The Science of Rheumatoid Arthritis Flashcards
What is rheumatology?
Rheumatology = medial speciality that deals with patients with arthritis and other related conditions
What is arthritis?
Arthritis = inflammation of a joint
What is the clinical presentation of arthritis?
- Symptoms
- Pain
- Stiffness
- Swelling
- Functional impairment
- Systemic symptoms
- Signs
- Tenderness
- Swelling
- Restriction of movement
- Heat
- Red
- Systemic features
What are examples of rheumatic diseases?
- RA
- Sero nergative arthritis
- Crystal arthritis
- Connective tissue diseases
- Systemic vasculitis
- Bone disease
- Osteoarthritis (most prevalent kind of arthritis)
What does RA stand for?
Rheumatoid arthritis
What is the most prevalent kind of arthritis?
Osteoarthritis
What is rheumatoid arthritis?
Rheumatoid arthritis (RA) = chronic, autoimmune systemic illness characterised by a symmetrical peripheral arthritis and other systemic features
What can RA be associated with?
- Joint damage
- Disability
- Premature mortality
Describe how RA is classified?
Score of 6 or above is needed for classification of patient to deffinitely have RA:
- joint involvement
- serology
- acute-phase reactants
- duraction of symptoms
What is the prevalence of RA?
1% of population
What sex and age group does RA mostly affect?
- Females > males 3:1
- Age groups 4th and 5th decade
What is the aetiology of RA?
- 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
Describe the pathology of RA?
- Synovitis
- Inflamed synovium
- Inflamed joint capsule
- Damages surrounding structures
- Cartilage
What investigations are done for RA?
- Immunology
- Rheumatoid factor (IgG, IgM)
- Not used anymore
- Anti-cyclic citrullinated antibodies (anti CCP, ACPA)
- Rheumatoid factor (IgG, IgM)
- Imaging
- X-ray
- USS
What antibodies are checked to diagnose RA?
- Anti-cyclic citrullinated antibodies (anti CCP, ACPA)
What are the clinical features of RA?
- 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
How many joints are usually inflammed in RA?
With RA usually more than 1 joint is inflamed, normally bilateral (symmetrical polyarthritis)
How is the severity of RA assessed?
- Disease severity score (DAS)
-
www.das28.com
- DAS <2.4 represents clinical remission
- SAD >5.1 represents eligibility for biological therapy
-
www.das28.com
What does DAS stand for?
Disease severity score
What is the main concern in terms of the prognosis of RA?
- 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
What are the functions of a Synovium?
- maintenance of intact tissue surface
- lubrication of cartilage
- control of synovial fluid volume and composition (hyaluronan, lubricin)
- nutrition of chondrocytes within joints
The Synovium consist of how many layers?
2-3 layers
- consist of two cell types
- Macrophages
- fibroblast
Definition of RA
- 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)•
What is Pannus?
- 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.
What auto-bodies are associated with RA?
RFs and anti-citrullinated protein antibodies
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
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
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
*
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.
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
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
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).
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.
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
What cytokines perpetuate synovial Inflammation?
TNF-α, IL-6, IL-1, IL-15, IL-18, IL-23 etc. perpetuate synovial inflammation
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
What is responsible for cartilage and bone destruction?
- Bone- Osteoclasts
- Cartilage- Fibroblast (releases an enzyme call metalloproteinases)
