Clinical aspects of rheumatoid arthritis
Introduction
Rheumatoid arthritis is a chronic, systemic, inflammatory disorder of unknown etiology that primarily involves the joints but can also cause multiple extra-articular manifestations. RA is the most common autoimmune disease, affecting 1–1.5% of the population worldwide [1], [2], [3], [4], [5]. Rheumatoid arthritis (RA) is characterized by synovitis and autoantibody formation (RF). The hallmark feature of the disease is persistent symmetric polyarthritis (synovitis) that affects the hands, wrists and feet, although almost all diarthrodial joints may become involved. In addition to articular manifestations, systemic involvement may cause constitutional symptoms (such as weight loss, low-grade fever, malaise), rheumatoid nodules, serositis and vasculitis. The severity of RA may fluctuate over time, but chronic RA most commonly results in the progressive development of various degrees of joint destruction, deformity, significant decline in functional status and a premature death [6], [7].
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Epidemiology
RA is one of the many chronic autoimmune diseases that predominates in women. The ratio of female to male patients is approximately 2–4:1 [8]. The basis of the gender differences is not known but presumably is related to effects of the hormonal milieu on immune function. Throughout the world, ethnic groups like the North American Pima Indians and southeast Alaskan Indians have a much higher incidence of RA [8]. The incidence of RA rises dramatically during adulthood and peaks in individuals
Etiology
Although the etiology remains a mystery, several studies suggest environmental and genetic factors are responsible. Aho et al. showed the most compelling example for both by finding a 30% concordance in monozygotic twins, compared to 5% in fraternal twins and first degree relatives [10]. Environmental factors must be related to RA development otherwise monozygotic twins would have a 100% concordance. A recognized RA genetic risk factor is the presence of the HLA-DR4 or HLA-DRB1 class II MHC
Pathophysiology
The role of the mediators of inflammation, cytokines, growth factors, chemokines, adhesion molecules and matrix metalloproteinases (MMPs) has not been clearly defined in the pathogenesis of RA. These substances appear to be involved in attracting and activating immune cells and contributing to the activation, proliferation and phenotypic transformation of synoviocytes into pannus. Pannus behaves similar to a locally invasive tumor by invading and eroding articular cartilage, subchondral bone,
General
The initial symptoms of RA (frequently articular) typically can present one of two ways; with a slow insidious onset or an explosive sudden onset. The 55–65% of cases begin insidiously, over weeks to months [21]. The 8–15% of patients have an acute onset of symptoms that peak within a few days. In some individuals, fatigue, malaise, puffy hands, diffuse musculoskeletal pains or morning stiffness may be the first nonspecific complaints, with synovitis occurring later. Asymmetric presentations
The hand
Symmetric involvement of the hands is the hallmark of RA, with swelling of the MCP and PIP joints. MCP involvement, with the development of palmar subluxation and ulnar deviation, is more characteristic of progressive RA. Synovitis within the MCP joints weakens the dorsal and radial structures and loosens the collateral ligaments. This loosening allows reducible (not fixed) radial deviation of the wrists and associated ulnar deviation of the fingers.
Three additional PIP deformities can occur as
Extra-articular manifestations
The number and severity of extra-articular features vary with the duration and severity of the disease. Extra-articular manifestations of RA are associated with the observed excessive mortality [30], [31], [32].
Differential diagnosis
Other diseases must be considered which appear similar to RA [58] include:
- 1.
Spondyloarthropathies:
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ankylosing spondylitis,
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enteric infections,
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inflammatory bowel disease,
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psoriatic arthritis,
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reiter's arthritis,
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whipple's disease;
- •
- 2.
Infectious causes:
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acute rheumatic fever,
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bacterial endocarditis,
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gonococcal arthritis,
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lyme disease,
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viral infections (parvo-B 19, HIV, Hep.C);
- •
- 3.
Metabolic and endocrinecauses:
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arthritis of thyroid disease,
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gout,
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hemochromotosis,
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hemoglobinpathies,
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pseudogout;
- •
- 4.
Connective tissue diseases:
- •
Laboratory work up
Serum protein abnormalities are often present. Rheumatoid factor (RF), an antibody directed against the Fc fragment of immunoglobulin G (IgG), is present in the sera of more than 75% of patients. High titers of RF are commonly associated with severe rheumatoid disease. Antinuclear antibodies are demonstrable in 20% of patients, though their titers are lower in RA than in SLE. However, the specificity of RF for RA is 74–98%.
The amount of rheumatoid factor in blood can be measured as follows.
Imaging studies
Plain radiography of affected joints is essential in the evaluation of patients. The earliest changes occur in the wrists or feet and consist of soft-tissue swelling and juxta-articular demineralization. Later, the diagnostic changes of uniform joint-space narrowing are evident, and erosions develop. The erosions are often first evident at the fifth metatarsal head or ulnar styloid and at the juxta-articular margins, where the bony surface is not protected by cartilage. These changes frequently
MRI
Currently, magnetic resonance imaging is the best imaging modality to detect erosions. Specially designed magnetic resonance imaging (MRI) equipment called extremity MRI depicts soft-tissue changes and damage to cartilage and bone even better and at an earlier stage than does computed tomography. However, its cost precludes its widespread use.
Ultrasound
Special ultrasound techniques called power Doppler ultrasonography (PDUS) or quantitative ultrasound (QUS) may be helpful in RA. Doppler ultrasound can aid in the initial diagnosis of RA even in the presence of minimal radiographic data on presentation. PDUS may be reliable for monitoring inflammatory activity in the joint. QUS, which is used for osteoporosis, has been used to detect bone loss in fingers, which may prove to be a good indicator of early RA. US is a sensitive method for assessing
Disease outcome and functional capacity in rheumatoid arthritis
RA is the most common form of inflammatory arthritis, and causes a substantial cost, disability, and lost work productivity [65]. Physical job demands, low functional capacity, old age, and low education may predict work disability and eventual premature death in patients with RA [6], [7].
Depression in RA has been linked to low levels of physical activity, functional disability, pain, fatigue, poor perception of health, increased use of health services, social stress, low level of education,
Management of rheumatoid arthritis
The management of the patient with RA is directed at preserving joint integrity and function as well as preventing extra-articular manifestations. All affected joints may become destroyed thus; every patient with established disease should receive treatment as early as possible. The management of patients with RA is with disease-modifying anti-rheumatic drugs (DMARDS) and anticytokine therapies. While the treatment of RA has evolved from the empiric (use of injected gold salts) to targeted
Summary
Rheumatoid arthritis (RA) is a chronic systemic inflammatory polyarthritis of unknown etiology. In addition to the joint manifestations, RA is an illness, which affects most organ systems with significant morbidity and mortality. However, the new medications and treatment regimens may decrease the observed morbidity and mortality from this disease.
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