Autoimmunity

Question 1

What is immune mediated polyarthritis?

Answer 1

An inflammatory joint disease of non-infectious aetiology

Question 2

What systemic signs are seen with immune mediated polyarthritis?

Answer 2

• Lethargy
• Stiffness
• Pyrexia

Question 3

Where does immune mediated polyarthritis afffect?

Answer 3

The polyarticular (affecting multiple joints) and often causes problems in all 4 limbs.

Question 4

How can the joints affected by immune mediated polyarthritis be classified?

Answer 4

Non-erosive or erosive

Question 5

What is the pathophysiology of immune mediated polyarthritis?

(I’m sorry this answer is not short..)

Answer 5

Immunocompetence develops during foetal / early post-natal life as the lymphoid system matures and is paralleled by the development of ‘self-tolerance’. Self-tolerance results from either the removal of potentially autoaggressive cells as part of normal cell maturation (clonal deletion), or by functional inactivation of autoaggressive cells (clonal anergy). Auto-immune mediated disease occurs when the body fails to recognise ‘self’.

Question 6

What does organ specific immune mediated disease mechanism relate to?

Answer 6

Antibodies and cel mediated immunity

Question 7

What does non-organ specific immune mediated disease mechanism relate to?

Answer 7

Anigen-antibody complex

Question 8

How can bacterial products (antigens) attaching to cells and altering cell surface receptors trigger immune mediated disease?

Answer 8

If ‘self’ becomes altered

Question 9

What can immune mediated polyarthritis be precipitated by?

Answer 9

Systemic or distant diseases such as endocarditis or neoplasia

Question 10

What is the diference between primary and secondary immune mediated disease?

Answer 10

Many times we are unable to find an underlying trigger factor and we assume the disease is a primary immune mediated disease (also known as idiopathic immune mediated disease). If we are able to identify the underlying cause of an immune mediated disease (so called secondary immune mediated disease)

Question 11

What is different about the treatment of secondary immune mediated disease?

Answer 11

Target treatment at the underlying cause

Question 12

What type of reaction is immune mediated disease?

Answer 12

Type III hypersensitivity

Question 13

What happens in immune complex mediated reactions?

Answer 13

Large amounts of IgG or IgM bind to ‘antigen’ to form microprecipitates, which become ‘trapped’ in the synovial membrane (an important phagocytic tissue).

Question 14

Where is a common site where the antigen/antibody complex can be trapped? What is the consequence?

Answer 14

Kidney which can cause glomerular disease

Question 15

What are the 4 classifications of IMPA?

Answer 15

Type I uncomplicated idiopathic form 50%

Type II associated with remote infections 25%

Type III associated with gastro-intestinal disease 15%

Type IV associated with remote neoplasia 10%

Question 16

What happens if immune complexes are in the synovium?

Answer 16

Results in complement activation, inflammatory cell (neutrophil, macrophage) chemotaxis and cytokine release –> synovitis, inflammatory joint effusion, joint swelling and pain.

Question 17

Name clinical signs of IMPA

Answer 17

• Generalised stiffness, difficulty rising
• May or may not be obviously lame
• Possible multi-system involvement - pyrexia, depression, anorexia
• Multiple joints ± painful joints ± swollen joints
• Joint palpation and manipulation may reveal heat, swelling, crepitus and ligamentous laxity

Question 18

How do we investigate/diagnose IMPA?

Answer 18

• Synovial fluid analysis
• Radiography of joints? (justifiable if erosive disease is suspected)
• Routine haematology + biochemistry- very non specific changes associated with inflammation
• Urinalysis?- rule out infection as a trigger? Any evidence of glomerular damage?
• Screen for underlying disease – thoracic radiographs, abdominal ultrasound ± lymph node aspirates

Question 19

What is seen in synovial fluid with IMPA?

Answer 19

Increased volumes of turbid fluid from multiple joints; high numbers of non-degenerate, non-toxic neutrophils are found.

Question 20

Why might there not be any bony changeson radiographs wih IMPA?

Answer 20

Primary idiopathic non-erosive arthritis is the most common form of the disease, and therefore no bone abnormalities

Joint effusions are often seen but can be subtle

Question 21

What is the prognosis with non erosive IMPA?

Answer 21

Often very good especially if the disease is primary (Type I) or the underlying cause is treatable

Question 22

What is th prognosis of erosive forms of IMPA?

Answer 22

Erosive forms of the disease are rare, but very destructive, with severe clinical consequences and a very poor prognosis.

Question 23

What is the pathophysiology of erosive arthiritis?

Answer 23

• Chronic synovitis leads to production of proliferative granulation tissue (pannus)
• Pannus invades articular cartilage and can erode subchondral bone
• Pannus + inflamed synovium produce enzymes including proteases and collagenases ® further joint destruction e.g. Rheumatoid arthritis

Question 24

What does this show?

Answer 24

Normal carpus

Question 25

What is this?

Answer 25

Carpus affected by erosive arthritis

Question 26

What is the primary treatment type of immune mediated polyarthritis?

Answer 26

Medical

Question 27

What medical treatment can be given for IMPA? (5)

Answer 27

• Prednisolone - immunosuppressive doses initially 2-4mg/kg daily (divided doses)
• additional drugs are often required and can include one or more of the following:
  
  • Azathioprine (never in cats due to severe side effects)
  • Cyclosporine (becoming more popular as a relatively safe immune suppressive agent)
  • Cyclophosphamide has lost favour in recent years with poor evidence to support it’s use as an effective treatment (risk of severe haemorrhagic cystitis, use for <3 m)
  • Leflunomide – newer drug, used in refractory cases, some published work in recent years suggesting it is beneficial.

Question 28

What should we monitor animals on cytotoxic drugs for?

Answer 28

Myelosuppression

Question 29

How long is initial treatment for IMPA?

Answer 29

3 weeks

Question 30

Over what period do we reduce immunosuppressive drugs?

Answer 30

3-6 months

Question 31

What is seen with equine IMPA? What is it associated with?

Answer 31

Rarely reported. Synovitis with immunoglobulin G complex deposition has been reported in foals. In one case, equine herpes virus 4 was involved. In other cases, polysynovitis and vasculitis associated with streptococcal infection, and Rhodococcus equi infection, have been reported.

Question 32

What drug is contraindicated in IMPA when an infection is present?

Answer 32

Corticosteroids

Question 33

What is crysal based arthritis? How common is it in cats and dogs?

Answer 33

Deposition of crystals in and around joints causing inflammation – often excruciatingly painful.

Very rare in dogs and cats

Question 34

What species is true gout seen in and why is this?

Answer 34

In species in which urate is the major excretory end product of nitrogen metabolism - birds, most reptiles, and some amphibians

Question 35

What is pseudogout?

Answer 35

Peri-articular and synovial deposits of calcium phosphate or pyrophosphate

Question 36

What is the signalment of synovial cell sarcoma?

Answer 36

Mean age 6-8years

Males at a slightly greater risk

Question 37

What is the treatment of synovial cell sarcoma?

Answer 37

Limb amputation