Polymyalgia rheumatica pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Polymyalgia rheumatica (PMR) is a chronic inflammatory disease of the articular and periarticular structures of the cervical region, shoulder girdle and hip girdle. The underlying pathophysiology of PMR remains unknown. It has been hypothesized that genetic and environmental factors are implicated, particularly due to the seasonal and geographical differences in the prevalence of this disease. It has also been hypothesized that PMR is associated with infections such as parainfluenza virus type 1, mycoplasma pneumoniae, chlamydia pneumoniae, and parvovirus B19. In addition, histological examinations of synovial biopsies of affected individuals reveal mild synovitis with predominance of CD4 T cells and macrophages. Although myalgia is a symptom of PMR, there is no inflammation of the muscles.

• PMR is a chronic inflammatory disease of the articular and periarticular structures of the cervical region, shoulder girdle and hip girdle.
• The cause of PMR remains unknown; however, there is evidence in the literature of possible involvement of genetic and environmental factors.^[1]
• This hypothesis is supported by the seasonal and geographical variations of the prevalence of PMR. In fact, the prevalence of PMR is the highest among patients from northern European descent and Scandinavian countries, which suggests a genetic and/or environmental role in the pathophysiology of PMR.^[2][3][4]
• Several genes have been reported to be involved in PMR, such as:^{[5][6][7][3][8]}
  • HLA DRB1
  • Interleukin 6
  • Interleukin 1 receptor antagonist
  • Tumor necrosis factor 3b (TNFb3)

• Moreover, the association between PMR and infections is another hypothesis for the development of PMR through viral stimulation of the immune system. This hypothesis is supported by the highest incidence of PMR in the time of some infection epidemics. Some of the infections that have been linked to PMR are:^[9][10]
  • Parainfluenza virus type 1
  • Mycoplasma pneumoniae
  • Chlamydia pneumoniae
  • Parvovirus B19

• In addition to the previous hypotheses, it has been postulated that PMR can be explained by an age related dysregulation in the hypothalamus, pituitary gland and gonads. This disturbance leads to adrenal insufficiency and decrement in dehydroepiandrosterone or androstenedione.^[11]

• Imaging studies such as ultrasound and MRI reveal inflammation in the articular and periarticular regions. The examination of histopathological specimens demonstrates mild synovitis with a predominance of T helper cells and macrophages.^[12]

• Polymyalgia rheumatica may be associated with the following conditions:^[13][14]
  • Giant cell arteritis (temporal arteritis)
  • Systemic lupus erythematosus
  • Rheumatoid arthritis

• In cases the polymyalgia rheumatica associated with giant cell arteritis, microscopic histopathological analysis will show the following findings of arteritis:^[15][16][17]
  • Skip lesions and normal intervening segments
  • Intimal thickening, with prominent cellular infiltration
  • Lymphocytes in the internal or external elastic lamina or adventitia
  • Areas of necrosis may be present in the arterial wall
  • Granulomas containing multinucleated histiocytic and foreign body giant cells, helper T-cell lymphocytes, plasma cells, and fibroblasts^[18]