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

Rheumatoid arthritis

doc.MUDr. Želmíra Macejová, PhDdoc.MUDr. Želmíra Macejová, PhDIII. Internal clinic LF UPJŠ III. Internal clinic LF UPJŠ

Rheumatoid arthritis Chronic systemic diseaseChronic systemic disease Prevalence 1%Prevalence 1% More common in women, women: men 3:1More common in women, women: men 3:1 autoimuniy disease- production of rheumatoid autoimuniy disease- production of rheumatoid

factor – antibody agains human IgGfactor – antibody agains human IgG synovitis, deformity, destraction, instability, synovitis, deformity, destraction, instability,

subluxatiosubluxatio symetrical involvement of periferial jointssymetrical involvement of periferial joints possibility of involvement of all joints in the bodypossibility of involvement of all joints in the body

Chronical diseaseChronical disease

Clinical features:Clinical features: general: general: Fatigue, general malaise, subfebrility, Fatigue, general malaise, subfebrility,

weight loss, depressionweight loss, depression

local:local: arthralgia, myalgia, morning stiffness, joint arthralgia, myalgia, morning stiffness, joint

pain, pain, Pain is the worst in the morning: PIP, Pain is the worst in the morning: PIP,

MCP, wrist, MTP - symmetricalMCP, wrist, MTP - symmetrical

Pathogenesis of RA unknownunknown Multifactorial:Multifactorial:

genetic: genetic: associátion with specific type of associátion with specific type of HLA (HLA DR-4)HLA (HLA DR-4)

pro-inflammatory cytokines: pro-inflammatory cytokines: TNF alfa, IL-17, IL-1, IL-6TNF alfa, IL-17, IL-1, IL-6

hormonal factorshormonal factors: : prolactine, lack of prolactine, lack of testosteronetestosterone

Clinical features

pain and stiffness in the small joints of the hand and feet, pain and stiffness in the small joints of the hand and feet, chronic bilateral symmetrical peripherial polyarthritischronic bilateral symmetrical peripherial polyarthritis

involvement of all joints in the body: knees, wrists, elbows, involvement of all joints in the body: knees, wrists, elbows, etc.etc.

Symptoms: Symptoms:

Joint painJoint pain

Morning stiffness: several hours (more than one hour)Morning stiffness: several hours (more than one hour)

General symptoms: fatigue, general malaiseGeneral symptoms: fatigue, general malaise

DisabilityDisability

Non-articular symptomsNon-articular symptoms

Sings

SwellingSwelling

WarmthWarmth

TendernessTenderness

DeformitiesDeformities

NodulesNodules

Involvement of joints is symmetricalInvolvement of joints is symmetrical

Diagnostic criteria of RA

1. Morning stiffness (more than 1 hour)1. Morning stiffness (more than 1 hour)

2. Arthritis of three and more joints2. Arthritis of three and more joints

3. Arthritis of hand joints (PIP, MCP, wrist)3. Arthritis of hand joints (PIP, MCP, wrist)

4. Symetrical arthritis4. Symetrical arthritis

5. Rheumatoid nodules5. Rheumatoid nodules

6. Rheumatoid facktor6. Rheumatoid facktor

7. X-ray changes7. X-ray changes

Laboratory findings

RFRF ( Latex, ELISA) – ( Latex, ELISA) – seropositivityseropositivity : anaemia: anaemia

trombocytosistrombocytosis CRP, ESRCRP, ESR gamaglobulins, alfa2globulinsgamaglobulins, alfa2globulins Synovial fluidSynovial fluid: aseptic : aseptic

Steinbrocker – X-ray classification

I.st: periartikular osteoporosisI.st: periartikular osteoporosis

II.st: destruction, loss of joint space, erosions, II.st: destruction, loss of joint space, erosions, cysts cysts

III. st.: + subluxationIII. st.: + subluxation

IV. st.: ankylosisIV. st.: ankylosis

Treatment

NSANSA DMARDsDMARDs Biologic treatmentBiologic treatment

NSA

Fosfolipidy cell membranesFosfolipidy cell membranes

fosfolipasefosfolipase inhibition by inhibition by

corticosteroidscorticosteroids

Arachidonic acidArachidonic acid

cyklooxygenasecyklooxygenase inhibition by NSAinhibition by NSA

EndoperoxidsEndoperoxids

tromboxane B2 PGE2 PG2F2 prostacyklinetromboxane B2 PGE2 PG2F2 prostacykline

NSA

CyklooxigenaseCyklooxigenase:: COX-1 :COX-1 : fyziological effect fyziological effect

(stomach, colon, (stomach, colon, kidney, Trc)kidney, Trc)

COX-2:COX-2: inflammationinflammation

NSA clasificationNSA clasificationI. Inhibition of both I. Inhibition of both

isoforms: COX-1 a isoforms: COX-1 a COX-2COX-2

II. Most inhibition of II. Most inhibition of COX-2COX-2

III. Selective inhibition III. Selective inhibition of COX-2of COX-2

DMARDs: disease modifying antirheumatic drugs

AntimalaricsAntimalarics MethotrexateMethotrexate SulfasalazineSulfasalazine GoldGold LeflunomideLeflunomide Imunosupressive drugs: cyklosporineImunosupressive drugs: cyklosporine

cyklofosfamide cyklofosfamide

DMARDs: combinationDMARDs: combinationMost common combination: Most common combination: metotrexate +sulfasalazine metotrexate +sulfasalazine

metotrexate+antimalaricsmetotrexate+antimalarics

metotrexate+cyklosporinemetotrexate+cyklosporine Possible combination: NSA, DMARDs, Possible combination: NSA, DMARDs,

corticosteroidscorticosteroids synergic effectsynergic effect lower doseslower doses less AEless AE remission of diseaseremission of disease

Corticosteroid drugs p.o.p.o.

i.a.i.a.

i.m.i.m.

i.v.i.v.

lokálnelokálne

Rapid effectRapid effect

Strong Strong antiinflammatory antiinflammatory effecteffect

Analgetic effektAnalgetic effekt

AE, SAE !!AE, SAE !!

Biological treatment

Anticytokine treatmentAnticytokine treatment Anti - TNF alfa: Anti - TNF alfa:

infliximab,adalimumab,etaneinfliximab,adalimumab,etanerceptrcept

Anti - IL-1: anakinraAnti - IL-1: anakinra Anti - CD20 B-lymfocyt: Anti - CD20 B-lymfocyt:

rituximabrituximab Many others on clinical trialsMany others on clinical trials

Rapid effectRapid effect Strong effectStrong effect

AE:AE: Activation of TBCActivation of TBC