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

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

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

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

Clinical features 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. Symptoms: Joint pain Morning stiffness: several hours (more than one hour) General symptoms: fatigue, general malaise Disability Non-articular symptoms

Sings Swelling Warmth Tenderness Deformities Nodules Involvement of joints is symmetrical

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

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

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

Treatment NSA DMARDs Biologic treatment

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

NSA Cyklooxigenase: NSA clasification COX-1 : fyziological effect (stomach, colon, kidney, Trc) COX-2: 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

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

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

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

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