Rheumatoid Arthritis Flashcards
Pattern of RA?
Symmetric
Etiology of RA?
Unknown, thought to be genetic
What is associated with increased incidence of rheumatoid and lupus
STAT4 haplotypes chromosome 2
What is associated with increased risk of CCP positive RA?
TRAF1-C5 on chromosome 9
What does TRAF1-C5 code for?
Intracellular protein that mediates signal transduction through TNF receptors 1 and 2
Primary orchestrator of the cell mediated immune response in rheumatoid arthritis?
CD4 helper T-cells
What do patients with RA express at much greater rate than patients w/o RA?
HLA DR4 haplotypes
TNF, IL-1, IL-6 cause what?
Erosion of bone and cartilage
IL-1 and TNF do what?
Stimulate adhesion molecules
Increase recruitment of polymorphonuclear cells into the joints
What do polymorphonuclear cells release that degrades cartilage?
Elastase and proteases
Function of rheumatoid factor?
Unknown
How is rheumatoid factor released?
Stimulated CD4 stimulates B cells to produce immunoglobulins including rheumatoid factor
Function of IL-4 and IL-10?
Down regulate the inflammatory response
What happens to the synovial membrane in early RA?
Membrane becomes thickened due to hyperplasia and hypertrophy of synovial lining cells
When RA is established what does synovial membrane become?
Inflammtory tissue (pannus)
What is Pannus made up of?
Type A (macrophage like), type B (fibroblast like), and plasma cells
Constitutional features of RA?
Morning stiffness lasting for hours
Malaise, fatigue
Men or women more likely to get RA?
Womean 3:1 ratio
Peak onset of RA?
30-55
How do the joints feel in RA?
Joints have a warm boggy feel (soft and squishy)
What joint does RA never infect?
DIP
What does infection of DIP joints indicate?
OA or psoriatic arthritis
Does RA get to the lower back?
NO!
Finding between cardiac and RA?
Fourfold increase in cardiovascular events in rheumatoid population
Treatment problems for RA involving ocular?
Corticosteroids cause Glaucoma and cataracts
Hydroxychloroquin causes retinal pigment epithelial toxicity
Increase of sedimentation rate says what?
More inflammation
Rheumatoid factor only predictive n which patients?
Those with polyarthritis
Rheumatoid factor test best used in conjunction with what to up specificity to 98%?
Cyclic citrullinated peptide anitbodies ( anti-CCP)
Polymyalgia Rheumatica very responsive to what?
Corticosteroids
How do NSAIDS work?
Inhibition of COX in production of prostaglandin
How many forms of COX?
2
COX1 does what?
Constitutive functions (maintaining mucosal linking stomach, platelet function)
COX2 does what?
Mediation of pain and inflammation
Function of corticosteroids?
Inhibits synthesis of almost all Cytokines
Affects chemotaxis resulting in less inflamatory cells at site
Affects synthesis of COX2
Decrease circulating T cells
What does the DMARD Sulfasalazine do?
Inhibits production of various prostanoids
Results in reduction of circulating activated lymphocytes
Inhibition of B cell activation
How does Gold therapy work?
Numerous functions but importance of them is unknown
What does Gold therapy inhibit?
Acid phosphatase
Collagenase
Protein kinase C
Phospholipase C
What inhibits synthesis of purine nucleotides?
Methotrexate and azathioprine
What inhibits pyrimidine?
Leflunomide (Arava)
