Signs, Symptoms & RFs

• What is the genetic risk factor of RA?

  HLA-DRB1 gene shared epitope
• How does anti-CPP lead to an increased risk of RA?

  Recognises & attacks modified proteins containing citrulline (e.g. fibrin, collagen & keratin) in synovial joint
• What are the clinical signs of rheumatoid arthritis?

  Pain & swollen joints

  Morning stiffness (1 hour or more)

  Joint deformities (e.g. swan neck, Boutonniere's)

  Rheumatoid nodules

  Dry eyes

  Chest pain
• What are the risk factors for RA?

  Genetics (HLA-DRB1/4)

  Women

  Age (30-50)

  Stress

  Antibodies (RF & anti-CPP)

  Environmental factors (smoking, obesity)
• Why do people with RA have joints that feel spongy?

  Caused by pannus (abnormal tissue that develops due to excess inflammation)

  Pannus leads to painful arthritis symptoms
• Why is fatigue a prominent symptoms for patients with an inflammatory condition?

  Disturbed sleep - due to pain

  Active inflammation

  Anaemia of chronic disease or iron-deficiency anaemia -> common if taking NSAIDs

  Side effects of other medication
• What is tenosynovitis & how is it seen on ultrasound?

  Inflammation of tendon & its synovial sheath

  Characterised by increased vascularity -> can extend into tendon sheath & oedema
• Why do people with RA get lung issues?

  Direct effect of RA on lungs

  Adverse effects of RA treatment

  Chest infection due to RA or from immunosuppressants
• How does HLA-DR4 increase the risk of RA?

  HLA-DR4 has a peptide binding groove which is more accepting of citrullinated antigens

  So AP cells present citrullinated proteins -> SR T cells bind to citruillinated protein being presented -> immune response triggered

  SR B cell also binds to citrullinated proteins -> T follicular cell co-stimulates B cell -> production of antibodies against citruillinated proteins (ACPA)
• What is citrullination?

  Post-translational modification of proteins, specifically the conversion of arginine residues to citrulline.

  Makes altered self more likely to get an immune response against it
• How does smoking increase the risk of RA?

  Drives inflammation

  May be involved in the initial break of tolerance

  Theory that smoking may lead to increased citrullination
• What are the complications of RA?

  Septic arthritis

  Amyloidosis
• What is amyloidosis?

  Systemic disorder of protein folding -> progressive organ dysfunction & death
• What causes painful & swollen joints in RA?

  Active inflammation in synovium
• What causes morning stiffness in RA?

  Active inflammation in synovium
• What causes joint deformities in RA?

  Due to secondary damage caused by pannus invading cartilage & bone
• What are 2 typical joint deformities in RA?

  Ulnar deviation

  Swan-neck deformities
• Give 5 non-articular manifestations of RA.

  Pericarditis

  Dry eyes

  Anaemia

  Pleural effusion

  Splenomegaly
• Why do you get non-articular manifestations in RA?

  Systemic symptoms may be due to presence of circulating cytokines (TNF-a)
• What is septic arthritis?

  Joint infection

  Serious complication

  Medical emergency

  Significant morbidity & mortality
• What are the typical signs of septic arthritis?

  Young people - red, hot, swollen & agonisingly painful joint

  Elderly/immunosuppressed pts - may be present with lack of systemic symptoms
• What is the treatment of septic arthritis?

  Systemic antibiotics