Elderly-onset rheumatoid arthritis versus polymyalgia rheumatica: A systematic review and meta-analysis on pathophysiology, diagnosis and clinical progression.
TL;DR
It is highlighted that the distinction between EORA and PMR cannot be reliably established at a single time point and that longitudinal reassessment integrating clinical, serological, and imaging findings remains essential for the differential diagnosis.
Abstract
Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are among the most frequent inflammatory rheumatic diseases in patients over 50, yet their clinical differentiation, particularly when EORA presents with polymyalgic onset, poses a common diagnostic challenge. This systematic review aimed to identify the pathophysiological, clinical, imaging and treatment-response features that distinguish EORA from PMR. MEDLINE, CENTRAL and Scopus (inception to January 2026), with supplementary searches of LILACS, Google Scholar and trial registries (June 2026) were searched, including studies that compared EORA with PMR or reported separately extractable data for both; risk of bias was appraised with design-specific tools and the evidence weighted accordingly. Seventy-one studies across four domains were included: pathophysiology (22 studies), clinical presentation and final diagnosis at follow-up (24 studies), imaging (21 studies), and treatment response (4 studies). Genetically, in one low risk of bias study that stratified EORA by rheumatoid factor status, PMR and seronegative EORA shared HLA-DRB1*13/*14 associations, a pattern distinct from the shared epitope-driven susceptibility of seropositive RA. However, divergent metabolomic signatures suggest different downstream inflammatory mechanisms. An exploratory random-effects meta-analysis yielded a pooled PMR-to-RA reclassification rate of 7% (95% CI 4-12%; 9 studies), narrowing to 4% (95% CI 2-7%) in methodologically robust studies, though rates of reclassification to RA were considerably higher (up to 20%) when patients with undifferentiated polymyalgic presentations were included. Peripheral arthritis occurred in 28% of PMR patients (95% CI 20-35%; 6 studies), with a significant difference between baseline prevalence (21%) and cumulative incidence over follow-up (34%) on subgroup meta-analysis (p = 0.026), and was characteristically transient and glucocorticoid-responsive, whereas persistent synovitis involving wrists and small joints was associated with reclassification to RA. On imaging, evidence from low-to-moderate risk of bias, ultrasound studies showed that shoulder findings overlapped substantially between conditions, whereas bilateral hip synovitis was significantly more frequent in PMR (47% vs 0% in RA), suggesting the hip as a stronger proximal informative site. However, distal joint synovitis demonstrated the highest discriminatory value, with the presence of at least one among RF positivity, hand grey-scale ≥2, or hand power Doppler ≥1 achieving 89% sensitivity and 93% specificity for EORA identification. This review highlights that the distinction between EORA and PMR cannot be reliably established at a single time point and that longitudinal reassessment integrating clinical, serological, and imaging findings remains essential for the differential diagnosis. However, the evidence is limited by clinical and methodological heterogeneity and the predominance of observational designs.