Risk factors Definitions/Symptoms/Pathology Labs/Radiology Diagnostic criteria Management
  • Age - occurs almost exclusively in people ≥ 50 years old (mean age of onset 73 years); risk increases with advancing age
  • Female sex
  • Northern European descent
  • Increasing latitude - more common at higher latitudes [1,2]

  • Seasonal - may be more common in summer months
  • Rural areas - more common in rural vs urban areas
  • Genetics - HLA-DRB1
  • Parainfluenza virus type 1 infection
  • Varicella-zoster virus - highly prevalent in GCA-positive arteries
  • Infections - peaks in incidence seem to coincide with epidemics of Mycoplasma pneumoniae, parvovirus B19, and Chlamydia pneumoniae infections [1,2,10,11]
    Polymyalgia rheumatica and Giant Cell Arteritis
    • PR and GCA share many similarities and may be different manifestations of the same disease
    • 40 - 60% of patients with GCA have PR symptoms at diagnosis
    • 16 - 21% of patients with PR have GCA
    • The two diseases share much of the same pathology including chronic inflammation, immune activation, and elevated levels of interleukin-6 [1]
    • GCA is sometimes referred to as "temporal arteritis," but this term should not be used since other vasculitis syndromes may involve the temporal artery [3]

    Polymyalgia Rheumatica
    • Pain and stiffness - primarily affects the shoulder, hip, and neck muscles; stiffness is worse in AM and after sitting; stiffness in AM lasts for ≥ 1 hour; symptoms are typically bilateral
    • Low-grade fever - 40 - 50% of patients
    • Distal musculoskeletal symptoms - seen in 50% of patients; non-erosive arthritis
    • Swelling of the hands and feet - 8 - 12% of patients
    • Malaise
    • Fatigue
    • Weight loss [1,2,4]

    Giant Cell Arteritis
    • Headache - 75% of patients; temporal or occipital, bilateral, constant, not relieved with analgesics
    • Scalp tenderness - 50% of patients; commonly seen with headache
    • Jaw claudication (pain with chewing) - 50% of patients
    • Vision loss - ≤ 20% of patients; ischemia of optic nerve
    • Neuropathies - around 20% of patients
    • Aortic arch syndrome - 10 - 15% of patients; marked by claudication of the arms and bruits over the carotid, subclavian, axillary, and brachial arteries
    • Fever - up to 15% of patients; usually low-grade [1,3,4]

    Polymyalgia rheumatica
    • The cause of PR is unknown
    • PR is marked by inflammation of extra-articular synovial structures including bursitis of the shoulders, hips, and cervical spine
    • Synovial inflammation of the shoulder and hip joints may also occur
    • While muscle pain is common, muscle inflammation is not typically seen [1]

    Giant Cell Arteritis
    • GCA is marked by granulomatous inflammation of the arterial wall
    • Lymphocytes, macrophages, and fused macrophages (giant cells) are seen on histology. Despite the name, giant cells are only seen in 50% of cases.
    • Arterial stenosis and occlusion may occur

      • Affected arteries include:
        • Cranial arteries - branches of the internal and external carotid; intracranial vessels are rarely affected
        • Aortic arch and thoracic aorta - large-vessel vasculitis occurs in up to 25% of patients. Can be diagnosed with CT angiography or MR angiography.
        • Primary branches of the aorta - subclavian, left common carotid, brachiocephalic artery [3,4,5,9]
    Erythrocyte Sedimentation Rate (ESR)
    • Test: The ESR test measures how fast red blood cells separate from plasma and fall to the bottom of a test tube. Results are reported in millimeters of clear plasma that are present at the top portion of the tube after one hour. Cells tend to fall faster when inflammatory markers such as fibrinogen, immunoglobulins, and acute phase reactants are present. Therefore, a higher ESR indicates more inflammation. [8]
    • Diagnostic value: The ESR is used to determine if inflammation is present. A big drawback to the ESR test is that it is nonspecific, and a number of noninflammatory processes can cause an elevated ESR.

      • Causes of elevated ESR:
        • Infection
        • Inflammation
        • Anemia
        • Pregnancy
        • Advanced age
        • Immune disorders (Multiple Myeloma, Waldenstrom's macroglobulinemia)
        • Menstruation
        • Medications (oral contraceptives, methyldopa, theophylline)
        • Vitamin A
        • Obesity
        • Fatty liver [8]

C-Reactive Protein (CRP)
  • Test: C-Reactive Protein (CRP) is an "acute phase reactant." CRP is made in the liver and released into the bloodstream within a few hours of the start of an inflammatory process (ex. infection, tissue injury, trauma, etc.) [8]
  • Diagnostic value: CRP is used to determine if inflammation is present. Much like the ESR test, it is nonspecific, and can be elevated in patients who do not have an inflammatory process. CRP increases faster and decreases more rapidly than the ESR therefore it is a more acute measure of inflammation

    • Causes of elevated CRP:
      • Infection
      • Inflammation (CRP is often elevated in RA, but not SLE)
      • Pregnancy
      • Cancer
      • Medications (oral contraceptives, estrogens)
      • Obesity [8, 9]

  • Ultrasound (US)
    • Ultrasound of the hips and shoulder has been utilized to help diagnose PR
    • Findings that are consistent with PR include bicipital tenosynovitis, subacromial bursitis, subdeltoid bursitis, and trochanteric bursitis
    • Shoulder and hip joint effusions may also be seen
    • The addition of US to other findings can increase the specificity of the diagnosis
    • The ACR 2012 PR classification guidelines include US findings as part of the diagnostic criteria [1,6]

ACR 2012 PR Classification criteria
PR diagnosis - ALL patients MUST have the following:
  • Age ≥ 50 years
  • Bilateral shoulder aching
  • Elevated ESR or C-reactive protein

If the above criteria are met, then the diagnosis is based on a scoring system with the criteria below. The score required for diagnosis differs on whether Ultrasound (US) results are available.

