Vesiculobullous diseases

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)

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

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

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.

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

Epithelial attachment apparatus.

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

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 .

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

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

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

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.

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

PEMPHIGUS VULGARIS

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

Intraoral Blisters

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

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.

PEMPHIGUS VULGARIS histology

PEMPHIGUS VULGARIS histology

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

Tzank cells

PEMPHIGUS VULGARIS tazank cells

Intraoral image:-

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

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.

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

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

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

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

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

Usually Buccal mucosa Gingiva & soft palate

PEMPHGOID

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 .

PEMPHGOID occular involvement

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.

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.

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.

PEMPHGOID

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

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

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

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

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

BULLOUS PEMPHGOID

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

BULLOUS PEMPHIGOID HISTOLOGY

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

EPIDERMOLYSIS BULLOSA

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.

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

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

EPIDERMOLYSIS BULLOSA

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

EPIDERMOLYSIS BULLOSA

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

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.

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

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.

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.

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

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)