2 Rheumatology - Rheumatoid Arthritis Flashcards
Define Rheumatoid Arthritis
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
What are key features of chronic arthritis?
- is it symmetrical/asymmetrical?
- what time of the day?
- what might be seen on radiographs?
- Polyarthritis - swelling of the small joints of the hand and wrists is common
- Symmetrical
- Early morning stiffness in + around joints (marker for treatment)
- May lead to joint damage and destruction - ‘joint erosions’ on radiographs
What rheumatoid factor might be found in blood if you have rheumatoid arthritis ?
IgM autoantibody against IgG
in terms of genes,
what gene variants are strongly associated with rheumatoid arthritis?
HLA-DRB gene variants mapping to amino acids 70-74 of the DRb-chains = strongly associated with rheumatoid arthritis
what environmental factor can contribute to arthritis?
smoking
What are the commonest affected joints in rheumatoid arthritis?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
What is characteristic of Joint Damage and Destruction in rheumatoid arthritis?
damage to: _____ _______
damages articular cartilage
What is Swan-neck Deformity in RA
o Hyperextension at PIP
o Hyperflexion at DIP
What is Boutonniere Deformity in RA
Hyperflexion at PIP
why might you get deformity of joints in RA?
Synovitis has damaged joints, so surrounding tendons are pulling on abnormal joint –> causes deformity
- -> joints are not aligned
- -> joints are eroded
primary site of pathology of RA is in the _____ which includes
- synovial joints
- Tenosynovium surrounding tendons
- Bursa
primary site of pathology of RA is in the Synovium which includes
- synovial joints (synovitis)
- Tenosynovium surrounding tendons (tenosynovitis)
- Bursa (bursitis)
Sub-cutaneous nodules may present in patients with RA
what is Sub-cutaneous nodules?
- when Central area of fibrinoid necrosis = surrounded by histiocytes and peripheral layer of connective tissue
- -> typically presents in ulnar border of forearm
note: Associated with - Severe disease - Extra-articular manifestations - Rheumatoid factor
What are rheumatoid factors?
- Antibodies that recognize the Fc portion of IgG as their target antigen
- typically IgM antibodies i.e. IgM anti-IgG antibody
- usually positive for RA
Antibodies to Citrullinated Protein Antigens (ACPA/CCP): highly specific for RA
what are they mediated by?
Citrullination of peptides mediated by peptidyl arginine deiminases (PADs)
arginine = converted to –> citrulline (via PADs)
NOTE: peptidyl arginine deiminases PADs found in high conc. in neutrophils + monocytes –> common in inflamed sites e.g. synovium
- ACPA strongly associated with smoking + HLA ‘shared epitope’
- chronic inflammation –> increase in inflammation + citrullination
causes e.g smoking/ gingivitis
What are some Extra-articular features of RA?
Common:
- Fever
- weight loss
- malaise, lethargy (driven by cytokines)
- Subcutaneous nodules
Uncommon:
- vasculitis
- Ocular inflammation e.g. episcleritis
- Neuropathies
- Amyloidosis
- Lung disease
- Felty’s syndrome
What are Radiographic abnormalities you might find in a patient with RA at
a) early stages
b) Later
c) Later still
Early= Juxta-articular osteopenia
Later= Joint erosions at margins of the joint
Later still= Joint deformity and destruction
Describe the pathology of RA.
Normally, synovium contacting bone = NOT articular cartilage
–> so there’s small space of bone in synovium not covered by articular cartilage (bare area)
- In synovitis, articular cartilage = susceptible to damage by inflammation –> see erosion first at bare area + edges of articular cartilage
- Can also see joint space narrowing –> less articular cartilage –> bones come closer
i. e synovitis, bone erosion, cartilage degradation
Synovium = made up of _______
synoviocytes
describe the composition of Synovial joint
- 1-3 cell deep lining containing type A synoviocyte + type B synoviocyte
- Type I collagen
Describe the pathogenesis of RA
Synovium becomes a proliferated mass of tissue (pannus) due to:
o Neovascularisation - formation of new blood vessels
o Lymphangiogenesis - formation of new lymphatics
o Many inflammatory cell
o cytokine imbalance
What are some methods of biological therapy against RA?
- interleukin-6 + interleukin-1 blockade
- anti-TNF
- deplete B cells
- -> (intravenous) administration of an antibody against a B cell surface antigen, CD20
- -> rituximab
- Modulation of T cell co-stimulation
Management of RA
- multidisciplinary approach (physiotherapy/ occupational therapy etc.)
- DMARDs
- Glucocorticoid therapy
- Biological therapies
What is DMARD Therapy?
drugs that may induce remission (not cure) and prevent joint damage
by:
- reducing the amount of inflammation in the synovium
- slow/ prevent structural joint damage e.g. bone erosions
