Infectii virale cutanate

Download Infectii virale cutanate

Post on 25-Oct-2015

55 views

Category:

Documents

11 download

Embed Size (px)

TRANSCRIPT

<ul><li><p>1INFECTII CUTANATEVIRALE</p></li><li><p>2Conflict de interese</p><p> Astellas Pharma Glaxo SmithKline Hoffman LaRoche Janssen Pharma Schering AG Schering Plough LOreal</p><p> Sir Samuel Scott ofYews Trust</p><p> European DermatoEpidemiologyNetwork</p><p> Archives ofDermatology</p></li><li><p>3Foarte variateDepind de:</p><p>Tipul virusuluiLocalizarea infectieiRaspunsul imun al gazdei</p><p>Unele virusuri pot doar coloniza epidermul, fara aproduce manifestari clinice (ex: HPV, v.molluscumului contagiosum)</p><p>Manifestari clinice</p></li><li><p>4Virusuri care produc infectiicutanate (I)</p><p>Papilomavirusuri umaneVirusuri herpetice</p><p>Virusul herpes simplex 1, 2Virusul varicelo-zosterianVirusul Epstein-BarrHerpesvirusul uman 6, 7, 8</p><p>Pox-virusuriVirusul molluscumului contagiosumVirusul nodulilor mulgatorilorVirusul ectimei contagiosum (orf)</p></li><li><p>5Virusuri care produc infectiicutanate (II)</p><p>Virusurile bolilor eruptive ale copilariei(rujeola, rubeola, varicela)Virusul hepatitei B (vasculite, urticariecronica)</p></li><li><p>6Despre ce voi vorbi...</p><p> Papilomavirusuri umane Herpes simplex Herpes zoster Poxvirusuri Pitiriazis rozat Sarcom Kaposi Manifestari cutanate in infectia HIV</p></li><li><p>7Papilomavirusuri umane</p><p>Caractere generaleGrup de &gt;100 virusuri ADNProduc proliferarea epiteliilor pielii simucoaselorDetermina de obicei leziuni benigneUnele tipuri pot produce leziuni displazicesau neoplazice</p></li><li><p>8Papilomavirusuri umanemanifestari clinice (I)</p><p>Veruci vulgareVeruci plantare</p><p>ProfundeSuperficiale (in mozaic)</p><p>Veruci plane (juvenile)Papiloame (veruci filiforme/digitate)</p></li><li><p>9Papilomavirusuri umanemanifestari clinice (II)</p><p>Condiloame (veruci) anogenitaleCondiloame acuminateCondiloame plane ale colului uterinCondilomatoza giganta</p><p>Papuloza bowenoidaEpidermodisplazia veruciforma</p></li><li><p>10</p></li><li><p>11</p></li><li><p>12</p></li><li><p>13</p></li><li><p>14</p></li><li><p>15</p></li><li><p>16</p></li><li><p>17</p></li><li><p>18</p></li><li><p>19</p></li><li><p>20</p><p>Papilomavirusuri umane tratament</p><p>Acid salicilic 15-25%Acid mono-, tricloracetic 25-30%Podofilina 25%/podofilotoxina 0,5%CrioterapieSensibilizanti de contact (DNCB, DCP)Citostatice topice/intralezionaleMetode chirurgicale: curetaj,electrocoagulare, laser CO2</p></li><li><p>21</p><p>Papilomavirusuriinfectii genitale (I)</p><p>Cea mai frecventa ITSIncidenta in crestere: 25% barbati,28% femei - 1999 vs. 199390% din condiloame sunt produse detipuri neoncogene (PVU 6, 11)Majoritatea celor infectati nu aucondiloame vizibile (posibil doar 1%dintre cei infectati)</p></li><li><p>22</p><p>Papilomavirusuriinfectii genitale</p><p>Cu risc oncogen mare (16, 18)Majoritatea cazurilor de carcinom de col uterin secoreleaza cu PVU 16, 18; frecvent produc infectiiasimptomatice</p><p>Cu risc oncogen mic (6, 11)Produc un carcinom spinocelular neagresiv (Buschke-Loewenstein)</p><p>Sunt posibile coinfectii cu mai multe tipuri</p></li><li><p>23</p></li><li><p>24</p></li><li><p>25</p></li><li><p>26</p><p>Papilomavirusuriinfectii genitale</p><p>Testarea ADN-ului pentru tipurilorcu risc mare:</p><p>Utilitatea testarii