Rheumatoid and Other Inflammatory Arthritis Flashcards
Arthritis divisions
Osteoarthritis (degenerative)
Inflammatory arthritis (red, warm, swelling)
Secondary inflammation in response to noxious insult?
- Infection - septic arthritis and TB
- Crystal arthritis - gout and pseudo gout
Primary inflammation?
Autoimmune
Non-sterile inflammation?
Infection - septic arthritis and TB
Sterile inflammation?
Crystal arthritis - gout and pseudo gout
Autoimmune
Inflammation, onset, synovial fluid analysis, CRP and WCC in osteoarthritis?
Inflammation - no
Onset - slow
Synovial fluid analysis - no inflammatory cells, sterile
CRP - normal
WCC - normal
Inflammation, onset, synovial fluid analysis, CRP and WCC in immune-mediated arthritis?
Inflammation - yes - autoimmune
Onset - subacute
Synovial fluid analysis - inflammatory cells, sterile
CRP - high
WCC - normal
Inflammation, onset, synovial fluid analysis, CRP and WCC in crystal arthritis?
Inflammation - yes, secondary to crystals
Onset - rapid
Synovial fluid analysis - inflammatory cells, sterile, crystals
CRP - high or very high
WCC - normal
Inflammation, onset, synovial fluid analysis, CRP and WCC in septic arthritis?
Inflammation - yes, secondary to infection
Onset - rapid
Synovial fluid analysis - inflammatory cells, bacteria
CRP - very high
WCC - high
Septic arthritis presentation, investigations and management?
Presentation - acute hot, swollen joint
Investigations - joint aspiration, send fluid for gram stain and culture
Management - joint lavage and IV Abx
Rheumatoid arthritis definition and primary site?
Chronic autoimmune disease
Primarily at synovium
Synovitis?
Inflammation of synovial membrane
Can be at synovial joint (PIP), (extensor) tenosynovium, bursa
Rheumatoid arthritis key features?
Chronic polyarthritis
Pain, swelling and early morning stiffness
May lead to joint erosions
Rheumatoid arthritis risk factors?
(Genetics)
Smoking
Micro biome
Porphyromonas gingivalis
Poor oral health
citrulination
RA and anti-citrullinted protein antibodies?
Smoking -> citrulination of lung epithelium
P. gingivalis also causes citrulination
Rheumatoid strongest genetic risk factor?
HLA-DR
polygenic
HLA class 1?
HLA A, B, C
Expressed on all cells
Present peptide to CD8 T cells
HLA-B27 in ank spond implicates CD8 T cells
HLA class 2?
HLA D
Only on professional APCs (dendritic, macrophages, B cells)
Present peptide to CD4 T cells (which provide help to B cells)
HLA-DR4 in RA implicates CD4 T and B cells
FITS WITH AUTOANTIBODIES IN RA BUT NOT ANK
RA pattern of joint involvement?
Symmetrical, poly arthritis
MCP, PIP, wrists, knees, MTP
High small and large joints but nearly always involves small - particularly hands and feet
RA vs osteoarthritis hands?
RA - PIP, MCP, wrists. Prolonged morning and inactivity stiffness
OA - PIP, DIP, thumb CMC, pain worse with activity. MCP SPARED
RA extra-articular features? Systemic
Fatigue
Fever
Weight loss
RA extra-articular features? Organ specific.
Subcutaneous nodules
Lung disease (nodules, ILD, fibrosis, pleuritis)
Ocular inflammation (episcleritis)
Vasculitis (can lead to digital ischaemia)
Neuropathies
Felty’s syndrome
Amyloidosis
Felty’s syndrome?
Extra-articular feature of RA
Triad of splenomegaly, leukopenia and RA
RA - subcutaneous nodules
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Associated with severe disease, extra-articular manifestations, rheumatoid factor
Typical position - forearm, PIPs
Healthy synovial membrane?
1-3 cell layer that lines synovial joints
Contains - macrophage-like cells (type A synoviocyte), fibroblast-like cells (type B synoviocyte), type I collagen
maintains synovial fluid
Synovial membrane in RA?
Synovium becomes a proliferated mass of tissue (pannus) due to:
Neovascularisation
Lymphangiogenesis
Inflammatory cells
Which inflammatory cells cause synovium to become proliferated mass of tissue?
