Transcript HISTOPATHOLOGY OF IMMUNOBULLOUS DISORDERS

HISTOPATHOLOGY OF
IMMUNOBULLOUS
DISORDERS
DR.SHUBHA
INTRAEPIDERMAL BULLOUS
DISORDERS
TARGET ANTIGENS
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Located in the desmosomes the most
prominent adhesion junction in stratified
squamous epithelium.
Desmosome complex contains desmogleins
and desmocollins as transmembrane
components and desmoplakins , phakoglobins
as intracellular components.
PEMPHIGUS VULGARIS
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Autoimmune disease characterised by large
flaccid blisters ;primarily in older individuals .
Scalp, face, flexures, groin and pressure points.
Lesions characteristically involves the oral
mucosa.
It is important that early blisters preferably
smaller ones are selected for biopsy.
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Greek pemphix-blister or bubble
Disruption of intercelular cementing substance
Most common 80%
Fourth to sixth decade
50-70% mucosal lesions
Bullae rupture spontaneously, no tendency to
heal spontaneously
Nikolsky’s sign (Asboe-Hansen sign)
HISTOPATHOLOGY
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Target antigen is desmoglein 3 which is 130 kD
localised in spinous layer and in mucus
membrane.Early blisters; smaller in size selected.
Earliest change – spongiosis in lower epidermis.
Acantholysis is suprabasal ,may extend into the
adenexa.
Basal keratinocytes though seperated from one
another remain attached to the basement membrane
;”Row of tombstones appearance”.
IMMUNOFLOURESCENCE
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DIF -Edge of the blister with intact
sorrounding skin is selected; transported in
michael’s medium.
Very sensitive and reliable test esp. in oral
lesions.
Squamous intercellular or cell surface IgG
deposition seen in 95 % of cases.
IDF – IgG antibodies in 80 % of cases using
monkey oesophagus as substrate.
PEMPHIGUS VEGETANS
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Rare variant of pemphigus vulgaris .
Vegetating lesions in flexures.
Initially bullae or pustule
Two types – Neumann and Hallopeau.
Antibodies against Pemphigus vulgaris
antigens – 130 KDa.
HISTOPATHOLOGY
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Vegetating lesions are acanthotic ,
hyperkeratotic and papillomatous.
Suprabasal clefts contain acantholytic cells and
eosinophils. Intraepidermal eosinophilic
abscesses seen in older lesions.
Hallopeau lesions – pustules on normal skin
with acantholysis and small suprabasal clefts.
Dermis – heavy infiltrate of lymphocytes and
eosinophils with few neutrophils.
IMMUNOFLOURESCENCE
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DIRECT -Intercellular deposition of IgG in all
reported cases.
INDIRECT -Positive in most of the patients.
Differential diagnosis – Pyoderma vegetans ;
seen in association with inflammatory bowel
disease. Neutrophils are more common .
Eosinophilic abscesses and acantholytic cells
are rare.Mimicks pemphigus vegetans
clinically and histologically.
PEMPHIGUS FOLIACEOUS
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Subcorneal blister
Ig G antibodies against desmoglein 1
Les severe, crusted moist, scaly lesions in
seborrheic distribution
Very transient
Better prognosis
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Early lesions – Vacoulation in intracellular
spaces in the upper level of epidermis which
coalesce to form clefts and bullae in granular
layer or immediately beneath the stratum
corneum.
Bullae contain fibrin , acantholytic cells and
neutrophils.
Dyskeratotic cells in granular layer important.
Dermis shows mixed infiltrate of eosinophils
and neutrophils .
IMMUNOFLOURESCENCE
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DIRECT - Intercellular IgG and C3
deposition throughout the epidermis or
restricted to upper part of epidermis.
INDIRECT– Positive in 85 % of sera.
Pemphigus foliaceous antibody
DESMOGLEIN 1 is expressed more in the
upper layers of epidermis.
Staphylococcal scalded skin syndrome
DIFFERENTIAL DIAGNOSIS
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Marked dyskeratosis distinguishes pemphigus
foliaceous from p.vulgaris.ultrastructurally ,
there is early loss of intercellular cement
substance in lower half of epidermis,
perinuclear homogenisation of tonofilaments
in mid epidermis.
