SDR. VASCULARITICE

inflamaia +/- necroza vasccategoriiboal primar ce afecteaz exclusiv vasele n contextul unei alte boli vasculite intricate: overlap syndroms

Vasculite prin hipersensibilizarePurpura Henoch - SchonleinPoliarterita nodoasaChurg-StraussGranulomatoza WegenerArterite cu celule giganteBoala Behcet

CalibruVASE MARI AORTA SI RAMURI VASE MEDII tegumentar vasele medii aa. si vv. mici - (

Mecanisme formarea CIC mec. IC - formare granuloame atc anti-celule, anti-enzime lizozomale efectul direct al agenilor infecioi invazia pereilor vasc. de ctre celulele tumorale

Mecanisme elem esentiale - vasculita prin CI :CIC solubile n exces de antigendepunerea CIC n pereii vasc elib. de amine vasoactive - creterea permeabilitii vasc. activarea C, n special C5a, cu efect chemotactic pt PMNPMN infiltreaz pereii vaselor, fagociteaz CIC - LEUCOCITOCLAZIE

Mecanismerspunsul prin vasculit - la anumii subieci: predispoziie genetic;mec. reglatorii asociate cu rspunsul imun la anumite atg ;capacitatea de clearance al CIC (SRH) alte mec - n agresiunea peretelui vascular -vasculita granulomatoas! uneori i CI pot induce granuloame

Mecanisme atc anticitoplasma neutrofilelor (ANCA) n granulomatoza Wegenervasculite neimunologice:infiltraia pereilor vaselor/es. perivascular cu ageni microbieniinvazia direct a pereilor vasculari de ctre celulele neoplaziceadesea - mec neidentificat

CLASIFICARE

Tipul de vase predominant afectat

Sindromul clinic vascularitic

Aorta i ramurile primare

Boala Takayasu XE "Arterit Takayasu"

Arterele mari craniene

Arterita temporal XE "Arterit temporal" (boala Horton XE "Boal Horton" \t "Vezi Arterit temporal" )

Arterele membrelor

Trombangeita obliterant XE "Trombangeit obliterant" (boala Buerger XE "Boal Buerger" )

Artere medii i micii:

fr granulomatoz extravascular

Poliarterita nodoas XE "Poliarterit nodoas"

Boala Kawasaki XE "Boal Kawasaki"

XE "Vascularite:n boli reumatismale" Vascularite n boli reumatismale (poliartrita reumatoid XE "Poliartrit reumatoid" , sindrom Behet XE "Sindrom:Behet" )

cu granulomatoz pulmonar i eozinofilie

Angeita alergic i granulomatoas Churg-Strauss XE "Angeit alergic i granulomatoas Churg-Strauss"

Artere i vene mici cu granulomatoz a cilor respiratorii i plmnilor

Granulomatoza Wegener XE "Granulomatoz Wegener"

Arteriole, capilare, venule postcapilare

Vascularite de hipersensibilitate XE "Vascularite:de hipersensibilitate" (boala serului XE "Boala serului" , reacii la droguri)

Purpura Henoch-Schnlein XE "Purpur Henoch-Schnlein"

Poliangeita microscopic XE "Poliangeit microscopic"

Crioglobulinemia mixt XE "Crioglobulinemia mixt"

Vascularita hipocomplementemic XE "Vascularit hipocomplementemic"

Vascular XE "Vascularite:asociate bolilor maligne" ita asociat bolilor maligne (leucemia cu celule proase XE "Leucemie cu celule proase" ), colagenozelor, cirozei biliare XE "Ciroz biliar" , colitei ulceroase XE "Colit ulceroas" .

Vascularitele sistemice necrozante XE "Vascularite:sistemice necrozante"

Vascularitele de hipersensibilitate XE "Vascularite:de hipersensibilitate"

XE "Vascularite:ale vaselor mici" \t "Vezi Vascularite ale vaselor mici" (ale vaselor mici)

Poliarterita nodoas XE "Poliarterit nodoas"

Purpura reumatoid XE "Purpur reumatoid"

Angeita alergic i granulomatoas XE "Angeit alergic i granulomatoas"

Boala serului XE "Boala serului"

Poliangeite intricate XE "Poliangeit intricat" (overlap syndromes)

Vascularite induse de droguri XE "Vascularite:induse de:droguri"

Vascularite asociate XE "Vascularite:asociate: bolilor de colagen"

XE "Vascularite:asociate: hepatitei B"

XE "Vascularite:asociate: infeciei cu virus citomegalic"

XE "Vascularite:asociate: leucemiei cu celule proase" bolilor de colagen, hepatitei B, infeciei cu virusul citomegalic, leucemiei cu celule proase

Vascularite induse de proteine strine XE "Vascularite:induse de: proteine strine"

XE "Vascularite:induse de: alimente"

XE "Vascularite:induse de: antigene exogene" , alimente, alte antigene exogene

Vascularita asociat bolilor XE "Vascularita:asociat bolilor sistemice"

XE "Vascularita:hipocomplementemic" sistemice

Vascularita hipocomplementemic

Deficit congenital al sistemului complement

Arteritele arterelor mari

Boala Behet XE "Boala Behet"

XE "Arterit cu celule gigante" Arterita cu celule gigante (temporal)

