Polymyalgia Rheumatica 

Polymyalgia rheumatica (PMR) is a relatively common clinical syndrome of unknown etiology that affects elderly individuals. It is characterized by proximal myalgia of the hip and shoulder girdles with accompanying morning stiffness that lasts for more than 1 hour. Approximately 15% of patients with polymyalgia rheumatica develop giant cell arteritis (GCA), and 40-50% of patients with giant cell arteritis have associated polymyalgia rheumatica. Despite the similarities of age and some of the clinical manifestations, the relationship between GCA and PMR is not yet clearly established.^[1]

Polymyalgia rheumatica is a clinical diagnosis based on the complex of presenting symptoms and exclusion of the other potential diseases (see Clinical and Workup.) Corticosteroids are considered the treatment of choice, and a rapid response to low-dose corticosteroids is considered pathognomonic (see Treatment). Patients have an excellent prognosis, although exacerbations may occur if steroids are tapered too rapidly, and relapse is common (see Prognosis).

The cause of polymyalgia rheumatica (PMR) is unknown. PMR is closely linked to giant cell arteritis (GCA, temporal arteritis), although it is controversial whether GCA and PMR are 2 separate diseases or part of the same spectrum of disease. One hypothesis is that in a genetically predisposed patient, an environmental factor, possibly a virus, causes monocyte activation, which helps determine the production of cytokines that induce manifestations characteristic of PMR and GCA. However, although several infectious agents have been investigated as possible triggers, results are inconclusive.^[2]

Immunogenetic studies support a polygenic basis for GCA and PMR. Occurrence in siblings and increased prevalence in those of Northern European heritage also suggests a genetic role in the pathophysiology of the disease. Although most studies confirm an association between HLA-DRB1*04 alleles and GCA, the strength of this association with PMR varies between different populations. Interleukin (IL)–1 and tumor necrosis factor (TNF)–alpha gene polymorphisms have weak association with GCA and PMR. In Spain, an IL-6 polymorphism was associated with the expression of PMR symptoms in GCA patients. Additionally, in this Spanish population, the RANTES polymorphism was associated with PMR and not GCA.^[3]

Pathologically, GCA and PMR are similar, with the exception of the absence of significant vascular involvement in pure PMR. Synovitis, bursitis, and tenosynovitis around the joints, especially the shoulders, hips, knees, metacarpal phalangeal joints, and wrists, are seen in PMR. Inflammation is thought to initiate within the synovium and bursae, with recognition of an unknown antigen by dendritic cells or macrophages.

Systemic macrophage and T-cell activation is characteristic of both GCA and PMR. Patients often have elevated levels of IL-6, which is likely responsible for the systemic inflammatory response in both GCA and PMR. Most studies in PMR shows that decreases in the level of circulating IL-6 correlate to remission of clinical symptoms. Data on other circulating cytokines (eg, IL-1, IL-2, TNF-alpha, IL-10) are too scant to draw any conclusions. However, recent studies do show that interferon-gamma (IFN-γ) is expressed in nearly 70% of temporal artery biopsy samples from patients with GCA but is not detected in patients with isolated PMR, suggesting IFN-γ may be crucial to the development of GCA.^{[2, 3, 4, 5]}

Although PMR causes severe pain and stiffness in the proximal muscle groups, no evidence of disease is present on muscle biopsy. Muscle strength and electromyographic findings are normal. Instead, the inflammation is at the level of the synovium and bursae, with MRI studies revealing periarticular inflammation as well as bursitis in the bursae associated with both the shoulder and hip girdles.^{[6, 7]}

Some evidence suggests the presence of cell-mediated injury to the elastic lamina in the blood vessels in the affected muscle groups. A prospective study of 35 patients with isolated PMR noted vascular [¹⁸ F] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging at diagnosis in 31% of patients, predominately at the subclavian arteritis, but at a much lower intensity than in GCA patients. Increased FDG uptake in the shoulders was seen in 95% of the patients, in the hips in 89%, and in the spinous processes of the cervical and lumbar vertebrae (correlating with interspinous bursitis) of 51% of the patients with isolated PMR.^[8]

The exact cause (or causes) of polymyalgia rheumatica (PMR) is unknown. The disease is more common among northern Europeans, which may indicate a genetic predisposition. Other risk factors for PMR are an age of 50 years or older and the presence of giant cell arteritis (GCA).

An autoimmune process may play a role in PMR development. PMR is associated with the HLA-DR4 haplotype. High levels of IL-6 are associated with increased disease activity.

Many investigators believe that nonerosive synovitis and tenosynovitis are responsible for many symptoms of PMR.

In the United States, the average annual incidence of polymyalgia rheumatica is 52.5 cases per 100,000 persons aged 50 years and older. The prevalence is approximately 0.5-0.7%.

Worldwide, the frequency varies by country. In Europe, the frequency of decreases from north to south, with a high incidence in Scandinavia and low incidences in Mediterranean countries. In Italy, for example, the incidence is 12.7 cases per 100,000 persons.

Whites are affected more than other ethnic groups. Polymyalgia rheumatica is twice as common in females. The incidence increases with advancing age. Polymyalgia rheumatica rarely affects persons younger than 50 years. The median age at diagnosis is 72 years.^[9]

Polymyalgia rheumatica is usually self-limited. Untreated patients often feel unwell and have an impaired quality of life. With prompt diagnosis and adequate therapy, patients have an excellent prognosis. The average length of disease is 3 years. However, exacerbations may occur if corticosteroids are tapered too rapidly, and relapse is common, affecting up to 25% of all treated patients. Arteritic relapse in a patient who presented exclusively with polymyalgia rheumatica is unusual.

With appropriate treatment, the survival rate is similar to that of unaffected persons of the same age; however, some reports document increased mortality from vascular disease among men with polymyalgia rheumatica beyond the initial 2 years after diagnosis. Accelerated atherosclerosis secondary to uncontrolled systemic inflammation likely plays a role in this increased mortality.^{[2, 3]}

Generally, polymyalgia rheumatica is not associated with serious complications. Patients treated with corticosteroids are at risk for long-term complications of corticosteroid therapy. Every patient should be considered at risk for giant cell arteritis. Additionally, cases of systemic amyloidosis-associated polymyalgia rheumatica have been reported.

Inform the patient about the potential benefits and risks of corticosteroid treatment, and encourage the patient to participate in choosing the treatment plan. Emphasize the importance of healthy dietary habits and ensure adequate calcium and vitamin D supplementation. Baseline screening for osteoporosis is encouraged and bisphosphonate therapy to prevent glucocorticoid-induced osteoporosis is recommended as the majority of patients require a prolonged course of corticosteroids.

Emphasize compliance with long-term treatment plans and follow-up care in order to prevent relapses, flares, and subsequent morbidity secondary to corticosteroid therapy. Advise patients to immediately seek medical care if symptoms recur.

For patient education information, see the Muscle Disorders Center, as well as Chronic Fatigue Syndrome.