(msk) rheumatology Flashcards
1
Q
what is rheumatology?
A
the medical speciality dealing with diseases of the musculoskeletal system including
- bones
- muscles
- tendons
- ligaments
- cartilage
2
Q
what is a synovial joint?
A
a fluid-filled joint cavity contained in a fibrous capsule where two bones meet
(diarthrosis = freely mobile)
3
Q
what is the synovium?
A
lining of the fibrous synovial capsule
(1-3 cells deep)
i.e. synovial membrane
4
Q
which two cells types are present in the synovium?
A
type A synoviocytes
type B synoviocytes
(together with type I collagen)
5
Q
what are type A synoviocytes?
A
macrophage-like phagocytic cells
6
Q
what are type B synoviocytes?
A
fibroblast-like cells that produce hyaluronic acid
7
Q
what type of collagen is present in the synovium?
A
type I collagen
8
Q
what is the main component of synovial fluid?
A
hyaluronic acid
rich viscous fluid
9
Q
what type of collagen is present in the articular cartilage?
A
type II collagen
10
Q
where is the proteoglycan Aggrecan found in a synovial joint?
A
a proteoglycan found in the articular cartilage
11
Q
what is arthritis?
A
inflammation of the joints
12
Q
what are the three divisions of arthritis?
A
degenerative (osteoarthritis)
inflammatory (rheumatoid arthritis)
septic arthritis
13
Q
what is inflammation?
A
a physiological response to deal with injury or infection
14
Q
what are the manifestations of inflammation?
A
redness (rubor) heat (calor) pain (dolor) swelling (tumor) loss of function
15
Q
what physiological changes underlie inflammation?
A
increased blood floew
increased activation and recruitment of leukocytes to site of injury/infection
cytokine release (TNFa, IL1, IL6, IL17)
16
Q
which cytokines are released in inflammation?
A
TNFa, IL1, IL6, IL17
17
Q
when does crystal arthritis occur?
A
crystals deposit in the joint triggering inflammation
18
Q
what are the two types of crystal arthritis?
A
gout
pseudogout
19
Q
what is gout?
A
a syndrome caused by deposition of urate (uric acid) crystals in the joints
= inflammation
20
Q
what is the biggest risk factor for gout?
A
hyperuricaemia (high uric acid levels in the blood)
21
Q
what are the main causes of gout?
A
genetic tendency
increased consumption of purine-rich foods
kidney failure (reduced excretion)
22
Q
what is pseudogout?
A
a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals
= inflammation
23
Q
what are the risk factors for pseudogout?
A
background osteoarthritis
elderly patients
intercurrent infections
24
Q
name two diseases that can be caused by the excessive deposition of MSU (monosodium urate) in tissues due to hyperuricaemia
A
1) gout arthritis
2) tophi
25
what is tophi?
aggregated deposits of MSU (monosodium urate) in tissue
| subcutaneous deposits of MSU
26
which joint is affected most commonly in gout and what is this called?
the 1st metatarsophalangeal joint ('big toe')
= podagra
27
how does podagra present?
```
pain
redness
swelling, tenderness
abrupt onset
usually resolves in 3-10 days
```
28
what is podagra?
gout of the 1st MTPJ 'big toe'
29
gout causes monoarthritis most commonly - what is this?
arthritis affecting a singular joint
| gout can cause polyarthritis but not initially
30
what are the signs of gout on an X-ray?
juxta-articular rat-bite erosions of the 1st MTPJ
31
how are suspected gout and pseudogout investigated?
```
joint aspiration
(synovial fluid analysis)
```
32
how is acute gout managed?
NSAIDs
steroids
colchicine
33
how is chronic gout managed?
allopurinol
34
how are synovial fluid samples analysed for pathogens?
rapid gram stains followed by culture and antibiotic sensitivity assays
35
how are synovial fluid samples analysed for gout crystals?
polarising light microscopy to identify crystals
36
what kind of crystals are seen in gout on synovial fluid analysis?
urate crystals
needle shape
negative birefringence
37
what kind of crystals are seen in pseudogout on synovial fluid analysis?