Granulomatoza Wegener XE "Granulomatoz Wegener"

Arterita Takayasu XE "Arterit Takayasu"

Trombangeita obliterant XE "Trombangeit obliterant"

Arterita XE "Arterit:asociat: spondilitei anchilozante"

XE "Arterit:asociat: sindromului Reiter"

XE "Arterit:asociat: policondritei recidivante" care complic spondilita anchilozant, sindromul Reiter, policondrita recidivant

Angeitele izolate ale sistemului nervos central XE "Angeite izolate ale sistemului nervos central"

Boala Kawasaki XE "Boala Kawasaki"

Aortita luetic XE "Aortit luetic"

Sindroame vascularitice diverse

Screening paraclinicHLG completauree /creatininatestarea functiei hepatice ex urinahemoragii oculte Serologie VHB, VHCcrioglobulineatc antifosfolipidiciImunograma (IgG, IgA, IgM)complement (CH50, C3, C4)CICANCA pANCA, cANCAAANFR

VASCULITE PRIN HIPERSENSIBILITATEvase mici

Vasculite de hipersensibilitategrup heterogen de sdr. clinice caracterizate de inflamaia arteriolelor, capilarelor i venulelor indus prin r. de hipersensibilitate - urmare a expunerii la un ATG (agent infecios, drog, subst strine/ endogene)tabloul clinic: dominat de afectarea tegumentIncidenamai mare dect a vasculitelor necrozante orice vrst, uoar predominan la F

Etiopatogeniedepunerea CIC = mec principalageni cauzali:exogeni: microorganismeproteine strine vaccinuri, veninurisubstane chimice (insecticide, ierbicide, produi petrolieri)droguri (sulfamide, penicilina i alte antibiotice, AINS, allopurinol, unele antihipertensive i antiaritmice etc.)endogeni:proteine proprii organismului cu rol de autoantigen: ADN/Ig (LES, PR)antigene tumorale (vasculita din neoplazii)

Vasculite de hipersensibilitateatg

Anatomie patologicstd acutnecroz fibrinoidinfiltrat PMN, unele alterate cu resturi nucleare (leucocitoclazie) infiltrat eozinofilictumefacia endoteliuluidistrugerea integritii vasculare std subacutinfiltrat inflam.mixt acut (PMN) + cronic (ly)std cronic: infiltrat inflam. cu ly

VASCULITA LEUCOCITOCLAZICA A VASELOR MICI-purpura palpabila; IF CI IgM, IgA-

Vasculita leucocitoclazica severa vase mici si medii musculare distructie extensiva a patului vascular superficial si profund venular, arteriolar

Tablou clinicpredomin leziunile cutanatepurpura palpabil - mb inferioareelem. eritemo-papuloase de tip urticariannoduli mici dermiciuneori - edem faa dorsal a picioarelor i perimaleolar, vezicule, bule i ulceraii episodic (2-4 S), pot lsa zone hiperpigmentatefebr, mialgii, fatigabilitate, anorexie. uneori:artralgii/artritemono/polinevritdureri abdominale +/- hemoragie digestivinfiltrate pulmonare, pleurezieafectare renal frecvent, poate evolua spre IRrar - atingere SNC i cord

Explorri paracliniceNU exist teste de laborator specificeleucocitoz moderat +/- eozinofilie; creterea Ig E n serVSH crioglobuline, FR la unii pacienianomalii date de disfuncia unor organe biopsia cutanat = dg

Diagnostic pozitivbiopsie DD sdr asociate cu vasc. vaselor mici: dozarea C seric electroforeza i imunoelectroforeza anti-ADN factorul reumatoid Diagnostic diferenial anevrisme micotice i microembolii bacteriemia endocardita infecioas trombocitopenia

Evoluie variabil forme pur cutanate sunt autolimitate, rar cronic forme cu atingere visceral (renal) - letale forme iatrogene - potential fatale iniial, frecvent se vindec

Tratament prednison 0,5-1 mg/kc/zi lez. cutanat extins /manif. extracutanate

plasmafereza, imunosupresie (ciclofosfamida, azathioprina) - in rspuns insuf./ intoleran GC

antihistaminice anti-prurit

Purpura Hench-Schnleinforma sistemic a vasculitei vaselor mici

purpur palpabil - mb inf, feseartralgiimanifestri gastrointestinale (dureri, HD)afectare renal (GN)

Purpura Hench-Schnlein

Epidemiologiemai frecvent copii ntre 4-10 anipredominant la Metiologie:infecii CRS (uneori streptococice) medicamente (antibiotice, tiazide)imunizareaintolerana alimentar (lapte, ou, pete etc.)nepturi de insecte AHC: frecven a manifestrilor alergicePatogenie CI constituite din IgA care activeaz C pe cale altern

debut frecvent cu erupie cutanat i febr, mai rar cu dureri abdominale /articulareleziunile cutanate:predominent pe membre inferioare, fese, simetrice, evolueaz stadial: iniial leziuni mici urticarienepurpura palpabil placarde echimotice, macule, plci eritematoase sau eritemato-papuloase, rar leziuni necrotice rezoluie n 1-2 sptmni, fr cicatrici, pot lsa pete brune favorizate de ortostatism + edeme ale picioarelor, gambelor, faa dorsal a minilor i periorbitarpusee succesive

