Seminar prepared under the guidance of Dr Abhirami mam during my first year of post graduation

1. Moderator : Dr. Abhirami
Presentor : Dr. Ravindra G O

2.  Introduction
 Etiology
 Diseases
 Approach

3.  Vesiculobullous disorders are common in children.
 Primary vesiculobullous disorders include
vesicles, bullae and pustules.
 It can either be very benign or potentially fatal in
somencases.
 They can be either inherited or acquired
depending on the etiology.

5. Pemphigus vulgaris(Dsg3)
Folicaeous(Dsg1)
Paraneoplastic(plakin)
Hailey hailey
Dariers
Grovers
Staphylococcus scaleded skin (Dsg 1)

6. VESICLE & BULLA
 A clear fluid lesion just below the epithelium which
ruptures to form an ulcer.
 If this is smaller than 5mm then it is a vesicle ,if
larger than 5mm than it is a bulla.

7. Intraepidermal blister Subepidermal blister
Thin, flaccid blisters which rupture
easily
Erosion, scaling or crusting
Pigmentation and scarring are not
common unless secondary infection
occurs
Tense bullae
Base Devoid of any pigmentation
Other Factor :
Scaling, Crusting , Pustules
Scarring
Erosions and ulcers
Haemorrhagic, petechiae
photosensitivity

10.  Infections
 Genodermatosis
 Inflammatory
 Drug reactions
 Traumatic
 Autoimmune
 Metabolic

11. Etiology
Infections
a) Viral (mc) HFMD
Varicella
Herpes labialis
Herpes zoster
b) Bacterial Bullous impetigo
SSSS
c) Fungal Congenital cutaneous candidiasis
Genodermatosis Epidermolysis bullosa simplex
Junctional epidermolysis bullosa
Dystrophic epidermolysis bullosa
Inflammatory dermatoses Pompholyx
Bullous papular urticaria
Bechets disease
Erythema toxicum neonatorum
Drug reaction Steven Johnson syndrome
Bullous fixed drug eruption
Bullous drug reaction
Traumatic Burns
Extravasation injuries

12. Autoimmune disorders Bullous SLE
Bullous pemphigoid
Metabolic disorders Acrodermatitis enteropathica

13.  Inflammatory eruptions characterized by
symmetrical erythema, edematous, or bullous
lesions of the skin or mucous membrane.
Causes :
 Infections – herpes simplex, coxsackie and echo
viruses, mycoplasma pneumonia.
 Drugs- penicillins, sulphonamides, and
barbiturates.
 Vaccines : BCG, Polio.

14. Pathogenesis:
 Hypersenstivity
 Cell mediated immune response to antigenic
stimulus resulting in damage to keratinocytes.
 HSV pol1 gene.

15. Clinical presentation
 Morphology- varying from erythematous macule,
papule, vesicle, bullae or urticaria appearing
plaque to patch of confluent erythema.
 Classical lesion: doughnut shaped, target like(
iris or bull’s eye) papule with an erythematous
outer border, an inner pale ring, and a dusky
purple to necrotic center.

19.  Abrupt onset, symmetrical cutaneous eruptions
most commonly involving extensors upper
extremities, palms and soles.
 Hemorrhagic lesions of lips( vermilion border) and
oral mucosa can also occur.
 Red macule or urticarial plaqua that expand
centrifugally to form lesion upto 2cm with a dusky to
necrotic centre.
 Appear with in 72 hr and remain fixed in place (7
days ) .
 Malaise, fever and arthralgia.
 Typically resolves in 2- 4wks.

20.  Pathology

21. Differential diagnosis
 Skin lesions- bullous pempghigoid, urticaria and
dermatitis herpatiformis.
 Oral lesions- apthous stomatitis , pemphigus,
herpetic stomatitis.

