Autoimmunity Flashcards
What is immune mediated polyarthritis?
An inflammatory joint disease of non-infectious aetiology
What systemic signs are seen with immune mediated polyarthritis?
- Lethargy
- Stiffness
- Pyrexia
Where does immune mediated polyarthritis afffect?
The polyarticular (affecting multiple joints) and often causes problems in all 4 limbs.
How can the joints affected by immune mediated polyarthritis be classified?
Non-erosive or erosive
What is the pathophysiology of immune mediated polyarthritis?
(I’m sorry this answer is not short..)
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’.
What does organ specific immune mediated disease mechanism relate to?
Antibodies and cel mediated immunity
What does non-organ specific immune mediated disease mechanism relate to?
Anigen-antibody complex
How can bacterial products (antigens) attaching to cells and altering cell surface receptors trigger immune mediated disease?
If ‘self’ becomes altered
What can immune mediated polyarthritis be precipitated by?
Systemic or distant diseases such as endocarditis or neoplasia
What is the diference between primary and secondary immune mediated disease?
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)
What is different about the treatment of secondary immune mediated disease?
Target treatment at the underlying cause
What type of reaction is immune mediated disease?
Type III hypersensitivity
What happens in immune complex mediated reactions?
Large amounts of IgG or IgM bind to ‘antigen’ to form microprecipitates, which become ‘trapped’ in the synovial membrane (an important phagocytic tissue).
Where is a common site where the antigen/antibody complex can be trapped? What is the consequence?
Kidney which can cause glomerular disease
What are the 4 classifications of IMPA?
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%
What happens if immune complexes are in the synovium?
Results in complement activation, inflammatory cell (neutrophil, macrophage) chemotaxis and cytokine release –> synovitis, inflammatory joint effusion, joint swelling and pain.
Name clinical signs of IMPA
- 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
How do we investigate/diagnose IMPA?
- 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
What is seen in synovial fluid with IMPA?
Increased volumes of turbid fluid from multiple joints; high numbers of non-degenerate, non-toxic neutrophils are found.
Why might there not be any bony changeson radiographs wih IMPA?
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
What is the prognosis with non erosive IMPA?
Often very good especially if the disease is primary (Type I) or the underlying cause is treatable
What is th prognosis of erosive forms of IMPA?
Erosive forms of the disease are rare, but very destructive, with severe clinical consequences and a very poor prognosis.
What is the pathophysiology of erosive arthiritis?
- 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
What does this show?
Normal carpus
What is this?
Carpus affected by erosive arthritis
What is the primary treatment type of immune mediated polyarthritis?
Medical
What medical treatment can be given for IMPA? (5)
- 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.
What should we monitor animals on cytotoxic drugs for?
Myelosuppression
How long is initial treatment for IMPA?
3 weeks
Over what period do we reduce immunosuppressive drugs?
3-6 months
What is seen with equine IMPA? What is it associated with?
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.
What drug is contraindicated in IMPA when an infection is present?
Corticosteroids
What is crysal based arthritis? How common is it in cats and dogs?
Deposition of crystals in and around joints causing inflammation – often excruciatingly painful.
Very rare in dogs and cats
What species is true gout seen in and why is this?
In species in which urate is the major excretory end product of nitrogen metabolism - birds, most reptiles, and some amphibians
What is pseudogout?
Peri-articular and synovial deposits of calcium phosphate or pyrophosphate
What is the signalment of synovial cell sarcoma?
Mean age 6-8years
Males at a slightly greater risk
What is the treatment of synovial cell sarcoma?
Limb amputation
