Giant Cell Arteritis

Aka: Giant Cell Arteritis, Cranial Arteritis, Granulomatous Arteritis, Temporal Arteritis, Arteritic Ischemic Optic Neuropathy

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II. Epidemiology

  1. Closely associated with Polymyalgia Rheumatica
    1. Polymyalgia is present in 27-53% of those with Temporal Arteritis
  2. Prevalence: 500 per 100,000 over age 50 years
  3. Rarely occurs under age 50 years
  4. Average age of presentation: 72 years (peak age 70-80 years old)

III. Pathophysiology

  1. Inflammation of medium and large arteries originating from aortic arch
    1. Most commonly affects external Carotid Artery branches (esp. temporal artery, occipital artery)
    2. Infiltration of arterial wall with inflammatory cells
    3. Localized to elastic laminae
      1. May extend to panarteritis
  2. Intima thickens results in lumen narrowing, Occlusion
    1. Causes Arteritic Ischemic Optic Neuropathy

IV. Symptoms

  1. See Polymyalgia Rheumatica for rheumatologic symptoms
  2. Onset of symptoms
    1. Insidious over months or
    2. Sudden Onset
  3. New Onset Headache (LR+ 3.6, LR- 0.43)
    1. Test Sensitivity >50 to 70%
    2. Test Specificity 82%
    3. Over temporal or occipital arteries (but may occur elsewhere)
    4. Boring ache of moderate intensity with minimal relief from Analgesics
    5. Scalp tenderness, and touch may provoke Headache
  4. Jaw Claudication (LR+ 20, LR- 0.62)
    1. Test Sensitivity: 39%
    2. Test Specificity: 98%
    3. Facial Muscle pain or weakness with chewing and relieved with rest
    4. May be atypical with tooth, sinus, Tongue or Ear Pain
  5. Visual symptoms (LR+ 2.5, LR- 0.81)
    1. Test Sensitivity: 28%
    2. Test Specificity: 89%
    3. May precede permanent Vision Loss by hours or days
    4. Vision may be partially obscured
    5. Visual Field cuts
    6. Diplopia
    7. Acute Vision Loss or Amaurosis Fugax
  6. Systemic symptoms (at least one systemic symptom occurs in 75% of patients)
    1. Fever of Unknown Origin
    2. Malaise
    3. Fatigue
    4. Anorexia
    5. Weight loss
  7. Respiratory and other symptoms (10% of cases)
    1. Sore Throat
    2. Dry Cough
    3. Tongue Pain (or tongue Claudication)
    4. Pharyngitis
    5. Dysphagia
    6. Choking Sensation
    7. Lower extremity Claudication

V. Signs

  1. See Polymyalgia Rheumatica for rheumatologic findings
  2. Tenderness or Hypersensitivity over temporal or occipital arteries or scalp (LR+ 21, LR- 0.6)
    1. Test Sensitivity: 41%
    2. Test Specificity: 98%
  3. Temporal artery abnormalities (LR+ 19, LR- 0.44)
    1. Test Sensitivity: 57%
    2. Test Specificity: 97%
    3. Palpate superior to ear tragus and compare to contralateral side
      1. Pulse reduction
      2. Nodular, beaded or thickened
  4. Eye Exam to exclude other causes of Vision change
    1. Visual Acuity
    2. Extraocular Movements
    3. Pupillary Light Reflex
      1. Observe for Afferent Pupillary Defect
    4. Funduscopic Exam
  5. Cardiovascular Exam (large vessels including the aorta may be affected)
    1. Peripheral pulses (evaluate for symmetry, esp. between radial pulses)
  6. Complete Neurologic Exam
    1. Evaluate for neurologic deficits suggestive of Cerebrovascular Accident

VI. Complications

  1. Sudden Vision Loss (Anterior Ischemic Optic Neuropathy)
    1. Occurs in 8-15% of Temporal Arteritis patients
    2. See Amaurosis Fugax
    3. Secondary to narrowing of arterial lumens
      1. Ophthalmic terminal branches
      2. Posterior ciliary arteries
    4. Visual deficit is permanent
      1. May be preceded by visual changes or Headaches by hours or days
      2. Contralateral eye is typically affected within 1-2 weeks (requires prompt management)

VII. Associated Conditions

  1. Polymyalgia Rheumatica (50%)
  2. Jaw Claudication (see above)
  3. Aorta involvement (15% of cases)
    1. Aortic Arch Syndrome
    2. Vertebrobasilar Artery thrombosis
    3. Upper extremity Claudication
    4. Raynaud Phenomenon
    5. Thoracic Dissection
    6. Myocardial Infarction
    7. Mesenteric Infarction