22. Treatment
 Supportive- emollients, NSAID, systemic anti
histaminics.
 Vesicles and bullous or errosive lesions can be
treated with intermittent burrows solution , saline or
tap water compression.
 Severe mucosal disease- opiods for pain, diligent
oral hygiene.
 If frequent or sever EM is preceded by herpes
simplex, acyclovir 200mg orally five times daily may
prevent attack.

23.  Steven johnsons syndrome (SJS) and toxic
epidermal necrolysis (TEN) exist along a
spectrum.
 SJS –defined as affected body surface area
<10%.
 SJS- TEN overlap syndrome- 10-30%.
 TEN- > 30%.-MOST SEVERE DISORDER of
the spectrum
 HLA-B*1502 and HLA-B*5801.(han chinese pts
receiving carbamazepine and in japanese-
allopurinol)

24. Etiology
 Drugs- sulfonamides, NSAIDS, antibiotics, and
anticonvulsants.
 .

25. Clinical manifestation
 Erythematous macules develop central necrosis
to form vesicles, bullae, and areas of denudation
of face, trunk, and extremities.
 Involvement of 2 or more mucosal surfaces,
eyes, oral cavity, upper airway or esophagus,
GIT or anogenital mucosa.
 Burning sensation oedema and erythema of the
lips and buccal mucosa, followed by
development of bullae, ulcerations, and
hemorrhagic crusting.

26.  Pain from mucosal ulceration is severe, but skin
tenderness is minimal to absent.
 Corneal ulceration, anterior uveitis,
panopthalmitis, bronchitis, pneumonitis,
myocarditis, hepatitis, enterocilitis, polyarthiritis,
hematuria, acute tubular necrosis leading to
renal faliure may occour.
 Disseminated cutaneous bullae and erosions
may result in increased insensible water loss
and a high risk of bacterial superinfection and
sepsis.

28. Pathogenesis
 Drug specific CD8+ cytotoxic T cells, with
perforins/granzyme B triggering keratinocyte
apoptosis.
 Followed by expanded entacemnet of apoptosis
involving the interaction of soluble Fas ligant with
Fas receptor.

29.  Supportive and symptomatic.
 Discontinue the offending drug.
 Ocular- cryopreserve amniotic membrane during acute
phase, early topical steroids.
 Oral – mouthwashes and glycerin swabs, topical
anesthetics( diphenhydramine, viscous lidocaine)
before eating.
 Skin lesions- denuded- saline or burrows solution
compression.
 Iv fluids, nutritional support, sheep skin or airfluid
bedding .

30.  Antibiotics – documented urinary or cutaneous
infections or suspected bacteremia(
staphylococcus aureus or pseudomonas
aeruginosa) , leading cause of death.
 IV immunoglobulin ( 1.5-2g/kg/day x 3 days)
considered in early disease.

31.  Mainly caused by drugs .
 Sulfonamides, barbiturates, NSAIDS, phenytoin,
allopurinol, and penicillin , carbamezapine,
phenobarbiton, valproic acid, quinolones,
 Dermatological emergency with mortality rate of
61%.

32. Clinical features
 Prodrome – fever, malaise, locaised skin
tenderness and diffuse erythema.
 Inflammation of eyelids, conjuctiva, mouth and
genitals may precede skin lesions.
 Painful localized erythema disseminates rapidly,
flaccid blisters occur or the epidermis peels off in
large sheets with gentle touching or
pulling(Nikolsky’s sign).
 Widespread area of erosions with involvement of
all mucous membranes occurs in 24-72 hrs, and
patient may become gravely ill.
 Affected area mimic like 2nd degree burn.

34.  Dislogement or pealing of epidermis layers on
shearing or tangential pressure.
 Denotes acantholysis.
 True – only partial thickness of epidermis peals
off, elicited over perilesional areas or distinct
sites. Eg: pemphigus vulgaris.
 Pseudo- full epidermal thickness peals off, only
on inflammed site or purpuric skin. Eg: TEN,
SJS.

