Rheumatoid Arthritis Flashcards
1
Q
What is rheumatology?
A
medical speciality of diseases of the MSK system
2
Q
What is a tendon?
A
cords of strong fibrous collagen tissue attaching muscle to bone
3
Q
What is a ligament?
A
flexible fibrous tissue which connects 2 bones
4
Q
What is synovium?
A
1-3 deep cell lining containing:
- macrophage-like phagocytic cells (type A synoviocyte)
- fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
5
Q
What is synovial fluid?
A
hyaluronic acid-rich viscous fluid
6
Q
What is articular cartilage made of?
A
- Type 2 collagen
- proteoglycan (aggrecan)
7
Q
What is arthirtis?
A
Disease of the joints
8
Q
What are the main 2 different types of arthritis?
A
- osteoarthritis (degenerative)
- inflammatory (rheumatoid)
9
Q
What is inflammation?
A
a physiological response to deal with injury or infection
10
Q
How does inflammation manifest?
A
- red
- painful
- hot
- swelling
- loss of function
11
Q
What are the physiological, cellular and molecular changes caused by inflammation?
A
- increased blood flow
- WBC migration (leukocytes) into tissues
- activation/differentiation of leucocytes
- cytokine production
12
Q
What are the different causes of joint inflammation?
A
- crystal arthritis (gout/pseudogout)
- immune-mediated
- infection
13
Q
What are the different infectious causes of joint inflammation?
A
- septic arthiritis
- tuberculosis
14
Q
Which causes of joint inflammation are primary and secondary?
A
- immune mediated = primary inflammation
- infection and crystal arthiritis = secondary inflammation in response to noxious insult
15
Q
Which causes of inflammation are sterile and non sterile?
A
- crystal arthirtis and immune-mediated = sterile
- infection = nonsterile
16
Q
What should be assumed when a patient presents with an acute hot, swollen joint
A
Septic arthiritis because it is a medical emergency
17
Q
What is the key investigation for septic arthiritis?
A
Joint aspiration, send fluid for gram stain and culture
18
Q
What is the management for septic arthiritis?
A
- Joint lavage
- IV antibiotics
19
Q
What are some examples of different immune-mediated causes of joint inflammation?
A
- rheumatoid arthritis
- seronegative spondyloarthropathies
- connective tissue diseases
20
Q
What is gout?
A
a syndrome caused by the deposition of uric crystals leading to inflammation
21
Q
What is pseudogout?
A
a syndrome cause by the deposition of calcium pyrophosphate dehydrate (CPPD) crystal deposition.
22
Q
What is tested in a synovial fluid test?
A
- gram stain, culture and ABx sensitivity
23
Q
What is rheumatoid arthritis?
A
- chronic autoimmune disease
- characterised by pain, stiffness and symmetrical synovitis
24
Q
What is synovitis?
A
Inflammation of the synovial membrane
25
What happens in rheumatoid arthritis?
synovium becomes a proliferated mass of tissue (pannus)
26
What is the aetiology of rheumatoid arthiritis?
Genetic and environmental
27
What are some environmental risk factors for rheumatoid arthirits?
- smoking
- microbiome
- P. gingivalis
- poor oral health
28
What do both smoking and P. gingivalis cause?
Citrullination of proteins in the lung epithelium
29
What are the genetic risk factors for rheumatoid arthiritis?
- female sex
- HLA-DR shared epitope
- cumulative genetic burden of other genetic loci (polygenic disease)
30
What are class 1 HLAs?
- HLA A, B and C
- expressed on all cells
- presented with antigen to CD8 T cells
31
What are class 2 HLAs?
- HLA D
- only expressed on APCs
- presented with antigen to CD4 T cells which stimulates B cells
32
Why are autoantibodies found in rheumatoid arthirtis but not ankylosing spondylitis?
- ankylosing spondylitis is associated with class 1 HLA (HLAB27)
- rheumatoid arthirits associated with class 2 HLA (HLADR4)
- only class 2 HLAs stimulate B cells which secrete antibodies
33
What causes the synovium to become a proliferated mass of tissue?
