Rheumatoid arthritis (RA) is a
chronic progressive inflammatory arthritis of unknown origin involving multiple
joints and characterized by disorganization of connective tissue of the
synovial membrane and articular cartilarge and development of their
deformation. RA is likely an
autoimmune disease.
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RA is basically a severe form of chronic synovitis
that can lead to destruction and ankylosis of affected joints. The small joints
of hands and feet are usually the first and most common to be involved, with
lesions of the large joints appearing later in the course of the disease.
·
Although the skin, eyes, heart, lungs, spleen, lymph
nodes, sceletal muscle, central and peripheral nervous system, and other organs
can be affected.
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Females are affected three times more often than males
and there is peak prevalence in the third to fourth decades of life.
Pathogenesis of RA
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Rheumatoid disease is often accompanied by
characteristic immunoglobulin (often IgM), called rheumatoid
factosr (RF), in affected person serum. These factors are against
the own immunoglobulins (often IgG) and are of considerable complexity; they
are capable of acting as antiglobulins and of forming complexes with abnormal
antigenic gammaglobulins in vivo and in vitro.
·
RF forms locally in joint fluid; an immune complex
binds complement and forms the intra-articular chemotactic factors C3a and C5a.
The resultant accumulation of neutrophils contributes to the pathogenesis of
the joint disease.
·
Other autoantibodies are also found in RA, and in
addition to circulating immune complexes, cell-mediated immune systems also
contribute to the pathogenesis of the articular and extra-articular
manifestations of RA.
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The cells and mediators that likely play a role in the
RA include neutrophils, synovial lining cells, lymphocytes, and macrophages.
The last-mentioned produce IL-1 and tumor necrosis factor, cytokines known to
stimulate release of collagenases and other lytic enzymes.
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The trigger for these immunologic reactions remains
unknown; some authors have suggested Epstein-Barr virus (EBV) infection.
Morphology of RA
Main morphological appearance of RA
is synovitis
RA generally first affects the small, proximal joints of the hands and
feet, but then may involve, usually symmetrically, the wrists, elbows, ankles,
and knees.
Stages of synovitis:
1. First stage
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Acute
inflammatory reaction with development of edema, hyperemia, and infiltration by
small and large lymphocytes, plasma cells, plasmoblasts, mast cells, and
macrophages, indicating the presence of both humoral and cellular immune
response arises.
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There often are small areas of superficial necrosis of
synovial lining cells with formation of superficial erosions covered by
fibrinoid deposits; these deposits are composed of fibrin and small amounts of
gamma globulin and complement components.
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An exudate
containing polymorphonuclear leukocytes, may with ingested immune complexes,
accumulates in joint cavity.
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Not
infrequently, 2 to 3 mm “rice” bodies, composed of fibrin, fibronectin, collagen and
immunoglobulin are present in joint cavities of seropositive patients.
2. Second stage
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Hypertrophy of the synovium, synoviocytic hyperplasia,
and an intense lymphoplasmacytic and hystiocytic infiltrate take place.
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Granulation tissue composed of synovial fibroblasts
and capillaries causes grossly recognizable villous thickening of the synovium,
whose lining cells become hypertrophic and hyperplastic.
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In some of these lining cells as well as lymphocytes
and plasma cells of the synovium and in leukocytes of the synovial fluid occur.
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This exuberant synovium is known as pannus, which eventually fills the joint space, encroaching upon
the articular surfaces.
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Release of destructive enzymes (proteases and
collagenases) and cytokines (particularly IL-1) and pannus formation destroy
cartilage, leading to changes very reminiscent of degenerative joint disease.
3. Third stage
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Fibrous and bony ankylosis can result.
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As the pannus ages, vascularity decreases, the
fibrosis and collagenization lead to shrinkage of the capsule, progressive
narrowing of the joint space, and displacement or increasing approximation of
the ends of the bones.
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Closely opposing bones may become fused by bone
bridges developing in the scar tissue, or they may be telescoped into each
other, with complete elimination of the joint.
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Other features include rheumatoid nodules (or
rheumatoid granuloma) in subcutaneous tissues (areas of necrosis surrounded by
palisade of fibroblasts and white cells at pressure points such as elbows),
acute vasculitis (in patients with high rheumatoid factors), and nonspecific,
fibrinous inflammatory lesions of lungs, pleura, pericardium, myocardium,
peripheral nerves, and eyes.
The most common
extra-articular lesion
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The most common extra-articular lesion is the
subcutaneous nodule, a granuloma of a few millimeters to several centimeters in
size, developing usually in areas close to the joints and subject to minor
mechanical insults.
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Vasculitis associated with deposition of immune
complexes in vessel walls is seen especially in patients with high serum titers
of IgM-RF complex; occlusion of the vessel may result in ischemia and
microinfarcts. Occlusion of the large vessels can cause gangrene of the
terminal phalanges of fingers or toes.
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Cardiac lesions may involve the pericardium,
myocardium, and endocardium, with focal accumulation of lymphocytes and plasma
cells, vasculitis, granulomas, fibrosis, and amyloidosis.
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Pulmonary lesions may be focal and granulematous or
diffuse, interstitial, or intraalveolar. The result is focal fibrosis.
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Lymph nodes show hyperplasia and, less commonly,
granulomas. Several types of scleritis and retinopathy have been described in
about 1% of patients with rheumatoid disease.
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Amyloidosis is a late complication of RA with data on
the frequency varying from 25% to 60%.
Clinical features
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Variable. Most patients experience a prodrome of
malaise, fever, fatigue, and musculoskeletal pain before joint involvement
occurs.
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The lucky patient experiences mild transient disease
without sequelae, but most has fluctuating disease with the greatest
progression during the initial 4 to 5 years. In a minority the onset in acute,
with rapidly progressive development of joint deformities.
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Characteristic deformities are radial deviation of the
wrist with ulnar deviation of the fingers.
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Extra-articular manifestations (mentioned above),
although infrequent, are rarely the presenting features of the disease, and
tend to develop in patients with high RF titers.
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Some of the total morbidity of RA is caused by GI
bleeding from long-term aspirin therapy, infections from steroid use, or
amyloidosis in long-term severe disease.
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The death is caused by uremia.
