2. Introduction
• A blister is a fluid filled cavity formed within or beneath the
epidermis.
• Can be categorized as vesicles or bullae.
• Vesicle- < 0.5 cm in diameter
• Bulla- > 0.5 cm in diameter
• Blisters are an obvious sign of disease that always draw
attention of patient and physician.
6. • Disorders, in which blistering is the primary event are
traditionally termed as blistering disorders or vesiculobullous
disorders.
• This group includes hereditary blistering disorders and
immunobullous diseases.
8. Age of onset
Pemphigus vulgaris
Middle age (40-60 yrs)
Pemphigus foliaceus
Middle age
Paraneoplastic pemphigus
Adult, children
Bullous pemphigoid
Elderly (60-75 yrs)
Mucous membrane pemphigoid
Old age (60-80 yrs)
Pemphigoid gestationis
Pregnant women
Dermatitis herpetiformis
Adult
Linear IgA disease
Before 5 & after 60 yrs
EBA
Adults & children
Hailey- hailey disease
Adults
Epidermolysis bullosa
At birth or during infancy
9. Initial site
Pemphigus vulgaris
Oral mucosa
Pemphigus foliaceus
Scalp, chest
Bullous pemphigoid
extremities
Mucous membrane pemphigoid
Oral or other mucosa
Pemphigoid gestationis
Periumblical, extremities
Dermatitis herpetiformis
Trunk, scalp
Linear IgA disease
Genital in children; no
predilection in adults
EBA
Mucosa, extremities
Hailey- hailey disease
Friction sites
10. Mucosal involvement
Pemphigus vulgaris
Almost all
Pemphigus foliaceus
None
Intercelluar IgA dermatosis
Uncommon
Paraneoplastic pemphigus
Severe mucositis
Bullous pemphigoid
10 – 40%, transient, mild
Mucous membrane pemphigoid
Almost all
Pemphigoid gestationis
Rare
Dermatitis herpetiformis
Rare
Linear IgA disease
80%
EBA
50%
Hailey- hailey disease
Uncommon
15. Pemphigoid gestationis
Urticated plaques, tense blisters
Dermatitis herpetiformis
Papulovesicles
Linear IgA disease
Urticated plaques, annular lesions,
tense blisters
EBA
Urticated plaques, tense blisters,
milia ,Scarring
Hailey- Hailey disease
Flaccid vesicopustules, crusted
erosions or expanding circinate
plaques appear in areas exposed to
friction
16. Pemphigus vulgaris
A: flaccid blisters on normal skin.
B: superficial blisters and erosions which take long to heal.
17. Pemphigus vegetans: heaped up vegetating
plaques in flexures
Pemphigus foliaceus: extensive areas of scaling and crusting
and no blisters. removal of scale-crust reveals a minimally
moist area.
20. Chronic bullous disease of childhood: string of
pearl appearance is typical
Dermatitis herpetiformis: grouped vesicles
develop either on normal or erythematous
skin. Since the lesions are extremely itchy,
they are rapidly excoriated
21. Differentiating features of Epidermolysis bullosa
Type
Time of inhe Clinical features
present riatn
ation
ce
MM/Nail Associated
/Teeth
features
WeberCockyne
EBS
Childho AD
od
Localised to palms, Normal
soles, waist or
neck, no scarring,
more in summers
Hyperhydrosis good
of palms,
soles
Koebner
EBS
At birth AD
or
infancy
On occiput, back
or legs in infancy,
Hands or feet in
childhood, no
scarring
Aggravated by
warm
weather,
Hyperhydrosis
of palms,
soles
Normal
Progno
sis
May
improv
e after
puberty
22. Epidermolysis bullosa
Type
Time of inhe Clinical features
present ritan
ation
ce
MM/Nail/Te Associated
eth
features
Progno
sis
Severe
in
infancy,
better
with
age
DowlingAt birth AD
meara EBS or
infancy
Herpitiform
blisters on trunk,
limbs, neck,
No scarring
MM, nails
involved
Milia,
hyperpigme
ntation
seen
EBS with
muscular
dystrophy
Blisters on hands
and feet then
generalized
Nail
deformities,
MM
involvement
, alopecia
Muscle
Poor
weakness
early or late