- neovascularisation
- lymphangiogenensis
- activated B and T cells
- plasma cells
- mast cells
- activated macrophages
- excess of pro-inflammatory cytokines
34
What is the dominant pro-inflammatory cytokine in rheumatoid arthritis?
- TNF-alpha
- IL-6, IL-1
- produced by activated macrophages
35
Which cells are invloved in the pathogenesis of rheumatoid arthiritis?
Autoreactive B and T cells
36
What is the impact of the excess TNF-alpha production?
- osteoclast activation
- chemokine release
- endothelial cell activation
- leukocyte accumulation
- angiogenesis
- lymphangiogenesis
- inflammatory cell recruitment
- matrix metalloproteinases
- chondrocyte activation
- pro-inflammatory cytokine release
37
What causes pannus formation?
- inflammatory cell recruitment
- angiogenesis
- lymphangiogenesis
38
What do matrix metalloproteinases cause?
Cartilage loss
39
What does osteoclast activation cause?
bone loss
40
What are the key features of rheumatoid arthritis?
- chronic
- polyarthritis (swelling of small joints)
- symmetrical
- early morning stiffness
- may cause joint damage and destruction
- rheumatoid nodules
- systemic with extra-articular manifestations
- autoantibodies usually detected in blood
41
What can be used to detect rheumatoid arthritis?
rheumatoid factor, autoantibody against IgE
42
What are the most commonly affected joints with rheumatoid arthritis?
- Metacarpophalangeal joints (MCP)
- Proximal interphalangeal joints (PIP)
- Wrists
- Knees
- Ankles
- Metatarsophalangeal joints (MTP)
- nearly always invloves small joints
43
Where are the primary sites of the pathology of rheumatoid arthritis?
- synovial joints
- tenosynovium surrounding tendons
- bursa
44
What are the extra-articular features of rheumatoid arthritis?
- fever
- fatigue
- weight loss
- subcutaneous nodules
- vasculitis
- ocular inflammation
- neuropathies
- amyloidosis
- lung disease (nodules, fibrosis and pleuritis)
- Felty's syndrome
45
What is Felty's syndrome?
- splenomegaly
- leukopenia
- rheumatoid arthritis
46
What are subcutaneous nodules in rheumatoid arthritis?
central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
47
What are subcutaneous nodules associated with?
- severe disease
- extra-articular manifestations
- rheumatoid factor
48
Where do subcutaneous nodules tend to be found?
- the ulnar border of the forearm
- in the hands
49
Which blood tests are done for rheumatoid arthiritis?
- ESR
- CRP
- PLT
- autoantibodies
- all increased
50
What antibodies are found in those with rheumatoid arthritis?
- rheumatoid factor
- antibodies to citrullinated protein antigens (anti-CCP)
51
Is rheumatoid factor only present in people with rheumatoid arthiritis?
No
52
What imaging is done for rheumatoid arthiritis?
- X-ray
- US (best at picking it up early)
- MRI
53
What are the features of rheumatoid arthiritis which show on a radiograph?
- soft tissue swelling
- peri-articular osteopenia
- bony erosions
- limited to information on bony structures only
54
Which ultrasound changes are seen in rheumatoid arthirtis?
- synovial thickening
- increased blood flow
- erosions which can't be seen on plain radiograph
55
Which imaging is used in sn early arthiritis clinic?
Ultrasound
56
What does rheumatoid arthritis treatment require?
- Early recognition of symptoms, referral and diagnosis
- Prompt initiation of treatment
- Aggressive treatment to suppress inflammation
- multidisciplinary input
- goal is to prevent joint damage
57
What are the main pharmological treatments for rheumatoid arthiritis?
- glucocorticoid therapy (acute use)
- disease-modifying anti-rheumatic drugs (DMARDS)
58
What is the action of glucocorticoids?
- bind to GR receptor in cytoplasm
- steroid-GR complex translocates to nucleus and binds to DNA
- affects transcription
59
What are the different methods of steroid administration?
- oral
- intramuscular
- intravenous
- intra-articular
60
What are the side effects of steroid use?
Cushing's syndrome
61
What is the first line treatment of rheumatoid arthritis?