depinde de Sb, Sp siprevalenta infectiei cu risc mareCel mai utilizat test (Digene) are Sb90%, Sp 15-20% rata mare defals+testul este autorizat de FDA pentruprobe recoltate din colul uterin</p></li><li><p>27</p><p>Papilomavirusuri - infectii genitaleepidemiologie</p><p>Transmiterea este facilitata de existentaleziunilor (dar nu exclusiva)Transmiterea mediata de obiecte esteposibila, dar nedoveditaTransmiterea cu ocazia nasterii este rara(papiloame laringiene sau condiloameanogenitale la luni de zile post-partum)Infectivitatea inter-parteneri: 60%Utilizarea prezervativului reducetransmiterea</p></li><li><p>28</p><p>Papilomavirusuri - infectii genitalefactori de risc</p><p>Numarul partenerilor sexualiFrecventa contactelor sexualePrezenta condiloamelor la partenerFumatul (factor de risc independent)</p></li><li><p>29</p><p>Condiloame acuminatediagnostic</p><p>Clinicutilizarea acidului acetic (aceto-whitening) nerecomandabila, pt caSb, Sp, 25% rezultate fals+ (CDC)</p><p>HistopatologicReactie de amplificare genica</p><p>cercetare, beneficiu minim pt dg sitratamentul de rutina</p></li><li><p>30</p><p>Condiloame acuminate evolutie naturala</p><p>Pot spontan regresa, creste, ramaneneschimbateNetratate, 10-30% dispar spontan incca 3 luni</p></li><li><p>31</p><p>Condiloame acuminateprincipii de tratament</p><p>Nu exista o metoda terapeutica unica sisatisfacatoare in toate cazurileRatele de succes initiale sunt 50-75%cu majoritatea tratamentelorRecurentele sunt obisnuiteVaccinuri anti-PVU pot preveni infectia</p></li><li><p>32</p><p>Condiloame acuminatetratament</p><p>Metode aplicabile de catre pacientPodofilotoxina (Condyline) 3/7, 4-6 saptImiquimod (Aldara) 3/7, max 16 sapt</p><p>Metode aplicabile de personal medicalCrioterapiePodofilinaAcid tri-, bi-cloraceticCuretareElectrocauterizareFotovolatilizare laser</p></li><li><p>33</p><p>Vaccin anti-PVU (Gardasil)</p><p>Vaccinul este impotriva celor mai frecvente tulpinide PVU (6, 11, 16, 18)Este puternic imunogen - induce un raspuns imunfoarte intens, de 50 de ori mai mare decat raspunsulimun obtinut prin contactul natural cupapilomavirusul.Vaccinul nu are nici un risc din punct de vedere alinfectiozitatii sau riscului oncogenic, intrucat esteobtinut prin recombinare genica.Este in prezent autorizat si pentru vaccinareabaietilor (FDA 2010)</p></li><li><p>34</p><p>Vaccin anti-PVU - limitariLipsa datelor referitoare la durata raspunsului imunDate insuficiente referitoare la intensitatearaspunsului imun (titrul Ac este un marker surogat alraspunsului imun)Posibile infectii cu alte tipuri, deci screening-ultrebuie sa continueAcceptabilitatea sociala a vaccinuluiVaccinarea barbatilor (vaccinarea exclusiva afemeilor este cu 60-75% mai putin eficienta inprevenirea cancerului de col decat vaccinareaambelor sexe)</p></li><li><p>35</p><p>Tratamentrezultate asteptate</p><p>Scopul nu este eradicarea PVU (imposibila dincauza infectiei clinice subiacente)Tratarea leziunilor vizibile poate reduceinfectiozitatea si transmiterea (nedemonstrat)Tratamentul este exclusiv simptomatic si poatecontribui la cresterea perioadelor fara leziuniRecurentele sunt &gt; 25% in primele 3 luniTratamentul este mai eficace pentrucondiloamele recente (&lt; 1an)</p></li><li><p>36</p><p>Duct tape therapy for warts.Jerry Litt, 1978.