Polymyalgia Rheumatica

Updated: Sep 19, 2016
  • Author: Ehab R Saad, MD, MA, FACP, FASN; Chief Editor: Herbert S Diamond, MD  more...
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Overview

Background

Polymyalgia rheumatica (PMR) is a relatively common chronic inflammatory condition 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 PMR develop giant cell arteritis (GCA), and 40-50% of patients with GCA have associated PMR. Despite the similarities of age at onset and some of the clinical manifestations, the relationship between GCA and PMR is not yet clearly established. [1]

PMR is a clinical diagnosis based on the complex of presenting symptoms and the exclusion of the other potential diseases (see Presentation and Workup). Corticosteroids are considered the treatment of choice, and a rapid response to low-dose corticosteroids is considered pathognomonic. Patients who are at risk for relapse, have steroid-related adverse effects, or need prolonged steroid therapy may benefit from the addition of methotrexate. [2] (See Treatment.)

Patients have an excellent prognosis. Exacerbations may occur if steroids are tapered too rapidly, however, and relapse is common.

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Pathophysiology

The cause of PMR is unknown. PMR is closely linked to giant cell arteritis (GCA, temporal arteritis), although it is controversial whether GCA and PMR are two separate diseases or part of the same spectrum of disease. [3] 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. [4]

Immunogenetic studies support a polygenic basis for GCA and PMR. Occurrence in siblings and increased prevalence in those of Northern European heritage suggest 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–alpha (T ) 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. [5]

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 start within the synovium and bursae, with recognition of an unknown antigen by dendritic cells or macrophages. [6]

Systemic macrophage and T-cell activation are characteristic of both GCA and PMR. Patients often have an elevated IL-6 level, which is likely responsible for the systemic inflammatory response in both GCA and PMR. Most studies in PMR show that a decrease in the level of circulating IL-6 correlates with 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, 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. [4, 5, 7, 8]

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. [9, 10]

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. [11]

A study of circadian variation in PMR found that plasma concentrations of IL-6, IL-8, TNF-α, and IL-4 peaked between 4 and 8 am in both untreated patients and controls,although levels of those cytokines were higher throughout the day in patients. The peak in cytokines matched the early-morning peak of pain and stiffness in untreated patients. In addition, melatonin levels were consistently higher in patients than in controls and varied with time, peaking around 2 am, suggesting that melatonin stimulates cytokine production, which in turn accounts at least partly for PMR symptoms. [12]

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Etiology

The exact cause (or causes) of 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 GCA.

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

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

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Epidemiology

In the United States, the average annual incidence of polymyalgia rheumatica (PMR) 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 decreases from north to south, with a high incidence in Scandinavia and a low incidence in Mediterranean countries. In Italy, for example, the incidence is 12.7 cases per 100,000 persons. In a systematic review of case records from a large primary care practice in the United Kingdom, the prevalence of PMR in patients age 55 years and older ranged from 0.91% to 1.53%, depending on the criteria set used for diagnosis. [13]

Whites are affected more than other ethnic groups. PMR is only occasionally reported in African-American persons. PMR is twice as common in females.

The incidence increases with advanced age. PMR rarely affects persons younger than 50 years. The median age at diagnosis is 72 years. [14]

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