- DMARD therapy (methotrexate in combination with hydroxychloroquine or sulfasalazine)
- IM or oral steroids
62
What is the second line treatment of rheumatoid arthritis?
- Biological therapies offer potent and targeted treatment strategies
- New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitini
63
What are the targets of the biologics used in the treatment of rheumatoid arthritis?
- Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
- B cell depletion
- Modulation of T cell co-stimulation
- Inhibition of IL-6 signalling
64
What is treat to target?
- suppress disease activity to improve outcome
- uses DAS28
65
What is DAS28?
- score, if not suppressed then escalate treatment
- number of tender joints
- number of swollen joints
- patient visual analogue score
- ESR/CRP
66
What is the mechanism of infliximab and etanercept?
- Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
- infliximab targets antibodies
- entanercept targets fusion proteins
67
What is the mechanism of rituximab?
- B cell depletion
- antibody against B cell antigen CD20
68
What is the mechanism of Abatacept?
- Modulation of T cell co-stimulation
- blocks CD80/CD86 on APC binding to CD28 on T cell
69
What is the mechanism of Tocilizumab and Sarilumab?
Inhibition of interleukin-6 signalling
70
What is seronegative arthiritis?
- inflammatory arthiritis where RF and CCP antibodies are not present in blood
- still immune mediated
71
What are the different types of seronegative arthiritis?
- psoratic arthiritis
- reactive arthiritis
- ankylosing spondylitis
- IBD-associated arthiritis
72
What is reactive arthritis?
- Sterile inflammation in joints following infection
- especially urogenital (e.g. Chlamydia trachomatis) and gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections) infections
73
What are the extra-articular features of reactive arthritis?
- Enthesitis (tendon inflammation)
- Skin inflammation
- Eye inflammation
74
What can reactive arthritis be a sign of?
- HIV
- Hep C
75
What are the risk factors of reactive arthritis?
- genetic predisposition (HLA-B27) and environmental trigger
76
How long does it take for reactive arthritis to present after an infection?
1-4 weeks
77
What is Psoriasis?
- an autoimmune disease affecting the skin
- scaly red plaques on extensor surfaces eg elbows and knees
- 10% of patients have joint inflammation
78
What is the dominant pathogenic pathway for psoratic arthiritis?
IL-17 and IL-23
79
What is the relationship between skin disease and joint manifestations of psoratic arthiritis?
- skin disease severity is not correlated to joint manifestations
- nail changes may be the only skin manifestations
- need to carefully examine the skin for small areas of psoriasis
80
How does Psoriatic arthritis present?
- Classically asymmetrical arthritis affecting IPJs
- Enthisitis
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
81
What is lupus?
a multi-system autoimmune disease associated with antibodies to self antigens (‘autoantibodies’) which are directed against components of the cell nucleus
82
What is associated with lupus?
- Multi-site inflammation: can affect any almost any organ.
- Often joints, skin, kidneys, haematology.
- Also: lungs, CNS involvement
83
What clinical tests can be done when lupus is suspected?
- Antinuclear antibodies (ANA)
| - Anti-double stranded DNA antibodies (anti-dsDNA Abs):
84
Why are antinuclear antibodies measured for suspected lupus?
- High sensitivity for SLE but not specific.
| - A negative test rules out SLE, but a positive test does not mean SLE.
85
Why are Anti-double stranded DNA antibodies measured for suspected lupus?
High specificity for SLE in the context of the appropriate clinical signs.
86
When is lupus most common?
- 15-40 years old
| - asian and african populations
87
What is management plan for Ankylosing spondylitis?
- physiotherapy
- exercise regimes
- NSAIDs
- peripheral joint deposition (DMARDs)
88
Can you definitively test for Ankylosing spondylitis?
no, seronegative spondyloarthropathy – no positive autoantibodies
89
What happens in Ankylosing spondylitis?
- Chronic sacroillitis (inflammation of sacroiliac joints)
| - Results in spinal fusion (ankylosis) and deformity
90
What is Ankylosing spondylitis associated with?
HLA B27
91
When is Ankylosing spondylitis most common?
