les
DESCRIPTION
Lupus eritematos sistemicTRANSCRIPT
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LUPUS ERITEMATOS SISTEMIC (LES) la copil
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LES
Definitie: boala inflamatorie cronica cu afectare
multisistemica (cutaneo-mucoasa, articulatii, sistem nervos, seroase, rinichi)
Prototip de boala autoimuna(Ac impotriva Ag nucleare proprii complexe imune + disfunctie a sistemului imun afectare organica)
Heterogenitate clinica Evolueaza cu exacerbari si remisiuni Prognostic imprevizibil LES la copil mai “acuta” si severa decat la adult
Potential fatala!
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EPIDEMIOLOGIE
– 1 - 6 /100 000 copii fc. de grup etnic• albii cea mai mica prevalenta• negrii, hispanicii medie• orientalii cea mai
– virf pubertar precoce, copii peste 10 ani ; f.rara < 5 ani
– la sexul F F/M: 8/1
frecventei bolii in ultimii ani dat: cresterea reala a incidentei dg. metode performante lupus indus medicamentos
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ETIOPATOGENIE
• cauza necunoscuta
• intervin factori:
– genetici
– hormonali
– imunologici
– mediu
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ETIOPATOGENIE
1. FACTORI GENETICI• rata aparitiei LES gemeni monozigoti 70 %, heterozigoti - 3 % ;
• rude gr. I au o frecv de 6-8 ;
• frecv mai mare la bolnavii cu LES a HLA D/DR( mai frecvent intalnite DR2 , DR3 – sunt implicate in reglarea imuna, induce hiperactivitate imuna generalizata)
• deficit congenital de C2, C4 se asocieaza cu boala lupica(insuf. de neutralizare si eliminare a antigenelor straine)
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ETIOPATOGENIE
2. HORMONI
• sustinut de predominanta bolii la fete: in LES s-au decelat nivele mai mari de metaboliti estrogenici, iar anticonceptionalele agraveaza boala;
• capacitatea hormonilor sexuali de a modula reactivitatea imuna
• estrogenii actioneaza pe limfocitele T supresor/CD8+(deprima) cat si pe SRE (reducerea epurararii complexelor imune circulante)
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ETIOPATOGENIE
3. IMUNOLOGI anomalii imunologice ce au la baza
• hiperactivitatea limfocitelor B • alterare functiei celT
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ETIOPATOGENIE
4. MEDIU
- raze UV
- virusurile
- superantigene(streptococ, mycoplasma)
- medicamente (β blocante, HIN, hidralazina)
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ETIOPATOGENIEFactorii de mediu care actioneaza pe un teren genetic si hormonal predispus modifica
balanta intre imunitate si toleranta imunologica AUTOIMINITATE - I anomaliile imune - II leziunile imuneI. Anomalii imune:
1. Hiperactivitatea cel. B(superantigene)-capacitate de proliferare de 7-8 > producerea
in exces de AutoAc 2. perturbrea echilibrului Thelper/Tsupresor=CD8() ; modif raportului in sensul Th/CD4 cooperarea acestuia cu limfocitul B si producerea de autoanticorpi 3. celule NK au activitate - susceptibilitate la infectii in LES 4. reactivitate incrucisata - Ac anti Sm din LES reactioneaza incrucisat cu proteine din retrovirusuri 5. SRH isi pierde functia de epurare CIC se depun tisular ;
TINTA antigenica este reprezentata de: antigene de suprafata ale diferitelor celule:hematii, limfocite, trombocite, comp. intracelulare : DNA histone(nucleosomi)
ribonucleoproteine nucleare, ribonucleoproteine citoplasmatice Cei mai frecventi autoanticorpi in LES suntANA(95%), DNAdublu catenar, Sm, La, LA
II Leziunile imune –apar ca urmare a deunerii CIC in tesuturiactivarea complementului, din care se detaseaza peptide cu actiune proinflamatorie,vasoactive si chemotactice pt neutrofileeliberarea enzimelor lizozomale determina leziunile inflamatorii
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LES CLINIC
DEBUT– insidios sau brusc– semne generale:febra, astenie, scadere in
greutate, artrita, rash
STARE- manifestarile pot apare simultan sau succesiv in
evolutia bolii
• Afectare cutaneo- mucoasa• Artrita• Serozita• Sistem nervos• Afectare renala• Alte organe (cord,ochi,pulmon)-rar la copil
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Afectare cutaneo- mucoasa
Leziuni cutanate tipice - leziuni acute = Rash malar- eritem “in fluture”(vespertilio)
“ lup d carnaval”??pe eminentele malare si nas; exacerbata
la soare - leziuni subacute- initial eritematoase, devin in timp
papuloscuamoase simulind psoriazisul sau lichen plan; uneori pot fi policiclice sau inelare cu margini eritematoase(lupus bite)
- leziuni cronice- discoide, eritemul e urmat de hipercheratoza si atrofie; dispozitie pe fata, urechi, brate, spate;
Alte manifestari cutanate; eruptii eritematomaculopapuloase, mai ales pe zonele expuse la soare(decolteu, frunte, barbie) sau de tip vasculitic: purpura, macule eritematoase pe eminente tenare si hipotenare, fen.Raynaud+/- ulceratii pe pulpa degetelor(pentru confirmare necesita uneori biopsie)
Ulcere orale Alopecie- circumscrisa, rar difuza Fotosensibilitate-eritem accentuat la soare
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Rash malar
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Manifestari cutaneo-mucoase
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ULCERE ORALE
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Alte manifestari cutanate
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ALOPECIE
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ARTRITA-frecventa 90%;simetrica, afecteaza articulatiile mici(interfalangiene, metacarpofalangiene) si mijlocii (pumn,cot), cele mari(umar,sold)sunt exceptionale; este neeroziva(exudativa, NU proliferativa-PR);
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SEROZITA- pleurita(de obicei bilaterala, in cantitate mica; clinic se manifesta ca durere toracica, frecatura pleurala)pericardita sau ascita( rar , de obicei desc.
