2. Cause remains unknown
Factors that contribute to development,
progression and chronicity :
Genetic Susceptibility
▪ HLA-DRB1: shared epitope is specific binding site of
arhritogens
▪ PTPN22: activation and control of inflammatory cells
Environmental arthritogens
▪ Microbial agents
▪ Citrullinated proteins
Autoimmunity
▪ Rheumatoid factors
3. Genetic susceptibility
Arthritogens
Activation of CD4+ helperT cells
Release of cytokines
INF-γ & IL-17
Stimulation of synoviocytes and macrphages
Production of pro-inflammatory molecules:
IL-1, 6, 23,TNF, PGE2, NO,GF, GM-CSF,TGF-β
Increase production
of cartilage matrix
metalloproteinases
Stimulation of
osteoclastogenesis and
osteoclast activity
Synoviocytes up-
regulate vascular cell-
adhesion molecule
Edematous, hyperplastic, sticky synovium
Pannus formation and resorption of the adjacent bone
PATHOGENESIS
4.
5. Inflammatory infiltrate composed
of lymphoid aggregates
Increased vascularity
Accumulation of neutrophils
Pannus formation
6.
7. Manifestations:
Mild general aching and stiffness
Inflammation may be apparent first in the wrists and
fingers
Joints appear red and swollen and often very sensitive
to touch as well as painful
Joint stiffness
“burned out”
Systemic signs are marked during exacerbations and
inclued fatique, anorexia, mild fever,
lymphadenopathy and genralized aching
8. Complications:
Effects on the Skin
▪ Rheumatoid Nodules
Eye Complications
▪ Inflammation of the episclera
▪ Scleritis
▪ Sjogren's syndrome
9. Effects on Heart and BloodVessels
Pericardial Effusion
Pericarditis
Myocarditis
Diseases of the Blood and Blood-Forming
Cells
Anemia
Felty's syndrome