Rheumatoid And Other Inflammatory Arthritis Flashcards
1
Q
What are tendons?
A
Cords of strong fibrous collagen tissue attaching muscle to bone
2
Q
What are ligaments?
A
Flexible fibrous connective tissue which connect two bones
3
Q
What are the three key components of an synovial joint?
A
Articular capsule
Synovial membrane
Synovial fluid
4
Q
What does synovium contain?
A
Macrophage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
Type 1 collagen
5
Q
What are type A synoviocytes
A
Macrophage-like pahogocytic cells
6
Q
What are type 2 synoviocytes?
A
Fibroblast-like cells that produce hyaluronic acid
7
Q
What type of fluid is synovial fluid, and what is it rich in?
A
Viscous fluid, rich in hyaluronic-acid
8
Q
What type of collagen is articular cartilage composed of?
A
Type 2 collagen
9
Q
What are the two components of articular cartilage?
A
Type 2 collagen and proteoglycans (aggrecan)
10
Q
What is arthritis?
A
Disease of the joints
11
Q
What are the two major divisions of arthritis?
A
Osteoarthritis (degenerative arthritis)
Inflammatory arthritis
12
Q
What are two common features of osteoarhritis as seen on an x-ray?
A
Lack of joint space indicating loss of articular cartilage
Bony spurs (osteophyte)
13
Q
What are the three causes of joint inflammation?
A
Infection
Crystal arthritis
Immune-mediated
14
Q
What are two examples of crystal arthritis?
A
Gout, pseudo gout
15
Q
What are three examples of immune mediated joint inflammation?
A
Rheumatoid arthritis
Seronegative spondyloarthropathies
Connective tissue disease
16
Q
List two examples of infective joint inflammation
A
Septic arthritis, TB
17
Q
Which of the three types of joint inflammation is due to primary inflammation?
A
Immune-mediated
18
Q
Which two types of joint inflammation are caused by secondary inflammation in response to a noxious unit?
A
Infection
Crystal arthritis
19
Q
Which type of joint inflammation is non-sterile?
A
Infective
20
Q
What causes septic arthritis?
A
Bacterial infection of a joint - usually spread from the blood
21
Q
What are the risk factors associated with septic arthritis?
A
Immunosupression, pre-existing joint damage, intravenous drug use
22
Q
Why is septic arthritis a medical emergency?
A
If left untreated can rapidly destroy a joint
23
Q
What is inflammation?
A
A physiological response to deal with injury or infection
24
Q
What are the four manifestations of inflammation?
A
Rubor, calor, Dolor, tumour
Rubor = red, calor = heat, dolor = pain, tumor = swelling
25
What physiological changes occur in response to inflammation?
Increased blood flow
Migration of white blood cells into the tissues
26
What cellular changes occur as a response to inflammation?
Activation or differentiation of leukocytes
27
What molecular changes occur as a result of inflammation?
Cytokine production: TNF-alpha, IL1, IL6, IL17
28
Outline the clinical presentation of septic arthritis?
Acute red, hot, painful swollen joint
Usually only 1 joint is affected (mono arthritis)
Fever, patient often systemically unwell
29
Consider septic arthritis in any patient with …….
An acute painful, red, hot, swelling of a joint, especially is there is fever
30
How is septic arthritis diagnosed?
By joint aspiration, followed by sending sample for urgent gram stain and culture
31
What organisms commonly cause septic arthritis?
Staph.a , streptococci, gonococcus
32
What is different about septic arthritis that is caused by a gonococcus infection?
It often affect many joints (poly arthritis)
It is less likely to cause joint destruction
33
How is septic arthritis treated?
Surgical wash out (lavage) and intravenous antibiotics
34
What causes gout?
Deposition of monosodium urate (MSU)crystals in/around joints leading to inflammation
35
What risk factors are associated with gout?
Hyperuricaemia- high Uric acid levels
36
What causes hyperuricaemia?
Genetic tendency
Increased intake of purine rich foods
Increased cell turnover - chemotherapy
Reduced excretion - kidney failure
Increased alcohol intake
37
What causes pseudogout?
Deposition of calcium pyrophosphate dihydrate (CPPD) crystals leading to inflammation
38
What risk factors are associated with pseudogout?
Background osteoarthritis, elderly patients, inter current infection
39
What does the tissue deposition of MSU crystals lead to?
Gouty arthritis and/or Tophi (aggregated deposits of MSU in tissue)
40
Where do Tophi often develop?
Around hands, feet, elbows, ears
41
What are the clinical features of gout?
Abrupt onset, usually mono arthritis, joint red, warm, swollen and tender
42
Gouty arthritis most commonly affects which joint?
1st metatarsophalangeal joint of big toe - hallux
43
How is gout resolved?
