Transcript vesicubullous

Vesiculo-Bullous Disorders
Definitions
Vesiculo-Bullous Disorders : group of skin
diseases in which blistering in the form of
vesicle or bullae occurs as a primary event
either by genetic mutation or autoimmune
response
Vesicle: visible accumulation of fluid which is
<0.5cm in size
Bulla: visible accumulation of fluid which is
>0.5cm in size
Classification
A: Depending upon the site of blistering
Intra epidermal
Sub corneal
Spinous
Supra basal
P. foliaceous
IgA pemphigus
P. vulgaris
P. erythematosus
Dermatitis
P. vegetans
Endemic pemphigus
Miliaria rubra
Paraneoplastic
pemphigus
P. herpetiformis
Varicella
Bullous impetigo
Herpes zoster
S.S.S.S.
Herpes simplex
Classification
A: Depending upon the site of blistering
Lamina lucida
Lamina lucida
Lamina densa
Sub lamina densa
Bullous pemphigoid
Cicatricial
pemphigoid
Epidermolysis
bullosa
dystrophicans
Dermatitis
herpetiformis
Linear IgA
dermatosis
Classification
B: depending upon cause

Autoimmune: Pemphigus, Pemphigoid, Dermatitis
herpetiformis, Pemphigoid gestationis, Bullous SLE,
Linear IgA dermatosis, Epidermolysis bullosa
acquisita, Paraneoplastic pemphigus, Chronic
blistering disease of childhood

Familial: Hailey Hailey disease, epidermolysis
bullosa

Infectious: Varicella , herpes zoster, herpes simplex,
candidiasis, bullous impetigo, bullous scabies.

Others: Burns, diabetic blister, TEN, SJS, Fixed
drug eruption, Porphyrias, Bullous erythema
multiforme
Pemphigus

“Pemphix” in Greek means ‘Bubble’

Chronic autoimmune bullous dermatosis

Immunopathologically characterised by auto
antibodies directed against the cell surface of
epithelial cells
Types and variants
Types
Variants
Pemphigus vulgaris
Pemphigus vegetans,
Drug induced
Pemphigus foliaceus
Pemphigus erythematosus,
Fogo selvagem,
Drug induced
Paraneoplastic
pemphigus
IgA pemphigus
Subcorneal pustular
dermatosis,
Intraepidermal neutrophilic
IgA dermatosis
Pemphigus
Epidemiology

4th - 5th decade, M=F
Etiology

Genetics: HLA DRB1, HLA DQB1

Antigens: Desmogleins, desmocollins and
desmoplakins present in the desmosomes act
as the auto antigens

Antigen: Desmoglien1, Desmoglien3
Pathogenesis
Circulating autoantibodies bind to cell surface
lysis of intercellular cement substance
acantholysis
intraepidermal blister
The blister cavity consists of mainly acantholytic cells
Clinical features

Thin walled flaccid bullae that rupture easily to
form painful raw surfaces with tendency to
spread; long time to heal

Sites: Starts in the oral cavity; then the groins,
genitals, axillae, scalp, face, neck

Nikolsky’s sign: Positive, shearing stress
applied to bony prominences on normal skin
away from the lesion causes separation of the
epidermis from the dermis

Bulla spread sign: Vertical pressure causes
extension of blistering into the surrounding
apparently normal skin
Diagnosis
Tzanck smear

Acantholytic cell - Large round cell with
hyperchromatic nucleus and perinuclear halo due
to peripheral condensation of cytoplasm
Histopathology

Supra basal cleft with acantholytic cells

Tomb stone appearance

Perivascular infiltrate of lymphocytes, neutrophils
Immunofluorescence

Intercellular IgG and C3 deposits showing
(Fishnet or Honey-comb pattern)
Treatment
Systemic:

Steroids (mainstay of treatment) 1.5-2 mg/kg/day

Anti metabolites : Azathioprine,
Cyclophosphamide, Cyclosporine

Pulse therapy: Dexamethasone Cyclophosphamide pulse (DCP), Methylprednisolone pulse