</p></li><li><p>37</p><p>Tratamentul verucilor cu bandaadeziva (duct tape)</p><p>Metoda nedureroasa, lipsita de riscuri, ieftina sieficace pt verucile peri- si subunghiale</p><p>Tehnica:Infasurati complet veruca cu banda adezivapentru a realiza ocluzie completaLasati banda 6,5 zile, apoi faceti o pauza de12 ore; se repeta pana la disparitia veruciiDupa cateva sapt, veruca se micsoreaza, semacereaza si dispare</p></li><li><p>38</p><p>Dont Excise - Exorcise.Duct tape therapy for warts.</p><p>Jerry Litt. Cutis 1978; 22: 673-76.</p></li><li><p>39</p><p>Ce este duct tape?</p><p> Duct tape, or duck tape, is a polyethylene, reinforced,multi-purpose pressure sensitive tape with a soft andflexible shell and pressure sensitive adhesive. It isgenerally silver or black in color but many othercolors have recently become available. With astandard width of 1+78 inches (48 mm), duct tapewas originally developed during World War II in 1942as a water resistant sealing tape for ammunitioncases.</p><p>(http://en.wikipedia.org/wiki/Duct_tape)</p></li><li><p>40</p></li><li><p>41</p><p>Duct tape for the treatment of commonwarts in adults: a double-blind RCT</p><p>Arch Dermatol 2007 90 immunocompetent adult volunteers with at least 1</p><p>wart measuring 2 to 15 mm enrolled. 80 completedthe study.</p><p> There were no statistically significant differences inthe proportions of patients with resolution of thetarget wart (8 [21%] of 39 patients in the treatmentgroup vs 9 [22%] of 41 in the control group).</p><p> Of patients with complete resolution, 6 (75%) in thetreatment group and 3 (33%) in the control group hadrecurrence of the target wart by the sixth month.</p><p>Arch Dermatol. 2007 Mar;143(3):309-13.</p></li><li><p>42</p><p>If the patient is you, try aplacebo or two.</p></li><li><p>43</p><p>Despre ce voi vorbi...</p><p> Papilomavirusuri umane Herpes simplex Herpes zoster Poxvirusuri Pitiriazis rozat Sarcom Kaposi Manifestari cutanate in infectia HIV</p></li><li><p>44</p><p>Herpes simplex</p><p>Virus ADN - 2 tipuri antigenice (VHS1,VHS2)Produce infectie cronica, persistenta aggl nervilor senzitivi si recurentemucoase variabile si imprevizibile</p></li><li><p>45</p><p>Herpes simplex manifestari clinice</p><p> A. Primo-infectia herpeticaF. inaparente (80-95% din infectiile VHS1)Gingivostomatita herpeticaHerpesul genital primarAlte forme:</p><p>Panaritiu herpeticKeratoconjunctivita</p><p>Forme graveEczema herpeticumHerpesul neonatalHerpesul la imunodeprimati</p><p> B. Herpesul recurent</p></li><li><p>46</p><p>Herpes simplex - diagnostic</p><p> Clinic - suficient pt cazurile tipice Paraclinic</p><p>CitodiagnosticIFDCultura viralaSerologia - nu este utila pt dg. recurentelor</p></li><li><p>47</p><p>Herpes simplex - tratament</p><p>1.Antivirale care inhiba ADN-polimerazavirala dupa o fosforilare prealabilamediata de timidinkinaza (TK)herpetica (*ciclovir-uri)</p><p>2.Antivirale care inhiba ADN-polimerazavirala independent de timidinkinazaherpetica</p></li><li><p>48</p><p>Efectele tratamentului antiviral</p><p>Tratamentul recurentelor (intermitent)Scurteaza durata si severitate recurenteirespectiveNu influenteaza durata frecventa, duratasi severitatea recurentelor ulterioare</p><p>Tratamentul continuuReduce frecventa (cu &gt;60-70%) siseveritatea recurentelor si eliminarileasimptomatice de virus</p></li><li><p>49</p><p>Indicatiile tratamentului antiviralcontinuu</p><p>Recurente frecvente (&gt;6/an)Recurente complicateImunodeprimatiGravide