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EVALUARE SI MONITORIZARE IN ARTRITA REUMATOIDA
Codrina AncutaMD, PhD, CCDSef lucrari
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EVALUARE versus MONITORIZARE
Evaluarecaracterizeaza boala laun moment dat- activa/ inactivaà
remisiune; - severa/ potential
severa- refractara la
tratament
Monitorizareevalueaza schimbarile- activitatea AR- severitatea ARintr-o perioada de timp:- ameliorare- remisiune- agravare
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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
Evaluare in dinamica(monitorizare)
• Eficacitate tratament– Clinico-biologica– Radiologica (progresie)– Functionala
• Tolerabilitate/ toxicitatetratament
raspuns la tratamentactivitate boala
DOMENII EVALUAREclinicfunctional (dizabilitate)damage (imagistic)
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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 Ritchie53 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, reproductibilaNu se foloseste de rutina
Indexul de tumefierearticulara 44
- elimina 9 artic- tumefierea 0-1:
- 0 = fara tumefiere- 1 = tumefiere
Indexul articular 28- ignora TT, picior- durereà NAD- tumefactieà NAT- scala 0-1- Si studii clinice!
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Articulatii 66/68 artic
Ritchie Index
44 artic 36 artic 28 artic 42 artic
Temporomandibulare + +Sternoclaviculare + + +Acromioclaviculare + + +scapuloumerala + + + + +Cot + + + + + +
Pumn + + + + + +MCF + + + + (-1) + +IFP mana + + + + + +IFD mana +Coxo-femurala + + +Genunchi + + + + + +Tibio-tarsiana + + + + +Talocalcaneal +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 unghealal examinatorului”
• NU deformarea artic sauedemul
• Amplitudine redusa de mobilizare articulara
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ARTICULATII IFP (interfalangiene proximale)
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ARTICULATII MTF(metacarpofalangiene)
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ARTICULATII SCAPULO-HUMERALE
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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)
Raspuns la tratament§ EULAR
– raspuns bun = responder– raspuns moderat,
suboptimal– fara raspuns = non-
responder§ ACR
– ACR20, 50, 70, 90– ACR hibrid
Evolutia bolii
Modificare scor variabila continua Valori limita pentru nivele de
raspunsUn anumit nivel de activitate
masurabil
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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 28DAS44
• 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– SAV 0-100mm
DAS28
= DAS modificat
• NAD (0-28)• NAT (0-28)• lnVSH
– Log natural VSH (mm/h)• GH = general health
– 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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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, cot, degete, sold, gen, TT, haluce**
0-48
*-<30 min =1; 30 min-1h=2; 1-2h=3; 2-4h=4; >4h=5; toata ziua=6**- dr/stg; fara, usoara, moderataRaspunsul la intrebarile 4 si 5 se transforma pe scala 0-10 àscorurile se aduna si se impart la nr intrebari
RADAI – Rheumatoid Arthritis Disease Activity Index
de catre pacientusor, valid, sensibilpt studii observationale termen lung
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EVALUARE DAMAGE
RADIOLOGICULTRASONOGRAFIC
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 patogeniceAVANTAJE
§ 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”
DEZAVANTAJE§ limitarea tehnica (pozitionare,
tehnica), § leziuni caracteristice detectate
tardiv (floor limiting effect) § progresie Rg dupa raportarea
scor maxim (ceiling limiting effect )
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INTERVALE DE MONITORIZARE RG
BILANT RG BASELINEBILANT RG BASELINE§ confirma diagnosticul/
permite diagnosticarea cind informatia clinico-biologica este echivoca§ realizeaza stadializarea
AR § documenteaza si § cuantifica extensia,
activitate, severitatea
BILANT ULTERIORBILANT ULTERIOR(Rg seriate)
§ monitorizeaza progresia § evalueaza raspunsul
terapeutic
La 6 luni – in primii 2 aniUlterior anual
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ARTICULATII EVALUATE IN AROBLIGATORIU
• 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 antero-
posterioara§ calitatea Rg§ pozitionare§ expunere§ rezolutie film
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”
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ANOMALII RG§ tumefactie parti moi§ edem, ↑ cantitatea lichid sinovial,
sinovita
§ demineralizare/ osteoporoza peri-articulara si/sau regionala § activare OC
§ chisturi/geode intraosoase
§ eroziuni marginale§ sist RANK-RANKL-OPG, TNF, IL-1;
OC
§ pensare uniforma spatiu articularà anchiloza§ afectarea cartilaj articular (MMP,
inhibarea sintezei Pg, IL-1)
§ subluxatii/ luxatii
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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, pensarespatiu articular) § Sharp, van der Heijde/ Sharp, SENS
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SCORUL STEINBROKERStadiul IEarly
1.Fara modificari distructive Rg2. Eventual osteoporoza in banda, fara leziuni distrutive
Stadiul IIModerat
1.osteoporoza, cu/fara minima distructie os si cartilaj2.Fara deformari artic, cu limitarea mobilitatii3.Atrofie musculara adiacenta4.Manifestari extraarticulare: noduli, tenosinovita
Stadiul IIISever
1.Semne distructie cartilaj si os subchondral, osteoporoza2.Deformare articulara (subluxatie, deviatie cubitala)3.Atrofie musculara extensiva4.Manifestari extraarticulare: noduli, tenosinovita
Stadiul IVTerminal
1.Fibroza/ anchiloza osoasa2.Criteriile std III
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LARSEN MODIFICAT
LARSEN
§ Scor global ce evalueaza nivelul de osteopenie, eroziune si ingustare a spatiuluiarticular§ Un scor intre 0–5 se atribuie fiecareiarticulatii evaluate§ Scor maxim = 160§ toate artic§ rapid de efectuat, dar apreciaza global
