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)
