It is a systemic inflammatory disease that is more common in the elderly (over 50 years of age). There is proximal myalgia, i.e. muscle pain in the upper extremities (shoulder, neck and hip). Morning stiffness and pain complaints are at the forefront. Synovitis in proximal joints and inflammation in extra-articular structures occur.
Sudden onset and usually symmetrical involvement is observed. Coexistence with giant cell arteritis is common: before, after, together. There is a possibility of vasculitis development, patients should be monitored carefully.
It is common over the age of fifty and the incidence increases with advancing age. The mean age of onset is 73 years. The prevalence over the age of fifty is 12.7-68.3/100.000. The lifetime risk of development is 2.43 per cent in women and 1.66 per cent in men.
Geographical clustering is observed: environmental risk factors (Scandinavian countries and Northern Europe). Annual incidence in Norway at age 50 years and older: 112.6/100,000, UK, Denmark, Sweden: 41.3-84/100,000, Italy, Spain: 12.7-18.7/100,000 and Turkey: 3.5/100,000.
The cause is unknown. Genetic predisposition is thought to be present. Familial clustering is rare, but has been reported. Polymorphism in specific genes related with immune regulation, intracellular adhesion molecules, IL-1 receptor antagonist, IL 6 and HLA-DRB1-04 have been reported. There are reports that environmental factors play a role as a triggering factor.
Articular and periarticular inflammatory events are at the centre of the pathogenesis. Activation of the innate immune system has been demonstrated. Synovial biopsy examination shows mild synovitis dominated by macrophages and CD4 T cells.
There is a high proportion of monocytes/macrophages in the circulation and these spontaneously release proinflammatory mediators such as IL-6. Dentritic cells were found in the internal adventitia of the temporal artery.
These cells cause chemokine release and local T cell activation in PMR patients. It causes the formation of adaptive immune response in the vessel wall.
In Giant Cell Arteritis, inflamed temporal artery tissue contains IFN-γ, a product of T lymphocytes, and IL-1 β, IL-6 and TGF-β, products of macrophages. IFN-γ is absent in polymyalgia rheumatica.
Myalgia is common, but muscle inflammation is absent. Increased proinflammatory cytokines were found in the interstitium of proximal extremity muscles (trapezius and vastus lateralis). Cytokine levels return to normal levels within 2 weeks with corticosteroid treatment in parallel with the improvement of symptoms.
What Are The Clinical And Laboratory Findings?
Although muscle pain is present, muscle enzymes are normal, muscle biopsy and EMG do not show any evidence of muscle damage. Morning stiffness is 30 minutes or more, and stiffness increases after rest.
Fever, fatigue, weight loss, anorexia, subfebrile fever, which we call constitutional symptoms, are detected in 40-50% of patients. Very high fever is rare unless giant cell arteritis is present.
In 90% of patients, the onset is with sudden onset of muscle pain and stiffness affecting the neck, shoulder and upper arm. Shoulder pain is 75-99%, while hip pain and neck pain are less common (50-90%). The pain is prominent in the morning hours and increases with getting up from a sitting position, moving from a lying to a sitting position or movements requiring the use of the arms.
Symmetrical myalgia is typical, involving both new sides. However, not necessarily, the onset may be unilateral. The extremities are not affected, but pain may radiate to the elbows and knees. There may also be pain in the neck, upper arm, waist and thighs. In distal musculoskeletal involvement, carpal tunnel syndrome, nonerosive asymmetric peripheral arthritis (involvement of the small joints of the knee, foot and hand) are observed in half of the patients. Asymmetric proximal joint involvement as an atypical presentation or at an earlier age is rare, but may occur.
Active range of motion is limited and painful, but passive range of motion may be open. Both active and passive range of motion are painful and limited, often in the shoulders and hips, but there is no significant joint swelling. There may be muscle tenderness.
There is no real weakness in muscle strength, but there is inability to use it due to pain. Myositis should be investigated if there is real muscle weakness on examination.
What Can Happen In Distal Musculoskeletal System Involvement?
Carpal tunnel syndrome (14%), distal tenosynovitis (3%), asymmetric peripheral arthritis (25%) usually involving the knees and wrists may be present.
