This document describes different types of vesiculobullous diseases classified according to the Fitzpatrick system based on the anatomical level of blister formation. It discusses conditions such as pemphigus vulgaris, pemphigus vegetans, pemphigus foliaceus, paraneoplastic pemphigus, bullous pemphigoid, cicatricial pemphigoid, and familial benign pemphigus. For each condition, it provides details on pathogenesis, clinical features, histopathology, immunopathology, and oral manifestations when present.

1. • FITZ PATRICK CLASSIFICATION - ACCORDING TO
ANATOMICAL PLANE
A. INTRA EPIDERMAL BLSTER
I. GRANULAR LAYER
a) PEMPHIGUS FOLIACEOUS
b) PEMPHIGUS ERYTHEMATOSUS
c) FRICTIONAL BLISTERS
d) STAPHYLOCOCCAL SCALDED SYNDROME
Vesiculo-bullous Diseases

2. II. SPINOUS LAYER
a) ECZEMATOUS DERMATITIS
b) SECONDARY TO HEAT OR COLD
c) HERPES VIRUS INFECTION
d) FAMILIAL BENIGN PEMPHIGUS
III. SUPRABASAL
a)PEMPHIGUS VULGARIS
b)PEMPHIGUS VEGETANS
c)DARIER’S DISEASE
IV. BASAL LAYER
a)ERYTHEMA MULTIFORMAE
b)TOXIC EPIDERMAL NECROLYSIS
c)LUPUS ERYTHEMATOSUS
d)LICHEN PLANUS
e)EPIDERMOLYSIS BULLOSA SIMPLEX

3. B. DERMAL-EPIDERMAL JUNCTIONAL ZONE
I. LAMINA LUCIDA
a) BULLOUS PEMPHIGOID
b) CICATRICIAL PEMPHIGOID
c) EPIDERMOLYSIS BULLOSA – JUNCTIONAL
II. BELOW BASAL LAMINA
a) ERYTHEMA MULTIFORMAE
b) EPIDERMOLYSIS BULLOSA – DYSTROPHICA

4. 1. PRIMARY BLISTERING
a) PEMPHIGUS
b) BULLOUS PEMPHIGOID
c) CICATRICIAL PEMPHIGOID
d) EPIDERMOLYSIS BULLOSAACQUTISA
2. SECONDARY BLISTERING
a) CONTACT DERMATITIS/ STOMATITIS
b) ERYTHEMA MULTIFORMAE
c) TOXIC EPIDERMAL NECROLYSIS
2nd Classification

5. 3. INFECTION
a) VARICELLA ZOSTER
b) HERPES SIMPLEX
c) BULLOUS IMPETIGO
4. SYSTEMIC DISEASE
a) INFECTION – CUTANEOUS EMBOLI
5. METABOLIC
a) DIABETIC WITH BULLAE
b) PORPHYRIA CUTANEA TARDA

6. Pemphigus

7. • Pemphix = Bubble / Blister
• Pemphigus is a serious, autoimmune chronic skin disease
characterized by appearance of vesicles and bullae, small to
large fluid filled blisters on skin as well as mucous membrane
that develop in cycles.
• Characterized by the finding of circulating immunoglobulin
G (IgG) antibody directed against the cell surface of
keratinocytes
• Derieved from Greek word
• Whichman in 1971.
• It affects 0.1 to 0.5 patients per 100000 population per year

8. • Four primary subsets:
– Pemphigus Vulgaris
– Pemphigus Vegetans
– Pemphigus Foliaceous
– Paraneoplastic pemphigus
• 70% of pemphigus cases are Pemphigus vulgaris

9. • Pathogenesis:
– It is an autoimmune disease where autoantibodies attack
the kertinocyte cell junctions leading to destruction of
tonofilament complex, resulting in the loss of attachment
from cell to cell
– These antibodies are reactive against the desmosomes or
the tonofilament complex , specifically to Desmoglein-1
and Desmoglein-3
– The Circulating antibodies are of type IgG1 & IgG4
subclasses
Pemphigus Vulgaris

