This document discusses rheumatoid arthritis (RA), a chronic inflammatory disease characterized by joint inflammation and damage. The clinical presentation of RA involves symmetric joint pain, swelling, and morning stiffness. The pathogenesis involves an immune response involving T cells, B cells, and cytokines like TNF-alpha that promote inflammation. Disease activity is the main driver of joint damage and disability in RA. Treatment involves conventional disease-modifying antirheumatic drugs (DMARDs) and biologic agents to reduce inflammation, prevent further joint destruction, and improve function.

2. By
Dr.ESSAMT. ATWA
PROFESSOR OF RHEUMATOLOGY &
REHABILITATION

5.  Rheumatoid arthritis (RA) is a systemic disease
characterized predominantly by a chronic
inflammatory polyarthritis, with frequent
progression to joint destruction and disability.
 The clinical picture seen in RA is the result of a
complex cascade involving T cells, B cells, antigen-presenting
cells, and a complex set of costimulation
signals that lead to the production of proinflammatory
cytokines, including tumor necrosis factor (TNF)-
alpha, interleukins, and other mediators.

6.  The hallmarks of RA are inflammation and synovitis
leading to joint damage, and an overexpression of
inflammatory cytokines, such as TNF-alpha, IL-1, and
IL-6.
 Although disease activity is the major cause for active joint
damage in RA leading to disability, measuring disease
activity in patients with RA remains a challenging issue.
 A number of composite disease scoring systems have been
developed over the past decade, which consider physical and
radiographic evaluations as well as overall physician and
patient assessment.
 In addition, acute-phase reactant inflammatory markers,
such as CRP and ESR, can provide additional information of
the disease state.

8. NORMAL RA
Synovial
membrane
Cartilage
Capsule
Synovial
fluid
Inflamed
synovial
membrane
Pannus
Major cell types
T lymphocytes •
macrophages •
Minor cell types
fibroblasts •
plasma cells •
endothelium•
dendritic cells •
Major cell type
neutrophils •
Cartilage thinning
Feldmann M, et al. Annu Rev Immunol. 1996;14:397-440.

9. Expansion of the synovial
membrane forms an
invasive pannus1
Synovial cells and
chondrocytes release
destructive enzymes that
degrade cartilage1
Pannus invades cartilage,
leading to bone erosion
and joint instability1
Surgically resected pannus
from a patient with advanced
RA
1Harris ED Jr. N Engl J Med. 1990;322:1277-1289.

10. Foreign antigens bind to
receptors on antigen-presenting
cells1
Complementary receptors
on T cells recognize the
antigens, triggering an
immune response1
1Harris ED Jr. N Engl J Med. 1990;322:1277-1289.

11. Activation of T cells
triggers a series of
intercellular reactions1
Lymphocytes and
macrophages release
proinflammatory
cytokines1,2
Cytokines induce synovial
proliferation and release of
destructive enzymes1,2
1Rosenberg AE. In: Cotran RS, Kumar V, Robbins SL, eds. Robbins Pathologic Basis of Disease. 5th ed. Philadelphia, Pa: W.B. Saunders
Company; 1994:1213-1271.
2Goronzy JJ, Weyand CM. In: Klippel JH, ed. Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation; 1997:155-161.

12. Protein

13. disequilibrium
Adapted from Feldmann M et al. Cell 85:307-310, 1996 and Moreland LW et al. Arthritis Rheum 40:397-409, 1997.

14. TNF
Macrophages
Endothelium
Hepatocytes
Synoviocytes
Pro-inflammatory cytokines
Chemokines
Adhesion molecules
Vascular endothelial
growth factor (VEGF)
Acute phase response
Metalloproteinase synthesis
Increased
inflammation
Increased cell
infiltration
Increased
angiogenesis
Increased
CRP in serum
Articular
cartilage
degradation
Osteoclast
Progenitors RANKL expression
Bone erosions

15. TNF
osteoclasts synoviocytes chondrocytes
bone resorption
bone erosion
joint
inflammation
cartilage
degradation
joint space
narrowing
pain/joint
inflammation

19. The diagnosis of RA is made
using :
The patient's history and
examination results
In conjunction with laboratory
and radiographic data.

20. CLINICAL

23. ◦ Symmetric joint pain
◦ Swelling of small peripheral
joints
◦ Morning joint stiffness of
variable duration
◦ Other diffuse aching
Fatigue, malaise, and
depression
may precede other symptoms
by weeks or months
Grassi W et al. Eur J Radiol. 1998;27(suppl 1):S18–S24.