35.  Fluid and electrolyte imbalance and multiorgan
sequelae ( pneumonia, GI bleeding,
glomerulonephritis, hepatitis, infections) can
lead to death.
 Difficult to distinguish from morbilliform drug
eruptions or erythema multiforme minor, and
stevens- johnson syndrome before widespread
erythema or epidermal denudation occours.

39. Character Staphycoccal
scalded skin
syndroem
Stevens johnson
syndroem
Toxic epidermal
necrolysis
Presentation Sick child Very sick child Very sick child
Clinical Vesicle, bulla,
pustule
Bulla , target
lesions
Denuded skin
Mucosal
involvement
No Yes No
history Infection,
throat,eye,vagina
Infections and
drugs
Drugs
Body surface area NA 10% >30%
Usual sites Around orifice In and around
orifice
All over
biopsy Subcorneal, sub
epidermal
Intra epidermal subcorneal
Cytology Not contributory Inflammatory cells Epithelial cells
Treatment antibiotics Antibiotics and
steroids
Antibiotics,
steroids and IV Ig

40.  Hospitalization
 Suspected drug stopped immediately.
 Isolated to minimize exogenous infections.
 Treated as severe burns by protecting the skin
and denuded area from trauma and infection
and by replacing fluid and electrolyte losses.
 Septicemia recognised early and treated
promtly.
 Opthalmic, urological and skin care.

41.  Younger children, particularly neonates
 Extensive skin involvement
 Increases respiratory rate
 Increased cardiac rate
 Drop in systolic BP
 Reduced neutrophil count
 Decreased urinary output

42. Simplified acute physiological score(SAPS)
 Hourly RR, PR,BP,UO
 Fourth hourly temp, consiouness, gastric
emptying.
 Daily body weight, extension of skin involvement,
fluid losses, blood chemistry, and ABG. Urine-
Glycosuria.
 Bacteriology of skin lesion atleast once every day.

44.  Heterogenous group of congenital genetic
blistering disorders.
 Characterized by induction of blisters by trauma
and exacerbation of blistering in warm weather.
Types
 Epidermolysis bullosa simplex(EBS)
 Junctional epidermolysis bullosa(JEB)
 Dystrophic epidermolysis bullosa(DEB)
 Kindler syndrome.

46.  Non-scarring autosomal dominant disorder.
 Defect keratin 5 or 14 , which makes up
intermediate filaments of basal keratinocytes.
 Cytolysis of the basal cells – intraepidermal bullae.

47. EBS generalized ( formally koebners)-
 At birth or neonatal period.
 Sites – hands, feet, elbows, knees, legs, and scalp.
 Intraoral-minimal
 Healing- with minimal or no scar.
 Secondary infection.
 Propensity reduces with age, good long term
prognosis.
 Treatment- drainage by puncturing, top intact to

49. EB- localized ( weber – cockayne)
 Manifests when the child begins to walk, or untill
puberty or early adulthood, when heavy shoes are
worn or feet are exposed to increased trauma.
 Sites- hand and feet.

51. EB- Dowling- Meara ( herpetiformis)
 Grouped blisters resembling those of herpes
simplex.
 During infancy- blistering severe and extensive,
nail dystrophy, sheeding and milia formation,
mild pigmentory changes without scarring .
 Hyperkeratosis and hyperhydrosis of the palms
and soles may develop.

52.  Two types
 JEB- Herlitz ( lethal)
 JEB- Non Herlitz ( non Lethal)
 Defect in laminin 322, glycoprotein, associated
with anchoring filaments beneath the
hemidesmosomes.
 Defect in other hemidesmosome components
such as type XVII collagen(BP 180).
 In JEB – pyloric atresia- defect in α6β4 integrin.

