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2. ORAL PEMPHIGUS
VULGARIS:A CASE REPORT
WITHDIRECT
IMMUNOFLUORESCENCE
STUDY
LEKSHMYJAYAN
I MDS,ORALANDMAXILLOFACIALPATHOLOGY
SRMDENTALCOLLEGE,CHENNAI

3. INTRODUCTION
 Named by Wichman (1791)
 name derived from the Greek word ‘PEMPHIX’
- bubble or blister
DEFINITION : Pemphigus refers to autoimmune disorders,
mucocutaneous blistering disease, in which the keratinocyte antigens
are targets of autoantibodies leading to acantholysis and blister
formation.

4. TYPES
PEMPHIGUS
VULGARIS
PEMPHIGUS
FOLIACEUS
PARA
NEOPLASTIC
PEMPHIGUS
DRUG
INDUCED
PEMPHIGUS
IgA
PEMPHIGUS

5. PREDISPOSINGFACTORS
 DRUGS
 DIET
 RADIATION
 STRESS
 SURGERY
 PREGANANCY
 VIRUS
 PESTICIDES
Shamimul Hasan et al :
Pemphigus vulgaris –
a case report and
detailed review of
literature(2011)

6. EPIDEMIOLOGY
INCIDENCE:
 0.5 to 3.2 per year per 1,00,000 population
 Male: Female = 1:2
 Ashkenazi Jews and people in Mediterranean origin
 80-90% patients develop oral lesions, 60% develop
oral lesions as first symptom.
 Occasionally associated with other autoimmune
disorders, Herpes simplex infection, internal
malignancies
[Rai Arpita et al, 2015, ORAL PEMPHIGUS
VULGARIS : A CASE REPORT ]

7.  ST18- gene regulating apoptosis and
inflammation, identified in predisposing individuals
 Genetic predisposition to HLA
[Frank.A.Santoro et al : Pemphigus 2013 October]

8. INTERCELLULAR JUNCTIONS
OCCLUDING
JUNCTION
COMMUNICATIN
G JUNCTION
ANCHORING
JUNCTION

12. DESMOSOMES(Maculaadherens)(GiulioBizzagero)
 Small disk shaped- spot welds between adjacent cells
 Link cytoskeletal structure of two cells
 Resist shearing force and prevent mechanical stress
 Desmosomes are found in many tissues especially abundant in skin, heart,
muscle, the neck of the uterus.

13. EXTRACELLULAR
PART(DESMOGLEA)
Transmembrane proteins
Cadherin superfamily
-Desmoglein and Desmocollin
INTRACELLULAR
PART(DESMOSOMAL
PLAQUES)
Two protein groups
1st group- Plakin family
desmoplakin, envoplakin,
periplakin
2nd group- Plakoglobin and
DESMOGLEIN 1- Pemphigus Foliaceus plakophilin
DESMOGLEIN 3- Pemphigus Vulgaris

15. THEORIES OF PATHOGENESIS
1) DESMOGLEIN COMPENSATION THEORY
2) MULTIPLE HIT HYPOTHESIS
3) ANTIBODY- INDUCED APOPTOSIS THEORY
4) BASAL CELL SHRINKAGE THEORYAND
APOPTOLYSIS THEORY

16. DESMOGLEINCOMPENSATION
THEORY (Amgai & Stanley,1999)
 Based on the distribution of Dsg1 and Dsg 3 in
the skin and mucosa
 Existence of anyone type of Dsg is sufficient to
maintain the integrity of epithelium and mucosa.

