1. CLASSIFICATION OF VESICULOBULLOUSCLASSIFICATION OF VESICULOBULLOUS
DISEASESDISEASES
VESICLE & BULLAVESICLE & BULLA
A clear fluid lesion just below theA clear fluid lesion just below the
epithelium which ruptures to form an ulcer,epithelium which ruptures to form an ulcer,
if this is smaller than 5mm then it is aif this is smaller than 5mm then it is a
vesicle ,if larger than 5mm than it is a bullavesicle ,if larger than 5mm than it is a bulla
2. CLASSIFICATION OF VESICULOBULLOUSCLASSIFICATION OF VESICULOBULLOUS
DISEASESDISEASES
CLASSIFICATIONCLASSIFICATION
INTRA EPITHELIAL VESICLESINTRA EPITHELIAL VESICLES: The lesion is formed: The lesion is formed
within the epitheliumwithin the epithelium
Acantholytic vesicles :Acantholytic vesicles : This is because of the breakThis is because of the break
down of specialized attachments called thedown of specialized attachments called the
desmosomesdesmosomes
Nonacantholytic vesiclesNonacantholytic vesicles: It is usually in the viral: It is usually in the viral
infections because of the death or the rupture of theinfections because of the death or the rupture of the
group of cells.group of cells.
SUB EPITHELIAL VESICLESSUB EPITHELIAL VESICLES: Lesions formed between the: Lesions formed between the
epithelium and the lamina propria eg:epithelium and the lamina propria eg:
Erthyma multifomeErthyma multifome
PhempegoidPhempegoid
Dermatitis herpetiformisDermatitis herpetiformis
Epidermolysis bullosaEpidermolysis bullosa
3. PEMPHIGUS VULGARISPEMPHIGUS VULGARIS
Autoimmune disease.Autoimmune disease.
Common in Ashkenazi and Mediterranean jews .Common in Ashkenazi and Mediterranean jews .
Middle aged females.Middle aged females.
Other variants are:Other variants are:
Pemphius vegetansPemphius vegetans
Paraneoplastic pemphgusParaneoplastic pemphgus
4. PEMPHIGUS VULGARISPEMPHIGUS VULGARIS
CLINICAL FEATURES:CLINICAL FEATURES:
Painful ulcers or bulla are formed which are fluidPainful ulcers or bulla are formed which are fluid
filled.filled.
They can be formed any where in the oral cavity .They can be formed any where in the oral cavity .
The bulla is rapidly ruptured leaving a collapsed roofThe bulla is rapidly ruptured leaving a collapsed roof
of grayish membrane with a red ulcerated base.Theof grayish membrane with a red ulcerated base.The
ulcer may look like an apthous ulcer or may be largeulcer may look like an apthous ulcer or may be large
map shaped.map shaped.
Nikolsky sign is positive.Nikolsky sign is positive.
5. PEMPHIGUS VULGARISPEMPHIGUS VULGARIS
Sometimes the ulcers are joined together to make aSometimes the ulcers are joined together to make a
confluence. this condition is very painful.confluence. this condition is very painful.
It has a variable course might involve skin,It has a variable course might involve skin,
oesophagus, cervix.oesophagus, cervix.
Protein/fluid,electrolyte and weight loss /secondaryProtein/fluid,electrolyte and weight loss /secondary
infections.infections.
Fatal if untreated.Fatal if untreated.
7. PEMPHIGUS VULGARISPEMPHIGUS VULGARIS
PATHOGENESIS:PATHOGENESIS:
It is an autoimmune diseaseIt is an autoimmune disease
There are circulating antibodies of type IgG.There are circulating antibodies of type IgG.
These antibodies are reactive against theThese antibodies are reactive against the
desmosomes or the tonofilament complex.desmosomes or the tonofilament complex.
There destruction or disruption of theseThere destruction or disruption of these
tonofilament complex ,resulting in the loss oftonofilament complex ,resulting in the loss of
attachment from cell to cellattachment from cell to cell
path.cont…dpath.cont…d
8.
