The Science of Rheumatoid Arthritis Flashcards
(37 cards)
1
Q
What is rheumatology?
A
Rheumatology = medial speciality that deals with patients with arthritis and other related conditions
2
Q
What is arthritis?
A
Arthritis = inflammation of a joint
3
Q
What is the clinical presentation of arthritis?
A
- Symptoms
- Pain
- Stiffness
- Swelling
- Functional impairment
- Systemic symptoms
- Signs
- Tenderness
- Swelling
- Restriction of movement
- Heat
- Red
- Systemic features
4
Q
What are examples of rheumatic diseases?
A
- RA
- Sero nergative arthritis
- Crystal arthritis
- Connective tissue diseases
- Systemic vasculitis
- Bone disease
- Osteoarthritis (most prevalent kind of arthritis)
5
Q
What does RA stand for?
A
Rheumatoid arthritis
6
Q
What is the most prevalent kind of arthritis?
A
Osteoarthritis
7
Q
What is rheumatoid arthritis?
A
Rheumatoid arthritis (RA) = chronic, autoimmune systemic illness characterised by a symmetrical peripheral arthritis and other systemic features
8
Q
What can RA be associated with?
A
- Joint damage
- Disability
- Premature mortality
9
Q
Describe how RA is classified?
A
Score of 6 or above is needed for classification of patient to deffinitely have RA:
- joint involvement
- serology
- acute-phase reactants
- duraction of symptoms
10
Q
What is the prevalence of RA?
A
1% of population
11
Q
What sex and age group does RA mostly affect?
A
- Females > males 3:1
- Age groups 4th and 5th decade
12
Q
What is the aetiology of RA?
A
- Genetic
- Genetic contribution estimated to be about 50%
- Closes association with specific amino acid sequences at positions 70-74 of DRB1
- Environment
- Smoking
- Chronic infection
- Such as periodontal disease
13
Q
Describe the pathology of RA?
A
- Synovitis
- Inflamed synovium
- Inflamed joint capsule
- Damages surrounding structures
- Cartilage
14
Q
What investigations are done for RA?
A
- Immunology
- Rheumatoid factor (IgG, IgM)
- Not used anymore
- Anti-cyclic citrullinated antibodies (anti CCP, ACPA)
- Rheumatoid factor (IgG, IgM)
- Imaging
- X-ray
- USS
15
Q
What antibodies are checked to diagnose RA?
A
- Anti-cyclic citrullinated antibodies (anti CCP, ACPA)
16
Q
What are the clinical features of RA?
A
- Symptoms
- Pain
- Stiffness
- Immobility
- Poor function
- Systemic symptoms
- Nonspecific – fatigue, weight loss, anaemia
- Specific – eyes, lungs, nerves, skin, kidneys
- Long term – CVS, malignancy
- Signs
- Swelling
- Tenderness
- Limitation of movement
- Redness
- Heat
17
Q
How many joints are usually inflammed in RA?
A
With RA usually more than 1 joint is inflamed, normally bilateral (symmetrical polyarthritis)
18
Q
How is the severity of RA assessed?
A
- Disease severity score (DAS)
-
www.das28.com
- DAS <2.4 represents clinical remission
- SAD >5.1 represents eligibility for biological therapy
-
www.das28.com
19
Q
What does DAS stand for?
A
Disease severity score
20
Q
What is the main concern in terms of the prognosis of RA?
A
- Massive impact on work
- About 33% stopped working within 2 years, 50% within 10 years
- 40 sick days per year instead of average 6.5
21
Q
What are the functions of a Synovium?
A
- maintenance of intact tissue surface
- lubrication of cartilage
- control of synovial fluid volume and composition (hyaluronan, lubricin)
- nutrition of chondrocytes within joints
22
Q
The Synovium consist of how many layers?
A
2-3 layers
- consist of two cell types
- Macrophages
- fibroblast
23
Q
Definition of RA
A
- The rheumatoid synovitis (pannus) is characterised by inflammatory cell infiltration, synoviocyte proliferation and neoangiogenesis
- The synovial fluid in the joint cavity contains neutrophils, particularly during acute flares of RA
- The synovial pannus causes bone and cartilage destruction (deformities)•
24
Q
What is Pannus?
