Latest Advances in the Diagnosis and Treatment of Polymyalgia Rheumatica
Polymyalgia rheumatica (PMR) is a chronic inflammatory condition that predominantly involves large joints and periarticular structures. Following rheumatoid arthritis, PMR is the second most common autoimmune rheumatic disease, with a lifetime risk of approximately 2%.1
PMR affects adults over the age of 50 years and becomes more frequent with advancing age, peaking among individuals aged 70 to 80 years. Additionally, women are affected 1.5 to 2 times more often than men.
Although the etiology and pathogenesis of PMR are not known, epidemiologic studies suggest that there are both genetic and environmental factors involved in the development of this disease.
This is further evidenced by a geographic variance in the incidence of PMR, with the highest rates seen among inhabitants of and descendants from Northern European countries.2 While PMR has been observed in people of Hispanic, Asian, and African heritage, incidence rates among these ethnicities are notably lower.
The hallmark clinical picture of PMR is characterized by pain and stiffness (Table 1). Stiffness typically lasts greater than 30 minutes and is worse after rest or inactivity. Patients often describe difficulty getting dressed or discomfort when turning in bed at night that interferes with sleep. Shoulder range of motion may be limited, causing difficulty in performing activities at or above head level.
Compared to symptoms of non-inflammatory conditions, symptoms of PMR typically are symmetrical and get better with activity. In clinical practice, it can be challenging to distinguish PMR from elderly-onset rheumatoid arthritis. Indeed, inflammatory arthritis of peripheral joints (eg, wrists, knees) can be seen in up to one-third of patients with PMR.3 However, synovitis and erosions of distal joints, including the metacarpophalangeal and proximal interphalangeal joints and the feet, are more indicative of rheumatoid arthritis than PMR.4
Weakness of the proximal muscles is not a feature of PMR and its presence should prompt evaluation for a myopathic process. Similarly, diffuse muscle tenderness is not a prominent feature and should raise suspicion for electrolyte abnormalities, metabolic disturbances, or fibromyalgia.
Constitutional symptoms of low-grade fever, malaise, fatigue, anorexia, and weight loss can occur in 40% to 50% of patients with PMR.5 These non-specific symptoms often lead clinicians to consider evaluating for other diagnoses, such as infection or malignancy.
It is well recognized that PMR is associated with giant cell arteritis (GCA), a systemic vasculitis affecting the large arteries that can cause blindness, stroke, and aortic aneurysm. Although 40% to 60% of patients with GCA have associated PMR symptoms at diagnosis,6 only 10% to 20% of patients with isolated PMR will develop symptoms of GCA.
Therefore, when evaluating patients for PMR, health care providers also should evaluate for symptoms of GCA—headache, scalp tenderness, jaw claudication, diplopia, vision loss, and upper or lower extremity claudication. If any symptoms are present, testing for GCA should be undertaken, including the consideration of temporal artery biopsy.
Making the Diagnosis
Because of the broad differential diagnosis and potential mimicking disease states (Table 2), clinicians evaluating patients for PMR should obtain a detailed history and conduct a comprehensive physical examination, focusing particularly on the musculoskeletal, vascular, and neurologic systems.
Laboratory parameters in PMR are not specific but typically show evidence of a systemic inflammatory state. Such abnormalities can include a mild normocytic anemia due to chronic inflammation, leukocytosis, and thrombocytosis. Inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]) frequently are elevated. The ESR, however, can be normal in 6% to 20% of patients with PMR.7,8 Therefore, CRP may be a more sensitive marker of inflammation in these patients.9
Rheumatoid factor (RF) and anticitrullinated protein antibodies (ACPA) typically are absent, and their presence should raise suspicion for rheumatoid arthritis. Additional laboratory studies that are useful in the differential diagnosis include liver transaminases, creatine kinase, calcium, sodium, potassium, magnesium, creatinine, thyroid-stimulating hormone, serum protein electrophoresis, and urinalysis with microscopy.
Several sets of diagnostic criteria for PMR have been proposed, but they have not been validated or universally accepted. Common features among these criteria have included a minimum age (50–65 years), bilateral shoulder girdle and hip girdle aching, morning stiffness, and elevated inflammatory markers.
In response to a lack of standardized criteria, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) recently developed a set of classification criteria based on expert consensus and evaluation of a prospective cohort of 125 patients with new-onset PMR and 169 patients with disorders mimicking PMR (Table 3).4 Use of this classification scoring algorithm in patients who are at least 50 years of age and have new-onset bilateral shoulder pain and elevated inflammatory markers demonstrated a sensitivity of 68% and a specificity of 78% for the diagnosis of PMR if at least 4 clinical criteria points were present.
Role of Imaging
In recent years, there has been an increased use of imaging modalities to evaluate patients with suspected PMR. Ultrasonography and magnetic resonance imaging (MRI) commonly have identified abnormalities in large joints and periarticular structures. Characteristic findings in patients with PMR may include bicipital tenosynovitis, subacromial/subdeltoid bursitis (Figure 1), greater trochanteric bursitis (Figure 2), and glenohumeral (Figure 3) or hip joint synovitis. Although these findings also can be seen in other forms of inflammatory arthritis, identification of these abnormalities can be helpful to differentiate PMR from other conditions.
Indeed, the addition of ultrasonography to the EULAR/ACR classification scoring algorithm improved the specificity to 81% for differentiating PMR from non-PMR patients and to 89% in discriminating PMR from other shoulder disorders.4 Compared to ultrasound, MRI can additionally show extracapsular soft-tissue edema in the shoulders and cervical interspinous bursitis in the neck, but its utility is limited by cost and availability, making ultrasound the preferred modality to evaluate musculoskeletal structures in these patients.