imagistic)
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Manifestari SNC
NEUROLOGICE• Cefalee• Convulsii• Coree• Accident ischemic• Cerebrita• Paralizie de nervi cranieni• Nevrite periferice
(mononevrite, polinevrite)• Pseudotumor cerebriPSIHICE• Tulburari de comportament memorie, orientare, intelect• Psihoze
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OCHI
• Edem papilar
• Retinopatie ( corpi citoizi-prezenta lor denota vasculita capilarelor retiniene cu microinfarcte ;risc de afectare SNC)
• Cheratoconjunctivita(sicca)
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Nefrita lupica WHO(OMS)
manif. renale mai frecvente la copil
biopsia renala 70% af. glomerulara
nu e oblig.in cazurile corticosensibile
expresie clinica: proteinurie moderata
+/-hematurie, sindrom nefrotic, nefritia severa( +/- IRA sau HTA severa)
CLASIFICARE WHO(OMS)Clasa I NORMALClasa II MEZANGIALAClasa III PROLIFERATIVA - focala sau segmentaraClasa IV PROLIFERATIVA - difuzaClasa V MEMBRANOASAClasa VI SCLEROZA GLOMERULARA
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Clasa II(mesangiala)
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Clasa II imunoflorescenta
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Clasa III- MO
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Clasa IV +crescent
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Clasa V (membranoasa)
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Clasa VI(sclerotica)
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• Alte afectari:- cardiaca(pericardita,miocardita)-rara; vascular-
fenomene tromboembolice la +Ac antifosfolipidici- pulmonara- musculara- miozite- va
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Criterii de diagnostic ARA- 1997
1. Rash malar(in vespertilio???”lup de carnaval”) 2. Rash discoid 3. Fotosensibilitatea4. Ulceratii orale/ naso-faringiene5. Artrita noneroziva( cel putin 2 articulatt periferice)6. Serozita – pleurita/pericardica7. Nefropatie - proteinurie persistenta(>0,5g/zi) +/- hematurie8. Neurologic - convulsi - psihoze9. Hematologice = Citopenii - anemie hemolitica(HAI)
- leucopenie - mai putin de 4000 / mm3
- limfopenie - < 1500/mm3
- trombocitopenie - < 100000/mm3
10. Imunologice: - Ac. anti AND nativ,Ac anti-Sm,Ac anti LA; la noi “celule lupice”
- reactii fals pozitive pentru sifilis persistente 6 luni, Ac anticardiolipina
sau LA(anticoagulant circulant tip lupic)11. Anticorpi antinucleari - in absenta medicamentelor care induc LES
DIAGNOSTIC 4/11 criterii
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DG. LABORATOR
SINGE• Investigatii nespecifice leucopenie anemie hemolitica(Coombs+) trombocitopenie hipocomplementemie VSH (!!! CRP +/- N)
creatinina,uree,Cl la creatinina, +/- biopsie-pt afect. renala
• Investigatii imunologice ANA + anti ADN- cei mai specifici Ac anti Ag nucleare solubile:
AC anti Sm anti SSA,si SSB asocierea cu Ac. antifosfolipidici (predictor al fenomenului trombotic)+/ - anticoagulant lupic LA, anti
beta 2 glicoproteina 1URINA-in prezenta nefropatiei: proteinurie+/- hematurie, cu tablou de nefrita sau sindrom nefrotic;
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TRATAMENT
MASURI GENERALE• Se evita expunerea la soare, doar cu crema de protectie UV• Se evita vaccinarile, transfuzii de singe, unele
medicamente
MEDICAMENTOS• AINS
• CORTICOSTEROIZI
• IMUNOSUPRESIVE
• ANTIMALARICE
• ALTI AGENTI
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AINS -TRATAMENT
AINS
