Pemphigus

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Pemphigus

• Tiffany Hsu 529
• Joanne Kim 140
• Jonathan Miller 149
• Hamid Shafizadeh 174

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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

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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.

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Clinical Presentation

• Three major types of pemphigus
• Pemphigus vulgaris
• Pemphigus folaceus
• Paraneoplastic pemphigus
• Pemphigus vulgaris is by far the most common of
  the three types.

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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
• Face and scalp
• Chest and armpits
• groin

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Pemphigus vulgaris
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Pemphigus vulgaris
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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.

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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

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Pemphigus Immunofluorescence
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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.

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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

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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

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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
  (Anti-inflammatory 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

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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

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• 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