Pathogenesis, Clinical Manifestations, and Diagnosis of Pemphigus - UpToDate4

29/8/2017 Pathogenesis, clinical manifestations, and diagnosis of pemphigus - UpToDate
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www.uptodate.com 2017 UpToDate
Patogenia, manifestaciones clnicas y diagnstico de pnfigo
Autores: Michael Hertl, MD, Cassian Sitaru, MD

Editor de seccin: John J Zone, MD
Editor secundario: Abena O Ofori, MD
Todos los temas se actualizan a medida que hay nuevas pruebas disponibles y nuestro proceso de revisin por
pares es completo.
Revisin de la literatura a travs de: Jul 2017. | Este tema se actualiz por ltima vez: 23 de mayo de
2017.
INTRODUCCIN - El pnfigo se define como un grupo de trastornos vesiculares potencialmente mortales

caracterizados por acantolisis (prdida de la adhesin de queratinocitos a los queratinocitos) que resulta en la
formacin de ampollas intraepiteliales en las membranas mucosas y en la piel [ 1 ]. El proceso de acantolisis es
inducido por la unin de autoanticuerpos circulantes a las molculas de adhesin intercelular [ 1 - 3 ]. Los
pacientes con pnfigo desarrollan erosiones mucosas y / o flacidez, erosiones o pstulas en la piel.
Las cuatro entidades principales del grupo de pnfigo incluyen pemphigus vulgaris, pemphigus foliaceus,
pemphigus de IgA, y pemphigus paraneoplastic. Las diferentes formas de pnfigo se distinguen por sus
caractersticas clnicas, autoantgenos asociados y hallazgos de laboratorio.
La patognesis, las caractersticas clnicas y el diagnstico del pnfigo se discutirn aqu. El manejo del pnfigo
y un mayor detalle del pnfigo paraneoplsico se revisan por separado. (Ver "Tratamiento inicial del pnfigo
vulgar y del pnfigo foliceo" y "Tratamiento del pnfigo vulgar y del pnfigo foliceo refractarios" y "Pnfigo
paraneoplsico" ).
CLASIFICACIN - Las caractersticas comunes de los principales tipos de pnfigo se examinan brevemente a
continuacin. En la tabla ( tabla 1 ) se ofrece un resumen ms amplio de las caractersticas clnicas y de
laboratorio del pnfigo .
Pnfigo vulgar
Principales caractersticas: Envoltura mucosal o mucosa y cutnea, ampollas acantolticas

suprabasales, autoanticuerpos contra desmoglein 3 o ambos desmoglein 1 y desmoglein 3
Variantes clnicas: Pemphigus vegetans, pemphigus herpetiformis
Pemphigus foliaceus
Caractersticas clave: Afectacin cutnea slo, ampollas acantolticas subcorneales, autoanticuerpos

contra la desmoglena 1
Variantes clnicas: Pemphigus foliaceus endmico (fogo selvagem), pnfigo eritematoso (sndrome de
Senear-Usher), pemphigus herpetiformis
El
pnfigo IgA
Subtipos: Pemphigus del tipo IgM de dermatosis pustular subcorneal (distinto de la dermatosis
pustular subcorneal clsica [enfermedad de Sneddon-Wilkinson]), dermatosis IgA neutroflica
https://www.uptodate.com/contents/pathogenesis-clinical-manifestations-and-diagnosis-of-pemphigus/print?source=search_result&search=acantolisis 1/58
intraepidrmica
Caractersticas principales: vesculas agrupadas o pstulas y placas eritematosas con cortezas,

ampollas acantolticas subcorneales o intraepidrmicas, autoanticuerpos contra la desmocollina 1 en el
pnfigo IgA de la dermatosis pustular subcorneal [ 4 ]
Pnfigo paraneoplsico
Caractersticas principales: estomatitis extensa e intratable y hallazgos cutneos variables;

Enfermedad neoplsica asociada; Ampollas acantolticas suprabasales; Autoanticuerpos contra
desmoplakins u otros antgenos desmosmicos (ver "Pnfigo paraneoplsico" )
EPIDEMIOLOGA - El pnfigo vulgar, que representa la forma ms comn de pnfigo, es una enfermedad
rara. Aunque el pnfigo vulgar se produce en todo el mundo, la frecuencia est influenciada por la ubicacin
geogrfica y el origen tnico. Las tasas de incidencia entre 0,1 y 0,5 por 100.000 personas por ao han sido
reportadas con mayor frecuencia; Sin embargo, las tasas ms altas se han documentado en ciertas poblaciones
[ 5 ]. Los individuos con ascendencia juda (en particular los judos asquenazes) y los habitantes de la India, el
sudeste de Europa y el Oriente Medio tienen el mayor riesgo de tener el pnfigo vulgar.
En la mayora de las localizaciones geogrficas, el penfigo vulgar es ms comn que el pnfigo foliceo. Sin
embargo, en ciertos lugares, como el norte de frica, Turqua y Sudamrica, la prevalencia de pnfigo foliceo
supera el pnfigo vulgar [ 6 ]. El pemphigus foliaceus endmico (fogo selvagem) contribuye a la mayor tasa de
pnfigo foliceo en algunos de estos pases. En una regin endmica del estado de Mato Grosso do Sul en
Brasil, la prevalencia de pemphigus foliaceus a mediados de la dcada de 1990 fue de alrededor del 3 por
ciento [ 7 ]. Una forma endmica de pnfigo vulgar tambin se ha informado en un pequeo nmero de
pacientes que residen en una regin endmica de pnfigo foliceo en Brasil [ 8 ].
El pnfigo por lo general ocurre en adultos, con una edad promedio de inicio de 40 a 60 aos para el pnfigo
vulgar y nonendemic pemphigus foliaceus [ 9 , 10 ]. El pnfigo es raro en los nios, con la excepcin del penfigo
foliceo endmico, que frecuentemente afecta a nios y adultos jvenes en reas endmicas [ 11 ]. El pnfigo
neonatal es una forma transitoria rara de pnfigo que ocurre como consecuencia de la transmisin placentaria
de autoanticuerpos al feto de una madre con la enfermedad (ver "Pnfigo neonatal" a continuacin).
En general, la proporcin de sexos para el pnfigo vulgar y el pnfigo foliceo parece ser equivalente o casi
equivalente [ 12 ]. Sin embargo, algunos estudios han encontrado grandes desequilibrios en la distribucin del
sexo, como un estudio que encontr una proporcin de 4: 1 de mujeres a los hombres con pnfigo foliceo en
Tnez [ 13 ] y un estudio que encontr una proporcin de 19: 1 de los hombres a Mujeres en situacin endmica
en Colombia [ 14 ].
La informacin epidemiolgica sobre el pnfigo IgA es escasa. El trastorno puede ocurrir a cualquier edad y
puede ser ligeramente ms comn en las mujeres [ 4 ]. El pnfigo paraneoplsico es raro. El trastorno es ms
comnmente visto en adultos de mediana edad, pero tambin puede ocurrir en nios. (Ver "Pnfigo
paraneoplsico", seccin "Epidemiologa" ).
PATOGENESIA
Informacin general - investigaciones intensivas para dilucidar la patognesis de pnfigo [ 2,15 ] han
conducido a una amplia aceptacin de la teora de que acantlisis inducida por la unin de autoanticuerpos a
epiteliales antgenos de superficie celular conduce a las manifestaciones clnicas de pnfigo. Esta teora se
apoya en la deteccin sistemtica de autoanticuerpos intercelulares en tejido perilesional de pacientes con
pnfigo ( figura 1A-B ) (ver "Diagnstico" a continuacin). Los descubrimientos experimentales que ofrecen ms
apoyo incluyen los siguientes:
Los estudios in vitro han demostrado que los autoanticuerpos de pacientes con pnfigo vulgar, pemphigus
foliaceus y pnfigo de IgA son capaces de inducir la destruccin de clulas epidrmicas [ 16-19 ].
Estudios in vivo han demostrado que la transferencia pasiva de autoanticuerpos IgG de pacientes con
pemphigus vulgaris en ratones neonatos induce ampollas y erosiones con caractersticas histolgicas,
ultraestructurales e inmunofluorescentes consistentes con pnfigo [ 20,21 ]. El potencial inductor de
ampollas de autoanticuerpos en pemphigus foliaceus y pemphigus paraneoplastic se ha demostrado en
estudios similares in vivo en ratones [ 22 - 24 ].
Eliminacin de autoanticuerpos de pnfigo del suero de pacientes con pemphigus vulgaris o pemphigus
foliaceus a travs de inmunoadsorcin especfica de antgeno antes de la inyeccin en ratones neonatal
previene ampollas [ 25 , 26 ].
Los mecanismos moleculares a travs de los cuales la unin de los autoanticuerpos a las clulas epiteliales
conduce a la acantolisis siguen siendo intensamente debatidos. Se han propuesto varios mecanismos para la
acantolisis mediada por anticuerpos, incluyendo la induccin de eventos de transduccin de seales que
desencadenan la separacin celular y la inhibicin de la funcin de la molcula adhesiva a travs del estorbo
estrico [2, 27 , 28 ]. En particular, la teora de la apoptlisis sugiere que la acantolisis resulta de la induccin
mediada por autoanticuerpos de las seales celulares que desencadenan cascadas enzimticas que conducen
al colapso estructural de las clulas y la contraccin celular [ 29 ].
Antgenos objetivo - Se han identificado autoanticuerpos contra una variedad de antgenos de superficie de
clulas epiteliales en pacientes con pnfigo.
Pemphigus vulgaris y pemphigus foliaceus - Las desmogleinas, que son glicoprotenas transmembrana
en la familia de la cadherina (molcula de adhesin celular dependiente del calcio), son los antgenos que han
sido estudiados ms extensamente en el pnfigo vulgar y el pnfigo foliceo. Desmogleins son componentes de
desmosomas, estructuras integrales para la adhesin de clula a clula ( figura 1 ).
IgG autoanticuerpos a desmogleins se detectan consistentemente a travs de enzima vinculada al ensayo

