Polymyalgia rheumatica (PMR) characteristically demonstrates symmetrical pain and stiffness in and around shoulders, neck and hip girdle.  Pain and stiffness are the worst in the morning and also worsen after rest or prolonged inactivity.  Restricted range of motion of shoulder is common. Patients often complain of pain and stiffness in the upper arms, hips, thighs, upper and lower back. The onset of symptoms is rapid, usually from a day up to 2 weeks.  It affects the quality of life as pain may impair sleep at nighttime and daytime routine activities like getting out of bed or chair, taking a shower, making own hair, driving, etc.[18]

The pain and stiffness associated with PMR are most probably related to inflammation of the glenohumeral and hip joints and in the upper extremity the subacromial, subdeltoid, and trochanteric bursae.[19] Almost up to half of the patients experience systemic symptoms like fatigue, malaise, anorexia, weight loss or low-grade fever.[20] Persistent high fever is uncommon in PMR and should alert suspicion of GCA.[18]  

Peripheral involvement is also frequent with arthritis in a fourth of patients. Other peripheral features like carpal tunnel syndrome, distal extremity swelling with pitting edema, and distal tenosynovitis can be present. Arthritis does not lead to erosions or deformities or development of rheumatoid arthritis.[21]  Distal extremity swelling with pitting edema responds promptly to glucocorticoids.[22]

On physical examination, diffuse tenderness is usually in evidence over the shoulder without localization to specific structures. Pain usually restricts the active shoulder range of motion, and passive range of motion could be normal when carefully examined. Restriction of neck and hip movements because of pain is also common. Muscle tenderness of neck, arms and thigh may be present. Even though the patient might complain of non-specific weakness, muscle strength is usually intact on a more thorough examination.[18]

Laboratory studies:

Elevated ESR is a common feature in polymyalgia rheumatica. ESR higher than 40mm has been considered significant by the majority of authors.[23][24][25]  ESR lower than 40 mm/h is present in 7% to 20% of patients. Patients with low ESR usually have a lower frequency of systemic features like fever, weight loss, and anemia. Response to therapy, the frequency of relapses and the risk of developing GCA among these patients appear to be comparable with high ESR patients.[26][27] CRP is also typically elevated. CRP was found to be a more sensitive indicator of disease activity in one study while ESR found to be a superior predictor of relapse.[28]

Normocytic anemia and thrombocytosis can occur.  Liver enzymes and especially alkaline phosphatase are occasionally elevated. Serologic tests, such as ANA, RF, and Anti-CCP Ab are negative. CPK value is within the normal range. 

Imaging studies:

Ultrasound: 

Ultrasound is useful in diagnosis and monitoring of treatment by assessing degrees of subacromial/subdeltoid bursitis, long head biceps tenosynovitis, and glenohumeral synovitis. In one study power Doppler (PD) signal at subacromial/subdeltoid bursae was observed in a third of PMR patients.  The positive PD signal at diagnosis correlated with the increased frequency of relapses but the persistence of PD findings did not correlate with relapses/recurrences.[29] The 2012 ACR/EULAR PMR classification criteria include ultrasound.[30]

MRI:

MRI helps depict bursitis, synovitis and tenosynovitis similar way the ultrasound does, however, it is more sensitive for hip and pelvic girdle findings.[31] Pelvic MRI frequently shows often bilateral, peri-tendinous enhancement of pelvic girdle tendons and occasional low-grade hip synovitis. An enhancement of the proximal origin of rectus femoris appears to be highly specific and sensitive finding.[32]

PET:

PET scan shows FDG uptake in shoulders, ischial tuberosities, greater trochanters, glenohumeral and sternoclavicular joints in PMR patients.[33] Role of PET in diagnosing large vessel vasculitis is described in a discussion below with GCA.  

2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative[30]

Patients aged 50 years or older with bilateral shoulder aching and abnormal C-reactive protein concentrations or ESR, plus at least four points (without ultrasonography) or five points or more (with ultrasonography) from

• Morning stiffness in excess of 45 minutes duration (two points)
• Hip pain or restricted range of motion (one point)
• Absence of rheumatoid factor or anti-citrullinated protein antibodies (two points)
• Absence of other joint involvement (one point)
• If ultrasonography is available, at least one shoulder with subdeltoid bursitis, biceps tenosynovitis or glenohumeral synovitis (either posterior or axillary); and at least one hip with synovitis or trochanteric bursitis (one point)
• If ultrasonography is available, both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis (one point)

"A score=4 had 68% sensitivity and 78% specificity for discriminating all comparison subjects from PMR. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. Adding ultrasound, a score=5 had increased sensitivity to 66% and specificity to 81%. These criteria are not meant for diagnostic purposes."[30]

PMR and GCA

PMR and GCA  frequently overlap, and 20% of patients with PMR will get diagnosed with GCA later. In biopsy-proven GCA, PMR features are present in up to 50% of cases.[18]

In a study, among PMR patients with persistence of classic symptoms but no cranial GCA like symptoms, a PET/CT scan was positive for large vessel vasculitis in 60.7%.  Inflammatory low back pain, pelvic girdle, and diffuse lower limb pain were also predictors of positive PET/CT scan these patients.[34] In another study among patients who required higher doses of steroids or those who had atypical features like low-grade fever and weight loss among others, 48% had large vessel vasculitis in PET/CT.  Elevated CRP values were found to correlate with large vessel vasculitis.[35]

In a study where a random sample of 68 patients with "pure' PMR, histological examinations of biopsy specimens of the temporal artery revealed inflammatory changes in three patients only (4.4%).[36]

PMR patients should undergo evaluation for features suggestive of GCA at every visit.  Routine biopsy of the temporal artery is not a recommendation. Features like the development of a new headache, vision and jaw symptoms, tenderness and lack of pulses in temporal artery, lack of pulses in the periphery, the persistence of inflammatory markers, high-grade fever and refractoriness of classic symptoms are the red flags that should prompt an urgent evaluation for GCA. 