Others : Plasmapheresis, Iv Gammaglobulins
Dapsone, Nicotinamide and Tetracycline,
Antimalarials
Course and prognosis

Lesions subside with hyperpigmentation; with few
recurrences and requires a longterm
maintenance therapy

The most common cause of death: Septicemia
and pulmonary embolism
Bullous pemphigoid
Bullous Pemphigoid is an

acquired autoimmune blistering disease of the
elderly

characterized clinically by tense bullae

histopathologically by sub-epidermal bullae

immunopathologically by deposition of antibodies
and complement along the basement membrane
zone
The term bullous pemphigoid was termed by Lever
in 1953
Etiology
Epidemiology

Age-60 to 75, M=F
Etiology

Genetics: HLA DQ7, HLA DRB1

Antigens: BPAg1(230 kDa) and BPAg 2(180 kDa)
present in hemidesmosomes act as autoantigens

Antibodies: IgG, IgA, IgE
Pathogenesis
Circulating antibodies bind to the lamina lucida
activate the complement pathway
eosinophils accumulate in dermis
adhere to basement membrane zone (BMZ),
release destructive enzymes
BMZ separates
Sub-epidermal blister is formed
Clinical features

Large tense sub-epidermal bullae on normal or
erythematous base → on rupture form large
denuded areas with tendency to heal

Urticarial plaques and patches with tendency to
central clearing

Nikolsky’s sign: negative

Modified bulla spread sign: positive

Sites : Lower abdomen, inner thighs, groins,
flexural aspect of limbs. Mucosal surfaces are
involved in 10- 40% cases

Association : Malignancy, diabetes, ulcerative
colitis, multiple sclerosis
Diagnosis

Tzanck smear : Plenty of eosinophils

Histopathology :
Epidermis is usually normal
Sub epidermal bulla filled with fibrin and
eosinophils
Dermis shows infiltrate of eosinophils,
mononuclear cells and neutrophils

Immunopathology :
C3, IgG, IgA, IgM seen along BMZ and in
circulation
Treatment

Topical : Steroids

Systemic:
Steroids 40-80 mg/day and tapered when disease
under control
Dapsone
Tetracycline and Nicotinamide
Immunosuppressants

Others:
Plasmapheresis
IV Gamma globulins
Prognosis

Benign self limiting disease lasting from months
to years

Mortality rate less after advent of steroids

Most common cause of death is usually some
underlying associated disease
Dermatitis Herpetiformis (DH)
A rare chronic blistering disease of the skin
characterized by:

Intensely pruritic grouped vesicles on an
erythematous base

Granular IgA deposits on the dermal papillae on
direct immunofluorescence

Association with gluten-sensitive enteropathy
DH was first described by Duhring in 1884
Etiology
Epidemiology

Age-20 to 40 yrs , M=F, Whites > Blacks/Asians
Etiology

Genetics: HLA B8, DRw17 and DQw2

External factors: Gluten containing diet like
wheat, barley, oats and rye

Antigen: Gut epithelial antigen that cross reacts
with skin

Antibodies: IgA directed against gliadin and
autoantigens like reticulin and endomysium
C3, IgG, IgM may be seen
Pathogenesis
Gluten or its fragments are taken up by antigen
presenting cells like lymphocytes
activation of cytokines and inflammatory cells
plasma cells release IgA2 directed against gliadin
cross-reacts with autoantigens of skin and gut like
reticulin, endomyosium
Clinical features

Severely pruritic grouped, papulovesicles on
erythematous base

Sites: Symmetrical involvement of extensor
aspect of knees, forearms, axillae, shoulders,
sacrum, buttocks, face, nuchal area and on scalp

Associations: Gluten sensitive enteropathy,
autoimmune diseases like diabetes, thyroid
disease, pernicious anemia
Diagnosis

