1. Vesiculobullous diseases

2. A vesiculobullous disease is a type of mucocutaneous disease that is characterized by vesicles and bullae (i.e. blisters).
Both vesicles and bullae are fluid-filled lesions, and they are distinguished by size (vesicles being less than 5 mm and bulla being larger than 5 mm)

3. CLASSIFICATION OF VESICULOBULLOUS DISEASES
INTRA EPITHELIAL VESICLES: The lesion is formed within the epithelium
Acantholytic vesicles : This is because of the break down of specialized attachments called the desmosomes
Nonacantholytic vesicles: It is usually in the viral infections because of the death or the rupture of the group of cells.
SUB EPITHELIAL VESICLES: Lesions formed between the epithelium and the lamina propria eg:
Erthyma multifome
Phempegoid
Dermatitis herpetiformis
Epidermolysis bullosa

4. Classification:- Viral diseases Immunologic Disease Hereditary Disease
Herpes simplex infection
Varicella-Zoster infection
Immunologic Disease
Pemphigus Vulgaris
Mucous membrane pemphigoid (MMP)
Bullous Pemphigoid (BP)
Dermatitis Herpetiformis
Hereditary Disease
Epidermolysis Bullosa
Angina bullosa heamorrhagica

5. What is an Immunologic Disease ?
A disease resulting from A disordered immune reaction in which antibodies are produced against one's own tissues, as systemic lupus erythematosus or rheumatoid arthritis.

6. PEMPHIGUS It is an autoimmune disease
There are circulating antibodies of type IgG.
These antibodies are reactive against the desmosomes or the tonofilament complex.
There destruction or disruption of these tonofilament complex ,resulting in the loss of attachment from cell to cell

7. Epithelial attachment apparatus.

8. Types:- Pemphigus Vulgaris Pemphigus Foliacues Pemphigus Erythematous
Pemphigus Vegetans
Vulgaris/vegetans Affect the Whole Epithelium
Erythematous/Foliaceus Upper Prickle cell layer

9. PEMPHIGUS VULGARIS
The epithelial damage is directly proportion to the number of the circulating antibobies.
The tonofilament or desmosomes are disrupted by a proteolytic enzyme which is released by these antibodies .

10. Pathogenesis:- Circulating autoantibodies IgG
Reactive against epithelial desmosome-tonofilament complexes
(Desmoglein 3)
result in dissolution or disruption of intercellular junctions & loss of cell to cell adhesion

11. Immunologic Disease Pemphigus Vulgaris Immunobullous disorder
Middle-age disease (40-60yr)
Affects :- Skin & Mucous membrane
50% cases begin in mouth (First to SHOW last to GO)
Characterized by :-
1)Intraepithelial Blister formation
2)Painful ulcers preceded by bulla
3)Bullae are fragile & breakdown rapidly to form CRUSTED, ERODED lesions
4)Ulcers range from small APTHOUS like to large MAP
like lesions

12. Pemphigus vulgaris. Multiple erosions of the left buccal mucosa.
Pemphigus vulgaris. Large, irregularly shaped ulcerations involving the floor of the mouth and ventral tongue.

13. PEMPHIGUS VULGARIS
Some time the ulcers are joined together to make a confluence this condition is very painful.
It has a variable course might involve skin, oesophagus, cervix.
Protein/fluid,electrolyte and weight loss /secondary infections.
Fatal if untreated.

14. Pemphigus vulgaris. This flaccid cutaneous bulla is characteristic of skin involvement.
Pemphigus vulgaris. Multiple erosions affecting the marginal gingiva.

15. PEMPHIGUS VULGARIS

16. Nikolsky’s Sign
Gentle traction on clinically unaffected mucosa may produce stripping of epithelium, a +ve nikolsky sign

17. Intraoral Blisters

18. Diagnosis:- Skin biopsy History Clinical examination
Red painful ulcers
Bullae formation
+ve nikolsky’s sign
small vesicles on soft palate, buccal mucosa, floor of the mouth
Skin biopsy
Immunofluorescence
(DIF) Fish-net appearance (IgG, C3 )
(IDIF) +ve IgG 90%
ELISA

21. PEMPHIGUS VULGARIS HISTOPATHOLOGY:
Intra epithelial vesicles or bulla and cleft like spaces are produced by acantolysis
These changes are in the stratum spinosum or the prickle cell layer
The basal cell remain attach to the lamina propria and project into the bulla like tombstones.
Inflammatory cells are very scanty however eosinophils may be seen.
Acantholytic stratum spinosum cells occur singly or are in the forms of clumps lying freely within the blister fluid. These cell loose there polyhedral morphology rather they are small rounded and contain hyper chromatic nuclei called the TAZANK CELLS.

