Pemphigus Vulgaris

Faraihun Bachmid
Yuli Safitri
Siti Hanisa Malik Lutuh
Melda Sari Al Iddrus
Gita Regina
Andi Aslinda Amri

Pembimbing:
dr., M.Kes. Sp.KK
 INTRODUCTION
 Two major types: Pemphigus Vulgaris and Pemphigus Foliaceus.
 Pemphigus vulgaris: erosions on mucous membranes and skin;
flaccid blisters on skin.
 Pemphigus foliaceus: crusted, scaly skin lesions.
 Diagnosis depends on histology showing intraepidermal
acantholysis and immunofluorescence studies documenting the
presence of cell surface autoantibodies, either bound to patient
skin or in the serum.
 Pemphigus vulgaris histology: suprabasal acantholysis.
 Pemphigus foliaceus histology: subcorneal acantholysis.
 Direct immunofluorescence shows immunoglobulin G (IgG) on
the keratinocyte cell surface of the patient’s skin; indirect
immunofluorescence shows IgG in patient serum that binds the
cell surface of normal keratinocytes.
 Autoantigens are desmogleins, transmembrane
desmosomal adhesion molecules.
 Therapy includes topical and systemic corticosteroids and
immunosuppressive agents.
 DEFINITION

The term pemphigus refers to a group of autoimmune blistering

diseases of skin and mucous membranes that are characterized
histologically by intraepidermal blisters due to acantholysis (i.e.,
separation of epidermal cells from each other) and
immunopathologically by in vivo bound and circulating
immunoglobulin (Ig) directed against the cell surface of
keratinocytes.
 EPIDEMIOLOGY

 Similarly, the incidence of pemphigus varies by region.

 In Jerusalem, the incidence of PV has been estimated to be 1.6
per 100,000 people per year and in Iran approximately 10.0 per
100,000 people per year.
 Elsewhere in Europe, the incidences are lower, ranging from a
high of 0.7 PV cases per 100,000 person years in the United
Kingdom to tenfold less, 0.5–1.0 per million person years, in
Finland, France, Germany, and Switzerland.
 PV: Rare, more common in Jews and people of Mediterranean
descent. In Jerusalem the incidence is estimated at 16 per
million, whereas in France and Germany it is 1.3 per million.
 PF: Also rare but endemic in rural areas in Brazil (fogo
selvagem), where the prevalence can be as high as 3.4%.
 Age of Onset. 40–60 years; fogo selvagem also in children and
young adults.
 Sex. Equal incidence in males and in females, but
predominance of females with PF in Tunisia and Colombia.
 ETIOLOGY AND PATHOGENESIS

 The discovery of pemphigus as an organ-specific, autoantibody-

mediated disease of desmosomes highlights the synergy
between clinical care and basic science research.
 An autoimmune disorder. Loss of cell-to-cell adhesion in the
epidermis (acantholysis). Occurs as a result of circulating
antibodies of the IgG class, which bind to desmogleins,
transmembrane glycoproteins in the desmosomes, Members
of the cadherin superfamily. In PV, desmoglein 3 (in some, also
desmoglein 1). In PF, desmoglein 1. Autoantibodies interfere
with calcium-sensitive adhesion function and thus induce
acantholysis.
 Desmoglein (Dsg) compensation

Figure Desmoglein (Dsg) compensation. Triangles represent the distribution of Dsg1 and 3 in skin and mucous membranes. In early
pemphigus vulgaris, antibodies are present only against Dsg3, which cause blisters only in the deep mucous membrane where Dsg3
is present without compensatory Dsg1. However, in mucocutaneous pemphigus, antibodies against both Dsg1 and Dsg3 are
present, and blisters form in both mucous membrane and skin. The blister is deep probably because antibodies diffuse from the
dermis and interfere first with the function of desmosomes at the base of the epidermis.
DIAGNOSIS
ANAMNESIS
 LABORATORY TESTS
Diagnosis of pemphigus relies on skin biopsy of a fresh lesion for
histology to determine the site of blister formation, as well as a
confirmatory immunochemical study to document the presence
of skin autoantibodies, either by direct immunofluorescence of
perilesional skin, or indirect immunofluorescence or ELISA of
patient serum
 HISTOLOGY

Figure. Histopathology of pemphigus Suprabasilar acantholysis. The row of

tombstones
 IMMUNOFLUORESCENCE

Figure.Immunofluorescence in pemphigus. A. Direct immunofluorescence for

immunoglobulin G (IgG) of perilesional skin from a patient with pemphigus vulgaris.
Note cell surface staining throughout the epidermis. B. Indirect immunofluorescence
with the serum from a patient with pemphigus foliaceus on normal human skin. Note
IgG on the cell surface throughout the epidermis.
 DIRECT IMMUNOFLUORESCENCE

 Essentially all patients with active PV or PF have a positive

finding on a direct immunofluorescence study, which tests for
IgG bound to the cell surface of keratinocytes in perilesional
skin. The diagnosis of pemphigus should be seriously
questioned if the test result of direct immunofluorescence is
negative
 INDIRECT IMMUNOFLUORESCENCE.

 Indirect immunofluorescence is performed by incubating

serial dilutions of patients’ sera with epithelial substrates. It is
reported as a semiquantitative titer (indicating the last
dilution at which the serum demonstrates a positive cell
surface staining pattern). The test is offered by most major
national laboratories and can remain positive for weeks to
months after healing of skin lesions, making it a good
diagnostic test if a patient should present with no active skin
lesions, for example, due to empiric treatment with
prednisone by a referring physician.
 ENZYME-LINKED
IMMUNOSORBENT ASSAY

For diagnosis of disease, antigen-specific ELISAs have been shown

to be more sensitive and specific than immunofluorescence, and
their titer correlates better than that of indirect
immunofluorescence with disease activity. Additionally, ELISAs are
easier to perform and less subjective than immunofluorescence,
and may replace the latter as the preferred first diagnostic test for
pemphigus, although currently some major national laboratories
do not offer desmoglein ELISA
 TREATMENT

CORTICOSTEROIDS
 The systemic administration of glucocorticoids, usually
prednisone, is the mainstay of therapy for pemphigus.
 The full systemic dose of glucocorticoids has been defined
in the consensus guidelines as 1.5 mg/kg/day of prednisone
equivalent for 3 weeks.
 Therefore, patients whose total daily prednisone dose
exceeds approximately 100 mg should be considered for
adjunctive treatments
IMMUNOSUPPRESSIVE AGENTS
 Prospective randomized studies have shown that
immunosuppressive agents such as mycophenolate
mofetil, azathioprine, and cyclophosphamide have a
steroid-sparing effect; retrospective studies suggest
decreased mortality with use of adjuvants plus steroids
compared to steroids alone
 There are additional therapies that can be used when the
more standard treatments, discussed previously, are not
effective. Example Rituximab, Intravenous,
Immunoglobulin, Plasmapheresis.
 DIFFERENTIAL DIAGNOSIS
 Pemphigus vulgaris
 PROGNOSIS

Before the advent of glucocorticoid therapy, PV was almost

invariably fatal due to severe blistering of the skin and mucous
membranes leading to malnutrition, dehydration, and sepsis. PF
was fatal in approximately 60% of patients. PF was almost
always fatal in elderly patients with concurrent medical
problems; however, in other patients its prognosis, without
therapy, was much better than PV.
 COMPLICATION

 Secondary infection, which may be either systemic or

localized to the skin, may occur because of the use of
immunosuppressants and the presence of multiple
erosions. Cutaneous infection delays wound healing
and increases the risk of scarring
THANK YOU