32. INVESTIGATIONS

43. 1987 Revised American Rheumatism Association Criteria
for the Classification of Rheumatoid Arthritis
Criterion Definition
Morning stiffness in and around the
joints, lasting at least 1 h.
1. Morning stiffness
At least three joint areas simultaneously
have had soft tissue swelling or fluid (not
bony overgrowth alone) observed by a
physician. The 14 possible areas are right
or left PIP, MCP, wrist, elbow, knee, ankle,
and MTP joints.
2. Arthritis in three or more joint areas
At least one area swollen (as defined
above) in a wrist, MCP, or PIP joint.
3. Arthritis of hand joints
Simultaneous involvement of the same
joint areas (as defined in Criterion 2) on
both sides of the body (bilateral
involvement of PIPs, MCPs, or MTPs is
acceptable without absolute symmetry).
4. Symmetric arthritis

44. Cont. Criterion Definition
Subcutaneous nodules over bony
prominences or extensor surfaces or
juxtaarticular regions observed by a
physician.
5. Rheumatoid nodules
Demonstration of abnormal amounts of
serum rheumatoid factor by any method
for which the result has been positive in
<5% of normal control subjects.
6. Serum rheumatoid factor
Radiographic changes typical of
rheumatoid arthritis on the
posteroanterior hand and wrist
radiographs, which must include erosions
or unequivocal decalcification localized
in, or most marked adjacent to, the
involved joints (osteoarthritis changes
alone do not qualify).
7. Radiographic changes
MCP, metacarpophalangeal; MTP, metatarsophalangeal; PIP, proximal
interphalangeal.

45.  For classification purposes, a patient shall be said to
have rheumatoid arthritis if he or she has satisfied at
least four of these seven criteria.
 Criteria 1 through 4 must have been present for at
least 6 weeks.
 Patients with two clinical diagnoses are not
excluded.
 Designation as classic, definite, or probable
rheumatoid arthritis is not to be made.

46. The 2010 American College of
Rheumatology/European League Against
Rheumatism classification
criteria for rheumatoid arthritis
Target population (Who should be tested?): Patients
who
1) have at least 1 joint with definite clinical synovitis
(swelling)
2) with the synovitis not better explained by another
disease
Classification criteria for RA (score-based algorithm:
add score of categories A–D; a score of 6/10 is needed
for classification of a patient as having definite RA)

47. A-Joint Involvement Score
1- large joint. 0
2- 10 large joints 1
1-3 small joints (with or without involvement of
large joints)
2
4-10 small joints (with or without involvement
of large joints)
3
>10 joints (at least 1 small joint) 5

48. B. Serology (at least 1 test result
is needed for classification)
Score
Negative RF and negative ACPA 0
Low-positive RF or low-positive
ACPA
2
High-positive RF or high-positive
ACPA
3

49. C. Acute-phase reactants (at
least 1 test result is needed for
classification)
Scor
e
Normal CRP and normal
ESR
0
Abnormal CRP or abnormal
ESR
1

50. D.Duration of
symptoms
Score
< 6 weeks 0
> 6 weeks 1

53. Provides both rapid and sustained efficacy°
Highly effective for symptom relief°
Leads to prevention of joint destruction°
Prevents functional disability°
Useful in combination treatment°
Well tolerated, with minimal monitoring required°
Allows for simple dosing and administration°

54. 1928
1948
1985
2000
Milestones Steps foreward
Parenteral Gold
Corticosteroids
Methotrexate
TNF blockers
Antimalarials
Modern NSAIDs
Azathioprine
D-Penicillamine
Sulfasalazine
Cyclosporin A
Leflunomide
COXIBS
DMARD
Combination

56. Current Approach Evolving Paradigm
Initial Treatment Initial Treatment
Conventional DMARDs DMARD
Biologic
agent
Monotherapy or Combination
If Disease
Controlled
Wolfe F, et al. J Rheumatol. 2001;28:1704-11.
Fleischmann RM. Clin Ther. 1999;21:1429-42.
Matteson EL. Mayo Clin Proc. 2000;75:69-74.
If Poor Response
Add
additional
DMARDs
Add
biologic
agent
If Poor
Response
Combination
therapy
Discontinuation/
reduction of
DMARDs

57. THANK YOU