Rheumatoid and other inflammatory arthritis Flashcards
What is arthritis
Joint inflammation
What are the two major divisions of arthritis
Osteoarthritis - degenerative
Inflammatory arthritis
Clinical signs of joint inflammation
Rubor - redness
Tumour - swelling
Dolor - pain
Calor - heat
What are three causes of joint inflammation?
Infection,
Crystal Arthritis,
Immune-Mediated (autoimmune)
What are two types of infection causing joint inflammation?
Septic arthritis
TB
What are two types of crystal arthritis?
Gout - uric acid crystals
Pseudogout - CPPD (calcium pyrophosphate)
Which of the three types are primary inflammation?
Autoimmune (others are secondary to toxins)
Which of the three is the only non-sterile inflammation?
Infection (others are sterile)
Distinguishing features of osteoarthritis
Very little inflamm
Slow onset
Sterile
Distinguishing features of Autoimmune arthritis
Inflamm
Subacute onset
Sterile
^ CRP
Distinguishing features of Crystal arthritis
2º inflamm to crystals
Rapid onset
Sterile, crystals present in synovial fluid
^ CRP
Distinguishing features of Septic arthritis
2º inflamm to infection
Rapid onset
Bacteria present
^ CRP
^ WBC
What is the clinical presentation of septic arthritis?
Acute, red, hot, painful, swollen monoarthritic joint
What is the diagnosis for septic arthritis?
Joint aspiration for gram stain and culture
What are the common organisms that cause septic arthritis?
Staph aureus, strep, gonococcus
What is the treatment for septic arthritis?
Surgical lavage (wash out) and IV antibiotics
What is the primary site of pathology for rheumatoid arthritis?
Synovium
What is rheumatoid arthritis
Chronic autoimmune disease leading to synovial inflammation
Where is synovium found?
Synovial Joints, Tenosynovium (around tendons), Bursa
What are the key features of rheumatoid arthritis?
Polyarthritis, Pain, Swelling, Early Morning Stiffness, Extra-articulate manifestations
How can you identify RA on an x ray
joint erosions due to damage
How can you estimate the contribution of genetics vs environment in these conditions?
Twin studies - monozygotic/dizygotic twins
If the concordance is greater in monozygotic twins this indicates there is a greater genetic component
What are some environmental risk factors for rheumatoid arthritis?
Smoking,
Microbiome,
Poor oral health (P. gingivalis)
lead to citrullination of proteins in the lung epithelium which can increase prevalence of ACPA - anti citrullinated protein antibodies
What is the strongest genetic risk factor for rheumatoid arthritis?
HLA-DR shared epitope
polygenic, cumulative genetic burden rather than any specific locus
Implications of HLA class 1 genetic association
e.g. HLA-B27 in AnkS, implicates CD8 cells in pathogenesis
It is expressed on all cells and presented to CD8 cells
Implications of HLA class 2 genetic association
e.g. HLA-DR4 in RA implicates CD4 T cells and B cells
Only expressed on APCs which are presented to CD4 cells
B cells activated by CD4 .: pathogenesis causes prod of autoantibodies
What is the pattern of joint involvement for rheumatoid arthritis?
Symmetrical,
polyarthritis,
small jts: hands/wrists/feet
Rheumatoid vs Osteoarthritis
RA - prolonged morning and inactivity stiffness.
- affects PIPJs, MCPJs, wrist
OA - pain worse with activity
- affects PIPJs, DIPJs , thumb CMCJs
Common extra articular features of RA due to systemic inflammation
Fever
Fatigue
Weight loss
extra articular features of RA due to organ specific inflammation
subcutaneous nodules,
lung fibrosis/ lung disease
episcleritis,
vasculitis leading to digital ischaemia
What is Felty’s syndrome
extra-articular presentation of RA
triad incl: splenomegaly, leukopenia, RA
Describe the subcutaneous nodules in rheumatoid arthritis
Central area of fibrinoid necrosis surrounded by histiocytes (macrophage-like) and connective tissue
present on the hand/ulna
What is the pathogenesis of rheumatoid arthritis?
