POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS

• ACR - American College of Rheumatology
• GCS - Giant cell arteritis
• PR - Polymyalgia rheumatica
• US - Ultrasound

• 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]

• 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]

• 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]

• 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]

• 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]

• 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 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]

Diagnostic criteria - GCA

• GCA is diagnosed with a temporal artery biopsy
• Since GCA can be segmental with skip lesions, a length of 20 mm 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]

• Design: Randomized, controlled trial (N=251, length - 52 weeks) in patients with active GCA
• Baseline characteristics: Average age - 69 years | Newly-diagnosed GCA - 48%, Relapsing GCA - 52% | Average duration of disease - 296 days | Symptoms of PR - 61% | Average ESR - 24 mm/hr
• Treatment:
• Group 1 (100 patients): Tocilizumab 162 mg SQ once weekly + 26-week prednisone taper
• Group 2 (50 patients): Tocilizumab 162 mg SQ every other week + 26-week prednisone taper
• Group 3 (50 patients): Placebo + 26-week prednisone taper
• Group 4 (51 patients): Placebo + 52-week prednisone taper
• Prednisone was initiated at a previously used dose or continued at current dose and then tapered weekly
• Primary outcome: Rate of sustained glucocorticoid-free remission at week 52 in each tocilizumab group as compared with the rate in the placebo group that underwent the 26-week prednisone taper
• Results:
• Primary outcome: Group 1 - 56%, Group 2 - 53%, Group 3 - 14%, Group 4 - 18% (1 or 2 vs 3: p<0.001)
• The incidence of adverse events was similar in all the trial groups, but fewer patients reported serious adverse events in Group 1 (15%) and Group 2 (14%) than in Group 3 (22%) and Group 4 (25%)
• Findings: Tocilizumab, received weekly or every other week, combined with a 26-week prednisone taper was superior to either 26-week or 52-week prednisone tapering plus placebo with regard to sustained glucocorticoid-free remission in patients with giant-cell arteritis. Longer follow-up is necessary to determine the durability of remission and safety of tocilizumab.