Tzanck smear: plenty of neutrophils

Histopathology: Neutrophilic microabscesses in
dermal papilla with sub-epidermal vesicle

Immunopathology:
Clinically normal skin on forearm or buttock
shows granular IgA deposits in the dermal papilla.
IgM, IgG may also be found
Treatment

Strict gluten free diet

Systemic steroids not the mainstay of therapy

Dapsone 100-200 mg/day

Sulphapyridine 1.5 g/ day

Tetracycline with nicotinamide

Colchicine when the above drugs are
contraindicated
Prognosis

Disease present life long; with remissions and
exacerbations

Strict gluten free diet causes remission of the skin
and gut disease

About 10%-15% have spontaneous remissions

Increased risk of developing gastro-intestinal tract
lymphoma
Epidermolysis bullosa acquisita (EBA)
EBA is a mechanobullous disease of the elderly
characterized by

Sub epidermal blistering on histopathology

Tissue bound and circulating anti bodies to type
VII collagen
Etiology

Genetics- HLA DR2

Antigen- 290 kDa protein in type VII collagen
(found in basement membrane zone)

Antibodies - IgG
Pathology
The antigen antibody complex cause

direct destruction of anchoring filaments (noninflammatory type) or

inflammatory response via complement system
activation (inflammatory type)
This causes the BMZ split and thus a sub epidermal
blister
Clinical features
4th to 6th decade, M=F
Non-Inflamatory type

Flaccid blisters over the trauma prone areas

Heal with scarring, milia and hyperpigmentation

Cicatricial alopecia and dystrophic nails seen
Inflammatory type

Tense blisters and urticarial plaques on
erythematous base that heal without scarring

Sites: Dorsa of hands and feet, elbows, knees

Associations: SLE, inflammatory bowel disease
Diagnosis

Histopathology

Sub-epidermal blister with or without lymphocytic
infiltrate

Immunopathology
Linear deposition of IgG, C3 and sometimes IgM,
IgA
Salt - splitting technique : Antibodies on dermal side
Treatment

Steroids in combination with dapsone/
sulphonamides (first line)

Colchicine

Cyclosporine

IV immunoglobulin
Prognosis

Chronic protracted disease with remission and
exacerbations

Inflammatory type is amenable to treatment

Non-inflammatory type is difficult to suppress

Rarely the disease may remit spontaneously
Approach to vesiculobullous disorders

Clinical history and classical features

Tzanck smear

Histopathology : to find out the level of blister and
type of cellular inflammatory infiltrate

Immunofluorescence : both direct and indirect
methods for autoimmune bullous dermatoses
Approach to vesiculobullous disorders
Features
Pemphigus Vulgaris
Bullous Pemphigoid
Age Group
20-40 years
> 60 years
Onset
Oral cavity
Upper trunk
Prodrome
Absent
Itching with urticarial
plaques
Bulla
Flaccid
Tense
Nikolsky’s sign
Positive
Negative
Histopathology
Intraepidermal blister
Row of tombstones
appearance
Negative
Target antigen
Desmoglein-3
BP230, BP180
Immunoflorescence
Desmoglein-3
BP230, BP180
Prognosis
Bad
Good
Approach to vesiculobullous disorders
Disease
Tzanck
Histopathology
Immunofluorescence
Acantholytic
cell
Suprabasal
blister with
acantholytic cell
and tombstone
appearance of
basal layer
Intercellular
intraepidermal IgG in
fishnet pattern
Bullous
pemphigoid
Eosinophils
Sub epidermal
blister with
dermal
eosinophilic
infiltrate
C3 and IgG along the
BMZ
Dermatitis
herpitiformis
Neutrophils
Sub epidermal
blister
Granular IgA at tips of
dermal papillae
E.B. acquisita
Neutrophils/
eosinophils
Sub epidermal
blister
IgG and C3 with IgA &
IgM along the BMZ
Pemphigus
vulgaris
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