Oral glucocorticoid is a well-proven treatment. The following summarizes the essential points of EULAR-ACR 2015 recommendations for management[37]

• 12.5 to 25 mg/d prednisone equivalent as an initial therapy
• Glucocorticoids should be tapered gradually
• Taper to an oral dose of 10 mg per day prednisone equivalent within 4 to 8 weeks
• Once remission is achieved, taper daily oral prednisone by 1 mg every 4 weeks until discontinuation 
• Minimum of 12 months of treatment
• For relapse, increase oral prednisone to the pre-relapse dose and decrease it gradually (within 4 to 8 weeks) to the dose at which the relapse occurred
• individualize dose-tapering schedules, based on regular monitoring of patient disease activity, laboratory markers, and adverse events
• Consider early introduction of methotrexate (MTX) in addition to glucocorticoids, particularly in patients at high risk of relapse and/or prolonged therapy as well as in cases with risk factors, comorbidities and/or concomitant medications where GC-related adverse events are more likely to occur

Clinical trials used oral MTX at oral doses of 7.5 to 10 mg/week.[37]  A study shows leflunomide is an effective steroid-sparing agent can be used in PMR as well.[38] It could be an alternative if the patient is not able to take MTX for various reasons. Sparse data for azathioprine exist for treatment of PMR, and its use may be an option in cases with contraindications for methotrexate.[39]. EULAR-ACR 2015 recommendations advise against the use of anti-TNF agents.[37]

Most of the data for the use of tocilizumab (TCZ) in PMR come from PMR coexisting with GCA. Case series and open-label studies have shown TCZ is useful in PMR with relapse or insufficient response to GC.[40]  An open-label study suggested that when used in newly diagnosed PMR patients,  relapse-free remission without GC treatment at 6 months was achievable.[41] Randomized controlled trials are needed to evaluate if TCZ is routinely beneficial in certain PMR patients. 

Vitamin D and calcium supplementation are routine recommendations for patients on long-term steroid. Bisphosphonate prophylaxis is a recommended option for patients in moderate to high fracture risk categories that would include patients over 40 years with FRAX score of >1% and 10% risk of hip and major osteoporotic fracture respectively.[42]

Close follow up is recommended. Guidelines published by BSR and BHPR recommends follow up at weeks 0, 1 to 3, and 6, then months 3, 6, 9, and 12 in the first year (with extra visits for relapses or adverse events).[43] It seems prudent to follow up patient every 3 months till remission and after that every 6 months to annually to monitor recurrence. Relapses often entail an increase in ESR and CRP and the return of symptoms. Increased risk of relapse is found to correlate with a higher initial dose of steroid used, rapid steroid tapering, HLA-DRB1*0401, and persistently high inflammatory markers.[12][44][45]

Polymyalgia rheumatica has nonspecific features that many other entities could mimic. Other entities need to be excluded with the investigations, as deemed needed by clinical suspicion, before diagnosing PMR. Some important differentials are listed below[20][46]

• Rheumatoid arthritis
• GCA
• ANCA related vasculitis
• Inflammatory myositis and statin-induced myopathy
• Gout and CPPD disease
• Fibromyalgia
• Overuse or degenerative shoulder pathology e.g. osteoarthritis, rotator cuff tendinitis and tendon tear, adhesive capsulitis
• Cervical spine disorders e.g. osteoarthritis, radiculopathy
• Crown dens syndrome
• Hypothyroidism
• Obstructive sleep apnea
• Depression
• Viral infections like EBV, hepatitis, HIV, Parvo B19
• Systemic bacterial infections, septic arthritis
• Cancer
• Diabetes

Mortality among individuals with polymyalgia rheumatica is not significantly increased compared to the general population.

Discussion of Giant-cell arteritis was under the evaluation heading. 

Polymyalgia rheumatica patients have an increased risk of cardiovascular diseases by 1.15 to 2.70 as per different studies. Premature atherosclerosis resulting from chronic inflammation is the most likely cause if premature CAD.[47]

Cancer association with PMR is not entirely clear.[48] In a study increased the risk of lymphoplasmacytic lymphoma - Waldenstrom macroglobulinemia correlated with PMR with OR of 2.9.[49]

PMR patients have higher chances of developing inflammatory arthritis. Features of small joint synovitis, younger age and positive anti-CCP positivity in PMR patients were found to have an association with risk of developing inflammatory arthritis.[50]

Patients with polymyalgia rheumatica usually receive an initial evaluation by primary care doctors or nurse practitioners.  Low threshold for suspicion, timely referral to rheumatology and excluding giant cell arteritis are important aspects in the initial care of these patients. PMR has a long list of differentials and mimickers and diagnosis may be even more challenging if the patient already has one of those as a coexisting condition. Essential aspects of long-term management are the need for frequent follow-up, vigilance in detecting developing GCA, and the management of relapse or refractory disease.