May28 M1-Rheumatoid Arthritis Flashcards
(imp) location and charact of pain in RA
- wrist, MCPs (hands) and MTPs (toes), PIPs (hands and toes)
- pain (with the inflammation) is symmetrical (many joints affected on both sides) but doesn’t have to be the exact same joint
charact of the painful joints in RA
synovitis
- swelling (focal) around the joint
- shiny skin over joint
- is an inflammatory disease so may expect to see the 5 signs of inflammation*
typical labs that would confirm the diagnosis for a presentation typical of RA
- high CRP (over the max 5.0 normal)
- high platelets = thrombocytosis (over the 450 normal) (is possible in chronic systemic inflammation)
- high rheumatoid factor (over the max normal 20.0)
- high anti-CCP (above the max normal 5)
(EXAM) inflammatory joint symptoms charact (as in RA)
- pain is accompanied with SWELLING
- worse with immobility
- morning stiffness lasts over 60 minutes
- associated systemic symptoms (fatigue, anorexia, fever)
(EXAM) non-inflammatory joint symptoms
- pain WITHOUT swelling
- worse with mobility and use
- morning stiffness <30 minutes
- no associated systemic symptoms
important epi things in RA
- more common in females
- small genetic influence
RA classification purposes + main things
for research, not clinical
- joint distribution
- serology (RF and ACPA + low vs high positive)
- symptom duration (has to be >6 weeks)
- acute phase reactants (CRP and ESR)
why is symptom duration important in classification of RA
some viruses can give a transient arthritis. but will not last>6 weeks
how to dx RA in the clinic
- 3+ joints + symmetrical
- positive RF and-or anti-CCP
- elevated CRP and-or ESR
- exclude ddx
- duration sx > 6 wks
important thing about joint distribution in RA in making the dx
can start with knee sx and develop into the wrist and hands sx typical of RA
important thing about serology in RA in making the dx
seronegative RA exists (RF and anti-CCP negative.) (but this dx may also be discovered to be something else later in life)
early vs interm vs late RA
- early = swelling joints + shiny
- interm = crooked fingers
- late = very deformed fingers
RA on XR
erosions, space between bones narrowing bc cartilag ebeing eaten out
in early disease, what is a good marker of the level of disability in RA
level of inflammation
in not early disease, what is a good marker of the level of disability in RA
radiographic severity
want to prevent damage therefore
pathology of RA
- > 1-2 layers of synoviocytes (hypertrophy)
- inflammatory medium with pannus (tumor of many cells of innate and adaptive immunity. pannus hypertrophied causing destruction of cartilage and bone)
branches of immune system involved in RA
- FIRST, adaptive immunity involved (slow, specific antigen R, memory, T and B cells)
- LATER, innate immunity involved (fast, microbial patterns, lacks memory, macrophages, neutrophils, mast cells)
* so inversed ordered and it’s an AUTOIMMUNE DISEASE*
what’s an autoinflammatory disease
diseas eof innate immune response, no B and T cells involved
most abundant cells in the synovium in RA
T cells (especially CD4 helper). they recognize Ags on MHC2 cells
alleles associated with RA
HLA-DRB1
- shared sequence of hypervariable region
- 30% of the genetic effect
one of main APCs in RA
B cells
- make cytokines
- propagate inflam
- regulate immunity down (IL-10)
- make Abs
rheumatoid factor is what
- Ab that binds the Fc portion of an IgG (so Ab to an Ab) = immune complexes, propagation of immune resp, complement cascade, chronic inflam
- 20% pts are seronegative
- 70% sensitivity
- 60-80% specif
important thing about RF
if positive, doesn’t mean RA bc many diseases can have + RF
(imp) serology better than RF in RA
anti-CCP (cuclic citrullinated peptide). during apoptosis, cells downregulate proteins by deiminating arginine of proteins, this is caleld citrullination)
- better sensitivity**
- can be found BEFORE the arthritis**
- indicates a POOR prognosis
most important environmental risk factors for RA (for citrullination. bc RA = Abs attack citrullinated proteins)
#1 smoking #2 periodontal disease
immune cascade in RA and most imp thing
- APC to T cell then cytokines and Abs
- synovium has IMMUNE COMPLEXES***
- innate recruited (macrophages, mast cells) and make cytokines
- this destroys bone and causes synovial hypertrophy
some RA tx (biologics)
- rituximab (anti-CD20) for B cells
- anti-TNF, anti-IL1, anti-IL6 (cytokines of mast cells)
effect of TNF cytokine in RA
- recruits macrophages
- makes endothelial cells more permeable in fibrous joint capsule so that more cells recruited
- synoviocites activation: THEY produce MMP which causes cartilage destruction
(imp) what cells cause the cartilage destruction in RA
synoviocytes (make MMP in resp to cytokines)
bad cytokines produced by synoviocytes (on top of them making MMP) in RA
- TNF, IL-1, IL-6, RANKL: activate osteoclasts
- DKK-1: reduces osteoblast precursors transformation to osteoblasts
starting cell in pathogenesis of RA
T cell
what’s pre-RA
anti-CCP positive before clinical disease (but like for RF, there’s a ddx for that)
extra-articular manifestations of RA
- rheumatoid nodules on extensor surface of elbow and hands
- episcleritis (red eye) inflam of superficial lining of sclera
- ILD (interstitial lung disease on CT)
RA non pharma tx
- pt education
- psychosocial
- rest, exercise, PT OT
- nutrition counselling
- reduce CV risk, smoking, lipid control
- tx and screen osteoporosis
note about risk of infections in RA patients
just having RA = higher risk for infections than normal population
pharma tx in RA
- NSAIDs, CSs (for sx management but NOT DISEASE MODIFYING)
- DMARDs (methotrexate, leflunomide, sulfasalazine, hydroxychloroquine)
- new bio drugs
how to monitor RA pts
XR for following erosion