18. DRAWBACKS:
1)Assumption that the integrity of stratified squamous epithelium of skin
and oral mucosa relies entirely on Dsg 1 and Dsg 3 molecules.
2)Ignores complex interactions of chromosomal cadherins for integrity of
epidermis.
[Sergei.A.Grande, 2011, PEMPHIGUS AUTOIMMUNITY: HYPOTHESIS
AND REALITY ]

19. MULTIPLEHITS HYPOTHESIS
PEMPHIGUS
DESMOSOMAL
ANTIBODIES
NON DESMOSOMAL
PROTEINS
KERATIONOCYTE
ANTIBODIES
MITOCHONDRIAL
ANTIBODIES

20. ANTIBODYINDUCEDAPOPTOSIS
THEORY
 Apoptosis may be responsible for the underlying
mechanism of acantholysis.
 IgG and anti- Fas receptor antibody activate
apoptosis

22. BASALCELLSHRINKAGEHYPOTHESISAND
APOPTOLYSISTHEORY
 Acantholysis occurs in the suprabasal layers –
tombstone like transformation of the basal layers
 Shrinkage of keratinocytes
 Apoptolysis [GRANDE ETAL,2009] links
acantholysis and cell death pathways to cell
shrinkage

23. MAIN DIFFERENCE BETWEEN APOPTOSIS
AND APOPTOLYSIS IN PEMPHIGUS:

24. PEMPHIGUS
VULGARIS
 Present with oral lesions
and then develop
cutaneous lesions
 Often misdiagnosed as
aphthous ulcer
COMMON SITES : Oral
mucosa, Skin, Nose,
Pharynx, Larynx,
Oesophagus, Genital area

25. CLINICAL FEATURES :
 AGE- 40-60 years approximately
 Rapid appearance of multiple large flaccid bullae
 Fragile, ruptures easily- painful haemorrhagic erosion
 Early lesion- watery fluid and later purulent or sanguineous
fluid

26.  COURSE IS VARIABLE : 1) Acute fulminating
(days to weeks)
2) Slow, prolonged (months
to years)
VESICLE V/S BULLAE

27. NIKOLSKY’S SIGN (Pyotr Vasilyevich
Nikolsky, 1896)
 lateral pressure to the border of intact bullae
peripheral extension of the bullae.
 Positive upper dermis separates from basal
layer
 Differentiate intraepidermal from subepidermal
bullae
 Also seen in FAMILIAL BENIGN CHRONIC
PEMPHIGUS, EPIDERMOLYSIS BULLOSA

28. Asboe- Hansen sign or Indirect Nickolsky’s sign(Gustav Asboe-Hansen)
 Extension of a blister to adjacent unblistered skin when pressure is put on the top of
the bulla
NIKOLSKY’S PHENOMENON
 When superficial layer of the epidermis is felt to move over the deeper layer- new
bullae develops within 24 hours

29. ORAL MANIFESTATIONS :
 Intact bullae rare due to fragility
 Patchy erosions are seen- painful on chewing
 Desquamative gingivitis (2-3%)
 Common sites-
Buccal mucosa T
ongue
Palate Lips
Supriya.s.Venugopal et al,
2012,[DIAGNOSIS AND
CLINICAL FEATURES OF
PEMPHIGUS VULGARIS ]

30. HISTOLOGICAL FEATURES
 Acantholysis
 Formation of bullae above the basal cell layer
 Split is characteristically suprabasilar and cells remain
attached to the basal lamina- tombstone appearance
 Presence of tzanck cells
 Vesicular fluid and connective tissue- scanty to dense
inflammatory cell infiltration
 Spongiosis and acantholysis of adjacent epithelium

31. epithelium exhibiting spongiosis, tombstone appearance,
suprabasilar split and dense inflammatory infiltrate

32. Suprabasilar cleft showing acantholysis of the keratinocytes, Tzanck
cells, red blood cells and inflammatory cells

33. DIAGNOSIS
 Clinical examination
 Biopsy
 Tzanck smear
 Compressed air test
 Immunofluorescence study
 ELISA

34. TZANCKCELLS
 Multinucleated giant cell formed by the fusion of acanthoytic keratinocytes
 Seen in – Pemphigus vulgaris, Chicken pox, Herpes simplex, Herpes zoster
TZANCK TEST: (ARNAULT TZANCK, 1947)
Simple diagnostic cytological method for
mucocutaneous lesion
 Stains- Giemsa stain, H&E, Methylene blue,
Papanicolaou, Toluidine blue

