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EVALUARE SI MONITORIZARE

IN ARTRITA REUMATOIDA
Codrina Ancuta
MD, PhD, CCD
Sef lucrari

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EVALUARE versus
MONITORIZARE
Evaluare
caracterizeaza boala la
un moment dat
- activa/ inactiva
remisiune;
- severa/ potential
severa
- refractara la
tratament

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Monitorizare
evalueaza schimbarile
- activitatea AR
- severitatea AR
intr-o perioada de timp:
- ameliorare
- remisiune
- agravare

Evaluare initiala

Diagnostic cert
crt clasificare ACR 1987
crt early referral
crt AR precoce
Aprecierea activitatii AR
Manifestari extra-articulare
Factori prognostic negativ
generali
Pt damage structural
Factori risc cardio-vasculari
Bilant pt initiere tratament
hepatic, renal, pulmonar,
etc

DOMENII EVALUARE

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Evaluare in dinamica
(monitorizare)

Eficacitate tratament
Clinico-biologica
Radiologica (progresie)
Functionala

Tolerabilitate/
tratament

toxicitate

raspuns la tratament
activitate boala

clinic
functional (dizabilitate)
damage (imagistic)

EVALUAREA ACTIVITATII AR

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PARAMETRI OBLIGATORII ACR

Numar Articulatii Tumefiate (NAT)


9.1
evaluare functionala
9.0
evaluarea durerii
8.6
Numar Articulatii Dureroase (NAD)
8.2
evaluare radiologica
8.1
evaluarea globala activitate AR de pacient 8.0
reactanti faza acuta
7.3
evaluare globala activitate AR de medic
4.3

OMERACT (Outcome Measures in RA Clinical Trials), 1992


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INDICI EVALUARE
Indici simpli
- Articulari (numar articulatii
dureroase si tumefiate)
- durere
- evaluare globala activitate AR
medic
- evaluare globala activitate AR
pacient
- HAQ-DI evaluare functionala
- SF-36 evaluare functionala
- FACIT pt fatigabilitate

Indici compusi

ACR
DAS/ DAS28
CDAI
SDAI
RADAI

PRO = PATIENT REPORTED OUTCOME


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INDICI ARTICULARI: NUMAR ARTICULATII


DUREROASE SI TUMEFIATE
Index articular Ritchie
53 articulatii:
IFP,
MCF,
TM,
acromioclaviculare,
sterno-costoclaviculare
= grupuri
sensibilitatea: 0-3

0 = fara durere
1 = durere la palpare
2 = durere + grimasa
3 = durere + retragere

Simpla, reproductibila
Nu se foloseste de rutina
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Indexul de tumefiere
articulara 44
- elimina 9 artic
- tumefierea 0-1:
- 0 = fara tumefiere
- 1 = tumefiere

Indexul articular 28
ignora TT, picior
durere NAD
tumefactie NAT
scala 0-1
Si studii clinice!

66/68
artic

Ritchie
Index

Temporomandibulare

Sternoclaviculare

Acromioclaviculare

scapuloumerala

Cot

Pumn

MCF

IFP mana

IFD mana

Coxo-femurala

Genunchi

Tibio-tarsiana

Articulatii

Talocalcaneal

44 artic 36 artic 28 artic 42 artic

+ (-1)

+
+

Tars

MTF

IFD picior

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DURERE versus SINOVITA


Durere la presiune, in
repaus (MCF, carp)
Durere la mobilizarea
articulara (SH)
Durere la chestionarea
pacient (CF)
Presiunea realizata de
police si index =
albirea patului ungheal
al examinatorului

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NU deformarea artic sau


edemul
Amplitudine redusa de
mobilizare articulara

ARTICULATII IFP
(interfalangiene proximale)

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ARTICULATII MTF
(metacarpofalangiene)

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CARP

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COT

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ARTICULATII SCAPULOHUMERALE

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GENUNCHI

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ARTIC TIBIO-TARSIENE

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ARTIC MTF
(metatarsofalangiene)

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DUREREA SI ACTIVITATEA GLOBALA


A BOLII

Scala analoga vizuala SAV 0-100 mm/ 0-10


cm Huskisson:

0=absenta durerii/ 100= durere f intensa


ultimele 48 h

Scala gradata numeric


Scala gradata verbala
Scala semi-cantitativa Likert 0-5
Absenta durere
Durere minima, usoara
Durere medie
Intensa
Dureref. intensa

PRO = PATIENT REPORTED OUTCOME


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INDICI COMPOZITI
(COMPUSI)
ACR
DAS (44, 28)
CDAI, SDAI, RADAI

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ACTIVITATE versus
RASPUNS LA TRATAMENT
Activitate boala
(status)

remisiune
activitate joasa
actvitate moderata
activitate inalta

DAS/DAS28, CDAI, SDAI


Minimal Disease Activity
State (MDAS)
Patient Acceptable Symptom
State (PASS)
Un anumit nivel de activitate
masurabil
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Raspuns la tratament

EULAR

ACR

raspuns bun = responder


raspuns moderat,
suboptimal
fara raspuns = nonresponder
ACR20, 50, 70, 90
ACR hibrid
Evolutia bolii

Modificare scor variabila continua


Valori limita pentru nivele de
raspuns

ARTRITA ACTIVA (FDA)


Minim 3 din 4 criterii
NAD > 6
NAT > 6
RM > 45 min
VSH > 28 m

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INDICI ACTIVITATE: DAS 44 SI DAS 28


DAS44
RAI = Ritchie articular
index
53 artic; durere la
presiune; scor max= 78

NAT44
fara alta cuantificare; scor
max=44

lnVSH
Log natural VSH (mm/h)

GH = general health

DAS28
= DAS modificat
NAD (0-28)
NAT (0-28)
lnVSH
Log natural VSH (mm/h)

GH = general health
SAV 0-100mm

SAV 0-100mm

Disease Activity Score (cu 3 sau 4 variabile)


nr articulatii tumefiate si dureroase + evaluare globala pac + VSH
D. Van der Heijde
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Formula de transformare: DAS28= 1.072 (DAS) + 0.938

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INDICI DE ACTIVITATE: SDAI


(Simplified Disease Activity Index)

NAD(0-28)
NAT (0-28)
Evaluare Globala Pacient si Medic (EGP, EGM)
SAV 0-10 cm

CRP (mg/dl)

NAD+NAT + EGP + EGM + CRP

evaluarea activitate si raspuns la tratament (validat,


sensibilitate crescuta)
Util in practica clinica

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INDICI DE ACTIVITATE: SDAI


(Simplified Disease Activity Index)

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INDICI DE ACTIVITATE: CDAI


(Clinical Disease Activity Index)
SDAI modificat
NAD, NAT (0-28);
EGP (SAV, 0-10cm)
EGM (SAV, 0-10cm)
NAD+NAT+ EGP + EGM
Exclude reactanti faza ac
Validat
Calculare imediata, simpla

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ACTIVITATEA BOLII

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RADAI Rheumatoid Arthritis Disease Activity Index


Intrebari

Scala

Activitatea artritei in ultimele 6L ?

0-10

Cat de activa este artrita (durere + tumefactie) azi ?

0-10

Cum este durerea articulara azi?

0-10

Ati avut redoare azi? Cat a durat

0-6*

Cat de intensa a fost durerea astazi in fiecare arie: SH, 0-48


cot, degete, sold, gen, TT, haluce**
*-<30 min =1; 30 min-1h=2; 1-2h=3; 2-4h=4; >4h=5; toata ziua=6
**- dr/stg; fara, usoara, moderata
Raspunsul la intrebarile 4 si 5 se transforma pe scala 0-10
scorurile se aduna si se impart la nr intrebari

de catre pacient
usor, valid, sensibil
pt studii observationale termen lung
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EVALUARE DAMAGE
RADIOLOGIC
ULTRASONOGRAFIC
IRM

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SCOPUL EXPLORARII RG IN AR
cea mai accesibila si utilizata metoda imagistica
clasic gold standard
diagnostic AR
monitorizarea progresiei AR
evaluarea eficacitatii terapiei patogenice

AVANTAJE
cost redus
usurinta in realizare
disponibilitate mare
rezultate rapide
inregistrare permanenta (trialuri
clinice!)
metoda reproductibila
evalueaza severitatea si progresia
evidentiaza single point damage
evidentiaza vindecarea

