Rheumatoid Arthritis 1. Chronic systemic inflammatory disease of unknown cause. Persistent symmetric polyarthritis that affects the hands and feet, but can affect any synovial joint. Extra- articular involvement of skin, heart, lungs and eyes can be significant. 2. Epidemiology: 3/10,000 ww, ~2.1mill ppl. Peaks in ages 35-50yo, mostly females (2-3X > males) 3. Etiology: a. Genetic factors: certain histocompatibility genes make ppl more prone to get RA. HLA DR allels (DR4,1,10,14) are often increased in RA patients. HLA-DR4/1 are present in 90% of cases, 40% of normal ppl. b. Humoral immunity: lymphocytes and plasma cells accumulate in synovium and make antibodies (IgG). Immune-complexes also deposit in joint. 80% of patients with classic RA are + for rheumatoid factor (RF) which is mostly IgM but can be IgG/A that is directed against the Fc fragemetn of IgG. RF is also found in patients with collagen vascular disease (systemic lupus erythematous, progressive systemic sclerosis, dermatomyositis). It is also present in many other disease. c. Cellular immunity: abundant T-cells in rheumatoid synovium are frequently Ia positive (activated) and are usually Thelper cells. Usually in close contact with HLA-DR-+ cells (macP or dendritic cells. T cells usually in contact with macP and dendritic cells through cytokines, usually TNF and IL-1 d. Infectious agents: not detected in joints of ppl with RA. Most patients with RA make antibodies agasint nuclear antigen in B cells infected with Epstein-Barr virus (EBV) (RA-associated nuclear antigen (RANA), also EBV makes B cells make RF e. Local factors: synovial cells from RA patient’s joints have decreased response to glucocorticoids and increased production of hyaluronate, release peptide (connective tissue-activating peptide) that causes increased amounts of prostaglandins (particularly PGE2) 4. Pathogenesis: a. Genetically susceptible person gets a joint infected (with maybe EBV) or some other tissue and causes antibody formation b. Antibodies act as new antigens triggering production of antiidiotype antibodies (RF) c. Immune complexes form with RF and deposit in joints activating complement increasing vascular permeability and uptake of immune complexes by leukocytes which release lysosomal enzymes and ROS and other damaging products d. Activated macP in joint present to T cells stimulating production of cytokines which amplify inflammation and injury 5. Pathology: a. Early synovial changes: edema, accumulation of plasma cells, lymphocytes and macP. Vascularity increases with exudation of fibrin into joint which may result in small fibrin nodules that float in joint (rice bodies) b. Pannus formation: synovial lining increases from 1-3 layers to 8-10 layers, may form multinucleated giant cells. Synovial mem is heavily infiltrated by chronic inflamm cells (lymphocytes and plasma cells). Lymphocytes get together and eventually develop follicular centers (Allison-Ghormely Bodies= inflammatory synovium creeps over surface of articular cartilage transforming into pannus (cloak) which is a sheet of inflamm granulation tissue that spreads from synovial mem into joint. Pannus able to destroy both articular cartilage and bone.). pannus covers the articular cartilage, isolating it, it then erodes articular cartilage using collagenase . osteoclasts are made in the mutated synovium (stim by PGE2 and IL-1 and mediate marginal bone erosion in the areas that don’t have articular cartilage over them cause of the pannus. Pannus also destroys cartilage by depriving it from nutrients, stim T-cells to secrete something causing the release of lysosomal enzymes. Once entire cartilage destroyed joint goes through fibrous fusion called ankylosis c. Changes in synovial fluid: massive increase in volume, turbidity, decreased viscosity, increased protein content and inflamm cells d. Rheumatoid nodules: found in extra-articular location, has central core of fibrinoid necrosis (mix of fibrin and other proteins). Surrounding rim of macP arranged in radial fashion, outside of which are lymphocytes, plasma cells and other mononuclear cells. Resembles granuloma surrounding fibrinoid necrosis core. Found in areas of pressure, movable, firm, rubbery, tender. Often reoccur. May also be seen in lupus erythematous and rheumatic fever. Sometimes found in organs (heart lungs GI) e. Rheumatoid vasculitis: RA may also be joined with acute necrotizing vasculitis of small vessels, affecting any organ. Probably due to immune complexes 6. Clinical