35. CYTODIAGNOSIS BY TZANCK SMEAR
DISEASE CYTODIAGNOSIS BY TZANCK SMEAR
Pemphigus Vulgaris Multiple tzanck cells
Mourning edged cells
Sertoli rosette
Streptocytes
Bullous Pemphigoid, Steven Johnson Syndrome and
Erosive Lichen Planus
Non-specific
No acantholytic
Rules out Pemphigus Vulgaris
Herpes simplex, Varicella, Herpes zoster Rapid and reliable
Multinucleated syncytial giant cells (tadpole, teardrop shape) &
acantholytic cells
Ballooning degeneration
Nuclear molding
Basal cell epithelioma Highly reliable
Cluster of basaloid cells
Cytoplasm is scant, poorly defined and basophilic
Squamous cell carcinoma (nodular, ulcerated, non
keratotic)
Isolated cells , pleomorphism
Nuclear alteration

36. IMMUNOFLUORESCENCE
• Technique allowing visualisation of specific protein or antigen by finding
specific
antibody chemically conjugated with a fluorescent dye.
• Specific antibodies labelled with Fluorescein Isothiocyanate[FITC]
- apple green under polarised light

37. DIRECT
IMMUNOFLUORESCENCE
INDIRECT
IMMUNOFLUORESCENCE

38. IMMUNOFLUORESCENCEIN
PEMPHIGUSVULGARIS
– DIRECT
IMMUNOFLUORESCENCE IN
PEMPHIGUS VULGARIS
– INDIRECT
IMMUNOFLUORESCENCE IN
PEMPHIGUS VULGARIS

40. DIFFERENTIAL DIAGNOSIS
1) Bullous pemphigoid
2) Cicatricial pemphigoid
3) Dermatitis herpetiformis
4) Erythema multiforme
5) Erosive lichen planus
6) Allergic stomatitis

41. TREATMENT
AIM OF TREATMENT
1)Decrease bullae formation
2)Promote healing of bullae and erosions
3)Determine minimal dose of medication necessary
to
control the disease process.

42. PERIODONTALTHERAPY
CORTICOSTEROIDTHERAPY
PLASMAPHERESIS
[Shamimul Hasan et al- Pemphigus vulgaris- A case report and detailed
review of the literature,2011]

43. ORAL PEMPHIGUS VULGARIS:
A CASE REPORT WITH DIRECT
FLOURESCENCE STUDY
BY,
SANGEETHA JEEVAN KUMAR, SP NEHRU ANAND,
NANDHINI GUNASEKARAN, RAJKUMAR KRISHNAN
DEPARTMENT OF ORAL PATHOLOGYAND ORAL
MEDICINE, SRM DENTAL COLLEGE, RAMAPUARAM

44. BIBLIOGRAPHY
Sergei. A. Grando- Pemphigusautoimmunity: /Hypothesisand realities(2011)
Frank. A. Satoro et al- Pemphigus (2013)
Sreeshyla.H.S et al – Oral Pemphigus Vulgaris- Report of a case and review of the
etiopathogenesis(2011)
A.Rocher et al – Revaluating Tzanck Test: A comparative study with direct
immunofluorescence for Herpes virus (2016)
Atiya Yaheen et al- Diagnostic value of Tzanck smear in various erosive, vesicular and
bullous skin lesions (2015)
 Supriya.S. Venugopal et al- Diagnosis and clinical features of Pemphigusvulgaris (2012)

45. Shamimul Hasan et al- Pemphigusvulgaris- A case report and detailed
review of literature (2011)
Yasuo Kitajima- New insights into desmosome regulation and pemphigus
blistering as a desmosome-remodelling disease(2013)