Tablou clinicleziunile cutanate:biopsia cutanatmicroangeit necrozant infiltrat celular n special cu ly i monociteIgA, C3 i fibrin n pereii vaselor interesateartriteleconstante, adesea inauguralearticulaii mari ale membrelor inferioare, mai rar RCC, coatesemne celsiene importante

semnele gastro-intestinale = consecina purpurei mucoaseidureri abdominale colicative, grea, vrsturidiaree sau constipaie, eliminare de snge i mucus.rar severe: dureri abdominale intense oprirea tranzitului intestinalmelen abundentinvaginaie intestinalafectare renal:

hematurie microscopicproteinurie discret / moderatuneorie hematurie macroscopic, oligurie, proteinurie abundent cu SN, HTA, IR progresiv.biopsia renal: GN focal i segmental cu proliferare mezangialGN proliferativ difuz IF: depozite mezangiale de IgA, C3 i fibrin

Explorri paraclinice leucocitoz cu neutrofilie la pacienii febrili VSH moderat crescut IgA crescut la 1/2 din pacieni C3 seric normal CIC cu IgA - frecvent decelate AAN - abs

Evoluiela copiiunul sau mai multe pusee de 7 14 ziledurata total - 1- 3 lunirecderile- excepionale > 1 an de remisiune excepional - IR progresivla adultmult mai rarGN = mai frecvent i mai grav, cu evoluie spre IR progresiv -15% recurente mai frecvente, forme cronice

Tratament repaussuportiv, monitorizarea semnelor vitaleAINS - ameliorarea simptomatologiei articulare

pt. nefropatia glomerular: prednison 1 mg/kc/zi ciclofosfamida uneori - plasmafereza hemodializ - IR progresiv

tratament etiologic:antibiotic ntreruperea administrrii unui drog posibil implicat

Poliarterita nodoas (PAN)

vasculit necrozant sistemic cu afectarea aa viscerale, predilect renale, de calibru mediu muscIncidennecunoscutraport B/F = 3/2vrsta medie la debut = 50 ani

etiopatogenieantigenul HBs - 30%, formeaz CIC cu IgPAN fr antigen HBs = vasculit cu CI, dar antigenele - necunoscute.alte antigene posibile:VHCinfecie ac a CRSvasculit necrozant tip PAN la toxicomani (amfetamin, heroin)asociat unei neoplazii ( tricoleucemie, cancere epitelial)

etiopatogenie

patogenia imun:antigen HBs, IgM, C3 n peretele vaselor de-a lungul membranei elastice interne scderea C , creterea -globulinelor prezena FR prezena crioglobulinelor rspuns la CG/ imunosupresoare

PAN anat-pat.

inflamaia necrozant a arterelor mici i medii (de tip muscular):predilecie pentru bifurcaiile arterelorsegmentare nodulii palpabili corespund ngrorilor localizate/ dilataiilor anevrismale)

PANMO:la debut - infiltrat PMN, care cuprinde toate straturile peretelui vascular i perivascularproliferarea intimeidegenerarea peretelui vascularevoluia subacut, cronic: limfocite i plasmociteNU - celule gigantenecroza fibrinoid a medieidistrugerea mb elastice interne anevrisme lumenului vascular tromboze +/- necroz is-chemic, uneori hemoragiin stadiul cicatriceal: depunerea colagenuluiendarterita fibrozant ce accentueaz lumenuluigranuloamele extravasculare = absente

PAN evoluie n pusee, cu leziuni n diferite stadii organele afectate:rinichiulcordulnervii perifericistomaculintestinulficatul tegumentularterele pulmonare NU sunt afectaterinichi: predomin arteritaleziunile de GN - 30% din cazurin caz de HTA important: posibil glomeruloscleroz

PAN - clinic

NESPECIFIC, afectarea multiorganicamanifestri generale/constitutionale:astenie fiziccefaleemialgiifebr: - domina tabloul clinic - sptmniscdere ponderalaalterarea strii generale

PAN - clinic

manifestri renale: prin afectarea ischemic glomerular (prin arterit necrozant) i GN necrozant, proliferativ, frecvent focal i segmentar (30%)proteinurie moderat (> 60%), rar SNhematurie microscopic (rareori macroscopic)HTA ( 50%) prin poliarterit renal i GNevoluie spre IR (10% IRA oliguric, letala)infarcte corticale, uneori asimptomatice hematom perirenal - prin rupturi arteriale

Multiple painful, erythematous nodules in PAN. Biopsy demonstration of muscular-vessel vasculitis (arteritis) is the key to diagnosis. The involved vessel is typically at the dermal-subcutis junction where arteries bifurcate.

Manifestri neurologicemono/polinevrite senzitivo-motorii prin afectarea vasa nervorum, care afecteaz simultan sau la intervale scurte n. sciatic, radial sau ulnar.

rar paralizii de nervi cranieni (oculomotor, facial) afectarea SNC: rar, tardiv cu prognostic rezervatAVC, convulsiihemoragii meningeene, mielitalterri ale memorieisindrom cerebelosspecific = mononevrita extensiv, determinat de infarcte simultane vasa nervorum - nervi periferici. Debut brusc - dureri vii, parestezii, hipoestezie, diminuarea Fm, amiotrofie, areflexie, edeme, tulburri vasomotorii

Manifestri articulare i musculare

artralgii/artrite asimetrice, nedeformante i neerozive (50-70%), mai frecvent n PAN cu antigen HBsmialgii frecventecompresia maselor musculare - dureroasdureri gambiere spontane/n timpul mersuluiEMG: alterri de tip miogenicconcentraia seric a enz musc. normal !!