A
- Inflammation and exuberant proliferation of the synovium leads to formation of pannus and destruction of cartilage, bone, tendons, ligaments, and blood vessels.
- Basically, the hypertrophied synovium is called pannus.
25
What auto-bodies are associated with RA?
RFs and anti-citrullinated protein antibodies
26
Can RA be detected before onset of clinical features?
* Evidence of autoimmunity can be present in RA many years before the onset of clinical arthritis
* Autoantibodies occur in RA that recognise either joint antigens, such as type II collagen, or systemic antigens, such as glucose phosphate isomerase
* The autoantibodies potentially can contribute to inflammation through several mechanisms, including activation of complement
27
How are the RA patients classified?
* Seropositive rheumatoid arthritis
* Rheumatoid factor
* Anti-citrullinated protein antibody (ACPA)
* Diagnostic anti-CCP assays recognise citrullinated self-proteins
* α-enolase, keratin, fibrinogen, fibronectin, collagen, vimentin
* Patients with ACPA+ disease have a less favourable prognosis
* * Seronegative rheumatoid arthritis
* not detectable
28
What is Seropositive Rheumatoid Arthritis?
* Seropositive rheumatoid arthritis will have detectable:
* Rheumatoid factor
* Anti-citrullinated protein antibody (ACPA)
* Diagnostic anti-CCP assays recognise citrullinated self-proteins
* α-enolase, keratin, fibrinogen, fibronectin, collagen, vimentin
* Patients with ACPA+ disease have a less favourable prognosis
*
29
What is Rheumatic Factor?
* It's an auto antibody to self IgG Fc and IgM
* but it's not very specific because rheumatoid factor can also be detected in other conditions, such as Sjogren's syndrome.
30
What genes plays a role in susceptibility to RA?
* Several genes are implicated in susceptibility to RA and severity of disease, including class II major histocompatibility complex genes and PTPN22
* Distinct genetic associations for ACPA-positive and ACPA-negative RA
31
What are the environmental factors for RA?
* Smoking and bronchial stress (exposure to silica)
* Infectious agents have been associated with RA
* Viruses (EBV, CMV)
* E. Coli
* Mycoplasma
* Periodontal disease (Porphyromonas gingivalis)
* Microbiome (gut microbes)
* Repeated insults in a genetically susceptible individual would lead to–Formation of immune complexes and rheumatoid factor (high-affinity autoAb against the Fc portion of Ig)
* Altered citrullination of proteins and breakdown of tolerance, with resulting ACPA response
32
What is Citrullination?
* Citrullination (or deimination) is the conversion of the amino acid arginine in a protein into the amino acid citrulline.
* Enzymes called peptidylarginine deiminases (PADs) replace the primary ketimine group (=NH) by a ketone group (=O).
33
What happens in abnormal Citrullination?
* abnormal citrullination results in auto antigens to be no longer be recognised as self antigens,
* therefore triggering an immune mediated response.
34
What are the key features to be found in Synovitis?
* Villous hyperplasia
* Infiltration of T cells, B cells, macrophages and plasma cells
* Intimal cell proliferation (fibroblasts)
* Production of cytokines and proteases
* Increased vascularity
* Self-amplifying process
35
What cytokines perpetuate synovial Inflammation?
TNF-α, IL-6, IL-1, IL-15, IL-18, IL-23 *etc*. perpetuate synovial inflammation
36
How does Neo-angiogenesi affect RA?
* Provides nutrients to the hyperplastic synovium
* Hypoxic conditions and angiogenic factors such as IL-8 and VEGF enhance blood vessel proliferation in the synovium
* Microvascular endothelia in the synovium express adhesion molecules that guide circulating cells into the joint under the influence of chemoattractants
* All of this further amplify inflammation
37
What is responsible for cartilage and bone destruction?
* Bone- Osteoclasts
* Cartilage- Fibroblast (releases an enzyme call metalloproteinases)