inmunoabsorbente (ELISA) en pacientes con pnfigo, y la expresin de estos autoanticuerpos a menudo se
correlaciona con el tipo de enfermedad [ 30 , 31 ]. Los autoanticuerpos contra la desmoglena 1 se han
relacionado con el pnfigo foliceo y los autoanticuerpos con la desmoglena 1 y la desmoglena 3 se han
relacionado con el pnfigo vulgaris mucocutneo. Las porciones amino-terminales de las desmogleinas
parecen ser los eptopos importantes para la patogenicidad, como lo demuestran estudios que demuestran que
la IgG dirigida contra una fraccin recombinante amino-terminal de la desmoglina 3 (EC1-2), pero no la porcin
carboxiterminal, induce epitelio Ampollado cuando se inyecta en ratones neonatal o expuestos a la piel humana
cultivada [ 32 , 33 ]. Los autoanticuerpos considerados patognicos son de la subclase IgG4 [ 21 , 33-35 ].
En la dcada de 1990, la teora de la compensacin desmoglena fue propuesto como una explicacin para la
correlacin observada entre las caractersticas clnicas y los perfiles de autoanticuerpos de pnfigo vulgar y
pnfigo foliceo [ 36 ]. Aunque la teora sigue siendo ampliamente citado, los datos posteriores han planteado
preguntas sobre si este concepto explica suficientemente el mecanismo patognico de estas enfermedades [ 37
].
Segn la teora de la desmoglein compensacin, la correlacin entre los hallazgos clnicos y los resultados
ELISA refleja diferencias innatas en la expresin de desmoglena en la piel y las membranas mucosas [ 36 ]. En
la piel, la desmoglena 1 se expresa ms intensamente en las porciones superiores de la epidermis, mientras
que la desmoglena 3 se expresa ms fuertemente en las capas basal y parabasal. En las membranas
mucosas, la desmoglena 3 est presente en abundancia en todo el epitelio. En contraste, la expresin de
desmoglein 1 es mucho ms baja en todo el epitelio mucoso ( figura 2 ).
La interpretacin de esta teora en lo que se refiere a los hallazgos clnicos en el pnfigo es la siguiente:
Los pacientes con slo autoanticuerpos contra la desmoglena 3 deben tener pnfigo vulvar de la
mucosa dominante porque en la piel, la desmoglena 1 compensa la prdida de desmoglena 3. En las
membranas mucosas, la expresin de desmoglena 1 es insuficiente para la compensacin.
Los pacientes con slo autoanticuerpos contra la desmoglena 1 deben tener penfigo foliar (ampollas
cutneas superficiales y sin afectacin de las membranas mucosas) debido a que los autoanticuerpos
contra la desmoglena 1 dan lugar a la separacin de clulas en el epitelio superficial, pero no en el epitelio
ms profundo, Desmoglein 1 disfuncin. Las membranas mucosas se libran debido a los altos niveles de
desmoglein 3 y los niveles relativamente bajos de desmoglein 1 expresado en la mucosa.
Los pacientes con ambos autoanticuerpos contra la desmoglena 1 y 3 deben tener pemphigus vulgaris
mucocutneo debido a que la disfuncin tanto de la desmoglena 1 como de la 3 impide la capacidad de
estas glucoprotenas para compensarse entre s, dando como resultado una prdida de la adhesin celular
en la piel y las membranas mucosas .
Sin embargo, es probable que la patognesis del pnfigo sea ms compleja de lo que predice este modelo.
Discordancia entre los perfiles clnicos y serolgicos (p. Ej., Pacientes con pnfigo foliceo que tienen
autoanticuerpos contra la desmoglena 3, pacientes con penfigo vulgar de mucosa pura que tienen
autoanticuerpos contra la desmogleina 1 y pacientes con pnfigo que no tienen autoanticuerpos contra la
desmogleina 1 ni autoanticuerpos contra la desmoglena 3 ) Puede ocurrir en alrededor de un tercio de los
casos [ 37 , 38 ]. Esta observacin y el conocimiento de que la presencia de autoanticuerpos tanto desmoglein 1
y desmoglein 3 no da lugar a la disolucin completa del epitelio sugieren que otros factores contribuyen al
desarrollo de estas enfermedades.
Los autoanticuerpos contra la desmocollina 3 pueden contribuir al pnfigo en algunos pacientes. Al igual que las
desmoginas, las desmocollinas son glicoprotenas transmembranas encontradas dentro de los desmosomas (
figura 1 ). Desmocollin 3 autoanticuerpos especficos de pacientes con pnfigo han inducido la prdida de la
adhesin de queratinocitos ex vivo y en animales de experimentacin [ 39 , 40 ]. Adems, se ha identificado un
subconjunto de pacientes con caractersticas clnicas ms consistentes con pemphigus herpetiformis o
pemphigus vegetans y los hallazgos de inmunofluorescencia directa consistente con pnfigo que tienen
autoanticuerpos contra la desmocollina pero sin autoanticuerpos contra la desmoglena [ 41 , 42 ].
Autoanticuerpos adicionales detectados en el suero de pacientes con pnfigo incluyen autoanticuerpos contra
desmoglein 4, el receptor de acetilcolina, pemphaxin, y otros [ 29 , 43 - 47 ]. Queda por determinar si alguno de
estos autoanticuerpos son patgenos en el pnfigo vulgar o en el pnfigo foliceo.
IgA pemfigus - A diferencia de las otras formas de pnfigo, que se caracterizan por autoanticuerpos IgG
dirigidos a antgenos de superficie de clulas epiteliales, el pnfigo de IgA se caracteriza por anticuerpos anti-
queratinocitos de superficie celular de la clase IgA [ 48 ]. El antgeno diana en el tipo de dermatosis pustular
subcorneal del pnfigo IgA es la desmocollina 1 , una glicoprotena transmembrana dentro de desmosomas [
49-51 ].
Por el contrario, los antgenos dirigidos en la variante de la dermatosis neutroflica intraepidrmica del pnfigo
IgA parecen ser ms heterogneos. Mientras que autoanticuerpos contra desmogleins 1 y 3 han sido reportados
en varios pacientes [ 50 , 52-54 ], estudios de microscopa inmunoelectrnica sugieren que los autoanticuerpos
IgA en estos pacientes reconocen una protena transmembranosa non-desmosomal no identificados [ 55 ]. Por
lo tanto, un autoantgeno comn sigue siendo difcil de alcanzar y el mecanismo de formacin de ampollas en el
pnfigo IgA no se entiende completamente [ 19 ].
Pnfigo paraneoplsico - Se han detectado mltiples autoanticuerpos en pacientes con pnfigo

