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INFECTII CUTANATE
VIRALE
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Conflict de interese
• Astellas Pharma
• Glaxo SmithKline
• Hoffman LaRoche• Janssen Pharma
• Schering AG
• Schering Plough
• L’Oreal
• Sir Samuel Scott of
Yews Trust
• European DermatoEpidemiology
Network
• Archives of
Dermatology
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Foarte variate
Depind de:
Tipul virusului
Localizarea infectiei
Raspunsul imun al gazdei
Unele virusuri pot doar coloniza epidermul, fara a
produce manifestari clinice (ex: HPV, v.
molluscumului contagiosum)
Manifestari clinice
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Virusuri care produc infectiicutanate (I)
Papilomavirusuri umane
Virusuri herpetice
Virusul herpes simplex 1, 2Virusul varicelo-zosterian
Virusul Epstein-Barr
Herpesvirusul uman 6, 7, 8
Pox-virusuriVirusul molluscumului contagiosum
Virusul nodulilor mulgatorilor
Virusul ectimei contagiosum (orf)
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Virusuri care produc infectii
cutanate (II)
Virusurile bolilor eruptive ale copilariei(rujeola, rubeola, varicela)
Virusul hepatitei B (vasculite, urticariecronica)
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Despre ce voi vorbi...
• Papilomavirusuri umane
• Herpes simplex
• Herpes zoster
• Poxvirusuri
• Pitiriazis rozat• Sarcom Kaposi
• Manifestari cutanate in infectia HIV
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Papilomavirusuri umane
Caractere generale
Grup de >100 virusuri ADNProduc proliferarea epiteliilor pielii si
mucoaselor
Determina de obicei leziuni benigne
Unele tipuri pot produce leziuni displazice
sau neoplazice
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Papilomavirusuri umane
manifestari clinice (I)
Veruci vulgare
Veruci plantareProfunde
Superficiale (in mozaic)
Veruci plane (juvenile)Papiloame (veruci filiforme/digitate)
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Papilomavirusuri umane
manifestari clinice (II)
Condiloame (veruci) anogenitale
Condiloame acuminateCondiloame plane ale colului uterin
Condilomatoza giganta
Papuloza bowenoidaEpidermodisplazia veruciforma
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Papilomavirusuri umane
tratamentAcid salicilic 15-25%
Acid mono-, tricloracetic 25-30%
Podofilina 25%/podofilotoxina 0,5%Crioterapie
Sensibilizanti de contact (DNCB, DCP)
Citostatice topice/intralezionale
Metode chirurgicale: curetaj,
electrocoagulare, laser CO2
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Papilomavirusuri
infectii genitale (I)Cea mai frecventa ITS
Incidenta 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)
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Papilomavirusuri
infectii genitale
Cu risc oncogen mare (16, 18)Majoritatea cazurilor de carcinom de col uterin se
coreleaza cu PVU 16, 18; frecvent produc infectii
asimptomatice
Cu risc oncogen mic (6, 11)Produc un carcinom spinocelular neagresiv (Buschke-
Loewenstein)
Sunt posibile coinfectii cu mai multe tipuri
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Papilomavirusuri
infectii genitaleTestarea ADN-ului pentru tipurilor cu risc mare:
Utilitatea testarii depinde de Sb, Sp siprevalenta infectiei cu risc mare
Cel mai utilizat test (Digene) are Sb90%, Sp 15-20% → rata mare de
fals+testul este autorizat de FDA pentru
probe recoltate din colul uterin
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Papilomavirusuri - infectii genitaleepidemiologie
Transmiterea este facilitata de existentaleziunilor (dar nu exclusiva)
Transmiterea mediata de obiecte este
posibila, dar nedoveditaTransmiterea cu ocazia nasterii este rara
(papiloame laringiene sau condiloame
anogenitale la luni de zile post-partum)
Infectivitatea inter-parteneri: 60%
Utilizarea prezervativului reduce
transmiterea
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Papilomavirusuri - infectii genitalefactori de risc
Numarul partenerilor sexualiFrecventa contactelor sexuale
Prezenta condiloamelor la partener
Fumatul (factor de risc independent)
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Condiloame acuminate
diagnosticClinic
utilizarea acidului acetic (aceto-
whitening) nerecomandabila, pt caSb↓, Sp↓, 25% rezultate fals+ (CDC)
Histopatologic
Reactie de amplificare genicacercetare, beneficiu minim pt dg si
tratamentul de rutina
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Condiloame acuminateevolutie naturala
Pot spontan regresa, creste, ramaneneschimbate
Netratate, 10-30% dispar spontan in
cca 3 luni
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Condiloame acuminateprincipii de tratament
Nu exista o metoda terapeutica unica si
satisfacatoare in toate cazurileRatele de succes initiale sunt 50-75%
cu majoritatea tratamentelor
Recurentele sunt obisnuiteVaccinuri anti-PVU pot preveni infectia
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Condiloame acuminatetratament
Metode aplicabile de catre pacientPodofilotoxina (Condyline) 3/7, 4-6 sapt
Imiquimod (Aldara) 3/7, max 16 sapt
Metode aplicabile de personal medicalCrioterapie
Podofilina
Acid tri-, bi-cloracetic
Curetare
Electrocauterizare
Fotovolatilizare laser
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Vaccin anti-PVU (Gardasil)
Vaccinul este impotriva celor mai frecvente tulpinide PVU (6, 11, 16, 18)
Este puternic imunogen - induce un raspuns imun
foarte intens, de 50 de ori mai mare decat raspunsulimun obtinut prin contactul natural cu
papilomavirusul.
