PEMFIGUS BENIGN FAMILIAL

HAILEY- HAILEY
Descris de fraii Hailey n 1939

Boal cronic autosomal dominant cu penetran
incomplet

2/3 din pacieni au istoric familial de boal

Femei= brbai

Debut n adolescen sau la adult

Mutaie ATP2C1, pe cromozomul 3- codific
Ca
2+
/Mn2ATPase (hSPCA1)

Plci eritematoase, eritemato-veziculo-crustoase genital,
axilar, pe piept, gt

Uneori secreie urt mirositoare (suprainfecie)

Afectare mucoas rar

Senzaie de arsur, prurit

Factori agravani cldur, friciune, suprainfecie
Acantholysis at all levels of the epidermis (hematoxylin and eosin
stain, original magnification X20).
Dilapidated brick wall

IFD negativ
Semn Nikolsky absent

Tratament
Comprese astringente (acetat de aluminiu 1:40)
Corticosteroizi topic
Antibiotice topic (clindamicin, eritromicin)
Antibiotice sistemic (tetraciclin, eritromicin)
Tacrolimus topic
Cazuri refractare Mtx, corticosteroizi sistemic
DERMATOZA ACANTOLITIC
TRANZITORIE ( BOALA GROVER)
Caracterizat de Grover n 1970

Benign, autolimitat, totui uneori f greu de tratat

Etiopatogenie necunoscut

Afecteaz mai frecvent brbai albi, de vrst
mijlocie

Femei=3x brbai

Debut presternal, parte superioar torace posterior,
parte inferioar cutie toracic

Pacieni cu leziuni diseminate gt, umeri, brae, picioare

Scalp, tlpi, palme de obicei neafectate

Papule keratozice eritematoase/roietic maronii discrete,
fr tendin la confluare

Uneori leziuni acneiforme, veziculoase, pustuloase, rar
chiar buloase

Prurit intens, chiar la leziuni minime
Acantoliz focal
Diskeratoz
Spongioz

5 patternuri HP - simuleaz Hailey-Hailey
- simuleaz b Darier
- caract predom prin spongioz
- simuleaz pemfigus vulgar
- simuleaz pemfigus foliaceu
un pattern poate predomina, toate patternurile pot fi
gsite n diferite leziuni la acelai pacient
necesare corelaii clinico- histopatologice
Histopathology of Darier-type Grover disease. A focus of
acantholytic dyskeratosis is present in the epidermis with slight
epithelial hyperplasia and hyperkeratosis, a sign of rubbing as a
consequence of the pruritic nature of the disease (hematoxylin and
eosin, original magnification X40).

Higher magnification reveals the acantholytic dyskeratosis to better
advantage. Note the corps ronds and grains (hematoxylin and
eosin, original magnification X400).

Tratament
Corticoizi topici poteni

Loiuni mentolate

Cazuri refractare retinoizi po, corticosteroizi po, UVB,
PUVA, MTX

EPIDERMOLIZA BULOAS
DOBNDIT
- leziuni cutanate similare celor din EB distrofica(fragilitate cutanata, bule si
eroziuni postbuloase posttraumatic, cicatrici atrofice, milium,distrofie
unghiala)

Istoric familial negativ

Debut tardiv la varsta adulta

Excluderea altor boli buloase

Prezenta de IgG la nivelul membranei bazale

Localizarea bulelor sub lamina bazala
Ex histopatologic: bule subepidermice, infiltrat inflamator moderat sau
absent

IFD: depozite liniare de IgG si C3 la jonctiunea dermo-epidermica(
imunoreactanti sub lamina densa

IFID: Ac circulanti IgG se fixeaza liniar in zona MB ; tinta = portiunea
corboxiterminala a procolagenului tip VII
Direct immunofluorescence performed on perilesional skin biopsy
specimen from a patient with epidermolysis bullosa acquisita
detects a linear band of immunoglobulin G deposit along the
dermoepidermal junction.
Indirect immunofluorescence performed on salt-split normal human
skin substrate using serum from a patient affected with
epidermolysis bullosa acquisita detects immunoglobulin G class
circulating autoantibodies that bind to the dermal (base) side of the
basement membrane.

PEMFIGOID BULOS
PEMFIGOID BULOS
Boal buloas subepidermic cronic, autoimun

Cea mai frecvent boal buloas autoimun n Europa
de Vest
43/1 milion/an UK
7-13/1 milion/an alte pri ale Europei

Ac IgG specifici pentru Ag hemidesmozomale ale PB
- BP230 (BPAg1)
- BP180 (BPAg2 )


Vrsta medie de debut 80 ani (literatur)

PB se asoc cu boala cerebro-vascular, demen, b.
Parkinson, epilepsie; acestea antedateaz debutul PB i
sunt considerate factori predispozani

Medicamente care ar induce PB
gliptin (dipeptidyl peptidase-IV inhibitor) n asoc cu
metformin
Fr spironolacton, neuroleptice
UK furosemid
Ac Ig G se leag de zona MB cutanate activare C i
mediatori ai inflamaiei atragere celule inflamatorii
eliberare proteaze degradare proteine
hemidesmozomale formare bule

Clinic: - bule n tensiune pe piele de aspect normal sau
eritematoas
- pot exista bule i/sau eroziuni pe mucoasele oral
i genital
- pruritul asociat sau nu cu eritem i/sau plci
urticariene poate precede apariia bulelor cu sptmni
sau luni
Biopsie cutanat (bul proaspt, col HE)

clivaj subepidermic
infiltrat inflamator compus predominant din Eo




IFD
depozit linear de Ig G i/sau C
3
de-a lungul zonei MB
pot fi prezente Ig A, Ig M, Ig E

IFID (ser, lichid din bul)
substrat folosit teg uman normal (salt- split skin): Ac se
depun pe Ag din tavan
dg dif EBD, MMP (Ac se depoziteaz pe partea
dermic a teg splitat)

ELISA se pot determina niv serice de Ac anti BP180 i
BP230




Direct immunofluorescence study performed on a perilesional skin
biopsy specimen from a patient with bullous pemphigoid detects a
linear band of immunoglobulin G deposit along the dermoepidermal
junction.

Indirect immunofluorescence study performed on salt-split normal
human skin substrate with the serum from a patient with bullous
pemphigoid detects immunoglobulin G class circulating
autoantibodies that bind to the epidermal (roof) side of the skin
basement membrane.
Dg Dif
Alte boli buloase autoimune
Boli buloase genetice (grupul epidermolizelor buloase)
nepturi de insecte
Eritem polimorf
Arsuri
Dermatita de contact buloas
Celulita forma buloas
Tratament
De obicei boal autolimitat, cu evoluie clinic ce poate
dura luni, ani

Factori de prognostic prost vrsta naintat, stare
general proast

Scopul tratamentului- controlarea simptomelor cu efecte
adverse minime

Alegerea tratamentului n funcie de pacient ( severitatea
PB i comorbiditi
Corticosteroizi sistemici
prednison, prednisolon 0,75-1-2 mg/kgc/zi
metilprednisolon 1g/zi iv 3 zile
CS topic clobetasol propionat 0,05%
Azathioprina
AB (tetraciclina 0,5-2 g/zi, doxiciclina 200-300 mg/zi,
minociclina 100-200 mg/zi) + nicotinamida (500-
2500mg/zi)
Methotrexat
Mycophenolate mofetil 0,5-1 g de 2x/zi
Dapsona, sulfonamide
IVIg
Clorambucil, ciclofosfamida, ciclosporina
DERMATITA
HERPETIFORMA
DUHRING-BROCQ
Boal buloas autoimun asociat cu enteropatie gluten
sensibil (90% din pacieni)

Descris n 1884 de Louis Duhring, Univ Pennsylvania

10 cazuri/ 100000 locuitori

Mai frecvent n N-E Europei, rar Asia, Africa

Femei/ brbai= 2/1

Debut tipic decade 2-4; rar la copii

Predispoziie genetic HLA-A1, HLA-B8, HLA-DR3,
HLAQ2
Predispoziia genetic pentru sensibilitate la gluten +
diet bogat n gluten formare Ac Ig A mpotriva t-TG
(gluten-tissue transglutaminase), care se gsete n
intestin