la risc, dupa saptamana 36</p></li><li><p>50</p><p>Rezistenta la antivirale</p><p>Nu se dezvolta la persoaneimunocompetenteRisc mare de dezvoltare a rezistenteila imunodeprimatiMecanism: mutatii ale genei TK cudisparitia completa a genei rezistenta incrucisata la *ciclovir-uri</p></li><li><p>51</p><p>Herpes simplex - tratament</p><p>AciclovirAnalog ciclic al guanozineiBiodisponibilitate 15%Trat recurentelor: 200 mg x 5/ziTrat continuu: 800 mg/zi in 1-2 prize</p><p>ValaciclovirEsterul L-valil al acicloviruluiBiodisponibilitate 54%Trat recurentelor: 500 mg x 2/ziTrat continuu: 500 mg/zi in 1-2 prize</p></li><li><p>52</p><p>Herpes simplex - tratament</p><p>FamciclovirTransformat in penciclovir (f. activa)Biodisponibilitate 77%Trat recurentelor: 250 mg x 3/ziTrat continuu: 125 mg x 2/zi</p></li><li><p>53</p><p>Herpes simplex - tratament</p><p>La persoanele cu rezistenta la antiviraleleclasice:Foscarnet</p><p>Nu se absoarbe oral, se adm i-vIndicat in infectiile cu VHS1,2 VVZ, CMV laimunodeprimati</p><p>CidofovirEficace topic si sistemic pe mutantii rezistenti laaciclovir si foscarnet</p></li><li><p>54</p><p>Despre ce voi vorbi...</p><p> Papilomavirusuri umane Herpes simplex Herpes zoster Poxvirusuri Pitiriazis rozat Sarcom Kaposi Manifestari cutanate in infectia HIV</p></li><li><p>55</p><p>Herpes zoster</p><p>Reactivarea dermatomerica a virusuluivaricelo-zosterian nu poate apareadecat la cei care au avut varicela</p><p>98% din adulti in decada 3 au Ac anti-VVZEruptia este unilaterala, formata dinvezicule grupate pe fond eritematos</p></li><li><p>56</p><p>Herpes zoster</p><p>VarstaIncidenta: &lt; 1/1000 la copii vs. 12/1000 lapersoane &gt; 65 ani</p><p>Factori de risc: imunitatii la VVZ cu inaintarea in varstaImunosupresiaInfectia HIV</p><p>Varstnicii sunt mai expusi, deoarece odata cu inaintareain varsta are loc o reducere a imunitatii fata de virusul V-Z. De aceea, 66% dintre pacienti au peste 50ani</p><p>Mult mai rar, zosterul afecteaza si copii (5% dintre cei sub15 ani).</p><p>Alti factori de risc suntimunosupresia (mai ales cea indusa de bolilimfoproliferative si/sau tratmente chimioterapice)Infectia HIV (creste de 8 ori riscul de zoster).</p></li><li><p>57</p><p>Herpes zoster</p><p>Cele mai afectate teritorii:Ramurile trigemenuluiNervii intercostali</p><p>Complicatii:Forme severe hemoragice/necroticeVaricelizareSuprainfectie bacterianaAlgii post-zosteriene - cea mai frecventa</p><p>Varstnicii sunt mai expusi, deoarece odata cu inaintareain varsta are loc o reducere a imunitatii fata de virusul V-Z. De aceea, 66% dintre pacienti au peste 50ani</p><p>Mult mai rar, zosterul afecteaza si copii (5% dintre cei sub15 ani).</p><p>Alti factori de risc suntimunosupresia (mai ales cea indusa de bolilimfoproliferative si/sau tratmente chimioterapice)Infectia HIV (creste de 8 ori riscul de zoster).</p></li><li><p>58</p></li><li><p>59</p></li><li><p>60</p><p>Herpes zoster - tratament</p><p>Prevenire - prin imunizarea impotrivaVVZ sau prin vaccinarea adultilorVaccinarea persoanelor de &gt;60 ani aredus:</p><p>Incidenta h. zoster cu 51.3%Incidenta algiilor postherpetice cu 66.5%Severitatea totala a h. zoster cu 61%</p><p>(NEJM 2005; 352: 2271-2284)</p><p>Exista vaccin cu virus viu atenuat (Varilrix, Varivax) - cu oeficienta de 80% in prevenirea infectiei simptomatice cuVVZ. 5% dintre copiii vaccinati fac rash. Vaccinul produceatat un raspuns mediat celular cat si unul umoral.