Vaccinul nu are nici un risc din punct de vedere al
infectiozitatii sau riscului oncogenic, intrucat este
obtinut prin recombinare genica.
Este in prezent autorizat si pentru vaccinarea
baietilor (FDA 2010)
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Vaccin anti-PVU - limitari
Lipsa datelor referitoare la durata raspunsului imun
Date insuficiente referitoare la intensitatea
raspunsului imun (titrul Ac este un marker surogat al
raspunsului imun)Posibile infectii cu alte tipuri, deci screening-ul
trebuie sa continue
Acceptabilitatea sociala a vaccinului
Vaccinarea barbatilor (vaccinarea exclusiva afemeilor este cu 60-75% mai putin eficienta in
prevenirea cancerului de col decat vaccinarea
ambelor sexe)
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Tratamentrezultate asteptate
Scopul nu este eradicarea PVU (imposibila dincauza infectiei clinice subiacente)
Tratarea leziunilor vizibile poate reduce
infectiozitatea si transmiterea (nedemonstrat)
Tratamentul este exclusiv simptomatic si poate
contribui la cresterea perioadelor fara leziuni
Recurentele sunt > 25% in primele 3 luni
Tratamentul este mai eficace pentru
condiloamele recente (< 1an)
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Duct tape therapy for warts.Jerry Litt, 1978.
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Tratamentul verucilor cu bandaadeziva (“duct tape”)
Metoda nedureroasa, lipsita de riscuri, ieftina sieficace pt verucile peri- si subunghiale
Tehnica:
Infasurati complet veruca cu banda adeziva
pentru a realiza ocluzie completa
Lasati banda 6,5 zile, apoi faceti o pauza de
12 ore; se repeta pana la disparitia veruciiDupa cateva sapt, veruca se micsoreaza, se
macereaza si dispare
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Don’t Excise - Exorcise.
Duct tape therapy for warts.Jerry Litt. Cutis 1978; 22: 673-76.
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Ce este “duct tape”?
• Duct tape, or duck tape, is a polyethylene, reinforced,
multi-purpose pressure sensitive tape with a soft and
flexible shell and pressure sensitive adhesive. It is
generally silver or black in color but many other colors have recently become available. With a
standard width of 1+7⁄8 inches (48 mm), duct tape
was originally developed during World War II in 1942
as a water resistant sealing tape for ammunitioncases.(http://en.wikipedia.org/wiki/Duct_tape)
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Duct tape for the treatment of common
warts in adults: a double-blind RCT
Arch Dermatol 2007• 90 immunocompetent adult volunteers with at least 1
wart measuring 2 to 15 mm enrolled. 80 completedthe study.
• 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).
• Of patients with complete resolution, 6 (75%) in the
treatment group and 3 (33%) in the control group hadrecurrence of the target wart by the sixth month.
Arch Dermatol. 2007 Mar;143(3):309-13.
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If the patient is you, try a
placebo or two.
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Despre ce voi vorbi...
