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Current Concepts of Rheumatoid Arthritis

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Title: Current Concepts of Rheumatoid Arthritis


1
Current Concepts ofRheumatoid Arthritis
  • Vladimir Ognenovski, MDJoseph McCune, MD
  • University of Michigan

2
Rheumatoid Arthritis
  • A chronic, systemic autoimmune disease of unknown
    etiology
  • Characterized by symmetric, errosive,
    diarthrodial joint synovitis
  • May involve multiple organ systemscardiovascular
    , pulmonary, renal, hematologic, and peripheral
    nervous systems, skin and eyes

3
Epidemiology
  • affects 1 of U.S. adults
  • has an incidence of 150,000 new cases annually
  • most frequently diagnosed during the 4th-6th
    decade of life
  • occurs at a female-to-male ratio of 21 to 31

4
Genetic Factors
  • Strong association with class II major
    histocompatibility complex human leukocyte
    antigen on chromosome 6
  • HLA-DR4 - N European and Americans
  • HLA-DR1 - Italian, Israeli Jewish, some Hispanics
  • HLA-DR14 - Yakima Indians

5
Etiology and Pathogenesis
  • Suspected infectious agents
  • bacteria (mycoplasma, mycobacteria, enteric
    bacteria)
  • viruses (HTLV, retrovirus, herpesvirus,
    Epstein-Barr virus, rubella, parvovirus)
  • Defective recognition of autoantigen
  • pregnancy induced remission linked to
    maternal-fetal HLA mismatch

6
Rheumatoid Factor
  • most common autoantibody in RA
  • binds to the Fc portion of IgG molecule
  • usually an IgM antibody
  • less often an IgG or IgA antibody
  • detected in 70-80 of RA patients
  • high titer predicts adverse outcome
  • erosive arthritis, vasculitis

7
Rheumatoid Factor
  • Methods of detection
  • agglutinationIgG coated latex beads or
    erythrocytes
  • laser nephelometry
  • indirect immunofluorescence
  • radioimmuno assay
  • enzyme-linked immunosorbent assay

8
Disease associated with RF
  • rheumatoid disease
  • viral disease
  • parasitic infections
  • chronic bacterial infections
  • other hyper-?-globulinemic states

9
Disease associated with RF
  • 1. Rheumatoid disease
  • rheumatoid arthritis
  • systemic lupus erythematosus
  • scleroderma
  • mixed connective tissue disease
  • Sjogrens syndrome

10
Disease associated with RF
  • 2. Viral disease
  • AIDS
  • mononucleosis
  • epatitis
  • influenza

11
Disease associated with RF
  • 3. Parasitic infections
  • trapanosomiasis
  • malaria
  • Kala-azar
  • schistosomiasis
  • filariasis

12
Disease associated with RF
  • 4. Chronic bacterial infections
  • tuberculosis
  • syphilis
  • leprosy
  • brucellosis
  • yaws
  • salmonellosis
  • subacute bacterial endocarditis

13
Disease associated with RF
  • 5. other hyper-?-globulinemic states
  • hyper-?-globulinemic purpura
  • cryoglobulinemia
  • chronic liver disease
  • sarcoidosis
  • other chronic pulmonary diseases

14
Rheumatoid Arthritis pathology
  • Hallmark - synovitis characterized by hypertrophy
    and hyperplasia of the synovial cells and
    subsynovil stroma
  • inflammatory cells infiltrate the synovial lining
  • microvascular endothelial injury is the principal
    abnormality

15
Rheumatoid Arthritisclinical features and
diagnosis
  • synovitis (joint inflammation)
  • onset is usually insidious (wks-months) and
    unrelenting
  • 15 may be acute (within a few days)
  • earlier clinical features
  • morning stiffness
  • joint tenderness and swelling with restricted
    range of motion

16
Rheumatoid Arthritisclinical features and
diagnosis
  • Progressive clinical features
  • joint deformity and dysfunction from tendon and
    ligament inflammation
  • ulnar deviation, z-deformity of the thumb,
    swan-neck and boutonniere deformities of the
    interphalangeal joints
  • low grade fever
  • subcutaneous nodules of extensor area