onset,
milia
At birth AD
or early
infancy
23. Epidermolysis bullosa
Type
Time
inhe Clinical features
of
ritan
presen ce
tation
MM/Nail/
Teeth
Associated
features
Progno
sis
Autosomal
recessive
lethal EBS
At
birth
AR
Generalised more
on distal limbs
Normal,
oral
mucosa
mildly
affected
No scarring
or milia
seen
Poor
EBS with
mottled
pigmentati
on
At
AD
birth
or
infancy
Reticulate pattern
of macular
pigmentation over
trunk, limbs
Nails
involved,
MM, teeth
normal
Punctate
Improv
keratoses on es with
palms and
age
soles
24. Epidermolysis bullosa
Type
Time of inhe Clinical features
present ritan
ation
ce
MM/Nail Associated
/Teeth
features
Prognosi
s
Poor,
child
may die
in early
infancy
due to
infection
Herlitz JEB At birth AR
or soon
after
birth
Severe generalised
blistering, skin
fragility, difficult to
handle child,
erosions slow to
heal
Mm,
nails
teeth
involved,
larynx
may be
involved
Sepsis or
multiorgan
failure may
occur
NonAt birth AR
Herlitz JEB
Generalised
blistetrs, scalp
involvement
causes alopecia
Involved
Pigmentation Improve
and nevi
s with
seen
age
25. Epidermolysis bullosa
Type
Time inhe Clinical features
of
ritan
prese ce
ntatio
n
MM/Nail/ Associated
Teeth
features
Progno
sis
JEB with
pyloric
atresia
At
birth
AR
Generalised skin
and mucosal
blisters
Nail, teeth Non- bilious
involved
vomiting in
newborn
Very
poor
Progressive
JEB
5-8
years
AR
Hands, feet, knees, Nail, teeth Finger
elbows (sites of
involved
contractures,
friction)
deafness
good
26. Epidermolysis bullosa
Type
Time of inhe Clinical features
present ritan
ation
ce
MM/Nail/T Associated
eeth
features
Progno
sis
Dominant At birth AD
dystrophic or early
EB
infancy
Hands, feet, knees, Nail
elbows (sites of
dystrophy,
friction)
MM, teeth
normal
White
Good
papules on
trunk, pasini
variant
Hallopeau
- siemens
EB
At birth AR
or early
infancy
Large, flaccid
bullae at sites
friction, healing
slow, scarring
Dystrophic
nails,
scarring
alopecia,
carious
teeth
Flexural
contractures
, esophagial
strictures,
inability to
protude
tongue
Poordeath
by 3-4
decade
Non
Hallopeau
- siemens
EB
At birth AR
Skin and mucosae
are fragile
Changes
are
localised
Few
complicatio
ns
good
27. Configuration
• Grouping of blisters: dermatitis herpetiformis.
• String of pearls sign- annular, polycyclic lesions often with
blistering around the edge in CBDC
28. NIKOLSKIY SIGN
• A positive Nikolskiy sign indicates intraepidermal cleavage and
differentiates intraepidermal blisters from subepidermal
blisters.
• It is pathognomonic of pemphigus and staphylococcal scalded
skin syndrome
• The sign is best elicited by applying lateral pressure with the
thumb or fingerpad on skin over a bony prominence.
• This results in a shearing force that dislodges the upper layers
of epidermis from the lower epidermis producing an erosion.
29. • Specifically, elicitation of the sign can help distinguish
pemphigus vulgaris, which is strongly associated with the sign,
from bullous pemphigoid, in which the sign is usually absent.
• other diseases associated with a positive Nikolsky’s sign
-toxic epidermal necrolysis, bullous impetigo, and
epidermolysis bullosa
30. (a) Eliciting Nikolsky's sign on perilesional skin. Note the tangential
pressure, (b) Eliciting Nikolsky's sign, peeling of skin revealing moist
erosion
31. BULLA SPREAD SIGN
• In the traditional "bulla spread" sign or Lutz sign, the margin
of an intact bulla is first marked by a pen.
• Slow, careful and unidirectional pressure applied by a finger to
the bulla causes peripheral extension of the bulla beyond the
marked margin.
