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Rheumatoid Arthritis
(RA)
I. General Considerations
Systemic autoimmune disease
Chronic poly-arthritis, usually
symmetric
Mainly involve peripheral
joints
II. Etiology
Genetic Background
HLA-DR
Infections Agents
especially Epstein-Barr Virus
III. Pathogenesis
Activation of both B and T
lymphocytes
IV. Pathology
Synovitis:
Infiltrates of
inflammatory cells
Angiogenesis
Synovial cell
proliferations
Formation of Pannus
Destruction of cartilage
and Subchondral bone
↓
Narrowing of
joint space and
bone erosion
Pathology
• IV. Pathology
V. Clinical Features of RA
1. Articular Manifestations
a. polyarthritis:
(1)symmetrical
(2)≥6 weeks
(3)wrists, hand joints, knee, feet joints
commonly affected
(4)erosive
(5)deformity
b. motion of joints limited
Frequently involved joints
PIP
proximal
interphalangeal joint
 DIP
Distant
Interphalangeal joint
 MCP
Metacarpophalangeal
joint
 Wrist

MTP
Metatarsophalangeal
joint
Spindle finger
Swollen of
the PIP
joints
makes the
finger
spindle
shape
Common deformities
Swan-neck deformity:
Hyperextension of the
PIP in conjunction
with flexion of DIP
joint .
Boutonniere deformity: Flexion of PIP joints
and extension of the DIP joints.
ulnar deviation
frequently accompanied
by palmar subluxation of
the proximal phalanges.
Ulnar deviation with muscle atrophy
2. Extra-articular Manifestations
Skin:
(1) Subcutaneous nodules
(2) Vasculitis
Subcutaneous nodules with muscle atrophy
ulnar deviation with the vasculitis-induced
finger necrosis after surgical resection
ischemic necrosis due to vasculitis
Cardiac Manifestations
(1)Pericarditis
(2)myocarditis
(3)valvular insufficiency
Pulmonary Manifestations
1. Rheumatoid pleural disease: pleural
effusion: exudative, low glucose,
LDH elevated, Low complement,
RF+ Multiple subpleural nodules.
2. Nodular change: Rheumatoid nodule in the lung.
3. Diffuse
interstitial fibrosis
Neurologic Manifestations
(1) Mononeuritis Multiplex:
Sensory loss, foot, wrist drop
(2) Carpal tunnel Syndrome
Ocular Manifestations:
Sjogren Syndrome Causing corneal and
conjunctival lesions along with
dryness of the eyes.
episcleritis, scleritis
Felty Syndrome:
Splenomegaly, lymphadenopathy,
anemia, Bpc ↓ WBC ↓ , RF positive
VI. Lab Findings in RA
Test
Characteristic
Results
Blood Elements Moderate normochromic, normocytic anemia
Erythrocytes
Low plasma iron, decreased total iron binding
Capacity
Leukocytes
Normal or slightly elevated
Leukopenia rare ( Felty Syn. )
Acute-phase Reactants and immunoglobulin
ESR
Increased
C-Reactive Protein (CRP): positive
Ig.
IgG increased, IgA, M increased
Immune Factors
ANA
Present in 15%
RF
Present in 70%
Complement Normal or slightly elevated
Rheumatoid Factors
RF are now defined as antibodies specific to
antigenic determinants on the Fc fragments of
human or animal immunoglobulin.
Seropositivity of patients with RA or with other
disease is usually defined by the latex fixation test
or red cell agglutination tests. These assays
reflect the presence of IgM Rheumatoid factors
(IgM-RFs). The presence of RF is not unique to RA,
and a positive RF should not be used as the sole
criterion for the diagnosis of RA.
Occurrence of RF in various Dis
IgM-RF +
Negative
Rheumatoid Arthritis
Osteoarthritis
Other rheumatic Diseases
Ankylosing Spondylitis
Sjogren*s Syn
SLE, PSS, PM
Gout
Infections Diseases
Psoriatic arthritis
SBE
TB
Non-infections Disease
Normal individuals (Aged)
Chronic active hepatitis
Diffuse Interstitial pulmonary fibrosis
Radiological Examination:
S-soft tissue
A-alignment
B-bone
C-cartilage
erosion
Classification of Progression of RA
Stage 1, Early
1. No destructive changes on X-ray film
2. Radiological evidence of osteoporosis
Stage II, moderate
Osteoporosis with Slight Subchondral bone
destruction, No joint deformities
Stage III, Severe
1. Radiological evidence of cartilage
and bone destruction
2. Joint deformity without ankylosis
Stage IV
1. Fibrous or bony ankylosis
2. Criteria of Stage III.
VII. Proposed 1987 Revised ARA criteria for RA
1. Morning stiffness for at least one hour and
Present for at least six weeks
2. Swelling of three or more joint≥6 weeks
3. Swelling of wrist, MCP or PIP joints≥6 weeks
4. Symmetric Joint swelling
5. Hand X-ray changes typical
of RA that must include erosions or
unequivocal bony decalcification
6. Rheumatoid nodules
7. Serum RF positive
Four or more criteria must be present to diagnose RA
Differential Diagnosis
Rheumatic Fever
Osteoarthritis
SLE
Ankylosing Spondylitis ( AS )
The Hand in Rheumatoid Arthritis
and in Osteoarthritis
Criteria
Rheumatoid Arthritis Osteoarthritis
Character of Swelling Synovial, Capsular,
Soft-tissue, bony
only in late stages
Tenderness
Usual
DIP involvement
PIP involvement
MCP involvement
Wrist involvement
Not usual, except
thumb
Characteristic
Characteristic
Usual or common
Bony with
irregular
Spurs
None or mild
except during
occasional
acute onset
Characteristic
Frequent
Rare
Rare, except
base of thumb
Clinical Course of RA
Progressive Chronic disease with remission
and exacerbations but continuing
disease activity (70%)
Intermittent Brief attacks with intermittent
remissions with no disease
activity (25%)
Malignant
Severe disease with extra-articular
manifestations, especially vasculitis
VIII. Treatment
Objective of treatment