17
Rheumatoid Arthritisclinical features and
diagnosis
  • Joint involvement
  • typically symmetrical
  • MCP, wrist, PIP, MTP, shoulder, knee, ankle, and
    elbow joints (in order of decreasing frequency of
    involvement)
  • cervical spine involvement may lead to
    atlantoaxial subluxation

18
Rheumatoid Arthritisimaging studies
  • radiographic features
  • bony erosion
  • cartilage loss
  • juxta-articular osteopenia
  • soft tissue swelling
  • magnetic resonance imaging
  • atlantoaxial subluxation

19
Rheumatoid Arthritisextra-articular
manifestations
  • dermatologicsubcutaneous nodules
  • hematologicanemia, thrombocytopenia,
    eosinophilia, leukopenia (Feltys syndrome)
  • hepaticelevated transaminases, nodular
    regenerative hyperplasia

20
Rheumatoid Arthritisextra-articular
manifestations
  • cardiacpericarditis, myocardial nodular
    granulomas
  • pulmonaryfibrosis, nodules, pleural effusion
  • ocularkeratoconjunctivitis, episcleritis,
    sleritis

21
Rheumatoid Arthritislaboratory abnormalities
  • Serologic findingsanemia, thrombocytopenia, mild
    leukocytosis, positive RF and elevated ESR,
    C-reactive protein, serum globulin
  • Synovial fluid findingsstraw-colored and
    slightly cloudy fluid, leukocytosis 5,000 to
    25,00/mm3, 85 polymorphonuclear cells

22
Rheumatoid Arthritisdifferential diagnosis
  • osteoarthritis
  • spondyloarthritis
  • gout and pseudogout
  • chronic fatigue syndrome, fibromyalgia
  • polymyalgia rheumatica, giant cell arteritis
  • systemic lupus erythematosus
  • infectious arthritis

23
Rheumatoid Arthritistreatment
  • Goal prevention of joint disease progression to
    irreversible damage
  • remission is rare
  • multidisciplinary approach
  • patient education treatment plan, compliance,
    understanding of disease
  • psychotherapy manage pain and stress
  • rehabilitation exercise, joint protection

24
Rheumatoid Arthritisdrug therapy
  • early aggressive treatment
  • control swelling and pain
  • reduce the probability of irreversible joint
    damage

25
Rheumatoid Arthritis Non-steroidal
anti-inflammatory drugs
  • NSAIDS are anti-inflammatory and analgesic
  • do not modify the disease course
  • GI side effects are common
  • take NSAIDS with food or misoprostol
  • monitor older patients closely (hypertension,
    congestive heart failure, diabetes, and renal
    insufficiency)
  • ? substitute low-dose prednisone in the elderly
    because of risk of GI bleed

26
Rheumatoid Arthritis Disease-modifying
antirheumatic drugs
  • DMARDs can alter the progression of RA
  • should be used before joints are damaged
  • may be initiated within the first 3 months of
    diagnosis in patients with ongoing inflammation
    despite treatment with NSAIDS
  • a rheumatologist should be consulted when
    steroids or DMARDs are used
  • may take 2wks - 6 months for a response

27
Rheumatoid Arthritis choice of DMARDs
  • cost
  • convenience of administration
  • convenience of toxicity monitoring
  • compliance
  • comorbid disease
  • toxicity
  • severity and prognosis of patient

28
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • hydroxychloroquine retinal toxicity, diarrhea
  • sulfasalazine bone marrow suppression, GI
    intolerance
  • HCQ and sulfasalazine are often initially
    selected for milder disease because of the safety
    and convenience of the drugs
  • need semiannual eye exam for HCQ

29
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • methotrexate bone marrow suppression, hepato
    and pulmonary toxicity GI intolerance,
    stomatitis, rash
  • MTX is selected for more severe disease
  • has the most rapid onset and sustained benefit
  • given on a weekly basis
  • requires close monitoring

