VESICULOBULLOUS DISORDERS

1. VESICULOBULLOUS
DISORDERS
DR PRIYANKA DAYALANI
DERMATOLOGY RESIDENT
DR PDMMC AMRAVATI

2.  Definition -The immunobullous disorders represent a group of conditions
characterized by antibody-mediated autoimmune responses against structural
elements of the skin resulting in blistering of the skin and mucosae.
 IMMUNOBULLOUS disorders can be broadly grouped into the pemphigus group
(intra epidermal split ) and pemphigoid group (sub epidermal split ).

6. Pemphigus vulgaris Dsg3>>Dsg 1
Pemphigus foliaceous Dsg 1
Bullous pemphigoid BP Ag 2>>BP Ag 1
Linear IgA Disease BP Ag 2
Mucous membrane pemphigoid BP Ag1, BP Ag 2, Laminin 5,
Collagen 7
Epidermolysis bullosa aquisita Collagen 7
Pemphigus herpetiformis ,
Drug induced pemphigus
Dsg1>Dsg3
IgA pemphigus Dsg 1,Dsg 3,Desmocollin

7. PEMPHIGUS
 Definition- Pemphigus is a group of chronic autoimmune blistering diseases
characterized by the presence of antibodies against desmosomal adhesion
proteins.
 The incidence of pemphigus is low but variable worldwide, ranging from 0.05 to
2.7/100 000/year.
 PV can occur at any age but is usually seen between the fourth and sixth
decades of life
 Pemphigus seems to affect men and women equally though some studies have
suggested a slight female preponderance

8. ENVIRONMENTAL FACTORS
 Smoking may have a protective role in pemphigus .
 Endemic form of the disease (FOGO SELVAGUM )-
Majority of patients live near rivers and black flies (simulium spp) have thought to be
involved in the pathogenesis of the disease.
 Organophosphate pesticides block the acetylcholine breakdown pathway and so may
lead to acetylcholine accumulation with resulting loss of cell–cell adhesion in the
epidermis

9. PATHOGENESIS
 AutoAbs go and bind to desmosomes and this leads to release of mediators
causing keratinocyte apoptosis .
 ACANYHOLYSIS +APOPTOSIS - APOPTOLYSIS
 Number of mechanisms have been suggested to be involved including stearic
hinderance by
 ANTI –Dsg antibodies .
 Protease activation.
 Disruption of intracellular signalling pathways .

10. PEMPHIGUS VULGARIS
CLINICAL FEAUTURES
 ORAL LESIONS - PV presents with oral lesions in 50–70% of patients.
Intact bullae are rare in the mouth and more commonly patients have ill‐defined irregularly shaped
buccal or palatal erosions which are slow to heal.
Can be collapsed bullae covered with greyish necrotic slough having little or no surrounding
inflammation .
The erosions extend peripherally with shedding of the epithelium.
Other mucosal surfaces may be involved, including the conjunctiva, nasopharynx, larynx,
oesophagus ,urethra, vulva and cervix .

11.  FLACCID BULLAE - Flaccid blisters filled with clear fluid either arise on normal skin or
an erythematous base.
 The contents may become turbid or the blisters rupture, producing painful erosions
which extend at the edges as more epidermis is lost.
 The head and neck ,axillae ,trunk ,groin ,pressure points are common sites of afflication
.
 Healing occurs without scarring.
Some lesions might heal with seborrheic keratosis like changes called post pemphigus
acanthomata .
 Nikolsky sign – Positive

15. HISTOLOGY
 Intraepithelial blister formation just above the basal layer forming a “suprabasal
split”
 Basal cells remain attached to the basement membrane but separate from one
another and stand like a ‘row of tombstones’ on the floor of the blister.

16. TZANCK SMEAR
 PREPARED from the base of the blister ,stained with Giemsa stain .

17. PEMPHIGUS VEGETANS
 Most benign Variant of pemphigus vulgaris characterised by vegetating erosiions
primarily in the flexures .
 2 subtypes are :
1. The severe NEUMANN type
2. The milder HALLOPEAU type.
Tumid ,vegetating ,papillomatous and hypertrophic plaques are formed in the
intertriginious areas (axillae ,groin ,inframammary folds )and the flexural areas .
Cerebriform tongue may also be seen .

20. PEMPHIGUS FOLIACEOUS
 The onset is usually insidious with scattered, scaly lesions involving the
‘seborrhoeic’ areas of the scalp, face, chest and upper back ,also has a
characteristic musty odour .
 Scales separate leaving well‐demarcated crusted erosions surrounded by
erythema, sometimes with small vesicles along the borders.
 Nikolsky sign is positive
 Small flaccid bullae with crusting and scaling .
 Target antigen is Dsg1 .

