Rheumatoid arthritis pathogenesis: risk factors, synovial inflammation and joint destruction
From shared epitope, smoking and citrullination through the preclinical autoantibody phase to pannus, RANKL-driven erosion and systemic effects, with the likelihood-ratio maths of RF and anti-CCP and how each biologic maps onto a step.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- RA affects about 2.0% of Australians on self-report (AIHW, 2022 National Health Survey: 2.5% of women, 1.6% of men). Onset peaks at 35 to 64 years. Formal studies give a lower true prevalence, about 0.5 to 1%.
- Disease develops in stages: genetic risk, an environmental trigger at a mucosal surface, autoantibodies years before symptoms, then synovitis and erosion.
- Seropositive (anti-CCP or RF positive) RA is more erosive and more often extra-articular. Seronegative RA has weaker HLA links and is probably several diseases.
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Sources
- Rheumatoid arthritis (Chronic musculoskeletal conditions)AU/NZAustralian Institute of Health and Welfare, 2024 release, 2022 National Health Survey data
- Therapeutic Guidelines: RheumatologyAU/NZTherapeutic Guidelines Limited (eTG complete), current online version, accessed November 2026
- Firestein and Kelley's Textbook of Rheumatology (11th ed.)Elsevier, 2021
- Smolen JS et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018;4:18001Nature Reviews Disease Primers, 2018
- Nishimura K et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med 2007;146:797-808Annals of Internal Medicine, 2007
- Nielen MMJ et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004;50:380-6Arthritis and Rheumatism, 2004
- Humby F et al. Rituximab versus tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis (R4RA): 16-week outcomes of a stratified, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial. Lancet 2021;397:305-17The Lancet, 2021
- Rivellese F et al. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nat Med 2022;28:1256-68Nature Medicine, 2022
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy