Vesiculobullous diseases

Vesiculobullous Vesiculobullous diseasesdiseases

PEMPHIGUS VULGARISPEMPHIGUS VULGARISPEMPHGOIDPEMPHGOID

ERYTEMA MULTIFORMEERYTEMA MULTIFORMEEPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSALUPUS ERYTHEMATOSISLUPUS ERYTHEMATOSIS

Dr.khurram zafar Dr.khurram zafar

CLASSIFICATION OF VESICULOBULLOUS CLASSIFICATION OF VESICULOBULLOUS DISEASESDISEASES

VESICLE&BULLAVESICLE&BULLA

A clear fluid lesion just below the A clear fluid lesion just below the epithelium which ruptures to form an ulcer, epithelium which ruptures to form an ulcer, if this is smaller than 5mm then it is a if this is smaller than 5mm then it is a vesicle ,if larger than 5mm than it is a bulla vesicle ,if larger than 5mm than it is a bulla

CLASSIFICATION OF VESICULOBULLOUS CLASSIFICATION OF VESICULOBULLOUS DISEASESDISEASES

CLASSIFICATIONCLASSIFICATIONINTRA EPITHELIAL VESICLESINTRA EPITHELIAL VESICLES: The lesion is formed : The lesion is formed

within the epithelium within the epithelium Acantholytic vesicles : Acantholytic vesicles : This is because of the break This is because of the break down of specialized attachments called the down of specialized attachments called the desmosomes desmosomes Nonacantholytic vesiclesNonacantholytic vesicles: It is usually in the viral : It is usually in the viral infections because of the death or the rupture of the infections because of the death or the rupture of the group of cells.group of cells.

SUB EPITHELIAL VESICLESSUB EPITHELIAL VESICLES: Lesions formed between the : Lesions formed between the epithelium and the lamina propria eg:epithelium and the lamina propria eg: Erthyma multifomeErthyma multifome PhempegoidPhempegoid Dermatitis herpetiformisDermatitis herpetiformis Epidermolysis bullosaEpidermolysis bullosa

PEMPHIGUS VULGARISPEMPHIGUS VULGARIS

Autoimmune disease.Autoimmune disease.

Common in Ashkenazi and Mediterranean jews .Common in Ashkenazi and Mediterranean jews .

Middle aged females.Middle aged females.

Other variants are:Other variants are:

Pemphius VegitansPemphius Vegitans

Pemphigus Foliaceus & ErthematosusPemphigus Foliaceus & Erthematosus

Paraneoplastic pemphigus.Paraneoplastic pemphigus.


CLINICAL FEATURES:CLINICAL FEATURES:

Painful ulcers or bulla are formed which are fluid Painful ulcers or bulla are formed which are fluid filled. filled.

They can be formed any where in the oral cavity .They can be formed any where in the oral cavity .

The bulla is rapidly ruptured leaving a collapsed roof The bulla is rapidly ruptured leaving a collapsed roof of grayish membrane with a red ulcerated base.The of grayish membrane with a red ulcerated base.The ulcer may look like an apthous ulcer or may be large ulcer may look like an apthous ulcer or may be large map shaped.map shaped.

Nikolsky sign is positive.Nikolsky sign is positive.

C/F con…dC/F con…d


Some time the ulcers are joined together to make a Some time the ulcers are joined together to make a confluence this condition is very painful.confluence this condition is very painful.

It has a variable course might involve skin, It has a variable course might involve skin, oesophagus, cervix. oesophagus, cervix.

Protein/fluid,electrolyte and weight loss /secondary Protein/fluid,electrolyte and weight loss /secondary infections.infections.

Fatal if untreated. Fatal if untreated.



PATHOGENESIS:PATHOGENESIS:It is an autoimmune diseaseIt is an autoimmune diseaseThere are circulating antibodies of type IgG.There are circulating antibodies of type IgG.These antibodies are reactive against the These antibodies are reactive against the desmosomes or the tonofilament complex.desmosomes or the tonofilament complex.There destruction or disruption of these There destruction or disruption of these tonofilament complex ,resulting in the loss of tonofilament complex ,resulting in the loss of attachment from cell to cellattachment from cell to cell

path.cont…dpath.cont…d


The epithelial damage is directly proportion to The epithelial damage is directly proportion to the number of the circulating antibobies.the number of the circulating antibobies.The tonofilament or desmosomes are disrupted The tonofilament or desmosomes are disrupted by a proteolytic enzyme which is released by by a proteolytic enzyme which is released by these antibodies .these antibodies .The cell to cell break down also takes place The cell to cell break down also takes place through a complement system but this process through a complement system but this process is not clearly understood . is not clearly understood .


PEMPHIGUS VULGARISPEMPHIGUS VULGARISHISTOPATHOLOGY:HISTOPATHOLOGY:

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

PEMPHIGUS VULGARISPEMPHIGUS VULGARIShistologyhistology

PEMPHIGUS VULGARISPEMPHIGUS VULGARIS histologyhistology

PEMPHIGUS VULGARISPEMPHIGUS VULGARIStazank cellstazank cells

PEMPHIGUS VULGARISPEMPHIGUS VULGARISimmunoflorecenceimmunoflorecence


DIFFRENTIAL DIAGNOSIS:DIFFRENTIAL DIAGNOSIS:

Pempegiod Pempegiod

Erthema multiformeErthema multiforme

Bullous lichen plannus Bullous lichen plannus


TREATMENT:TREATMENT:

High mortality rates previously High mortality rates previously

Introduction of systemic corticosteroids Introduction of systemic corticosteroids like prednisolone in stable cases.like prednisolone in stable cases.

