rheumatoid and other inflammatory arthritis Flashcards
degenerative osteoarthritis distinguishing features- inflammation/non-inflammatory? onset?
what is in synovial fluid?
CRP?
WCC?
little-no inflammation
slow onset
sterile
CRP/WCC normal
immune mediated distinguishing features- inflammation/non-inflammatory? onset?
what is in synovial fluid?
CRP?
WCC?
inflammation
subacute onset
sterile with inflammatory cells
CRP high
WCC normal
crystal arthritis distinguishing features- inflammation/non-inflammatory? onset?
what is in synovial fluid?
CRP?
WCC?
inflammation secondary to crystals
rapid onset
synovial fluid analysis: sterile, crystals, inflammatory cells
CRP high
WCC normal
septic arthritis distinguishing features- inflammation/non-inflammatory? onset?
what is in synovial fluid?
CRP?
WCC?
inflammation secondary to inflammation
rapid onset
synovial fluid analysis: inflammatory cells/bacteria
CRP/WCC both high
what is synovitis
inflammation of synovial membrane
RA is synovial inflammation. Where are synovium found
-proximal inter-phalangeal joint synovitis
-extensor tenosynovitis
-olecranon bursitis
RA overview. Sex, age?
Key features? What’s seen in radiographs? What can be detected in blood?
Sex bias F:M ~2:1
Age of onset 30-50s
Key features:
Chronic arthritis
Polyarthritis
Pain, swelling and early morning stiffness in and around joints
joint damage - ‘joint erosions’ on radiographs
Auto-antibodies usually detected in blood
RA- genetic/environmental aetiology
genetic
-twin studies - higher concordance in monozygotic than dizygotic =mix of genetic and environment (as there are still dizygotic)
environmental-
smoking
microbiome
p.gingivalis
poor oral health
contribute to ACPA
RA- genetics-
WHAT is the strongest genetic risk factor and what has GWAS found?
Strongest genetic risk factor = HLA-DR
GWAS- polygenic- cumulative genetic burden rather than 1 variant determines risk
how to do GWAS
-Compare allelic frequencies at specific SNP between cases vs controls
-Repeat across the genomes for millions of SNPs
-Identify the SNPs associated with disease risk
implications of HLA genetic associations: HLA class 1
HLA A,B,C
present on all cells- cells present peptide in association with HLA class 1 to CD8 killer T cells
HLA-B27: Ankylosing spondylitis
implications of HLA genetic associations: HLA class 2
HLA D
Expressed on APC
APC present peptide associated with HLA class 2 to CD4 helper T cells
(HLA-DR4 in RA)
RA VS OA
RA: prolonged morning stiffness and inactivity stiffness
OA: pain worse with activity
RA extra-articular features
Systemic inflammation
Fatigue (v common)
Fever
Weight loss
Organ-specific
Subcutaneous nodules
Lung disease
episcleritis
Vasculitis-> digit ischaemia
Neuropathies
Felty’s syndrome – triad of splenomegaly, leukopenia and RA
Amyloidosis
Rheumatoid arthritis: subcutaneous nodules what are they
fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Associated with:
Severe disease/RF
where can subcutaneous (rheumatoid) nodules be found
hands
elbow/ulnar border of forearm
what happens to RA synovium and how
Synovium becomes a proliferated mass of tissue (pannus) due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells:
activated B and T cells
mast cells
activated macrophages
what is seen in a healthy synovial membrane
macrophage-like (type A synoviocyte)
fibroblast-like (type B synoviocyte) cells
type I collagen
Functions: maintenance of synovial fluid
what is cytokine imbalance seen in RA
Excess of pro-inflammatory vs. anti-inflammatory cytokines (‘cytokine imbalance’)
RA: TNF-a effect from action
Inflammatory cell recruitment, angiogenesis, lymphangiogenesis -> Pannus formation
Matrix metalloproteases -> Cartilage loss
Osteoclast activation -> Bone loss (erosions, osteopenia)
RA investigations
bloods:
high ESR/CRP
Normocytic anaemia= high PLT
Autoantibodies=
RF (binds to IgG)
Anti-CCP antibodies
what does anti-CCP antibodies stand for
anti-cyclic citrullinated protein antibodies
RA pharmacological treatment
First line
Combination DMARD therapy:
Methotrexate + hydroxychloroquine +/- sulfasalazine
PLUS
IM or short course of oral steroids
if disease is still active- second line for RA treatment:
Biological therapies
cytokines target
1. anti-TNFa-infliximab
2. IL-6 receptors Inhibitor (tocilizumab)
lymphocyte target
3. B cell depletion- rituximab
4. blocking T cell co-stimulation: abatacept