Impetigo
Subcorneal pustular dermatosis
SSSS.
PEMPHIGUS ERYTHEMATOSUS
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Senear Usher syndrome
Variant of pemphigus foliaceous.
Clinically resembles lupus erythematosus ;
erythematous plaques and patches in butterfly
distribution .
HPE – Light microscpic changes similar to P.
foliaceous. Rarely interface dermatitis in older
lesions.
Direct immunoflourescence – squamous intercellular
deposition of IgG , granular IgG and IgM at
dermoepidermal junction.ANA positive in 30 – 80 %
of cases.
IgA pemphigus
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Pruritic pustular eruption in middle aged and
elderly characterised by intercellular IgA
deposition and intraepidermal neutrophils.
Two types –1. Subcorneal pustular dermatosis
type – subcorneal vesicles and pustules with
minimal acantholysis.2. intraepidermal
neutrophilic dermatosis
Antibodies against Desmocollin -1 in SCPD
type and Desmoglein 2 in latter type.
PARANEOPLASTIC PEMPHIGUS
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Most common neoplasm – Nonhodgkins
lymphoma , CLL , castlemans tumour
,thymomas and sarcomas.
Histological pitcure depends on various
clinical presentations – unique combination of
erythema multiforme like , lichen planus like ,
pemphigus vulgaris like and pemphigoid like
features.
HISTOPATHOLOGY
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Suprabasal acantholysis.
Basal apoptosis
Interface dermatitis (erythema multiforme like
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With or without lichenoid inflammation.
desmoplakin
IMMUNOFLOURESCENCE
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DIRECT – Squamous intercellular deposition
of IgG in perilesional skin ; At
dermoepidermal junction linear deposition of
C3 and IgG seen.
IgG antibodies directed against desmoplakins ,
envoplakins and desmogleins.
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Endemic P.Foliaceous
Bite of black fly
Drug
Penicillamine,captopril, penicillin,rifampicin
Neonatal pemphigus
Transplacental transfer, resolves in 2 weeks
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Treatment
Systemic steroids
DCP
Dapsone
Methotrexate
Azathioprine
Ciclosporine
plasmapheresis
SUBEPIDERMAL BLISTERING
DISORDERS
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BULLOUS PEMPHIGOID –
Elderly
Preceded by pruritis by 2-3 weeks
Tense bullae on flexures
Face and scalp relatively spared
Heals spontaneously with PIH
Nikolsky negative
Mucosa rare
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Underlying malignancy-gastric carcinoma
DM, RA, psoriasis
Better prognosis than pemphigus
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Topical and systemic steroids
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Antibodies react with two antigens ; 230 –
kD(BPAg1) , 180kD (BPAg2).
Blister is subepidermal with intact and often
viable epidermis forming the roof.
Early lesions show papillary edema with cell
rich or cell poor perivascular lymphocytes and
eosinophilic infiltrate. Eosinophilic spongiosis
or microabscesses may be seen.
Blister lumen contains inflammatory cells .
IMMUNOFLOURESCENCE
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Direct -Linear C3 deposition at dermo –
epidermal junction in 100 % of cases and IgG
in 65 – 95 % .IgG is located within lamina
lucida and specifically bound to
hemidesmosomes.
Salt split technique – IgG at roof or floor of
artificially induced blister.
Indirect – circulating IgG antibodies to
basement membrane zone in 70 – 80 %.
MUCUS MEMBRANE
PEMPHIGOID
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Subepidermal blister that may extend down the
adenexa.
Neutrophils , lymphocytes and histiocytes
predominate in the infiltrate with less
eosinophils.
Late lesions –Lamellar fibrosis is the hallmark.
Mucosal lesions show cell rich lichenoid
infiltrate.
HERPES GESTATIONALIS
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non viral auto immune
21-28 weeks of pregnancy, 1st post natal
Severe pruritis with urticaria, wheals
Peri umbilical, lower abdomen, thigh
Rarely mucosa
Recurs with OCP, pregnancies, premenstrually
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Early urticated lesions show marked edema of
papillary dermis with foci of eosinophilic
spongiosis.
Blister is subepidermal with split at lamina
lucida.
DIF – linear deposition of C3 and IgG at
basement membrane zone. Split skin – binding
at epidermal side of the blister.