- 20-30 years old
| - male
92
What tests should be done in suspected Ankylosing spondylitis?
- FBC
- CRP, ESR
- test for HLA-B27
- XR
- MRI
93
What would blood tests show in Ankylosing spondylitis?
FBC: normocytic anaemia
CRP, ESR: raised
HLA-B27: present
94
What would imaging (MRI/XR) show in Ankylosing spondylitis?
- Squaring Vertebral bodies, Romanus lesion
- Erosion, sclerosis, narrowing SIJ
- Bamboo Spine
- Bone Marrow Oedema
95
What are some other examples of connective tissue disorders?
- Systemic Sclerosis
- Myositis
- Sjogrens syndrome
- Mixed connective tissue disease
96
What is the site of inflammation in Ankylosing spondylitis?
enthesis
97
what are the seronegative spondyloarthropathies?
- Ankylosing spondylitis
- Reactive Arthritis (Reiters syndrome)
- Psoriatic arthritis
- Arthritis associated with GI inflammation (enteropathic synovitis)
98
What is SLE?
Chronic tissue inflammation in the presence of antibodies directed against self antigens
(multi-site inflammation: joints, skin and kidney)
99
What autoantibodies are associated with SLE?
- Antinuclear antibodies
- Anti-double stranded DNA antibodies
- Anti-phospholipid antibodies
100
What are the connective tissue diseases?
- SLE
- Sjogren’s syndrome
- Autoimmune Inflammatory muscle disease
- Systemic sclerosis (scleroderma)
- Overlap syndromes
101
What is common in connective tissue disorders?
Reynaud's phenomenon
102
What is Reynaud's phenomenon?
Intermittent vasospasm of digits on exposure to cold
(white to blue to red)
- leads to blanching of digit
- Cyanosis as static venous blood deoxygenates
- Reactive hyperaemia
103
What information do serum autoantibodies provide?
- correlate to disease activity
- directly pathogenic
- can aid in diagnosis
104
What is typically non-erosive?
- arthralgia
| - arthritis
105
When is SLE typically diagnosed?
in females aged 15-45 years old
106
What are the different clinical manifestations of SLE?
- Malar rash
- Photosensitive rash
- Mouth ulcers
- Hair loss
- Raynaud’s phenomenon
- Arthralgia and sometimes arthritis
- Serositis (pericarditis, pleuritis, less commonly peritonitis)
- Renal disease – glomerulonephritis (‘lupus nephritis’)
- Cerebral disease – ‘cerebral lupus’ e.g. psychosis
107
What is a Malar rash?
erythema that spares the nasolabial fold
108
What is the pathogenesis of SLE?
- Apoptosis leads to translocation of nuclear antigens to membrane surface
- Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells
- B cell autoimmunity
- Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement
109
What are anti-phospholipid antibodies associated with?
risk of arterial and venous thrombosis
110
What autoantibodies are associated with systemic vasculitis?
antinuclear cytoplasmic antibodies (ANCA)
111
What is the significance of antinuclear antibodies in SLE?
- seen in all SLE cases
| - not specific for SLE
112
What is the significance of anti-double stranded DNA antibodies in SLE?
- specific to SLE
| - serum level correlates to disease activity
113
What is the significance of anti-phospholipid antibodies in SLE?
- associated with risk of arterial and venous thrombosis in SLE
- may also occur in absence of SLE in what is termed the ‘primary anti-phospholipid antibody syndrome
114
What is the significance of anti-Sm antibodies in SLE?
- specific to SLE
| - serum level does not correlate to disease activity
115
What is the significance of anti-Ro and Anti-La antibodies in SLE?
- secondary sjögren's syndrome
| - neonatal lupus syndrome (transient rash, permanent heart block)
116
What is the significance of anti-ribosomal P antibodies in SLE?
cerebral lupus
117
What are the two different types of twin studies?
- monozygotic twins = identical DNA
- dizygotic twins = share 50% DNA
118
What does the concordance rate of twin studies indicate?
- concordance rate of monozygotic twins higher than dizygotic twins indicates genetic cause
- if a disease is purely genetic the concordance rate for monozygotic twins is 100% the disease is purely genetic
