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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