features: a. Joint involvement: mostly small joints of hands and feet, symmetric distribution. Most common joints are MCP, wrist, PIP, knee, MTP, shoulder, ankle, C- spine, hip, elbow and temporomandibular b. Systemic manifestations of RA: i. Skin: subcutaneous nodules (rheumatoid nodules) present over pressure points. Vasculitic lesions of skin may occur as palpable purpura or skin ulceration ii. Rheumatoid heart disease: myocardial infarction, myocardial dysfunction, asymptomatic pericardial effusions are common iii. Rheumatoid lung disease: pleural effusions, interstitial fibrosis, rheumatoid nodules with lung parenchyma (caplan syndrome), and bronchiolitis obliterans-organizing pneumonia iv. GI: secondary to associated processes such as medication effects, inflammation and other diseases. Liver is most often affected in patietns with felty syndrome = triad of seropositive rheumatoid arthritis, splenomegaly, and granulocytopenia (1-3% of patients). Clinically characterized by severe joint destruction, high frequency of rheumatoid nodules, lymphadenopathy, hepatopathy, vasculitis, leg ulcers, skin pigmentation. v. Renal: kidneys (like GI) are usually affected through secondary involvement due to medicaitons (NSAIDs, gold, cyclosporine) , chronic inflammation, and disease vi. Vascular: vasculitic lesions in skin most common (palpable purpura, ulcers or digitial infarcts) vii. Hematologic: anemia of chronic disease viii. Neurologic: entrapment of nerves common (median in carpel tunnel) ix. Ocular: keratoconjuctivitis sicca is common. Eye may also have episcleritis, uveitis, and nodular sceritis 7. Common deformities from RA a. Ulnar deviation of fingers: due to swelling of MCP get displaced toward little finger b. Swan neck deformity: hyperextension of PIP and flexion of DIP c. Rheumatoid nodules: subcutaneous nodule in 20-30% of cases just outside joint on pressure points due to increased intra-articular pressure causing outpouches of synovium d. Boutonniere deformity: hyperflexion of PIP and hyperextension of DIP 8. Pathophysiology of joint deformities a. Early articular stage: mostly small joints. Early on synovitis of MCP and PIP are the main Sx. Symmetrical pattern. Inflamm chronically damages joints, marginal erosion develops, articular cartilage destroyed, articular space disappears, joint capsule becomes fibrotic and shrinks, fibrous or bony ankylosis develops b. Later periarticular stage: joint effusions lead to stretching of tendons and ligaments which can lead to scarring and shortening and deformities c. Established deformities: all the previous stuff leads to this. Capsular contraction and tendon shortening leads to joint subluxation and malalignment. 9. Differences btw RA and Osteoarthritis (OA) a. RA: not a condition of wear and tear, its autoimmune disease. Causes bilateral symmetrical pain and stiffness lasting 30+min in morning or long rest. affects smaller joints. RA likes PIP and MCP of the hand b. OA: not autoimmune, condition of wear and tear associated with aging and injury. OA stiffness gets worse with use. Sx are joint stiffness, pain, enlarged joints, often asymmetrical, affects larger joints. OA prefers the DIP and CMC joint of thumb 10. DX: requires presence of four of the following. a. Morning stiffness b. Arthritis in 3 or more joints c. Arthritis of typical hand joints d. Symmetric e. Rheumatoid nodules f. Serum rheumatoid factor g. Typical radiographic changes: juxtaarticular osteopenia and bone erosions with narrowing of joint spaces, destruction of tendons, ligaments, joint capsules leading to deformities. 11. Lab studies: a. Erythrocyte sedimentation rate and C-reactive protein: both increased b. CBC: demonstrates anemia of chronic diease c. Antinuclear antibody (ANA): present in 40% of patients. Titers of 1:40 or lower are negative d. Rheumatoid factor (RF): present in 60-80% of those with RH, fewer than 40% of those with early RA. RF not specific for RA e. Anti-citrullinated protein antibodies (ACPAs): higher sensitivity and specificity than RF and increased + for early RA. Precens of ACPAs is specific for RA and indicates worse prognosis 12. Prognosis: 40% of patients become disabled after 10 yrs. Cardiovascular morbidity and mortality increased, mortality of those with RA is 2.5X > regular pop mostly b/c of cardiovascular disease, infection, respiratory disease, vasculitis, and malignancies (Hodgkin lymphoma).
Pages to are hidden for
"Rheumatoid-Arthritis"Please download to view full document