Epidemiology

• The incidence of the disease in patients aged over 50 is about 100 per 100,000.^[4]
• The average age of onset is just over 70 years of age. It is seldom diagnosed in people younger than 50 years of age.^[5]
• Polymyalgia rheumatica (PMR) is seen mainly in people of north European ancestry, although it can occur in any ethnic group.^[4]
• Women are more frequently affected than men with a female:male ratio of approximately 3:1.

Aetiology

• The aetiology of PMR is as yet unknown; however, family clusterings of the disease and an association with the HLA-DRBI*04 and *01 alleles, suggest that a genetic predisposition to environmental factors may play a part.^[6]
• A viral or infectious cause has also been suspected due to the increased prevalence of antibodies to respiratory syncytial virus and adenovirus in PMR and the association between the increased incidence of the disorder and epidemics of Mycoplasma pneumoniae, parvovirus B19 and Chlamydophila pneumoniae.

Presentation

The presenting symptoms are nonspecific but polymyalgia rheumatica (PMR) should be suspected in patients aged over 65 who have subacute to acute onset of bilateral, severe, persistent pain in the neck, shoulders and pelvic girdle. Core inclusion criteria for a diagnosis of PMR include:^[7]

• Age over 50 years and duration of symptoms more than 2 weeks.
• Bilateral shoulder or pelvic girdle aching, or both.
• Morning stiffness duration of more than 45 minutes' duration.
• Evidence of an acute-phase response (raised ESR/CRP).
• PMR can be diagnosed with a normal ESR and/or CRP if there is a classic clinical picture and response to steroids. These patients should be referred for specialist assessment.^[7]

The most characteristic presenting feature of PMR is bilateral shoulder pain and stiffness of acute or subacute onset with bilateral upper arm tenderness.^[4] Other symptoms and signs may include:

• Pain on active and passive movement of joints (shoulders 70-95%, hips and neck 50-70%).
• Morning stiffness; stiffness after periods of rest and morning stiffness of more than one hour are typical.^[4]
• Systemic symptoms, especially present at the onset of the disease, include lethargy, loss of appetite, weight loss, low-grade fever and depression.^[4]
• Lethargy.
• Mild asymmetrical synovitis may occur, especially in the wrists and knees.
• Oedema of hands, wrists, ankles and feet.
• Carpal tunnel syndrome.

Muscle weakness is not a feature of the disease but disuse atrophy may occur with protracted and untreated symptoms.^[4]

Differential diagnosis^[4]

• Inflammatory disorders:
  • Rheumatoid arthritis
  • Late onset spondyloarthropathy, including ankylosing spondylitis, psoriatic arthritis
  • Systemic lupus erythematosus, scleroderma, Sjögren's syndrome, vasculitis
  • Dermatomyositis, polymyositis
• Noninflammatory disorders:
  • Osteoarthritis, spinal spondylosis
  • Rotator cuff disease, adhesive capsulitis (frozen shoulder)
  • Drug-induced myalgia
  • Infections, including viral syndromes, osteomyelitis, bacterial endocarditis, tuberculosis
  • Malignancy, eg lymphoma, leukaemia, myeloma, prostatic carcinoma
  • Amyloidosis
  • Parkinsonism
  • Chronic pain syndromes, fibromyalgia, depression
  • Endocrinopathy and metabolic bone disease: hyperthyroidism, hypothyroidism, hyperparathyroidism, hypoparathyroidism, osteomalacia, pseudogout with calcium pyrophosphate deposition

Investigations

Investigations are essential to support the diagnosis of polymyalgia rheumatica (PMR) but also to rule out any other possible diagnosis. Investigations which will be useful in making a diagnosis of PMR include:

• Inflammatory markers (ESR, plasma viscosity and/or CRP):
  • An ESR greater than 40 mm/h is a characteristic laboratory finding in PMR, but up to 20% of patients may have a normal ESR at diagnosis.^[8]
  • CRP is more sensitive than ESR.
• Full blood count: anaemia of chronic disease may be present.
• Other investigations before starting steroid treatment include renal function, electrolytes, liver function tests, bone profile, protein electrophoresis (and possibly Bence Jones' protein), thyroid function tests, creatine kinase, autoantibodies, urinalysis and chest X-ray.^[7]
• Ultrasound scan of the hip and shoulders:^[4]
  • Ultrasound scanning shows characteristic pathological findings of the shoulders and hips that can help distinguish PMR from other diseases.
  • Typical findings on ultrasound include subdeltoid bursitis and biceps tendon tenosynovitis of the shoulders and, less frequently, synovitis of the glenohumeral joint.
  • In the hips, ultrasound often reveals synovitis and trochanteric bursitis.
• Other diagnostic tests, such as magnetic resonance imaging and bone and radionuclide labelled bone and joint scanning, have been used in case series to evaluate PMR, but their clinical usefulness has yet to be established.^[4]

Associated diseases^[4]

• Consider giant cell arteritis (GCA) in all people with polymyalgia rheumatica (PMR).
• Symptoms of GCA include new headache, jaw claudication (jaw muscle pain on chewing), and visual disturbance.
• The temporal artery may be abnormal to palpation; biopsy of this artery usually yields characteristic findings of vascular inflammation. Such a biopsy should be considered in any patient with polymyalgic symptoms and new headache.

Management^[4]

• Glucocorticosteroids are the only known effective treatment. Non-steroidal anti-inflammatory agents are of little value for the management of this disease.
• Lack of complete response to recommended doses of prednisone, as well as atypical clinical features (younger age, muscle weakness, peripheral joint disease, and predominance of pain with little or no stiffness), should lead to consideration of alternative diagnoses.
• There is little evidence for the efficacy of steroid-sparing agents, eg methotrexate or anti-tumour necrosis factor agents.
• Manage any residual physical or psychosocial disability caused by the disease. Patients with PMR are frequently elderly and may have mobility problems and difficulty with many aspects of daily living. Many patients will benefit from referral to a physiotherapist and occupational therapist for assessment.
• Monitor response to steroid treatment by:
  • Improvements in symptoms: morning stiffness, proximal hip and girdle pain, disability related to polymyalgia rheumatica
  • Adverse events including osteoporotic stress fractures
  • Symptoms and signs suggesting an alternative diagnosis
  • Laboratory markers: CRP and ESR

Steroid therapy^[7]

• Unlike GCA, urgent institution of steroid therapy is not necessary and can be delayed to allow full assessment. However, if the patient does present with symptoms suspicious of GCA, then urgent institution of high dose steroid therapy is required.
• Patients should be assessed for response to an initial dose of prednisolone 15 mg daily orally. A patient-reported global improvement of at least 70% within a week of commencing steroids is consistent with PMR, with normalisation of inflammatory markers in 4 weeks. A lesser response should prompt the search for an alternative condition.
• Recommended treatment regime:
  • The suggested regimen is daily prednisolone 15 mg for 3 weeks; then 12.5 mg for 3 weeks; then 10 mg for 4-6 weeks; then reduction by 1 mg every 4-8 weeks or alternate day reductions (eg 10/7.5 mg alternate days).
  • It is important to treat the patient’s symptoms and not to rely exclusively on the inflammatory markers to guide treatment. A persistently or recurrently raised ESR or CRP may indicate an underlying or intercurrent disease.
  • After the first few months of treatment, once the disease is controlled, asymptomatic patients with persistently raised inflammatory markers should not continue to be treated with high doses of prednisone just to reduce these markers.
  • The recommended continuing dose of prednisone is the lowest dose that keeps symptoms in remission. Patients with chronic disease are usually maintained on 2.5-5 mg prednisone daily.
  • Glucocorticosteroids are often needed for two to three years, although about 10% of patients will relapse within 10 years and require longer courses of treatment.
• Adverse effects of treatment:
  • Glucocorticosteroid related adverse events are common and include osteoporosis, avascular necrosis, infections, diabetes, insufficiency fractures, steroid myopathies, hypertension, hyperlipidaemia and cataracts.
  • Drug related side effects include hyperlipidaemia, and osteoporosis. These side effects must be monitored and measures should be taken to prevent and manage them.
  • Overtreatment with corticosteroids is often the result of underlying degenerative symptoms being misinterpreted as persistent polymyalgia rheumatica, or a persistently raised ESR being attributed to underlying active disease.