VIII. Differential Diagnosis

  1. Jaw Claudication
    1. Dental Pain
    2. Temporomandibular Joint Disease
  2. Vision Changes
    1. Optic Neuritis
    2. Retinal Artery Occlusion
    3. Embolic conditions (e.g. endocarditis)
  3. Facial Pain
    1. Acute Otitis Media
    2. Otitis Externa
    3. Acute Sinusitis
    4. Herpes Zoster
  4. Headache or other Neurologic Findings
    1. Small and medium vessel Vasculitis (e.g. Polyarteritis Nodosa, drug-induced Vasculitis)
    2. Migraine Headache
    3. Trigeminal Neuralgia
    4. Cerebrovascular Accident
    5. Meningitis
    6. Encephalitis
    7. Malignancy (Brain Mass, Lymphoma, Multiple Myeloma)
    8. Hypothyroidism

IX. Diagnosis

  1. Precautions
    1. Strongly consider GCA in over age 60 years old with sudden onset Vision Loss or Diplopia (including transient)
    2. Delayed treatment may result in blindness
    3. Start Corticosteroids immediately when diagnosis suspected
    4. Do not wait for biopsy results prior to starting Corticosteroids
    5. Obtain biopsy within 2 weeks of starting Corticosteroids (first 2-3 days preferred)
  2. Temporal Artery Biopsy
    1. Biopsy shows chronic inflammation, necrotizing arteritis
      1. Mononuclear cell predominance OR
      2. Granulomatous process with multinucleated giant cells
    2. Obtain at least 1 cm sample from most symptomatic side
      1. Long biopsy specimens (>2 cm) are preferred
    3. Test Sensitivity: 80-92%
      1. False Negative Rate up to 20%
      2. Consider biopsy of contralateral side if negative biopsy despite high clinical suspicion
      3. Consider empiric treatment despite negative biopsy if high clinical suspicion
    4. Biopsy positive for 2 weeks after starting Prednisone
      1. Biopsy is best within 48 to 72 hours
  3. Findings most suggestive of Temporal Arteritis
    1. Beaded (nodular thrombus) temporal artery (+LR 4.6)
    2. Prominent temporal artery (+LR 4.3)
    3. Jaw Claudication (+LR 4.2)
    4. Diplopia (+LR 3.4)
    5. Temporal artery pulse absent (+LR 2.7)
    6. Temporal artery tender (+LR 2.6)
    7. Smetana (2002) JAMA 287:92-101 [PubMed]
  4. American College of Rheumatology criteria (3 of 5 criteria required)
    1. Age 50 years or older
    2. Localized Headache of new onset
    3. Tenderness or decreased pulse over the temporal artery
    4. ESR 50 mm/h or higher
    5. Temporal artery biopsy with necrotizing arteritis (see findings above)

X. Labs

  1. See Polymyalgia Rheumatica for complete lab evaluation of differential diagnosis
  2. Acute phase reactants
    1. Obtain both ESR and C-RP
      1. Test Sensitivity approaches 99% in Temporal Arteritis when both are obtained
    2. Erythrocyte Sedimentation Rate (ESR, Westergren) Increased
      1. See Polymyalgia Rheumatica for interpretation
      2. ESR typically >50 mm/h (averages 83 mm/h in Temporal Arteritis, often >100 mm/h)
        1. However, ESR <50 mm/h does NOT completely exclude Temporal Arteritis
      3. Age based cut-offs
        1. Men: Age/2
        2. Women: (Age + 10)/2
    3. C-Reactive Protein increased
      1. Higher Test Sensitivity than ESR for initial diagnosis
      2. No well defined cut-off criteria (unlike ESR with cutoff of 50 mm/h)
    4. Interleukin-6
      1. May be elevated in new or recurrent GCA and returning to normal with remission
      2. Consider when ESR and C-RP are normal despite high clinical suspicion
  3. Nonspecific Lab findings
    1. Moderate normocytic, normochromic Anemia
    2. Thrombocytosis
    3. Decreased Serum Albumin
    4. Increased Alkaline Phosphatase (50% of cases)

XI. Imaging

  1. Indications
    1. Strong clinical suspicion for GCA, but negative biopsy or biopsy unavailable
  2. Doppler Ultrasound of temporal artery
    1. Positive (abnormal) if noncompressible, hypoechoic temporal artery with wall thickening
    2. Sufficient for Temporal Arteritis diagnosis if positive
    3. Luqmani (2016) Health Technology Assessment
      1. https://www.ncbi.nlm.nih.gov/books/NBK401227/
    4. Karassa (2005) Ann Intern Med 142(5): 359-69 [PubMed]
    5. Aranda-Valera (2017) Clin Exp Rheumatol 35 Suppl 103(1):123-127 +PMID:28244857 [PubMed]
  3. Other advanced imaging studies
    1. Fluorodeoxyglucose PET Scan
    2. MRI
    3. CT Aortic Survey (or MRI equivalent)
      1. Consider aortic imaging for symptoms or signs of large vessel involvement
      2. Consider in all new GCA cases (esp. if comorbid Hypertension)

