- ACRONYMS AND DEFINITIONS
- ACR - American College of Rheumatology
- ACPA - Anti-cyclic citrullinated peptide antibodies
- CRP - C-Reactive Protein
- ESR - Erythrocyte sedimentation rate
- EULAR - European League Against Rheumatism
- GCA - Giant cell arteritis
- PMR - Polymyalgia rheumatica
- US - Ultrasound
- EPIDEMIOLOGY
- PMR and GCA share many similarities and may be different manifestations of the same disease
- The incidence of PMR is 2 - 10 times that of GCA, but the diseases overlap with 40 - 60% of patients with GCA having symptoms of PMR and 1 - 21% of patients with PMR having temporal arteritis on biopsy
- The estimated lifetime risk of PMR in the USA is 2.43% for women and 1.66% for men. PMR is most commonly seen in whites of Northern European descent (up to 112 cases per 100,000) and is uncommon in Asians and African-Americans (1 case per 100,000). [1,2,4]
- RISK FACTORS
- Overview
- PMR and GCA are similar diseases that share common risk factors
- 1 - 21% of patients with PMR will also have GCA, and 40 - 60% of patients with GCA will have symptoms of PMR
- Known risk factors (PMR and GCA)
- 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 - up to 112 cases per 100,000
- Increasing latitude - more common at higher latitudes [1,2]
- Possible risk factors (PMR and GCA)
- 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]
- SYMPTOMS
- 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]
- PATHOPHYSIOLOGY
- Overview
- PMR and GCA share many similarities and may be different manifestations of the same disease
- 40 - 60% of patients with GCA have PMR symptoms at diagnosis
- The incidence of GCA in patients with PMR varies widely depending on the study with anywhere from 1 - 21% of PMR patients having a temporal artery biopsy positive for 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
- The cause of PMR is unknown
- PMR 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]
- DIAGNOSIS
- ESR and CRP
- Two laboratory markers of inflammation (ESR and CRP) play an important role in the diagnosis of PMR and GCA
- Most patients with GCA will have an elevated ESR, but in some studies, up to 11% of patients with GCA had an ESR of < 50 mm/hr
- For PMR, an elevated ESR or CRP is part of the diagnostic criteria, but in some studies, a normal ESR has been seen in up to 20% of patients diagnosed with PMR
- ESR and CRP can be elevated in a number of common conditions. See ESR and CRP for more. [1,4]
- Rheumatoid factor and ACPA
- The ACR lists a negative rheumatoid factor or ACPA as part of its diagnostic criteria for PMR
- Rheumatoid factor and ACPA are markers for rheumatoid arthritis, a condition that can mimic PMR, so their absence makes PMR more likely
- See rheumatoid factor and ACPA for more
- Ultrasound
- Ultrasound of the hips and shoulder has been utilized to help diagnose PMR
- Findings that are consistent with PMR 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 PMR classification guidelines include US findings as part of the diagnostic criteria [1,6]
ACR 2012 PMR Diagnostic Criteria | |
---|---|
PMR diagnosis - ALL patients MUST have the following:
|
|
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 | Score |
Morning stiffness for > 45 minutes | 2 |
Hip pain or limited range of motion | 1 |
Negative Rheumatoid factor or ACPA | 2 |
Absence of other joint pain | 1 |
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 |
-
GCA diagnostic criteria
- 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 an ESR of less than 50 mm/hr has been seen in up to 11% of patients with GCA
- Imaging with ultrasound, arteriography, and MRA/MRI are being used more frequently to diagnose GCA. In one study, MRI had a sensitivity of 94% and a specificity of 78% for GCA diagnosis when temporal artery biopsy was used as a reference standard. [4,5,12]
- Large-vessel vasculitis occurs in up to 25% of patients with GCA. CT angiography or MR angiography may be needed to confirm a diagnosis. [9]
- TREATMENT
ACR/EULAR 2015 Polymyalgia Rheumatica Treatment Recommendations |
---|
Overview
|
Corticosteroids
|
Methotrexate
|
Exercise
|
Complications
|
Giant cell arteritis treatment |
---|
Overview
|
Corticosteroid dosing
|
Complications
|
- DISEASE RELAPSE
- PMR
- Relapse is common, occurring in up to 50% of patients [1]
- GCA
- Relapse is common, occurring in up to 77% of patients who discontinue corticosteroids [5]
- STUDIES
- The trial enrolled 251 patients with active giant cell arteritis
Main inclusion criteria
- ≥ 50 years of age
- Active giant-cell arteritis within 6 weeks before baseline
- ESR > 30 mm/hour or CRP ≥ 1 mg/dL (including a presenting history of ESR> 50 mm/hour)
- Cranial symptoms of GCA or symptoms of polymyalgia rheumatica
- Evidence of GCA on imaging or temporal artery biopsy
Main exclusion criteria
- Major ischemic event, related or unrelated to GCA, within 12 weeks of screening
- History of GI disease (e.g. diverticulitis, Crohn's, ulcerative colitis) that might predispose a patient to perforations
- Serum creatinine > 1.4 mg/dL
- Total bilirubin > ULN
- ALT or AST> 1.5 X ULN
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
Randomized treatment groups
- 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
Duration: 52 weeks | |||||
Outcome | Group 1 | Group 2 | Group 3 | Group 4 | Comparisons |
---|---|---|---|---|---|
Primary outcome | 56% | 53% | 14% | 18% | 1 or 2 vs 3: p<0.001 |
|
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.
- Design: Randomized, placebo-controlled trial (N=72 | length = 76 weeks) in patients with newly diagnosed PMR
- Treatment: Methotrexate 10 mg/week vs Placebo for 48 weeks. All patients received prednisone at a starting dose of 25 mg/day with a goal to taper off within 24 weeks.
- Primary outcomes: The proportion of patients no longer taking prednisone, the number of flare-ups, and the cumulative prednisone dose after 76 weeks
- Results:
- Stopped prednisone: Methotrexate - 88%, Placebo - 53% (p=0.003)
- Experienced ≥ 1 flare-up: Methotrexate - 47%, Placebo - 73% (p=0.04)
- Median cumulative prednisone dose: Methotrexate - 2.1g, Placebo - 2.97g (p=0.03)
- Findings: Prednisone plus methotrexate is associated with shorter prednisone treatment and steroid sparing. It may be useful in patients at high risk for steroid-related toxicity.
- BIBLIOGRAPHY
- 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 PMR classification criteria
- 7 - PMID 19919443 - BSR PMR 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)
- 13 - PMID 26359488 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative Arthritis & Rheumatology, (2015)