1. relief of pain

2. reduction or suppression of inflammation

3. minimizing undesirable effects

4. preservation of muscle and joint function

5. return to a desirable and productive life
Drug Therapy
1. Non-steroid Anti-inflammatory
Drugs ( NSAIDs )
 a. Analgesic
 b. Anti-inflammatory
 c. Anti-pyrexia
Processes influenced by NSAIDs
Prostaglandin
Production
Leukotriene
Synthesis*
Superoxide
Generation
Lysosomal enzyme release
Neutrophil aggregation
Adverse effects of NSAIDs
 a. Gastrointestinal
 b. Hepatic effects
 c. Renal effects
 d. others: skin rash
effects
COX-1/COX-2 Theory
COX-1
Constitutive
Homeostatic functions
GI tract
Renal function
Platelet function
COX-2
Regulated
Inflammation
The advantage of selective COX-2 inhibition
• NSAIDs
with a good GI side effect profile have been
shown to have lower ratios of COX-2/COX-1 inhibition
• Newly
designed selective COX-2 inhibitors have
significantly fewer GI side effects compared with traditional
NSAIDs
2. Disease - Modifying Anti-rheumatic
Drugs ( DMARDs)
Features of DMARDs:

a. Modifying the progression of RA

b. Slow acting

c. More adverse effects
Disease-Modified Anti-rheumatic Drugs ( DMARDs)
Drug
Methotrexate (MTX)
Major adverse reaction
Hepatic fibrosis, Nausea, Cytopenia
Anti-malanial (CQ & HCQ)
Visual disturbance
Leflunomide (LEF)
Hepatic damage
Sulfasalazine (SASP)
GI irritation, rashes
D-penicillamine (D-PA)
Rashes, Proteinuria, Cytopenia,
Taste disturbance
Principles for DMARDs therapy
1.
early use
2. combination therapy
Common combination therapy
MTX+CQ(HCQ)
MTX+SASP
MTX+LEF
3. Corticosteroids
usually low dose (below 10mg/day)
combined with DMARDs
Indications for Large doses:
Rheumatoid vasculitis
Felty Syn
High fever (Systemic Onset)
Biological agents
preparations
Infleximab and Etanercept
 Anti-TNFα
Surgical treatment
1.
2.
Synovectomy
Joint replacement
Comprehension questions
 female,
30 years old , joint pain
with low fever for two months,
RF (+)

diagnosis : RA ?
 Choice: yes ,no, uncertain
Thank you