Rheumatoid arthritis is a chronic systemic inflammatory disorder that principally attacks the joints, causing inflammation of the synovium and eventual destruction of cartilage and bone. It is caused by an autoimmune process involving macrophages, T cells, B cells, and cytokines such as TNF-α and IL-1. Diagnosis is based on clinical features of symmetric peripheral polyarthritis affecting small joints of the hands and feet, morning stiffness lasting over an hour, and possible extra-articular manifestations. Laboratory tests show elevated inflammatory markers like ESR and CRP as well as rheumatoid factor in 75-80% of patients. Radiographs can demonstrate joint damage over time. Treatment involves controlling inflammation and preventing further joint destruction.

1. RHEUMATOID ARTHRITIS(RA)

2. Learning objectives:
 At the end of this lecture the student should be able
to :
 understand definition,genetic predisposition of RA.
 Discuss pathophysiology, clinical features of RA.
 Identify Diagnostic Criteria ,Laboratory Features
and bad prognostic Features of Rheumatoid
Arthritis.

3. Definition
 Rheumatoid arthritis (RA) is a chronic systemic
inflammatory disorder that may affect many
tissues and organs—skin, blood vessels, heart,
lungs, and muscles—but principally attacks the
joints, producing a non-suppurative proliferative
and inflammatory synovitis that often progresses
to destruction of the articular cartilage and
ankylosis of the joints.

4.  Although the cause of RA remains
unknown, autoimmunity plays a pivotal
role in its chronicity and progression.
 About 1% of the world's population is
afflicted by RA, women two to three times
more often than men.

5.  It is most common in those age 40 to 70,
but no age is immune.
 It is a systemic inflammatory autoimmune
disorder

6. Genetics
 Patients who have HLA-DRB have
Increased risk for :
RA development.
Increased joint damage
Increased joint need for surgery

7. PATHOPHYSIOLOGY

8. Role of Immunology in RA
 Macrophages:
Produce cytokines
Cytokines (TNF-α) cause systemic
features
Release chemokines  recruit PMNs
into synovial fluid/membrane

9.  TNF-α & IL-1:
Proliferation of T cells
Activation of B cells
Initiates pro-inflammatory/joint-damaging
processes

10.  TH-1 cells:
Mediate disease processes
Activate B cells
 B cells:
Release cytokines
Plasma cells that produce Ab

11.  Osteoclasts induce:
Bone erosion
Juxta-articular & Systemic
osteoporosis

12. Pathophysiology
 Swelling of Synovial lining
 Angiogenesis
 Pannus formation in form of :
 Synovial thickening/hyperplasia
 Inflammatory vascularized tissue
 Generation of Metalloproteinases
 Cytokine release
 Infiltration of leukocytes
 Change in cell-surface adhesion molecules &
cytokines
 Destruction of bone & cartilage

14. Sequence of events :
 Proliferation of synovial membrane
cells with inflammatory cell infiltrate
 Destruction of joints
 Disability

15. DIAGNOSIS:
1- CLINICAL CRITERIA
2- INVESTIGATIONS

16. 1- Diagnostic Criteria
 Symmetric peripheral polyarthritis
 Morning Stiffness >1 hour
 Extra-articular manifestations
 Rheumatoid nodules

17. Symmetric Peripheral
Polyarthritis
 3 or more Joints for >6 weeks
 Intermittent or Migratory involvement
 Small Joints
Hands & Feet
Peripheral to Proximal
 Leads to Deformity & Destruction of Joints
Erosion of cartilage and bone

18. Stiffness
 Morning or after Prolonged Inactivity
 Bilateral
 > 1 hours
Reflects severe joint inflammation
 Better with movement
 Pain with pressure to joint

19. ….Stiffness
 Pain with movement of joint
 Swelling due to hypertrophy of
synovium
 Effusion
 Hotness
 Redness

20. Physical Exam
 Decreased grip strength
 Carpal tunnel syndrome(condition
characterized by pain and numbing or tingling
sensations in the hand and caused by
compression of a nerve in the carpal tunnel at
the wrist.
 Ulnar deviation
 Boutonniere/Swan neck deformities
 Extensor tendon rupture

