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 Arachidonic acid cyklooxygenase Endoperoxids inhibition by corticosteroids inhibition by NSA tromboxane B2 PGE2 PG2F2 prostacykline



Cyklooxigenase

: COX-1 : fyziological effect (stomach, colon, kidney, Trc) COX-2: inflammation

NSA

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

 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

 p.o.

Corticosteroid drugs

 Rapid effect  i.a.

 i.m.

 i.v.

 Strong antiinflammatory effect  Analgetic effekt  AE, SAE !!

 lokálne

Biological treatment

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