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Review of GCA and PMR

In Morning Report we reviewed a case of a patient presenting with bilateral hip pain and stiffness with associated headache who was found to have both polymyalgia rheumatica and giant cell arteritis and successfully treated with steroids I’ve included details about the clinical features, diagnosis and management of PMR and GCA below.

1. Giant Cell Arteritis (GCA)

Giant cell arteritis (GCA; also known as temporal arteritis because of frequent involvement of the temporal arteries) is a systemic vasculitis involving medium to large sized vessels. It is the most common vasculitis in those >50 years of age

  • Clinical Features of GCA:
    • Early recognition of GCA is essential!
    • Symptoms due to involvement of cranial vessels:
      • Headache
      • Visual disturbance (amaurosis fugax or permanent vision loss )
      • Jaw claudication,
      • Scalp tenderness
      • Abnormalities of the temporal artery (tender and/or enlarged and/or pulseless temporal artery)
    • Symptoms due to involvement of the great vessels (aorta and branches):
      • Claudication of the extremities (especially arm)
    • Symptoms due to Systemic Inflammation:
      • Fever, night sweats, weight loss
    • PMR:
      • Proximal myalgia, stiffness of neck, shoulder and pelvic girdles
  • As per the JAMA rational clinical exam, the most specific findings on history are diplopia (+LR 3.5) and jaw claudication (+LR 4.3)
  • Features of GCA on Examination:
    • Head and Neck Exam:
      • Specific exam findings include beaded, prominent or tender temporal artery (LR+ 4.6, 4.3, 2.6; (see JAMA RCE below)
      • Fundoscopy, look for a RAPD, assess visual acuity and/or consult ophthalmology for dilated examination
    • To look for aortic involvement:
      • BP discrepancy between arms.
      • Palpate and auscultate (for a bruit) carotid, brachial, radial, femoral and pedal pulses
      • Listen for AR murmur
    • Consider exam for PMR (see below)
  • According to the JAMA RCE, there are no physical exam features that can rule out GCA
JAMA Rational Clinical Exam
  • Differential Diagnosis:
    • Differential diagnosis will depend on whether the patient presents with prominent cranial/visual symptoms or not (e.g., aortitis alone)
    • With cranial symptoms:
      • Inflammatory: other vasculitides (though usually distinguishable)
      • Other inflammatory: sarcoid, idiopathic orbital inflammation
      • Neoplastic: B cell lymphoma, primary orbital tumors
      • Neuro-optho: non-arteritic ischemic optic neuropathy, optic neuritis, other opthalmic causes acute vision loss
      • Infection: Bacterial sinusitis extension, infective endocarditis TB, fungal infections, syphilis
      • Many other causes of headache (e.g., migraine)
    • Without cranial symptoms (Koster et al., 2018):
      • Hematology: Amyloid, multiple myeloma, erdheim-chester disease
      • Rheum: idopathic aortitis, IgG4 disease, vasculitis (Takayasu’s, PAN, ANCA-associated, Behcet’s), RA, lupus, spondyloarthritis
      • Infection: Syphilis, Zoster, EBV/CMV, endocarditis
      • Vascular: atherosclerotic disease
  • Investigations for GCA:
    • Lab investigations:
      • CBC (normocytic anemia, thrombocytosis)
      • Creatinine, LFTs
      • Vitamin D, Ca, ALP consider baseline bone density
      • Glucose and/or HbA1c
      • ESR, CRP
        • A normal ESR is very sensitive with a LR of 0.2
      • PMR work up as needed
    • Biopsy:
      • Temporal artery biopsy (TAB; at least 2 cm in length) important but 30-50% false negatives, thus should not delay treatment with steroids if suspect GCA.
      • If unable to obtain biopsy or unilateral biopsy is negative despite strong suspicion: consider other imaging modalities (e.g., MRA, potentially ultrasound), may consider bilateral biopsies
    • Imaging:
      • Consider CXR and other arterial imaging if concern for aortic involvement. During treatment CXR q2 years.
  • Diagnostic Criteria for GCA:
    • 1990 ACR criteria (require 2 of 5 of the following)
      • age >50 years
      • new headache
      • superficial temporal artery tenderness or decreased pulsation
      • elevated ESR >50
      • abnormal temporal artery biopsy (Vasculitis)
        • 3/5 criteria sensitivity 93.5%, specificity 91.2%
  • 2016 revised ACR criteria for diagnosis of GCA:
    • ≥3/11 points with ≥1 point from Domain 1 = GCA
  • Treatment of GCA:
    • Uncomplicated GCA: prednisone 1mg/kg with slow taper,
    • Complicated (e.g., evolving vision loss or history of amaurosis fugax) : IV pulse steroids 500-1000mg x3 days then oral prednisone
    • All patient receive low dose daily ASA
    • Additional DMARDs may be used (eg methotrexate)
      • NEJM 2017 trial: Tociluzimab + steroid taper superior to steroid taper + placebo in sustained steroid-free remission in patients with GCA
    • Bone protection (bisophophonate + VitD/Ca)
    • GI protection
    • Treatment of relapses will depend on the nature of symptoms that recur