12. • Age of onset approx. 50-60yrs
• Numerous rapidly appearing vesicles and bullae of varying
diameter
• Contain thin, watery fluid in beginning which later becomes
purulent or sanguineous
• Ruptured vesicles and bullae leave raw eroded surface
General Clinical Features

14. • Nikolsky’s sign: dislodgement of intact superficial epidermis
by a shearing force, indicating a plane of cleavage in the
skin. Rubbing of apparently unaffected skin leading to loss
of superficial epithelium.
• Characteristic sign of pemphigus and is caused by
perivesicular edema which disrupts the dermal-epidermal
junction

16. • Mucosal lesions may precede skin manifestations by months
• 50-70% of pts with P. Vulgaris show mucosal involvement
• Intact vesicles & bullae are rare and most often pts present
with ill-defined, irregularly shaped, gingival, buccal or
palatine erosions which are painful and slow to heal
• Erosions can spread to involve larynx with subsequent
hoarseness of voice.
• Other mucosal surfaces may be involved such as conjunctiva,
genital regions, etc.
Oral Manifestations

20. • Intraepithelial blister formation just above the basal layer
producing “Suprabasilar Split”
• Prevesicular edema weakens the junctions and intercellular
bridges between epithelial cells disappear, resulting in loss of
cohesiveness or Acantholysis
• Fluid filled vesicular space is formed between the basal and
parabasal layers of epithelium.
• Basal cells are intact and show a “tomb-stone” appearance
Histologic Features

22. • Tzanck cells: Clumps of epithelial cells found within the
vesicular space of freshly opened vesicles or bulla
• Characterized by degenerative changes including swelling of
nuclei, hyperchromatic staining and marked increase in
RNA content of the cytoplasm.
• Such Smears from pts with pemphigus comfirming the
typical tzanck cells is called as “Tzanck Test”

24. • 1-2 day old vesicles and bullae contain variable numbers of
Neutrophils and lymphocytes
• Relative scarcity of inflammatory cell infiltration in vesicle
and at the connective tissue base is confirmatory of
Pemphigus

25. • Direct immunofluorescence demonstrates immunoglobulins,
especially IgG alone or in combination with C3, IgA or IgM,
in the intercellular spaces of clinically normal adjacent
epithelium
• GRANULAR or FISH-NET pattern seen in
immunoflourescence
• Indirect immunofluorescence can also be used in diagnosis
Immunoflourescence studies

28. • Rare variant and Occurs in 1-2% of pemphigus vulgaris
• 2 clinical variants exist according to initial presentation:
– Neumann Type: Flaccid bullae & Erosions seen
– Hallopeau: Pustules seen
• Both subtypes eventually develop hyperpigmented
vegetative plaques with pustules and hypertrophic
granulation tissue at periphery
Pemphigus Vegetans

29. • Clinical lesions typically located at Intertrigenous areas
and Oral mucosa
• Cerebriform tongue is a characteristic feature seen on
tongue of Pemphigus vegetans characterized by a pattern
of Gyri & Sulci on dorsum of tongue
• The surfaces of the vermillion border of the lips, the gums,
and the hard palate show multiple white verrucous
papules, fissures, erosions, and crusts forming a
cobblestone pattern.

31. • IgG4 subclass autoantibodies directed to Desmoglein-1
expressed mainly in granular cell layer of epidermis
• Precipitating factors : Medications or Ultraviolet Rays
• 6 subtypes exist :
– Pemphigus erythematosus
– Pemphigus herpetiformis
– Endemic Pemphigus foliaceus
– Immunoglobulin A Pemhigus
– Paraneoplastic Pemphigus foliaceus
– Drug-induced Pemphigus foliaceus
• Mild type of pemphigus and Oral lesions are rare
Pemphigus Foliaceus

