Rheumatoid Arthritis 2a Flashcards
Describe symptoms of RA [5]
Slowly progressive, SYMMETRICAL swollen, painful and stiff:
* MCP
* PIP
* Metatarsophalangeal (MTP) of the feet
* Wrists, elbows, shoulders, kness and ankles
Morning stiffness lasting MORE than 30 minutes
Joints swollen, tender and WARM
Movement limitation and muscle wasting
Tenosynovitis - inflammation of tendons
Describe 5 extra-articular manifestations of RA:
Lungs [6]
Eyes [3]
Neurological [3]
Skin [1]
Haemotological [1]
(not in lecture)
Lungs:
* Pleural effusions, fibrosing alveolitis, pneumoconiosis (Caplan’s syndrome, especially in miners), interstitial lung disease, bronchiectasis
Eyes:
- Dry eyes, episcleritis (non severe mild redness of eyes), scleritis (severe pain, can’t look at bright lights)
Neurological:
* Peripheral sensory neuropathies
* Compression/entrapment neuropathies - soft tissue swelling due to inflammation at site where rigid structures contain nerves i.e. wrist and elbow e.g. carpal tunnel (median nerve) syndrome
* **Cord compression **- due to instability of the cervical spine, occurs in severe RA, presents with sensory loss, weakness and disturbed bladder function
Skin:
- Subcutaneous nodules
Blood:
- * Normochromic normocytic ANAEMIA
Describe 3 specifc hand defomities seen in RA [3]
Hand deformities:
* Ulnar deviation
* Swan neck/Z thumb
* Boutonniere deformity
Which of these joints would you least likely see swollen & painful joints in RA?
metacarpophalangeal (MCP)
Metatarsophalangeal (MTP)
proximal interphalangeal (PIP)
distal interphalangeal (DIP)
Which of these joints would you least likely see swollen & painful joints in RA?
metacarpophalangeal (MCP)
Metatarsophalangeal (MTP)
proximal interphalangeal (PIP)
distal interphalangeal (DIP)
State 5 aetiolgoical causes of RA? [7]
Multifactoral:
Genetics
Environmental
Smoking
Infection
Gut biome infections
Obesity
Stress
Female
Which HLA variation is most associated with RA? [1]
HLA DR4
State and explain the two different subclasses of RA [2]
- Which populations are they more common in? [1]
- Which type of infection are each more common with? [1]
- Which HLA types are more risky for each?
Describe the factors that cause each [4] & [3]
Seropostive (ACPA positive): more common
* Smokers
* Bacterial infections
* HLA DRB1 alleles
* PTPN22
Seronegative (ACPA negative)
* Viral Infections:EBV, cytomegalovirus
* HLA-DR risk alleles
* Contribution of HLA alleles much lower and different (HLA-DR3)
* IRF5 = human interferon regulatory factor-5: Mediates virus induced immune response
Describe the prognosis of seropositive (ACPA positive) RA (compared to seronegative) [3]
Seropostive:
* More CV complications
* More joint destruction
* Higher death rate
What type of infection is Seropositive (ACPA positive) driven by? [1]
What type of infection is Seronegative (ACPA negative) driven by [1]
Seropositive (ACPA positive)
* driven by bacterial infections (amongst other factors): neutrophils invasion
Seronegative (ACPA negative):
* Driven by viral infections
Describe how the onset of RA often occurs [1]
Can have predisposition but acute triggers can trigger RA (e.g. pregnancy; adverse life events; trauma)
Explain the process of NETosis in the initiation of RA [3]
- Ca2+ dependent
- Bacterial stimulus attracts neutrophils
- Neutrophils release NET fibres (made from DNA) that entrap microorganism: forms a scaffold for enzymes, peptides etc. High concentrations kill microbes.
- Results in neutrophils dying / suicidal NETosis
State a key enzyme found in NETosis net [1]
DNA associated with proteins citrullinated by protein-arginine deiminase 4 (PAD4)
What is the normal role of protein-arginine deiminase 4 (PAD4)? [1]
What effect does PAD4 have when found in NETosis net? [1]
PAD4 citrullinates (arginine to citrulline) histones promoting chromatin decondensation.
Found in NETosis net: acts as antigen - antibodies come and causes further inflammation
Describe the effect of bacterial infection and smoking have on ACPAs [1]
Where? [1]
Increase ACPA; outside of joint
The real problem occurs when the ACPAs are inside the joint
Which type of cells are the most abundant in synovial fluid of RA patients? [1]
Neutrophils - multi lobular (up to 7)
Rheumatoid factor is found on which Ig
IgG
IgA
IgM
IgD
IgE
Rheumatoid factor is found on which Ig
IgG
IgA
IgM
IgD
IgE
Rheumatoid factor is found on IgM and binds to Fc portion of
IgG
IgA
IgM
IgD
IgE
Rheumatoid factor is found on IgM and binds to Fc portion of
IgG
IgA
IgM
IgD
IgE
RF autoantibodies do not seem to play a major pathogenic role
State the predictive factor of anti-citrullinated peptide antibodies [1] vs the predictive factor of rheumatoid factor? [1]
ACPA:
* 98% specific for RA
* 80% sensitivity for RA: used diagnostically
RF:
* Found in 60-80% in patients; but one of the last autoantibodies to be produced in RA so poor predictive factor
State the predictive factor of rheumatoid factor? [1]
Found in 60-80% in patients; but one of the lasts of autoantibodies to be produced in RA so poor predictive factor
RA
Describe which specific joints are effected in swan neck deformity [1] and boutonniere deformity? [1]
Swan neck deformity: the PIP joint is hyperextended with flexion at the distal interphalangeal (DIP) joint.
In a boutonniere deformity, there is flexion the PIP joint with hyperextension of the DIP joint