Manifestri cardiovasculare

HTA frecventsdr Raynaud, gangrena membrelor inferioare - rarcoronarit frecventrar angin / IMAtulburri de ritm i conducere (Ex, BR, disociaie AV )tulburri de repolarizare (EKG)n evolutie - cardiomegalie, ICpericardita +/- lichid - raranevrisme coronariene - rupere n pericard

Manifestri gastrointestinale: vasculit mezentericgrea, vrsturi, diaree / constipaiedureri abdominale complicaii grave: HDSperforaii jejunale, colice, apendiculare, gastrice, vezicularepancreatit ac. + instalarea rapid a DZAfectarea hepatic latenthepatomegalie, creteri FA, TGP, TGO rar - tablou de hepatit cronic activ

Manifestri cutanate

noduli dermohipodermici 0,5-2 cmla niv gambelor i faa post a memb superioare, dureroi spontan, adereni la teg, roii/ violacei.

.polimorfism cutanat livedo reticularis microinfarcte digitale purpur palpabil peteial /echimotic eritem maculopapulos urticarie vezicule, bule ulceraii

livedoreticularis

Manifestri oculare datorit HTA (hemoragii, exudate retiniene, edem papilar)arterit oftalmic cu ambliopieconjunctivit, sclerit, keratit, uveit

nu exist teste serologice specifice !!!!!hemoleucograma:anemie moderat de tip inflamator;leucocitoz (> 10000/mm3, uneori > 25000/mm3) cu predominana PMNeozinofilie sanguin moderat la 20-30% din cazuritrombocitoz (inflamaia cronic)VSH teste de inflamaie nespecifichiper--globulinemie moderatFR prezent - (10%)CIC, uneori crioglobulineC seric normal / sczut (C3 i C4)antigen HBs prezent (30%)

afectarea specific a unor organeangiografii: ngustri, stenozri sau anevrisme arteriale la nivelul arterelor mici i medii, de tip muscularangiografia abdominal:microanevrisme la nivelul aa. intraparenchi-matoase hepatice, renale, pancreatice: multiple, saculare, d < 5 mmstenoze, dilataii, obstrucii arterialeangiografia coronarian: anevrisme coronarieneangiografia cerebral: la pacienii cu afectare SNC

Biopsia DG de CERTITUDINE !!!!! inflamaia necrozant aa medii, mici, de tip muscular

PBR - n absena anevrismelor: arterit / GNbiopsia n. sural (nevrit): vasculita vasa nervorumbiopsia musc = pozitiv dac muchiul este dureros biopsia profund a unui nodul dermohipodermic

Diagnostic pozitiv:manifestrile clinice multiorg. + exam histopat i/sau modif arteriografice.simptomele i semnele localizate trebuie evaluate pentru a decide practicarea biopsiei/arteriografieiDiagnostic diferenial foarte dificil prezena manifestrilor unui singur organ sau sistem limiteaz afeciunile incluse n diagnosticul diferenialapariia leziunilor tegumentare indic prezena fenomenelor vasculitice

Criterii de diagnostic min. 3: 1. scdere ponderal > 4 kg2. livedo reticularis3. mialgii, slbiciune muscular4. mono/polineuropatie5. durere/ sensibilitate testicular6. TAD > 90 mmHg7. uree > 40 mg/dl, creatinin > 1,5 mg/dl8. VHB9. anomalii arteriografice ocluzia vaselor viscerale 10. biopsia vaselor mici/medii- aa conin PMN

Prognosticextrem de rezervat n PAN netratatdeces < 1 an ant. corticoterapieiEvoluiedeteriorare fulminant / progresie lent, ntrerupt de exacerbri acute.Deces:insuficien renalcomplicaii cardio-vasculareinfarcte intestinale cu perforaii AVCHTA determin afectare renal, cardiac i a SNC

Tratamentprednison (1 mg/kgc/zi) + ciclofosfamid (2 mg/kgc/zi), - remisiuni pe termen lung 90%azathioprin tratam. de ntreinerevidarabina + plasmaferez - atg HBs2 interferonIG i.v.Anti TNF- nu exist date suficientemycofenolat mofetiltratamentul HTA

Angeita alergic i granulomatoasCHURG-STRAUSSvasculit granulomatoas plurisistemic, n special pulmonar (astm sever) i eozinofilie

rar, la aduli

B/F = 1,3/1

ARTERITA EOZINOFILICA Churg-Strauss

vasculita ANCA-asociata (GW, PAM)vase medii si micivasculit granulomatoas plurisistemic, n special pulmonar (astm sever) i eozinofilie, GN necrotizanta

American College of Rheumatology (ACR), Consens CHAPEL HILL - 6 criterii de dg 4/> => DG+(1) astm sever (wheezing, raluri expiratorii), (2) eozinofilia > 10% in sangele periferic (3) sinuzita paranazala(4) infiltrate pulmonare chiar tranzitorii(5) dovezi histopat. de vasculita cu eozinofilie extravasculara(6) mononevrita multiplex /polineuropatie.

