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RHEUMATOID ARTHRITIS(RA)
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.
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.
 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.
 It is most common in those age 40 to 70,
but no age is immune.
 It is a systemic inflammatory autoimmune
disorder
Genetics
 Patients who have HLA-DRB have
Increased risk for :
RA development.
Increased joint damage
Increased joint need for surgery
PATHOPHYSIOLOGY
Role of Immunology in RA
 Macrophages:
Produce cytokines
Cytokines (TNF-α) cause systemic
features
Release chemokines  recruit PMNs
into synovial fluid/membrane
 TNF-α & IL-1:
Proliferation of T cells
Activation of B cells
Initiates pro-inflammatory/joint-damaging
processes
 TH-1 cells:
Mediate disease processes
Activate B cells
 B cells:
Release cytokines
Plasma cells that produce Ab
 Osteoclasts induce:
Bone erosion
Juxta-articular & Systemic
osteoporosis
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
Sequence of events :
 Proliferation of synovial membrane
cells with inflammatory cell infiltrate
 Destruction of joints
 Disability
DIAGNOSIS:
1- CLINICAL CRITERIA
2- INVESTIGATIONS
1- Diagnostic Criteria
 Symmetric peripheral polyarthritis
 Morning Stiffness >1 hour
 Extra-articular manifestations
 Rheumatoid nodules
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
Stiffness
 Morning or after Prolonged Inactivity
 Bilateral
 > 1 hours
Reflects severe joint inflammation
 Better with movement
 Pain with pressure to joint
….Stiffness
 Pain with movement of joint
 Swelling due to hypertrophy of
synovium
 Effusion
 Hotness
 Redness
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
Extraarticular Involvement
 Myalgia, fatigue, low-grade fever,
weight loss, depression.
 Anemia
 Rheumatoid nodules
 Pleuro-pericarditis
 Neuropathy
 Sicca features: Xerostomia &
Xerophthalmia
 Scleritis
 Splenomegaly
 Vasculitis
Xerostomia (Dry Mouth)
Xerophthalmia (Dry Eyes)
Rheumatoid Nodules
 Extensor surfaces
 elbows
 Very Specific
 Only occur in ~30%
 Late in Disease
Rheumatoid Vasculitis
RA Deformities
Investigations
Arthrocentesis
 Confirm diagnoses
 Differentiate between inflammatory &
non-inflammatory
 Labs:
White blood cell count if WBC
>2000/µL indicates inflammatory
arthritis
Gram stain & Culture
 Arthroscopy
Evaluate ligamentous &
cartilaginous integrity
Biopsy
Infection: aspirate thick
Rheumatoid arthritis : showing inflammatory cell
infiltrate in the synovium
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)
Rheumatoid Factor
 Antibodies to Fc portion of IgG
 75-80% of Patients have during
course of disease
 Useful for prognosis
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
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
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
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
 Infections
 Hepatitis C virus
 Acute viral infections
 Endocarditis
 Tuberculosis
 Miscellaneous
 Sarcoidosis
 Malignancies
 Aging
Radiology
 Evaluate disease activity & joint
damage
 Bony decalcification
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
DISEASE
SEVERITY
Mild Disease
 Arthralgias
 >3 inflamed joints
 Mild functional limitation
 Minimally elevated ESR & CRP
 No erosions/cartilage loss
 No extraarticular disease
Moderate Disease
 6-20 Inflamed joints
 Moderate functional limitation
 Elevated ESR/CRP
 Radiographic evidence of
inflammation
 No extraarticular disease
Severe Disease
 >20 persistently inflamed joints
 Rapid decline in functional capacity
 Radiographic evidence of rapid
progession of bony erosions & loss of
cartilage
 Extraarticular disease
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
Differential diagnosis of arthritis
 Seronegative polyarthritis
 Psoriatic arthritis
 Osteoarthritis
 SLE
 Paraneoplastic syndrome
 Crystal-induced arthritis
Tophaceous gout
Pseudogout
Rheumatoid arthritis.ppt

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Rheumatoid arthritis.ppt

  • 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
  • 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
  • 13.
  • 14. Sequence of events :  Proliferation of synovial membrane cells with inflammatory cell infiltrate  Destruction of joints  Disability
  • 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
  • 21.
  • 22.
  • 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
  • 26. Rheumatoid Nodules  Extensor surfaces  elbows  Very Specific  Only occur in ~30%  Late in Disease
  • 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
  • 41.
  • 42.
  • 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