Rheumatoid arthritis
A chronic, systemic inflammatory disease, rheumatoid arthritis (RA) primarily attacks peripheral joints and surrounding muscles, tendons, ligaments, and blood vessels. Partial remissions and unpredictable exacerbations mark the course of this potentially crippling disease.
RA occurs worldwide, striking nearly three times more women than men. It can occur at any age, but peak incidence is between ages 25 and 55. RA affects 1% to 2% of the total population.
This disease usually requires lifelong treatment and, sometimes, surgery. In most patients, it follows an intermittent course and allows normal activity, although 10% suffer total disability from severe articular deformity, associated extra-articular symptoms, or both. The prognosis worsens with the development of nodules, vasculitis, and high titers of rheumatoid factor (RF).
Causes
What causes the chronic inflammation characteristic of RA isn’t known. One theory states that abnormal immune activation (occurring in a genetically susceptible individual) leads to inflammation, complement activation, and cell proliferation within joints and tendon sheaths. Although no single environmental factor has been found to be a consistent and reproducible cause of this response, infection (viral or bacterial), hormonal factors, and lifestyle factors may all influence disease onset.
Some RA patients develop an immunoglobulin (Ig) M antibody against their body’s own IgG, which is called RF. Increased production of this antibody may also play a role in genetic inflammation.
Pathogenesis
Much more is known about the pathogenesis of RA than about its causes. If unarrested, the inflammatory process within the joints occurs in four stages.
In the first stage, synovitis develops from congestion and edema of the synovial membrane and joint capsule. Infiltration by lymphocytes, macro-phages, and neutrophils perpetuates the local inflammatory response. These cells, as well as fibroblast-like synovial cells, produce enzymes that help to degrade bone and cartilage.
Formation of pannus—thickened layers of granulation tissue—marks the onset of the second stage. Pannus covers and invades cartilage and eventually destroys the joint capsule and bone.
Progression to the third stage is characterized by fibrous ankylosis—fibrous invasion of the pannus and scar formation that occludes the joint space. Bone atrophy and malalignment cause visible deformities and disrupt the articulation of opposing bones, causing muscle atrophy and imbalance and, possibly, partial dislocations or subluxations.
In the fourth stage, fibrous tissue calcifies, resulting in bony ankylosis and total immobility.
Signs and symptoms
RA usually develops insidiously and initially produces nonspecific signs and symptoms. These include fatigue, malaise, anorexia, persistent low-grade fever, weight loss, lymphadenopathy, and vague articular symptoms.
Specific symptoms
As the disease progresses, more specific localized articular symptoms develop, commonly in the fingers at the proximal
interphalangeal (PIP), metacarpophalangeal (MCP), and metatarsophalangeal joints. These symptoms usually occur bilaterally and symmetrically and may extend to the wrists, knees, elbows, and ankles.
interphalangeal (PIP), metacarpophalangeal (MCP), and metatarsophalangeal joints. These symptoms usually occur bilaterally and symmetrically and may extend to the wrists, knees, elbows, and ankles.
The affected joints stiffen after inactivity, especially on rising in the morning. The fingers may assume a spindle shape from marked edema and congestion in the joints. The joints become tender and painful, at first only when the patient moves them, but eventually even at rest. They often feel hot to the touch. Ultimately, joint function is diminished. Deformities are common if active disease continues.
PIP joints may develop flexion deformities or become hyperextended. MCP joints may swell dorsally, and volar subluxation and stretching of tendons may pull the fingers to the ulnar side (“ulnar drift”).
The fingers may become fixed in a characteristic swan-neck or boutonnière deformity. The hands appear foreshortened and, the wrists boggy; carpal tunnel syndrome from synovial pressure on the median nerve causes paresthesia in the fingers.
Clinical TipEarly intervention, under the guidance of an occupational therapist, with splinting and joint protection devices can effectively delay the progression of joint deformities.
Extra-articular signs
The most common extra-articular finding is the gradual appearance of rheumatoid nodules—subcutaneous, round or oval, nontender masses. These are seen in 20% of RA patients who are RF-positive. They usually appear on pressure areas, such as the elbows, hands, and Achilles tendon.
Vasculitis can lead to skin lesions, leg ulcers, and multiple systemic complications. Peripheral neuropathy may produce numbness or tingling in the feet or weakness and loss of sensation in the fingers. Stiff, weak, or painful muscles are common.
Other common extra-articular effects include pericarditis, pulmonary nodules or fibrosis, pleuritis, scleritis, and episcleritis.
Other complications
Another complication is destruction of the odontoid process, which is part of the second cervical vertebra. With C1 or C2 instability and subluxation, spinal cord compression may occur, particularly in patients with long-standing deforming RA. Upper-motor-neuron signs and symptoms, such as a positive Babinski’s sign and muscle weakness, may also develop.
RA can also cause temporomandibular joint disease, which impairs chewing and causes earaches. Other extra-articular findings include infection, osteoporosis, myositis, cardiopulmonary lesions, lymphadenopathy, and peripheral neuritis.
Diagnosis
Typical signs and symptoms suggest RA, with a firm diagnosis supported by laboratory and other test results:
X-rays in early stages show bone demineralization and soft-tissue swelling; later, loss of cartilage and narrowing of joint spaces; and finally, cartilage and bone destruction and erosion, subluxations, and deformities.
RF is positive in 75% to 80% of patients, as indicated by a titer of 1:160 or higher.
Synovial fluid analysis shows increased volume and turbidity but decreased viscosity and elevated white blood cell counts (often greater than 10,000/μl).
Serum protein electrophoresis may show elevated serum globulin levels.
Erythrocyte sedimentation rate and C-reactive protein are elevated in 85% to 90% of patients (may be useful to monitor response to therapy because elevation typically parallels disease activity).
Complete blood count usually shows moderate anemia, slight leukocytosis, and thrombocytosis.