22. PEMPHIGUS VULGARIS histology

23. PEMPHIGUS VULGARIS histology

24. These changes are seen in the STRATUM SPINOSUM or THE PRICKLE CELL LAYER
The basal cells loose their intercellular bridges but they remain attach to the dermis, giving a TOMBSTONE appearance
The blister cavity contains acantholytic cells which often show degenerative changes

25. Tzank cells

26. PEMPHIGUS VULGARIS tazank cells

27. Intraoral image:-

28. D/D MMP EM Erosive lichen planus Paraneoplastic pemphigus
Apthous Ulcers

29. PEMPHIGUS VULGARIS TREATMENT: High mortality rates previously
Introduction of systemic corticosteroids like prednisolone in stable cases.
Prednisolone plus azathioprine methotrexate and cyclophospamide in progressed or advance cases.

30. PEMPHGOID Mucous membrane pemphigoid (cicatricial) CIKA-TRI-CIAL
Bullous pemphigoid

31. PEMPHGOID PATHOLOGY Autoimmune disease Not life threatening
Elderly females above 60 yrs of age
Loss of attachment and separation of full thickness epithelium from the lamina propria.
Alteration of rete pegs
Epithelium forms the roof of the blisters
Auto antibodies are formed against the hemidesmosomes (BPAG-1,230kd;BPAG-2; 180kd.
Inflammatory cells(lymphocytes,neutrophils,eosinophils) are seen in the later stages

32. PEMPHGOID CASCADEOF EVENTS Antibody antigen complex 
Complement activation
Neutrophils & Eosinophils recruited
Release of proteases by the recruited cells
Sub epithelial blister formation

33. Pathogenesis:- Auto-Antibodies IgG Target antigen BP 180 & laminin 5
Result in sub-epithelial clefting

34. Mucous membrane pemphigoid
Chronic blistering disease
Affects:- oral & ocular mucous membrane
Adults and elderly (affect women more than men)
Characterized by:-
Sub-epithelial bulla formation
intraoral intact bullae present on gingiva or soft palate
ulcerated area of mucosa involve buccal, palatal or lip mucosa
desquamative gingivitis
lesions are chronic & persistent heal with a scar (cicatrix) particularly lesions of eye

35. Usually Buccal mucosa Gingiva & soft palate

36. PEMPHGOID

37. PEMPHGOID CLINICAL FEATURES(MMP)
Oral mucosa is the first site- lesions are rarely wide spread
Subepithelial bullae, ruptured in the later stages.
Bleeding in the bullae – bleeding blisters
Slow progress, skin involvement absent or rare
Involvement of eyes, nose larynx, pharynx and osephaghus .

38. PEMPHGOID occular involvement

39. Mucous membrane pemphigoid
Mucous membrane pemphigoid. Although cutaneous lesions are not common, tense bullae such as these may develop on the skin of 20% of affected patients.

40. Mucous membrane pemphigoid
Mucous membrane pemphigoid. One or more intraoral vesicles, as seen on the soft palate. Usually, ulcerations of the oral mucosa are also present.
Mucous membrane pemphigoid. Large, irregular oral ulcerations characterize the lesions after the
initial bullae rupture.

41. Mucous membrane pemphigoid
Mucous membrane pemphigoid. Often the gingival tissues are the only affected site, resulting in a clinical pattern known as desquamative gingivitis. Such a pattern may also be seen with lichen planus and pemphigus vulgaris.

42. PEMPHGOID

43. Mucous membrane pemphigoid
Mucous membrane pemphigoid. Mediumpower photomicrograph of perilesional tissue shows
characteristic subepithelial clefting.
Mucous membrane pemphigoid. Direct immunofl uorescence studies show a deposition of
immunoreactants at the basement membrane zone of the
epithelium

44. D/D Pemphigus vulgaris Erosive lichen planus
If attatched gingiva involve then ;
atrophic lichen planus , contact allergy
D/D

45. Diagnosis History (Drug history, drug induced)
Biopsy (Sub epithelial blister formation)
Direct Immunofluorescence (linear BM)
Indirect Immunofluorescence (Pemphigoid antibodies)

46. Management Topical corticosteroids Systemic corticosteroids
Azathriopine
Dapsone (diaminodiphenylsulfone) 25 mg & 100 mg Tablets for Oral Use
Referral for Eyes, skin, larynx, genitalia