XII. Management

  1. Urgent referral to rheumatology in all cases
  2. Do not delay starting if high level of suspicion
    1. Biopsy within 2 weeks of starting Corticosteroids (best within first 48-72 hours)
    2. Alternatively, temporal artery Ultrasound may be performed
  3. Corticosteroids
    1. Starting Dose
      1. No visual symptoms or Jaw Claudication
        1. Prednisone 40-60 mg (at least 0.75 mg/kg) orally daily
        2. Consider 40 mg instead of 60 mg orally daily for those with Diabetes Mellitus
      2. Visual symptoms (e.g. Amaurosis Fugax), Jaw Claudication or other critical cranial ischemia
        1. Solumedrol 250 mg every 6 hours for 3 days
        2. Following solumedrol course, switch to oral Prednisone 60 mg orally daily (as above)
      3. Established Vision Loss
        1. Prednisone 60 mg (at least 0.75 mg/kg) orally daily
        2. Protects the contralateral, unaffected eye
    2. Taper protocol (typically after 4-8 weeks on initial dose)
      1. Start tapering after 4 weeks on Prednisone AND symptom resolution and ESR/CRP normalization
      2. Taper dose by 10 mg every 2 weeks until 20 mg dose is reached, then
      3. Taper dose by 2.5 mg every 2-4 weeks until 10 mg dose is reached, then
      4. Taper dose by 1 mg every 1-2 months
      5. Anticipate low dose (10 mg) reached by 6 months
    3. Efficacy
      1. Symptoms and Signs remit in approximately 1 month
      2. Targets: Vision change, fever, Headache, myalgias
      3. Do not use ESR normalization as a target
    4. Course
      1. Continue Prednisone 1-2 years if ocular complications
      2. Prednisone may require continuation up to 5 years in some cases
  4. Adjuvant medications
    1. Tocilizumab (Actemra)
      1. Monoclonal Antibody associated with significant sparing of Corticosteroids
      2. Dosed weekly or to every other week
      3. Unizony (2012) Arthritis Care Res 64(11):1720-9 +PMID:22674883 [PubMed]
    2. Aspirin 81 mg orally daily
    3. Concurrent Methotrexate is not typically recommended (unlike Polymyalgia Rheumatica)
      1. However its use, along with Biologic Agent are left to local expert opinion (e.g. rheumatology)
  5. Prevention of Bone Mineral Density Loss due to Corticosteroids (e.g. Prednisone)
    1. See Corticosteroid Associated Osteoporosis
    2. Vitamin D Supplementation
    3. Calcium Supplementation
    4. Consider DEXA Scan
    5. Consider Bisphosphonates
  6. Other Prevention of complications from Corticosteroids (e.g. Prednisone)
    1. See Polymyalgia Rheumatica
    2. Consider Gastrointestinal Prophylaxis (e.g. Omeprazole or other Proton Pump Inhibitor)

XIII. Management: Follow-up

  1. Rheumatology consult
    1. One week after starting steroids, then
    2. Three weeks after starting steroids, and then
    3. Six weeks
  2. Rheumatology or primary care
    1. Visit at 3 months, 6 months, 9 months and 12 months
  3. Labs (each visit)
    1. Complete Blood Count
    2. Erythrocyte Sedimentation Rate (ESR)
    3. C-Reactive Protein (C-RP)
    4. Basic chemistry panel (Electrolytes, Renal Function tests, and Serum Glucose)
  4. Imaging
    1. Chest XRay to assess aortic root every 2 years
  5. Evaluation
    1. Relapse symptoms
      1. Fever without other cause
      2. New or Recurrent Headache, sclp tenderness, Jaw Claudication or Vision change
      3. Extremity Claudication, CVA symptoms
      4. Proximal Muscle pain (Shoulder or pelvic girdle) or Morning stiffness
      5. Fatigue
    2. Adverse effects to treatment (Corticosteroid adverse effects)
      1. Gastritis or Peptic Ulcer
      2. Bone density
      3. Hyperglycemia

XIV. Course

  1. Self limited course over months to years with Corticosteroids
  2. Increased mortality related to other regions of Vasculitis
    1. Brekke (2019) Arthritis Res Ther 21(1): 154 [PubMed]
  3. Risk of permanent blindness if untreated
    1. Contralateral eye is typically affected within 1-2 weeks (requires prompt management)

XV. References

  1. Shoenberger and Ishimori in Herbert (2015) EM:Rap 15(5): 7-8
  2. Buttgereit (2016) JAMA 315(22): 2442-58 [PubMed]
  3. Caylor (2013) Am Fam Physician 88(10):676-84 [PubMed]
  4. Dasgupta (2010) Rheumatology 49(8): 1594-7 [PubMed]
  5. Hellmann (2002) JAMA 287:2996-3000 [PubMed]
  6. Loddenkemper (2004) Arch Neurol 61:1620-2 [PubMed]
  7. Raleigh (2022) Am Fam Physician 106(4): 420-6 [PubMed]
  8. Selvarani (2002) N Engl J Med 347:261-71 [PubMed]
  9. Unwin (2006) Am Fam Physician 74:1547-58 [PubMed]
  10. Weyand (2003) Ann Intern Med 139:505-15 [PubMed]

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