Activated B and T cells
Plasma cells
Mast cells
Activated macrophages
Pannus?
Proliferated mass of tissue
RA pathogenesis with treatments? B, T and cytokines
- Auto reactive B cells. Treatment - rituximab
- Auto reactive T cells. Treatment - abatacept
- Cytokines - TNF-a, IL-6, (IL-1). Treatment - anti-TNF-a, anti IL-6R
TNF-alpha in RA?
Dominant pro-inflammatory cytokine in rheumatoid synovium
TNF-a actions in RA?
Inflammatory cell recruitment, angiogenesis, lymphangiogenesis -> pannus formation
Matrix metalloproteases -> cartilage loss
Osteoclast activation -> bone loss
RA bloods?
Increased ESR, CRP
Sometimes normocytic anaemia, increased PLT
Rheumatoid factor, anti-CCP antibodies
RA autoantibodies?
Rheumatoid factor - binds IgG, can be positive in other conditions
Anti-CCP antibodies - most specific, suggest more aggressive/erosive disease
RA steps to symptoms?
Genetic predisposition -> pre-clinical autoimmunity -> tissue inflammation and disease (symptomatic)
RF and ACPAs precede symptom onset
Radiographic features of RA? X-rays
Soft tissue swelling
Peri-articular osteopenia
Bone erosions
RA ultrasound signs?
Synovial thickening (synovial hypertrophy)
Increased blood flow (Doppler signal)
Erosions
much better at detecting synovitis
DMARDs?
Disease-modifying anti-rheumatic drugs
Immunomodulatory drugs that halt or slow the disease process
RA first line pharmacological treatment?
Combination of DMARD therapy:
Methotrexate + hydroxychloroquine and/or sulfasalazine
PLUS
Steroids
RA second line pharmacological treatment?
Biological therapies (usually therapeutic monoclonal antibodies) e.g. TNF-alpha blockade
Glucocorticoids MOA?
Bind glucocorticoid receptor (in cytoplasm)
Steroid-GR complex translocates to nucleus and binds DNA response elements, affecting transcription
DAS28 score?
Used to calculate disease
Includes number of tender joints, number of swollen joints, visual analogue score, and ESR (or CRP)
Biological therapies targeting cytokines?
- Anti-TNF - Infliximab, adalimumab
- Anti-IL6 (tocilizumab)
Biological therapies targeting lymphocytes?
- B cell depletion - rituximab - antibody against B cell antigen CD20
- Blocking T cell co-stimulation - blocks CD80/CD86 on APC binding to CD28 on T cell
Seronegative arthritis examples?
Psoriatic arthritis
Ankylosing spondylitis
Reactive arthritis
Seronegative arthritis autoantibodies?
None present. NO anti-CCP nor RF.
Psoriatic arthritis?
Psoriasis - immune-mediated disease affecting the skin. Scaly red plaques on extensor surfaces.
10% also have joint inflammation
Seronegative.
Psoriatic arthritis pathogenic pathway? IL
IL-17/IL-23
Psoriatic arthritis signs?
Nail pitting, onycholitis, dactylitis
Asymmetrical affecting IPJs
Enthesitis
can also manifest as spinal and sacroiliac joint inflammation, oligoarthritis of large joints, arthritis mútilas, symmetrical small joints
Reactive arthritis?
Sterile inflammation in joints following infections elsewhere in body (usually after 1-4 weeks)
Reactive arthritis common infections?
Urogenital (chlamydia trachomatis)
Gastrointestinal (salmonella, shigella, campylobacter)
Reactive arthritis extra-articular manifestations?
Enthesitis
Skin inflammation
Eye inflammation
Septic arthritis vs reactive arthritis synovial fluid culture?
Septic - positive
Reactive - negative
Septic arthritis vs reactive arthritis antibiotic therapy?
Septic - yes, IV
Reactive - no, unless to treat underlying cause
Septic arthritis vs reactive arthritis joint lavage?
Septic - yes
Reactive - no
Osteoarthritis LOSS?
Loss of joint space
Osteophytes
Sclerosis
Subchondral cysts
Heberden’s vs Bouchard’s?
Heberden’s - DIPs
Bouchard’s - PIPs
osteoarthritis
Swan neck sign?
Chronic deformity of fingers. Hyperflexion of index finger DIPJ, hyperextension of PIPJ.
Sign of RA