• Indicatii: tratamentul simptomelor musculo-scheletale (artralgii, mialgii, artrita)
• Se pot folosi: Aspirina, Diclofenac, Ibuprofen• ! Ibuprofen: risc de meningita aseptica
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CORTICOSTEROIZII
De ELECTIE in cazurile de LES
Cel mai folosie medicamente•prednison 1-2mg/kg.c/zi
•prednisolon ( efect cushingoid >) •iv pulse methylprednisolone(forme clinice acute si severe, anemie hemolitica severa, afectare SNC, nefrita
lupica)
FOLOSIREA OPTIMALA A CORTICOIZILORReguli generale: dupa controlul manifestarilor acute(~4 sapt)
doza de steroid trebuie redusa de la 1-2 mh/kgc, pina la cea mai mica doza ce asigura remisia clinica;
Dupascaderea dozelor se trece la administrarea in priza unica, dimineata si ulterior la regimul alternativ (1zi da una nu)
Durata – la doza mica 15-20mg/zi 6-12 luniMonitorizare clinica si paraclinica frecventa pentru reactiile
adverse
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ANTIMALARICE
Indicatii• Rash cutanat efect antihiperlipidemic efect antiplachetar• Doza: < 6.5 mg/kg/day (max400 mg)
Efecte adverse Toxicitate retiniana
Monitorizarea toxicitatii- evaluare oftalmologica (inclusiv acuitate vizuala + cimp vizual) la 6 luni
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IMUNOSUPRESIVE
INDICATII
• ESEC TERAPEUTIC DE CORTICOSTEROIZI doze mari dupa 4-8 saptamini (clinic si serologic)
• CORTICODEPENDENTA• CORTICOINTOLERANTA• GLOMERULONEFRITA MEMBRANOPROLIFERATIVA• SNC-afectare severa• HEMATOLOGIC-citopenii severe
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CICLOFOSFAMIDA
Indicatii: glomerulonefrita proliferativa, afectare SNC, citopenii severe sau rezistente
Oral: 1-2 mg/kg/day 2-3 luni
IV puls.: 500mg/m2/zi (depresie medulara > ca la adm.po)
lunar x 6 doze la 3 luni inca 4 prize
Efecte adverse: leucopenie, discomfort gastrointestinal, caderea parului, cistita hemoragica, infectii, disfunctii gonadale, risc crescut de malignitate
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AZATHIOPRINE = IMURAN
Doza: oral 1-2 mg/kg/zi
Indicatii: corticorezistenta sau corticointoleranta, nefrita , terapie de continuare dupa 3 luni de Ciclofosfamida;
Durata tratamentului: 1-2 ani
Efecte adverse: leucopenie(+/- trombocitopenie sau anemie), discomfort gastrointestinal, afectare
hepatica, infectii, risc crescut de malignitate.
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ALTE TERAPII
TalidomidaCiclosporinaTacrolimusPlasmafereza(cazuri extrem de severe)Imunoglobuline iv doze mari
TRATAMENTUL COMPLICATIILORInfectioaseTrombozeHTA- inhib. canale de Ca sau ACEIRC- dializa/transplant
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MYCOPHENOLAT MOFETIL
• Doza: ~ 50mg/kg/zi p.o in 2 doze
• Indicatii: corticoresistenta sau corticotoxicitate
• Terapie de intretinere dupa Cyclofosfamida sau terapie de inductie
• Durata treatmentului: 0.5-2 ani
• Efecte adverse: toxicitate gastrointestinala, citopenii, infectii;
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COMPLICATII
RINICHI: Hipertensiune, dializa, transplant;SNC: Cerebritis, convulsii, psihoza, disfunctii cognitive ;INIMA: Ateroscleroza, infarct, cardiomiopatie,
valvulopatie;SISTEM IMUN: Infectii recurente, asplenie functionala,
malignitati;OSTEOARTICULAR: osteopenie/osteoporoza, fracturi, necroza aseptica;OCHI: cataracta, glaucom;ENDOCRIN: diabet, obezitate, esecul cresterii, sterilitate;
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ACTIVITATEEXACERBARE / REMISIUNE
LEZIUNI ORGANICERinichiul(IRC/HTA)
CALITATEA VIETII
PROGNOSTIC