paraneoplsico. Los antgenos diana para esta variante se revisan por separado. (Ver "Pnfigo paraneoplsico",
seccin sobre "inmunidad humoral" ).
Factores contribuyentes - Al igual que con muchas otras enfermedades autoinmunes, los factores
precipitantes de las enfermedades por pnfigo son poco conocidos. Ambos factores genticos y ambientales
pueden influir en el desarrollo de pnfigo [ 6 ].
Gentica - Varios estudios han evaluado la relacin entre el pnfigo vulgar y el pnfigo foliceo con
antgenos leucocitarios humanos (HLA) clase II alelos. El pnfigo vulgar est asociado con DR4 y DR14,
aunque el gen de susceptibilidad difiere dependiendo del origen tnico. HLA-DRB1 0402 se asocia con la
enfermedad en Ashkenazi judos [ 56 , 57 ], y DRB1 1401/04 y DQB1 0503 se asocian pemphigus vulgaris en
pacientes no judos de ascendencia europea o asitica [ 58 - 63 ]. El espordico y endmico pemphigus
foliaceus tambin se asocian con DR4, DR14, DR1 y alelos [ 6 ].
En contraste con el pnfigo vulgar, la asociacin con alelos HLA en el pnfigo foliceo es menos restringida. Se
han detectado subtipos de DRB1 0402, 0403, 0404, 0406, 1401, 1402, 1406, y 0102 a mayor frecuencia en
pacientes con pnfigo foliceo, mientras que DRB1 0301, 0701, 0801, 1101, 1104 y 1402 estn negativamente
asociados con esta enfermedad [ 64 - 67 ].
La participacin de factores genticos en la susceptibilidad al pnfigo se refuerza an ms mediante la

deteccin de ttulos bajos de desmoglein 3 autoanticuerpos especficos en familiares asintomticos de pacientes
con pnfigo vulgar y foliaceus [8, 68 ]. Adems, un estudio de casos y controles encontr que en comparacin
con los familiares de los controles sanos, los miembros de la familia de primer grado de los pacientes con
pnfigo tuvieron una mayor prevalencia de enfermedades autoinmunes [ 56 ]. Los hallazgos de un estudio
sugieren que el pemphigus vulgaris se agrupa con enfermedad tiroidea autoinmune, artritis reumatoide y
diabetes tipo 1 en pacientes y sus familias [ 69 ].
Medio ambiente - Aunque la mayora de los casos de pemphigus foliaceus son idiopticos, los factores
ambientales parecen contribuir al desarrollo del pnfigo foliceo endmico (fogo selvagem) [ 43,70 ]. Una mosca
negra (Simulium nigrimanum) u otros insectos pueden servir como vector para la forma endmica de esta
enfermedad [ 71 ].
La radiacin ultravioleta se ha propuesto como un factor exacerbador para el pnfigo foliceo y el pnfigo vulgar
[ 72-75 ], y el pnfigo se ha informado de desarrollar despus de quemaduras o lesiones elctricas cutneas [
76 ]. Se han sugerido infecciones virales, ciertos compuestos alimenticios, radiaciones ionizantes y plaguicidas
como estmulos adicionales para esta enfermedad [ 77-82 ].
Exposicin al frmaco - El pnfigo vulgar y el pnfigo foliceo pueden ser precipitados por frmacos. Thiol
drogas, incluyendo penicilamina y captopril , son los agentes ms comunes incitacin [ 83 ]. En una serie de 104
pacientes tratados con penicilamina durante al menos seis meses, el 7 por ciento desarroll pnfigo foliceo [ 84
]. Ejemplos de frmacos adicionales que se han asociado con pnfigo vulgar o pnfigo foliceo incluyen
penicilinas, cefalosporinas, enalapril , rifampicina y agentes antiinflamatorios no esteroideos ( tabla 2 ) [ 83,85,86
].
Las reacciones bioqumicas y / o inmunolgicas inducidas por frmacos pueden contribuir al desarrollo de
acantolisis en el pnfigo inducido por frmacos. Los mecanismos potenciales incluyen efectos sobre las
enzimas que median la agregacin de queratinocitos, interferencia directa a travs de la unin a molculas
implicadas en la adhesin celular, y estimulacin de la formacin de neoantigenos [ 85 ].
Los estudios de inmunofluorescencia directa (DIF) e inmunofluorescencia indirecta (IIF) son negativos en
algunos pacientes con pnfigo inducido por frmacos. En una serie de seis pacientes con este trastorno, DIF fue
negativo en un paciente y IIF fue negativo en dos pacientes [ 86 ]. El ensayo de inmunoabsorcin enzimtica
(ELISA) fue positivo para la desmogleina 1 o desmoglena 3 en todos los pacientes de esta serie.
Dieta - Los factores dietticos como el ajo, el puerro, la cebolla, la pimienta negra, el chile rojo, el vino tinto
y el t han sido implicados como inductores de pnfigo vulgar y pnfigo foliceo basados en informes de casos
concisos. Sin embargo, la evidencia existente no apoya un fuerte vnculo entre la dieta como factor ambiental y
el pnfigo [ 81 ].
CARACTERSTICAS CLNICAS
Pemphigus vulgaris - Casi todos los pacientes con pemphigus vulgaris desarrollan compromiso de la
mucosa. La cavidad oral es el sitio ms comn de las lesiones de la mucosa y con frecuencia representa el sitio
inicial de la enfermedad [ 87 ]. Las membranas mucosas en otros sitios tambin se ven afectados, incluyendo la
conjuntiva, la nariz, el esfago, la vulva, la vagina, el cuello uterino y el ano [ 88 , 89 ]. En mujeres con
afectacin cervical, los hallazgos histolgicos del pnfigo vulgar pueden ser confundidos con displasia cervical
en los frotis de Papanicolaou (Pap) [ 90 ].
Dado que las ampollas de la mucosa erosionan rpidamente, las erosiones son a menudo los nicos hallazgos
clnicos ( Figura 2A-C ). La mucosa bucal y la mucosa palatina son los sitios ms comunes para el desarrollo de
la lesin en la cavidad oral [ 91 ].
El dolor asociado con la afectacin mucosa del pnfigo vulgar puede ser severo. El dolor bucal es a menudo
aumentado por la masticacin y la deglucin, lo que puede resultar en una mala alimentacin, prdida de peso y
desnutricin.
La mayora de los pacientes tambin desarrollan una afectacin cutnea que se manifiesta como ampollas
flcidas en la piel normal o eritematosa ( figura 3A-B ). Las ampollas se rompen fcilmente, dando lugar a
erosiones dolorosas que sangran fcilmente ( figura 3B-D ). Por lo general, el prurito est ausente. Aunque
cualquier sitio cutneo puede ser afectado, las palmas y las plantas del pie se ahorran generalmente. El signo
de Nikolsky (induccin de ampollas a travs de la presin mecnica en el borde de una ampolla o en la piel
normal) a menudo se puede obtener [ 92 ]. (Ver "Abordaje del paciente con ampollas cutneas", seccin sobre
'Signo Nikolsky' .)
Rara vez, la membrana mucosa participacin no se observa a pesar de la presencia de autoanticuerpos