Synovium becomes proliferated mass of tissue (pannus) due to neovascularisation, lymphangiogenesis, pro-inflammatory cytokines (TNF-alpha)
synovial inflamm due to autoreactive T/B cells (HLA-DR4) cause compliment activation and raised pro-inflamm cytokines (TNF-a)
cellular causes of RA
autoreactive T/B cells
cytokine imbalance, more pro-inflammatory cytokines
What are some of the roles of TNF-alpha?
pro-inflamm cytokine
Leukocyte accumulation,
Osteoclast activation - bone absorption
Chondrocytes activation (cartilage destruction MMP prod)
How does TNF-a cause pannus formation
Inflamm cell recruitment
angiogenesis
lymphangiogenesis
How does TNF-a cause cartilage loss
Matrix metalloprotease
How does TNF-a cause bone loss
Osteoclast activation
leads to osteopenia, erosions
RA bloods presentation
^ESR,
^CRP
^Platelets
RF - rheumatoid factor (not a standalone indicator)
Anti-CCP, specific and associated with aggressive disease
What are the three methods of imaging in rheumatoid arthritis?
X-Rays, USS, MRI
What features can X-Rays pick up?
Soft tissue swelling,
peri-articular osteopenia - dark areas around jts
bony erosions
What can ultrasound see?
Synovitis - synovial hypertrophy,
increased blood flow using doppler,
erosions (more detail)
What are the disadvantages of MRIs?
Expensive and time-consuming
What is the treatment objective for rheumatoid arthritis?
Prevent joint damage
How can we prevent joint damage in RA
Early diagnosis,
prompt aggressive pharmacological treatment,
MDT input (physio, OT)
What is the first line treatment regime for rheumatoid arthritis?
IM or oral glucocorticoids (steroids),
DMARD therapy (disease-modifying anti-rheumatic drugs)
What are some examples of DMARDs?
Methotrexate, Hydroxychloroquine
What is the second line treatment for rheumatoid arthritis?
if the disease is still active
Biological therapies, targeting sp molecules
Janus Kinase (JAK) inhibitors
What are DMARDs
disease-modifying anti-rheumatic drugs
Immunomodulatory drugs that halt or slow the disease process
What are NSAIDs
Non-steroid anti inflammatory drugs
e.g. ibuprofen, naproxen
Provide partial symptom relief but do not prevent disease progression
What is the mechanism of glucocorticoids?
Bind to glucocorticoid receptor in cytoplasm, complex acts as transcription factor
Methods of steroid admin
oral
intramuscular
intravenous
intra-articular
Side effects of glucocorticoids
Cushing’s disease
T2DM
Weight gain
Infection risk
What do biological therapies usually target?
Inflammatory cytokines
How do you measure progression of disease
DAS28, swollen/tender jts
If not suppressed rq treatment escalation
What are four different biological therapies?
Inhibition of TNF-alpha,
IL 6 inhibition
B cell depletion,
T cell modulation,
What are examples of an anti-TNF drug?
Infliximab, Adalimumab
What is an example of an IL-6 inhibitor?
Tocilizumab
What is an example of a b cell depletion drug?
Rituximab
What antibody does rituximab target?
CD20
What is an example of a T cell modulator drug?
Abatacept
CTLA4-Ig
What are four examples of seronegative arthritis?
Psoriatic arthritis,
reactive arthritis,
ankylosing spondylitis,
IBD-associated
What is seronegative arthritis
Immune mediated but w/o antibodies in the blood
What are the clinical features of psoriatic arthritis?
Scaly red plaques on elbows and knees, (extensor surfaces)
joint inflammation,
asymmetrical arthritis affecting mainly IPJs
enthesitis
What is the main pathogenic pathway in psoriatic arthritis?
IL-17, IL-23
Nail changes in psoriatic arthritis
Pitting
Onycholysis
What is reactive arthritis?
Sterile inflammation from infections elsewhere in body (urogenital, gastrointestinal)
may be the first manifestation of HIV/Hep C
What are the extra-articular manifestations of reactive arthritis?
Enthesitis, Skin inflammation, eye inflammation
What is a genetic predisposition to reactive arthritis?
HLA-B27
What is an environmental trigger for reactive arthritis?
Salmonella infection
Septic arthritis vs Reactive arthritis
SA - positive culture RA - negative culture
AB therapy No AB
joint lavage No lavage
