Aetiology
The exact cause of polymyalgia rheumatica (PMR) is unknown. There have been conflicting observations regarding seasonal variation on the incidence of PMR. These observations have suggested a role of infectious agents such as adenovirus, respiratory syncytial virus, parainfluenza virus type I, parvovirus B19, Mycoplasma pneumoniae, and Chlamydia pneumoniae.[4][8] Although association studies may suggest an infectious agent as a possible aetiology, no study has yet established this fact. A role for genetic factors has been suggested based on observed ethnic differences and familial cases. There is an association between PMR and the HLA-DRB1*04 and -DRB1*01 alleles, and with the genetic polymorphisms for ICAM-1, tumour necrosis factor-alpha, and interleukin (IL)-1 receptor antagonist.[4][9] These factors may influence the susceptibility to PMR. A potential hormonal role has been suggested by the observation of adrenal gland hypofunction in untreated patients. Inappropriately normal cortisol levels and low levels of dehydroepiandrosterone have been observed.[10]
Pathophysiology
The pathogenesis of PMR remains unclear. Given the association of PMR with giant cell arteritis (GCA), it is thought that mechanisms similar to those contributing to GCA may be involved.[11] Although vasculitis is present in GCA, vasculitis involving vessels to the neck, shoulder girdle, and hip girdle has not been found. Increased interleukin (IL)-6 in the serum and in temporal artery biopsy specimens has been observed in both PMR and GCA patients, suggesting an inflammatory role for IL-6. Moreover, IL-6 promoter polymorphisms have been suggested to affect the clinical expression of PMR and GCA.[4] Study results suggest that both PMR and GCA patients share similar in situ macrophage-derived cytokine mRNA profiles. GCA-recruited T cells in vasculitic lesions were found to secrete IL-2 and interferon (IFN)-gamma; however, in PMR there was no IFN-gamma expression, suggesting a role for IFN-gamma in the progression to vasculitis.[12][13] A decline in immunosuppressive T-regulatory lymphocytes and an increase in proinflammatory T-helper 17 cells has been observed in a study of PMR patients compared with age-matched controls, suggesting an imbalance in immunological regulation.[14] Decreased numbers of B cells and a redistribution of B-cell subsets have been shown in newly diagnosed PMR patients compared with controls, suggesting a regulatory role for B cells in the pathogenesis of PMR.[15] Significant declines in muscle glutamate and prostaglandin E2 but not in muscle lactate or blood flow with successful corticosteroid treatment in one study of PMR patients suggested that tissue ischaemia may not be the underlying cause of PMR muscle symptoms.[16]
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