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PEMPHIGUS

A serious,
acute or chronic,
bullous
autoimmune disease
of skin and mucous membranes
based on acantholysis
CLASSIFICATION
OF
PHEMPHIGUS

Paraneoplastic
Phemphigus Phemphigus
phemphigus: IgA Phemphigus
vulgaris Foliaceus
a/w malignancy
Phemphigus Phemphigus Subcorneal pustular
vulgaris: localized & foliaceus: dermatosis
generalized generalized Intraepidermal
Phemphigus Phemphigus neutrophilic IgA
vegetans: localized erythematosus: dermatitis
Drug-induced localized
Fogo selvagem:
endemic
Drug-induced
2 Major Types
Pemphigus vulgaris (PV) Pemphigus foliaceus (PF)
1. Flaccid blisters on skin and
erosions on mucous
1. Scaly and crusted skin lesions
membranes
2. Suprabasal acantholysis
2. Subcorneal acantholysis
Circulating antibodies of IgG class
bind to desmogleins (desmoglein 3)
Epidemiology
Rare, more common in Jews & people
of Mediterranean descent
Age of onset = 40-60 years old Autoantibodies interfere with
Gender = F=M calcium-sensitive adhesion function
Equal incidence in males and in females

Acantholysis (loss of cell-to-cell


adhesion in epidermis)
Etiology & pathogenesis
- An autoimmune disorder
- Loss of cell-to-cell adhesion in
epidermis (acantholysis)
- Occurs as result of circulating
antibodies of IgG class, which bind to
desmogleins (transmembrane
glycoproteins in desmosomes),
members of cadherin superfamily.
- In Pemphigus Vulgaris, it is
desmoglein 3. (PF = desmoglein 1)
- Usually starts in oral mucosa
- Months may elapse before skin lesion occur
- Less frequently, there maybe generalized, acute eruption of bullae from beginning

- CF: no pruritus but burning & pain in erosions, painful & tender mouth lesions
- Painful mouth lesions may prevent adequate food intake
- Other CF: epistaxis, hoarseness, dysphagia, weakness, malaise, weight loss
Skin lesions Nikolsky Sign Sites of predilection
- Vesicles & bullae with - Dislodging of normal- - scalp, face, chest, axillae,
serous content, flaccid appearing epidermis by groin, umbilicus
(flabby) lateral finger pressure = - In bedridden patient,
- Easily ruptured, weeping erosion extensive involvement of
- Arising on normal skin - Pressure of bulla = lateral back
- Randomly scattered, extension of blister - Rarely seen in mucous
discrete. membrane (mouth, nose,
- Localized (mouth or pharynx, larynx, vagina)
circumscribed skin area) or
generalized
- Extensive erosions bleed
easily
- Crusts esp on scalp
Nikolsky sign
A positive Nikolskiy sign
indicates intraepidermal
cleavage and differentiates
intraepidermal blisters from
subepidermal blisters.
Pathognomonic of pemphigus
and staphylococcal scalded
skin syndrome.
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 upper layers of
epidermis from lower
epidermis.
Other types:
Phemphigus vegetans
o A PV variant
o Usually confined to
intertriginous regions,
perioral area, neck &
scalp
o Granulomatous Multiple papillomatous erosions in the oral
vegetating purulent mucosa. Verrucous, vegetating plaque
plaques that extend surrounded by pustules in the right axilla
centrifugally
Drug induced PV =
captopril, D-penicillamine
Dermatopathology
Light microscopy: early small bulla, or
margin of larger bulla/erosion
Separation of keratinocytes,
Lab examinations
suprabasally split just above basal
cell layer & vesicles, containing
acantholytic keratinocytes

Immunopathology
Direct immunofluorescence (IF)
staining = IgG & C3 deposits in lesional
& paralesional skin in intercelullar
substance of epidermis

Serum
Autoantibodies against 140-kDa
glycoprotein, desmoglein 3, in
desmosomes of keratinocytes
Titer correlates with activity of disease
Differential
diagnosis will
be difficult if
only mouth
lesions are
present
- aphthae
- mucosal
lichen planus
- erythema
multiforme
Biopsy of skin
& mucous
membrane,
direct IF, &
circulating
autoantibodies
confirm high
index of
suspicion
Management
Glucocorticoids Other measures
2-3mg/kg of prednisone until cessation of new Cleaning bath & wet dressings
blister formation & dissapearance of Nikolsky sign
Topical & intralesional glucocorticoids
Then rapid reduction to about intial dose until
patient is almost clear = slow tapering of dose to Antimicrobial therapy in bacterial
minmal effective dose infection
Correction of fluid & electrolyte
imbalance

Concomitant Immunosuppresive Therapy (given


concomitant for their glucocorticoid-sparing effect) Monitoring
Azathioprine 2-3mg/kg until complete clearing,
then tapered Clinical = improvement of
MTX oral/IM 25-35mg/wk. Dose adjustment like skin lesions, development
azathioprine of drug-related side effects
Cyclophosphamide 100-200mg daily =
maintenance dose 50-100mg/d. Bolus therapy* Lab monitoring of
Mycophenolate mofetil 1g 2x daily phemphigus antibody titers
Plasmapheresis
High-dose IVIG 2g/kg every 3-4 weeks
Hematologic & metabolic
Rituximab (monoclonal antibody to CD20) as IV indicators for drugs adverse
once a week for 4 weeks effects (glucocorticoid &
immunosuppresive)