30
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • gold salts bone marrow suppression, rash,
    stomatitis, proteinuria
  • administered intramuscularly on a weekly basis
    for 3-5 months, followed by less frequent dosing
  • requires close monitoring of bone marrow and
    renal toxicity

31
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • azathioprine bone marrow suppression, hepatoto
    xicity, GI symptoms
  • AZA is used when disease activity persists on
    other DMARDs
  • may be safer than MTX for patients gt 65 years
    with renal insufficiency

32
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • D-penicillamine bone marrow suppression, rash,
    stomatitis, dysgeusia, proteinuria, autoimmune
    disease
  • d-penicillamine is used when disease activity
    persists on other DMARDs
  • associated with high incidence of lupus,
    myasthenia gravis, pemphigus, Goodpastures

33
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • cyclophosphamide bone marrow suppression hemorrha
    gic cystitis, malignancy, infertility
  • oral immunosuppressive agent, very toxic
  • used for severe vasculitis and other
    extra-articular involvement

34
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • cyclosporin A renal toxicity, hypertension hepato
    toxicity
  • oral immunosuppressive agent
  • not yet approved for treatment of RA by the FDA

35
Rheumatoid Arthritis choice of DMARDs
  • Drug Side Effects
  • cyclosporin A renal toxicity, hypertension hepato
    toxicity
  • oral immunosuppressive agent
  • not yet approved for treatment of RA by the FDA

36
Rheumatoid Arthritis glucocorticoids
  • the most potent and rapidly acting
    anti-inflammatory agent
  • used as a bridge therapy until DMARDs become
    effective local injection is efficacious and
    less toxic than DMARDs
  • low dose systemic therapy, may slow the rate of
    joint damage, and is effective in refractory RA

37
Rheumatoid Arthritis glucocorticoids
  • Side effects
  • osteoporosis, cushingoid state, hypertension,
    premature athersclerosis, infection
  • Reducing the risk of osteoporosis
  • regular exercise, timely estrogen therapy,
    supplemental calcium and vitamin D
  • calcitonin or biphosphonates in patients with low
    bone mass and refractory to hormone replacement
    therapy

38
Rheumatoid Arthritis new drug therapies
  • Tetracycline
  • radiation synovectomy with isotopes
  • immunotherapy anti-CD4 monoclonal
    antibodiesanti-TNF-? antibodiesanti-IL-2r

39
Rheumatoid Arthritis surgical therapy
  • to prevent damage to joints or tendons by
    inflammatory synovium
  • to correct structural joint damage resulting in
    discomfort and limitation of function
  • most useful for upper extremity
  • tenosynovectomy for exuberant nodule formation or
    synovitis in extensor tendons
  • joint fusion or joint replacement

40
Rheumatoid Arthritis prognosis
  • Progressive in 2/3 of patients resulting in
    disabling and destructive disease
  • 20 may have mild and intermittent course
  • 10 may achieve complete remission
  • factors predicting poor prognosismale, age gt50,
    poor functional capacity, positive RF, presence
    of nodules, HLA-DR4 haplotype

41
Rheumatoid Arthritis prognosis
  • 3- to10-years decrease in survival in 50 of
    patients
  • cause of premature death
  • cardiovascular
  • malignancy
  • infection or sepsis
  • vasculitis, rheumatoid lung
  • GI hemorrhage and perforation

42
References
  • The American Rheumatism Association 1987 revised
    criteria for the classification of rheumatoid
    arthritis. Arthritis Rheum 198831315-324
  • Ad Hoc Committee on Clinical Guidelines
    Guidelines for the management of rheumatoid
    arthritis. Arthritis Rheum 199639713-722
  • Ad Hoc Committee on Clinical Guidelines
    Guidelines for monitoring drug therapy in
    rheumatoid arthritis. Arthritis Rheum
    199639723-731
  • Am College of Rheumatology Task Force on
    Osteoporosis Guidelines Recommendations for the
    prevention and treatment of glucocorticoid-induced
    osteoporosis. Arteritis Rheum 1996391791-1801
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