53. JEB – Herlitz
 AR, life threatening.
 Generalized and most severe form of JEB
where blisters appear all over the body and
often involve mucous membranes and internal
organs.
 Blisters appear at birth and become more
widespread soon after.
 Dystrophy of the nails, defective dentition with
early loss of teeth, growth retardation ,

54.  Hoarse cry or cough is indicative of internal
organ involvement.
 complications such as infections, malnutrition
and dehydration usually lead to death in early
infancy.

56. JEB- Non Herlitz
 Generalized blistering and mucosal involvement
present at birth or soon after.
 Scalp , nail and tooth are more commonly
involved.
 All conditions assosiated with Herlitz type may
be seen but are usually milder.
 Generalized atrophic benign EB- blistern heal
with a distinctive atrophic appearance, blister
worsens in warm climate.
 Pyloric atresia

58.  Light microscopy and electron microscopy-
 Cleavage plane in the lamina Lucida, between the
plasma membrane of the basal cells and basal
lamina.

59.  Dominant and Recessive forms.
 All form result due to mutation in collagen VII, a
major component of anchoring fibrils that tether
the basement membrane and overlying epidermis
to its dermal foundation.
 Sub-epidermal blister in all forms.

60. Dominant DEB-
 Most common type.
 Generalized blistering present at birth
 Blistering becomes localized to hands, feet ,
elbow or knees as child grows older and in
response to friction.
 Abnormal nails and nail losses.
 Lesions heals promptly, with formation of soft,
wrinkled scars, milia and alternation in
pigmentation.

61. Recessive DEB( recessive DEB Hallopeau-
siemens)
 Most incapacitating form.
 May be mild or severe presentation.
 Generalized severe blistering is more common
and involves large area of skin and mucous
membrane.
 Blisters heal but with scarring and deformity
causing limited movements as fingers and toes
may be fused together ( mitten hand deformity).

62.  Flexion contractures of joints secondary to
scaring of the integuments, esophageal erosions
and strictures , scarring of the buccal mucosa.
 Mucous membrane lesions may cause severe
nutritional deprivation even in older children,
whose growth may be retarded.

65.  No cure, symptomatic treatment .
 Primary aim to protect the skin and stop blister
formation, promote healing and prevent
complication.
 Multispecialty treatment

66. General measures in caring for patients:
 Maintain a cool environment and avoid
overheating.
 Foam padding or sheep skin to help reduce
friction on furniture such as beds, chairs.
 Clothing made of soft non irritating fabrics.
 Pierce, drain and dress blister to promote
healing.
 Avoid nappies in infants with severe EB, instead
place child on clean pad.

67.  Rare blistering disorder.
 Nearly identical to chronic bullous disease of
childhood.
 Chronic bullous disease presents before puberty
with abrupt onset of blister in genital region, later
affecting hands, limbs, feet and face.
 In adults limbs are first site.

69.  Clear round or oval blister arising form a normal
looking or red skin.
 Red flat or elevated patches may arise, studded
with small blister( vesicle) or large ones(
bullae),often target shaped.
 String of bead sign- tendency of new blister to arise
in a ring around the old one( cluster of jewels).
 Crust, scratch marks , sores and ulcers may arise.

70.  50% will have ulceration in the lips and inside the
mouth.
 Eyes- irritation , dryness, light sensitivity and
blurred vision.

72.  Biopsy- subepidermal blister.
 Direct immunofluorescence – immunoglobulin IgA
along the basement membrane of the epidermis in
a linear pattern.
 Indirect immunofluorescence- IgA antibodies in
blood.
 Target antigen- basement membrane components.

74.  Most children improve or clear with Dapsone 50-
100 mg daily.
 Other medications:
 Corticosteroids(prednisolone)
 Erythromycin

75.  Pemphigus is severe and potentially life-
threatening.
Types
1. Pemphigus vulgaris
 is the most common, which accounts for at least
three-quarter of all cases, and for most of the
deaths.
2. Pemphigus vegetans
3. Superficial pemphigus
 also has two variants: the generalized foliaceus
type and
localized erythematous type.
4. Paraneoplastic pemphigus
 arises in association with a neoplasm such as

76.  Autoimmune diseases, (IgG) antibodies bind to
antigens within the epidermis, mainly
desmoglein 3 (in pemphigus vulgaris) and
desmoglein 1 (insuperficial pemphigus), causing
the keratinocytes to fall apart (acantholysis).

