DR Medhat MRCP

Rheumatoid arthritis (RA)
• Def :
- It`s a chronic systemic inflammatory diseases characterized by:
1. Articular manifistations Symmetrical inflammatory polyarthritis (synovial j.)
Progressive joint damage.
2. Extra-articular manifistations (unlike OA which doesn`t have extra-articular
manifistations).
• Epidemiology:
- Peak onset = 30-50 years, although occurs in all age groups.
- Female : male ratio = 3:1.
‏(سؤال هام - Prevalence in UK = 1% (i.e 1000 /100,000
- Some ethnic differences e.g. High in native Americans.
- Associated with HLA-DR4 (especially felty's syndrome).
• Pathophysiology :
Rheumatoid arthritis - TNF is a key in pathophysiology
- Autoimmune response initiated after certain bacterial or viral infections in genetically
predisposed person (HLA-DR4), mediated by T-cell & macrophages derived cytokines
mainly TNF-α , IL1 & IL6.
- Exposure of genetically predisposed persons (HLA-DR4) to certain infections (e.g
CMV,Rubella,hepatitis& proteus mirabilis ‏(هام will lead to :
1. Normal immune response :
o Antibodies against the organism (IgG & IgM).
o Inflammatory reaction in synovial membrane of the joint.
o With inflammation,there is enzymatic conversion of synovial arginine to
cyclic citrullinated peptide (CCP).
2. Abnormal immune response(due to breakdown of immune tolerance) :
o Uncontrolled recruitment of innate & adaptive immunity cells
(Monocytes `which differentiate into macrophages & dendritic cells` and
T- helper cells `CD4+`) leading to :
a) Release of cytokines (TNF-α & IL1,6) recruit more inflamm.cells
e.g PNLs whith release of proteases that destruct the joint.
b) ++ of B-cells plasma cells auto antibodies :
Rheumatoid factor (RF) : IgM against IgG (Fc part).
Anti-CCP : against CCP (early detector of RA).
o This abnormal immune response will severe synovitis with ++ of
vascular endothelial growth factor (VEGF) which ++ new vascularisation
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