</p><p>La adulti, care au venit deja in contact cu VVZ, vaccinul arputea fi util ca un rapel de reactivarea a imunitatii umoralesi celulare si ar putea contribui la reducerea incidenteiherpesului zoster.</p><p>A Vaccine to Prevent Herpes Zoster and PostherpeticNeuralgia in Older Adults (NEJM, June 2, 2005)</p><p>Background. The incidence and severity of herpes zosterand postherpetic neuralgia increase with age inassociation with a progressive decline in cell-mediatedimmunity to varicellazoster virus (VZV). We tested thehypothesis that vaccination against VZV would decreasethe incidence, severity, or both of herpes zoster andpostherpetic neuralgia among older adults.</p><p>Methods. We enrolled 38,546 adults 60 years of age orolder in a randomized, double-blind, placebo-controlledtrial of an investigational live attenuated Oka/Merck VZVvaccine ("zoster vaccine"). Herpes zoster was diagnosedaccording to clinical and laboratory criteria. The pain anddiscomfort associated with herpes zoster were measuredrepeatedly for six months. The primary end point was theburden of illness due to herpes zoster, a measure affectedby the incidence, severity, and duration of the associatedpain and discomfort. The secondary end point was theincidence of postherpetic neuralgia.</p><p>Results. More than 95 percent of the subjects continued inthe study to its completion, with a median of 3.12 years ofsurveillance for herpes zoster. A total of 957 confirmedcases of herpes zoster (315 among vaccine recipientsand 642 among placebo recipients) and 107 cases ofpostherpetic neuralgia (27 among vaccine recipients and80 among placebo recipients) were included in theefficacy analysis. The use of the zoster vaccine reducedthe burden of illness due to herpes zoster by 61.1 percent(P</p></li><li><p>61</p></li><li><p>62</p><p>Herpes zoster - tratament</p><p>Tratament etiologic:Aciclovir 800 mg x 5/zi, 7 zileValaciclovir/Famciclovir/Brivudin -</p><p>echivalente ca eficacitate cu aciclovirulcomplianta mai buna pt ca se administreazamai rarmai scumpe</p><p>Tratamentul algiilor</p><p>Exista vaccin cu virus viu atenuat (Varilrix, Varivax) - cu oeficienta de 80% in prevenirea infectiei simptomatice cuVVZ. 5% dintre copiii vaccinati fac rash. Vaccinul produceatat un raspuns mediat celular cat si unul umoral.</p><p>La adulti, care au venit deja in contact cu VVZ, vaccinul arputea fi util ca un rapel de reactivarea a imunitatii umoralesi celulare si ar putea contribui la reducerea incidenteiherpesului zoster.</p><p>A Vaccine to Prevent Herpes Zoster and PostherpeticNeuralgia in Older Adults (NEJM, June 2, 2005)</p><p>Background. The incidence and severity of herpes zosterand postherpetic neuralgia increase with age inassociation with a progressive decline in cell-mediatedimmunity to varicellazoster virus (VZV). We tested thehypothesis that vaccination against VZV would decreasethe incidence, severity, or both of herpes zoster andpostherpetic neuralgia among older adults.</p><p>Methods. We enrolled 38,546 adults 60 years of age orolder in a randomized, double-blind, placebo-controlledtrial of an investigational live attenuated Oka/Merck VZVvaccine ("zoster vaccine"). Herpes zoster was diagnosedaccording to clinical and laboratory criteria. The pain anddiscomfort associated with herpes zoster were measuredrepeate...</p></li></ul>