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ARTRITA PSORIAZICAARTRITA PSORIAZICA
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SPONDILARTRITESPONDILARTRITE
ENTITATI
SPONDILITA ANCHILOZANTA
ARTRITA PSORIAZICA
ARTRITA REACTIVA
ARTRITA ENTEROPATICA
SPONDILITA CU DEBUT JUVENIL
SPONDILARTRITA NEDIFERENTIATA
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ARTRITA PSORIAZICAARTRITA PSORIAZICA
artropatie inflamatorie asociata psoriazisuluiartropatie inflamatorie asociata psoriazisului de regula seronegativa si fara noduli reumatoizi.de regula seronegativa si fara noduli reumatoizi. 5% din cei cu Ps fac afect articulara5% din cei cu Ps fac afect articulara
prevalenta Ps 2-3% APs 1%prevalenta Ps 2-3% APs 1%
distributie egala pe sexe cu particularitati in fctdistributie egala pe sexe cu particularitati in fctde forma clinicade forma clinica
forma axiala barbatforma axiala barbatforma poliarticulara femeiforma poliarticulara femei
debut 20-40 ani (rar 9-12 ani)debut 20-40 ani (rar 9-12 ani)
rasa albarasa alba
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ETIOPATOGENIEETIOPATOGENIE
FACTORIIMUNI
FACTORIGENETICI
FACTORI
DE MEDIU
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FACTORI GENETICIFACTORI GENETICI
argumente:argumente:agregarea familiala a boliiagregarea familiala a bolii
prevalenta crescuta la rudele de gradul I;prevalenta crescuta la rudele de gradul I;
concordanta inalta la gemenii monozigoti fata deconcordanta inalta la gemenii monozigoti fata dedizigoti (67-72% vs 15-30%)dizigoti (67-72% vs 15-30%)
existenta genelor de susceptibilitateexistenta genelor de susceptibilitate
asocierea cu Agasocierea cu Ag HLA B13, B39, B17, B27, DR4,HLA B13, B39, B17, B27, DR4,
HLA B27- afectare axialaHLA B27- afectare axiala
HLA DR4-forma poliarticulara si erozivaHLA DR4-forma poliarticulara si eroziva
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FACTORI DE MEDIUFACTORI DE MEDIU
Infectii virale/bacterieneInfectii virale/bacteriene
streptococ beta hemolitic de tip A sau B,streptococ beta hemolitic de tip A sau B,
HIV - scade nr LyT CD4+, cu cresterea CD8+/CD4+HIV - scade nr LyT CD4+, cu cresterea CD8+/CD4+
Ag infectiosi actioneaza fie caAg infectiosi actioneaza fie ca Ag clasiceAg clasice care activeazacare activeazaLy T, fie caLy T, fie ca superantigenesuperantigene care leaga direct MHC clasa IIcare leaga direct MHC clasa IIde Ly Tde Ly T
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FACTORI DE MEDIUFACTORI DE MEDIU
TraumatismTraumatism
Stress-ulStress-ul::
rol in declansarea bolii sau a unui nourol in declansarea bolii sau a unui noupuseupuseu
MedicamenteleMedicamentele (saruri de litiu, beta(saruri de litiu, beta
blocante, interferon, clonidina, digoxin)blocante, interferon, clonidina, digoxin) Fumatul, alcoolulFumatul, alcoolul: agraveaza leziunea: agraveaza leziunea
cutanatacutanata
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cutanatcutanat
sinovialasinoviala
cartilaj/oscartilaj/os
entezaenteza
hiperproliferarecelulara
activarea celulelorimune: Ly T, B, Mf
angiogeneza
MECANISME IMUNOPATOGENICE
degradare cartilaj,anomalii de
remodelare osoasa,anchiloza
http://images.google.ro/imgres?imgurl=http://www.lacoctelera.com/myfiles/reflexologiaparati/tendon_aquilesC.jpg&imgrefurl=http://www.lacoctelera.com/reflexologiaparati&h=354&w=300&sz=19&hl=ro&start=3&tbnid=udUT_GYXbQ6iMM:&tbnh=121&tbnw=103&prev=/images%3Fq%3Dentesitis%2B%26gbv%3D2%26svnum%3D10%26hl%3Dro%26sa%3DGhttp://newsimg.bbc.co.uk/media/images/41381000/gif/_41381405_skin_cancer.gif7/27/2019 Artrita psoriazica.pdf
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Citokinele i chemokineleCitokinele i chemokineleeliberate sau induse deeliberate sau induse depopulaia patogenic depopulaia patogenic deLyTLyT sunt coordonatoarelesunt coordonatoarele
infiltratului inflamator iinfiltratului inflamator iale hiperproliferriiale hiperproliferriicelulare cutanat sicelulare cutanat siarticulararticular
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celula cheie:celula cheie: Ly Th1Ly Th1
CK: INF gama, TNF alfa, IL1CK: INF gama, TNF alfa, IL1
activare Mo/Mfactivare Mo/Mf
CK: TNF alfa, IL1CK: TNF alfa, IL1
stimulare secretie:stimulare secretie:
mediatori pro-inflamatorimediatori pro-inflamatoriMMP: colagenaza,MMP: colagenaza,