  • Criteria without US - score of ≥ 4 establishes PR diagnosis
  • Criteria with US - score of ≥ 5 establishes PR diagnosis

Morning stiffness for > 45 minutes
Hip pain or limited range of motion
Negative Rheumatoid factor or ACPA
Absence of other joint pain
When US results are available
At least 1 shoulder with subdeltoid bursitis and/or biceps tenosynovitis and/or glenohumeral synovitis (either posterior or axillary) and at least 1 hip with synovitis and/or trochanteric bursitis 1
Both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis 1

ACPA - Anti-Citrullinated Peptide Antibodies
US - Ultrasound
Reference: ACR 2012 Proposed PR Criteria

  • GCA is diagnosed with a temporal artery biopsy
  • Since GCA can be segmental with skip lesions, a length of 20mm or more is typically taken to avoid false-negatives
  • Elevated ESR and C-reactive protein are typically present, but can be normal in up to 20% of patients with GCA
  • Imaging studies with ultrasound, arteriography and MRA/MRI have been used. In one study, MRI had a sensitivity of 94% and a specificity of 78% when temporal artery biopsy was used as a reference standard. [4,5,12]
  • Large-vessel vasculitis occurs in up to 25% of patients. CT angiography or MR angiography may be needed to confirm a diagnosis. [9]

  • Corticosteroids
    • Corticosteroids are the standard treatment for PR
    • Other therapies - methotrexate, azathioprine, tumor necrosis factor inhibitors - have been studied in small trials, but no conclusive benefit has been found [1]

      • The British Society of Rheumatology published the following recommendations in 2010:
        • Prednisolone or prednisone 15 mg a day for 3 weeks
        • Then 12.5 mg for 3 weeks
        • Then 10 mg for 4 - 6 weeks
        • Then reduction by 1 mg every 4–8 weeks or alternate day reductions (e.g. 10/7.5 mg alternate days, etc.)
        • Typically, 1-2 years of treatment are needed
        • An alternative regimen with IM methylprednisolone is given as: 120 mg IM every 3-4 weeks, reducing by 20 mg every 2-3 months [7]

  • Relapse
    • Relapse is common - up to 50% of patients [1]

  • Complications
    • Side effects of chronic steroid use - see corticosteroids
    • Increased risk of peripheral artery disease
    • Development of GCA [1]

  • Treatment
    • Corticosteroids are the standard treatment for GCA
    • In 2017, the FDA approved tocilizumab, an IL-6 receptor inhibitor, for the treatment of GCA. Approval was based on results from this study - Tocilizumab in GCA trial.
    • Low-dose aspirin may lower the risk of stroke and vision loss, although the evidence is not conclusive
    • Methotrexate has had mixed results in trials. Tumor necrosis factor inhibitors have not been found to be beneficial. Other disease-modifying drugs (e.g. azathioprine) have shown no conclusive benefit. [5,8]

      • The British Society of Rheumatology published the following recommendations in 2010:

        • GCA without jaw or tongue claudication or visual symptoms:
          • Prednisolone or prednisone 40 - 60 mg (not < 0.75 mg/kg) daily for 4 weeks (may need longer course if symptoms and laboratory abnormalities have not resolved)
          • Then dose is reduced by 10 mg every 2 weeks to 20 mg
          • Then by 2.5 mg every 2 - 4 weeks to 10 mg
          • Then by 1 mg every 1 - 2 months provided there is no relapse

        • GCA with visual symptoms:
          • Evolving visual loss or history of amaurosis fugax: IV methylprednisolone 500 mg to 1 gram daily for 3 days
          • Established vision loss: at least 60 mg prednisolone or prednisone daily
          • Continue for 4 weeks (may need longer course if symptoms and laboratory abnormalities have not resolved)
          • Then dose is reduced by 10 mg every 2 weeks to 20 mg
          • Then by 2.5 mg every 2 - 4 weeks to 10 mg
          • Then by 1 mg every 1 - 2 months provided there is no relapse [8]

  • Relapse
    • Relapse is common - up to 77% of patients who discontinue corticosteroids [5]

  • Complications
    • Side effects of chronic steroid use - see corticosteroids
    • Vision loss from narrowing or occlusion of the posterior ciliary arteries or retinal artery occlusion
    • Thoracic aortic aneurysms
    • Aortic dissections
    • Neuropathies [1,8]

  • References:
  • 1 - PMID 23051717 Lancet review
  • 2 - PMID 12140303 NEJM review
  • 3 - PMID 23795218 GCA review
  • 4 - PMID 18640460 - Lancet review 2008
  • 5 - PMID 21460132 - Clev Clinic review
  • 6 - ACR 2012 PR classification criteria
  • 7 - PMID 19919443 - BSR PR tx recs
  • 8 - PMID 20371504 BSR GSA tx recs
  • 9 - PMID 24988557 NEJM review
  • 10 - PMID 25695965 VZV study
  • 11 - PMID 27037084 VZV study II
  • 12 - PMID 27483045 High-Resolution Magnetic Resonance Imaging of Scalp Arteries for the Diagnosis of Giant Cell Arteritis: Results of a Prospective Cohort Study, Arthritis Rheumatol, (2017)