9. PEMPHIGUS VULGARISPEMPHIGUS VULGARIS
HISTOPATHOLOGY:HISTOPATHOLOGY:
Intra epithelial vesicles or bulla and cleft like spacesIntra epithelial vesicles or bulla and cleft like spaces
are produced by acantolysis .are produced by acantolysis .
These changes are in the stratum spinosum or theThese changes are in the stratum spinosum or the
prickle cell layerprickle cell layer
Inflammatory cells are very scanty howeverInflammatory cells are very scanty however
eosinophils may be seen.eosinophils may be seen.
Acantholytic statum spinosum cells occur singly orAcantholytic statum spinosum cells occur singly or
are in the forms of clumps lying freely within theare in the forms of clumps lying freely within the
blister fluid. These cell loose there polyhedralblister fluid. These cell loose there polyhedral
morphology rather they are small rounded andmorphology rather they are small rounded and
contain hyper chromatic nuclei called the TZANKcontain hyper chromatic nuclei called the TZANK
CELLS.CELLS.
12. DIAGNOSISDIAGNOSIS
Skin biopsySkin biopsy
Electron microscopy has shown thatElectron microscopy has shown that
widening of the intercellular space iswidening of the intercellular space is
followed by splitting of the desmosomefollowed by splitting of the desmosome
junctions.junctions.
Direct & indirect immunofluorescenceDirect & indirect immunofluorescence
ELISAELISA
16. PEMPHIGUS VULGARISPEMPHIGUS VULGARIS
TREATMENT:TREATMENT:
High mortality rates previouslyHigh mortality rates previously
Introduction of systemic corticosteroidsIntroduction of systemic corticosteroids
like prednisolone in stable cases.like prednisolone in stable cases.
Prednisolone plus azathioprinePrednisolone plus azathioprine
methotrexate and cyclophosphamide inmethotrexate and cyclophosphamide in
progressed or advanced cases.progressed or advanced cases.
18. DefinitionDefinition: Blistering in this group of: Blistering in this group of
autoimmune diseases is high in theautoimmune diseases is high in the
epidermis, either in the granular layer orepidermis, either in the granular layer or
just beneath the stratum corneum.just beneath the stratum corneum.
Antibody binding may have a direct effectAntibody binding may have a direct effect
on the function of the desmosomalon the function of the desmosomal
cadherins in the upper epidermis, causingcadherins in the upper epidermis, causing
detachment of keratinocytes.detachment of keratinocytes.
Desmoglein-l is present but only weaklyDesmoglein-l is present but only weakly
expressed in mucosae accounting for theexpressed in mucosae accounting for the
lack of mucosal involvement inlack of mucosal involvement in
pemphigus foliaceus.pemphigus foliaceus.
19. Clinical featureClinical feature
The onset is usually insidious with scattered, scalyThe onset is usually insidious with scattered, scaly
lesions involving the 'seborrhoeic' areas: scalp,lesions involving the 'seborrhoeic' areas: scalp,
face, chest and upper back. Blistering may not beface, chest and upper back. Blistering may not be
obvious because the cleavage is superficial and theobvious because the cleavage is superficial and the
small flaccid blisters rupture easily.small flaccid blisters rupture easily.
Oral lesions are uncommon.Oral lesions are uncommon.
Pemphigus foliaceus is generally regarded as aPemphigus foliaceus is generally regarded as a
benign disease which responds well to treatmentbenign disease which responds well to treatment
and may remit.and may remit.
22. TREATMENTTREATMENT
Potent topical or intralesional steroids or, ifPotent topical or intralesional steroids or, if
control is inadequate, prednisolone 20-40control is inadequate, prednisolone 20-40
mg/ day.mg/ day.
