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Pemphigus
Tiffany Hsu #529
Joanne Kim #140
Jonathan Miller #149
Hamid Shafizadeh #174
Pemphigus Pathogenesis
Intraepithelial blister formation results from breakdown
of intercellular adhesion, thus producing epithelial cell
separation known as acantholysis
Caused by antibody-mediated autoimmune reaction to
desmogleins (Dsg), desmosomal transmembrane
glycoproteins, leading to acantholysis
 Classified into pemphigus vulgaris (PV), with
suprabasal acantholysis, and pemphigus foliaceus (PF),
with acantholysis in the more superficial epidermis
Pemphigus vulgaris is characterized by IgG
autoantibodies against desmoglein 3 (Dsg 3), whereas
the target of PF is Dsg1, although about 50% of PV
patients also have Dsg1 autoantibodies; desmoplakin is
another target
Pathogenesis
 Circulating autoantibodies are responsible for
disruption of intercellular junctions and loss of
cell-to-cell adhesion.
 Extent of epithelial cell separation are directly
proportional to the titer of circulating
pemphigus antibody.
 It is believed pemphigus antibody, once bound
to the target antigen (desmoglein 1, desmoglein
3, desmoplakin), activates an epithelial
intracellular proteolytic enzyme that acts at the
desmosome-tonofilament complex.
Clinical Presentation
 Three major types of pemphigus:
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Pemphigus vulgaris
Pemphigus folaceus
Paraneoplastic pemphigus
Pemphigus vulgaris is by far the most common
of the three types.
Clinical Presentation
 Pemphigus presents with vesicles and/or bulla on skin
and mucous membranes.
 These vary in size from 1-3 cm in diameter.
 These rupture quickly and more often appear as
ulcerations.
 The mucous membranes of the mouth are the most
common site for pemphigus lesions
 Other common sites:
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Face and scalp
Chest and armpits
groin
Pemphigus vulgaris
Pemphigus vulgaris
Clinical Presentation
 Most common age group initially
diagnosed with pemphigus is 40-60 years
old.
 Children are very rarely affected.
 People of Jewish or Mediterranean descent
are most commonly diagnosed.
Diagnostic tests for Pemphigus
 Positive Nikolsky sign
 Indirect fluorescent antibody (IFA)
-the qualitative and semi-quantitative detection of antibodies
associated with pemphigus
 The direct immunofluorescence test
(DIF)
-detects the antibody deposition in the tissues
-very reliable diagnostic test for pemphigus
-can remain positive for several years after regression of the
disease
Pemphigus Immunofluorescence
Histology of Pemphigus
Pemphigus typically displays acantholysis with some dyscanthosis near
the granular layer. The acantholytic, rounded cells are termed Tzanck cells,
which are pathognomonic to Pemphigus Vulgaris
Within the papillary dermis there is a sparse
perivascular lymphocytic infiltrate with scattered
eosinophils.
Treatment Goals
 Reduce inflammatory response
-decrease blister formation
-promote healing of blisters and erosions
 Reduce autoantibody production
 Use minimal dose of medication needed to
control the disease
Conventional Therapy
 Systemic corticosteroids
-1 mg/kg prednisone initially used with gradual tapering
-severe adverse side effects: HTN, osteoporosis,
atherosclerosis, peptic ulcer disease, aseptic necrosis, diabetes,
susceptibility to infections, septicemia, others
 Immunosuppressive and anti-inflammatory
agents
-Used in combo with corticosteroids to provide a
potential corticosteroid-sparing effect (minimize steroid use)
-adverse side effects
Other Therapies
Dapsone
Methotrexate
Mycophenolate mofetil
Dexamethasone-Cyclophosphamide Pulse
Therapy
 Plasmapheresis
 Rituximab + Intravenous Immune
Globulin
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Other Therapies
 Dapsone (anti-inflammatory)
-clinical response usually seen after 1st week of treatment
-most common adverse effect: hemolytic anemia
 Methotrexate (immunosuppressant)
-risk of megaloblastic anemia, bone marrow suppression, liver and
renal toxicity
 Mycophenolate Mofetil (chemotherapeutic)
-inhibits lymphocyte proliferation
-more studies with long-term follow up are needed to determine
efficacy and proper dosing
 Dexamethasone-Cyclophosphamide Pulse Therapy (Antiinflammatory + chemotherapeutic agent)
-studies have shown remission of PV, but patients suffered multiple
infections due to receiving high doses of immunosuppressants
 Plasmapheresis
-reduces the autoantibody in the plasma through a filtration
mechanism
-for severe refractory PV
-few studies done; no established protocol
Other Therapies
 Rituximab (monoclonal antibody) + Intravenous Immune Globulin
(IVIg)
-study published October 2006: study on 11 patients who had inadequate
responses to conventional therapy
-Initially 2 cycles of rituximab given once weekly for 3 weeks and IVIg
given in the 4th week; followed by monthly infusion of rituximab and IVIg
for 4 consecutive months
-Of 11 patients, 9 had complete and rapid resolution of lesions and
a clinical remission lasting an average of 31 months. All
immunosuppressive therapy, including prednisone, could be
discontinued before ending rituximab treatment in all patients.
Side effects that have been associated with rituximab were not
observed, nor were infections.
-recommended for refractory PV
-larger, controlled study needed
1. Pemphigus is characterized by IgG autoantibodies against which proteins:
A. Desmogleins
B. Epiligrin
C. Collagen
D. Bullous pemphigoid antigen-2
Answer: A
2. What is the most common type of pemphigus?
A. Pemphigus foliaceus
B. Pemphigus vulgaris
C. Paraneoplastic pemphigus
D. None of the above
Answer: B