0702 - MSK Autoimmunity and Inflammation Flashcards
Where does the pathology occur in RA?
RA is cardinal example of a sinovitis. Leads to irreversible joint destruction. But pathology can occur anywhere?
What are the hallmarks of RA?
“Pannus” complex inflammatory infiltrate and abnormal differentiation of synovium.
Subcutaneous rheumatoid nodules on extensor surfaces - most common extra-articular manifestation (in 15% of cases).
Outline the epidemiology of RA
Prevalence 1%, rare in africa and china, more common in other groups. F:M 2:1
Gradual increase in incidence from 30-85yo.
How can RA progress?
10% progress rapidly to severe erosive disease less than 2 years after diagnosis
70% have erosions within 3 years
30% have no erosions.
Disability does not correlate exactly with erosions.
What are the Genetics of RA
60% genetic component
HLA-DRB1 (MHC II) accounts for 30% of genetic component.
What is a typical presentation of RA (demographic, symptoms, joints)
Non-chinese, non-African female, 30-85
Morning stiffness in joints for at least 1 hour.
Swelling of at least 3 joints for at least 6 weeks.
Typically hits peripheral synovial joints wrists/ankles, metacarpo/tarsophalangeal, or proximal interphalangeal joints.
Symmetric joint swelling.
How may an RA patient be tested?
Anti-CCP and RF together are sensitive for RA. Seperately they are not particularly.
Commonly have rheumatoid nodules
75% have rheumatoid factor.
ACPA/anti-CCP (anti-citrullinated protein antibody) more specific and maybe sensitive.
ANA very sensitive, not specific
Elevated CRP and ESR correlate with disease activity.
ENA following positive ANA
How are Seronegative Arthritides different from seropositive?
Not associated with RF and not necessarily autoimmune. Ankylosing spondylitis is the most typical. Enthesitis also occurs.
M more than F, begin in early adulthood.
What is the Genetic component of seronegative arthritides?
Most commonly HLA-B27 (MHCI), present in 94% of ankylosing spondylitis and a whole heap of others. But they are not necessarily the mechanism.
How do MSK autoimmune conditions typically associate (MHC and gender)?
Most MSK autoimmune conditions are MHCII, Female. Seronegatives are exception to rule with male bias and MHCI.
What determines an autoimmune condition?
Diagnosis demands evidence for a breakdown in self-tolerance by autoantibodies or autoreactive T-cells.
Autoantibodies ALWAYS provide evidence in support of autoimmunity but less supportive of diagnosis.
Autoantibodies SOMETIMES provide a mechanism for end organ damage (not necessarily pathogenic) (you can have autoimmunity without having end-organ damage).
What are the formal criteria for antibody-mediated disease? (how might you diagnose it)
- Reproduction of disease following introduction of antibodies into man or animals (not always practical).
- Induction of a lesion similar to the disease by immunisation with the autoantigen.
- In vitro stimulation of the pathogenic process
- Isolation of autoantibodies from a typical lesion
- Correlation of autoantibody levels with disease activity.
