8.5 - Rheumatoid and other inflammatory arthritis Flashcards
What is arthritis?
Disease of the joints
What are the two major divisions of arthritis?
- osteoarthritis (degenerative arthritis)
- inflammatory arthritis (arthritis with signs of inflammation)
- red, hot/warm, swelling/fluid
In osteoarthritis, what does lack of joint space indicate?
Loss of articular cartilage leading to bone in contact with bone
What are some causes of joint inflammation (and what type of inflammation are they)? (3)
- infection - septic arthritis, tuberculosis
- crystal arthritis - gout, pseudogout
- immune-mediated (autoimmune) - rheumatoid arthritis, psoriatic arthritis, reactive arthritis, SLE
- 1+2 = secondary inflammation in response to a noxious insult
- 3 = primary inflammation
- 2+3 = sterile inflammation (1 is non-sterile inflammation)
Compare inflammation in degenerative (osteoarthritis) vs immune-mediated vs crystal arthritis vs septic arthritis.
- OA: none/little
- IM: yes - autoimmune
- CA: yes - secondary to crystals
- SA: yes - secondary to infection
Compare speed of onset in degenerative (osteoarthritis) vs immune-mediated vs crystal arthritis vs septic arthritis.
- OA: slow
- IM: sub-acute
- CA: rapid
- SA: rapid
Compare synovial fluid analysis in degenerative (osteoarthritis) vs immune-mediated vs crystal arthritis vs septic arthritis.
- OA: no inflammatory cells, sterile
- IM: inflammatory cells, sterile
- CA: inflammatory cells, sterile, crystals
- SA: inflammatory cells, bacteria (not sterile)
Compare CRP in degenerative (osteoarthritis) vs immune-mediated vs crystal arthritis vs septic arthritis.
- OA: normal
- IM: high
- CA: high/very high
- SA: very high
Compare WCC in degenerative (osteoarthritis) vs immune-mediated vs crystal arthritis vs septic arthritis.
- OA: normal
- IM: usually normal
- CA: usually normal
- SA: high
What causes septic arthritis?
Bacterial infection of a joint (usually caused by spread from the blood)
Why is septic arthritis a medical emergency?
If untreated, it can rapidly destroy a joint
When do we consider septic arthritis?
Acute hot, red, swollen joint = SEPTIC ARTHRITIS until proven otherwise
How is septic arthritis presented clinically? (1a recap)
- acute red, hot, painful, swollen joint
- usually only one joint affected (monoarthritis) - gonococcal septic arthritis is an exception which often affects multiple joints (polyarthritis) and is less likely to cause joint destruction
- typically fever + patient often systemically unwell
- consider septic arthritis in any patient with an acute painful, red, hot, swelling of a joint, especially if there is a fever
What is the key investigation for diagnosis of septic arthritis?
Joint aspiration - send fluid for gram stain and culture (urgent)
How is septic arthritis managed?
Joint washout (lavage) & IV antibiotics
What organisms commonly cause septic arthritis - 1a recap? (3)
- Staphylococcus aureus
- Streptococcus
- Gonococcus
What is rheumatoid arthritis?
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial joints
What is the primary site of pathology of rheumatoid arthritis?
Synovium
What is synovitis?
Inflammation of the synovial membrane
Where is the synovium found (and therefore where is the primary site of pathology of rheumatoid arthritis)? (3)
- synovial joints - e.g. proximal inter-phalangeal (PIP) joint synovitis
- tenosynovium surrounding tendons - e.g. extensor tenosynovitis - patient cannot fully extend little and ring fingers
- bursa - fluid filled sacs that provide lubrication for easy movement e.g. olecranon bursitis
Describe the epidemiology of rheumatoid arthritis.
- common: prevalence 1%
- sex bias F:M 2:1
- age of onset usually 30-50s
What are the key features of rheumatoid arthritis?
- chronic arthritis:
- polyarthritis
- symmetrical
- pain, swelling and early morning stiffness in and around joints (around 30 min) - vs in OA<30min + better with movement
- may lead to joint damage and destruction - ‘joint erosions’ on radiographs
- systemic disease with extra-articular manifestations
- autoantibodies usually detected in blood (e.g. rheumatoid factor)
Is rheumatoid arthritis genetic or environmental?
A mixture of both
How can we use twin studies to estimate the contributions of genetics vs environment?
- look at concordance of a trait in monozygotic vs dizygotic twins
- look at pairs of twins - ask if one twin has the disease, how often does the other?
- if the concordance rate for MZ > DZ twins, this indicates a genetic component
- if the disease was purely genetic, the concordance rate would be 100% for MZ twins
What have twin studies shown about the genetic basis of rheumatoid arthritis?
- MZ ~15% concordance
- DZ ~4% concordance
- i.e. a mixture of genes and environment (as not 100%), but genes involved
What environmental factors can contribute to rheumatoid arthritis? (4)
- smoking (can cause citrullination of proteins in lung epithelium –> ACPA)
- microbiome
- Porphyromonas gingivalis (can cause citrullination of proteins in lung epithelium –> ACPA)
- poor oral health
What is the strongest genetic risk factor for rheumatoid arthritis?
HLA-DR4
In rheumatoid arthritis, what is the shared epitope?
- HLA-DRbeta chain amino acids 70-74 (= ‘shared epitope’)
- smoking and shared epitope synergistically increase risk
What have genome-wide association studies shown about rheumatoid arthritis?
- 100 other genetic loci (other than HLA-DR) contribute to RA risk (polygenic) e.g. PTPN22, IL6R
- effect of a risk allele at any given locus typically modest (small effect)
- cumulative genetic burden rather than any one variant determines risk
What is HLA class 1?
- HLA A, B and C
- HLA class 1 expressed on all cells
- cells present peptide in association with HLA class 1 to CD8 (killer) T cells
What is HLA class 2?
- HLA D
- HLA class 2 only expressed on professional antigen presenting cells including dendritic cells, macrophages, B cells
- APCs present peptide in association with HLA class 2 to CD4 (helper) T cells
- CD4 T cells provide ‘help’ to B cells (–> antibodies)
What are the implications of HLA genetic associations in rheumatoid arthritis and ankylosing spondylitis?
- HLA class 1 association (e.g. HLA-B27 in AS) implicates CD8 T cells in pathogenesis
- HLA class 2 association (e.g. HLA-DR4 in RA) implicates CD4 T cells and B cells
- this fits with autoantibodies (made by B cells) in RA but not in AS
What is the pattern of joint involvement in rheumatoid arthritis?
- symmetrical
- affects multiple joints - polyarthritis
- can affect both small and large joints, but nearly always small joints involved - particularly hands and feet