Rheumatoid arthritis (RA) is a chronic autoimmune multisystemic inflammatory disease which affects many organs but predominantly attacks the synovial tissues and joints.
The overall prevalence is 0.5-1% and the disease is 2-3 times more common in women 1.
Onset is generally in adulthood, peaking in the 4th and 5th decades. The pediatric condition, juvenile rheumatoid arthritis, is discussed separately.
Onset may be insidious or abrupt. Early features commonly include tiredness, malaise, and generalized aches. Arthritis symptoms typically first develop in the hands and wrists in a symmetric, proximal distribution. Feet and large joints may also be involved.
Etiology is unknown but is probably multifactorial. It is generally considered that a genetic predisposition (HLA-DR B1 which is the most common allele of HLA-DR4 involved in RA) and an environmental trigger (Epstein-Barr virus postulated as a possible antigen, but not proven) lead to an autoimmune response that is directed against synovial structures and other organs.
Activation and accumulation of T CD4 cells in the synovium starts a cascade of inflammatory responses which result in:
- activation of the macrophages and synovial cells and production of cytokines such as IL4 and TNF, which in turn cause proliferation of the synovial cells and increase production of destructive enzymes such as elastase and collagenase by macrophages
- activating B cell lymphocytes to produce various antibodies including rheumatoid factor (RF-IgM antibodies against Fc portion of the IgG) which makes immune complexes that deposit in different tissues and contribute to further injury
- directly activate endothelial cells via increased production of VCAM1, which increases the adhesion and accumulation of inflammatory cells
- producing RANKL which in turn activate osteoclasts causing subchondral bone destruction
The inflammatory response leads to pannus formation. Pannus is an edematous thickened hyperplastic synovium infiltrated by lymphocytes T and B, plasmocytes, macrophages and osteoclasts. Pannus will gradually erode bare areas initially, followed by the articular cartilage. It causes a fibrous ankylosis which eventually ossifies 2,3.
Diagnosis is based on a combination of clinical, radiographic, and serological criteria. The 2010 ACR - EULAR classification criteria for Rheumatoid Arthritis 4 has a maximal score of 10 and requires a score of >6 for a diagnosis of RA to be made:
- joint involvement
- 0: large joint
- 1: 2-10 large joints
- 2: 1-3 small joints (with or without involvement of large joints)
- 3: 4-10 small joints (with or without involvement of large joints)
- 5: >10 joints (at least 1 small joint)
- 0: negative RF and negative anti-CCP
- 2: low-positive RF or low-positive anti-CCP
- 3: high-positive RF or high-positive anti-CCP
- acute phase reactants
- duration of symptoms
- 0: <6 weeks
- 1: >6 weeks
Non-musculoskeletal features of RA tend to occur late in the disease and include:
- disease may involve the interstitum, airway, and/or pleura
- cardiovascular disease
- cutaneous involvement
- rheumatoid nodules are usually seen in pressure areas: elbows, occiput, lumbosacral 3
- occurs in RF-positive patients 9
- ocular involvement
There are several serological markers for rheumatoid arthritis:
- rheumatoid factor (RF): is an IgM antibody against FC portion of the IgG antibodies, and is a traditional marker but is nonspecific; associated with several autoimmune and chronic infectious diseases
- anti-cyclic citrullinated peptide (anti-CCP)/anti-citruillated plasma antibody (ACPA): it is more than 80% sensitive and more than 95% specific
- elevated ESR or CRP
- Felty syndrome: rheumatoid arthritis, splenomegaly and neutropenia
- Caplan syndrome 7: rheumatoid arthritis and pneumoconiosis
Musculoskeletal manifestations are the earliest and the dominant features of rheumatoid arthritis.
For further details, please refer to musculoskeletal manifestations of rheumatoid arthritis.
Pulmonary disease may involve the airway, interstitum, and/or pleura; a full description is available in respiratory manifestations of rheumatoid arthritis.