32. • Clinical features: Bullous lesions which rapidly rupture
and dry to leave masses of flakes or scales suggestive of
exfoliative dermatitis
• Brazilian pemphigus (Fogo selvagem / Brazilian wildfire)
is a mild endemic form seen often in children of brazil
• Histopathology similar to pemphigus vulgaris with the
Acantholysis seen in the superficial epidermis

35. • Oral lesions and bullous eruptions similar to pemphigus
developing in patients with underlying neoplasms
• Tumor antigens evoke an immune response that leads to
the development of an autoimmune response to
intercellular adhesins (plakins)
• Paraneoplastic pemphigus is mostly fatal
• Oral Manifestations: Painful Oral erosions & ulcerations
accompanied with cutaneous eruptions which could be
morbilliform / urticarial / bullous / papulosquamous / or
erythema multiforme like lesions
• Lips, gingiva, buccal mucosa, lingual mucosa, etc can be
affected. Lip lesions show erosions & crusting similar to
Steven johnson syndrome
Paraneoplastic Pemphigus

36. • Hailey – Hailey disease
• Autosomal dominant disease showing genetic defect of
“Calcium pump protein”
• Oral lesions occur occasionally and the lesions develop
crops or vesicles which rapidly rupture leaving raw
eroded areas
• Histopathology: More extensive acantholysis than in
pemphigus vulgaris and with less damage to the
acantholytic cells
• Occasional persistence of intercellular bridges between
acantholytic cells and adjacent normal cells gives a
DILAPIDATED BRICK WALL effect
Familial Benign Pemphigus

38. • Benign mucous membrane pemphigoid / Ocular pemphigus
• Autoantibodies targeted against basement membrane zone
antigens. Specifically IgG4 antibodies directed to:
– Bullous pemphigoid antigen -2 (BPAG2) (BP180)
– Epiligrin (Laminin-5)
• Female : Male = 2:1
• Usually between 40 – 50yrs of age
• Typically the vesiculobullous lesions occur on oral mucosa
and conjunctiva as well as skin lesions around genitalia and
near body orifices
• The ocular lesions typically heal with a SCAR formation
Cicatricial Pemphigoid

41. • Vesiculobullous lesions prominently seen on the Gingiva
which are thick-walled and may persist for 24-48hrs before
rupturing and desquamating
• Ruptured area is raw, eroded and shows bleeding surface
• Gingivae manifest persistent erythema for weeks to months
after healing
• Oral lesions rarely scar
Oral Manifestations

44. • Vesicles and bullae are sub-epidermal rather than supra-
basilar and there is no evidence of acantholysis
• Basement membrane structures detach along with the
epithelium from the underlying connective tissue
• Non specific chronic inflammatory infiltrate in the stroma
chiefly lymphocytes, plasma cells and eosinophils
• Immunofluorescence reveals continuous linear band of
fluorescence at the basement membrane region
Histological Features

47. Bullous Pemphigoid
Parapemphigus

48. • Parapemphigus
• Rarely involves mucous membrane
• Autoantibodies against basementmembrane zone antigens:
– Bullous pemphigoid antigen -1 (BPAG2) (BP230)
– Bullous pemphigoid antigen -2 (BPAG2) (BP180)
• IgG antibodies bind to basement membrane and activate
compliment and inflammatory mediators. The activated
compliment attracts inflammatory cells to the basement
membrane
Bullous Pemphigoid

49. • Disease of elderly people
• Generalized non-specific rash upon the limbs which later
shows the appearance of vesiculobullous lesions
• Vesicles and bullae are relatively thick walled and may
remain intact for some days
• Later it may rupture and leave a raw eroded area which
heals rapidly
• Oral lesions are rare and if present they are typically
similar to those of cicatricial pemphigoid and mostly seen
on the gingiva (desquamative gingivitis)

52. • Bullae are sub-epidermal and non-specific with No
evidence of acantholysis and epithelium appears normal
• Basement membrane structures remain attached to the
connective tissue and separate from the overlying
epithelium
• Vesicles contain fibrinous exudate admixed with occasional
inflammatory cells
Histological Features