What are the key features of Giant Cell Arteritis (GCA) relevant to the United States Medical Licensing Examination (USMLE) Step 1?

From the Guidelines

For USMLE Step 1, it is crucial to recognize that giant cell arteritis (GCA) is a granulomatous vasculitis affecting large and medium-sized arteries, particularly the branches of the carotid artery, and immediate treatment with high-dose corticosteroids is essential to prevent vision loss, as supported by the 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis 1.

Key Features of GCA

• GCA typically affects adults over 50 years old with a female predominance
• Key clinical features include:
  • New-onset headache (often temporal)
  • Jaw claudication
  • Scalp tenderness
  • Visual disturbances (including sudden vision loss)
  • Polymyalgia rheumatica (in 50% of cases)
  • Constitutional symptoms like fever and weight loss
• Laboratory findings show elevated ESR (often >100 mm/hr) and CRP
• Diagnosis is confirmed by temporal artery biopsy showing granulomatous inflammation with multinucleated giant cells, though skip lesions can occur

Importance of Immediate Treatment

• Treatment must begin immediately with high-dose corticosteroids (prednisone 40-60 mg daily) without waiting for biopsy results if GCA is suspected, as delay can lead to permanent blindness, as emphasized in the 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM guidelines for the diagnosis and management of patients with thoracic aortic disease 1
• The pathophysiology involves T-cell mediated inflammation and granuloma formation in the vessel wall, particularly at branch points of arteries

Clinical Presentation and Diagnosis

• Clinical presentation in elderly patients is critical, with a focus on recognizing the urgency of treatment to prevent vision loss
• Characteristic histopathological findings of granulomatous inflammation with giant cells are essential for diagnosis
• The 2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis provide a comprehensive framework for understanding the disease course, treatment, and outcomes of GCA 1

From the FDA Drug Label

Sustained remission was achieved by a patient meeting all of the following components: absence of GCA signs and symptoms†, normalization of ESR‡, normalization of CRP§ and adherence to the prednisone taper regimen¶ † Patients who did not have any signs or symptoms of GCA recorded from Week 12 up to Week 52. ‡ Patients who did not have an elevated ESR ≥30 mm/hr which was classified as attributed to GCA from Week 12 up to Week 52. § Patients who did not have two or more consecutive CRP records of ≥ 1mg/dL from Week 12 up to Week 52 ¶ Patients who did not enter escape therapy and received ≤ 100mg of additional concomitant prednisone from Week 12 up to Week 52.

The key features of Giant Cell Arteritis (GCA) relevant to the USMLE Step 1 are:

• Absence of signs and symptoms: No signs or symptoms of GCA recorded from Week 12 up to Week 52.
• Normalization of ESR: ESR < 30 mm/hr without an elevation to ≥ 30 mm/hr attributable to GCA from Week 12 up to Week 52.
• Normalization of CRP: CRP < 1 mg/dL, with an absence of successive elevations to ≥ 1mg/dL from Week 12 up to Week 52.
• Adherence to prednisone taper: Successful adherence to the prednisone taper defined by not more than 100 mg of excess prednisone from Week 12 through Week 52 2 2.

From the Research

Key Features of Giant Cell Arteritis (GCA)

• GCA is a systemic inflammatory vasculitis affecting medium and large vessels with potentially sight and life-threatening complications 3
• The disease is characterized by elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, and can be confirmed with superficial temporal artery biopsy 3
• Patients with suspected GCA should be started on high-dose corticosteroid therapy without delay, with treatment initiated urgently in cases of suspected ophthalmic involvement 4, 3

Treatment of GCA

• High-dose corticosteroid therapy is the mainstay of treatment, administered either intravenously or orally to prevent further vision loss and treat systemic vasculitis 4, 3
• Oral corticosteroid therapy is required for months to years, with careful follow-up and periodic laboratory evaluations with ESR and CRP 3
• Corticosteroids are tapered gradually over months, and may be associated with complications such as hypertension, diabetes mellitus, osteoporosis, psychosis, peptic ulcer disease, and infection 3
• Adjunctive immunomodulatory therapy may be considered in patients experiencing relapsing inflammation despite high doses of corticosteroids or those with corticosteroid-induced complications 5, 3

Adjunctive Therapies

• Methotrexate may be used as a glucocorticosteroid-sparing drug, although its efficacy in GCA is modest 6, 5
• Tocilizumab, an anti-IL-6 receptor antibody, has been shown to improve clinical symptoms, reduce the cumulative prednisone dose, and decrease the frequency of relapses in GCA patients 5
• Aspirin has been shown to decrease the rate of cranial ischemic complications secondary to GCA 6
• Other biologic agents, such as abatacept, ustekinumab, or anakinra, may be considered, although further confirmatory studies are needed 5