Etiopatogenienecunoscuthipersensibilitate de tip anafilacticanomalii imunologice: prezena CIC, Ig i C la nivelul peretelui vascularautoimunitate:hipergammaglobulinemieprezenta FR, ANCA

Clinic 3 FAZE

rinita alergica si astm; boala infiltrativa eozinofilica - , ex: pneumonia eozinofilica/ gastroenterita; vasculita sistemica a vaselor mici si medii cu inflamatie granulomatoasa dezv in 3 ani de la debutul astmului

simptome constitutionale - fatigabilitate, semne pseudogripale, scadere ponderala (70%), febra (57%), mialgii (52%) simpt astmatica (97%): persistenta, precede/sincrona cu vasculitasinuzita paranazala (61%) rinita alergica, polipoza nazala pulmonar (37%), - tuse, hemoptizie artralgii(40%)

cutanat (49%) - purpura noduli rash urticarianischemia digitalaCardiace IC, miocardita, pericardita, pericardita constrictiva, IMA Gastrointestinale (31%) vasculita GI, gastrita eozinofilica, colita - dureri abdominale [59%], diareea [33%], HD [18%].) Neuropatie periferica - Mononevrita multiplex - 77%

Churg-Strauss

Semne fizicefebraafectare cutanata idem + livedo reticularisafectarea CRS Rinita alergicaSinuzita paranazalapolipozaafectarea CRI astm +pneumonitis hemoptizie sec. capilaritei alveolareC-vasc Dispnee, ICIMA sec coronariteirenal - HTA, IRgastrointestinal HD Ischemie +/- perforatie intestinalagastroenteritapancreatitaSN mononevrita multiplex [77%]) SNC AIT, AVC - [5%])

Biologichematologiceosinofilia - > 10% eosinofile (or 5000-9000 elem/L) anemiaVSH, CRP - crescute test renale uree, creatinina; proteinurie, microhematurieANCA: 70% - perinuclear-ANCA (p-ANCA)pozitive ( atc antimieloperoxidaza) niveluri serice IgE - crescute hipergammaglobulinemia FR + la titruri mici

Eosinofilia in lavajul bronchioalveolar (BAL), - 33% din cazuri

imagisticRXopacitati pulmonare - 26-77% - bilat, periferice cavitatia - rara pleurezie eozinofilica - 5-30% adenopatii hilare - ocazional

imagisticCT scan condensari parenchimatoase periferice in sticla mata similar pneumoniei eozinofilice cronicemai rar - noduli (5 mm - 3.5 cm), cu cavitatie / bronhograma aericadilatatii bronsice High-resolution CT scanning - pattern vasculitic dilatare semnificativa a ram periferice ale arterelor pulmonare de tip stelat abdominal CT scan - pt. pancreatita, coronarografie - pt ischemie, IMAechocardiografie evaluarea ICEKG, EDS, EMG

BIOPSIADin organe interesate Daca NU - nerv sural !!! PBR GN focala /semilune; cutanat plaman Open/ toracoscopie videoasistatanervimuschi

ARTERITA EOZINOFILICA Churg-Strauss -. Granulom- centru eosinofilic inconjurat de macrofage, cel epiteloide gigante

Churg-Strauss histopat.

Complicatii. Prognosticfara trat, rata supravietuirii la 5 ani - 25%. cu trat, la 1 an - 90% ; la 5 ani 68%mortalitateIMA, ICIRC AVC HD Status asthmaticus

TratamentPrednison -Start - 0.5-1 mg/kg/d PO. Metilprednisolon - IV puls-terapie ind: afect cardiaca, hemoragie pulm, GN, neuropatie Ciclofosfamida doza unica 500 mg /m2 azathioprina mycophenolate mofetil, Ig IV Plasmafereza rez. limitate Interferon alpha

Granulomatoza Wegenervasculita granulomatoasa aa. si vv. de calibru mediu si mic

- afectarea CRS, plamanilor si rinichilor

EtiopatogenieExistenta rr. de hipersensibilitate evocate de:atg exogene + endogene => lez ale CRS si plamanilorgranuloamele pulmonare cu celule gigante =r. de corp strain r. tip IV IU - existenta CIC + CI depuse vasc. - atc fata de fract citoplasmatice ale neutrofilelor (ANCA) proteinaza3 atg tinta

Anatomie patologica2 tipuri lezionale- lez inflamatorii vascularitice PAN-like cu necroza fibrinoida, distructii ale muscularei, laminei elastice fara microanevrisme- lez granulomatoase vasculare + extravasculare, cu centru necrotic si periferie cu fibroblasti, histiocite, mononucleare, celule gigant

Anatomie patologica - CRS sinusuri nazofrontale lez inflamatorii granulomatoase cu ulceratii

Pulmonar noduli infiltrativi bilat. cu tendinta la escavare

Renal glomerulonefrita segmentara si focala depuneri de IgA, IgM + C3 la nivel capilar si mezangial

