Sunday, February 13, 2011

Rheumatoid Arthritis.


Systemic chronic inflammatory disease characterised by nonsuppurative proliferative synovitis, destruction of articular cartilage and underlying bone with resulting disabling arthritis

extra-articular involvement -for example, of the skin, heart, blood vessels, muscles, and lungs-RA may resemble SLE or scleroderma

five times more common in women than in men

Joint pathology in RA:

symmetric arthritis, principally affecting the small joints of the hands and feet, ankles, knees, wrists, elbows, and shoulders

Morning or inactivity stiffness shows inflammatory nature of the joint disease

proximal interphalangeal and metacarpophalangeal joints are affected, but distal interphalangeal joints are spared.

Axial involvement, when it occurs, is limited to the upper cervical spine

radiographic hallmarks are joint effusions and juxta-articular osteopenia with erosions and narrowing of the joint space and loss of articular cartilage

Destruction of tendons, ligaments, and joint capsules

radial deviation of the wrist,
ulnar deviation of the fingers,
flexion-hyperextension abnormalities of the fingers
swan-neck deformity
boutonnière deformity

radiographic hallmarks

joint effusions
juxta-articular osteopenia
erosions and narrowing of the joint space

Microscopic features:

chronic synovitis with synovial cell hyperplasia and proliferation

dense perivascular inflammatory cell infiltrates (frequently forming lymphoid follicles) in the synovium composed of CD4+ T cells, plasma cells, and macrophages

increased vascularity due to angiogenesis

neutrophils and aggregates of organizing fibrin on the synovial surface and in the joint space

increased osteoclast activity in the underlying bone, leading to synovial penetration and bone erosion.

pannus, formed by proliferating synovial-lining cells admixed with inflammatory cells, granulation tissue, and fibrous connective tissue, which will cause enzymatic erosion of articular cartilage and subarticular bone

periarticular soft tissue edema

fibrosis and calcification may cause permanent ankylosis

Systemic features of RA:

Fever, wt loss and malaise due to IL1 and TNF alpha

Rheumatoid subcutaneous nodules
along the extensor surface of the forearm or other areas subjected to mechanical pressure
they can form in the lungs, spleen, heart, aorta, etc
central focus of fibrinoid necrosis surrounded by a palisade of macrophages, which in turn is rimmed by granulation tissue

fibrinous pleuritis or pericarditis

Lung: progressive interstitial fibrosis

Ocular changes such as uveitis and keratoconjunctivitis

Vasculitis and peripheral neuropathy

rheumatoid factor
are at risk of developing vasculitic syndromes;
autoantibodies that bind to the Fc portions of their own (self) IgG.
20% of patients do not have RF

Raynaud phenomenon

reactive amyloidosis

chronic, remitting-relapsing course

Treatment: DMARD and anti-TNF alpha

Pathogenesis of RA:

Exact cause in unknown

Association with HLA-DR4

increased frequency of this disease among first-degree relatives and a high concordance rate in monozygotic twins shows that the disease has some genetic component.

Infections withEBV, Borrelia species, Mycoplasma species, parvoviruses, and mycobacteria might be a triggering factor

Activation of B cells, macrophages, endothelium, fibroblasts, chondrocytes and synovial cells to form pannus,which causes enzymatic digestion of the cartilage and the underlying bone

autoantibodies that bind to the Fc portions of their own (self) IgG rheumatoid factor (RF) are formed

20% of patients do not have RF.

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