• High-dose oral glucocorticoids (40-60 mg/day prednisone) for patients without cranial ischemia 1
• IV pulse glucocorticoids followed by high-dose oral for threatened vision loss 1
• Daily dosing (not alternate-day) 1

Steroid-Sparing Therapy

Add tocilizumab (IL-6 receptor antibody) to oral glucocorticoids rather than glucocorticoids alone for newly diagnosed GCA 1, 4

• Tocilizumab is FDA-approved for GCA treatment 4
• Reduces cumulative glucocorticoid dose and relapse frequency 5, 6
• Dose: 162 mg subcutaneously weekly 4

For extracranial large vessel involvement specifically, combine oral glucocorticoids with a non-glucocorticoid immunosuppressive agent (such as methotrexate or tocilizumab) 1

Adjunctive Therapy

Add low-dose aspirin (100 mg daily) for patients with critical or flow-limiting involvement of vertebral or carotid arteries 1, 7

Common Pitfalls to Avoid

1. Do not wait for biopsy results to start treatment - begin glucocorticoids immediately when GCA is suspected 1, 3
2. Do not use ACR 1990 classification criteria for clinical diagnosis - these were designed for research classification, not diagnostic decision-making 2, 7
3. Do not accept inadequate biopsy specimens <1 cm - lower diagnostic yield 1, 3
4. Do not rely on temporal artery ultrasound in US settings unless center has specific expertise, as it is operator-dependent and results are influenced by treatment 1
5. Do not assume normal inflammatory markers exclude GCA - while helpful, they are not absolute 1