23. Extraarticular Involvement
 Myalgia, fatigue, low-grade fever,
weight loss, depression.
 Anemia
 Rheumatoid nodules
 Pleuro-pericarditis

24.  Neuropathy
 Sicca features: Xerostomia &
Xerophthalmia
 Scleritis
 Splenomegaly
 Vasculitis

25. Xerostomia (Dry Mouth)
Xerophthalmia (Dry Eyes)

26. Rheumatoid Nodules
 Extensor surfaces
 elbows
 Very Specific
 Only occur in ~30%
 Late in Disease

27. Rheumatoid Vasculitis
RA Deformities

28. Investigations

29. Arthrocentesis
 Confirm diagnoses
 Differentiate between inflammatory &
non-inflammatory
 Labs:
White blood cell count if WBC
>2000/µL indicates inflammatory
arthritis
Gram stain & Culture

30.  Arthroscopy
Evaluate ligamentous &
cartilaginous integrity
Biopsy
Infection: aspirate thick

31. Rheumatoid arthritis : showing inflammatory cell
infiltrate in the synovium

32. Laboratory findings
 Anemia of moderate degree
 ESR  a useful parameter for assessing
response to therapy
 C-reactive protein 
 RF (usually IgM)
 CIC  , complements 
 ANA
 Anti-CCP (cyclic citrullinated peptide)

33. Rheumatoid Factor
 Antibodies to Fc portion of IgG
 75-80% of Patients have during
course of disease
 Useful for prognosis

34. Rheumatoid
Factor
 IgG Molecule
 Fc Portion
Antigen Binding
Groove
Autoantibodies (IgM)
directed against the
Fc Fragment of IgG
An Antibody to an
Antibody
Their Role in RA is
not understood

35. Rheumatoid Factor
 RFs are human auto-Abs that react with
the Fc portion of normal polyclonal IgG.
 Most routine clinical assays for RF detect
only IgM RFs, although RFs can be any
class of immunoglobulin
 Named thus because their first description
was in patients with rheumatoid arthritis

36. Rheumatoid Factor
 RF test is approximately 65%-75%
sensitive for the diagnosis
 The presence of RF, even in high titers or
large amounts, is not specific for RA

37. Condition Assoc . With(+) Tests for RF
 Rheumatologic Diseases
 Rheumatoid arthritis (~70%)
 Sjögren’s syndrome (~90%)
 Lupus (~20%)
 Cryoglobulinemia syndrome (90%)
 Lung Diseases
 Interstitial fibrosis
 Silicosis

38.  Infections
 Hepatitis C virus
 Acute viral infections
 Endocarditis
 Tuberculosis
 Miscellaneous
 Sarcoidosis
 Malignancies
 Aging

39. Radiology
 Evaluate disease activity & joint
damage
 Bony decalcification

40. Radiological Studies
 Plain Films
Bilateral hands & feet
 Color Doppler U/S & MRI
Early signs of damage i.e. Erosions
Bone Edema - even with normal
findings on radiography

43. DISEASE
SEVERITY

44. Mild Disease
 Arthralgias
 >3 inflamed joints
 Mild functional limitation
 Minimally elevated ESR & CRP
 No erosions/cartilage loss
 No extraarticular disease

45. Moderate Disease
 6-20 Inflamed joints
 Moderate functional limitation
 Elevated ESR/CRP
 Radiographic evidence of
inflammation
 No extraarticular disease

46. Severe Disease
 >20 persistently inflamed joints
 Rapid decline in functional capacity
 Radiographic evidence of rapid
progession of bony erosions & loss of
cartilage
 Extraarticular disease

47. bad prognostic Features
 RF +ve
 Early development of multiple inflamed
joints and joint erosions
 Severe functional limitation
 Female
 HLA epitope presence
 Lower socioeconomic status & Less
education
 Persistent joint inflammation for >12
weeks

48. Differential diagnosis of arthritis
 Seronegative polyarthritis
 Psoriatic arthritis
 Osteoarthritis
 SLE
 Paraneoplastic syndrome
 Crystal-induced arthritis
Tophaceous gout
Pseudogout