Laboratory findings are nonspecific and show signs of systemic inflammation.
- Elevation in acute phase reactants: ESR, CRP, IL-6
- Low ESR (≤30m/h) or Normal ESR 6-20
- CRP is a more sensitive marker
- Chronic disease anaemia, Leukocytosis, Thrombocytosis,
- Increased ALP levels
- Increased transaminases, abnormal thyroid tests
- Otoantikorlar negatif
- Rarely ANCA +
- Complement levels normal
- If ANA(+), connective tissue disease should be investigated.
- RF (+) is similar to healthy elderly population.
- If anti-CCP (+), a variant of RA should be considered.
- If RF and CCP (+), late-onset RA should be considered.
Which Tests Should We Order?
- Complete blood count
- Markers of inflammation
- RF, Anti-CCP
- Calcium and other electrolytes
- Serum protein electrophoresis
- Creatine phosphokinase
- Complete urinalysis
Imaging Studies: Scintigraphy, MRI, USG, PET
- Abnormalities in periarticular structures: Synovitis: Frequently detected by MRI and USG
- Hip and shoulder ultrasonography is clinically useful in patients with suspected PMR
- Bicipital tenosynovitis
- Subacromial bursitis, Subdeltoid bursitis
- Trochanteric bursitis
- Effusion or tenosynovitis of the hip or shoulder joint
When Should Imaging Studies Be Performed?
- Not routinely necessary to make a diagnosis
- Ultrasonography and MRI are equally effective: sensitivity and specificity above 90
Ultrasonography is the recommended modality. Bilateral bursitis in the shoulder supports the diagnosis of PMR, especially if ESR is normal. However, it is not specific. In rheumatoid arthritis, bilateral subacromial/subdeltoid bursitis is found in 20% and glenohumeral synovitis in 100%. Ultrasonography findings improve with corticosteroid treatment.
Radiographs are usually normal. If there are bone erosions in peripheral joints: PMR should be excluded and arthritis should be considered.
Which Findings Can Be Detected With MRI?
- Bicipital tenosynovitis
- Bilateral subacromial and subdeltoid bursitis and trochanteric bursitis
- Oedema in the soft tissues around the shoulder joint
- Cervical interspinous bursitis: demonstrated in all patients with new-onset untreated PMR
Which Tests Are Included In Vascular Imaging Studies And When Can They Be Performed?
USG, CT-angiography, MR-angiography may be ordered. To rule out giant cell arteritis, it may be ordered to investigate the presence of subclinical vascular inflammation. It is indicated if large vessel vasculitis is clinically suspected.
History may include limb claudication, constitutional symptoms and examination may include absence of pulse, presence of murmur and asymmetric blood pressure.
Can PET Be Requested?
It is an expensive test. It is rarely necessary in routine evaluation. It may be useful in the evaluation of patients with refractory or unexplained symptoms in underlying malignant disease.
It may be ordered if there is no response despite adequate steroid dose or if the constitutional symptoms are very severe or if the suspicion of subclinical large vessel vasculitis is high.
Should Temporal Artery Biopsy Be Performed In Every Patient?
It is not routinely indicated in the evaluation of patients. It is performed if there are clinical symptoms and findings suggestive of giant cell arteritis.
What Should We Pay Attention To In Anamnesis?
Patient age, gender, painful areas, morning stiffness, night pain, duration of complaint, constitutional symptoms, headache should be questioned.
How Is It Diagnosed?
The diagnosis is made clinically: Suspicion, careful anamnesis and physical examination
Clinical symptoms, increase in acute phase reactants, exclusion of other diseases, rapid response to corticosteroids are important in the diagnosis.
In many patients, the diagnosis is made by exclusion of other inflammatory diseases accompanied by polymyalgic syndrome. The most critical point is differentiation from Giant Cell arteritis. Temporal artery biopsy should be performed if there are suspicious vascular symptoms. Typical vasculitis findings invalidate the diagnosis of PMR. DHA may develop even years later.
Which Diseases Should Be Considered In Differential Diagnosis?