circulantes tanto desmoglein 1 y desmoglein 3 [ 93 - 95 ]. El trmino "pemphigus vulgaris de tipo cutneo" se
utiliza para referirse a esta presentacin de la enfermedad. (Ver "Antgenos objetivo" arriba).
Otras presentaciones clnicas poco frecuentes del pnfigo vulgar incluyen:
Pemphigus vegetans - Los pacientes con pnfigo vegetantes presentan placas vegetantes compuestas de
tejido de granulacin excesivo y costras ( figura 4 ). Las zonas intertriginosas, el cuero cabelludo y la cara
son los sitios ms comunes para estas lesiones. Se han descrito dos presentaciones clnicas de pnfigo
vegetantes [ 96 ]. En el pnfigo vegetal de Neumann , las placas vegetantes evolucionan de las lesiones
tpicas del pnfigo vulgar. El pnfigo vegetal de Hallopeau es una forma ms leve de pnfigo vegetal en el
que las placas vegetantes no estn precedidas de bullas. Las lesiones de pemphigus vegetans de
Hallopeau se encuentran generalmente en reas intertriginous.
Pemphigus herpetiformis - Pemphigus herpetiformis es un trmino que describe pemphigus vulgaris o

pemphigus foliaceus que se manifiesta con placas urticarias y vesculas cutneas dispuestas en un patrn
herpetiforme o anular ( Figura 5 ) [ 1,97-100 ]. Prurito frecuentemente presente. La afectacin mucosa es
infrecuente.
Las caractersticas clnicas del pnfigo vulgaris inducido por frmacos son similares a la enfermedad idioptica.
Pnfigo foliceo - Pnfigo foliceo es una variante superficial de pnfigo que se presenta con lesiones
cutneas. Las membranas mucosas suelen ser ahorrados [ 1 ].
El pnfigo foliceo generalmente se desarrolla en una distribucin seborreica. El cuero cabelludo, la cara y el
tronco son sitios comunes de participacin. Las lesiones cutneas suelen consistir en pequeas ampollas
superficiales dispersas que evolucionan rpidamente en erosiones escamosas y con costra ( figura 6A-C ). El
signo de Nikolsky a menudo est presente [ 10 ]. Las lesiones cutneas pueden permanecer localizadas o
pueden coalescer para cubrir grandes reas de la piel. Ocasionalmente, el pnfigo foliceo progresa para
involucrar a toda la superficie de la piel como un erythroderma exfoliative [ 9 ].
Las lesiones cutneas acompaan con frecuencia dolor o sensacin de ardor. Los sntomas sistmicos estn
generalmente ausentes.
Las variantes clnicas del pnfigo foliceo incluyen:
Penfigo foliceo endmico : El penfigo foliceo endmico presenta caractersticas clnicas similares a la
forma idioptica de la enfermedad [ 10 ]. Se cree que un desencadenante ambiental explica esta variante
de la enfermedad (ver "Epidemiologa" ms arriba).
Pemphigus erythematosus (sndrome de Senear-Usher): Este trmino pemphigus erythematosus se

utiliza para describir el pnfigo foliaceus localizado en la regin malar de la cara ( cuadro 7 ) [ 9 ].
Histricamente, el trmino se utiliz para referirse a pacientes que presentaban hallazgos de
inmunofluorescencia consistentes con pnfigo, as como caractersticas de laboratorio de lupus eritematoso
sistmico. Sin embargo, el trmino ya no se utiliza de esta manera.
Las manifestaciones clnicas del pnfigo foliceo inducido por frmacos son similares a la enfermedad
idioptica.
Pnfigo IgA - Tanto la dermatosis pustular subcorneal como la dermatosis intra-epidrmica neutroflica tipo IgA
de pnfigo se caracterizan por el desarrollo subagudo de vesculas que evolucionan en pstulas [ 4 ]. Las
vesculas y pstulas son usualmente, pero no siempre, acompaadas de placas eritematosas. Un patrn
herpetiforme, anular o circinada puede estar presente [ 4,51,91 ].
El tronco y las extremidades proximales son sitios comunes para la participacin. El cuero cabelludo, la piel
postauricular y las reas intertriginosas son sitios menos comunes para el desarrollo de la lesin [ 4,51,101 ]. El
prurito puede o no estar presente. Las membranas mucosas se suelen ahorrar.
El tipo de dermatosis pustular subcorneal del pnfigo IgA es clnicamente similar a la dermatosis pustular
subcorneal clsica (enfermedad de Sneddon-Wilkinson). Los estudios de inmunofluorescencia son necesarios
para distinguir estas enfermedades. (Ver "Dermatosis Neutrfilas", seccin sobre 'Dermatosis Pustular
Subcorneal' y 'Igagrama pemigiano' a continuacin).
Paraneoplastic pemphigus Paraneoplastic pemphigus (also known as paraneoplastic autoimmune