2. Relationship between GCA and PMR

  • ~50% of patients with GCA have PMR
  • ~15% of patients with PMR will have GCA
  • The two conditions may present together but may sometimes be separated by long intervals, and either one may present first

3. Polymyalgia Rheumatica (PMR)

  • Key Clinical Features:
    • Pain in neck, shoulder, hip girdle, prominent morning stiffness (≥1 hour) and tenderness.
      • Difficulty getting up from chair, rising from bed in morning, difficulty with ADLs
    • 40-50% have systemic symptoms: low grade fever, weight loss, fatigue and depression
    • Distal MSK manifestations: synovitis of proximal joints, periarticular arthritis, 25% peripheral arthritis, 15% carpal tunnel syndrome, 12% distal extremity swelling
  • Prevalence:
    • Like GCA, PMR is almost exclusive to patients > 50 years of age and 2-3x more common in women
  • Pathophysiology:
    • Unknown but some studies show a cyclical pattern in incidence, suggesting environmental infectious trigger, e.g., parvovirus B19, Mycoplasma pneumoniae,  Chlamydia pneumoniae.
  • Examination for PMR:
    • MSK and neurologic exams
      • Expect normal muscle strength with no muscle atrophy initially (can progress in later stages)
      • Tenderness to palpation with decreased active ROM in proximal hip and shoulder girdle
      • Synovitis, arthritis
    • Look for features of GCA as above
  • Differential Diagnosis:
    • Inflammatory: late onset RA, seronegative inflammatory arthritis, SLE, scleroderma, vascultiis, inflammatory myopathies. RS3PE
    • Non-inflammatory: OA, cervical spondylosis, rotator cuff disorder, adhesive capsulitis, fibromyalgia
    • Infection: TB (miliary), infective endocarditis, osteomyelitis, septic arthritis, other infections
    • Malignancy: lymphoma, multiple myeloma, leukemia, solid tumor or mets (e.g, prostate, bowel, lung, renal, breast)
    • Endocrine: Hypo/hyperthyroidism, hyper/hypoparathyroidism
    • Drug induced myalgias: E.g., Statins
    • Parkinson’s Disease
  • Investigations (EULAR, ACR, 2015)
    • To exclude mimicking condition, establish baseline:
      • RF and/or Anti-CCP,
      • CRP and/or ESR
      • CBC
      • HbA1c or FBG
      • Cr, LFTs, CK
      • Urinalysis
      • Bone profile (VItamin D, Calcium, ALP and consider baseline bone desnity)
      • TSH
      • Consider protein electrophoresis
    • If clinically indicated to rule out other diagnoses:
      • ANA
      • ANCA
      • TB tests +/- CXR
    • Temporal artery biopsy not needed in cases of isolated PMR
      • Monitor for GCA during treatment. Consider if develops signs of vasculitis, ESR or CRP rises despite symptoms resolution on steroids, response is incomplete with low dose prednisone (≤20 mg/d)
  • Diagnostic Criteria for PMR:
    • One set of Diagnostic Criteria (Healy, 1984):
      • Age >50
      • ESR ≥40 mm/h
      • Pain persisting for ≥1 month and involving 2 of the following areas: neck, shoulders, and pelvic girdle
      • Exclude other causes (e.g., active infections, RA or other inflammatory conditions, cancer, drugs, thyroid disorders)
      • Morning stiffness ≥1 hour
      • Rapid response to prednisone (≤20 mg)
  • 2012 EULAR/ ACR Classification Criteria (Not diagnostic criteria, but used for research purposes):
    • Score≥4 points = 68% sensitivity and 78% specificity
      ≥5 points= 66% sensitivity and 81% specificity
Latest Advances In the Diagnosis And Treatment Of Polymyalgia ...
  • Treatment of PMR
    • Prednisone 12.5-20mg/d x 2-4 weeks
    • Taper to 10-20mg/d within 1-2 months if response
    • Relapses should be assessed by symptoms, not exclusively inflammatory markers to guide treatment
    • If relapse, increase back to previously higher dose.
    • Involve specialist with consideration of steroid-sparing agents like methotrexate if recurrent relapses, prolonged treatment duration or contraindications to steroids
    • Bone protection
    • GI protection

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