What causes polymyalgia rheumatica (PMR)?

The Etiology 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 potential environmental triggers in individuals over 50 years of age. 1

Key Factors in PMR Pathogenesis

• PMR is characterized by activation of both innate and adaptive immune systems, with demonstrated activation of dendritic cells and monocytes/macrophages, along with an altered balance between Th17 and Treg cells 1
• The disease occurs almost exclusively in people over 50 years of age, strongly suggesting that age-related immune alterations play a crucial role in its development 1, 2
• Genetic predisposition appears to be a significant factor, as PMR shows higher prevalence in certain populations 1
• Disturbed B cell distribution and function have been demonstrated in PMR patients, indicating a more complex pathogenesis than previously thought 1

Potential Environmental Triggers

• Several infectious agents have been investigated as possible triggers of PMR, though results remain inconclusive 1
• The occurrence of PMR in married cohabiting couples suggests a potential environmental factor in disease development 3
• Some researchers have proposed PMR may be triggered by infectious agents in genetically susceptible individuals, though definitive evidence is lacking 3, 4

Relationship with Giant Cell Arteritis

• PMR is associated with giant cell arteritis (GCA) in approximately 20% of cases, suggesting potential shared pathophysiological mechanisms 5
• Modern imaging techniques suggest that subclinical GCA (e.g., aortitis) may be more prevalent in PMR patients than previously recognized 5
• It remains debated whether PMR and GCA represent the same disease process or two distinct pathologies with overlapping features 3

Inflammatory Markers and Disease Characteristics

• High levels of inflammatory markers at diagnosis, particularly ESR >40 mm/1st hour, may influence disease outcomes and are associated with higher relapse rates 6, 7
• Female sex has been associated with higher risk of glucocorticoid side effects and potentially higher relapse rates in PMR 7
• Peripheral inflammatory arthritis at diagnosis has been linked to higher relapse rates in some studies 7

Clinical Presentation and Diagnosis

• PMR typically presents with rapid onset of symmetric myalgias in the shoulder and pelvic girdles 5
• Myalgias are accompanied by synovitis and bursitis of the large proximal joints, which can be visualized by ultrasound or magnetic resonance imaging 5
• Unlike other autoimmune conditions, pathognomonic findings like specific autoantibodies are lacking in PMR 5
• Diagnosis requires exclusion of relevant mimicking conditions (non-inflammatory, inflammatory, drug-induced, endocrine, infective, and neoplastic) 7

PMR remains an enigmatic inflammatory condition affecting older adults, with current understanding pointing to a multifactorial etiology involving genetic, immunological, and potentially environmental factors 2, 1.