• Papilomavirusuri umane
• Herpes simplex
• Herpes zoster
• Poxvirusuri
• Pitiriazis rozat
• Sarcom Kaposi
• Manifestari cutanate in infectia HIV
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Herpes simplex
Virus ADN - 2 tipuri antigenice (VHS1,VHS2)
Produce infectie cronica, persistenta a
ggl nervilor senzitivi si recurente
mucoase variabile si imprevizibile
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Herpes simplex
manifestari clinice• A. Primo-infectia herpeticaF. inaparente (80-95% din infectiile VHS1)
Gingivostomatita herpetica
Herpesul genital primar Alte forme:
Panaritiu herpetic
Keratoconjunctivita
Forme grave
Eczema herpeticumHerpesul neonatal
Herpesul la imunodeprimati
• B. Herpesul recurent
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Herpes simplex - tratament
1.Antivirale care inhiba ADN-polimerazavirala dupa o fosforilare prealabila
mediata de timidinkinaza (TK)herpetica (*ciclovir-uri)
2.Antivirale care inhiba ADN-polimeraza
virala independent de timidinkinaza
herpetica
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Efectele tratamentului antiviral
Tratamentul recurentelor (intermitent)
Scurteaza durata si severitate recurentei
respectiveNu influenteaza durata frecventa, duratasi severitatea recurentelor ulterioare
Tratamentul continuu
Reduce frecventa (cu >60-70%) siseveritatea recurentelor si ↓ eliminarileasimptomatice de virus
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Indicatiile tratamentului antiviralcontinuu
Recurente frecvente (>6/an)Recurente complicate
Imunodeprimati
Gravide la risc, dupa saptamana 36
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Rezistenta la antivirale
Nu se dezvolta la persoaneimunocompetente
Risc mare de dezvoltare a rezistenteila imunodeprimati
Mecanism: mutatii ale genei TK cu
disparitia completa a genei →rezistenta incrucisata la *ciclovir-uri
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Herpes simplex - tratament
Aciclovir Analog ciclic al guanozinei
Biodisponibilitate 15%
Trat recurentelor: 200 mg x 5/ziTrat continuu: 800 mg/zi in 1-2 prize
Valaciclovir
Esterul L-valil al acicloviruluiBiodisponibilitate 54%
Trat recurentelor: 500 mg x 2/zi
Trat continuu: 500 mg/zi in 1-2 prize
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Herpes simplex - tratament
Famciclovir Transformat in penciclovir (f. activa)
Biodisponibilitate 77%
Trat recurentelor: 250 mg x 3/zi
Trat continuu: 125 mg x 2/zi
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Herpes simplex - tratament
La persoanele cu rezistenta la antiviraleleclasice:
FoscarnetNu se absoarbe oral, se adm i-v
Indicat in infectiile cu VHS1,2 VVZ, CMV la
imunodeprimati
Cidofovir Eficace topic si sistemic pe mutantii rezistenti la
aciclovir si foscarnet
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Despre ce voi vorbi...
• Papilomavirusuri umane
• Herpes simplex
• Herpes zoster
• Poxvirusuri
• Pitiriazis rozat
• Sarcom Kaposi
• Manifestari cutanate in infectia HIV
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Herpes zoster
Reactivarea dermatomerica a virusului
varicelo-zosterian → nu poate apareadecat la cei care au avut varicela
98% din adulti in decada 3 au Ac anti-VVZ
Eruptia este unilaterala, formata din
vezicule grupate pe fond eritematos
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Herpes zoster
Varsta
Incidenta: < 1/1000 la copii vs. 12/1000 lapersoane > 65 ani
Factori de risc:↓ imunitatii la VVZ cu inaintarea in varsta
ImunosupresiaInfectia HIV
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Herpes zoster
Cele mai afectate teritorii:
Ramurile trigemenului
Nervii intercostaliComplicatii:
Forme severe hemoragice/necrotice
VaricelizareSuprainfectie bacteriana
Algii post-zosteriene - cea mai frecventa
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Herpes zoster - tratament
Prevenire - prin imunizarea impotrivaVVZ sau prin vaccinarea adultilor
Vaccinarea persoanelor de >60 ani aredus:
Incidenta h. zoster cu 51.3%
Incidenta algiilor postherpetice cu 66.5%
Severitatea totala a h. zoster cu 61%(NEJM 2005; 352: 2271-2284)
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Herpes zoster - tratament
Tratament etiologic:
Aciclovir 800 mg x 5/zi, 7 zile
Valaciclovir/Famciclovir/Brivudin -
echivalente ca eficacitate cu aciclovirul
complianta mai buna pt ca se administreaza
mai rar mai scumpe
Tratamentul algiilor
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The young physician starts life withtwenty drugs for each disease,
and
the old physician ends life withone drug for twenty diseases.
(W. Osler)
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Despre ce voi vorbi...
• Papilomavirusuri umane
• Herpes simplex
• Herpes zoster
• Poxvirusuri
• Pitiriazis rozat
• Sarcom Kaposi
• Manifestari cutanate in infectia HIV
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Pox-virusuri
Virusul ectimei contagiosum (orf)
Virusul nodulilor mulgatorilor
Virusul moluscumului contagiosum
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Ectima contagiosumNodulii mulgatorilor
Produse de parapoxvirusuri ale caror gazde sunt:
Oile si caprele (ectima contagiosum)
Bovinele (nodulii mulgatorilor)
Contaminarea umana are lor prin
inoculare directa de la animalelebolnave
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Ectima contagiosumNodulii mulgatorilor
Manifestari clinice f. asemanatoare
Papule rosii → noduli fermi, sensibili
→ pustule/bule hemoragice, uneoriombilicate→ crusta
Localizare pe maini
Frecvent limfangita si adenopatie
satelita
Se vindeca spontan, fara cicatrice, in
4-6 saptamani
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(colectia dr. G. Turcu)
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Molluscum contagiosum
Manifestari:
Papule de culoarea pielii, hemisferice, cucentrul ombilicat
Cresc lent si ating 5-10 mm in 6-12 sapt
Prin exprimarea continutului → “grauntiide molluscum”
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Molluscum contagiosumtratament
CuretareCrioterapie
Exprimarea continutului + alcool iodat
Sol KOH 5%
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Never underestimate the
power of body to heal
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Despre ce voi vorbi...
