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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.gif
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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