25. Histopathology
 Its similar to that to pemphigus vulgaris ,only the acantholysis is seen in the
superficial epidermis

26. PEMPHIGUS ERYTHEMATOSUS
 Pemphigus erythematosus is a localized variant of PF, originally described by
Senear and Usher.
 Patients have immunological features of both lupus erythematosus and
pemphigus, with granular IgG and C3 at the basement membrane zone,
intercellular IgG and C3 in the epidermis and circulating antinuclear antibodies.
 The antibodies recognize Dsgs together with Ro, La and double‐ stranded DNA
antigens.

27. PEMPHIGUS ERYTHEMATOSUS
 C/F – Erythematous scaly lesions over the nose and cheeks in a butterfly
distribution simulate cutaneous lupus erythematosus /seborrheic dermatitis
 Sunlight may exacerbate the disease .
 Lesions on the trunk either localised or generalised are similar to those of
pemphigus foliaceous .

29. PEMPHIGUS HERPETIFORMIS
 Rare and atypical variant of pemphigus that clinically resembles dermatitis
herpetiformis.
 Widespread clusters of pruritic papules and vesicles develop on an erythematous
background.
 Biopsies shows subcorneal pustules, eosinophilic spongiosis or features of
dermatitis herpetiformis often without acantholysis but IF studies reveal
intercellular staining.

30. IgA Pemphigus
 It’s a rare autoimmune vesiculopustular eruption with neutrophilic infiltration
,occasional acantholysis ,and bound and circulating IgA autoantibodies that target
cell surface components of the epidermis .
 Two histological forms are –
1. An intraepidermal neutrophilic type .
2. A subcorneal pustular dermatosis type

31.  Patients with both histopathological types have flaccid vesicles or pustules arising
on either erythematous or normal skin.
 The lesions may be intensely pruritic and show a circinate or annular configuration
with central clearing, evolving to crusted or scaly erythematous macules.
 The sites of predilection are the axillae and groin though the trunk, face, scalp
and proximal limbs may be affected.
 The drug of choice is dapsone .

32. PARANEOPLASTIC PEMPHIGUS
 Associated with a variety of neoplasms, almost exclusively of haematological
origin
 . The commonest association is with non‐Hodgkin lymphoma but can also be seen
associated with chronic lymphocytic leukaemia, Castleman disease, thymoma and
Waldenström macroglobulinaemia.
 Target Antigen – Dsg3, Dsg1, Plakin gp , B.P Ag1 , BP Ag2
 CLINICAL PRESENTATION
1. POLYMORPHOUS CUTANEOUS LESIONS (flaccid /tense /target like lesions )
2. Recalcitrant blisters .
3. Erosive mucocutaneous lesions .

35. INVESTIGATIONS –
SKIN BIOPSY

36. DIRECT IMMUNOFLUORESCENCE
FISH NET APPEARANCEY
PEMPHIGUS VULGARIS our text
here

39. INDIRECT IMMUNOFLUORESCENCE
 Circulating pemphigus autoantibodies are detected by indirect IF in over 80% of
patients.
 Using ELISA, over 95% of PV patients have detectable Dsg 3 antibodies and
around 50% have Dsg 1 antibodies.
 In appropriate dilutions, anti-Dsg ELISA assays can be used to monitor disease
activity

40. TREATMENT
1.TOPICAL
 BSA involvement is high - Proper nursing care.
 Potassium permanganate and topical antiseptics may help reduce the risk of
cutaneous infection.
 Potent topical or intralesional steroids may reduce the requirement for oral
steroids.
 Paraffin gauzes to avoid adhesions /sticking

41. Systemic therapy
 SYSTEMIC CORTICOSTEROIDS –
For mild-to-moderate disease, the starting dose of prednisolone is 60–80 mg/day,
whereas for severe disease, treatment is started with 80–120 mg/day.
 The dose can be stepped up in increments of 50% every 4–7 days until the disease
activity is controlled (i.e., no new lesions appearing
 Tapering off by 50% every 2 weeks is started only after 80–90% of the lesions have
healed.
 Daily dosing schedules usually lead to many corticosteroid-induced side effects such
as iatrogenic Cushing’s syndrome, hypertension, diabetes mellitus, cataract, peptic
ulcer disease, osteoporosis, neuropsychiatric symptoms, and septicaemia.

42. DEXAMETHASONE CYCLOPHOSPHAMIDE PULSE
THERAPY
 STANDARD DCP THERAPY consists of four phases –
 PHASE 1-Dexamethasone 100 mg is given intravenously dissolved in 500 mL of 5%
dextrose over 3 hours on 3 consecutive days. Cyclophosphamide 500 mg is dissolved in
the same infusion on the second day. The same cycle is repeated again at 28 days .
 Patient also receives daily oral cyclophosphamide 50 mg.
 Phase I consists of these cycles till all lesions have completely healed and patient is off
daily corticosteroids.