• Papilomavirusuri umane
• Herpes simplex
• Herpes zoster
• Poxvirusuri
• Pitiriazis rozat
• Sarcom Kaposi
• Manifestari cutanate in infectia HIV
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Pitiriazis rozat
• Robert Willan 1798
• Camille Gibert 1860 (f. maculara)
• Pierre Bazin 1862 (f. inelara, cea maifrecventa)
• Louis Brocq 1887 - placa heraldica
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Epidemiologie
• Incidenta 0.39-4.80/100 pacienti de
dermatologie
• 172/100.000 pers-ani in populatia generala• Majoritatea sunt tineri: 10-35 ani
• Barbati-femei: 1:1.43
• Variatii sezoniere ale frecventei
• Agregari spatio-temporale ale cazurilor
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Etiologie
Infectioasa (virala, HHV-7?)
• Evolutie similara exantemelor virale
• Absenta recidivelor
• Asocierea cu infectii respiratorii
• Gruparea spatio-temporala a cazurilor
• Aparitia de PR dupa contact cu PR
Eruptiile pitiriazis rozat-like induse demedicamente sunt clasificate separat
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Manifestari clinice
• Placa heraldica - 40-76%
• Interval placa heraldica-eruptie: 2-84
zile (de obicei 7-14)• Eruptie eritemato-scuamoasa, ovalara,
cu descuamare “in coleret”, cu scuame
mai aderente la periferia leziunii si maidetasate in centrul ei
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Manifestari clinice
• Eruptia secunda: leziuni similara placii
heraldice, dar de dimensiuni mai mici
• Distributia leziunilor cu axul lung paralelcu liniile de tractiune ale pielii
• Localizata pe trunchi si radacina
membrelor • Traditional respecta fata
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Forme atipice
• Relativ frecvente
• Forme: veziculoase, purpurice,
hemoragice, cu placi gigante, cu placifoarte mici, inversata (afect reg axilare,
inghinale, fata)
• Afectarea cav orale - posibila
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Chuh AA. JEADV 2003;17:101-3.
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Tratament
• Nici un tratament
• Eritromicina (sau alte macrolide)
• Antivirale (aciclovir ? - eficacitateredusa pe HHV-7)
• Fototerapie (naturala, UVB)
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Sarcomul Kaposi
• Tumora multifocala, indusa de infectia cu
HHV-8, cu numeroase forme clinice
• Frecventa a crescut dupa aparitia HIV/SIDA
• Riscul bolii la cei cu SIDA care au ca factor
de risc homosexualitatea este de 106.000 ori
mai mare decat in populatia generala, iar la
cei cu alti factori de risc pentru SIDA de13.000 ori mai mare.
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Sarcomul Kaposi - investigatii
• Biopsie (pt
confirmare)
• test HIV
• investigatii uzuale
• investigatii de
extensie (echo, CT)
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Kaposi - forma clasica
• Barbat, >60 ani
• Placi violacee
• Debut mb inferioare• Hiperkeratoza
• Pot dezvolta noduli
• Pot ulcera
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Kaposi clasic vs. Kaposi sidatic
• pred barbati
• de obicei > 60 ani
• debut mb inferioare
• leziuni putine
• evolutie lenta
• rareori afecteaza 1/2
superioara corp• nu afecteaza
mucoasele
• pred la homosexuali
• in faza de SIDA
• fara zone electie
• leziui numeroase• evolutie rapida
• afect extracutanataprecoce
• afect mucoasafrecventa
• Kobnerizare
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Diagnostic diferential
• Angiom
• Granulom piogenic
• Angiokeratom• Insuficienta venoasa severa (pseudo-Kaposi)
• Sindromul Blue Rubber Bleb Nevus
• Nevi• Dermatofibrom
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Evolutie
• Variabila - de la afectare exclusiv
cutanata la afectare cutanata si
extracutanata rapid progresiva.• Influentata de forma de boala si de
teren.
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Tratament
• Conservator (watchful waiting)
• Excizia/cauterizarea ariilor sever afectate
• Radioterapie
• Antivirale (foscarnet, HAART)
• Chimioterapie intralezionala (eg vincristina) sausistemica (vinblastina, paclitaxel, docetaxel)
• Intreruperea imunosupresoarelor la ceiimunosupresati iatrogen
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The therapist walks a tight ropebetween faith and skepticism,
but should he fall, let if betoward faith.