Rheummatoid Arthritis Flashcards
General RA
- Chronic Systemic Inflammatory
- Many Tissues Affected
- Inflammatory Synovitis –> Articular Cartilage Destruction and Ankylosis
- Autoimmunity?
Gender RA
Women 3-5x more often
Morphology - RA - Joints
Synovium - Edematous, Thickened, Hyperplastic, Covered by Delicate Bulbous Fronds
Histology - RA - Joints
- Infiltration of Synovial Stroma (CD4+ T-Helper, B cells, Plasma Cells, Dendritic Cells, Macrophages)
- Increased Vascularity
- Rice Bodies - aggregation of organizing fibrin
- Neutrophil Accumulation
- Osteoclastic Activity
- Pannus Formation
What is a Pannus?
Mass of synovium and synovial stroma consisting of inflammatory cells, granulation tissue, and synovial fibroblasts
Pannus –> Fibrous Ankylosis –> Bony Ankylosis
Morphology - RA - Skin
Rheumatoid Nodules
- Most common cutaneous lesion
- Located in regions of skin subject to pressure
- Arise in SubQ tissue
Histology - RA - Skin - Rheumatoid Nodule
Central Zone of Fibrinoid Necrosis surrounded by a prominent rim of epithelioid histiocytes
Morphology - RA - Blood Vessels
Who at Risk? - Severe Erosive Disease - Rheumatoid Nodules - High Titers of Rheumatoid Factor Affects MEDIUM to SMALL arteries Kidneys NOT involved Obstruction of VASA NEVORUM/DIGITAL ARTERIES --> Nueropathy, Ulcers, Gangrene
Pathogenisis - RA - General
Exposure of a genetically susceptible host to an arthritogenic antigen –> Chronic Inflammatory Reaction
It is the CONTINUING AUTOIMMUNE REACTION - activation of
- CD4+ Helper T Cells, Inflammatory Mediators, Cytokines - that ultimatley destroys the cell
Pathogenisis - RA - Genetic Susceptibility
HLA-DRB1 - Antigen Binding Cleft - Location of binding for arthritogens PTPN22 -Encodes Tyrosine Phosphotase - Activation and Control of Inflammatory Cells
Pathogenisis - RA - Environmental
Infectious
- Epstein Barr Virus
- RetroVirus
- ParaVirus
- Mycobacteris
Citrullinated Proteins
- Proteins modified by Arg –> Citrullinate
- Many are Fibrins
- Common in Lugs of Smokers
- Cause robust immune reaction
Pathogenisis - RA - Autoimmunity
Starts as Initial Inflammatory
Chronically Progresses as Autoimmune(T cells)
Present early in affected joints
- CD4+ effector
- Memory T-cells
- Th17 cells - recruit Nuetrophil/Mono
MI - About 80% of individuals with RA have AUTOANTIBODIES to Fc of IgG
- Rheumatoid Factors
- Mostly IgM
- Associate with IgG (RA-IgG)
- Form Immune Complex
- In sera, synovial fluid, syn. membranes
- NOT CAUSE of Disease - Markers of Dz
Autoantibodies to Citrulline Modified Proteins (antiCCP antibodies) with T-cell response is also a sign of chronic RA
What mediators bring about the destructive proliferative synovitis?
Cytokines from T-Cells
- INF-G
- IL-17
…which activate synoviocytes and macrophages which produce pro-inflammatory molecules…
- IL-1
- IL-6
- IL-23
- TNF - ONLY THIS ONE HAS BEEN FIRMLY IMPLICATED IN PATHOGENISIS OF RA
- PGE2
- NO
- GMCSF
- TGF - B
…theses mediators activate endothelial cells in synovium…
- Facilitate Leukocyte Binding and Transmigration
…which causes…
- INCREASED PRODUCTION OF CARTILAGE MATRIX METALLOPROTEINASES
- Synovium rich in inflammatory cells causes build up of PANNUS
- PANNUS produces sustained, irreversible cartilage destruction and erosion of subchondral bone
Clinical Course - RA - Physical
Initial - Malaise, Fatigue, MuscSke Pain
Weeks/Months - Joint Pain
Joints - Symmetrical and Small (MCP,PIP, Feet) - Swollen, Red, Painful - Stiff on waking/inacivity (Symmetrical,Small, Swollen, Stiff)
Clinical Course - RA - Imaging
Joint Effusions Osteopenia Erosions with Joint Space Narrowing Loss of Articular Cartilage Radial Deviation of Wrist Ulnar Deviation of Fingers Synovial Cysts (Baker's Cyst)