Azathioprine or cyclophosphamide areAzathioprine or cyclophosphamide are
effective adjuncts to oral steroids in severeeffective adjuncts to oral steroids in severe
cases. Hydroxychloroquine 200/mg twicecases. Hydroxychloroquine 200/mg twice
per day has also been recommended asper day has also been recommended as
adjuvant therapy. Intravenous Ig has beenadjuvant therapy. Intravenous Ig has been
reported as effective in resistant cases.reported as effective in resistant cases.
23. BULLOUS PEMPHIGOIDBULLOUS PEMPHIGOID
Bullous pemphigoid is an affliction of elderlyBullous pemphigoid is an affliction of elderly
people,with onset usually after 60 years ofpeople,with onset usually after 60 years of
age.age.
The blister in bullous pemphigoid isThe blister in bullous pemphigoid is
subepidermal with an intact and often viablesubepidermal with an intact and often viable
epidermis forming the roof.epidermis forming the roof.
Bullous pemphigoid commonly starts withBullous pemphigoid commonly starts with
itching and a non-specific rash on the limbsitching and a non-specific rash on the limbs
that may be either urticaria-like orthat may be either urticaria-like or
occasionally eczematous and rarely mayoccasionally eczematous and rarely may
simulate vesicular eczema.simulate vesicular eczema.
24.
25. PEMPHGOIDPEMPHGOID
Blisters may arise on erythematous and onBlisters may arise on erythematous and on
normal skin and may be associated with dermalnormal skin and may be associated with dermal
edema. The blisters are tense and domeedema. The blisters are tense and dome
shaped, obtaining a diameter of manyshaped, obtaining a diameter of many
centimeteres.centimeteres.
The blisters are tough and may remain intact forThe blisters are tough and may remain intact for
several days, the contents often becoming jelly-several days, the contents often becoming jelly-
like with coagulated fibrin.like with coagulated fibrin.
Mucosal lesions occur less frequently and areMucosal lesions occur less frequently and are
less severe than in pemphigus vulgaris and areless severe than in pemphigus vulgaris and are
usually confined to the mouth.usually confined to the mouth.
28. PEMPHGOIDPEMPHGOID
Untreated bullous pemphigoid runs aUntreated bullous pemphigoid runs a
chronic, self limiting course over a numberchronic, self limiting course over a number
of months or years.of months or years.
The disease duration is usually 3-6 years,The disease duration is usually 3-6 years,
with most patients achieving completewith most patients achieving complete
remission off treatment.remission off treatment.
29. TREATMENTTREATMENT
Topical and systemic steroids are theTopical and systemic steroids are the
mainstay of treatment. For localized BP,mainstay of treatment. For localized BP,
very potent topical steroids are oftenvery potent topical steroids are often
sufficient.sufficient.
Corticosteroid therapy has lowered theCorticosteroid therapy has lowered the
morbidity from the disease considerablymorbidity from the disease considerably
and most patients achieve remission off alland most patients achieve remission off all
therapy, but significant mortality of bulloustherapy, but significant mortality of bullous
pemphigoid still remains at 15-40%, and ispemphigoid still remains at 15-40%, and is
nearly always treatment related or relatednearly always treatment related or related
to the general condition and age of theto the general condition and age of the
patients.patients.
30. DERMATITIS HERPETIFORMIS
Definition. Dermatitis herpetiformis (DH) is a
rare, intensely pruritic,chronic, recurrent,
papulovesicular disease.There is an underlying
gluten-sensitive enteropathy that may be
asymptomatic. The mechanism by which
ingestion of gluten induces granular IgA
deposition in the skin and blistering is still
obscure.
There is a family history of dermatitis
herpetiformis or coeliac disease in 10.5% of
patients and it has been reported to be both
concordant and discordant in monozygotic twins.
31. PATHOGENESIS
The IgA deposits are gluten dependent, and are slowly
cleared from the skin once gluten is removed from the
diet. The Ag within normal human skin to which IgA
antibodies from DH sera bind is still unknown.