Rheumatological diseases (RA, SpA, Connective tissue diseases, Inflammatory myopathies, Poly/dermatomyositis, Crystal arthropathies, RS3PE, Vasculitis, giant cell arteritis, ANCA-associated vasculitis, SLE)
Non-inflammatory musculoskeletal diseases (Rotator cuff syndrome, Adhesive capsulitis, Degenerative joint disease, Shoulder and hip OA, Fibromyalgia)
Endocrinopathies (Thyroid diseases, Parathyroid gland disorders)
Infections (viral, bacterial sepsis, endocarditis, septic arthritis, mycobacterial)
Malignant diseases (paraneoplastic myalgias, solid cancers)
Other diseases: Parkinson’s disease, Depression, D hypovitaminosis, Drug-related myopathy, Statin group drug use)
What Are The Treatment Options?
Self-limiting type is rarely encountered, some patients recover spontaneously. Musculoskeletal nonsteroidal painkillers are generally not recommended. Low dose glucocorticoids are the “standard of care”.
Typical starting dose is usually 15-20 mg/day prednisone/prednisolone. The initial corticosteroid dose is continued for 2-4 weeks. Thereafter, the dose should be gradually decreased until it is reduced to 10 mg, regardless of clinical findings and markers of inflammation. There is no standard protocol for corticosteroid dose reduction, 10% reduction (2.5 mg) can be made at 2-4 week intervals until the dose is 10 mg.
Afterwards, 1-2.5 mg per month can be reduced until the end of treatment. ESR and CRP are monitored. The absence of a decrease in IL-6 level in the first 4 weeks of treatment is a sign of a more serious disease picture. An initial dose of 15 mg prednisone is effective in most PMR patients.
In mild cases or if the comorbidities of the patients restrict the use of the drug, 120 mg intramuscular methylprednisolone can be administered every 3-4 weeks for 3 months at the beginning of treatment. Afterwards, treatment can be continued by decreasing 20 mg every 2-3 months.
The dose of continued treatment is adjusted according to clinical and laboratory (ESR and CRP) response. In patients who start with 15 mg at the beginning, the daily maintenance dose can be reduced by 1 mg every 2 months until it reaches 8-10 mg. Results are poor with rapid tapering.
After remission is achieved, when the stable prednisone dose is 10 mg daily, dose reduction should be less than 1 mg per month (1 mg every 2 months).
Most patients remain on treatment for 1-2 years. However, sometimes very long term treatment may be required. The lowest steroid dose required for remission is determined and continued at that dose (usually 2.5-5 mg).
Persistently high CRP and IL-6 levels may be associated with disease relapse. Elevation of inflammatory markers in the absence of clinical signs does not necessitate an increase in the dose of glucocorticoids. We should treat the patient’s clinical symptoms and not overly rely on inflammatory markers to guide treatment.
If relapse occurs, it may be necessary to return to the previous effective steroid dose. However, it should be kept as low as possible.
What Are The Complications Of The Disease?
There is no increased mortality due to the disease, but morbidity is increased.
- Corticosteroid-related side effects
- Diabetes mellitus
These conditions should be monitored regularly and precautions should be taken.
Long-term corticosteroid use is associated with significant morbidity. The risk of side effects is higher in older patients at diagnosis, in patients who have received a cumulative prednisone dose of 2 g or more and in female patients.
Long-term corticosteroid use is associated with significant morbidity. Prophylaxis for bone loss should be initiated in the first few weeks of treatment, and calcium and vitamin D and bisphosphonates should be added to treatment in high-risk individuals.
Blood pressure, lipid profile and blood glucose level should be monitorised for cardiovascular comorbidity.
What Are The Other Treatment Options?
Methotrexate can be added to treatment. It is not routinely started at diagnosis. It can be added if the disease progresses with relapses or in patients with a high risk of developing side effects with long-term corticosteroid use. Dose used: usually 7.5-10 mg/week.
Anti-TNF agents may be useful in long-term disease with relapses.
What Is The Prognosis Of The Disease?
Relapse is frequent (50%). Patients with high initial corticosteroid dose, patients whose corticosteroid dose is rapidly decreased, female patients, persistently high levels of CRP and IL-6 may be indicative of relapse.
It is difficult to say that the clinical diagnosis is definite. Initially, it is difficult to differentiate from late-onset RA. Long-term follow-up of patients is important.