Skin-nontumor / Clinical dermatology
Blistering disorders
Pemphigus

Author: Mowafak Hamodat, M.D., MB.CH.B, MSc., FRCPC (see Authors page)

Revised: 15 June 2016, last major update July 2011

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Pemphigus [title] skin

Cite this page: Pemphigus. PathologyOutlines.com website. http://pathologyoutlines.com/topic/skinnontumorpemphigus.html. Accessed December 9th, 2016.
Definition / General
  • Rare, nonhereditary, chronic, autoimmune disease wtih flaccid blisters and denuded skin
  • Associated with internal malignancies, including thymoma

Variants:
  • Erythematosus:
    • Also called SenearñUsher syndrome
    • Involves a localized area, like a lupus malar rash on face
    • Otherwise identical to pemphigus foliaceus combined with features of lupus erythematosus
    • Usually middle aged adults (Clin Exp Dermatol 2009;34:708)

  • Pemphigus foliaceus:
    • Endemic in Brazil; called fogo selvagem or "wild fire" in Portugese (Br J Dermatol 2006;155:446, Int J Dermatol 2005;44:293)
    • Crusts and shallow erosions on healthy appearing skin (often trunk) with blisters that form after rubbing (Nikolskyís sign)
    • Typically spares mucous membranes
    • Lesions may not appear bullous because crusts and erosions replace the bullae
    • Clinically mild

  • Paraneoplastic pemphigus:
    • Associated with lymphoma, thymoma, squamous cell carcinoma, carcinoma of bronchus, pancreas and breast
    • Oral and cutaneous erosions and bullae
    • Stomatitis may be the only symptom
    • Treat by treating the tumor
    • Due to autoantibodies targeting proteins of the plakin and cadherin families involved in maintenance of cell architecture and tissue cohesion; recently identified as alpha-2-macroglobuline-like-1 (A2ML1) (PLoS One 2010;5:e12250)

  • Pemphigus vegetans:
    • Rare (1 - 2% of pemphigus cases) variant of pemphigus vulgaris characterized by verrucous plaques in the flexural regions
    • Oral cavity is commonly affected; cerebriform or scrotal tongue is a diagnostic clue of early involvement
    • Reported in long standing nasal heroin abuse and with HIV+ patients

  • Pemphigus vulgaris:
    • 80% of all pemphigus
    • Oral mucosa; also scalp, face, eye, pharynx, larynx, axilla, groin, trunk; nail involvement
    • Direct pressure to the center of the lesion is followed by lateral extension, the AsboeñHansen sign
    • Healing is often accompanied by postñinflammatory hyperpigmentation but no scarring
    • Fatal if untreated because oral erosions impair swallowing
    • Deaths are due to staphylococcal infection or pulmonary embolism
Epidemiology
  • Ages 30 - 59; no gender preference
Case Reports
Treatment
  • Corticosteroids or immunosuppressive agents
Clinical Images

Images hosted on PathOut servers:

Pemphigus erythematosus (breast skin), courtesy of Mark R. Wick, M.D.



Pemphigus vulgaris (breast skin), courtesy of Mark R. Wick, M.D.



Images hosted on other servers:

Pemphigus erythematosus, various images

Paraneoplastic pemphigus

Paraneoplastic pemphigus associated with non-Hodgkin lymphoma

Pemphigus vegetans

Pemphigus vulgaris

Micro Description
  • Intraepidermal blister is just above basal layer and due to acantholysis from IgG against desmosomes and production of plasminogen activator
  • Epithelial cells are rounded due to loss of desmosomes
  • Often eosinophilic spongiosis

  • Pemphigus foliaceus:
    • Only the granular cell layer is affected with a discrete acantholytic bullae containing rounded, acantholytic keratinocytes and few inflammatory cells
    • Stratum corneum may be denuded
    • Often eosinophilic spongiosis
    • Blister may contain many neutrophils, which makes distinction from subcorneal pustular disorders especially difficult

  • Paraneoplastic pemphigus
    • Suprabasal acantholysis with cleft and vesicle formation
    • Vacuolar interface with spongiosis, dyskeratotic keratinocytes and lymphocyte excocytosis
    • Perivascular lichenoid chronic inflammatory cell infiltrate
    • Frequent pigment incontinence

  • Pemphigus vegetans:
    • Supra basal acantholysis is subtle, masked by exuberant proliferation of squamous epithelium which may show pseudo epitheliomatous hyperplasia
    • Large intraepidermal microabscesses filled with eosinophils and occasional acantholytic keratinocytes

  • Pemphigus vulgaris:
    • Numerous small, flaccid, suprabasilar bullae with single row of keratinocytes attached to basement membrane
    • Prominent extension of acantholysis into follicular infundibula
    • Ruptured bullae cause skin erosions
    • Minimal dermal infiltrate
Micro Images

Images hosted on PathOut servers:

Pemphigus foliaceus



Pemphigus vulgaris (breast skin), courtesy of Mark R. Wick, M.D.



Pemphigus vulgaris (breast skin), IgG stain, courtesy of Mark R. Wick, M.D.

Pemphigus foliaceus: C3 (left) and IgG (right)



Images hosted on other servers:

Pemphigus foliaceus, contributed by Asmaa Gaber Abdou, M.D.



Paraneoplastic pemphigus, Tzanck test

Paraneoplastic pemphigus, acantholytic blister

Pemphigus vegetans

Pemphigus vulgaris, various images

Positive Stains
  • Necessary to confirm diagnosis - IgG against desmoglein 1 (usually) or desmoglein 3 (desmosome components) or C3 are present in a fishnet-like pattern in intercellular squamous region
  • IgA is positive in IgA pemphigus
  • In paraneoplastic pemphigus, granular deposits of C3 are also present at basement membrane
Differential Diagnosis
  • Differential diagnosis of acantholysis includes:
  • Also:
    • Actinic keratosis
    • Focal changes associated with other tumors