Ac cross-reacioneaz cu e-TG depozitare complexe
Ig A-eTG n dermul papilar trigger pt cascada
imunologic recrutare neutrofile + activare C

Colagenaza i stromelizina 1 induse n cheratinocitele
bazale fie de citokinele eliberate de neutrofile, fie de
contactul cu cheratina din matricea MB lezate
Papule, plci eritematoase escoriate, cu vezicule
grupate herpetiform; frecvent papule i plci urticariene

Rar leziuni mucoase, fa, scalp

Respect palme, tlpi

Prurit intens, senzaii de arsur, neptur

EGS nu este simptomatic la majoritatea pacienilor cu
DH: <10% prezint diaree, malabsorbie


Boli autoimune asociate Dm, DZ tip 1, myastenia gravis,
artrita reumatoid, sdr Sjgren, LES, anomalii tiroidiene

Neoplazii asociate limfoame GI, limfoame non-Hodgkin

DH poate fi indus de KI, leuprolide acetat, inhibitori TNF
alfa, antigripale, contraceptive orale cu progesteron
Papillary microabscesses form and progress to subepidermal
vacuolization and vesicle formation in the lamina lucida, the
weakest portion of the dermoepidermal junction (hematoxylin and
eosin stain).

Light micrograph shows neutrophils in the dermal papillae, with
fibrin deposition, neutrophil fragments, and edema (hematoxylin
and eosin stain).

Immunofluorescence showing immunoglobulin A at the
dermoepidermal junction (direct immunofluorescence stain).

Dg dif
Alte boli buloase autoimune

Dermatoza acantolitic tranzitorie

Eritem polimorf

Scabie
Tratament
Diet fr gluten toat viaa

Dapsona, sulfapiridina
EA dapsona- anemie hemolitic, agranulocitoz,
methemoglobinemie, neuropatie


Colchicina
Ciclosporina
Azatioprina
Prednison
PORFIRIA CUTANAT TARDIV
Forme dobndite (80%) sau familiale (20%), cu variaii n
funcie de regiuni geografice, grupuri etnice

Defect al uroporfirinogen-decarboxilazei pentru
expresia clinic a bolii este necesar scderea sub 25%
a activitii enzimei

SUA 1/10000-25000

Ambele sexe

Porfirinele= molecule fotoactive absorb energia
fotoexcitare mediere distrucii oxidative ale intelor
biomoleculare leziuni cutanate
Fragilitate cutanat+ vezicule mini, antebrae, uneori
fa, picioare; vindecare cu milia, pete hiperpigmentare,
cicatrici atrofice hipopigmentate

Hipertricoz malar, temporal, dar i pe brae, picioare

Fa- pigmentare melasma-like

Facies pletoric

Plci sclerodermiforme piept, spate, preauricular, reg
nucal, cu/fr calcificri distrofice
HP bul subepidermic
infiltrat inflamator dermic minim
papile dermice protruzive n cavitatea bulei
zona MB i pereii capilarelor din dermul superior
ngroate ( HE, PAS)
elastoz, scleroz colagen, depozite hialine n derm
caterpillar bodies- globuli liniari PAS+ compui din
material al MB i cheratinocite degenerate

IFD
depozite de Ig i C n i n jurul capilarelor dermice
i n zona MB; se crede c sunt imunoproteine scurse
din vasele lezate

Subepidermal bulla, festooning of rete ridges, hyalinization of blood
vessel walls, solar elastosis, and caterpillar bodies
Urini hipercrome
Porfirine urinare crescute
Coproporfirine fecale frecvent anormal crescute,
predominant isocoproporfirine
Porfirine eritrocitare normale
Tratament
Fotoprotecie
Nu alcool
Alimente bogate n Fe consumate cu moderaie
Doze alim adecvate de vitamina C
Flebotomie
Clorochin (125-250 mg 2x/spt po), hidroxiclorochin
(100-200 mg 2-3x/spt po)
Desferoxamina