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DEZAVANTAJE
limitarea tehnica (pozitionare,
tehnica),
leziuni caracteristice detectate
tardiv (floor limiting effect)
progresie Rg dupa raportarea
scor maxim (ceiling limiting
effect )

INTERVALE DE MONITORIZARE RG
BILANT RG BASELINE

confirma

diagnosticul/
permite
diagnosticarea
cind informatia clinicobiologica este echivoca
realizeaza
stadializarea
AR
documenteaza si
cuantifica
extensia,
activitate, severitatea

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BILANT ULTERIOR
(Rg seriate)

monitorizeaza

progresia
evalueaza
terapeutic

raspunsul

La 6 luni in primii 2 ani


Ulterior anual

ARTICULATII EVALUATE IN AR

OBLIGATORIU
artic mici maini + carp
artic mici picior
In functie de caz:
alte artic afectate
regiunea cervico-occipitala, in flexie
pentru subluxatia atlanto-axoidiana
instabila

Radiografii comparative
proiectie anteroposterioara
calitatea Rg
pozitionare
expunere
rezolutie film

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Articulatii eligibile

afectate in majoritatea cazurilor


(MCF, IFP, carp, MTF, IF)
tehnic facil (tars NU)
corelatii leziuni cu alte artic
leziuni caracteristice std din initiale
(stiloida cubitala, MTF V)
inregistreaza progresie
evidentiaza healing

ANOMALII RG

tumefactie parti moi

demineralizare/
osteoporoza
peri-articulara si/sau regionala

edem, cantitatea lichid sinovial,


sinovita

activare OC

chisturi/geode intraosoase

eroziuni marginale

pensare uniforma
articular anchiloza

sist RANK-RANKL-OPG, TNF, IL-1;


OC

spatiu

afectarea cartilaj articular


inhibarea sintezei Pg, IL-1)

subluxatii/ luxatii

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(MMP,

METODE DE EVALUARE RADIOLOGICA

scoruri globale pentru toate articulatiile


Steinbroker, Kellgren

scoruri totale acorda un punctaj/articulatie: toate anomaliile


radiologice
Larsen & variante, SES (Simplified Erosion Score)

scoruri individuale scoruri separate pentru minim 2


variabile pt fiecare articulatie cuantificata (eroziuni, pensare
spatiu articular)
Sharp, van der Heijde/ Sharp, SENS

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SCORUL STEINBROKER
Stadiul I
Early

1.Fara modificari distructive Rg


2. Eventual osteoporoza in banda, fara leziuni distrutive

Stadiul II
Moderat

1.osteoporoza, cu/fara minima distructie os si cartilaj


2.Fara deformari artic, cu limitarea mobilitatii
3.Atrofie musculara adiacenta
4.Manifestari extraarticulare: noduli, tenosinovita

Stadiul III
Sever

1.Semne distructie cartilaj si os subchondral, osteoporoza


2.Deformare articulara (subluxatie, deviatie cubitala)
3.Atrofie musculara extensiva
4.Manifestari extraarticulare: noduli, tenosinovita

Stadiul IV
Terminal

1.Fibroza/ anchiloza osoasa


2.Criteriile std III

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LARSEN

Scor

global ce evalueaza nivelul de


osteopenie, eroziune si ingustare a spatiului
articular
Un scor intre 05 se atribuie fiecarei
articulatii evaluate
Scor maxim = 160
toate artic
rapid de efectuat, dar apreciaza global
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LARSEN
MODIFICAT

GENANT

SHARP

- Carp, MCF, IFP


- NU subluxatii & luxatii

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SCORUL SHARP VAN DER HEIJDE

PSA
Eroziuni (E)

1 discreta/punctiforma <20%
2 mai mare in acelasi cadran, 20-40%
3 - >1/2 cadran, 40-60%
4 E punctiforme in toate cadranele,
60-80%
5 - colaps complet, >80%

0-380

Pensare spatiu articular (PSA)