multiorgan syndrome) is an autoimmune multi-organ syndrome associated with neoplastic disease [23].
Typically, patients suffer from severe and acute mucosal involvement with extensive, intractable stomatitis
(picture 8A-C). The cutaneous manifestations are variable, and include blisters, erosions, and lichenoid lesions
that may resemble other autoimmune blistering diseases, erythema multiforme, graft versus host disease, or
lichen planus (picture 9A-B). Life-threatening pulmonary involvement consistent with bronchiolitis obliterans also
may be seen [102]. (See "Paraneoplastic pemphigus", section on 'Clinical manifestations'.)
Neonatal pemphigus Neonatal pemphigus is a rare transient condition in which neonates develop blisters
due to placental transmission of autoantibodies from a mother with pemphigus. Neonatal pemphigus vulgaris
occurs more frequently than neonatal pemphigus foliaceus [103,104]. The clinical, histological, and direct
immunofluorescence findings of neonatal pemphigus are consistent with pemphigus. Indirect
immunofluorescence has been positive in the majority of reported cases [103]. The disease manifestations
usually resolve within three weeks.
DIAGNOSIS The diagnosis of pemphigus is made through the assessment of clinical, histological,
immunopathological, and serological findings (table 1). Even in cases in which the clinical findings strongly
suggest pemphigus, laboratory investigations to confirm the diagnosis are indicated since other disorders may
present with similar clinical findings (see 'Differential diagnosis' below).
Pemphigus vulgaris and pemphigus foliaceus In addition to a complete examination of cutaneous and
mucosal surfaces, the clinical assessment should include a review of the patient's medications since clinical and
laboratory studies cannot reliably distinguish between idiopathic pemphigus and drug-induced pemphigus. In
addition, patients who may have pemphigus vulgaris should be questioned about ocular symptoms, hoarseness,
dysphagia, dysuria, and dyspareunia to evaluate for symptoms suggestive of extraoral mucus membrane
involvement (see 'Drug exposure' above and 'Clinical features' above).
Our standard laboratory work-up for patients with clinical findings suggestive of pemphigus foliaceus includes:
A lesional skin or mucosal biopsy for routine hematoxylin and eosin (H&E) staining
A perilesional skin or mucosal biopsy for direct immunofluorescence (DIF)
Serum collection for enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence (IIF)
Histopathology The biopsy for routine histological examination should be taken from an early lesion. The
biopsy should be placed at the edge of a blister or erosion. A 4 mm punch biopsy is usually sufficient. (See
"Approach to the patient with cutaneous blisters", section on 'Skin biopsy'.)
The characteristic findings in pemphigus vulgaris include:
Intraepithelial cleavage with acantholysis (detached keratinocytes) primarily localized to the suprabasal
region
Retention of basal keratinocytes along the basement membrane zone, resulting in an appearance that
resembles a "row of tombstones"
Sparse inflammatory infiltrate in the dermis with eosinophils
In the pemphigus vegetans variant of pemphigus vulgaris, the suprabasal cleavage is accompanied by
hyperkeratosis, papillomatosis, and prominent acanthosis with downward proliferation of the rete ridges [105].
Eosinophils may be present within the areas of cleavage.
The characteristic findings of pemphigus foliaceus include (picture 10) [105]:
Intraepithelial cleavage with acantholysis beneath the stratum corneum or within the granular layer;
neutrophils within the blister cavity are occasionally seen
Mixed inflammatory infiltrate in the superficial dermis with eosinophils and neutrophils; eosinophils may be
more prevalent in drug-induced pemphigus foliaceus
Direct immunofluorescence Unlike the biopsy for routine histological examination, the biopsy for DIF
should be taken from normal-appearing perilesional skin or mucosa. The biopsy should not be placed in
formalin. (See "Approach to the patient with cutaneous blisters", section on 'Direct immunofluorescence'.)
Both pemphigus vulgaris and pemphigus foliaceus demonstrate intercellular deposition of IgG on DIF (picture
1A-B). Although some cases of pemphigus foliaceus demonstrate deposition of IgG that is primarily distributed in
upper levels of the epidermis (picture 1B), DIF cannot be used to reliably distinguish between these diseases.
Essentially all patients with idiopathic pemphigus vulgaris or pemphigus foliaceus have positive DIF results.
Thus, if DIF is negative, the diagnosis should be questioned. In contrast, negative DIF studies may occur in
patients with drug-induced pemphigus (see 'Drug exposure' above) [83,86]. Occasionally, intercellular deposition
of antibodies occurs in other diseases (eg, spongiotic dermatitis, burns, toxic epidermal necrolysis, systemic
lupus erythematosus, or lichen planus) [91].
Serology IIF and ELISA are serological studies that can detect circulating autoantibodies that bind
epithelial cell surface antigens. In patients with positive DIF results, these tests are used to further support the
diagnosis of pemphigus.
Indirect immunofluorescence More than 80 percent of patients with pemphigus vulgaris or pemphigus
foliaceus have circulating antibodies detectable by IIF [96]. The substrate used influences the test sensitivity [96].
Monkey esophagus is the preferred substrate for the diagnosis of pemphigus vulgaris. In contrast, normal human
skin and guinea pig esophagus are the most sensitive substrates for the diagnosis of pemphigus foliaceus. In
both disorders, IgG deposits are found intracellularly (picture 11). IIF cannot be used to distinguish between
these diseases. (See "Approach to the patient with cutaneous blisters", section on 'Indirect
immunofluorescence'.)
Enzyme-linked immunosorbent assay ELISA for IgG antibodies to desmoglein 1 and desmoglein 3 is
commercially available. ELISA is more sensitive and specific than IIF for the diagnosis of pemphigus vulgaris
and pemphigus foliaceus [96]. The sensitivity of ELISA exceeds 90 percent [9].
In addition, since desmoglein antibody levels often fall in the setting of clinical improvement, ELISA may aid with
monitoring disease activity and the response to treatment [106-108]. In a retrospective study that assessed the
predictive values of pemphigus autoantibodies in patients with pemphigus vulgaris and pemphigus foliaceus,
desmoglein 1 autoantibodies were more closely correlated with the disease course than desmoglein 3
autoantibodies [107]. Desmoglein 3 antibody levels remained high during disease remissions in some patients
with mucosal pemphigus vulgaris. In patients with pemphigus vulgaris, levels of IgE antibodies to desmoglein 3
may also correlate with disease activity [109]. (See "Initial management of pemphigus vulgaris and pemphigus
foliaceus" and "Management of refractory pemphigus vulgaris and pemphigus foliaceus".)
Other Additional serological tests that may be used for the diagnosis of pemphigus vulgaris and
pemphigus foliaceus include immunoblotting and immunoprecipitation. However, these tests are more difficult to
perform than IIF and ELISA. Thus, they are infrequently used in the clinical setting.
Aside from the detection of pemphigus antibodies in serum, pemphigus is not associated with specific laboratory
abnormalities. Other laboratory abnormalities may occur related to complications of the disease or its treatment.
IgA pemphigus Similar to other forms of pemphigus, the diagnosis of immunoglobulin A (IgA) pemphigus is
based upon the combined assessment of clinical and laboratory findings. The standard laboratory workup
consists of histological examination, DIF, and IIF.
Typical histological findings of IgA pemphigus include [4,105]:
Intraepidermal clefts and pustules located in a subcorneal location (subcorneal pustular dermatosis-type IgA
pemphigus) or in the entire or mid-epidermis (intraepithelial neutrophilic dermatosis)
Slight or absent acantholysis
Mixed inflammatory infiltrate in the dermis
DIF microscopy of perilesional skin reveals intercellular IgA deposition within the epidermis that is occasionally
more pronounced in the upper epidermis. Weaker intercellular deposits of IgG and/or C3 may also be present
[4,51]. IIF on monkey esophagus demonstrating intercellular deposits of IgA offers further support for the
diagnosis. However, IIF on monkey esophagus is positive in less than or equal to 50 percent of patients [4,51].
IIF on human skin may demonstrate intercellular antibody deposition more frequently; in one series of patients
with IgA pemphigus, IIF of normal human skin showed intercellular deposition of IgA in 31 of 48 patients (65
percent) [51].
Other studies that have been utilized to identify circulating IgA pemphigus desmocollin autoantibodies include
immunoblotting [110], ELISA using recombinant desmocollin [51,101], and immunofluorescence molecular assay
using desmocollin-transfected COS-7 cells [49,51]. The availability of these studies is limited to specialized
centers and research settings.
Although autoantibodies against desmocollin 1 appear to be strongly associated with the subcorneal pustular
dermatosis type of IgA pemphigus, autoantibodies to desmogleins may be present in other patients with IgA
pemphigus [50,51]. In one series of 22 patients with IgA pemphigus, ELISA tests for IgA autoantibodies against
desmoglein 1 or desmoglein 3 were positive in three patients and one patient, respectively [50]. The patients with
desmoglein autoantibodies had either the intraepidermal neutrophilic type of IgA pemphigus or a presentation
that had clinical and pathological features of pemphigus foliaceus. None of the 10 patients with subcorneal
pustular dermatosis-type IgA pemphigus had autoantibodies against these desmogleins, but all 10 had serum
samples that reacted with desmocollin 1 expressing COS-7 cells.
Paraneoplastic pemphigus Similar to other forms of pemphigus, the diagnosis of paraneoplastic pemphigus
involves review of clinical, histological, immunopathological, and serological findings. The diagnosis of
paraneoplastic pemphigus vulgaris is reviewed separately. (See "Paraneoplastic pemphigus", section on
'Diagnosis'.)
DIFFERENTIAL DIAGNOSIS Multiple mucocutaneous blistering diseases share clinical features with the
different forms of pemphigus. In all forms of pemphigus, laboratory investigations, particularly
immunopathological tests, usually easily distinguish pemphigus from other diseases.
Pemphigus vulgaris Cutaneous involvement in pemphigus vulgaris must be distinguished from other
autoimmune blistering diseases. The morphology of cutaneous blisters in pemphigus vulgaris can be helpful
for narrowing the differential diagnosis. The flaccid blisters often seen in pemphigus vulgaris contrast with
the tense blisters that are frequently seen in association with subepithelial blistering diseases (picture 12A-
C). (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid" and
"Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on
'Bullous pemphigoid' and "Linear IgA bullous dermatosis", section on 'Clinical manifestations' and
"Epidermolysis bullosa acquisita", section on 'Clinical manifestations' and "Dermatitis herpetiformis", section
on 'Clinical findings'.)
Mucosal lesions pemphigus vulgaris can resemble other blistering or erosive disorders of the mucous
membranes. As examples, the possibility of other pemphigus variants, mucous membrane pemphigoid,
mucosal linear IgA bullous dermatosis or epidermolysis bullosa acquisita, erythema multiforme, and
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Stevens-Johnson syndrome should be considered. (See "Approach to the patient with cutaneous blisters",
section on 'Mucous membrane involvement'.)
Pemphigus foliaceus The lesions of pemphigus foliaceus may resemble other inflammatory disorders,
such as seborrheic dermatitis (picture 13), impetigo, subacute cutaneous lupus erythematosus (picture 14A-
B), IgA pemphigus, and the non-IgA pemphigus form of subcorneal pustular dermatosis (picture 15A-B).
(See "Neutrophilic dermatoses", section on 'Subcorneal pustular dermatosis'.)
IgA pemphigus The differential diagnosis of IgA pemphigus overlaps with pemphigus foliaceus. In
addition, disorders that may present with grouped vesicular lesions or pustules, such as dermatitis
herpetiformis (picture 16), bullous impetigo, linear IgA bullous dermatosis (picture 12B), and pustular
psoriasis (picture 17A-B) should be considered.
Paraneoplastic pemphigus The differential diagnosis of paraneoplastic pemphigus is reviewed

