Rheumatoid arthritis
- Autoimmune, chronic systemic inflammatory disorder that can affect many different tissues and organs such as;
- Skin
- Blood vessels
- Heart
- Lungs
- Muscles
- Skin
- Predominantly attacks the joints producing an nonsuppurative proliferative and inflammatory synovitis that often progresses to the destruction of articular surface and the ankylosis of joins
- Affects 1% of the worlds population
- Women 2-3 times more commonly affected than men
- Most common in age group between 40 to 70
Morphology
Joints
- Initially synovium becomes grossely thickened, hyperplastic and oedematous
- The characteristic histological features are;
- Infiltration of synovial stroma by CD4+ T cells and plasma cells which can form lymphoid follicles
- Increased vascularity owing to vasodilation and angiogenesis with superficial haemosiderin deposits
- Aggregation of organising fibrin covering portions of synovium and floating in the joint space as ‘rice bodies’
- Accumulation of neurtophils in the synovial fluid and along the surface of the synovium
- Osteoclastic activity in the underlying bone allowing synovium to penetrate into the bone fowming juxta-articular erosions and subchondral cysts
- Pannus formation. The pannus is a mass of synovium and synovial stroma consisting of inflammatory cells, granulation tissue and fibroblasts which grow over the articular surface and causes its erosion. In time after the cartilage has been destroyed, the pannus bridges the opposing bones, forming a fibrous ankylosis which eventually ossifies resulting in bony ankylosis
- Frequently accompanied by inflammation of the tendons, ligmanets and adjacent skeletal muscle
Skin
- Rheumatoid nodules are the most common skin lesion in RA
- Arise is regions subjected to pressure such as the elbow, occiput and lumbosacral region
- Less commonly they can affect the lungs, spleen, pericardium, myocardium, heart valves, aorta and other visera
- They are firm and non tender and  arise in subcutaneous tissue
- Microscopically they have a central zone of fibrinoid necrosis surrounded by a prominent rim of histiocytes and numerous lymphocytes and plasma cells
Blood vessels
- Involves medium to small arteries similar to those affected in polyarteritis nodosum
- Except that in RA the kidneys are not involved
- Frequently segments of small arteries such as vasa nervorum and digital arteries are obstructed by an abliterating endarteritis resulting in peripheral neuropathy, ulcers and gangrene
- Leukocytoclastic venulitis produces purpura, cutaneous ulcers and nail bed infarction
Pathogenesis
- Autoimmune disease triggered by exposure of a genetically susceptible host to an unknown arthritic antigen
- Destruction of the joint is due to activation of CD4+ cells, plasma cells are release of inflammatory mediators and cytokines
- B cells may act destructively by the production of antibodies which from immune complexes
- Most important destructive cytokines are TNF and IL-1 produced by macrophages and synovial lining cells that have been activated by T cells
- TNF and IL-1 in turn stimulate synovial cells to proliferate and produce various inflammatory mediators such as prostaglandins and MMP which contribute to cartilage destruction
- Activated T cells and synovial fibroblasts also express RANKL which activates osteoclasts and promotes bone destruction
- The hyperplastic synovium rich in inflammatory cells becomes adherent to and grows over the articular surface forming a pannus and stimulates the resorption of adjacent cartilage. In the end the pannus produces sustained and irreversible cartilage destruction and erosion of bone
- Genetic susceptibility – HLA-DRB1
- Some evidence that the triggering antigen is microbial but there is no proof this is the case
Clinical course
- Clinical course is variable. Generally it begins slowly and presents with malaise, fatigue and general musculoskeletal pain after which the joints become more clearly involved
- Approximately 10% of patients have an acute onset with severe symptoms are polyarticular involvement
- Small joints generally affected before the larger ones
- Symptoms generally develop in the MCP and PIP joints of the hand and MTP and IP joints of the feet, followed by wrists, ankles, elbows, knees. Cervical spine may be involved but the hips are generally involved later in diseaseand the lumbosacral area is typically spared
- Involved joints are swollen, painful, warm and stiff
- Course of disease fluctuates over the years with the greatest damage occurring over the first 4-5 years
- Destruction of the tendons, ligaments and joint capsule lead to characteristic deformities such as radial deviation of the wrist, ulnar deviation of the fingers, swan-neck and boutonniere lesions of the fingers
- Large synovial cysts may develop as the increased intra-articular pressure causes outpouching of the synvoium
- May patients are rheumatoid factor positive
- Synovial fluid contains neutrophils, high protein content and low mucin content
- Diagnosis is made with the presence of four of the following criteria;
1.     Morning stiffness
2.     Arthritis in three or more joint areas
3.     Arthritis of typical hand joints
4.     Symmetric arthritis
5.     Rheumatoid nodules
6.     Serum rheumatoid factor
7.     Typical radiographic changes
- Overall life expectancy is reduced by a mean of 3 to 7 years
- Fatalities are usually due to the complications of RA such as systemic amyloidosis and vasculitis which involves vessels of all sizes including the aorta
- There are also iatrogenic effects of therapy such as GI bleeding due to long term use of anti-inflammatories
- Infections associated with chronic steroid use of treatment with cytokine antagonists