CPPD crystals (calcium pyrophosphate dihydrate)
brick 'rhomboid' shape
positive birefringence
38
name some immune-mediated inflammatory joint diseases
rheumatoid arthritis
psoriatic arthritis
reactive arthritis
SLE
39
what is the most common immune-mediated inflammatory arthritis?
rheumatoid arthritis
40
what is rheumatoid arthritis?
chronic autoimmune disease characterised by
1) pain
2) stiffness
3) symmetrical synovitis of synovial joints
(inflammation of the synovial membrane)
41
is rheumatoid arthritis a polyarthritis or a monoarthritis?
polyarthritis
= affects multiple joints
(mainly small joints of the hands and wrist)
42
which joints are affected most in rheumatoid arthritis?
mainly small joints of the hands and wrist
43
what are the key features of rheumatoid arthritis?
pain
stiffness (early morning)
symmetrical synovitis
polyarthritis
44
what happens if rheumatoid arthritis is left untreated?
can lead to joint damage and joint erosions on radiographs
45
which rheumatoid antibody is often detected in the blood?
rheumatoid factor (anti-IgG antibody)
46
which joints are most commonly affected in RA?
UL = wrist, MCPJs, PIPJs
LL = knee, ankle, MTPJs
47
what is the primary site of pathology in RA?
synovium
48
besides the synovial joints, where can synovitis occur in RA?
1) tenosynovium surrounding tendons (i.e. synovial sheaths associated with tendons - extensors, flexors)
2) bursae (e.g. olecranon bursitis)
49
what is tenosynovitis and why is it important in RA?
inflammation of a tendon and its respective synovial sheath
= can occur due to synovitis in RA
e.g. extensor tenosynovitis
50
what are the common extra-articular manifestations of RA?
fever
weight loss
subcutaneous nodules
51
what are the rare extra-articular manifestations of RA?
```
vasculitis
episcleritis
neuropathies
amyloidosis
lung disease
Felty's sundrome
```
52
what is Felty's syndrome?
a rare extra-articular manifestation of RA
= triad of spenlomegaly, leukopenia and RA
53
where do subcutaneous nodules form most commonly in RA?
elbow
| extensor surfaces of hand
54
what are subcutaneous nodules in RA?
central fibrinoid necrosis w a peripheral layers of connective tissue and histiocytes
55
how common are subcutaneous nodules in RA and what are they indicative of?
approx 30% of RA patients
= indicate severe disease
56
why two antibodies are primarily found in RA patients?
1) rheumatoid factor (anti-IgG)
| 2) anti-CCP antibody
57
what is rheumatoid factor?
RF = pentameric IgM antibodies that bind to the Fc portion of the circulating IgG antibodies
58
how many RA patients have RF and how are these patients described?
approx 70% of patients have RF at disease onset
= said to be 'seropositive'
(further 10-15% become seropositive over the next 2 years following diagnosis)
59
what are anti-CCP antibodies?
antibodies to citrullinated peptides
| = highly specific for RA
60
which enzyme mediates the citrullination of peptides?
peptidyl arginine deaminases (PADs)
= convert arginine to citrulline
61
what are the three steps to managing RA effectively?
1) recognise symptoms early
2) initiate treatment early (joint destruction = inflammation x time)
3) choose aggressive treatment to suppress inflammation
62
which group of drugs is used to treat RA?
DMARDs
| disease-modifying anti-rheumatic drugs
63
what is the first-line treatment for RA?
methotrexate in combination hydroxychloriquine or sulfasalazine
64
what is the second-line treatment for RA?
biologics
Janus Kinase inhibitors (Tofacitinib & Baricitinib)
steroid therapy (prednisolone)
= multi-disciplinary approach
65
why is prednisolone avoided in RA treatment?
avoid long-term use because of systemic side-effects
| can inject to site of arthritis to avoid systemic side effects
66
what is ankylosing spondylitis?
inflammatory arthritis of the joints of the spine
| seronegative spondyloarthropathy = causes ankylosing
67
what is an early sign of ankylosing spondylitis?
