Rheumatoid Arthritis Flashcards
what is rheumatoid arthritis?
Systemic autoimmune disease characterized by joint inflammation
epidemiology of RA
most common systemic/inflammatory rheumatic disease
1% of adults
HLA-DR4 alleles for risk of disease
F>M
define autoimmune diseases
own immune system stimulated to act against self, produce Ab to self antigens
what is arthralgia
joint pain
where does the inflammation occur
synovium
pain due to nerve endings on subchondral bone
what are causes of RA
idiopathic
role of synoviocytes in RA
synovial hyperplasia
produce proinflammatory cytokines
role of macrophages in RA
APC
synoviocyte and tissue type macrophage
ingest and process antigens
present to HLA-DR matched T cells
role of dendritic cells in RA
APC, activate naive T cells
self-antigen presentation to T cells
inappropriate DC activation could convert self-tolerance to overt autoimmunity
role of T cells in RA
interact w APC through MHCI (HLA-A,B,C)) and MHCII (HLA-DR, DP, DQ) produce cytokines (interleukins, IFN gamma, TNF-alpha and beta)
3 critical roles of B cells in RA
antigen presentation and T cell activation
autoantibody production
cytokine production
role of fibroblasts in RA
produce hyaluronan
inflammation - produce metalloproteinases
role of complements in RA
immune complex activate cascade (rheumatoid factor is component of complex)
complement fragments attract neutrophils
degranulation –> enzymes damage cartilage
what are suspected pathogenic antigens
virus (CMB, herpes, EBV, rubella)
bacteria (staph, strep, borelia)
mycoplasma
what are suspected auto-antigens
type 2 collagen, proteoglycan, chondrocyte, IgG
describe TNF alpha action on macrophages
increase pro-inflammatory cytokines and chemokines, increases inflammation
describe TNF alpha action on endothelium
increase adhesion molecules (increased cell infiltration) and vascular endothelial growth factor (VEGF) (increased angiogenesis)
describe TNF alpha action on hepatocytes
increased acute phase response –> increased CRP in serum
describe TNF alpha action on synoviocytes
increased metalloproteinase synthesis –> articular cartilage degradation
how does IL-6 cause anemia of chronic inflammation
inducing hepcidin production by hepatocytes
hepcidin inhibits release of iron from macrophages
what genetic factors are associated with RA
HLA-DRB1 (increased risk)
HLA-DR4 (severe disease)
STAT4
infectious agents, smoking, and sex hormones
what is seen on XR for RA
early erosion, soft tissue swelling
5 steps in pathophysiology in RA
- antigen presentation to B & T cells
- T and B cells proliferate, cytokines released, angiogenesis occurs
- synovial hypertrophy with cell accumulation in joint space
- joint space invasion, enzymatic damage
- bone erosion, loss of cartilage
what causes systemic complaints in RA
effects of inflammatory mediators
fevers and poor appetite
what are extra-articular features of RA
nodules
vascular/resp system
cardiovascular
neurological
where do RA nodules occur?
where there is pressure (achilles tendon, pulp of digits)
extensor surfaces, peri-articular
on tendons
what are respiratory features of RA
pleural disease (chest pain, dyspnoea) interstitial lung disease
what are cardiovascular features of RA
pericardial disease (chest pain, dyspnoea) cardiac muscle disease (due to nodules)
what are vascular features of RA
small vessel disease
symptoms dependent on site of vasculitis (skin, bowel, nerve, eye)
what are neurological features of RA
peripheral nerves may be affected
median nerve (carpal tunnel, pain and/or paraesthesiae in palm or in 1st to 4th digits)
worse with activity or at night
describe Sjogren’s syndrome
immune system disorder that accompanies RA
dry eyes (eyelids sticking together)
dry mouth
other organ dryness
describe Felty’s syndrome
seropositive chronic RA
splenomegaly
granulocytopenia
causes joint damage, leg ulcers, recurrent infections
factors associated with poor prognosis in RA
load of disease (# of swollen and tender joints) presence of rheumatoid factor anti-CCP antibodies HLA-DR4 haplotype presence of erosions on XR