separately. (See "Paraneoplastic pemphigus", section on 'Differential diagnosis'.)
SUMMARY AND RECOMMENDATIONS
Pemphigus comprises a group of autoimmune blistering diseases that are characterized by histological
acantholysis (loss of cell-to-cell adhesion) and mucosal and/or cutaneous blistering. The four major types of
pemphigus are pemphigus vulgaris, pemphigus foliaceus, IgA pemphigus, and paraneoplastic pemphigus
(table 1). (See 'Classification' above.)
Pemphigus is rare. Pemphigus vulgaris is the most common form of pemphigus. However, in certain areas,
particularly in locations where an endemic form of pemphigus foliaceus occurs, pemphigus foliaceus is more
prevalent. (See 'Epidemiology' above.)
The intraepidermal blistering observed in pemphigus occurs due to an immune response that results in the
deposition of autoantibodies against epidermal cell surface antigens within the epithelium of mucous
membranes or skin. The mechanism through which acantholysis occurs is not fully understood. (See
'Pathogenesis' above.)
The desmoglein compensation theory has been proposed as an explanation for the frequently observed
correlation of the clinical presentation of pemphigus vulgaris and pemphigus foliaceus with specific
circulating autoantibodies (figure 2). Circulating autoantibodies to desmoglein 1 are associated with
cutaneous involvement, whereas circulating autoantibodies against desmoglein 3 have been linked to
mucosal disease. Since desmogleins are not the only molecules that contribute to cell adhesion and not all
patients exhibit antibody profiles consistent with this theory, it is likely that autoantibodies against other
epithelial antigens are involved in these diseases. (See 'Target antigens' above.)
Pemphigus vulgaris generally is a more severe disease than pemphigus foliaceus. Patients with pemphigus
vulgaris usually present with widespread mucocutaneous blisters and erosions (picture 2A-B, 3A-D).
Cutaneous blistering in pemphigus foliaceus tends to occur in a seborrheic distribution (picture 6A-C).
Compared with pemphigus vulgaris, blistering in pemphigus foliaceus is more superficial. (See 'Clinical
features' above.)
Vesicles, pustules, and crusts on skin are common features of IgA pemphigus. The skin lesions may appear
in an annular, circinate, or herpetiform distribution. (See 'IgA pemphigus' above.)
The diagnosis of pemphigus is based upon the recognition of consistent clinical, histological, and direct
immunofluorescence findings, as well as the detection of circulating autoantibodies against cell surface
antigens in serum. Laboratory studies are useful for distinguishing pemphigus from other blistering and
erosive diseases. (See 'Diagnosis' above.)
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107. Abasq C, Mouquet H, Gilbert D, et al. ELISA testing of anti-desmoglein 1 and 3 antibodies in the
management of pemphigus. Arch Dermatol 2009; 145:529.
108. Zone JJ. The value of desmoglein 1 and 3 antibody ELISA testing in patients with pemphigus. Arch
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110. Hashimoto T, Ebihara T, Nishikawa T. Studies of autoantigens recognized by IgA anti-keratinocyte cell
surface antibodies. J Dermatol Sci 1996; 12:10.
Topic 83684 Version 11.0
GRAPHICS
Key clinical and laboratory findings in pemphigus
Clinical Direct
Epidemiology Autoantigens Histopathology
features immunofluorescence
Pemphigus Primarily middle- Desmoglein 1 and Mucosal Suprabasal Intercellular deposition of

vulgaris aged adults desmoglein 3, erosions; acantholysis; "row IgG
others flaccid bullae of tombstones"
and erosions pattern of basal
on skin keratinocytes
Pemphigus Primarily middle- Desmoglein 1 Fragile Subcorneal or Intercellular deposition of

