What is the cause of polymyalgia rheumatica (PMR)?

The Cause of Polymyalgia Rheumatica

The exact cause of polymyalgia rheumatica (PMR) remains unknown, but current evidence suggests it likely results from a complex interaction of genetic predisposition, age-related immune system alterations, and possible environmental triggers in individuals over 50 years of age.

Pathophysiological Mechanisms

Immune System Involvement

• PMR involves activation of both innate and adaptive immune systems 1:
  • Activation of dendritic cells and monocytes/macrophages
  • Altered balance between Th17 and Treg cells
  • Disturbed B cell distribution and function

Age-Related Factors

• PMR occurs almost exclusively in people over 50 years of age 1, 2
• Age-related immune alterations appear to contribute to disease development in genetically predisposed individuals 1

Genetic Factors

• Genetic predisposition likely plays a role in PMR development 2
• The disease shows some genetic associations, though specific genes have not been conclusively identified

Environmental Triggers

• Several infectious agents have been investigated as possible triggers, though results remain inconclusive 1
• The occurrence of PMR in married cohabiting couples suggests potential environmental factors 3
  • Seven cases of PMR in married couples have been reported in literature
  • This supports the theory of environmental triggers, possibly infectious agents

Relationship with Giant Cell Arteritis

• PMR is associated with giant cell arteritis (GCA) in approximately 20% of cases 4
• Modern imaging techniques suggest that subclinical GCA (e.g., aortitis) may be more prevalent in PMR patients than previously recognized 4
• Some researchers question whether PMR is a distinct entity or part of a spectrum with GCA 4, 3

Clinical Implications

• The multifactorial etiology of PMR necessitates a comprehensive diagnostic approach to exclude mimicking conditions 5
• The European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) recommend:
  • Excluding relevant mimicking conditions (non-inflammatory, inflammatory, drug-induced, endocrine, infective, and neoplastic) 5
  • Comprehensive laboratory testing including rheumatoid factor, ACPA, inflammatory markers, and other relevant tests 5

Knowledge Gaps

• Despite advances in understanding PMR pathophysiology, the precise etiology remains elusive 2
• Recent discoveries involving novel immunopathologic targets may provide foundation for future treatment strategies 2
• The role of specific infectious triggers requires further investigation 1, 3

PMR remains an enigmatic inflammatory condition affecting older adults, with ongoing research needed to fully elucidate its cause and develop more targeted treatments beyond the current glucocorticoid-based approaches.