EPIDERMOLYSIS BULLOSA
AQUISITA
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Acquired autoimmune
Trauma induced sub epidermal blistering
Mucosal lesions
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Two forms – 1. Bullous pemphigoid like
eruption ; heavy inflammatory infiltrate mainly
neutrophils and lymphocytes., heals with
scarring, mechanobullous type, dystrophic
nails
2.classical form with sparse infiltrate.
DIF – Linear C3 deposition at basement
membrane ;IgG in some cases.
Salt split – Abs bind to lamina densa (type V11
collagen) and hence seen at floor of blister.
BULLOUS SLE
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Three histological patterns – 1.striking basal cell
vacuolization with subepidermal blister formation.
2.vasulitis with subepidermal blister formation. 3.
dermatitis herpetiformis like lesion.
Neutrophils prominent in blister cavity and
superficial dermis.
DIF – IgG and C3 at basement membrane zone
(linear or granular band like ).
Salt split – localization at floor.
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Treatment
Steroids
Dapsone
Immunosuppresive therapy
DERMATITIS HERPETIFORMIS
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Prutitic , chronic, recurrent, papulovesicular
lesions extensors, buttocks , shoulders
Gluten sensitivity
HLA-B8
20-55 years
MC males
Oral lesions
Provocation of lesions with iodides
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Typically seen in erythematous skin adjacent
to the early blisters.
Characteristic dermal papillary neutrophilic
microabscesses which separate the tips of
papillae from epidermis to form multilocular
blisters.
Papillary dermis beneath – intense infiltrate of
neutrophils and some eosinophils
IMMUNOFLOURESCENCE
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DIF – Granular IgA deposition in papillary
dermis in both lesional and perilesional skin.
IgA is exclusively IgA1 , both monomeric and
polymeric with J chain and secretory
components , associated with microfibrils.
IIF – Antiendomysial antibodies (smooth
muscle ) , antireticulin , antigliadin antibodies.
Antibodies against Trans-glutaminase II.
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Treatment
Dapsone 100-200 mg/day
Gluten free diet
LINEAR IgA DERMATOSES
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Two types 1.adult linear IgA dermatoses.
2.chronic benign bullous dermatoses of
childhood.
Adult – similar to dermatitis herpetiformis
i.e.papillary neutrophilic abscesses or
neutrophils along dermoepidermal junction.
Children – string of pearl appearance.urticarial plaques blistering at edge
IMMUNOFLOURESCENCE
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DIF – linear deposition of IgA along basement
membrane zone.
Salt split at lamina lucida – majority bind to
upper part of blister , few combined and few to
lower .
IIF – more positivity in children.
Drug induced – most common to vancomycin ,
diclofenac , lithium and captopril.
Disease
Direct
IMF
Isoty
pe
Pemphigus
vulgaris
Intercell- IgG,
ular
IgM
Target Antig Location
antige ens
ns
Desmo 130
Desmosomes
glein3
Vegetans
Intercell- IgG
ular
Desmo 160
glein1
Desmosomes
Foliaceus
Intercell- IgG
ular
Desmo 160
glein1
Desmosomes
Paraneoplast Intercell- IgG
ic
ular and
pemphigus subepide
rmal
plakins 230,2 Desmosomes,
50
BMZ
Disease Direct
IMF
Bullous
Pemphi
goid
Mucou
s
membr
ane
pemphi
goid
Pemphi
goid
Linear
BMZ
Isotype Bindin
g to
split
skin
IgG
Epider
mal
Linear
BMZ
IgG
Epider
mal
Linear
BMZ
IgG
Epider
mal
Target Locatio Structu
Antige n
re
ns
BP230 Hemid Dense
BP180 esmoso plaque
me
BP180, Lamina Anchor
BP230 lucida ing
Filame
nt
BP180, Hemid Dense
BP230 esmoso plaque
Linear IgA
disease
Linear IgA
BMZ
Epidermolys Linear IgG
is bullosa
BMZ
acquistia
Epider BP180 Hemid
mal
esmos
Derma Collag ome
l
en VII
Derma Collag Lamin Ancho
l
en VII a
ring
Densa Fibril
Bullous SLE Linear IgG,Ig Derma Collag Lamin Ancho
BMZ A
l
en VII a
ring
Densa Fibril
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