CLINICAManifestari respiratorii

- rinoree purulenta/sanghinolenta- perforatie de sept- sinuzita frontala, maxilara, etmoid.- faringita ulcerativa- otita medie seroasa- infiltrate pulmonare: tuse, dispnee,hemoptizii, dureri toracice

CLINICAManifestari renale grave

proteinuriehematurieretentie azotataIR rapid progresiva

CLINICAAlte manifestari

Oculare sclerite, uveite, conjunctivite Neurologice nevrite Articulare artrite, artralgii Cardiace mio-pericardita, coronarita Cutanate purpura palpabila, noduli, ulceratii

ParaclinicBiologic nespecific:- anemie, leucocitoza, VSH- FR, CIC, hiper - prezenta PR3 - cANCA + pANCAHistopatologic- biopsie muc. nazala inflam granulomatoasa necrozanta- biopsie pulmonara vasculita granulomatoasa- PBH GN segm, focala/proliferativ

Diagnostic diferential

angeita Churg Strauss sarcoidoza TBC pulmonara sdr. Goodpasture LES

Evolutie. Prognostic

netratata deces prin IR

sub terapie remisiuni durabile - ameliorari importanteRisc de cancer ! ! !- renal- vezica urinara- cutanat, leucemie, limfoame

Tratament de electie Ciclofosfamida 2mg/kg/zi po 12 luni, apoi scadere treptata asociere PDN 1mg/kg/zi + Cfm alternativ MTX + PDN- AZA + PDNDe actualitate- in cazuri refractare Cfm + GCSF apoi aferesis CD34+ 2,86X 106! ! ! MESNA 2-mercaptoetan sulfonat de NaCitoprotectiv pt afectarea uroteliala sub Cfm

Tratament de avangardaTNF rol central in inflamatie si in formarea granuloamelor

=> Infliximab => Etanercept

panarterita segmentara a Ao si ramurilor mai ales a. temporala superficiala, a. oftalmica

= arterita temporala = boala HORTONArterita cu celule gigante

incidenta crescuta la rasa albaprevalent la femei, 25:9 decada a 6-a frecv asimpt. 1,6 % la necropsie

Etiopatogenie

- necunoscuta - relatie cu HLA DR4 - IC tip IV - IU tip III prin CIC

- IU + IC riposta fata de elastina / antigene ale mediei arteriale

Etiopatogenie

la nivel molecular exista un ARNm specific pt citokinele din macrofage si celule T- IL- 1, 6 activare macrofage- IL -2 , ARNm pt IFN activ Cel Tcitokinele proinflam. rol central

IU argumentata de depozite Ig+C adiacent laminei elastice interne => inflamatia mediei si intimei infiltrat granulomatos + participarea moleculelor de adeziune

Anatomie patologica artere mari + medii electiv teritoriul carotidei externe(temporala,oftalmica,faciala,vertebrale)rar Ao iliace,subclavie,axilara, a. centala retina, carotida interna panarterita subac. segmentara polifocala infiltrat ly-plasmocitar + macrofage gigante + fragmentarea laminei elastice interne + proliferarea intimei =>ingustare tromboze + ischemie

Temporal arteritis with occlusion of the arterial lumen,thickened intima, neoangiogenesis and aggregates of giant cells

Clinica febra, astenie, scadere ponderala - ARTERITA in teritoriul CAROTIDEI EXTERNEcefalee difuza/temporalaartera hipopulsatila, indurata, sinuoasadureri/ hiper/hipoestezia scalpuluiclaudicatia maseterilor si limbii - arterita oftalmicascaderea AV, diplopie(claudicatia oculomotori), cecitate brusca prin nevrita optica- oligoartrite, polimialgie reumatica-like- ischemie Raynaud, membre, AVC, IMA, nevrite periferice SEMN PRECOCE asistolie tranzitorie la compresia sinusului carotidian

Paraclinic nespecifice HG, VSH cresteri IgG, CIC lipsesc FR, AAN exista cANCA la niv.< GW ex FO hemoragii, exudate, edem papilar - tardiv atrofia de nerv optic

Biopsii de artera min 2cm- ghidate arteriografic/echoDoppler- neg. - NU EXCLUDE DG.

NB ! Pot fi irelevante datorita afectarii SEGMENTARE

DIAGNOSTIC +

sugerat de clinica ex histopatologic

supozitia clinica - poate fi confirmata de raspunsul terapeutic la corticoizi

Diagnostic diferential

polimialgia reumatica arterita Takayasu infectii neoplazii

Evolutie. Tratament favorabila sub terapie prompta remisiuni durabile

de electie PDN 0,5 1mg/kg/zi 2-4 sapt. cu scadere treptata pana la 5-10 mg/zi 12 24 luni antiagregante in studiu anti IL-1

POLIMIALGIA REUMATICA varianta topografica a bolii HORTON prevalenta - in emisfera N- la varstnici- rasa alba

IDENTICE etiopatogenic si morfopatologic

DIFERA teritoriul vascularAA. Mari ce iriga musculatura centurilor sup. si inf., cefei

CLINICA dureri musculare + redoare difuza nocturna scaderea fortei musculare

caracteristic: - simetria - nu afecteaza distal - sinovite SH, FT, SC, RCC - tardiv atrofii musculare

