Introduction
Background
Rheumatoid arthritis (RA) is a systemic inflammatory disease that results in cartilage and bone destruction. RA is characterized by a typical pattern and distribution of synovial joint involvement. Disorganization of the joint leads to deformities and loss of function.
Pathophysiology
RA is characterized by diffuse cartilage loss and erosion of bone and cartilage. It starts in the synovial membrane, with the initial processes of edema, neovascularization, and hyperplasia of the synovial lining. Proliferation of synoviocytes and macrophages causes thickening of the synovial lining and, together with lymphocytes, plasma cells, and mast cells, develops into pannus.
Pannus is a sheet of invasive cellular tissue that is continuous with the synovial lining. As a result of the higher proportion of synoviocytes and macrophages, pannus causes erosion of bone and cartilage at the margin of joints. Prominent villous formation occurs in the synovium, as does an inflammatory joint effusion. The effusion causes capsule distention and stretching of the ligamentous tissues, resulting in laxity of the capsule. With further progression of the disease, the joint becomes unstable and begins to deform.
At the cellular level, cytokines, such as interleukin 1 and tumor necrosis factor-alpha, stimulate synoviocytes to produce cartilage-degrading enzymes. Other factors involved at this stage include other interleukins and transforming growth factor-beta. Cytokines also regulate production and expression of adhesion molecules, which allow pannus to attach to cartilage and bone.
Hyperplastic synovium and pannus produce several enzymes that are capable of degrading components of bone and cartilage. One important group of enzymes is the matrix metalloproteinases, which are secreted from synoviocytes and chondroblasts in response to cytokines. Other proteolytic enzymes also play a contributory role. Genetically, RA has been shown to be associated with positive human leukocyte antigen DR4; a strong association with human leukocyte antigen DRB1 has been shown as well.
Frequency
United States
The prevalence of RA is approximately 1%, with a range of 0.4-2%; however, a prevalence of 5% has been reported among some groups of North American Indians, especially in the Yakima, Pima, and Chippewa tribes.
International
Similar rates of 0.3-1% are seen in Europe and in Asia, and the rates are slightly lower in Africa.
Mortality/Morbidity
The primary effect of RA is in joint deformity and fusion, which occurs in the advanced stages.
- Although occasional flares of joint pain occur throughout the course of the disease, these can usually be controlled with the use of anti-inflammatory medication, especially early in their course.
- When joint subluxations and deformity take place, performing basic daily tasks (eg, writing and holding utensils) can become a problem. Some patients resort to the use of custom-designed writing instruments or utensils to overcome this difficulty.
- Permanent disability occurs in approximately 10-20% of patients.
Race
RA affects persons of all races.
Sex
Women are affected 2-3 times more commonly than men. In some groups, the female preponderance is greater; for example, the female-to-male ratio is as high as 9:1 in Asian Indians.
Age
The onset in women is slightly earlier than in men. RA begins in women in their mid 20s. RA rarely occurs in men younger than age 30 years. In both sexes, the incidence rises constantly, with a broad peak in individuals aged 60-70 years.
Anatomy
In the hands, the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and thumb interphalangeal (IP) joints are most frequently involved. The distal interphalangeal (DIP) joints are involved only in the presence of a coexisting MCP or PIP disease. Tenosynovitis of the flexor tendons causes a reduction in finger flexion and grip strength. Nodular thickening in the tendon sheath may also produce a trigger finger.
As RA progresses, its characteristic deformities become apparent. These include ulnar deviation of the fingers at the MCP joints, subluxation of the MCP joints with the proximal phalanx slipping to the volar side of the metacarpal heads, hyperextension of the PIP joint with flexion of the DIP joint (swan-neck deformity), flexion of the PIP joint with hyperextension of the DIP joint (boutonnière/button-hole deformity), Z-shaped deformity of the thumb from subluxation of the first MCP joint and compensatory hyperextension of the IP joint, and drooping of the ring and little fingers resulting from rupture of the extensor tendons at the point of crossing the inflamed, eroded ulnar styloid.
In the wrist, the early stages of RA cause tenosynovitis of the extensor tendons, causing swelling over the distal wrist. The ulnar styloid may become tender, which indicates inflammatory synovitis. The distal end of the ulna tends to sublux dorsally, and the carpal bones sublux anteriorly to the distal radius and ulna. Bony erosions and ankylosis of the carpal bones are also seen and appear to be prominent features in Asian patients.