47. Bullous Pemphigoid Sub epidermal blisters Elder 7th & 8th decade
Involves Skin & mucous membrane
Characterized by:-
Skin lesions (Tense vesicles on trunk and limbs) preceded by erythematous popular eruption
Oral lesions (bullae & erosions mostly noted on attached gingiva)
Other sites:- soft palate , buccal mucosa & floor of mouth

49. BULLOUS PEMPHGOID

50. Bullous pemphigoid. These oral lesions appear as large, shallow ulcerations involving the soft palate.

51. BULLOUS PEMPHIGOID HISTOLOGY

52. Diagnosis
History
Biopsy demonstrate IgG or c3 in a linear distribution
Main target antigen BP 230 & BP 180
BP 230 & BP Important proteins in maintaining the structural integrity of the basement membrane i.e. in providing COHESION of the dermis to the epithelium

53. EPIDERMOLYSIS BULLOSA

54. EPIDERMOLYSIS BULLOSA
Definition:
A large group of clinically similar desquamating disease processes of the skin and mucosa
Have in common the separation of the epithelium from the underlying connective tissue.
and the formation of large blisters that frequently result in extensive and often immobilizing scar formation.

55. EPIDERMOLYSIS BULLOSA
MAJOR CATEGORIES OF EPIDERMOLYSIS BULLOSA
Type Genetic Pattern Separation Level Defec. Structure
Hereditary
Simplex Autosomal dominant Intraepithelial linking proteins
Junctional autosomal recessive lamina lucida anchoring filaments
Dystrophic autosomal dominant sublamina densa type VII collagen
Acquired
Acquisita None/autoimmune sublamina densa type VII collagen

56. EPIDERMOLYSIS BULLOSA
HEREDITARY TYPES:
Congenital absence of components
ACQUIRED TYPES:
Autoantibodies (IgG; sometimes IgA) to type VII collagen.

57. EPIDERMOLYSIS BULLOSA

58. EPIDERMOLYSIS BULLOSA
CLINICAL FEATURES
1. Epidermolysis Bullosa Simplex
Mild form; autosomal dominant
Sites of trauma/friction
Involve hands, feet and neck; occ. knees and elbows
Teeth not affected; intraoral blisters seen
Appears during infancy

59. EPIDERMOLYSIS BULLOSA

60. EPIDERMOLYSIS BULLOSA
2. Junctional Epidermolysis Bullosa
Severe form; autosomal recessive
Haemorrhagic blisters; loss of nails, large blisters of face, trunk and extremities
Generalized scarring and atrophy
Intraorally-haemorrhagic blisters of palate, perioral and perinasal areas
Erupted teeth exhibit hypoplastic and severely pitted enamel prone to caries

61. Epidermolysis bullosa
Epidermolysis bullosa. Complete separation of the epithelium from the connective tissue is seen in this photomicrograph of a tissue section obtained from a patient affected by a junctional form of epidermolysis bullosa.

62. EPIDERMOLYSIS BULLOSA
3. Dystrophic Epidermolysis Bullosa
Both autosomal dominant and recessive; recessive is severe
Lesions are birth; arise at pressure sites
Blisters rupture leaving painful ulcers which heal with large scars that undergo contractures, leading to loss of motility and claw-like hands .
Teeth exhibit delayed eruption and enamel hypoplasia with rapid caries development
Scarring around mouth leads to diminished opening, ankyloglossia

63. Epidermolysis bullosa
Epidermolysis bullosa. A young girl, affected by the dominant dystrophic form of epidermolysis bullosa, shows the characteristic hemorrhagic bullae, scarring, and erosion associated with minimal trauma to the hands.

64. Epidermolysis bullosa
Epidermolysis bullosa. A teenaged boy, affected by dominant dystrophic epidermolysis bullosa, shows a reduced depth of the labial vestibule caused by repeated mucosal tearing and healing with scarring.

65. EPIDERMOLYSIS BULLOSA
Epidermolysis Bullosa Acquisita
Non-hereditary form; appears in adulthood
Clinically resembles autosomal dominant type of JEB-type VII collagen
Trauma/friction induced blisters of knees, elbows, hands and feet- heal with scars
Intraoral blisters rare- when present same picture same picture as JEB

66. EPIDERMOLYSIS BULLOSA
MANAGEMENT
No specific treatment available for hereditary types
Acquired form maybe treated with corticosteroids and immuno-suppressants
Maintenance of pt’s nutritional and oral hygiene status
Wound healing techniques
Prevention of infections
Systemic use of Phenytoin (also acts as a collagenase inhibitor)