NB ! Cauta B. HORTON asocieriNB ! Asocieri cu PR

PARACLINIC reactantii de faza acuta + + +

N - EMG - Creatinkinaza - biopsia musculara

Diagnostic +/ DD de excludere

- miopatii paraneoplazica- polimiozita- PR- miopatii neurologice

Tratament

PDN 10 20 mg/zi cu efect spectaculos in 24 ore

durata 1 2 ani

NB ! ! ! Recidive la sistarea terapiei

Arterita TAKAYASU sdr. de arc aortic boala fara puls

frecventa la F F : B = 9 : 1

< 40 ani

foarte rara

Etiopatogenie similara b.HORTON

afectara - Ao ascendenta, abd., descendenta - subclavie - carotida - artere renale

Clinicaconsecinta ocluziei vasculara+ ischemiei faza preocluziva- asimpt., luni,ani- semne generale- artrite, eritem nodos, f.Raynaud,pleuro-pericardite faza ocluziva fctie de localizare- claudicatie, cefalee, sincope, diplopie, amauroza, HTA (emergenta aa renale

Paraclinic arteriografie

- afectare arc Ao +ramuri tip I

- coarctatie atipica Ao tip II Ao descendenta + abdominala

- variante ale tipurilor I si II

Diagnostic + min. 3 din 6 criterii ACR1. debut < 40 ani2. claudicatia extremitatilor astenie/ disconfort musc de effort3. scaderea pulsului brahial,uni/bilat4. diferenta TAs dr. /stg > 10mm Hg5. sufluri la subclavie/Ao6. anomalii arteriografice: ingustari, ocluzii focale/segm in abs. ASC

Tratament In faza preocluziva- PDN 1mg/kg/zi- anticoagulante/antiagregante- vasodilatatoare la nonresponsivi- Cfm 2mg/kg/zi- AZA In faza ocluziva- angioplastii, by-pass

Boala KAWASAKY boala acuta, febrila, eruptiva a copiilor - 5 ani, complicata cu vasculita coronariana

Etipatogenic arterita a arterelor medii coronare si interlobulare renale - initiata ca perivasculita vaselor mici, apoi medii si mari

Clinica debut febril cu adenopatii + congestia mucoaselor

- exantem polimorf pe trunchi si membre- edem indurat+eritem+ descuamare

angor, tulb de ritm rar IMA greturi, varsaturi, dureri abdominale fen neurologice

Paraclinic L, VSH, T, PCR

ASLO = N

EKG QT >, unde Q, hipovoltaj, aritmii

Rx, echo cardiomegalie

coronarografic - caracteristic

DIAGNOSTIC + 5 din 6 simpt./ 4 + anevrisme coronariene obiectivate coronarografic/ echo

Febra persistenta > 5 zileModificari ale buzelor+ cav. bucaleAdenopatie cervicala nesupurativaCongestie conjunctivala bilateralaExantem polimorfModificari caracteristice ale extremitatilor

Tratament de urgenta - globuline iv 400mg/kg/zi 4 zile- aspirina 80 100 mg/ziEfect favorabil

2 -5 % - deces prin tromboza coronariana

SDR. BEHET vasculita sistemica ulceratii recurente orale + genitale uveita cecitateEpidemiologietineri decada 3agregare HLA-B51Turcia, Iran, Japoniausoara predilectie sex masculin

Etiopatogenie multifactoriala fen. autoimune- rol cheie TNF direct+- scadere ly T4/T8- CIC +++- HLA B51 corelat cu fctie exagerata a neutrofilelor- atc anticardiolipinici det. vasculitice retiniene- atc antimembranari pt mucoasa bucala

Anatomo-patologic vasculita venulelor infiltrat ly-plasmocitar + neutrofile si mastocite perivascular

SNC idem + fibroza perivasc + degenerarea fibrelor nervoase

mucoase edem + infiltrat

Clinica prima manifestare stomatita aftoasa, afte dureroase si pe faringe, trahee,esofag, intestin ulcetatii la niv organelor genitale externe eritem nodos lez acneiforme piodermii

reactie patergica

Clinica 80% - afectare oculara uveita bilat. ant si post.- edem papilar- corioretinita- nevrita optica

cecitate glaucom secundar cataracta

Clinica osteoarticular oligoartrita neeroziva G, TT - sacroiliita neurologic sdr iritatie meningiana - HIC - sdr piramidal - confuzie dementa - afectare nn cranieniArterial anevrisme aorta abd, carotide, mezenterice, femuraleVenos tromboze cave, renale, suprahepatice TEP

Paraclinic

anemie VSH, PCR crescute niveluri serice crescute IgA

CT, RMN, angioRMN, angiografii selective, Doppler

Diagnostic + criteriul clinic constant aftoza recurenta orala + 2 afectari organiceCriteriiUlceratii orale recurente, min 3 epis/ anUlceratii genitale recurenteUveita ant/post, vasculita retinianaEritem nodos, papulo-pustuloase, acneiforme, pseudofoliculitaPatergie citita de medic la 24 -48 h

Prognostic evolutie cu remisiuni si exacerbari- complicatii nefavorabil- meningoencefalita- uveita post. rar HDS, complicatii vasc, limfoame

Tratament oculare, SNC Medrol pulse + po - AZA 2,5mg/kg/zi - Ciclosporina A - Cfm -1g/ iv / luna articular AINS /corticizi i.a.