• The bulla thus extended has an irregular angulated border in
pemphigus vulgaris, while a regular rounded border is
observed in bullous pemphigoid or other subepidermal
blistering disorders.
32. • This sign is positive in all varieties of pemphigus and many
cases of subepidermal blisters, including bullous pemphigoid,
DH , EBA, cicatricial pemphigoid, dystrophic epidermolysis
bullosa, SJS, TEN.
• Due to fragility of the roof of the blister it is usually negative
in Hailey-Hailey disease and staphylococcal scalded skin
syndrome.
33. Tzanck Smear
• Is a quick bedside test.
• A fresh blister is ruptured, the roof detached and the floor
scraped using a scalpel blade.
• If blister not present, then taken from erosion, after removing
the crust.
• The material so obtained is spread on a glass slide and stained
with Giemsa stain.
35. PEMPHIGUS VULGARIS
• It reveals multiple acantholytic
cells (Tzanck cells).
• A typical Tzanck cell
–
–
–
–
Large round keratinocyte
Hypertrophic nucleus,
Hazy or absent nucleoli, and
Abundant basophilic cytoplasm.
• The basophilic staining is deeper
peripherally on the cell leading to
a perinuclear halo.
36. Other differentials
Differential
History
Examination
Herpes simplex
primary or recurrent outbreak of
herpes simplex virus (HSV) vesicles
associated with tenderness, burning,
or tingling; HSV-1 is spread primarily
through direct contact with infected
saliva or other infected secretions,
HSV-2 is spread primarily through
sexual contact, symptoms typically
start within 1 week after exposure
grouped vesicles on an
erythematous base, may
evolve to pustules or
erosions, lesions resolve
within 2 to 6 weeks
Herpes zoster
(shingles)
prior history of varicella infection,
presents with prodrome of pain,
itching, hyperesthesia followed by
vesicular eruption
painful, grouped vesicles
on an erythematous base
in a sensory dermatomal
distribution, rarely crosses
midline
37. Differential
History
Examination
Varicella,
initial viremia between days 4
acute(chickenpox) and 6; appearance of
characteristic vesicular eruption
on erythematous base, often
referred to as "dewdrops on rose
petals," low-grade fever, malaise,
and headache
successive crops of lesions
appear over several days on
trunk, face, and oral mucosa;
typically lesions are in
different stages of evolution
from vesicles to crust and do
not scar
Impetigo
bullae are ≥2 cm in diameter
and initially clear,
subsequently becoming
turbid; buccal mucosa may be
involved, classic facial
yellowish to golden crusting,
streptococcal form tends to
have thicker and darker crusts
typically occurs in children, very
contagious, risk factors include
increased humidity, poor
hygiene, malnutrition and
overcrowding, concomitant skin
disease
38. Differential
History
Examination
Staphylococcal typically child or adult with
scalded skin
renal insufficiency
syndrome
prodromal fever, tender skin
evolve to generalized erythema
with flexural accentuation and
then flaccid bullae formation;
Nikolsky sign present,
desquamation follows starting in
flexural areas; in contrast to toxic
epidermal necrolysis, does not
affect oral mucosa and may be a
helpful clue to diagnosis
Congenital
syphilis
primarily acrally located vesicles
and bullae, may be hemorrhagic
40% of infected newborns have
skin findings, neonate develops
lesions within first 2 weeks of
life through transplacental
transmission, mother with
history of secondary or tertiary
syphilis
39. Differential
History
Examination
Eczematous
dermatitis
(contact,
nummular, and
pompholytic)
personal or family history of atopy,
recent exposure to chemicals,
personal hygiene products, fabrics,
or plant allergens (e.g., poison ivy,
poison oak)
predominantly localized
distribution of vesicles and
papules with surrounding
erythematous base, later
lesions may be covered by
scale or crusting
Friction blister
recent activity involving affected
area (new shoes, gloves, or
products)
tense bullae in area of
pressure or friction
Miliaria
exposure to hot or humid climates, pruritic or asymptomatic
febrile illness in bedridden patient, papules or vesicles
layered clothing preventing
dissipation of heat or moisture
40. Differential
History
Examination
Coma bullae