```
chronic sacroillitis
(inflammation of sacroiliac joints)
```
= hallmark feature
68
is RF present in ankylosing spondylitis?
no!
ankylosing spondylitis is a seronegative spondyloarthropathy
= no RF antibody
69
which group of patients is most affected by ankylosing spondylitis?
males
| 20-30 years old
70
what causes ankylosing spondylitis?
no specific cause but increase genetic risk
= people who have a gene called HLA-B27 are at a greatly increased risk of developing ankylosing spondylitis
71
what does seronegative mean?
lack of rheumatoid factor (RF) and anti-CCP antibodies in teh blood
72
how does ankylosing spondylitis present?
leads to spinal fusion reducing the flexibility of the spine
| = causing hunched back
73
ankylosing spondylitis is a seronegative spondyloarthropathy - what does this mean?
ankylosing = bony fusion of the spine + stiffness
spondyloarthropathy = forms of arthritis that usually strike the bones in your spine and nearby, peripheral joints
74
what are the primary sites of pathology in ankylosing spondylitis?
joints of the spine
sacroiliac joints (causing chronic sacroillitis)
75
name other common spondyloarthropathies
reactive arthritis, psoriatic arthritis
76
which clinical symptoms must you have alongside a seropositive test (RF, anti-CCP present) result to be diagnosed with rheumatoid arthritis?
pain and swelling in the joints
polyarthritis (involves many joints)
morning stiffness in the joints
X-ray evidence of the characteristic bone damage of RA (soft tissue swelling, bony erosions, peri-articular osteopenia)
77
what are the symptoms of ankylosing spondylitis?
- lower back pain + stiffness (early morning, improves with exercise)
- reduced spinal movements
- peripheral arthritis
- plantar fasciitis, achilles tendonitis
- fatigue
78
what is the classic clinical presentation of patients with ankylosing spondylitis?
flexed neck
loss of lumbar lordosis
flexion of the hip and the knees
(45+, back pain for >3 months)
79
what makes the stiffness of ankylosing spondylitis characteristic to the condition?
usually early morning stiffness that improves on exercise
80
define extra-articular manifestations
symptoms outside of or other than a joint
81
what are the key features of an ankylosing spondylitis blood test?
normocytic anaemia
raised CRP + ESR
positive for HLA-B27 gene
82
which imaging modality is most commonly used to investigate ankylosing spondylitis?
MRI (but can also use X-ray)
83
what are the key features of an MRI that shows ankylosing spondylitis?
- shiny corner sign (i.e. Romanus lesion)
- squaring of the vertebral bodies
- bamboo spine (fusion of the joints)
- bone marrow oedema (fluid fills bone marrow)
- erosion, sclerosis, narrowing of the sacroiliac joint
84
how is ankylosing spondylitis managed?
physiotherapy, exercise regimes
NSAIDs, DMARDs (for peripheral joints)
85
why does psoriatic arthritis occur?
psoriasis occurs = formation of red, scaly plaques on extensor surfaces (knees, elbows)
= approx 10% of psoriasis cases have associated inflammation of the joints
86
what are the two similarities between ankylosing spondylitis and psoriatic arthritis?
- both seronegative (lack of RF in the blood)
| - can cause inflammation of the sacroiliac joints
87
what is the most common clinical presentation of psoriatic arthritis?
asymmetrical arthritis
bony erosions occur at ICPs, while MCPs are left unaffected
classic 'pencil in cup' sign
88
what are the less common manifestations of psoriatic arthritis?
- symmetrical arthritis
- sacroiliac and spinal inflammation
- oligoarthritis
- arthritis mutilans
89
what is arthritis mutilans?
bones around joint get completely dissolved
= telescoping of the digits
= shortened fingers, excess skin
(possible manifestation of psoriatic arthritis)
90
how is psoriatic arthritis investigated?
blood tests
- raised ESR + CRP
- lack of RF factor
imaging
- X-ray = 'pencil in cup' deformity
- MRI = sacroiliitis and enthesitis
91
how is psoriatic arthritis managed?