Resolves spontaneously over 3-10 days
44
How does gout present on an x-ray?
Damage to joint - erosions
45
What is the key investigation for any acute mono arthritis?
Septic joint
46
What investigations are done in the diagnosis of gout - determining wether is gout or pseudogout
Needle inserted into joint and fluid aspirated - send to lab for microbiology and polarising light microscopy
47
What is the difference in shape and birefringence seen in gout vs pseudogout?
Gout = needle shape and negative birefringence
Pseudogout = brick shaped and positive birefringence
48
When assessing arthritis what are the key history and examination points?
Speed of duration
Worse or better with movement
Prolonged morning stiffness?
No. Of joints
Spinal involvement
Signs of inflammation
49
How is gout managed in an acute attack?
Colchine, NSAIDS, steroids
50
How is chronic gout managed?
Allopurinol
51
How does allopurinol work?
Inhibits xanthine oxidase
Decreases uric acid production and decreases uric acid deposits in kidney
52
What type of disease is RA?
Chronic autoimmune disease
53
What is the primary site of pathology in RA?
Synovium
54
What is synovitis?
Inflammation of the synovial membrane
55
Where are synovium found?
Synovial joints, tenosynovium surrounding tendons, bursa
56
What abnormality of the hand is characteristic of extensor tenosynovitis?
Incomplete extension of little and ring fingers
57
How does the synovial membrane change in RA?
Synovium becomes a proliferated mass of tissue (pannus)
58
What causes the synovium to become a proliferated mass of tissue (pannus) as seen in RA?
-Neovascularisation
> Lymphangiogenesis
> inflammatory cells:
- activated B and T cells
- plasma cells
- mast cells
- activated macrophages
59
Recruitment, activation and effector functions of inflammatory cells in RA is controlled by what?
Cytokine network - cytokine imbalance
60
Does RA effect more men or women?
Women, 2:1 ratio
61
The onset of RA is often at what age?
30-50s
62
What are the key features of RA?
Poly arthritis
Pain, swelling and early morning stiffness
May lead to joint erosions on radiographs
63
Which cytokine is dominant in the pathogenesis of RA?
TNF-alpha
64
What is the name of the TNF-a inhibitor medication used in RA?
How does it work?
Inflixumab
TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
65
What are the actions of TNF-a in RA?
cytokine tumour necrosis factor-alpha (TNFα) is the dominant pro-inflammatory cytokine in the rheumatoid synovium • pleotropic actions are detrimental in this setting: • causes other inflammatory processes > other pro-inflammatory cytokines released like IL-1, IL-6 > osteoclast activation > angiogenesis > chondrocyte activation • leads to the symptoms of rheumatoid arthritis: > bone erosion, pain, swelling, joint space narrowing
66
What is the strongest genetic risk factor for RA?
HLA-DR
67
What are the environmental risk factors associated with RA?
Smoking
Poor oral health
Porphyromonas gingivalis
68
What are the most common affected joints in RA?
> Metacarpophalangeal joints (MCP)
> Proximal interphalangeal joints (PIP)
> Wrists, Knees, Ankles
> Metatarsophalangeal joints (MTP)
69
What are the common extra-articular features associated with RA?
Fever, weight loss
Subcutaneous nodules
70
What are the uncommon extra-articular features of RA?
• vasculitis • Ocular inflammation e.g. episcleritis • Neuropathies • Amyloidosis • Lung disease - nodules, fibrosis, pleuritis • Felty's syndrome - triad of splenomegaly, leukopenia and rheumatoid arthritis
71
What are subcutaneous nodules?
Feature of RA
• Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
72
What is the most common site of subcutaneous nodules in RA?
Elbows
73
Subcutaneous nodules are associated with_____
Severe disease
Extra-articular manifestations
Rheumatoid factor
74
Rheumatoid factor is an autoantibody against which classification of antibody?
IgG
75
What are the features of a healthy synovial membrane?
Healthy synovial membrane
• 1 to 3 cell layer that lines synovial joints
• Contains macrophage-like (type A synoviocyte) and fibroblast-like (type B synoviocyte) cells and type I collagen
• Functions include the maintenance of synovial fluid, the hyaluronate-rich viscous fluid within joint space
76
Which type of arthritis: rheumatoid arthritis, osteoarthritis, septic arthritis, can cause anaemia?
RA
77
Which type of arthritis: rheumatoid arthritis, osteoarthritis, septic arthritis, can cause an increase in RBC MCV?
None
78
Which type of arthritis: rheumatoid arthritis, osteoarthritis, septic arthritis, can cause an increase in white blood cells (leucocytosis)
Septic arthritis
79
Which type of arthritis: rheumatoid arthritis, osteoarthritis, septic arthritis, can cause an increased platelet count?
