Rheumatoid arthritis (RA) is a chronic, progressive inflammatory disorder of unknown aetiology characterised by polyarticular symmetric joint involvement and systemic manifestations.
WHAT ARE THE CAUSES OF RHEUMATOID ARTHRITIS?
RA results from dysregulation of humoral and cell-mediated immunity. Most patients produce antibodies called rheumatoid factors; these seropositive patients tend to have a more aggressive course than seronegative patients.
Immunoglobulins (Ig) activate the complement system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. Processed antigen is recognised by the major histocompatibility complex proteins on the lymphocyte surface, resulting in activation of T and B cells.
Tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6 are proinflammatory cytokines important in initiation and continuance of inflammation.
Activated T cells produce cytotoxins and cytokines, which stimulate further activation of inflammatory processes and attract cells to areas of inflammation. Macrophages are stimulated to release prostaglandins and cytotoxins. T-cell activation requires both stimulations by proinflammatory cytokines as well as the interaction between cell surface receptors, called costimulation. One such costimulation interaction is between CD28 and CD80/86.
Activated B cells produce plasma cells, which form antibodies that, in combination with the complement system, resulting in accumulation of polymorphonuclear leukocytes. These leukocytes release cytotoxins, oxygen-free radicals, and hydroxyl radicals that promote damage to synovium and bone.
Signalling molecules are important for activating and maintaining Inflammation. Janus kinase (JAK) is a tyrosine kinase responsible for regulating leukocyte maturation and activation. JAK also has effects on the production of cytokines and immunoglobulins.
Vasoactive substances (histamine, kinins, and prostaglandins) are released at sites of inflammation, increasing blood flow and vascular permeability. This causes oedema, warmth, erythema, and pain, and facilitates granulocyte passage from blood vessels to sites of inflammation.
Chronic inflammation of synovial tissue lining the joint capsule results in tissue proliferation (pannus formation). Pannus invades cartilage and eventually the bone surface, producing erosions of bone and cartilage and leading to joint destruction. End results may be loss of joint space and joint motion, bony fusion (ankylosis), joint subluxation, tendon contractures, and chronic deformity.
WHAT ARE THE SIGNS AND SYMPTOMS OF RHEUMATOID ARTHRITIS?
Nonspecific prodromal symptoms developing over weeks to months include fatigue, weakness, low-grade fever, anorexia, and joint pain. Stiffness and myalgias may precede the development of synovitis.
Joint involvement tends to be symmetric and affect small joints of the hands, wrists, and feet; elbows, shoulders, hips, knees, and ankles may also be affected.
Joint stiffness typically is worse in the morning, usually exceeds 30 minutes, and may persist all day.
On examination, joint swelling may be visible or apparent only by palpation. The tissue is soft, spongy, warm, and maybe erythematous. Joint deformities may involve subluxations of wrists, metacarpophalangeal joints, and proximal interphalangeal joints (swan neck deformity, boutonnière deformity, and ulnar deviation).
Extra-articular involvement may include rheumatoid nodules, vasculitis, pleural effusions, pulmonary fibrosis, ocular manifestations, pericarditis, cardiac conduction abnormalities, bone marrow suppression, and lymphadenopathy.
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