Rheumatoid arthritis Flashcards
Define autoimmune disease
Disease when one’s own body produces an inappropriate response against its own cells.
Define ‘rheumatoid arthritis’
It is a chronic inflammatory disease driven by failure of self-tolerance leading to immune response against self-antigens in joint.
What are the causes of RA?
Still unknown but there are some theories.
Genetic -> HLA Class 2 association (HLA-DRB1 “shared epitopes”):
- Class 2 MHC proteins are made of two heterodimers (DRB and DRA)
- Gene DRB1 encodes for part of the DRB dimer
- “Shared epitope” = alleles that share an amino acid sequence
- Two alleles of DRB1 are “shared epitopes” and are strong genetic risk for RA.
Environmental:
- smoking
- periodontitis
- Severe disease, resulting in elevated cyclic citrullinated peptides (CCP) or rheumatoid factor (RF)
- Microbiome
Epigenetic modifications Post-translational modifications Abnormal T-cell activation Abnormal B cell responses: - Elevated anti-CCP antibodies - Elevated RF proteins
Incidence rates of RA?
- Most common chronic inflammatory joint disease (1% of population)
- Females 3 times more likely
- Onset increases with age
Describe acute changes in pathogenesis of RA
- Increased vascular flow/pressure to synovial cavity: oedema, fibrin accumulates
- Endothelial activation: Adhesion molecules expressed, leukocytes leak into synovial cavity
- Vascular proliferation (esp. high endothelial venules)
- Giant cells form in synovial membrane from fibroblasts and macrophages:
1) replication of fibroblasts (type B synoviocytes) in synovial membrane
2) recruitment of macrophages (Type A synoviocytes) - Tissue proliferation to 5+ layers thick: forms pannus
- All immune cells are present (Neutrophils in synovial, B cell since clusters)
Describe chronic changes in RA
- Continuation of acute changes
- Biological changes: reduced apoptosis of synoviocytes , degradation of tissue (Activation of osteoclasts and cartilage breakdown enzymes)
- Formation of synovial pannus -> heaping up of synovial tissue into mounds
- Erosion of cartilage and bone
- X-ray: shows joint narrowing, juxta-articular osteopenia (low bone density next to joint)
Explain the mechanism involved in generation of pannus and destruction of bone and cartilage
Pannus = folded mass of synovial tissue caused by proliferation and recruitment of various cells:
- inflammatory cells
- granulation tissue
- Fibroblast that secrete proteolytic enzymes.
Cells in pannus release enzymes and cytokines that leads to the breakdown of cartilage and bone in the joint cavity.
Describe the clinical onset of RA
- Early morning stiffness (unlike OA)
- 3+ joints affected
- Inflammation -> red, swollen, painful joints with limited movement
- Most common clinical pattern: alternating periods of activity and quiescence
- Bilaterally affects joints (unlike OA)
- can cause osteoporosis
- Affected joints:
1) proximal finger joints: metacarpo-phalangeal joints, proximal interphalangeal joints
2) upper limb joints
3) Lower limb joints
4) TMJ
5) Metatarsophalangeal joints
6) Only affects spine at C1-C2 - Affected joints will have major deformities
Describe diagnosis of RA
- multiple joints presented
- presence of Anti-CCP antibodies (best predictor)
- Presence of Rheumatoid factor (high false positive rates - present in many other diseases)
- Raised erythryocyte sedimentation rate (ESR) - rate which RBC settles; general test for inflammation
- Raised C-reactive protein (CRP) - non-specific marker of inflammation
List systemic signs/symptoms of RA
- RA is a systemic disease -> infection spread to other tissues
- Weight loss, anorexia, fever, and fatigue
- Anaemia
- Osteoporosis
- Muscle wasting
List extra-articular manifesetations:
- Rheumatoid nodules -> large bumps at friction/pressure areas (not common)
- Granulomatous lesions in other tissue: lungs -> pleuritis, heart -> pericarditis, eye: scleromalacia performans (inflammation and rupture of sclera), sicca syndrome (dry eyes and mouth)
- Vasculitis: Felty’s syndrome - long standing RA:
1) neutropenia
2) leg ulcers
3) recurrent infection - Nail fold infarcts
Describe the oral manifestations of RA e.g. of the TMJ, oral lesions
- TMJ can be affected with limited jaw movement (~17%)
- complications with drug management
- Cervical vertebrae dislocation in dental chair due to weakened neck ligaments
- Oral lesions due to RA medication
What is the gold standard for RA treatment?
Methotrexate
- Anti-proliferative and immunosuppressant
- Inhibits dihydrofolate reductase, thus inhibiting folic acid activation
- Synthetic DMARD
- Weekly dose
- Side effects: mouth ulcer, abnormal liver function, increased risk of infection