0 = normal,
1 = PSA focal,
2 = <50%,
3 = > 50%
4 = anchiloza
0-168

Mana & picior; subluxatii si luxatii artic


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IRM IN AR
gold standard in imagistica AR (Ostergaard, 2003)
diagnostic precoce
monitorizarea progresivitatii AR
evaluarea eficacitatii terapiei
intelegerea mecanismelor patogenice
Dezavantaje: cost crescut, disponibilitate limitata,
tehnica de achizitie; scoruri validate
2002 RAMRIS; 2005 reference image atlas; 2007
RAMRIS-RV (Restricted field of View)
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RECOMANDARI OMERACT IRM

Tehnica/ secvente IRM (nativ, substanta contrast Ga )

Leziuni IRM:
Sinovita/panus = arie in compartimentul sinovial cu cresterea semnal
post-Ga, cu grosimea > sinovialei N (T1)

Eroziune osoasa = leziuni osoase bine delimitate, juxta-articular,


vizibile in 2 planuri, cu intreruperea corticalei in minim 1 plan, cu
semnal caracteristi (T1- pierderea hiposemnal os cortical si
hipersemnal os trabecular; rapida postGa panus activ!)

Edem osos = leziune in osul trabecular, prost delimitata, semnal ce


denota cresterea continut apa (hipersemnal T2, STIR, hiposemnal T1)
Lichid i-a, tenosinovita, la nivel col cervicala subluxatie C1-C2,
compresiune medulara

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RECOMANDARI OMERACT IRM

scor de activitate (OMERACT 2002 RAMRIS),


rheumatoid arthritis magnetic resonance imagining score
system:
evaluarea cantitativa si calititativa leziuni
inflamatorii si distructive de la nivelul mainii si pumnului

sinovita 3 regiuni carp, fiecare MCF (exceptie MCF1 si carpoMFC!); scor 0 3 (normal, minim, moderat, sever)

eroziuni fiecare os separat (carp, baza si cap MC, baza


falange); scala 0-10 = % os erodat omparativ cu vol osos
cuantificat (0: normal; 1 =1-10% os erodat, 2: 20%, etc)

edem osos fiecare os separat; scala 0-3 (0 fara edem, 1 =133%; 2 = 34-66%; 3 = 67-100%)

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MS-US (ecografia musculo-scheletala)

Scopuri:

Diagnostic precoce
Monitorizare activitatii si raspunsului terapeutic
Evaluarea progresiei si prognosticului bolii

Tehnici: standard, Doppler, power Doppler; sonda 7.510MHz

Elemente vizualizate sensibilitate superioara sau


echivalenta examenului clinic in evaluarea si
cuantificarea
inflamatiei
articulare
si
structuri
abarticulare artic mici:

sinovita si tenosinovita
lichidul intra-articular
pannus
eroziuni marginale

Factor prognostic, predictivi explorare moderna!

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EVALUARE FUNCTIONALA SI A
CALITATII VIETII

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INFLAMATIE

DIZABILITATE

DAMAGE

Severitate

Inflamatie
Dizabilitate
Lezare Rg
ACR

10

15

Durata AR (ani)

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20

25

30

CALITATATEA VIETII
Distructia articulara

Incapacitatea de munca

Afectare functionala

Reducerea
Calitatii
vietii
&

Afectarea psiho-sociala

Sperantei
de
viata

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Efecte adverse
terapie

Comorbiditati

INDICI DE EVALUARE FUNCTIONALA

afectarea functionala precoce (2-3 ani)


15% AR nu pot realiza activitatile
zilnice
incapacitatea de munca: 50% dupa
10 ani 90%
damage ireversibil - un an de la debut
90% pacienti au eroziuni in primii 2 ani
50% pacienti au scoruri HAQ ce
definesc dizabilitatea:
1 in primii 2 ani
(pierdere moderata a functiei)
2 in primii 6 ani
(pierdere severa a functiei)
2.5 in primii 10 ani
(pierdere ireversibila a functiei)

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HAQ
(Stanford
Health
Assessment Questionnaire )

HAQDI (HAQ-Disability Index) +


HAQ-durere + evaluare globala
pacient (SAV)
HAQ 100
M-HAQ (Modified - HAQ)
MD-HAQ (Multidimensional HAQ)

