Rheumatoid arthritis (RA) is a chronic autoimmune multisystemic inflammatory disease which affects many organs but predominantly attacks the synovial tissues and joints.
RA has an overall prevalence of 0.5-1%. There is a female predominance, with the disease being 2-3 times more common in women 1.
Onset is generally in adulthood, peaking in the 4th and 5th decades. The paediatric condition, juvenile rheumatoid arthritis, will be discussed separately.
Onset may be insidious or abrupt, and the early features commonly include tiredness, malaise and generalised aches. Usually, arthritis symptoms first develop in the hands and wrists in a characteristic symmetric, proximal distribution. Feet and large joints may also be involved.
Aetiology is unknown, and 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 (EBV 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 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 deposits 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 oedematous thickened hyperplastic synovium infiltrated by lymphocytes T and B, plasmocytes, macrophages and osteoclasts. Pannus gradually erodes bare areas initially, and 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 American College of Rheumatology revised criteria require that 4 out of 7 of the following are present 4:
- morning stiffness lasting at least 1 hour before maximal improvement
- soft tissue swelling of 3 or more joints observed by a physician
- swelling of the proximal interphalangeal, metacarpophalangeal, or wrist joints
- symmetric swelling
- rheumatoid nodules
- rheumatoid factor
- radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints
Non-musculoskeletal features of RA tend to occur late in the disease and include:
- pulmonary involvement
- please refer to the article on respiratory manifestations of rheumatoid arthritis
- cardiovascular disease
- cutaneous involvement
- rheumatoid nodules are usually seen in pressure areas: elbows, occiput, lumbosacral 3
- occurs in RF-positive patients 9
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): it is more than 80% sensitive and more than 95% specific
- elevated ESR or C-reactive protein
- Felty syndrome: rheumatoid arthritis, splenomegaly and neutropenia
- Caplan syndrome 7: rheumatoid arthritis + pneumoconiosis
Musculoskeletal manifestations are the earliest and the dominant features of rheumatoid arthritis.
For further details, please refer to musculoskeletal manifestations of rheumatoid arthritis.
Please refer to the article on 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, NSAIDs, DMARDs (disease modifying antirheumatic drugs) and TNF antagonists. 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.
- seronegative spondyloarthritides
- Jaccoud arthropathy
- juvenile idiopathic arthritis
- lyme arthritis
- rheumatoid arthritis
- systemic lupus erythematosus
- erosive osteoarthritis
- osteoarthritis (mnemonic)
- primary cystic arthrosis of the hip
- rapidly destructive osteoarthritis of the hip
- secondary synovial osteochondromatosis
- miscellaneous disorders
- related articles
- 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. Arnett FC, Edworthy SM, Bloch DA et-al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31 (3): 315-24. - Pubmed citation
- 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