Treatment and prognosis
Treatment of RA is aimed at improving the symptoms and slowing disease progression. Therapy is with a combination of corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), disease modifying anti-rheumatic drugs (DMARDs), and TNF antagonists (e.g. etanercept) The anti-TNF treatments and variants of, which suppress the immune system, are known collectively as biological therapies.
The disease carries a significant burden of disability. There is also a reduction in life expectancy, with excess mortality usually related to its non-articular manifestations 5,6.
History and etymology
Rheumatoid arthritis was a term first coined by British physician Sir Alfred Baring Garrod (1819-1907) in 1859 11.
- 1. Gabriel SE. The epidemiology of rheumatoid arthritis. Rheum. Dis. Clin. North Am. 2001;27 (2): 269-81. - Pubmed citation
- 2. Sommer OJ, Kladosek A, Weiler V et-al. Rheumatoid arthritis: a practical guide to state-of-the-art imaging, image interpretation, and clinical implications. Radiographics. 25 (2): 381-98. doi:10.1148/rg.252045111 - Pubmed citation
- 3. Robbins SL, Kumar V, Abbas AK et-al. Robbins and Cotran pathologic basis of disease. W.B. Saunders Company. (2010) ISBN:1416031219. Read it at Google Books - Find it at Amazon
- 4. Daniel Aletaha, Tuhina Neogi, Alan J. Silman, Julia Funovits, David T. Felson, Clifton O. Bingham, III, Neal S. Birnbaum, Gerd R. Burmester, Vivian P. Bykerk, Marc D. Cohen, Bernard Combe, Karen H. Costenbader, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Johanna M. W. Hazes, Kathryn Hobbs, Tom W. J. Huizinga, Arthur Kavanaugh, Jonathan Kay, Tore K. Kvien, Timothy Laing, Philip Mease, Henri A. Ménard, Larry W. Moreland, Raymond L. Naden, Theodore Pincus, Josef S. Smolen, Ewa Stanislawska-Biernat, Deborah Symmons, Paul P. Tak, Katherine S. Upchurch, Jirˇí Vencovsky´, Frederick Wolfe, and Gillian Hawker. ARTHRITIS & RHEUMATISM Vol. 62, No. 9, September 2010, pp 2569–2581 DOI 10.1002/art.27584 © 2010, American College of Rheumatology http://www.rheumatology.org/Portals/0/Files/2010%20Rheumatoid%20Arthritis%20Classification_EXCERPT%202010.pdf
- 5. Chehata JC, Hassell AB, Clarke SA et-al. Mortality in rheumatoid arthritis: relationship to single and composite measures of disease activity. Rheumatology (Oxford). 2001;40 (4): 447-52. doi:10.1093/rheumatology/40.4.447 - Pubmed citation
- 6. Young A, Koduri G, Batley M et-al. Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis. Rheumatology (Oxford). 2007;46 (2): 350-7. doi:10.1093/rheumatology/kel253 - Pubmed citation
- 7. Caplan A. Certain unusual radiological appearances in the chest of coal-miners suffering from rheumatoid arthritis. Thorax. 1953;8 (1): 29-37. doi:10.1136/thx.8.1.29 - Free text at pubmed - Pubmed citation
- 8. Turesson C, Jacobsson L, Bergström U. Extra-articular rheumatoid arthritis: prevalence and mortality. Rheumatology (Oxford). 1999;38 (7): 668-74. doi:10.1093/rheumatology/38.7.668 - Pubmed citation
- 9. Ziff, Morris. Arthritis & Rheumatism. doi:10.1002/art.1780330601
- 10. Reddy SC, Rao UR. Ocular complications of adult rheumatoid arthritis. Rheumatol. Int. 1996;16 (2): 49-52. - Pubmed citation
- 11. Storey GD. Alfred Baring Garrod (1819-1907). (2001) Rheumatology (Oxford, England). 40 (10): 1189-90. Pubmed
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