Polymyalgia Rheumatica

Introduction

Polymyalgia rheumatica (PMR) is an inflammatory disorder characterised by pain and stiffness around the proximal muscles, specifically the shoulders, neck and hips.¹

PMR can exist in isolation but often co-exists with other rheumatological disorders. PMR commonly affects Caucasian females over the age of 50 years with the peak age of onset being 70-80 years.²

Aetiology

The exact aetiology of PMR is not fully understood. It is recognised as an immune-mediated inflammatory disorder with some autoimmune and familial associations, but the link is not well defined.

Additionally, because the age of onset is older adults, it is believed that those with a genetic predisposition may develop PMR as their immune system ages along with changes to neurohormonal regulation.³

While the term “polymyalgia” suggests PMR has a muscle-related aetiology, PMR tends to primarily affect the peri-articular structures such as tendons, bursa and synovium.⁴ There is often no pathology seen in a muscle biopsy.

Risk factors

Risk factors for polymyalgia rheumatica include:

• Age over 50 years
• Prior history of giant cell arteritis (GCA)
• Female
• Family history

Clinical features

History

PMR tends to present acutely or sub-acutely over days to weeks.

Patients describe pain, stiffness and weakness in the muscles of their neck, shoulders, buttocks and hips which affect their activities of daily living.

The distal muscles of the upper and lower limbs are rarely affected. Symptoms are worst first thing in the morning often lasting over an hour.⁵

Typical symptoms of PMR include:

• Shoulders: patients describe a reduced range of motion and difficulty with reaching overhead
• Hips: patients have difficulty getting up from a chair or climbing stairs without support
• Constitutional symptoms: low-grade fevers, weight loss, night sweats, malaise, fatigue and anorexia

The symptoms of PMR overlap with many systemic infections or malignancies so red flag symptoms of unintentional weight loss, night sweats, fevers, and personal or family history of malignancy should prompt consideration for sinister pathologies. 

PMR has a strong association with giant cell arteritis (GCA) leading most clinicians to consider them as disorders on the same spectrum of disease.⁶ Patients who present with PMR should be screened for GCA symptoms.

Clinical examination

Typical findings of PMR on clinical examination include:¹⁰

• Bilateral proximal muscles may be diffusely tender to touch. Tender points may indicate bursitis.
• Active and passive range of motion is limited by pain
• Muscle strength is normal or limited by pain in the proximal muscles
• The scalp may be tender to touch suggestive of GCA
• An examination of the temporal artery may demonstrate a thickened temporal artery with diminished or lack of palpable pulse

The neurological examination is usually normal.

Differential diagnoses

Differential diagnoses to consider in the context of PMR include:

• Inflammatory conditions: rheumatoid arthritis, myositis, fibromyalgia
• Infectious conditions: Lyme disease, infective endocarditis
• Malignancy: multiple myeloma
• Other: osteoarthritis, hypothyroidism

Investigations

Laboratory investigations

Relevant laboratory investigations include:

• Full blood count (FBC): normocytic anaemia or thrombocytosis may be seen in ongoing inflammation
• Inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are almost always elevated in PMR. CRP is sensitive for acute disease activity and is followed up to assess response to treatment.¹¹

Because the symptoms of PMR can be generalised and non-specific, further blood tests should be considered to exclude other conditions. These tests include LFTs, renal function tests, immunoglobulins, rheumatoid factor (RF), anti-CCP, thyroid function tests, calcium and alkaline phosphatase.

Imaging

Relevant imaging investigations include:^12,15

• Ultrasound (US): commonly shows joint effusion, synovitis or bursitis which can be useful in assessing the degree of inflammation and monitoring response to therapy
• Magnetic resonance imaging (MRI): MRI is a more sensitive test to assess for synovitis and bursitis (not routinely performed)
• Fluorodeoxyglucose F18- positron emission tomography (FDU PET): new imaging modality used to see increased uptake in the bursa and synovium of the shoulders, ischial tuberosity and greater trochanters consistent with the pain of PMR. FDU PET is also useful for assessing vasculitis (not routinely performed).

Diagnosis

There is no single test for the diagnosis of PMR. It is a clinical diagnosis based on the following features:

• Age of onset over 50 years
• The classical presentation of symptoms with proximal muscle stiffness and pain that is worse in the mornings
• A blood test showing elevated inflammatory markers (ESR and CRP)
• Improvement of symptoms with the initiation of steroid therapy

Management

Medical management

Glucocorticoids (e.g. prednisolone) are the mainstay of treatment for PMR.

Glucocorticoids should be tapered (a reducing course) over a period of weeks to months as symptoms resolve and inflammatory markers improve. 

Steroid side effects

Glucocorticoids have numerous side effects, both with short term and long-term use:

• Diabetes: glucocorticoids cause hyperglycaemia and can precipitate a hyperglycaemic hyperosmolar state (HHS) in patients with co-morbid diabetes
• Gastro-oesophageal reflux disease (GORD)/peptic ulcer disease: glucocorticoids can worsen acid reflux, so the addition of a proton-pump inhibitor (PPI) may be indicated
• Osteoporosis: given that elderly women have lower bone density and are the main demographic of PMR, glucocorticoids can further increase fracture risk. This group may benefit from bone prophylaxis like denosumab (RANKL antagonist), calcium and vitamin D supplements.

Glucocorticoid sparing therapy

Glucocorticoid sparing drugs are used in PMR and GCA to limit the adverse effects of extended glucocorticoid use. These may include disease-modifying anti-rheumatic agents (DMARDs) or biologics.

Methotrexate is an anti-folate DMARD that can be used to manage PMR symptoms as part of a glucocorticoid taper. Tocilizumab is a licensed IL-6 inhibitor that reduces the acute inflammatory response.  

Complications

PMR can have a relapsing and remitting course, with asymptomatic periods and acute flares.

Most long-term complications of PMR are linked to glucocorticoid therapy. There has been a concern regarding increased cardiovascular mortality, but a recent (2015) meta-analysis suggests that with control of systemic inflammation, the risk of cardiovascular mortality is equivalent to the general population.¹⁵

Patients presenting with PMR or GCA should be counselled about GCA symptoms and advised to seek advice immediately if symptoms arise. GCA can present at any time in the disease progression. Active inflammation in GCA is linked with the following potentially significant complications:

• Blindness
• Stroke
• Aortitis leading to aortic aneurysm

Key points

• PMR is the second most common rheumatological condition which primarily affects the proximal muscles of the neck, shoulders, and hips. Patients describe difficulty reaching overhead and getting up from a chair
• PMR and GCA frequently occur together and are believed to be disorders on the same spectrum of disease
• GCA is a large vessel vasculitis that most commonly affects the temporal artery causing symptoms of scalp tenderness, jaw claudication and visual disturbances. It is treated as a medical emergency because untreated it causes blindness.
• Blood tests typically reveal elevated inflammatory markers (CRP and ESR), which can be used to assess response to treatment and relapse respectively
• The current gold standard test for GCA is a temporal artery biopsy, but new research is demonstrating superior outcomes with minimally invasive imaging modalities like ultrasound and MRA
• Both PMR and GCA respond well to steroid therapy. Steroids should be tapered and replaced with steroid-sparing drugs where possible to minimise the adverse effects of steroid use
• Long term prognosis is good with good control of vascular inflammation, and the ability to recognise a flare and to seek appropriate medical care

Reviewer

Dr Grainne Murphy

Consultant Rheumatologist

Editor

Dr Chris Jefferies

References

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