Pemphigus is a group of chronic autoimmune epidermal bullous disease affecting skin and mucous membranes. It is characterized histologically by intraepidermal blister formation and immunopathologicaly by the presence of bound and circulating autoantibodies directed against the intercellular adhesion structures of the epithelial cells.

1. PEMPHIGUS
MITHILA M
CRRI

2. CONTENTS
INTRODUCTION
CLASSIFICATION
PATHOGENESIS
CLINICAL FEATURES
DIAGNOSIS
MANAGEMENT
REFERENCES

3. INTRODUCTION
 Pemphigus is a group of chronic autoimmune epidermal bullous disease affecting skin and
mucous membranes.
 It is characterized histologically by intraepidermal blister formation and immunopathologicaly by
the presence of bound and circulating autoantibodies directed against the intercellular adhesion
structures of the epithelial cells.

4. CLASSIFICATION
Pemphigus vulgaris(PV)
 Mucosal-dominant type
 Mucocutaneous type
 Cutaneous type
Pemphigus foliaceus(PF)
Paraneoplastic pemphigus(PNP)

5. Pemphigus variants
• Pemphigus vegetans : a variant of pemphigus vulgaris with fungoid vegetations
• Pemphigus erythematosus: a variant of pemphigus foliaceus with localized involvement, mainly on
the face and upper part of the chest and back
• Fogo selvagem : an endemic form of pemphigus foliaceus found in rural areas in Brazil
• Herpetiform pemphigus: a subtype characterized by small vesicles and pustules
• Drug-induced pemphigus

6. PATHOGENESIS
Pathogenesis lies in the production of IgG
autoantibodies against extracellular domains of cell membrane proteins
of keratinocytes results in acantholysis
(the loss of cell–cell adhesion between keratinocytes).
These IgG autoantibodies are characteristically
directed against desmogleins (desmoglein 1 and desmoglein 3),
which are the cell–cell adhesion molecules
that are found in desmosomes, which are the structures primarily
responsible for maintaining intercellular adhesion in
stratified squamous epithelia, such as the skin and oral mucosa.

7. Desmoglein 1 is found particularly in the superficial layers of the epidermis, antibodies against this
protein alone result in pemphigus foliaceus.
Desmoglein 3 is more widely distributed in the lower parts of the epidermis and in mucosal epithelia
.Thus, antibodies against this protein are associated with pemphigus vulgaris, typically presenting
with mucosal ulceration.

8. CLINICAL FEATURES
PEMPHIGUS VULGARIS
 Characterized by flaccid blisters and erosions of the skin and
mucous membranes and affecting the trunk , face, scalp and
proximal limbs.
 In oral cavity the most affected area are the buccal and
palatine mucosa, lips, and gingivae.
 The erosions are multiple and present in different sizes and
irregular shapes.
 Gingival involvement manifests mainly as desquamative
gingivitis.The lesions may extend to the vermilion border of
the lips, forming a fissured hemorrhagic crust .
 Nail involvement (paronychia)is also seen in patients with
extended disease .

9. PEMPHIGUS FOLIACEUS
 Lesions develop only on the skin.
 It presents as erythema, with scaling and crusting with flaky circumscribed pathches,
so-called puff pastry-like scaling or corn flake like crusts.
 Blisters are rarely seen .

10. PARANEOPLASTIC PEMPHIGUS
 It presents as painful, persistent and therapy-refractory
haemorrhagic stomatitis.
 It mainly involves the vermilion border of the lips and
lateral borders of the tongue .
 It is associated with underlying neoplasms non-
Hodgkin's lymphoma, chronic lymphocytic leukemia ,
Castleman's disease, adenocarcinomas , squamous
cell carcinomas, sarcomas, thymoma, Hodgkin
lymphoma.

