RHEUMATOID ARTHRITIS
（ RA）
Jiang Lindi
(Zhongshan Hospital)
What is RA?
? RA is a chronic polyarticular inflammatory arthritis
that involves not only small joints of the hands and
feet but also systemic organs,
? Pathologic change,chronic synovitis with pannus (血管
翳 )formation,
? It will cause bony destruction,deformation,disability
if joint inflammation repeatedly occur,
? RF is present in the sera of more than 75%of patients,
? The prevalence rate of RA has been estimated to be
0.32%-0.36% in China,Women appear to be affected
three times more commonly than men,
ETIOLOGY
1,Infectious agents,Epstein-Barr virus,
mycoplasma,macobacteria,retroviruses
– T lymphocyte and macrophage activation
– B lymphocyte activation
– Change of the gene expression
– Molecular mimicry
2,Genetic factors
? A high incidence among monozygotic twins (30%
~50%),first-degree relative
? Role of HLA-DR4 in the susceptibility to and severity
of RA
? 70% RA patients, a relative risk of having RA with HLA-
DR4 of 4 to 5
? The susceptibility epitope (shared epitope 共同表位 ),
QKRAA或 QRRAA
? It was considered to be related with the severity of
established RA
3,Gender,
– Predominance in women
– Improvement or remission of RA during
pregnancy
4.Induced factors,tiredness,humidity,
cold,mulnutrition,psychical stimuli
antigen,HLA-DR(QKRAA),heat shock protein,IgG,type II collagen
antigen processing
macrophages +MHCII-peptide complexes
presentation
T cell
cytokine（ IL-1,2,3,4,6,TNF,r-INF）
B cell activation
immune damage RF and other antibody
collagenase,stromolysin
cartilage and bone destruction extra-articular symptom
PATHOLOGY
PATHOLOGIC FINDING
1,chronic synovitis
In acute phase,effusion and cell infiltration
In chronic phase,
the number of A type cell remarkably increases
the pannus erodes cartilage,bone,ligaments and tendons,
2,extra-articular,vasculitis,rheumatoid
nodule
CLINICAL FAETURES
? The usually age at onset is 35-50 years
? The ratio of female to male is 3:1
? The onset of RA is usually insidious
? Systemic symptom of fatigue,malaise,fever,
weight loss may be seen
1,Joint manifestation
（ 1） morning stiffness
– stiffness persisting for over 30 minutes is
prominent in the morning or after daytime
activity and subsides during the day
– The persisting length of morning stiffness is
associated with the degree of joint
inflammation,
– The duration of morning stiffness is used as
the index of disease activity,
（ 2） pain and tenderness,painful on rest
location,small (PIP,MCP),symmetric joint
characteristic,persisting,dull or swollen pain
（ 3） swelling,synovial proliferation,effusion,
swelling of soft tissue
（ 4） articular deformity,ulnar deviation of the
fingers,“swan-neck” deformity,atrophy of skin
and muscle (see figure1-5)
（ 5） involvement of special joint,atlantoaxial
subluxation,shoulders,temporomandibular joint,hips,
Figure1-4,尺侧偏移
钮扣花畸形
掌指关节肿胀
受累关节示意
（ 6） Functional capacity
1991 ACR criteria for classification of functional
status in RA
Class I Completely able to perform usual activities
of daily living (self-care,vocational,and avocational)
Class II Able to perform usual self-care and
vocational activities,but limited in avocational activities
Class III Able to perform usual self-care activities,
but limited in vocational and avocational activities
Class IV Limited in ability to perform usual self-care
vocational,and avocational activities
2,Extra-articular manifestations
（ 1） Rheumatoid nodules
– 20%-30% patients
– areas that are repeatedly subjected to friction,
such as the extensor surface of the forearm
– The advent indicates the disease is in the
active phase
（ 2） rheumatoid vasculitis,episcleritis,
scleritis
（ 3） pulmonary manifestation
– diffuse interstitial fibrosis,abnormal on CT scan,restrictive
diffuse pattern
– intrapulmonary nodules:,asymptomatic,infected,cavitate
– rheumatoid pleural disease,exudative,WBC<5 000/mm3,
lower level of glucose
? (4） pericarditis,30% pericardial effusion,asymptomatic
（ 5） gastrointestinal manifestation,
– nausea,loss of appetite
（ 6） kidney,drug-induced,amyloid degeneration
（ 7） Neurologic manifestations,
– A cervical myclopathy can result from atlantoaxial
subluxation,sensory abnormity and loss of strength
– peripheral neuropathies can be produced by proliferating
synovium causing compression of nerves and rheumatoid
vasculitis,carpal tunnel syndrome,
（ 8） Hematologic manifestations, anemia,Felty’s syndrome
LABORATORY FINDING
1,Anemia,a hypochromic normocytic anemia
2,Elevated ESR and CRP are demonstrated
an active condition of the disease
3,Joint fluid examination,WBC in the range
5000 to 20 000/mm3,with 50~70% as
polymorphonuclear leukocytes,a poor
mucin clot,normal level of glucose
6,RF
? RF is an IgG,IgA,IgM antibody directed against the Fc
