Q:
What are some different examples of inflammatory types of arthritis?

A:
* Rheumatoid Arthritis
* Psoriatic Arthritis
* Spondyloarthropathy Group
* Connective Tissue disease
* Crystal Induced Arthritis
* Juvenile Chronic Arthritis

Q:
What is the definition of rheumatoid arthritis?

A:
* It is a chronic, systemic inflammatory disorder characterised by symmetrical, predominantly peripheral small joint non-suppurative polyarthritis
* It is a proliferate synovitis which often progresses to destruction of articular cartilage and ankylosis of the joints

Q:
True or false? Slightly more females than males get rheumatoid arthritis, (55% females, 45% males).

A:
False. There is a 3:1 ratio of affected females to affected males.

Q:
What is known about the aetiology of rheumatoid arthritis?

A:
* Not much is known about the aetiology.

* Genetic predisposition is thought very significant. 
   - Perhaps involving an epitope on a MHC Class II molecule, commonly HLA-DR4
* Most evidence implicates a specific immune recognition event as the basis of the disease.
   - However it is not clear whether this results from contact with a foreign antigen or breakdown of tolerance to a self protein.

Q:
What macroscopic anomalies might you find in the synovium of established rheumatoid arthritis?

A:
* Highly vascular
* Oedematous 
* Protrudes into the joint cavity as slender villous projections

Q:
What microscopic anomalies might you find in established rheumatoid arthritis?

A:
* Synovial lining layer hyperplasia due to type A and B synoviocyte recruitment
* Infiltration by chronic inflammation cells such as monocytes and T and B lymphocytes
* Extensive angiogenesis

Q:
Why is it thought that neutrophils are found in higher numbers in the synovial fluid than in the synovium itself?

A:
It is thought that after being recruited to the synovium neutrophils migrate into the synovial fluid because they lack the adhesion molecules to remain within the cells.

Q:
True or false? Both immune complex mediated and cell mediated processes operate in RA.

A:
True.

Q:
What are the 2 key proinflammatory mediators in RA?

A:
* TNF
* IL-1

Q:
What are the early events of rheumatoid arthritis?

A:
Early events are related to acute inflammation.

* Subsynovial oedema
* Recruitment of neutrophils
* Lining layer proliferation

Q:
What are the stages of joint pathology in RA?

A:
* Synovitis.
* Destruction caused by the production of proteinases by inflammatory cells and by resident synoviocytes that are stimulated by pro-inflammatory cytokines.
* Rheumatoid pannus erodes articular cartilage and bone.
* Cartilage denudation causing bone on bone articulation.
* Inflammation spreads to synovial lining of tendon sheaths.
* Tendon thinning and rupture.
* Joint subluxation (partial dislocation resulting in abnormal movement).
* Capsular/ligament weakening.
* Rheumatoid deformities.

(Articular cartilage, subchondral bone and soft tissues are destroyed by inflammation centred on the synovium causing joint destruction and secondary degeneration.)

Q:
What is rheumatoid pannus?

A:
A vascular granulation type tissue composed of hyperplastic inflamed synovium that invades into and erodes articular cartilage and bone.

Q:
What findings would you be likely to get when examining the synovial fluid of a patient with rheumatoid arthritis?

A:
* Straw coloured to turbid appearance
* Glucose is 70% of serum level
* WBC count is 3000-50000, mostly neutrophils
* Viscosity is low compared to normal
* Poor mucin clot after addition of acetic acid
* Culture is negative
* Complement level is low
* Rheumatoid factor is usually positive even if serum RF is negative

Q:
What are the likely laboratory findings in rheumatoid arthritis?

A:
* Rapid/high ESR, elevated CRP
* Normochromic normocytic anaemia of 'chronic disease'
* Rheumatoid Factor standard assays test for IgM-RF
* Synovial fluid abnormalities
* Radiology - usually MRI
  - Periarticular osteoporosis
  - Uniform loss of joint space
  - Marginal erosions

Q:
What is rheumatoid factor?

A:
Rheumatoid factor is an immunoglobulin (can be IgG, IgM, IgA or IgE) with a specificity for antigenic sites on the Fc region of the heavy chain of IgG.

Standard tests detect IgM-RF.

Q:
What conditions are associated with IgM rheumatoid factor?

A:
* Rheumatoid Arthritis
* Sarcoidosis
* Pulmonary fibrosis
* Systemic Lupus Erythematosus
* Primary Sjorgen's syndrome
* Autoimmune Liver disease
* Infections (bacterial endocarditis, malaria, TB, leprosy)

Q:
What differential diagnoses must be considered when considerng rheumatoid arthritis?

A:
* Psoriatic arthritis - 'pseudo-rheumatoid pattern'
* Polyarticular gout
* Spondyloarthropathies
* Polymyalgia rheumatica
* Systemic Lupus Erythematosus (and other CT diseases)
* Sarcoidosis

Q:
What are the extra-articular manifestations of RA?

A:
Mostly resultant from depostion of antigen-antibody complexes, complement fixation and type III sensitivity.

* Skin lesions, due to small vessel vasculitis
   - Nail fold lesions
   - Digital infarcts
   - Leg ulcers
   - Skin nodules (rheumatoid nodules)
* Ocular
   - Episcleritis, scleritis
   - Scleromalacia perforans (perforation of the eye)
* Pulmonary
   - Pleurisy
   - Intrapulmonic nodules
   - Interstitial fibrosis
* Cardiac
   - Pericarditis
   - Rare nodules in myocardium or valves
* Neuropathy
   - Carpal tunnel syndrome
* Lymphadenopathy
* Splenomegally 
* Felty's syndrome

Q:
What joints are typically involeved in rheumatoid arthritis clinically?

A:
Characteristically symmetrical, affecting small peripheral joints.

* PIPs, MCPs, wrists, MTP and ankles commonly involved (DIPs rarely involved)
* Upper cervical spine, especially C1-2 articulation
* Any large joint can be subject to it

Q:
What is osteoarthritis?

A:
Osteoarthritis (also known as degenerative joint disease) is a syndrome of progressive disintegration of articular cartilage and formation of new bone in the floor of the cartilage lesion at the joint margins (osteophytes).

Any inflammation caused is secondary to the disease, not part of the pathogenesis.

Q:
What are some of the significant aetiological factors of osteoarthritis?

A:
* Repeated microtrauma to subchondral bone (wear and tear)
* Neuropathic joint degeneration
* Ageing
* Genetic factors
* Obesity - (metabolic/load problems)
* Congruity of joint surfaces
* Crystal deposition within cartilage
* Infection