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SHARP- Carp, MCF, IFP- NU subluxatii & luxatii
GENANT
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SCORUL SHARP VAN DER HEIJDE
Pensare spatiu articular (PSA)0 = normal,
1 = PSA focal, 2 = <50%, 3 = > 50%
4 = anchiloza0-168
E PSAEroziuni (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%
0-380Mana & 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; 2007RAMRIS-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 à 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 carpo-
MFC!); 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: à20%, etc)
– edem osos – fiecare os separat; scala 0-3 (0 – fara edem, 1 =1-33%; 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 7.5-10MHz
§ 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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Seve
ritat
e
0Durata AR (ani)
5 10 15 20 25 30
InflamatieInflamatieDizabilitateDizabilitateLezareLezare RgRg
© ACR
INFLAMATIE DIZABILITATE DAMAGE
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CALITATATEA VIETII
Reducerea Calitatii
vietii&
Sperantei de
viata
Distructia articularaDistructia articulara
Incapacitatea de muncaIncapacitatea de munca
Afectarea psihoAfectarea psiho--socialasociala
Afectare functionalaAfectare functionala
Efecte adverse Efecte adverse terapieterapie
ComorbiditatiComorbiditati
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INDICI DE EVALUARE FUNCTIONALA
§ afectarea functionala precoce (2-3 ani)§ 15% AR nu pot realiza activitatile
zilnice§ incapacitatea de munca: à 50% dupa
10 anià 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)
§ HAQ (Stanford Health Assessment Questionnaire )§ HAQ–DI (HAQ-Disability Index) +
HAQ-durere + evaluare globalapacient (SAV)§ HAQ 100 § M-HAQ (Modified - HAQ) § MD-HAQ (Multidimensional HAQ)
§ SF-36 (Short Form 36)§ EuroQoL§ RAQoL (Rheumatoid Arthritis
Quality of Life )§ AIMS-1 si 2 (Arthritis Impact
Measurement Scale)
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HAQ–DI (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 - Mers- Ridicare - Igiena - Mancat - Ridicare - Apucare - Alte activitati
§ Evaluare 0-3– 0 = fara dificultate - 2 = cu multa dificultate– 1 = cu oarecare dificultate - 3 = imposibil de realizat
§ Fact de prognostic§ Interpretarea depinde de stadiul AR
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M-HAQ vs MD-HAQM-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
MD - HAQ (Multidimensional-
HAQ)§ complex § mai multe activitati fizice § durerea + fatigabilitatea +
anxietatea + depresia !§ usor de aplicat
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HAQFactor predictiv pt:§ progresia AR
– ↑ cu 1 unitate/an a HAQ-DI in primii 2 ani à 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 à supravietuire 90% la 5 ani si 70% la 15 ani - HAQ crescut à > 50% supravietuiesc la 5 ani, NU la 15 ani
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FACIT
• Initial a fost dezvoltat pentru a evalua obosealaindusa 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 BIOLOGICASindrom inflamatorSindrom imunologic
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§ VSH § activitate AR ultimele sapt§ fact predictiv inflamatie
§ CRP § activitate AR termen scurt§ predictor inflamatie§ predictor independent
progresie AR
§ FR§ rata crescuta valori fals+/
fals-§ titru >50U/ml = specificitate
ridicata, predictor AR eroziva(FR IgA)
§ Ac anti-CCP (peptid cicliccitrulinat)§ specificitate > FR§ predictor AR eroziva
DEZAVANTAJE§ 10 - 30% AR = seronegative§ 30 - 60% AR = a-CCP negative§ à 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
§ vârsta avansată 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 educaţional status socio-economic scăzut
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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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MONITORIZARERASPUNS LA TRATAMENT
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CRITERII AMELIORARE ACR
ameliorare20507090
§ NAD§ NATcel 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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REMISIUNEADEFINITIA ACR
§ redoare matinala < 15 min § absenta durerii articulare § absenta tumefierii articulare § absenta fatigabilitatii§ VSH<30mm/1h
DEFINITIA EULAR§ DAS44 < 1.6 § DAS28 < 2.6
CRITERII ADITIONALE§ clinice şi biologice § NAD = 0§ NAT = 0§ CRP în titru normal§ DAS28< 2.6§ DAS 44<1.6
§ radiologice§ absenţa progresiei radiologice
§ funcţionale § absenţa dizabilităţii (HAQ < 0.5)
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• 1/ 5 pacienti– Predictia raspunsului la tratament à in 3 luni de la initierea
tratament à 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 FARA factori de risc àprogresie Rx absenta
• remisiunea constanta CU factori de risc (factor reumatoidpozitiv si/sau distructie articulara prezenta) à progresie Rx posibila
REMISIUNEA
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CONCLUZII
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Evaluarea in AR
l complexal NU exista un singur “gold standard” (TA,
colesterol) pt practica/ cercetare à indici compozitil Crt primare de evaluare = clinicel Patient reported outcome – functionale,
durerea, evaluarea globala
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ACR & EULAR3 parametri evaluati de medic1. NAD 2. NAT 3. Evaluarea globala a medicului
3 parametri evaluati de medicPRO1. Evaluare functionala: HAQ + variante2. durerea 3. Evaluarea globala a pacientului
2 parametri laboratorReactanti 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
Clinica• articular
– NAD, NAT = 28
• Rg– Eroziuni– Pensare spatiu articular?
• Laborator– VSH, CRP, FR, aCCP
• PRO– Simple <10 min
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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
• DAS28 actual• CDAI• SDAI• HAQ• EULAR(DAS)
• Trat DMARDs• - eficacitate/ toxicitate• corticsteroizi(local/sistemic)
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