43.  Phase 2 - In phase II, DCP is continued for another 9 months after complete
healing of lesions and stopping of oral steroids.
 PHASE 3 -monthly DCPs are stopped and cyclophosphamide 50 mg is continued
for another 9 months and then stopped
 PHASE 4 -It is the “disease-free, drug-free” period of observation where patient is
off all medications and is just kept under follow-up to note for any recurrences. E

44. OTHER IMMUNOSUPPRESANTS
 AZATHIOPRINE -2–3 mg/kg/day
Potential adverse effects of azathioprine include bone marrow suppression, nausea
and liver dysfunction and careful blood monitoring is MANDATORY .
Azathioprine toxicity is more frequent in patients with low levels of activity of the
enzyme thiopurine methyl transferase (TPMT) .
 MYCOPHENOLATE MOFETIL – antimetabolite
 Inhibits inosine monophosphate dehydrogenase thus inhibiting purine synthesis
in T and B cells
 (1–3 g/day) has been found helpful as a steroid‐sparing agent

45. CYCLOPHOSPHAMIDE PULSE THEARAPY
 Cyclophosphamide 15 mg/kg is dissolved in 200 mL of 5% dextrose or dextrose-
normal saline and infused over 1 hour, followed by hydration with 500 mL of 5%
dextrose or normal saline given intravenously over 5–6 hours after the pulse .
 Mesna (50% of dose of cyclophosphamide) is also added to the infusion of
cyclophosphamide to avoid risk of bladder toxicity.
 The intravenous bolus of cyclophosphamide is repeated every 28 days.

46. RITUXIMAB
 It’s a IgG-type chimeric monoclonal antibody against CD20, h
 Two infusions of 1 g, 2 weeks apart.
 Onset of action of rituximab is typically 8–16 weeks following the first infusion,
though it may take longer. Improvement may persist for 12–18 months.

47. TREATMENT PROTOCOLS –RITUXIMAB
 Lymphoma protocol: Rituximab is administered at a dose of 375 mg/m2 body
surface area weekly for 4 weeks.
 Rheumatoid arthritis (RA) protocol: Two doses of rituximab 1 g is administered at
an interval of 15 days. A

48. IVIG
 IVIG is believed to work by rapidly and selectively lowering serum levels of these
pathogenic antibodies that mediate pemphigus.
 The usual dose is 2 g/kg body weight per cycle divided over 3–5 days. The cycles
are repeated every 3–4 weeks

49. PLASMAPHERESIS AND
IMMUNOADSORPTION
 Selective immunoadsorption of IgG using columns containing protein A or other
immunoglobulin binders has been effective at inducing remission in pemphigus
patients, but concomitant immunosuppression with steroids and steroid‐sparing
adjuvants is required to prevent rebound increase in the synthesis of antibody.
 Removal of circulating antibodies by plasmapheresis can also be done .

52. SUB CORNEAL PUSTULAR DERMATOSIS
 SCPD is a rare, chronic disorder characterized by flaccid, sterile pustules with a
predilection for flexural surfaces
 known as Sneddon-Wilkinson disease
 Most common in individuals aged 40 yrs or older.
 Women >men
 C/P relapsing pustular eruption involving the flexural areas of the trunk and
proximal extremities .( pruritis present )
 Individual pustular lesions arise within few hours.
 Pustules are superficial and rupture easily ,resulting in a superficial crust .

53. SCPD
 No mucosal involvement.
 Classic lesion “half and half blister in which purulent fluid accumulates in the lower
half of the blister
 ASSOCIATIONS :PG , benign monoclonal IgA/Igg gammopathy ,multiple myeloma
,lymphomas ,CTD ,IBD .
 Dapsone is the first choice of therapy .

54. Annular lesions with erythematous base and
scales on the edge .

56. STAPHYLOCOCCAL SCALDED SKIN
SYNDROME ( SSSS)
 SSSS is a S. aureus epidermolytic toxin-mediated disease characterized by
cutaneous tenderness with superficial widespread blister and desquamation
 Onset may be preceded by a prodrome of fever, malaise, and irritability. There is
generalized macular erythema with tenderness and rapidly evolves into
scarlatiniform eruption. It first appears on the face, periorificial, axillae, and groins.
T
 hey become, confluent more erythematous and edematous. Later, the surface
becomes wrinkled, cracks with flaky desquamation particularly over the flexures
leaving large denuded areas.

58. MANAGEMENT OF SSSS

59. MILIARIA
 Miliaria is the commonest sweat gland disorder seen in the tropics

60.  MILIARIA CRYSTALLINA -Eccrine gland occlusion by sweat and possibly by the
extracellular polysaccharides of Staphylococcus epidermidis leads to the
development of minute superficial subcorneal vesicles (miliaria crystallina).
 A deeper level of occlusion within the epidermis with associated inflammation
leads to MILIARIA RUBRA, which manifests as 1- to 3-mm erythematous papules
and/or papulopustules.
 The condition resolves spontaneously once the inciting factors are addressed.

61. MILIARIA RUBRA

62. REFERENCES
 IADVL (5TH EDITION )
 ROOKS TEXTBOOK OF DERMATOLOGY (9 Th edition )

63. THANKYOU