Polymyalgia Rheumatica (PMR)

Polymyalgia rheumatica (PMR) is a term first used in 1957 to describe an inflammatory condition which is characterised by severe bilateral pain and morning stiffness of the shoulder, neck and pelvic girdle.^1,2 There is some controversy as to whether or not PMR represents a form of giant cell arteritis (GCA), however the balance of evidence would appear to suggest that they are two distinct and relatively common diseases which often co-exist and which share many common features.³

• The incidence of the disease in patients over 50 is about 100 per 100,000.⁴
• PMR is a common condition of older age. It is rare under the age of 50, but the incidence rises with age with a peak between the ages of 70-80.
• Polymyalgia rheumatica 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 M:F 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.⁵
• 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 (Chlamydia) pneumoniae.

The presenting symptoms are non-specific but polymyalgia rheumatica should be suspected in patients over 65 who have subacute to acute onset of bilateral, severe, persistent pain in the neck, shoulders and pelvic girdle.

The most characteristic presenting feature of polymyalgia rheumatica 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 be seen, 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

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

Investigations are essential to support the diagnosis of 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, CRP or both):
  • An ESR greater than 40 mm/h is a characteristic laboratory finding in polymyalgia rheumatica, but up to 20% of patients may have a normal ESR at diagnosis.⁶
  • CRP is more sensitive than ESR.
• Full blood count: anaemia of chronic disease may be present.
• Ultrasonography of the hip and shoulders:⁴
  • Ultrasound shows characteristic pathological findings of the shoulders and hips that can help distinguish polymyalgia rheumatica 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 polymyalgia rheumatica, but their clinical usefulness has yet to be established.⁴

• Patients must be assessed for the presence of giant cell arteritis, which is seen in about 30% of people with polymyalgia rheumatica. Consider GCA in all people with PMR.
• Symptoms of giant cell arteritis 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.

• 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 e.g. 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

• Dosage:
  • The usual initial dose of prednisolone is 10–15 mg daily compared with 40-60 mg daily for patients with giant cell arteritis (60 mg daily for those with visual symptoms).
  • The dose can be increased to 20 mg a day, but patients should never be given a higher dose, which would only contribute to delays in diagnosis of another condition and lead to more morbidity as a result of treatment with corticosteroids.
  • Often, within 24-48 hours patients will report a dramatic improvement and within three to four weeks patients should report at least a 70% global improvement, and the erythrocyte sedimentation rate and C reactive protein value should normalise.
  • 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 erythrocyte sedimentation rate being attributed to underlying active disease.
• Treatment of relapses:
  • If patients who are no longer taking corticosteroids have a relapse, the original dose of prednisone should be reinstated.
  • For the first and second relapses, increase the prednisone to the higher dose given initially. One intramuscular injection of depo-methylprednisolone, 40-120 mg, can also be given.
  • For further relapses, Increase the steroid dose more modestly to 1-2 mg above the previously effective dose with slow tapering, by 1 mg every one to three months, recognising that the disease may last for years.

Prevention and treatment of steroid-induced osteoporosis⁷

• Lifestyle advice: good calcium intake, exercise, stopping smoking, and alcohol.
• Assess and manage the risk of falls, especially in the elderly.
• Drug treatment is recommended for people who have taken, or who are likely to remain on oral corticosteroids for more than 3 months:
  • Those who have osteoporosis or a history of a fragility fracture should be offered drug treatment for osteoporosis, including people who are found to have a T-score of –1.5 or lower on dual-energy X-ray absorptiometry (DXA) scanning.
  • Those who are 65 years or older should be offered anti-osteoporosis treatment, without the need for a prior DXA scan.
  • Those who are younger than 65 years who have no history of osteoporosis or fragility fracture should have their bone mineral density measured using DXA scanning:
    • Drug treatment is recommended if the T-score is –1.5 or lower.
    • Consider starting treatment if there is a long wait for DXA scanning.

• The course and prognosis of PMR is very variable.
• PMR usually responds well to treatment with steroids resulting in remission in the majority of cases.
• Relapse may occur, usually within 2 years of stopping the steroids, but the condition remains steroid responsive.
• Morbidity and mortality may occur as a result of immunosuppression or steroid side effects, and patients should be regularly monitored whilst on steroids.