DMARDs (methotrexate)
| avoid oral steroids = cause pustular psoriasis
92
what classic feature is visible on an X-ray for psoriatic arthritis?
'pencil in cup' deformity
93
what is seen on a psoriatic arthritis MRI?
sacroiliitis and enthesitis
94
why are oral steroids avoided in psoriatic arthritis?
cause pustular psoriasis
95
what is reactive arthritis?
sterile inflammation of the joints secondary to an infection elsewhere in the body
primary infection is most commonly:
1) urogenital = chlamydia
2) gastrointestinal = salmonella, campylobacter
3) can also be due to HIV/Hep C
96
what possible pathogens cause reactive arthritis?
urogenital
- Chlamydia trachomatis
gastrointestinal
- Salmonella
- Shigella
- Campylobacter
HIV
hepatitis C
97
what are the extra-articular manifestations of reactive arthritis?
skin inflammation
eye inflammation
tendon inflammation (enthesitis)
98
what causes reactive arthritis?
genetic predisposition (HLA-B27) + environmental trigger (infection)
99
how is reactive arthritis treated?
condition is usually self-limiting
| can treat with DMARDs or NSAIDs
100
how is reactive arthritis different to septic arthritis?
septic = inflammation due to infection in the joint
reactive = inflammation due to infection elsewhere
101
SLE is a multi-system inflammatory disease - which parts of the body are affected?
kidney, lungs, skin, haematological features
102
what are antinuclear antibodies?
antibodies produced against nuclear components of the cell
= high sensitivity for SLE, but low specificity
103
what does a negative ANA indicate?
excludes the diagnosis of SLE
104
what does a positive ANA indicate and what is tested subsequently?
indicates SLE, only in the presence of other appropriate clinical signs
= anti-dsDNA tested for subsequently
105
what does anti-dsDNA indicate?
highly specific for SLE and can be used to monitor SLE progression
106
briefly explain the pathogenesis of rheumatoid arthritis
proliferation of the cells in the synovium to form an abnormal mass = pannus
due to
1) neurovascularisation
2) lymphangiogenesis
3) immune cell infiltrate
107
what is the term used to describe the structure that forms as a result of synovium proliferation in rheumatoid arthritis?
pannus
108
what is a pannus?
an abnormal proliferated mass (extra growth) that forms due to uncontrolled proliferation in the synovium
= leads to rheumatoid arthritis
109
within the inflammatory cell infiltrate, what causes cell recruitment, activation and effector functions?
inflammatory cytokine release
110
which type of cytokines are most active in rheumatoid arthritis: pro-inflammatory or anti-inflammatory?
pro-inflammatory
111
name the dominant pro-inflammatory cytokine in rheumatoid arthritis
TNFa
112
which three cell types does TNFa mainly affect in rheumatoid arthritis?
osteoclasts
synoviocytes
chondrocytes
113
how does TNFa affect osteoclasts?
activates osteoclasts
= increased bone resorption
= bone erosion
114
how does TNFa affect synoviocytes?
activates synoviocytes
= increased joint inflammation
= increased pain and swelling
115
how does TNFa affect chondrocytes?
= increased cartilage degradation
| = joint space narrowing
116
which cells produce TNFa in rheumatoid arthritis?
activated macrophages within the rheumatoid synovium
117
what is anti-TNFa?
monoclonal antibody that binds to and inactivates the inflammatory cytokine, TNFa
118
what are biological therapies?
proteins (usually antibodies) that specifically target another protein such as an inflammatory cytokine
119
what four biological therapies are available to treat rheumatoid arthritis?
1) inhibition of TNFa = influximab
2) B cell depletion (inactivating CD20) = rituximab
3) modulating T cell co-stimulation = abatacept
4) inhibition of IL-6 signalling = tocilizumab
120
which normal structural feature becomes pathological in rheumatoid arthritis?
synovium (i.e. synovial membrane)
121
in rheumatoid arthritis, which cells are found in the immune cell infiltrate preceding pannus formation?
activated T and B cells
activated macrophages
mast cells
plasma cells
