Definition
Rheumatoid arthritis is a chronic inflammatory polyarthritis with symmetric involvement of
synovial joints, autoimmune with systemic involvement.
Epidemiology
Females are affected more than males
25-55years of age
Environmental Factors such as
1. smoking
2. Implicated infections - (not proven)EBV,Porphyromonas gingivalis, Prevotella copri (gut
microbe seen in untreated RA patients)
3. Genetics HLA DRB1
-triggers increase in citrullinated proteins ,that is exchange of arginine with citrulline which is
known as post translational exchange of arginine with citrulline this occurs in interstitial proteins.
Pathophysiology
Antigen presenting cells dendritic cells and macrophages fail to identify the citrullinated
proteins as self antigen
(Citrullinated proteins are present in type II collagen & vimentin)
↓
These Antigen presenting cells go to the CD-4 T cells in the lymph node.
↓
CD4 T cells proliferate Th1 which produce IFN gamma,TNF alpha ,Lymphotoxin beta
And Th17 cells IFN gamma and IL17 all are proinflammatory cytokines
↓
T cells will cause proliferation of B-cells and will differentiate into plasma cells
↓
The Plasma cells will create specific antibodies against the targeted antigen.
antibodies include,
Anti-CCP, Ab against citrullinated protein
, RF - ab IgM ab against IgG Ab fc portion
↓
Now, the T-cells & antibodies will enter the circulation and reach the joint
↓
The T cells on reaching the joint will secrete Interleukin 17 & Interferon gamma which causes
fibroblast like proliferation and inflammation of synovial cell in synovium this inflamed
synovium with angiogenesis is known as pannus these inflamed cells produce protease which
damage the cartilage.
↓
This interleukins will recruit macrophages which inturn produces cytokines
IL 1 ,IL 6 ,TNF alpha .
RF antibodies activate complement system classical pathway
T cells will also increase RANKL which increases osteoclast activity leading to bone erosion.
Inflammatory cells cause systemic inflammation as they are in circulation most commonly
affected organ lungs→ leading to Pulmonary fibrosis ,eyes → episcleritis,blood vessel →
vasculitis→ increased risk of strokes, CVD
Clinical features of RA
1 morning stiffness >1hr
2 fever malaise
3 symmetrical polyarthritis
Seen esp in MCP and PIP joints and wrist commonly affected also atlantoaxial joint which is
also synovial joint
4 Eyes - episcleritis , keratoconjunctivitis
sicca i.e dry eyes
5 Lungs - pleuritis and Pulmonary fibrosis
6 Heart - myocardial and pericarditis
6 Bursitis, rheumatoid nodules mostly seen in Extensor surfaces commonly around olecranon
process elbow also seen in lungs.
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