EPIDEMIOLOGY AND PATHOPHYSIOLOGY

RA affects approximately 1% of adults all over the world.^1,2

• RA is the most common autoimmune disease, and the second most common form of arthritis compared to osteoarthritis (OA).^1,2,4
• The prevalence of RA in adult Americans was estimated at 1.29 million, down from the previous estimate of 2.1 million based on data from a 1995-2005 study.³
• RA can occur at any age⁴

Individuals are usually diagnosed between the third and fifth decade of life and women are 2 to 3 times more likely to be diagnosed than men

Pathophysiology (see 3D video)

Rheumatoid arthritis (RA) is  a chronic autoimmune, inflammatory disease in which the immune system destroys synovial joints and accessory structures.^1,2,5-7 Although the exact cause of RA remains unknown recent findings suggest a genetic basis for disease development.

• The interplay between genetic risk factors and environmental triggers is believed to be responsible for initiating an inflammatory process that ultimately manifests clinically by typical signs and symptoms of disease, such as joint swelling and tenderness⁵
• The rheumatoid joint contains numerous cell types that are involved in these inflammatory and destructive processes ^6,7
• T cells, B cells and the orchestrated interaction of pro-inflammatory cytokines play key roles in the pathophysiology of RA.^8,9 Concurrently, CD4+ T cells that secrete IL-2 and IFN-γ infiltrate the synovial membrane.

• Synovitis is caused by the influx or local activation, or both, of mononuclear cells (including T cells, B cells, plasma cells, dendritic cells, macrophages and mast cells) and by angiogenesis.⁸

• As synovial proliferation continues, the pannus invades from the joint margins, triggering cartilage thinning mediated in part by release of matrix metalloproteinases from synovial fibroblasts, in addition to chondrocyte mediated destruction and failure of repair mechanisms
• Bone destruction is also initiated through the activation of osteoclasts^5-7

REFERENCES

1. O’Dell JR. Rheumatoid arthritis. In: Goldman L, Schafer AI, eds. Goldman’s Cecil Medicine, 24th ed. Philadelphia, PA: Saunders Elsevier; 2011:1681–1689.
2. Firestein GS. Etiology and pathogenesis of rheumatoid arthritis. In: Firestein GS, Budd RC, Harris ED Jr, et al, eds. Kelley’s Textbook of Rheumatology, 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1035–1086.
3. Helmick CG, Felson DT, Lawrence RC, et al; National Arthritis Data Workgroup. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. Arthritis Rheum. 2008;58(1):15-25.
4. Harris ED Jr, Firestein GS. Clinical features of rheumatoid arthritis. In: Firestein GS, Budd RC, Harris ED Jr, et al, eds. Kelley’s Textbook of Rheumatology, 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1087–1118.
5. Choy EHS, Panayi GSP. Cytokine pathways and joint inflammation in rheumatoid arthritis. NEngl J Med 2001;344:907-16.
6. Feldman M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 1996;14:397.
7. Moreland LW. Potential biologic agents for treating rheumatoid arthritis. Rheum Dis Clin North Am 2001;27:445-91.
8. Smolen JS, Steiner G. Therapeutic strategies for rheumatoid arthritis. Nat Rev Drug Discov 2003;2:473_88.
9. Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P.New therapies for treatment of rheumatoid arthritis. Lancet 2007;370:1861_74.