2. Rheumatoid arthritis (RA)
Chronic inflammatory disorder of autoimmune origin
principally attacks the joints, producing a nonsuppurative proliferative and
inflammatory synovitis
Articular lesions: destruction of the articular cartilage and, in some cases
ankylosis (adhesion) of the joints.
Extraarticular lesions: may occur in the skin, heart, blood vessels, and
lungs
Causes Symmetrical Polyarthritis: affects several joints in pairs on both
sides of your body
Epidemiology
• it is three times more common in women than in
men
• The peak incidence between the ages of 30 and
50 years
• There is an increased incidence in those with a
family history of RA
3. Etio-pathogenesis
Etiology:
Genetic predisposition: Human leucocyte antigen (HLA)-DR4 and HLA-DRB1*
0404/0401 alleles confer susceptibility to RA
Insults such as infection (including periodontitis) and smoking
Hormonal: Sex hormones In premenopausal women
Pathogenesis: as autoimmune diseases, genetic predisposition and
environmental factors contribute to the development, progression, and
chronicity of the disease
The pathologic changes are mediated by antibodies against self-antigens
(arthritogens: chemical or microbial modified self antigen)
and inflammation caused by cytokines, predominantly secreted by CD4+ T
cells
The T cells produce cytokines that stimulate other inflammatory cells to
effect tissue injury:
4. Pathogenesis continued
IFN-γ from TH1 cells activates
macrophages and synovial cells.
IL-17 from TH17 cells recruits
neutrophils and monocytes.
RANKL expressed on activated T
cells stimulates osteoclasts and
bone resorption
TNF and IL-1 from macrophages
stimulate resident synovial cells to
secrete proteases that destroy
hyaline cartilage.
Plasma cells produces Seum
antibodies against Citrullinated
peptides in which arginine residues
are posttranslationally converted to
citrulline
Ex. citrullinated fibrinogen, type II
collagen, α-enolase, and vimentin
deposit in the joints.
Serum antibodies are k/n as anti-
citrullinated protein antibodies
(ACPA)
Another antibodies About 80% of
patients have serum IgM or IgA
autoantibodies that bind to the Fc
portions of their own IgG. These
autoantibodies are called
Rheumatoid factor and may also
deposit in joints as immune
complexes
5. Pathogenesis continued
The inflammation localizes to the
joint, recruiting macrophages and
triggering activation and/or
proliferation of synovial cells,
chondrocytes, and fibroblasts.
The production of proteolytic
enzymes and cytokines contributes
to the destruction of cartilage and,
through increased osteoclast
activity, bone
6. Morphology
the synovium becomes
edematous, thickened, and
hyperplastic, transforming its
smooth contour to one covered by
delicate and bulbous villi
The characteristic histologic
features include:
(1) Synovial cell hyperplasia and
proliferation;
(2) dense inflammatory infiltrates of
CD4+ helper T cells, B cells, plasma
cells, dendritic cells, and
macrophages
(3) increased vascularity resulting
from angiogenesis;
(4) neutrophils and aggregates of
organizing fibrin on the synovial and
joint surfaces;
(5) Osteoclastic activity in underlying
bone, allowing the synovium to
penetrate into the bone, causing
periarticular erosions and
subchondral cysts.
Pannus Formation: a mass of
edematous synovium, inflammatory
cells, granulation tissue, and
fibroblasts that grows over the
articular cartilage and causes its
erosion
Pannus can lead to fibrous ankylosios
and bony ankylosis
7. Clinical Diagnosis:
ACPA and RF in blood and Radiographic findings
(x-rays)
Sign and symptoms
Early symptoms: malaise, fatigue, and
generalized musculoskeletal pain.
After several weeks to months the joint
become involved generally Symmetrical
Commonly joints of the hands and feet,
wrists, ankles, elbows, and knees
joints are swollen, warm, and painful
Stiffness of the joints when patient rises
in the morning or following inactivity
joint enlargement and decreased range
of motion
Inflammation in the tendons, ligaments,
and occasionally the adjacent skeletal
muscle
produces the characteristic ulnar
deviation of the fingers and flexion-
hyperextension of the fingers (swan-
neck deformity, boutonnière deformity).
Radiographic hallmarks are joint
effusions and juxtaarticular osteopenia
with erosions and narrowing of the joint
space and loss of articular cartilage
Joint effusion
8.
9. Extra-articular RA
•Systemic – Fever, Fatigue, Weight loss
•Eyes- Scleritis, Scleromalacia perforans (perforation of the eye)
•Neurological- Carpal tunnel syndrome, Atlanto-axial subluxation, Cord
compression
•Haematological-
• Felty’s syndrome (rheumatoid arthritis, splenomegaly, neutropenia),
• Anaemia (chronic disease, NSAID-induced, gastrointestinal blood loss, haemolysis,
hypersplenism),
• Thrombocytosis
Pulmonary - Pleural effusion, Lung fibrosis, Rheumatoid nodules,
Rheumatoid pneumoconiosis
Heart and peripheral vessels – Pericarditis, Pericardial effusion, Raynaud’s
syndrome
Vasculitis - Leg ulcers, Nail fold infarcts, Gangrene of fingers and toes
Kidneys - Amyloidosis causes the nephrotic syndrome and renal failure
10. Rheumatoid nodules
An infrequent manifestation of RA and
typically occur in subcutaneous tissue including the forearm, elbows,
occiput, and lumbosacral area.
Microscopically, they resemble necrotizing granulomas