SF-36 (Short Form 36)


EuroQoL
(Rheumatoid
Arthritis
RAQoL
Quality of Life )
AIMS-1 si 2 (Arthritis Impact
Measurement Scale)

HAQDI (Stanford Health Assessment


Questionnaire Disability Index)

Chestionar de evaluare personala


20 intrebari legate de capacitatea de a desfasura
activitati zilnice in ultima sapt
-

Imbracare si autoingrijire
Ridicare
Mancat
Apucare

- Mers
- Igiena
- Ridicare
- Alte activitati

Evaluare 0-3

Fact de prognostic
Interpretarea depinde de stadiul AR

0 = fara dificultate
1 = cu oarecare dificultate

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- 2 = cu multa dificultate
- 3 = imposibil de realizat

M-HAQ vs MD-HAQ

M-HAQ (Modified
HAQ)
8 categorii
8 intrebari
NU ajustare in functie de
utilizarea de instrumente
ajutatoare
usor de aplicat , foarte
rapid
neconcordant
cu
activitatea AR, (forma
evolutiva, avansata

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MD - HAQ
(MultidimensionalHAQ)
complex
mai multe activitati fizice
durerea + fatigabilitatea +
anxietatea + depresia !
usor de aplicat

HAQ

Factor predictiv pt:

progresia AR

cu 1 unitate/an a HAQ-DI in primii 2 ani dizabilitate cu


90% mai mare si costuri cu 87% mai mari in urmatorii 3 ani
Scadere cu 0.22 fata de scorul initial imbunatatire clinica
semnificativa

statusul functional
incapacitatea de munca
costul terapiei
chirurgia protetica articulara
mortalitate
-

HAQ scazut supravietuire 90% la 5 ani si 70% la 15 ani


HAQ crescut > 50% supravietuiesc la 5 ani, NU la 15 ani

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FACIT
Initial a fost dezvoltat pentru a evalua oboseala
indusa de anemie la pacientii cu cancer
Masoara oboseala pe o scala bazata pe un
chestionar cu 13 intrebari grupate in 4 categorii

Oboseala generala
Oboseala fizica
Oboseala mentala
Vigoarea / tonusul

Reducerea cu 4 fata de scorul baseline


ameliorare semnificativa clinic
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EVALUARE BIOLOGICA
Sindrom inflamator
Sindrom imunologic

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VSH

activitate AR ultimele sapt


fact predictiv inflamatie
activitate AR termen scurt
predictor inflamatie
predictor
independent
progresie AR

CRP

FR

rata crescuta valori fals+/


falstitru >50U/ml = specificitate
ridicata, predictor AR eroziva
(FR IgA)

Ac anti-CCP (peptid ciclic


citrulinat)

specificitate > FR
predictor AR eroziva

DEZAVANTAJE
10 - 30% AR = seronegative
30 - 60% AR = a-CCP negative
40% AR = VSH normal
Teste laborator negative NU exclud AR/ necesitatea
tratament agresivt
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EVALUARE FACTORI DE
PROGNOSTIC

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FACTORI DE PROGNOSTIC NEGATIV

sex feminin
vrsta avansat la debut
debut poliarticular (> 12 artic)
manifestari extraarticulare (noduli, vasculita, afectare visc)
afectare functionala (HAQ > 1 la un an de la debut)
prezenta eroziunilor osoase si cartilaginoase precoce
(<2ani)

titru factor reumatoid si a CCP


titru CRP/ VSH
teren genetic HLA DR1, DR4 (shared epitope DRB1*04)
nivelul educaional status socio-economic sczut
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FACTORI PREDCTIVI AI PROGRESIEI


RADIOLOGICE

forme seropozitive (FRIgA, aCCP)


prezenta eroziuni
afectarea functionala (HAQ)
Manifestari extra-articulare
Reactanti faza acuta
Sex feminin
Shared epitope
fumat
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FACT PROGNOSTIC NEGATIV IN AR