Prevention and treatment of steroid-induced osteoporosis^[7]

See also separate article Osteoporosis Risk Assessment and Primary Prevention.

• Individuals with high fracture risk, eg aged 65 years or older or prior fragility fracture:
  • Bisphosphonate with calcium and vitamin D supplementation.
  • Dual-energy X-ray absorptiometry (DEXA) scan is not required.
• Patients without high fracture risk:
  • Calcium and vitamin D supplementation when starting steroid therapy.
  • DEXA scan is recommended. Bisphosphonates may be indicated if T-score is 1.5 or lower.
• Individuals requiring higher initial steroid dose:
  • Bisphosphonate with calcium and vitamin D supplementation (higher cumulative steroid dose is likely).

Referral^[7]

Early specialist referral is recommended for:

• Atypical features or features that increase likelihood of a non-polymyalgia rheumatica (non-PMR) diagnosis:
  • Age under 60 years
  • Chronic onset (duration more than 2 months)
  • Lack of shoulder involvement
  • Lack of inflammatory stiffness
  • Prominent systemic features, weight loss, night pain, neurological signs
  • Features of other rheumatic disease
  • Normal or extremely high acute-phase response
• Treatment dilemmas such as:
  • Incomplete, poorly sustained or non-response to corticosteroids
  • Inability to reduce corticosteroids
  • Contra-indications to corticosteroid therapy
  • The need for prolonged corticosteroid therapy (over 2 years)

However, patients with a typical clinical picture and complete sustained response to treatment, and no adverse events can be managed in primary care.

Follow-up^[7]

• Recommended follow-up schedule: weeks 0, 1-3, 6; months 3, 6, 9, 12 in the first year (with extra visits for relapses or adverse events). Patients should continue to be regularly monitored whilst on steroids.
• Clinical assessment: at each visit, patients should be assessed for:
  • Response to treatment: proximal pain, fatigue and morning stiffness
  • Complications of disease including symptoms of giant cell arteritis (GCA), eg headaches, jaw claudication and large-vessel disease
  • Steroid-related adverse events
  • Atypical features or those suggesting an alternative diagnosis
• Laboratory monitoring: full blood count, ESR/CRP, urea and electrolytes, glucose
• Duration of treatment and follow-up:
  • Usually 1-3 years of treatment, although some will require small doses of steroids beyond this time
  • Steroids may be stopped when the patient is asymptomatic from their inflammatory symptoms
  • Isolated raised ESR or CRP is not an indication for continuing steroid therapy but may require investigation and referral
• Persistent pain may arise from coexisting osteoarthritis and rotator cuff tears.

Relapse of disease^[7]

Relapse is the recurrence of symptoms of polymyalgia rheumatica (PMR) or onset of giant cell arteritis (GCA), and not just unexplained raised ESR or CRP. Treatment of relapse:

• Clinical features of GCA: treat as GCA (usually oral prednisolone 40-60 mg daily) (see separate article Giant Cell (Cranial) Arteritis).
• Clinical features of PMR: increase prednisolone to previous higher dose. Single intramuscular injection of methylprednisolone (Depo-Medrone®) 120 mg can also be used.
• Further relapses: consider introducing immunosuppression therapy (eg methotrexate) after two relapses.

Prognosis^[5]

• The risk of giant cell arteritis (GCA) occurring while polymyalgia rheumatica (PMR) is being treated, is approximately 10-20%.
• The course and prognosis of PMR is very variable. Response to systemic corticosteroids is rapid and dramatic but treatment for 1-2 years is often required, and some people may need low-dose corticosteroids for longer periods.
• Relapse is common, but responds to restarting or increasing the dose of systemic corticosteroids.
• PMR is not associated with increased mortality but morbidity and mortality may occur as a result of immunosuppression or steroid side-effects.