Polymyalgia rheumatica

Polymyalgia rheumatica (PMR) is a chronic rheumatologic syndrome that is characterised by inflammation leading to pain and morning stiffness in the neck, shoulder girdle and pelvic girdle. It is most commonly seen in those over 50 years old and has a predisposition to females.

It is the most common inflammatory rheumatic diseases in the elderly population and it alone accounts for 22% of long-term corticosteroid prescriptions in the UK. It is commonly associated with giant cell arteritis (GCA) with 15-20% of individuals with PMR developing GCA, and 60% of individuals with GCA having symptoms of PMR.

Pathophysiology

Although the aetiology of PMR is not well understood, it is believed to be due to genetic, environmental and immunological factors:

1. Genetic factors - certain haplotypes of HLA are implicated, such as HLA-DRB1*04. Familial clustering and ethnic variations also point toward a genetic contribution.
2. Environmental factors - seasonal variations in the incidence of PMR as well as an association of preceding viral infections (such as parvovirus B19, CMV, adenovirus) suggest that infections may be a trigger (in genetically predisposed individuals).
3. Immunological factors - systemic inflammation is lead by elevated levels of IL-6 and IL-1 as well as TNF-α.

The inflammatory response mediated by the aforementioned cytokines leads to recruitment of inflammatory cells into affected tissues. This is commonly the synovial membrane of joints as well as bursae (synovitis and bursitis) - especially in the shoulder and hip joints and subdeltoid, subacromial and trochanteric bursae. The inflammation leads to stiffness and pain. Some patients develop GCA which is a large-medium vessel vasculitis and this may suggest a possible overlap in the pathophysiology.

⚠️ Risk factors

• Older age (>50 years old)
• Female sex - the lifetime risk in women is 2.4% as compared to 1.7% in men. Over 65% of PMR patients are female.
• Northern European ancestry
• Infections - such as parvovirus B19, adenovirus, CMV.
• Giant cell arteritis
• HLA-DRB1*04

😷 Presentation

Patients are usually >50 years old and have an acute onset of 2 core symptoms:

• Bilateral shoulder and/or pelvic girdle pain - it may be unilateral initially but becomes bilateral shortly after. The pain is worse with movmement and disrupts sleep. In most patients the shoulder pain will radiate to the elbows and the hip pain may radiate to the knees.
• Stiffness for at least 45 minutes after waking/rest - this may cause difficulty in getting up from the bed or turning over in the bed. This stiffness is also present in the shoulder and hip girdles. As such the patient may struggle to stand up from the seated/prone positions and may also find it difficult to lift their arms above their head.

Additional, constitutional symptoms include:

• Low-grade fever
• Anorexia and weight loss
• Fatigue
• Depression
• Peripheral arthritis and peripheral oedema
• Carpal tunnel syndrome - due to the peripheral synovitis.

💡 An additional hallmark sign of PMR is the rapid resolution of symptoms after administration of steroids.

Giant cell arteritis

Giant cell arteritis (GCA), also known as temporal arteritis is a medium to large-vessel vasculitis, particularly affecting the temporal arteries. The lining of the extracranial branches of the carotid artery (such as the temporal arteries) become inflamed. This inflammation leads to swelling in the affected arteries, which thereby narrows the artery. Subsequently, there is a reduction in the amount of blood and oxygen that is able to reach the tissues typically perfused by these arteries, like the masseter, or jaw muscles.

It is most prominent in individuals >50 years and older.

😷 Presentation It can have an acute or insidious onset. With the following symptoms:

1. Temporal headache - an elderly person with a temporal headache should always be considered for GCA.
2. Jaw claudication - pain associated with chewing.
3. Amaurosis fugax - due to the ophthalmic artery being affected. It is a true ophthalmic emergency as it can lead to permanent vision loss.
4. Thickened & tender temporal arteries - they may also be pulseless.
5. Polymyalgia rheumatica - it does not lead to PMR, but it is strongly linked with it and so we may often see its manifestations as well such as symmetrical proximal muscle weakness and oligoarthritis (swelling and inflammation of 2-4 joints).
6. Stroke - this is another serious complication that may occur.

🔍 Investigations

• 🥇 ESR - GCA is unlikely if ESR is not elevated
• 🥇 Vascular ultrasound - a non-compressible halo sign is the finding that most indicates GCA.
• FBC - normocytic, normochromic anaemia (similar to all ACDs).
• LFTs - deranged in 1/3rd of patients.
• 🏆 Temporal artery biopsy - a diagnostic procedure. However, GCA has skip lesions and so a negative biopsy does not rule out GCA.

🧰 Management

It is a medical emergency.

1. It requires high dose steroids:
1. Oral prednisolone - 60mg OD. The dose is reduced slowly over several months as treatment is needed for 1-2 years which can cause tolerance and lack of production endogenously (may lead to Addisonian crisis if stopped suddenly).
1. If weaning off the steroids will be problematic, give azathioprine instead.
2. Acute or intermittent vision loss
1. IV glucocorticoid (hydrocortisone) is first line.
2. Oral prednisolone - 60-100mg for 3 consecutive days.

3. Aspirin may be given to reduce the risk of stroke and amaurosis fugax.

❗️ With long-term steroid use we need to protect against osteoporosis and ulcers ❗️

→ Bisphosphonates, calcium and vitamin D

→ PPI

🔍 Investigations

Once the core symptoms are identified in an individual >50 years old, it is then important to exclude PMR-mimicking conditions.

Conditions to exclude:

• Giant cell arteritis - it is important to rule this out as it poses risks of serious complications if untreated, such as vision loss and aortic involvement.
• Cancer
• Ongoing infection
• Thyroid disease
• Arthritis
• Myositis
• Statin-induced myalgia

NICE provides guidelines on the blood tests that are important to order in the diagnosis of PMR:

1. 🥇 Erythrocyte sedimentation rate (ESR) + C-reactive protein (CRP) + plasma viscosity - these are all inflammatory markers which support the diagnosis. However, the diagnosis can be made without inflammatory markers being raised. 2
2. 🥇 Other blood tests that need to be done prior to giving steroids include:
1. FBC
2. U&Es
3. LFTs
4. Calcium
5. ALP
6. Protein electrophoresis
7. TSH
8. Creatine kinase
9. Rheumatoid factor
10. Urine dipstick analysis

💡 NICE also advises to consider urine Bence Jones protein (for multiple myeloma), ANA and anti-CCP antibodies, and a chest X-ray.

🏆 If PMR is the most likely diagnosis, a trial of prednisolone (15mg daily) should be prescribed and the patient should be followed-up after 1 week to assess the response. After 3-4 weeks the inflammatory markers should be re-assessed.

As such the working diagnosis for PMR can be made using the following checklist:

1. Presence of core features
2. Exclusion of alternative conditions
3. Positive response (70% improvement) to oral corticosteroids within a week
4. Normalisation of inflammatory markers within 4 weeks (if raised)

If the response is less than 70% then the dose can be increased to 20mg of prednisolone. If it remains low then consider an alternative diagnosis and refer to rheumatology.

✍️ Referral

A referral to rheumatology should be made for the following patients:

• Atypical features of PMR with no clear alternative diagnosis - this includes the following patients:
• <60 years old
• Red flag symptoms - such as weight loss, night pain and neurological symptoms.
• No core features of PMR
• Inadequate response to 20mg of prednisolone
• Patient experiences adverse effects from corticosteroids
• Corticosteroids needed for >2 years

🧰 Management