Presentation
Arthritis typically has an insidious onset, with symmetric, polyarticular involvement of the small joints in the hands and feet. Symptoms of pain and stiffness are usually present. The classic persistent aching pain tends to have a diurnal variation (ie, it is worse in the morning and eases with activity). Stiffness is also more common in the early morning after a period of inactivity. Stiffness lasting more than 1 hour is fairly specific for inflammatory joint disease.
Clinical signs include joint swelling, muscle wasting, instability, malalignment, and restriction of range of motion. Joint swelling may be real or apparent, with real swelling resulting from synovial thickening and joint effusion in active synovitis and apparent swelling resulting from malalignment.
In addition, RA is a systemic disease and a number of important extra-articular manifestations have been identified. Fatigue, malaise, and weight loss are prominent features and may reflect disease activity. Generalized osteoporosis involving both the appendicular and axial skeleton is common. A mild normochromic normocytic anemia is commonly present and is similar to anemia of chronic disease; however, a degree of anemia lower than 10 g/dL is unusual. Felty syndrome is the combination of neutropenia and splenomegaly in RA.
Rheumatoid nodules are small, firm, nontender subcutaneous nodules that are most often found over the proximal third of the ulna and at the olecranon. Nodules may also occur at the fingers and thumbs (particularly in the dominant hand) and elsewhere in the body. Nodules are strongly associated with a positive rheumatoid factor.
Pleural effusion and pleuritis are the most common pulmonary manifestations. Pulmonary rheumatoid nodules are associated with the presence of skin rheumatoid nodules and are usually peripheral. They may cavitate but rarely calcify. Multiple nodules on a background of pneumoconiosis is known as Caplan syndrome. In addition, the incidence of pulmonary fibrosis and bronchiectasis is increased in RA. Cardiac features include pericarditis and rheumatoid nodules in the heart.
RA vasculitis frequently manifests as obliterative endarteritis, with proliferation of the intima in digital vessels resulting in nailfold and digital infarcts. Several nerve entrapment syndromes, such as the median nerve in carpal tunnel syndrome, ulnar nerve compression within the Guyon canal, and the posterior tibial nerve in the tarsal tunnel are more common in RA. The eyes may show keratoconjunctivitis sicca and/or scleritis. Sjögren syndrome may occur together with keratoconjunctivitis sicca.
Rheumatoid factor is an immunoglobulin M antibody that is present in 60-80% of patients with RA at some stage during the disease; however, rheumatoid factor is not specific for RA and is also present in other connective tissue diseases, infection, and autoimmune disorders. In addition, rheumatoid factor is present in 1-5% of people without RA. Seropositive results are associated with nodules, vasculitis, and Sjögren syndrome.
Preferred Examination
Radiography remains the first choice in imaging RA. Magnetic resonance imaging (MRI) provides a more accurate assessment, as well as earlier detection of lesions. Ultrasonography of specific joints based on radiographs may have a role as well.
Limitations of Techniques
The mainstay of imaging RA in the hands is radiography. Radiography is cheap, is easily reproducible, and allows easy serial comparison for assessment of disease progression. The main disadvantage is the absence of specific radiographic findings in early disease, since visualization of erosions may only be seen later.
MRI continues to develop as a treatment tool, with the main thrust being detection of early disease at a stage at which disease-modifying drugs can be used; however, the cost of the examination and the small size of the joints involved limit widespread use. With further experience and cheaper scans, MRI scanning for the treatment of RA may gain acceptance in the future.
Patient Education: For excellent patient education resources, visit eMedicine's Arthritis Center. Also, see eMedicine's patient education articles Rheumatoid Arthritis and Understanding Rheumatoid Arthritis Medications.
Differential Diagnoses
[Reiter Syndrome, Musculoskeletal]
Ankylosing Spondylitis
Calcium Pyrophosphate Deposition Disease
Gout
Juvenile Rheumatoid Arthritis
Psoriatic Arthritis
Other Problems to Be Considered
Scleroderma
Dermatomyositis
Systemic lupus erythematosus
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Further Reading
Keywords
RA, human leukocyte antigen, DR4, DRB1, joint deformity, joint fusion, metacarpophalangeal joint, MCP joint, proximal interphalangeal joint, PIP joint, thumb interphalangeal joint, IP joint, distal interphalangeal joint, DIP joint, swan-neck deformity, boutonnière deformity, button-hole deformity, inflammatory joint disease, rheumatoid nodules
