Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are two related and immune-mediated inflammatory conditions that occur in the elderly. PMR coexists in 40% of patients with GCA. Similarly, 10% of PMR patients develop GCA at some point during their disease course. The relationship between PMR and GCA is further demonstrated by their preference for similar patient populations, linkage to the same human leukocyte antigen haplotypes, similar cytokine patterns in temporal artery biopsies, and similarities in anatomic involvement on positron emission tomography (PET) imaging.1-3 PMR and GCA represent two extremes of a disease spectrum.
Polymyalgia Rheumatica
Definition
Bruce is credited with the first description, in 1888, of PMR, which he described as "senile rheumatic gout."4 However, Barber coined the term polymyalgia rheumatica in 1957, and it has become the universally accepted name for this condition.5
PMR is characterized by proximal, symmetrical musculoskeletal pain and stiffness. Symptoms of systemic inflammation are also common. A dramatic response to low-dose corticosteroids can be a valuable diagnostic tool in patients for whom the diagnosis is uncertain. The lack of response to prednisone raises the possibility of a paraneoplastic process manifesting with proximal pain and stiffness. There is still a need for caution in patients who have a dramatic response to treatment because in some patients (about 11%) with an initial PMR-like presentation, the condition evolves into a phenotype that is more that of rheumatoid arthritis and, less often, other systemic rheumatic illnesses.6
Epidemiology
PMR has a predilection for patients older than 50 years. The mean age at onset is 73 years, and women are affected more often than men. Its annual incidence in Olmstead County, Minnesota, a population with mostly Scandinavian heritage, is 59 per 100,000. The annual incidence of the disease increases with age.7 Whites of northern European descent have a higher incidence of disease than people of African American or Latin American descent.8,9
Pathophysiology
Much has been learned about PMR and GCA, but their cause remains unknown. Their etiology is likely multifactorial, resulting in the interplay of age, environment, and genetic susceptibility. The suggestion that PMR may be a forme fruste of GCA was first advanced in the 1950s and 1960s.5 More recently, PET scans in PMR have revealed features of vasculitis in about 1/3 of patients.10 The pathophysiology for both diseases is similar, with abnormalities of cellular immunity leading to vessel and systemic inflammation. Cytokines such as interleukin (IL)-1, IL-2, IL-6, and tumor necrosis factor (TNF)-alpha are important in the development of inflammation in both PMR and GCA.11 In PMR, however, inflammation is believed to be predominantly limited to the articular and periarticular tissues, whereas GCA is characterized by the development of frank large-vessel vasculitis. The classic histologic feature of GCA is the presence of an inflammatory cell infiltrate consisting of T cells, dendritic cells and macrophages migrating from the adventitia of a muscular artery toward the media and intima.9 If histologic examination is performed, between 16% and 20% or more of PMR patients will actually demonstrate arteritis, requiring the diagnosis to be changed to GCA.12 Interestingly, while temporal artery biopsies from true PMR patients lack the inflammatory infiltrate, they do reveal similar cytokine profiles to those with GCA, suggesting that PMR may represent a form of early, subclinical vasculitis. One key difference in cytokine profile is the presence of IFN-gamma in the arterial wall of GCA patients, suggesting that this cytokine may ultimately be necessary for the histological development of vasculitis.2
Signs and Symptoms
Most patients describe a subacute onset of symptoms that remain persistent over time. The most common symptom (reported in 70% to 95% of patients) is symmetrical shoulder girdle pain and stiffness. Fifty percent to 70% report neck and pelvic girdle pain. Concurrent pain in the upper arms and thighs is common and is usually worse in the morning. Shoulder and leg discomfort can lead to difficulty dressing, hair grooming, and rising from a chair. One third of patients have flulike symptoms described as fever, malaise, anorexia, or weight loss.13
Physical examination findings may reveal pain that limits active range of motion in the shoulders and hips. Passive range of motion should be normal. Despite subjective symptoms of muscle weakness, muscle strength testing should be normal unless it is affected by examination discomfort or by another condition.13 Approximately 50% of patients have been said to present with distal extremity abnormalities including swelling of the knees, wrists, or metacarpophalangeal joints. Other reported findings include soft-tissue swelling; pitting edema of the hands, ankles, and feet; and median nerve compression. However, these findings are typical of inflammatory joint disease and not PMR. The examiner should direct the evaluation along other lines in attempting to define another diagnosis. Frank synovitis of the hands or feet should suggest rheumatoid arthritis or another inflammatory arthropathy. Further laboratory and imaging may be needed to differentiate the two. (See the chapter Rheumatoid Arthritis).
Diagnosis
The diagnosis of PMR is based primarily on clinical features. Elevated acute phase reactants provide secondary support for the diagnosis. The erythrocyte sedimentation rate (ESR) is greater than 40 mm/hr in 90% of cases. Other laboratory findings include an elevated C-reactive protein (CRP), normocytic normochromic anemia, thrombocytosis, and elevated alkaline phosphatase. Elevation of muscle enzymes such as creatine kinase and aldolase is not a feature of PMR and should prompt consideration of an alternative diagnosis.
Imaging is not routinely employed in the diagnosis, however, PET/computerized tomography (CT) has been used recently to better understand PMR. A prospective study of 35 patients with a clinical diagnosis of PMR and negative temporal artery biopsies underwent PET prior to starting steroid therapy. Significant tracer uptake was noted in the shoulders (94%), hips (89%), and vertebral spinous processes (51%) of PMR patients. In addition, 31% had large-vessel uptake at diagnosis, again suggesting that subclinical vasculitis may be very common in these patients.10 Additional imaging modalities such as U/S and magnetic resonance imaging may be useful in ruling out other entities in the differential diagnosis such as rheumatoid arthritis, calcium pyrophosphate deposition disease, or true large-vessel vasculitis. The differential diagnosis may become confusing, however, when one considers that the average age of patients with PMR is >70 years, an age when osteoarthritis and calcium pyrophosphate deposition are common, thus increasing the likelihood that a patient with PMR may also have these comorbidities.
In 2012, the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) joined forces to create new classification criteria. A scoring system was determined, whereby a patient over the age of 50 presenting with new onset bilateral shoulder pain and elevated ESR or CRP may be classified as having PMR if at least four clinical points or five points from clinical and ultrasound criteria are met.14 Although these criteria may serve as general guidelines for the diagnosis of PMR, it should be noted that they were developed as classification criteria for study enrollment, not for strict clinical diagnostic purposes. Most authorities agree that no single feature is necessary to diagnose PMR in all cases. The features noted in these criteria are common enough that if patients present without these symptoms or have a suboptimal response to corticosteroids, the diagnosis should be reconsidered. Conditions that can mimic PMR include malignancies, chronic infections, drug reactions, metabolic conditions (such as hypothyroidism), and other rheumatic diseases, including seronegative rheumatoid arthritis, calcium pyrophosphate disease, or polymyositis.6