RHEUMATOID ARTHRITIS ( RA ) Jiang Lindi (Zhongshan Hospital) RHEUMATOID ARTHRITIS ( RA )...

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RHEUMATOID ARTHRITIS RHEUMATOID ARTHRITIS RA RA Jiang Lindi Jiang Lindi (Zhongshan Hospital) (Zhongshan Hospital)

Transcript of RHEUMATOID ARTHRITIS ( RA ) Jiang Lindi (Zhongshan Hospital) RHEUMATOID ARTHRITIS ( RA )...

Page 1: RHEUMATOID ARTHRITIS ( RA ) Jiang Lindi (Zhongshan Hospital) RHEUMATOID ARTHRITIS ( RA ) Jiang Lindi (Zhongshan Hospital)

RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS(( RARA ))

Jiang LindiJiang Lindi(Zhongshan Hospital)(Zhongshan Hospital)

RHEUMATOID ARTHRITISRHEUMATOID ARTHRITIS(( RARA ))

Jiang LindiJiang Lindi(Zhongshan Hospital)(Zhongshan Hospital)

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What is RA? RA is a chronic polyarticular inflammatory arthritis tha

t 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.

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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

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2. Genetic factors A high incidence among monozygotic twins (30% ~50

%),first-degree relative Role of HLA-DR4 in the susceptibility to and severity o

f 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 ): QKRA

A 或 QRRAA It was considered to be related with the severity of establish

ed RA

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3. Gender: – Predominance in women– Improvement or remission of RA during p

regnancy

4.Induced factors: tiredness, humidity, cold, mulnutrition, psychical stimuli

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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

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PATHOLOGIC FINDING1. 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

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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, weig

ht loss may be seen

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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.

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( 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.

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Figure1-4: 尺侧偏移

钮扣花畸形

掌指关节肿胀

受累关节示意

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( 6 ) Functional capacity 1991 ACR criteria for classification of functional status in RAClass 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 activitiesClass III Able to perform usual self-care activities, but limited in vocational and avocational activitiesClass IV Limited in ability to perform usual self-care vocational, and avocational activities

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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

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( 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

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( 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

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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

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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, sar

coidosis, infective endocarditis, tuberculosis, leprosy ,viral infection and parasitic infections, other autoimmune disease (SLE, PSS, DM), healthy people(10%).

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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 findingRheumatoid nodule and synovial biopsy

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1988 Revised ARA Criteria for Classification of RA

Criterion definition1.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 nodules6.Serum rheumatoid factor7.Radiographic changes including erosions or unequivocal bony decalcification

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Differential Diagnosis

Osteoarthritis: – occurs in 40 or more– pain increase through day or with use– involve DIP, weight-bearing joints– radiologic findings: subchondral sclerosis, oste

ophytes– lab findings: normal

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RA AS HLA-DR4 HLA-B27 women,30-50 years young maleSmall 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(-)

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TREATMENT The primary objective:Reduction of inflammation and painPrevention of joint deformity Preservation of muscle strength and joint

functionMinimizing undesirable drug side effects

and improvement of quality of life

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1. General approach : Acute phase: rest and restriction of mot

ion Inactive phase: exercise therapy

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Drug therapyNSAIDs (nonsteroidal anti-inflammatory dr

ugs)GlucocorticoidsDMARDs (disease modifying anti-inflammat

ory drugs)

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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: gas

trointestinal tract , kidney, hematopoietic system, central nervous system and liver.

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Cell membrane phospholipids

Inhibited by glucocorticoidsphospholipase

Arachidonic acid

Inhibited by NSAIDsO2+Cyclooxygenase

Cyclic endoperoxides(PGG2, PGH2)

Thromboxane B2 PGE2 PGF2

ThromboxaneA2

6-Keto-PGE1

Toxic oxygen radicals

PGI2

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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

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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.

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DMARDsMTX: gastrointestinal and oral ulceration, liver failure,7.5-15mg/qwDP: hematocytopenia, proteinuria, myasthenia gravis, Good-pasture’s syndromeSASP: head ache, gastrointestinal upset ,2- 3g/dAntimalarials: retinal lesion,loss of vision hydroxychloroquine200mg/qd

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Glucocorticoid GC is the most powerful anti-inflammtory and immunos

uppressive drugs. GC rapid and substantial control of symptoms of inflam

mation. Other therapies (NSAID or DMARDs) failed or systemic in

volvement(neuropathy,pleuritis,vasculitis,) occur Long-term or higher doses use : infection, osteoporosis, hypertension. Recent evidence:low dose GC treatment with 5-7.5mg d

aily decreases radiographic progression in early RA

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Drug thearpyThe first drug used to treat RA is an N

SAID(nonsteroidal anti-inflammatory drug).

DMARDs should be added early and used aggressively to lessen the deformity.

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surgeryEffective for RA patients with the

following conditions: impending tendon rupture, functional limitation, joint instability.

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PROGNOSIS

Patients die 10-15 earlier Mortality curve resembles that for stage IV Hodgki

n’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

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