RA and septic arthritis
80
Which type of arthritis: rheumatoid arthritis, osteoarthritis, septic arthritis, can cause a high ESR?
Usually in RA, sometimes in septic
81
Which type of arthritis: rheumatoid arthritis, osteoarthritis, septic arthritis, causes an increased CRP?
RA and septic arthritis
82
Which portion of the IgG does Rheumatoid factor recognise as its antigen?
Fc portion
83
what type of antibody are rheumatoid factor?
Typically IgM
84
What are the two key antibodies in RA?
Rheumatoid factor and ACPA - antibodies to citrullinated protein antigens
85
Citrullination of peptides is mediated by enzymes termed:
Peptidyl arginine deiminases (PADs)
86
What change do PADs enzymes cause?
Arginine to citrulline
87
ACPAs predate first clinical symptoms of RA by a median of how many years?
4.5
88
What are the radio graphic features of RA?
Soft tissue swelling
Peri-articular osteopenia
Bony erosions - in established disease
89
Is an x-ray or ultrasound better for detecting synovitis?
Ultrasound
90
What are the US changes seen in RA?
Synovial hypertrophy
Increased blood flow - Doppler signal
91
What is the treatment goal for RA?
Prevent joint damage
92
In order to prevent damage in RA, what is required?
Early recognition and diagnosis
Prompt initiation of treatment
aggressive pharmacological treatment
93
What is the drug treatment for RA?
Disease-modifying anti-rheumatic drugs ('DMARDs') = drugs that control the disease process
1st line treatment: - methotrexate in combination with hydroxychloroquine or sulfasalazine
2nd line treatment: - Biological therapies offer potent and targeted treatment strategies
94
What is the mechanism of methotrexate?
Inhibits dihydrofolate reductase
95
what are the side effects associated with methotrexate?
Nausea
Hair loss
Fall in WCC
Abnormal liver function
Pneumonitis
Infection risk
96
What are the four aims of use of biological therapies in RA?
Inhibition of TNF-a
B cell depletion
Modulation of T-cell co-stimulation
Inhibition of IL-6 signalling
97
What biologic is used for B cell depletion in RA
Rituximab - antibody against CD20
98
What biologic is used for modulation of T cell co-stimulation in RA?
Abatacept
99
What is psoriasis?
An immune-mediated disease affecting the skin with characteristic scaly red plaques on extensor surfaces
100
Why is psoriatic arthritis seronegative?
Rheumatoid factors are not present
101
What is the dominant pathogenic pathways in psoriatic arthritis?
IL-17/IL-23
102
What is reactive arthritis?
Sterile inflammation in joints following infection elsewhere in the body
103
What are the common infections that cause reactive arthritis?
Urogenital - chlamydia trachomatis
Gastrointestinal - salmonella . Shigella
104
What are the important extra-articular manifestations of reactive arthritis?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
105
Reactive arthritis can be the first manifestation of what two diseased?
HIV or hepatitis C
106
Reactive arthritis commonly efffects young adults with _______
Genetic predisposition (HLA-B27) and environmental trigger
107
Symptoms of reactive arthritis follow how many weeks after infection?
1-4 weeks
108
What are the key differences between septic arthritis and reactive arthritis?
Synovial fluid culture - positive in septic
Antibiotic therapy - yes for septic
Joint lavage - yes for septic for large joints
109
What is an example of inflammatory spondyloarthritis?
Ankylosing spondylitis (AS)
110
What is ankylosing spondylitis?
Inflammation of the spine and sacro-iliac joints
Can also effect peripheral joints (entheses)
111
Ankylosing spondylitis is associated with which gene?
HLA B27
112
What is the presentation of ankylosing spondylitis?
• Lower back pain + stiffness
- Early morning
- Improves with exercise
• Reduced spinal movements
• Peripheral arthritis
• Plantar Fasciitis, Achilles Tendonitis
• Fatigue
• Back pain >3 months, <45 years is suggestive of possible Ank Spond
113
What is seen in the bloods of someone with ankylosing spondylitis?
Normocytic anaemia
Raised CRP and ESR
114
What is seen in the imaging of someone with ankylosing spondylitis?
Squaring vertebral bodies
romanus lesion
Erosion, sclerosis , narrowing SIJ
Bamboo spine (fusing together)
Bone marrow oedema
115
What management is used for ankylosing spondylitis?
Physiotherapy NSAIDs
116
What are the three seronegative spondyloarthropathies?
Ankylosing spondylitis
Psoaritic arthritis
Reactive arthritis
117
Subchondral sclerosis with osteophytes affecting the DIPJ is a classic presentation of what?
Osteoarthritis
118
loss of joint space in MCPJs with erosion and osteopenia are features of___
Rheumatoid arthritis