actualitate Infliximab 5mg/kg 0, 2, 6, 12 sapt. remisiuni de durata

Cutaneous vasculitis. Most examples of cutaneous vasculitis are the result of vascular immune complex deposits, which lead to a neutrophilic small-vessel (leukocytoclastic) vasculitis (a) manifesting as palpable purpura (b). Immune complexes can also arise in the setting of infection, producing secondary leukocytoclastic vasculitis. This patient had a history of ventricular septal defect that was complicated by streptococcal septicemia and was associated with IgA and IgM vascular immunoglobulin deposition (c). Infections have been associated with the development of IgA vascular immune complexes.[

Severe cutaneous leukocytoclastic angiitis. Pan-dermal small- and/or muscular-vessel vasculitis leads to severe cutaneous vasculitis characterized by multiple superficial ulcerations and infiltrated erythema. Extensive compromise of the vascular bed (superficial and deep venular plexus and arterioles) explains the presence of ulcerations in this patient with severe cutaneous leukocytoclastic angiitis.

Churg-Strauss

Churg-Strauss histopat.

Wegener. granulom

Cutaneous vasculitis. Most examples of cutaneous vasculitis are the result of vascular immune complex deposits, which lead to a neutrophilic small-vessel (leukocytoclastic) vasculitis (a) manifesting as palpable purpura (b). Immune complexes can also arise in the setting of infection, producing secondary leukocytoclastic vasculitis. This patient had a history of ventricular septal defect that was complicated by streptococcal septicemia and was associated with IgA and IgM vascular immunoglobulin deposition (c). Infections have been associated with the development of IgA vascular immune complexes.[

Severe cutaneous leukocytoclastic angiitis. Pan-dermal small- and/or muscular-vessel vasculitis leads to severe cutaneous vasculitis characterized by multiple superficial ulcerations and infiltrated erythema. Extensive compromise of the vascular bed (superficial and deep venular plexus and arterioles) explains the presence of ulcerations in this patient with severe cutaneous leukocytoclastic angiitis.

Differentiation of nodular vasculitis from polyarteritis nodosa (PAN). Nodular vasculitis can be differentiated from PAN by the presence of panniculitis centered on a muscular vessel, most commonly a vein (see arrow) [a]. Veins (b) [elastic tissue stain] can be differentiated from arteries (c) [elastic tissue stain] by the presence of collagen and elastic fibers intermixed with haphazard smooth muscle bundles, whereas arteries are denoted by round muscular vessels with a continuous wreath of smooth muscle fibers. Furthermore, in contrast to the rich elastic fibers in the muscular layer of veins (b), there are minimal elastic fibers in the arterial wall and a well defined internal elastic lamina (c) that can be fragmented or discontinuous in a lesion of PAN or other arteritis such as giant cell arteritis.

Churg-Strauss syndrome presents with necrotizing leukocytoclastic vasculitis and nodules on the extensor surfaces (shown). The nodules represent Churg-Strauss granulomas. Systemic features include asthma, cardiac vasculitis, and rapidly progressive glomerulonephritis. Peripheral antineutrophil cytoplasmic antibodies (p-ANCAs) are characteristically present.Churg-Strauss granuloma presents with histiocytes surrounding a core of collagen and degranulated eosinophils, as shown.Wegener granulomatosis presents with necrosis of the upper airway (shown) along with renal disease. Cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) are characteristically present.A reticular (net-like) pattern of purpura correlates with vasculitis involving medium-sized vessels, producing necrosis of the endothelium (shown). Common causes include Churg-Strauss syndrome, Wegener granulomatosis, microscopic polyangiitis, rheumatoid vasculitis, and septic vasculitis. Nonvasculitic causes of retiform purpura include thrombotic or embolic vascular diseases Leukocytoclastic vasculitis involving postcapillary venules may produce thumbprint or polycyclic purpura (shown). Common causes include medications, connective tissue disease, mixed cryoglobulinemia, Henoch-Schnlein purpura, and serum sickness.Histologically, leukocytoclastic vasculitis demonstrates deeply staining red fibrin within the vessel wall together with fragmented neutrophils (leukocytoclasis), as shown.Polyarteritis nodosa (shown) is a systemic vasculitis characterized by necrotizing inflammatory lesions affecting medium and small muscular arteries. This results in microaneurysm formation, which leads to hemorrhage, thrombosis, and tissue ischemia. The classic skin manifestations include livedo reticularis, lower-extremity ulcerations, digital ischemia, and firm, tender subcutaneous nodules (shown). Common systemic symptoms include fever, malaise, fatigue, weight loss, myalgias, and arthralgias.Churg-Strauss syndrome presents with necrotizing leukocytoclastic vasculitis and nodules on the extensor surfaces (shown). The nodules represent Churg-Strauss granulomas. Systemic features include asthma, cardiac vasculitis, and rapidly progressive glomerulonephritis. Peripheral antineutrophil cytoplasmic antibodies (p-ANCAs) are characteristically present.Churg-Strauss granuloma presents with histiocytes surrounding a core of collagen and degranulated eosinophils, as shown.Wegener granulomatosis presents with necrosis of the upper airway (shown) along with renal disease. Cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) are characteristically present.