stromelizinastromelizina
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MASTOCITE
KERATINOCITE
GRANULOCITE
Ly T
Monocite/Macrofage
TNF
IL-1, IL-6, IL-8, MCP-1, VEGF,angioneogeneza, recrutarea de ly T
si alte cel inflamatorii
TNFTNF : CK cheie: CK cheie
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TABLOU CLINICTABLOU CLINIC
debut insidios (exceptie HIV+)debut insidios (exceptie HIV+)
raportul temporal intre afectarea cutanataraportul temporal intre afectarea cutanata
si cea articulara are 3 modele:si cea articulara are 3 modele: succesiune 75%succesiune 75%
coincidenta 15%coincidenta 15%
inversiune 10%inversiune 10%
debut mono-/oligo-/poliarticulardebut mono-/oligo-/poliarticular
durere, RM, tumefiere articularadurere, RM, tumefiere articulara
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manifestarile musculo-manifestarile musculo-
scheletalescheletale afectarea articularaafectarea articulara - 5 modele ce se pot- 5 modele ce se potcombina intre ele sau pot evolua din unul incombina intre ele sau pot evolua din unul inaltul:altul:
oligoartrita asimetrica: artic mici MS + artic mareoligoartrita asimetrica: artic mici MS + artic mare
MI + dactilita + lez cutanate minimeMI + dactilita + lez cutanate minime
poliartrita simetrica: artic mici MS (MCF, IFP, IFD)poliartrita simetrica: artic mici MS (MCF, IFP, IFD)tip raza (toate artic unui deget, in timp ce altetip raza (toate artic unui deget, in timp ce altedegete sunt normale)degete sunt normale)
forma cu afectarea IFD: + onicopatie psoriazicaforma cu afectarea IFD: + onicopatie psoriazica
artrita mutilantaartrita mutilantaforma axialaforma axiala
alte manifestarialte manifestari: dactilita, entezita,: dactilita, entezita,
tenosinovitetenosinovite
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manifestari extra-articularemanifestari extra-articulare
leziunea cutanata psoriaziformaleziunea cutanata psoriaziforma
onicopatia psoriazicaonicopatia psoriazica uveita anterioara/conjunctivitauveita anterioara/conjunctivita
insuficienta aorticainsuficienta aortica
amiloidozaamiloidoza
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EVALUAREA PARACLINICAEVALUAREA PARACLINICA
RFA- titru crescutRFA- titru crescut Bilant hematologic: anemie cronica simpla/Bilant hematologic: anemie cronica simpla/
pancitopenie secundara/leucocitozapancitopenie secundara/leucocitoza
Teste fct hepatice normaleTeste fct hepatice normaleTeste fct renala normale/ hiperuricemieTeste fct renala normale/ hiperuricemie Sdr imunologic:Sdr imunologic:
FR absent (excepie 25% din cazuri cuFR absent (excepie 25% din cazuri cuforma poliarticulara)forma poliarticulara)
ANA absentiANA absenti
Lichid sinovial: exsudat, L cu PMN,Lichid sinovial: exsudat, L cu PMN,
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EVALUAREA PARACLINICAEVALUAREA PARACLINICA
Radiografie maini/antepiciorRadiografie maini/antepicior
lipsa osteoporozei juxtaarticularelipsa osteoporozei juxtaarticulare eroziuni marginale extensive cu osteoliza capeteloreroziuni marginale extensive cu osteoliza capetelor
osoase ( creion in cupa)osoase ( creion in cupa)
telescoparea oaselortelescoparea oaselor largirea spatiului articularlargirea spatiului articular periostita pufoasaperiostita pufoasa anchilozaanchiloza
Radiografie talonRadiografie talon entezitaentezitaRadiografie bazin (pt SI) /jonctiune D-LRadiografie bazin (pt SI) /jonctiune D-L
sacroiliita asimetricasacroiliita asimetrica sindesmofit atipic, nonmarginalsindesmofit atipic, nonmarginal
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DIAGNOSTIC DIFERENTIALDIAGNOSTIC DIFERENTIAL
Alte SAp - artrita reactivaAlte SAp - artrita reactiva
AR- fara interesarea IFDAR- fara interesarea IFD
Artroza IFD noduli HeberdenArtroza IFD noduli Heberden
Guta-forma pseudoreumatoidaGuta-forma pseudoreumatoida
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EVOLUTIE SI PROGNOSTICEVOLUTIE SI PROGNOSTIC
boala cronica cu evolutie ondulantaboala cronica cu evolutie ondulanta
factori de prognostic negativ:factori de prognostic negativ:varsta la debut < 20 anivarsta la debut < 20 ani
afectarea poliarticularaafectarea poliarticulara
teren genetic HLA B27-progresiva, DR4-erozivateren genetic HLA B27-progresiva, DR4-eroziva
asocierea cu HIVasocierea cu HIVpsoriazis extensivpsoriazis extensiv