PRECOCE
Factori prognostic negativ structural

Sindrom inflamator intens, persistent


FR tip IgA
Ac aCCP
Eroziuni precoce

Prognostic functional
HAQ>0.5
DAS28>3.2
Eroziuni precoce Rg

Prognostic vital: manifestari sistemice = rare la


debut

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FACTORI RISC MORTALITATE IN AR


factori sociali
Status precar socioeconomic
Status precar educational
Stress psiho-social
HAQ mare
Factori AR
Manif extra-articular
Titruri crescute CRP, VSH
Titruri crescute FR
Eroziuni
Durata bolii

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MONITORIZARE
RASPUNS LA TRATAMENT

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CRITERII AMELIORARE ACR

NAD
NAT

ameliorare
20
50
70
90

cel putin 3 din urmatoarele


VSH sau CRP
evaluarea globala a bolii de
catre medic
evaluarea globala a bolii de
catre pacient
durerea (SAV)
afectarea functionala

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CRITERIILE AMELIORARE PAULUS


Ameliorare minim 20% a cel putin 4 din 6 parametri
Durata redorii matinale
VSH
Durere articulara
NAT
Evaluarea globala pacient cel putin 2 pct pe
scala semicantitativa 0-5
Evaluarea globala medic cel putin 2 pct pe scala
semicantitativa 0-5

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ACTIVITATEA BOLII

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CRITERII REMISIUNE PINALS


Minim 5 din urmatoarele, minim 2 luni
consecutiv:
RM < 15 min
Absenta asteniei
Absenta durerii articulare
Absenta durerii articulare la mobilizare
Absenta tumefactiei articulare
VSH < 30 mm/h (F) si < 20 mm/h (B)

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REMISIUNEA

DEFINITIA ACR
redoare matinala < 15 min
absenta durerii articulare
absenta tumefierii articulare
absenta fatigabilitatii
VSH<30mm/1h

DEFINITIA EULAR
DAS44 < 1.6
DAS28 < 2.6

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CRITERII ADITIONALE

clinice i biologice

NAD = 0
NAT = 0
CRP n titru normal
DAS28< 2.6
DAS 44<1.6

radiologice

absena progresiei radiologice

funcionale

absena dizabilitii (HAQ < 0.5)

REMISIUNEA
1/ 5 pacienti
Predictia raspunsului la tratament in 3 luni de la initierea
tratament evaluare raspuns la 3-6 luni + switching la cei ce nu
obtin low disease activity

remisiunea clinica: NU exclude progresia radiologica


(studiile BeST, TICORA)
remisiunea constanta
progresie Rx absenta

FARA

factori

de

risc

remisiunea constanta CU factori de risc (factor reumatoid


pozitiv si/sau distructie articulara prezenta) progresie Rx
posibila

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CONCLUZII

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Evaluarea in AR
l complexa
l NU exista un singur gold standard (TA,
colesterol) pt practica/ cercetare indici
compoziti
l Crt primare de evaluare = clinice
l Patient reported outcome functionale,
durerea, evaluarea globala

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ACR & EULAR


3 parametri evaluati de medic
1. NAD
2. NAT
3. Evaluarea globala a medicului
3 parametri evaluati de medic
PRO
1. Evaluare functionala: HAQ + variante
2. durerea
3. Evaluarea globala a pacientului
2 parametri laborator
Reactanti de faza ac VSH, CRP
+ damage: Rg

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PRACTICA CLINICA versus


medicina bazata pe dovezi
Cercetare clinica
Evaluare articulara
68/70 NAD, NAT

Evaluare Rg
Larsen/ Sharp van der
Heijde

Laborator
VSH, CRP, FR, aCCP

PRO
Complete, complexe
durata

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Clinica
articular
NAD, NAT = 28

Rg
Eroziuni
Pensare spatiu articular?

Laborator
VSH, CRP, FR, aCCP

PRO
Simple <10 min

Fisa de evaluare AR

NAD, NAT
Durere (0-100 mm)
Redoare matinala
Aprecierea globala a bolii
de medic si pacient
VSH, CRP cantitativ
FR, aCCP
Scoruri Larsen/ Sharp (Rg)
Manifestari extraarticulare
Factori prognostic negativ

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DAS28 actual
CDAI
SDAI
HAQ
EULAR(DAS)

Trat DMARDs
- eficacitate/ toxicitate
corticsteroizi(local/sistemic)

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