foliaceus aged adults; blisters, granular layer IgG
endemic form shallow acantholysis
most common in erosions,
children and erythematous
young adults patches,
crusts;
mucosal
involvement
absent
Paraneoplastic Primarily adults, Envoplakin, Severe Variable findings; Intercellular and/or

pemphigus but may occur at periplakin, others stomatitis, suprabasal basement membrane zone
any age variable acantholysis, deposition of IgG and/or C3
cutaneous keratinocyte
findings (eg, necrosis, and
blisters, lichenoid interface
erosions, dermatitis are most
lichenoid common
lesions),
bronchiolitis
obliterans
IgA pemphigus
Subcorneal Any age Desmocollin 1 Vesicles, Subcorneal clefts Intercellular deposition of

pustular pustules, and pustules; IgA
dermatosis- crusts on minimal
type IgA skin; annular, acantholysis; mixed
pemphigus circinate, or infiltrate in dermis
herpetiform
morphology;
mucosal
involvement
usually
absent
Intraepidermal Any age Poorly defined Vesicles, Intraepidermal Intercellular deposition of

neutrophilic pustules, pustules; minimal IgA
dermatosis crusts on acantholysis; mixed
skin; annular, infiltrate in dermis
circinate, or
herpetiform
morphology;
mucosal
involvement
usually
absent
* Indirect immunofluorescence is negative in around 50 percent of patients with IgA pemphigus.

Test availability restricted to specialized laboratories.
Graphic 87920 Version 2.0
Pemphigus vulgaris direct immunofluorescence
An intercellular pattern of IgG antibody binding is evident on direct immunofluorescence

in this specimen from a patient with pemphigus vulgaris.
Courtesy of Kristin M Leiferman, MD, Immunodermatology Laboratory, Department of

Dermatology, University of Utah, Salt Lake City, Utah.
Pemphigus foliaceus direct immunofluorescence
Intercellular antibody binding is evident within the upper epidermis in this direct
immunofluorescence specimen from a patient with pemphigus foliaceus.

The desmosome in skin and mucous membranes
The desmosome is a critical junction for cell to cell adhesion in the skin and mucous
membranes. The major desmosomal proteins are desmogleins, desmocollins, plakoglobin,
plakophilins, and desmoplakin. Desmogleins and desmocollins are
transmembrane glycoproteins of the cadherin (calcium-dependent cell adhesion molecule)
family. Plakoglobin and plakophilins are components of the desmosomal plaque. Desmoplakin
binds to plakoglobin and links the desmosomal plaque to keratin filaments of the
cytoskeleton. Envoplakin and periplakin are additional desmosomoal proteins found in the
desmosomal plaque.
Desmoglein compensation theory
Graphic depiction of the desmoglein compensation theory. The desmoglein compensation

theory is a proposed explanation for the correlation between the clinical features of
pemphigus vulgaris and pemphigus foliaceus and the autoantibody profiles of
these disorders. In the skin, desmoglein 1 (Dsg1) is expressed mostly in the upper portions
of the epidermis, while desmoglein 3 (Dsg3) is expressed mostly in the basal and
suprabasal layers of the epithelium. In the mucous membranes, Dsg3 is present in
abundance throughout the epithelium, while Dsg1 is expressed to a much lower degree.
Mucosal dominant pemphigus vulgaris (A) is characterized by autoantibodies against Dsg 3
and results in only mucosal lesions because Dsg1 compensates for the loss of Dsg3 in the
skin. In the mucous membranes, Dsg1 cannot compensate resulting in intraepithelial
blistering. In mucocutaneous pemphigus vulgaris (B), autoantibodies against both Dsg1
and Dsg3 are present. Thus, compensation occurs neither in the skin nor the mucous
membranes, and blistering occurs in both locations. Pemphigus foliaceus (C)
is characterized by autoantibodies against only Dsg1. This results in very superficial blisters
in the skin. The mucous membranes are spared due to high levels of Dsg3 expression
throughout the epithelium and low levels of Dsg1 expression.
Drugs involved in pemphigus
SH drugs
SH drugs
Bucillamine
Captopril
D-penicillamine
Gold sodium thiomalate
Pyritinol
Thiopronine
Drugs with SH metabolites
Carbimazole
Penicillin
Piroxicam
Non-SH drugs
Antibiotics
Cephalosporins
Ethambutol
Isoniazid
Pentachlorophenol
Rifampicin
Pyrazol drugs
Aminophenazone
Aminopyrine
Azapropazone
Noramidopyrine
Phenylbutazone
Other drugs
Acenocoumarol
Enalapril
Heroin
Hydantoin
Imiquimod
Immunomodulators: interleukin-2, interferon alpha, interferon beta, isosorbide trinitrate
Isotretinoin
Levodopa
Lysine acetylsalicylate
Phenobarbital
Progesterone
Propranolol
SH: sulfhydryl group.
Reproduced with permission from: Maruani A, Machet MC, Carlotti A, et al. Immunostaining with antibodies to desmoglein
provides the diagnosis of drug-induced pemphigus and allows prediction of outcome. Am J Clin Pathol 2008; 130:369.
Copyright 2008-2013 American Society for Clinical Pathology.
Pemphigus vulgaris - oral lesions
Multiple erosions on the palate in a patient with pemphigus vulgaris.
Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.
Pemphigus vulgaris
Erosions on the tongue and lips are present in this patient with pemphigus vulgaris.
Pemphigus vulgaris
Gingival erosions are present in this patient with pemphigus vulgaris.
Pemphigus vulgaris
Flaccid bullae and erosions on the skin of a patient with pemphigus vulgaris.
Pemphigus vulgaris
Erosions and small blisters are present in this image taken from a patient with pemphigus
vulgaris.
Pemphigus vulgaris
Multiple erosions on the trunk skin of this patient with pemphigus vulgaris.
Pemphigus vulgaris
Widespread erosions are present on the skin in this patient with pemphigus vulgaris.
Pemphigus vegetans, axilla
In pemphigus vegetans, blisters and erosions develop in intertriginous areas and evolve
in vegetating plaques due to excessive granulation tissue formation.
Pemphigus herpetiformis
Annular and arcuate erythematous plaques with erosions and occasional vesicles were
present in this patient with pemphigus herpetiformis.
Reproduced with permission from: Kleker BM, Ramirez-Fort MK, Puchalsky D, et al. A
generalized annular eruption with occasional vesicles. Arch Dermatol 2012; 148:531. Copyright
2012 American Medical Association. All rights reserved.
Pemphigus foliaceus
Pemphigus foliaceus lesions exhibit erythema, scaling, and crusting. The face
and scalp are often the initial sites of involvement.
Reproduced with permission from: Stedman's Medical Dictionary. Copyright 2008

Lippincott Williams & Wilkins.
Pemphigus foliaceus
The scalp and periauricular lesions resemble those of seborrheic dermatitis in

this patient with pemphigus foliaceus.
Pemphigus foliaceus
Pemphigus foliaceus is characterized by erythema, scaling, and crusting that

first appears on the face and scalp, and later involves the chest and back.
Reproduced with permission from: Bystryn J, Ruldolph J. Pemphigus. Lancet 2005;

266:61. Copyright 2005 Nicholas Soter, MD. Reproduced in Lancet with permission
from: the New York University Department of Dermatology.
Pemphigus erythematosus
Erosions are on the malar region of the face.
Paraneoplastic pemphigus
An erosive mucositis in a patient with paraneoplastic pemphigus associated with

Castleman's tumor; mucous membrane and cutaneous lesions cleared with
tumor removal.
Copyright Chris Ha, MD, Dermatlas; http://www.dermatlas.org.
Multiple erosions are present on the tongue.
Gingival erosions are present.
Vesicles and flaccid bullae are present on the skin.
Bullae, erosions, and crusts are present on the skin.
Pemphigus foliaceus
Blister formation within the superficial granular layer in pemphigus foliaceus.
Pemphigus vulgaris indirect immunofluorescence
Pemphigus vulgaris. Indirect immunofluorescence performed on monkey esophagus

demonstrates intercellular IgG antibody deposition.