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TRATAMENTTRATAMENT
SIMPTOMATICSIMPTOMATIC
AINS-manif articulare usoareAINS-manif articulare usoare
CSCSintraarticularintraarticular
topictopic
po-f.rarpo-f.rar
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TRATAMENTTRATAMENT
PATOGENIC (REMISIV)PATOGENIC (REMISIV)
pt lez cutanata si articulara:pt lez cutanata si articulara: MTX,MTX,CSPCSP, SSZ,, SSZ, LEFLEF, AZA, MMF, derivati, AZA, MMF, derivati
acid retinoic,acid retinoic, terapia biologicaterapia biologica
pt lez articulara: saruri aur,pt lez articulara: saruri aur, HCQHCQ, D-, D-penciliaminapenciliamina
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MTX 10-25mg/saptMTX 10-25mg/sapt
CSP 3-5mg/kgc/zi; lez cutanata > articularaCSP 3-5mg/kgc/zi; lez cutanata > articulara
SSZ 2-3 g/zi; artrita perifericaSSZ 2-3 g/zi; artrita periferica
AZA 2,5mg/kgc/ziAZA 2,5mg/kgc/zi
LEF 20mg/ziLEF 20mg/zi
MMF 2g/ziMMF 2g/zi
HCQ 400 mg/zi..200mg/ziHCQ 400 mg/zi..200mg/zi
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TERAPIA BIOLOGICA ANTI TNFTERAPIA BIOLOGICA ANTI TNF
inaintea initierii tratamentului esteinaintea initierii tratamentului esteobligatoriu:obligatoriu:
screening TBC: test PPD si Rg toracicascreening TBC: test PPD si Rg toracica
screening infectie virala: Ag HBs, Ac antiscreening infectie virala: Ag HBs, Ac anti
HVC, HIVHVC, HIV
excluderea neoplaziei, boli demielinizanteexcluderea neoplaziei, boli demielinizante
excluderea fen autoimune asociate Acexcluderea fen autoimune asociate Ac
anti ADN dcanti ADN dc
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TERAPIA ANTI TNFTERAPIA ANTI TNF-CONTRAINDICATII-CONTRAINDICATII
LESLES
Scleroza multiplaScleroza multipla
Nevrita opticaNevrita optica
Infectii active/ cronice/ recurenteInfectii active/ cronice/ recurente
Antecedente de tuberculoza sau testAntecedente de tuberculoza sau testPPD pozitivPPD pozitiv
Insuficienta cardiaca cronica severaInsuficienta cardiaca cronica severa
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INFLIXIMAB (REMICADEINFLIXIMAB (REMICADE))
se adm. in combinatie cu MTX-se adm. in combinatie cu MTX-efect sinergicefect sinergic
prelungeste durata remisiuniiprelungeste durata remisiunii
inhiba formarea Ac impotriva portiunii muriniceinhiba formarea Ac impotriva portiunii murinice
doza: 5 mg/kgc,piv, So, S2, S6 sidoza: 5 mg/kgc,piv, So, S2, S6 siulterior la 8 saptamani intervalulterior la 8 saptamani interval
raspuns insuficient:raspuns insuficient:se creste doza pana la maxim 10se creste doza pana la maxim 10
mg/kgc saumg/kgc sau
se poate micsora intervalul dintrese poate micsora intervalul dintre
administrari la 4-6 saptadministrari la 4-6 sapt
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ADALIMUMAB (HUMIRAADALIMUMAB (HUMIRA))
doza: 40 mg, sc, la 2 saptdoza: 40 mg, sc, la 2 saptintervalinterval
adm. in monoterapie sau terapieadm. in monoterapie sau terapiecombinata (+MTX)combinata (+MTX)
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ETANERCEPT (ENBRELETANERCEPT (ENBREL))
doza: 25mg x 2/sapt saudoza: 25mg x 2/sapt sau50mg/sapt, sc50mg/sapt, sc
in monoterapie sau in terapiein monoterapie sau in terapiecombinata (+MTX)combinata (+MTX)
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REACTII ADVERSEREACTII ADVERSE
reactii adverse acute ale piv: febra, frisoane, cefalee,reactii adverse acute ale piv: febra, frisoane, cefalee,prurit, urticarie, hipotensiune, dispnee infliximabprurit, urticarie, hipotensiune, dispnee infliximab
infectii reactivarea tuberculozei toate anti TNFinfectii reactivarea tuberculozei toate anti TNF
hipersensibilitate de tip intarziat: mialgii, artralgii,hipersensibilitate de tip intarziat: mialgii, artralgii,eritem, edemeeritem, edeme fen autoimune: anticorpi antimolecula chimericafen autoimune: anticorpi antimolecula chimerica
(HACA), ANA, Ac anti ADNdc (fen lupus-like)-infliximab(HACA), ANA, Ac anti ADNdc (fen lupus-like)-infliximab fen CV: agravarea insuf cardiace, aritmiifen CV: agravarea insuf cardiace, aritmii fen digestive: greata , diareefen digestive: greata , diaree
fen neurologice: sdr demielinizantefen neurologice: sdr demielinizante fen hematologice: leucopenie, anemie, trombocitopeniefen hematologice: leucopenie, anemie, trombocitopenie neoplazii: limfoameneoplazii: limfoame