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Rheumatoid arthritis doc.MUDr. Želmíra Macejová, PhD doc.MUDr. Želmíra Macejová, PhD III. Internal clinic LF UPJŠ

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1 Rheumatoid arthritis doc.MUDr. Želmíra Macejová, PhD doc.MUDr. Želmíra Macejová, PhD III. Internal clinic LF UPJŠ

2 Rheumatoid arthritis Chronic systemic disease Chronic systemic disease Prevalence 1% Prevalence 1% More common in women, women: men 3:1 More common in women, women: men 3:1 autoimuniy disease- production of rheumatoid factor – antibody agains human IgG autoimuniy disease- production of rheumatoid factor – antibody agains human IgG synovitis, deformity, destraction, instability, subluxatio synovitis, deformity, destraction, instability, subluxatio symetrical involvement of periferial joints symetrical involvement of periferial joints possibility of involvement of all joints in the body possibility of involvement of all joints in the body

3 Chronical disease Clinical features: general: Fatigue, general malaise, subfebrility, weight loss, depression Fatigue, general malaise, subfebrility, weight loss, depressionlocal: arthralgia, myalgia, morning stiffness, joint pain, arthralgia, myalgia, morning stiffness, joint pain, Pain is the worst in the morning: PIP, MCP, wrist, MTP - symmetrical Pain is the worst in the morning: PIP, MCP, wrist, MTP - symmetrical

4 Pathogenesis of RA unknown unknown Multifactorial: Multifactorial: genetic: associátion with specific type of HLA (HLA DR-4) genetic: associátion with specific type of HLA (HLA DR-4) pro-inflammatory cytokines: pro-inflammatory cytokines: TNF alfa, IL-17, IL-1, IL-6 TNF alfa, IL-17, IL-1, IL-6 hormonal factors: prolactine, lack of testosterone hormonal factors: prolactine, lack of testosterone

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6 Clinical features pain and stiffness in the small joints of the hand and feet, chronic bilateral symmetrical peripherial polyarthritis pain and stiffness in the small joints of the hand and feet, chronic bilateral symmetrical peripherial polyarthritis involvement of all joints in the body: knees, wrists, elbows, etc. involvement of all joints in the body: knees, wrists, elbows, etc.Symptoms: Joint pain Morning stiffness: several hours (more than one hour) General symptoms: fatigue, general malaise Disability Non-articular symptoms

7 Sings SwellingWarmthTendernessDeformitiesNodules Involvement of joints is symmetrical

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9 Diagnostic criteria of RA 1. Morning stiffness (more than 1 hour) 2. Arthritis of three and more joints 3. Arthritis of hand joints (PIP, MCP, wrist) 4. Symetrical arthritis 5. Rheumatoid nodules 6. Rheumatoid facktor 7. X-ray changes

10 Laboratory findings RF ( Latex, ELISA) – seropositivity RF ( Latex, ELISA) – seropositivity : anaemia : anaemia trombocytosis trombocytosis CRP, ESR CRP, ESR gamaglobulins, alfa2globulins gamaglobulins, alfa2globulins Synovial fluid: aseptic Synovial fluid: aseptic

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12 Steinbrocker – X-ray classification I.st: periartikular osteoporosis II.st: destruction, loss of joint space, erosions, cysts III. st.: + subluxation IV. st.: ankylosis

13 Treatment NSA NSA DMARDs DMARDs Biologic treatment Biologic treatment

14 NSA Fosfolipidy cell membranes fosfolipase inhibition by fosfolipase inhibition by corticosteroids corticosteroids Arachidonic acid cyklooxygenase inhibition by NSA cyklooxygenase inhibition by NSAEndoperoxids tromboxane B2 PGE2 PG2F2 prostacykline

15 NSA Cyklooxigenase: Cyklooxigenase: COX-1 : COX-1 : fyziological effect (stomach, colon, kidney, Trc) fyziological effect (stomach, colon, kidney, Trc) COX-2: COX-2: inflammation inflammation NSA clasification I. Inhibition of both isoforms: COX-1 a COX-2 II. Most inhibition of COX-2 III. Selective inhibition of COX-2

16 DMARDs: disease modifying antirheumatic drugs Antimalarics Antimalarics Methotrexate Methotrexate Sulfasalazine Sulfasalazine Gold Gold Leflunomide Leflunomide Imunosupressive drugs: cyklosporine Imunosupressive drugs: cyklosporine cyklofosfamide cyklofosfamide

17 DMARDs: combination DMARDs: combination Most common combination: metotrexate +sulfasalazine metotrexate +sulfasalazine metotrexate+antimalarics metotrexate+antimalarics metotrexate+cyklosporine metotrexate+cyklosporine Possible combination: NSA, DMARDs, corticosteroids Possible combination: NSA, DMARDs, corticosteroids synergic effect synergic effect lower doses lower doses less AE less AE remission of disease remission of disease

18 Corticosteroid drugs p.o. p.o. i.a. i.a. i.m. i.m. i.v. i.v. lokálne lokálne Rapid effect Strong antiinflammatory effect Analgetic effekt AE, SAE !!

19 Biological treatment Anticytokine treatment Anticytokine treatment Anti - TNF alfa: infliximab,adalimumab,etane rcept Anti - TNF alfa: infliximab,adalimumab,etane rcept Anti - IL-1: anakinra Anti - IL-1: anakinra Anti - CD20 B-lymfocyt: rituximab Anti - CD20 B-lymfocyt: rituximab Many others on clinical trials Many others on clinical trials Rapid effect Strong effect AE: Activation of TBC

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