fragment
? RF is Present in the sera of more than 60%-70% patients
? Despite the extremely strong association of RF’s with RA,they
clearly do not cause the disease,
? RF production occurs commonly in other disorders,syphilis,
sarcoidosis,infective endocarditis,tuberculosis,leprosy,viral
infection and parasitic infections,other autoimmune disease
(SLE,PSS,DM),healthy people(10%),
7.X- ray changes
Class I swollen of soft tissue,juxta-articular
osteoporosis
Class II joint space narrowing
Class III bony cysts and bony erosions
Class IV subluxation,fibrous and bony ankylosis
8,Pathologic finding
Rheumatoid nodule and synovial biopsy
1988 Revised ARA Criteria for
Classification of RA
Criterion definition
1.Morning stiffness lasting at least 1hr
2.Arthritis of three at least three joint areas simultaneously
or more joint areas having soft tissue swelling or fluid
3.Arthritis of hand joints at least one joint area swollen or above
in wrist,MCP,PIP joint
4.Symmetric arthritis simultaneous involvement of the same
areas on both sides of the body
5.Rheumatoid nodules
6.Serum rheumatoid factor
7.Radiographic changes including erosions or unequivocal bony
decalcification
Differential Diagnosis
?Osteoarthritis,
– occurs in 40 or more
– pain increase through day or with use
– involve DIP,weight-bearing joints
– radiologic findings,subchondral sclerosis,
osteophytes
– lab findings,normal
RA AS
HLA-DR4 HLA-B27
women,30-50 years young male
Small joint,symmetric lower extremity,asymmetric
polyarticular oligoarthropathy
wrist,finger sacroilitis,lumbar spine
synovitis periarticular soft tissue inflammation
ulnar deviation marginal bridging sundesmophytes,
swan-neck deformity bamboo spine
RF(+) RF(-)
TREATMENT
The primary objective,
?Reduction of inflammation and pain
?Prevention of joint deformity
?Preservation of muscle strength and joint
function
?Minimizing undesirable drug side effects
and improvement of quality of life
1,General approach,
? Acute phase,rest and restriction of
motion
? Inactive phase,exercise therapy
Drug therapy
?NSAIDs (nonsteroidal anti-inflammatory
drugs)
?Glucocorticoids
?DMARDs (disease modifying anti-
inflammatory drugs)
NSAIDs
? NSAIDs is used as the first drug of treating RA
? NSAIDs have analgesic and anti-inflamatory effects but
are believed not to be capable of preventing erosions or
altering progression of the disease,
? NSAIDs,ibuprofen,naproxen,sulindac,diclofenac
? NSAIDs share a common spectrum of clinical toxicities,
gastrointestinal tract,kidney,hematopoietic system,
central nervous system and liver,
Cell membrane phospholipids
Inhibited by glucocorticoids
phospholipase
Arachidonic acid
Inhibited by NSAIDs O2+Cyclooxygenase
Cyclic endoperoxides(PGG2,PGH2)
Thromboxane B2 PGE2 PGF2?
ThromboxaneA2
6-Keto-PGE1?
Toxic oxygen
radicals
PGI2
Advance
? Two isoforms of COX have been discovered,COX-1
and COX-2
– COX-1 is expressed constitutively in gastric mucosa,Kidney,
platelets,
– COX-2 expression is inducible by cytokines and growth factors in
macrophages,monocytes,synoviocytes,
? COX-2 played a key role in inflammatory conditions
? Selective COX-2 inhibitors have been developed
DMARDs
(disease-modifying antirheumatic drugs)
?DMARDs have the potential to inhibit the
abnormal immune response and delay the
progression of the disease,
? DMARDs should be suggested within 3 to
6 months,
?The time of action will be retarded 3-6
month after taking DMARDs,
?Careful monitoring for toxicity is required,
DMARDs
?MTX,gastrointestinal and oral ulceration,
liver failure,7.5-15mg/qw
?DP,hematocytopenia,proteinuria,myasthenia
gravis,Good-pasture’s syndrome
?SASP,head ache,gastrointestinal upset,2-
3g/d
?Antimalarials,retinal lesion,loss of vision
hydroxychloroquine200mg/qd
Glucocorticoid
? GC is the most powerful anti-inflammtory and
immunosuppressive drugs,
? GC rapid and substantial control of symptoms of
inflammation,
? Other therapies (NSAID or DMARDs) failed or
systemic involvement(neuropathy,pleuritis,vasculitis,)
occur
? Long-term or higher doses use, infection,osteoporosis,
hypertension,
? Recent evidence:low dose GC treatment with 5-7.5mg
daily decreases radiographic progression in early RA
Drug thearpy
?The first drug used to treat RA is
an NSAID(nonsteroidal anti-
inflammatory drug),
?DMARDs should be added early and
used aggressively to lessen the
deformity,
surgery
?Effective for RA patients with the
following conditions,impending
tendon rupture,functional limitation,
joint instability,
PROGNOSIS
? Patients die 10-15 earlier
? Mortality curve resembles that for stage IV
Hodgkin’s disease or triple-vessel coronary artery
disease
? Risk factors of poor prognosis,positive RF; poor
functional status; more than 30 inflamed joints;
extra-articular manifestations