One of the most exciting developments of recent years
has been the recognition that autoantibodies and T-cell
reactions to tissue transglutaminases, and in particular
transglutaminase 2, are relevant to the pathogenesis of
coeliac disease .These antibodies have been
demonstrated in dermatitis herpetiformis.In addition, it is
now clear that the previously recognized antireticulin and
endomysial antibodies, in coeliac disease and dermatitis
herpetiformis, are associated with these antibodies and
require transglutaminase 2 to bind to tissues.
32. PATHOLOGY
Diagnostic histological changes are best seen in
the vicinity of early blisters or in lesions that
have not yet blistered.Neutrophils and
eosinophils accumulate within the dermal
papillae and form microabscesses. The
surrounding collagen is degraded, resulting in
detachment of the epidermis and a
subepidermal vesicle. Multilocular vesicles may
coalesce to form blisters; Direct
immunofluorescence is always positive. There
are granular deposits of IgA in the dermal
papillae There may also be C3 and IgG.
34. CLINICAL FEATURES
Dermatitis herpetiformis presents mainly between the
ages of 20 and 55 years, but can present both in
childhood and old age. The onset may be acute or
gradual, and pruritus is usually the first and predominant
symptom. Early lesions on the skin are erythematous
papules, urticarial weals or groups of small vesicles often
excoriated so rapidly that it may be impossible to find
one intact. The vesicles are usually grouped together on
plaques of erythema, and rarely blisters 1-2 cm in
diameter occur.
The distribution of the lesions is characteristic. The
extensor aspects of the limbs, especially the knees, just
below the point of the elbows, buttocks and the natal
cleft, are affected in the majority of patients The axillary
folds, shoulders, trunk, face and scalp are all frequently
involved.
35. There may be a feeling of malaise with the acutely active
disease. In addition, constitutional symptoms due to the
glutensensitive enteropathy can be present. The patient
may experience bouts of abdominal pain, constipation
and diarrhoea, and be undernourished.
Associated diseases. There are often associated
autoimmune diseases, particularly thyroid disease,
pernicious anaemia and diabetes.There is an association
with thyroid disease in up to 30% of patients. Lymphoma
is a well-recognized complication of dermatitis
herpetiformis, as are other malignancies although a
recent study contradicts this . Moreover, the protective
role of a gluten-free diet for the lymphomas has been
established.
36.
37. Differential diagnosis
The diagnosis should be suspected when any
persistent, pruritic, symmetrical eruption resists
topical treatment. In view of the pruritus and
involvement of the axillary folds and buttocks,
many patients are thought to have scabies, but
the absence of burrows or of contact cases
should help with the diagnosis. The most difficult
diagnostic problem is the group of patients with
chronic exudative eczema, papular urticaria and
chronic prurigo, some of whom may be dapsone
responsive. The histology and the lack of IgA
deposition should help establish the correct
diagnosis.
38. TREATMENT
Dapsone is the most widely used treatment for dermatitis
herpetiformis. The dose needed for the average case is
100-200 mg/ day but a few may require 400 mg/ day.
Patients at risk of glucose-6-phosphate dehydrogenase
deficiency should be screened prior to treatment.
Methaemoglobinaemia is common, reaching a steady
state after about 2 weeks, and may cause cyanosis,
breathlessness and angina. Hepatitis, the dapsone
syndrome (lymphadenopathy and hepatitis) and
agranulocytosis are serious, usually early complications.
Motor neuropathy may occur.
Although systemic corticosteroids are in the main
ineffective and not indicated, topical steroids may be
helpful in lessening symptoms.
39. A gluten-free diet is the treatment of choice in
the long term. It has been shown not only to
improve the enteropathy, but also to allow
discontinuation of drug therapy. It is usually
many months and sometimes years before
patients are able to reduce their dapsone
requirements. Often dapsone can be
discontinued altogether after 2-3 years on a
strict gluten-free diet, but some patients take
much longer . Reintroduction of gluten in
selected patients produced a relapse in skin
lesions .The gluten-free diet after 5-10 years
protects patients from lymphoma, and this is an
additional reason to recommend a gluten-free
diet.
