Rheumatoid arthritis Flashcards
What are the functions of synovial fluid?
1) Metabolite exchange medium
2) Lubricant for synovial joints
What are the four theories of autoimmunity?
1) Defects in regulatory T cells
2) Molecular mimicry between pathogens and self-peptides
3) Polyclonal activation of B cells during immune responses or infection ( EBV) recognition of self antigens
4) Sequestered antigen not seen by developing T and B cells so –> seen as foreign antigen (e.g. sperm)
What is the HLA associated with ankylosing spondylitis?
HLA-B27
What is the HLA associated with diabetes mellitus type 1?
HLA-DQ2/DR3
What is the HLA associated with rheumatoid arthritis?
HLA-DR4
What is the HLA associated with multiple sclerosis?
HLA-DR2
What is the HLA associated with coeliac disease?
HLA-DQ2
What would be some features in the clinical history of someone with RA?
- Often young-middle age females (20-50 years)
- Pain and stiffness in joints
- Gradual or sudden onset
- Usually symmetrical, Hands, feet, other joints
- Often a family member has RA
- Smoking increases risk of developing RA
What are some systemic symptoms of RA?
- Systemic: fatigue, anorexia, weight loss
- Low grade fever, anaemia
- Articular- joint aching and stiffness
What are some hand deformities found in RA?
1) Early fusiform swelling
2) Ulnar deviation / MCP subluxation
3) Swan neck deformities
4) Boutonniere deformities
What are some extra-articular manifestations of RA?
Cardiac: pericarditis, valve problems, atherosclerosis –> IHD & CVA
Pulmonary: pleural effusions, rheumatoid nodules, pulmonary fibrosis
Blood: anaemia of chronic disease, splenomegaly (Felty’s syndrome)
Bones: osteoporosis (localised)
Skin: rheumatoid nodules, vasculitis, leg ulcers
Neurological: C1/C2 atlanto-axial subluxation, nerve compression
Eyes : scleritis, xerophthalmia
(2° Sjögren’s syndrome)
Describe the pathogenesis of RA
Autoimmune: circulating autoantibody –rheumatoid factor in ~80% (seropositive arthritis). This complexes to IgG to form immune complexes found in joint synovium, fluid and elsewhere.
Wayward immune response causes synovial inflammation
Recruitment of PMNs, macrophages and lymphocytes
Phagocytosis of immune complexes and release of lysosomal enzymes
Destruction of joint cartilage and recruitment of further inflammatory cells
Vasodilation causes redness and swelling
Hyperplasia of synovium and angiogenesis: vascular granulation tissue – pannus
Inflammatory cells in pannus destroy cartilage and bone and cause ankylosis (stiffening and fusion)
If RA is untreated, what can happen to the joints?
Loss of cartilage Erosion of bone Damage to joint capsule- Subluxation of joint Deformities
What are some lab features of RA?
Haematological anaemia thrombocytosis Hepatic increased alkaline phosphatase decreased albumin Acute phase response increased ESR / CRP
Immunology
Rheumatoid factor (RF) : raised in ~70% of cases
(and in some healthy people)
Anti-CCP: positive in ~60% patients with RA
Positive anti-nuclear antibodies (ANA) are also common in RA patients
What would you see in an X-ray of RA hands and feet
soft tissue swelling juxta-articular osteopenia joint space narrowing erosions subluxation Deformity Periarticular osteopenia