coma from trauma, illness, or an
overdose of a narcotic drug
erythema with vesicles or
bullae at sites subjected to
pressure (hands, wrists,
scapulae, sacrum, knees,
heels)
Bullous arthropod recent arthropod exposure in a
bite reaction
sensitized patient, typically present
as grouped pruritic or
asymptomatic blisters in patients
who are otherwise well
grouped pruritic or
asymptomatic blisters,
distribution and location of
the lesions usually localized
to a specific area of body
(depending on causative
arthropod)
41. Differential
History
Examination
Nutritional
deficiencies (zinc,
biotin, niacin,
essential fatty
acids)
inherited or acquired deficiency,
breastfed newborns, history of
parenteral nutrition, characteristic
cutaneous finding is a
photosensitive eruption
(preferentially involving the face,
neck, upper chest, dorsal hands,
and extensor forearms), which
worsens in spring and summer
dermatitis is bullous or
pustular, periorificial and
acral locations, associated
erythematous eroded,
crusted patches; with
repeated sun exposure, the
involved areas become
thickened, scaly, and
hyperpigmented
Diabetic bullae
(bullosis
diabeticorum)
longstanding history of diabetes,
spontaneously healing blisters
within 4 to 5 weeks of onset
painless noninflammatory
blisters typically on acral
locations, including
amputation sites
42. Differential
History
Porphyria cutanea photosensitivity, fragility of suntarda
exposed skin that results in
blistering and erosions of the
dorsal hands, forearms, ears, feet,
and face; ingestion of alcohol,
estrogens, and polychlorinated
cyclic hydrocarbons exacerbates
condition
Pseudoporphyria
cutanea tarda
Examination
tense blisters on sunexposed skin, heal with
scarring, dyspigmentation,
and milia; hypertrichosis,
sclerodermatous
thickenings, and scarring
alopecia
hemodialysis, drug exposures
bullae on sun-exposed body
(NSAIDs, furosemide, nalidixic acid, areas (face, ears, dorsal
tetracycline), skin fragility,
hands, forearms)
photosensitivity, absence of
hypertrichosis, and skin sclerosis
43. Differential
History
Examination
Incontinentia
pigmenti
X-linked dominant, female infant 4
to 6 weeks old with vesicles in a
patterned distribution (Blaschko
lines), cutaneous features evolve
through 4 stages from infancy to
adolescence
noninflammatory vesicles in
a patterned distribution
(Blaschko lines),
abnormalities of teeth, eyes,
hair
Bullous
ichthyosiform
erythroderma
(epidermolytic
hyperkeratosis)
presents at birth, or shortly after,
with erythema, blistering, or
peeling; may be confused with
staphylococcal scalded skin
syndrome or epidermolysis bullosa
widespread erythema,
blistering and peeling infant
with or without palmarplantar involvement
44. Differential
History
Examination
Mastocytosis
acquired solitary or widespread
cutaneous eruption, lesion
periodically urticates and blisters
then returns to original form
5 mm to 15 mm papules,
yellow-brown to yellow-red
in color; edema, urtication,
and vesicle and bullae
formation, urticaria
surrounding erythematous
flare when rubbed (Darier
sign)
Bullous lupus
erythematosus
occurs in patients with a diagnosis
of systemic lupus, sun-exposed
skin is preferentially involved
lesions are not pruritic or
symmetric, do not have a
predilection for extensor
surfaces of arms, elbows,
knees, or scalp; vesicles and
bullae typically photodistributed or widespread,
asymptomatic
45. Differential
History
Examination
Erythema
multiforme
ingestion of new medications in
the days or weeks before onset,
implicated medications include
antibiotics (trimethoprimsulfamethoxazole), anticonvulsants
(lamotrigine), NSAIDs, and
allopurinol
characterized by atypical
targetoid lesions, macules,
vesicles, bullae on palms and
soles; may be generalized
Stevens-Johnson
syndrome
more fulminant form of erythema
multiforme with systemic and
mucosal involvement of <10% of
body surface area, severe
mucocutaneous reaction with
prodrome of fever, malaise, chills,
1 day to 2 weeks before onset
palms, soles, and extensor
surfaces with macules, may
evolve to papules, vesicles,
bullae, urticarial plaques, or
confluent erythema; center
of lesions purpuric, vesicular,
or necrotic imparting
targetoid appearance,
secondary infection follows