Bullous pemphigoid
Multiple tense bullae on skin with one eroded blister base.
Linear IgA bullous dermatosis
Tense bullae, erosions, and crusts, often in pattern described as "clusters of jewels" or
"strings of pearls," on skin of a patient with linear IgA bullous dermatosis.
Epidermolysis bullosa acquisita
Tense bullae, erosions, and crusts on skin of patient with epidermolysis bullosa acquisita.
Seborrheic dermatitis of the scalp
Diffuse erythema and scaling of the scalp.
Subacute cutaneous lupus erythematosus
Erythematous, annular plaques with scale.
Subacute cutaneous lupus erythematosus
Multiple erythematous, scaly papules are present on the upper back.
Subcorneal pustular dermatosis (Sneddon-Wilkinson

disease)
Multiple flaccid pustules and crusted plaques are present.
Subcorneal pustular dermatosis (Sneddon-Wilkinson

disease)
Multiple flaccid pustules and areas of crusting are present on the skin. The
largest lesion has a somewhat annular configuration.
Dermatitis herpetiformis
Multiple inflammatory papules and vesicles are present near the elbow.
Courtesy of Scott Florell, MD, Department of Dermatology, University of Utah.
Pustular psoriasis
Numerous small pustules are present on erythematous plaques.
Courtesy of Jeffrey Callen, MD, FACP.
Pustules in pustular psoriasis
Contributor Disclosures
Michael Hertl, MD Grant/Research/Clinical Trial Support: Biotest Pharmaceuticals Corporation [Pemphigus
(Immunoglobulin G)]; Fresenius [Pemphigus (Immunoadsorption device)]. Speakers Bureau: Janssen-Cilag
[General immunodermatology, bullous diseases (Ustekinumab)]. Consultant/Advisory Boards: Novartis
[Psoriasis, immunodermatology, academic mentoring programs (Secukinumab)]. Cassian Sitaru, MD Nothing to
disclose John J Zone, MD Grant/Research/Clinical Trial Support: GlaxoSmithKline [Pemphigus
(Ofatumumab)]. Abena O Ofori, MD Nothing to disclose
Las revelaciones de los colaboradores son revisadas para los conflictos de inters por el grupo editorial. Cuando
se encuentran, stas se abordan mediante la verificacin a travs de un proceso de revisin de varios niveles ya
travs de los requisitos para que se proporcionen referencias para respaldar el contenido. Se requiere un
contenido adecuadamente referenciado de todos los autores y debe ajustarse a los estndares de evidencia de
UpToDate.
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29/8/2017 Pathogenesis, clinical manifestations, and diagnosis of pemphigus - UpToDate

Reimpresin oficial de UpToDate

Patogenia, manifestaciones clnicas y diagnstico de pnfigo

Autores: Michael Hertl, MD, Cassian Sitaru, MD

INTRODUCCIN - El pnfigo se define como un grupo de trastornos vesiculares potencialmente mortales

Principales caractersticas: Envoltura mucosal o mucosa y cutnea, ampollas acantolticas

Variantes clnicas: Pemphigus vegetans, pemphigus herpetiformis

Caractersticas clave: Afectacin cutnea slo, ampollas acantolticas subcorneales, autoanticuerpos

Caractersticas principales: vesculas agrupadas o pstulas y placas eritematosas con cortezas,

Caractersticas principales: estomatitis extensa e intratable y hallazgos cutneos variables;

IgG autoanticuerpos a desmogleins se detectan consistentemente a travs de enzima vinculada al ensayo

Pnfigo paraneoplsico - Se han detectado mltiples autoanticuerpos en pacientes con pnfigo

La participacin de factores genticos en la susceptibilidad al pnfigo se refuerza an ms mediante la

Rara vez, la membrana mucosa participacin no se observa a pesar de la presencia de autoanticuerpos

Otras presentaciones clnicas poco frecuentes del pnfigo vulgar incluyen:

Pemphigus herpetiformis - Pemphigus herpetiformis es un trmino que describe pemphigus vulgaris o

Las variantes clnicas del pnfigo foliceo incluyen:

Pemphigus erythematosus (sndrome de Senear-Usher): Este trmino pemphigus erythematosus se

Paraneoplastic pemphigus Paraneoplastic pemphigus (also known as paraneoplastic autoimmune

A perilesional skin or mucosal biopsy for direct immunofluorescence (DIF)

The characteristic findings in pemphigus vulgaris include:

Sparse inflammatory infiltrate in the dermis with eosinophils

The characteristic findings of pemphigus foliaceus include (picture 10) [105]:

Typical histological findings of IgA pemphigus include [4,105]:

Slight or absent acantholysis

Mixed inflammatory infiltrate in the dermis

Paraneoplastic pemphigus The differential diagnosis of paraneoplastic pemphigus is reviewed

SUMMARY AND RECOMMENDATIONS

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 83684 Version 11.0

Key clinical and laboratory findings in pemphigus

Pemphigus Primarily middle- Desmoglein 1 and Mucosal Suprabasal Intercellular deposition of

Pemphigus Primarily middle- Desmoglein 1 Fragile Subcorneal or Intercellular deposition of

Paraneoplastic Primarily adults, Envoplakin, Severe Variable findings; Intercellular and/or

Subcorneal Any age Desmocollin 1 Vesicles, Subcorneal clefts Intercellular deposition of

Intraepidermal Any age Poorly defined Vesicles, Intraepidermal Intercellular deposition of

* Indirect immunofluorescence is negative in around 50 percent of patients with IgA pemphigus.

Graphic 87920 Version 2.0

Pemphigus vulgaris direct immunofluorescence

An intercellular pattern of IgG antibody binding is evident on direct immunofluorescence

Courtesy of Kristin M Leiferman, MD, Immunodermatology Laboratory, Department of

Graphic 82837 Version 2.0

Pemphigus foliaceus direct immunofluorescence

Courtesy of Kristin M Leiferman, MD, Immunodermatology Laboratory, Department of

Graphic 82838 Version 2.0

The desmosome in skin and mucous membranes

Graphic 87355 Version 2.0

Desmoglein compensation theory

Graphic depiction of the desmoglein compensation theory. The desmoglein compensation

Graphic 87356 Version 1.0

Drugs involved in pemphigus

Gold sodium thiomalate

Drugs with SH metabolites

Immunomodulators: interleukin-2, interferon alpha, interferon beta, isosorbide trinitrate

SH: sulfhydryl group.

Graphic 88293 Version 2.0

Pemphigus vulgaris - oral lesions

Multiple erosions on the palate in a patient with pemphigus vulgaris.

Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.

Graphic 57924 Version 4.0

Reproduced with permission from: www.visualdx.com. Copyright Logical Images, Inc.

Graphic 77462 Version 4.0

Gingival erosions are present in this patient with pemphigus vulgaris.