11. DIAGNOSIS
Diagnosis of pemphigus is based on
• clinical presentation and clinical tests
• direct immunofluorescence microscopy of a perilesional biopsy
• Serology
• histopathology of a perilesional biopsy

12. It is elicited by applying tangential/lateral pressure by a thumb
or a finger in the perilesional skin, affected skin, or normal skin,
which results in a force that dislodges upper layers of epidermis
from lower layers.
Also called a bulla spread sign. It is the ability to enlarge a
blister in the direction of periphery by applying mechanical
pressure on the roof of the intact blister.
NIKOLSKY SIGN
ASBOE HANSENS SIGN/ BULLA SPREAD TEST
CLINICAL TESTS

13. HISTOPATHOLOGY
 Histopathological examination will reveal acantholysis and a sparse inflammatory infiltrate.
Separation of epithelial cells from the basal layer forms a space between the basal cells and the cells
above it- suprabasilar split.
 This leaves a single layer of basal keratinocytes attached to the dermal-epidermal basement
membrane that project into the blister cavity - ‘row of tombstones’ appearance.
Suprabasilar split

14.  Clumps of epithelial cells are found lying free in the vesicular space, showing
degenerative changes. These cells are called to be ‘Tzanck cells.’
 Apperance of this can be used as technique to analyze vesiculobullous diseases and it
forms the basis for the ‘Tzanck test.’

15. IMMUNOFLUORESCENCE
 Most reliable and sensitive diagnostic test for all forms of pemphigus
 In both pemphigus vulgaris and pemphigus foliaceus, IgG antibodies, and occasionally
complement C3 protein, deposit on the cell surface and are visible as a honeycomb-like pattern.
 In some cases of paraneoplastic pemphigus, an additional deposition of IgG can be seen along the
dermal–epidermal junction in a band-like pattern.
Direct immunofluorescence microscopy of a
lesional skin biopsy showing intercellular deposits of IgG
in the epidermis

16. SEROLOGY
 The molecular specificity of circulating pemphigus
autoantibodies can be analysed using highly sensitive
and specific ELISA.
 These can detect circulating IgG autoantibodies
to Dsg1 and Dsg3.

17. MANAGEMENT
Treatment mainly aims to improve symptoms through the reduction of serum autoantibodies ,and
immunosuppression thus controlling the disease, which means preventing the formation of new blisters and
starting the healing process of the existing ones.
• Systemic corticosteroids remain the mainstay treatment .
Oral prednisone or oral prednisolone are the mainstay corticosteroid treatment.
• Immunosuppression using immunusuppresive adjuvants
Azathioprine (2–3 mg/kg),mycophenolate mofetil (1.5–3 g daily)
• Pulse therapy
• Monoclonal antibody therapy
• Intravenous Immunoglobulin
• Immunoadsorption

18. REFERENCES
 Kasperkiewicz M, Ellebrecht CT, Takahashi H, Yamagami J, Zillikens D, Payne AS, Amagai M. Pemphigus. Nat Rev Dis Primers.
2017 May 11;3:17026. doi: 10.1038/nrdp.2017.26. PMID: 28492232; PMCID: PMC5901732.
 Porro AM, Seque CA, Ferreira MCC, Enokihara MMSES. Pemphigus vulgaris. An Bras Dermatol. 2019 Jul 29;94(3):264-278.
doi: 10.1590/abd1806-4841.20199011. PMID: 31365654; PMCID: PMC6668932.
 Lancet 2019; 394: 882–94 Enno Schmidt, Michael Kasperkiewicz, PascalJolyhttps://www.thelancet.com/article/S0140-
6736(19)31778-7/fulltext
 Kanwar AJ, De D. Pemphigus in India. Indian J Dermatol Venereol Leprol 2011;77:439-449
 Shafers ;Textbook of oral pathology 8 th edition.
 Subadra K, S S, Warrier S A (September 15, 2021) Oral Pemphigus Vulgaris. Cureus 13(9): e18005. doi:10.7759/cureus.18005
 Sanders, W.J. A brief review of pemphigus vulgaris. biomed dermatol 1, 7 (2017). https://doi.org/10.1186/s41702-017-0008-
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