77. Pemphigus vulgaris
 is characterized by flaccid blisters of the skin
and mouth which rupture easily to leave
widespread painful erosions.
 Most patients develop the mouth lesions first.
 Shearing stresses on normal skin can cause
new erosions to form (a positive Nikolsky
sign).

78.  Sometimes the ulcers are joined together to
make a confluence, this condition is very painful.
 It has a variable course might involve skin,
oesophagus, cervix.
 Protein/fluid,electrolyte and weight loss
/secondary infections.
 Fatal if untreated.

80. PATHOGENESIS:
 It is an autoimmune disease
 There are circulating antibodies of type IgG.
 These antibodies are reactive against the
desmosomes or the tonofilament complex.
 There destruction or disruption of these
tonofilament complex ,resulting in the loss of
attachment from cell to cell.

82. HISTOPATHOLOGY:
 Intra epithelial vesicles or bulla and cleft like
spaces
are produced by acantolysis . These changes
are in the stratum spinosum or the prickle cell
layer
 Inflammatory cells are very scanty however
eosinophils may be seen.
 Acantholytic statum spinosum cells occur singly
or
are in the forms of clumps lying freely within the
blister fluid.
These cell loose there polyhedral morphology
rather they are small rounded and contain hyper
chromatic nuclei called the TZANK CELLS.

85.  Skin biopsy
 Electron microscopy has shown that widening of
the intercellular space is followed by splitting of
the desmosome junctions.
 Direct & indirect immunofluorescence
 ELISA

86.  High mortality rates previously
 Introduction of systemic corticosteroids like
prednisolone in stable cases.
 Prednisolone plus azathioprine
 methotrexate and cyclophosphamide in
progressed or advanced cases.

88. Vesicobullous
lesion in an
infant/child
Locali
zed
Vesicles on an erythematous base
Grouped
painful
with lesion
HFM
Hs
hand, foot
and mouth
disease
Hz

91. Vesicobullous lesion in an infant/child
Localized
Papulovesicular
Itching Pain
Burrows Exposed areas
Scabies insect bite reaction ORF
Cow
pox

92. Vesicullobullous
Periorifacial Photosensitivity Localized Recurrent
(Palms & Sole)
(Penis/scrotum)
Vesicles/Bulla Atrophy
Erosions Milia/scar EBS(Weber-Cockayne)
FDR
Acrodermatitis PORPHYRIA( Neurovisceral Symptoms)
Enteropathica
No YES
No
Late Onset Early
Onset
PCT Variegate Porphyria
Mutilating
Hereditary Coproporphyria

93. Generalized
Systemically unwell Systemically well
Infections Drug Induced Nikolsky Sign
Varicella TEN Yes
No
Meningo- SJS Pemphigus
Coccemia Oral lesions Tense
Flaccid
No Yes Bulla
Vesiculo-
Pustule
Head & Neck Seborrheic Annular
Hailey-Hailey
Endemic PF IgA Pemphigus

94. Tense Bulla With Oral Lesions
Yes
No
Grouped
Lesion With
Subepidermal Genetic Blistering
Itching
Autoimmune Dermatitis
Herpetiform
Trauma prone site Grouped Lesion With
Scarring
EBS( Koebner) (Dowling
Meara)
Flexures Annular
Scarring(Milia)
Palms/sole Buttock/periorofacial

95.  Nelsons textbook of pediatrics 20th edition.
 Ijpp 2015 dermatological emergencies
 Ijpp 2005 dermatologucal emergencies
 Ijp vesicobullous disorders in children.