Prednisolone plus azathioprine Prednisolone plus azathioprine methotrexate and cyclophospamide in methotrexate and cyclophospamide in progressed or advance cases. progressed or advance cases.

PEMPHGOIDPEMPHGOID

PEMPHGOIDPEMPHGOID

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

Bullous pemphigoid Bullous pemphigoid

PEMPHGOIDPEMPHGOIDPATHOLOGYPATHOLOGY

Autoimmune diseaseAutoimmune diseaseNot life threateningNot life threateningElderly females above 60 yrs of ageElderly females above 60 yrs of ageLoss of attachment and separation of full thickness Loss of attachment and separation of full thickness epithelium from the lamina propria.epithelium from the lamina propria.Alteration of rete pegsAlteration of rete pegsEpithelium forms the roof of the blistersEpithelium forms the roof of the blistersAuto antibodies are formed against the Auto antibodies are formed against the hemidesmosomes (BPAG-1,230kd;BPAG-2; 180kd.hemidesmosomes (BPAG-1,230kd;BPAG-2; 180kd.Inflammatory Inflammatory cells(lymphocytes,neutrophils,eosinophils)are seen cells(lymphocytes,neutrophils,eosinophils)are seen in the later stagesin the later stages

PEMPHGOIDPEMPHGOID

PEMPHGOIDPEMPHGOID

CLINICAL FEATURES(MMP) CLINICAL FEATURES(MMP)

Oral mucosa is the first site- lesions are rarely Oral mucosa is the first site- lesions are rarely wide spreadwide spread

Subepithelial bullae, ruptured in the later stages.Subepithelial bullae, ruptured in the later stages.

Bleeding in the bullae – bleeding blistersBleeding in the bullae – bleeding blisters

Slow progress, skin involvement absent or rareSlow progress, skin involvement absent or rare

Involvement of eyes, nose larynx, pharynx and Involvement of eyes, nose larynx, pharynx and osephaghus osephaghus

Nikolsky sign is positive Nikolsky sign is positive

PEMPHGOIDPEMPHGOID

occular involvementoccular involvement

PEMPHGOIDPEMPHGOID

CASCADEOF EVENTSCASCADEOF EVENTSAntibody antigen complexAntibody antigen complex

Complement activationComplement activation

Neutrophils & Eosinophils recruited Neutrophils & Eosinophils recruited

Release of proteases by the recruited cellsRelease of proteases by the recruited cells

Sub epithelial blister formationSub epithelial blister formation

PEMPHGOIDPEMPHGOID

PEMPHGOIDPEMPHGOID

MANAGEMENTMANAGEMENT

Confirm diagnosisConfirm diagnosis

Topical corticosteroidsTopical corticosteroids

Ocular involvement –systemic steroids.Ocular involvement –systemic steroids.

ERYTEMA ERYTEMA MULTIFORMEMULTIFORME

ERYTEMA MULTIFORMEERYTEMA MULTIFORME

Mucocutaneous diseaseMucocutaneous disease

Males adolosents , young adults are Males adolosents , young adults are affected moreaffected more


AETIOLOGY /PATHOLOGYAETIOLOGY /PATHOLOGY

Unclear aetiology and pathogenesisUnclear aetiology and pathogenesis

Infections like HSV can trigger this diseaseInfections like HSV can trigger this disease

Drugs like Sulphonamides ,barbituratesDrugs like Sulphonamides ,barbiturates

Suggested cause is also given as to a type Suggested cause is also given as to a type III hypersensitivity reactionIII hypersensitivity reaction


CLINICAL FEATURESCLINICAL FEATURESProdomal signs:Prodomal signs:Upper respiratory infectionUpper respiratory infectionHeadache and malaise Headache and malaise Nausea and arthralgiaNausea and arthralgia

C/Fcont…dC/Fcont…d


Signs during the disease:Signs during the disease:Red macules – 1cm or more in diameter with Red macules – 1cm or more in diameter with cyanotic centercyanotic centerLips grossly swollen ,split crusted bleedingLips grossly swollen ,split crusted bleeding Widespread fibrin covered erosions and Widespread fibrin covered erosions and erythema in the mouth.erythema in the mouth.Mild feverMild feverConjunctivitis may be associated Conjunctivitis may be associated Attacks recur at the intervals of several monthsAttacks recur at the intervals of several monthsUsually self limiting.Usually self limiting.



HISTOPATHOLOGYHISTOPATHOLOGY

Necrosis of the kertinocytesNecrosis of the kertinocytes

Inter & intra cellular odema.Inter & intra cellular odema.

Subepithelial blisters are commonSubepithelial blisters are common

Infiltration of inflammatory cells.Infiltration of inflammatory cells.



MANAGEMENTMANAGEMENTNo specific treatment required , if HSV inf.. No specific treatment required , if HSV inf.. acycoviracycovirSystemic steroids may give relief to the Systemic steroids may give relief to the fever.fever.In severe cases antibiotics are used to In severe cases antibiotics are used to prevent ant secondary infections.prevent ant secondary infections.Symptomatic –analgesics, antipyretics, Symptomatic –analgesics, antipyretics, antihistamines. antihistamines.

EPIDERMOLYSIS EPIDERMOLYSIS BULLOSABULLOSA

EPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSA

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

EPIDERMOLYSIS BULLOSAEPIDERMOLYSIS BULLOSAMAJOR CATEGORIES OF EPIDERMOLYSIS BULLOSAMAJOR CATEGORIES OF EPIDERMOLYSIS BULLOSATypeType Genetic PatternGenetic Pattern Separation LevelSeparation Level Defec. Structure Defec. Structure HereditaryHereditarySimplexSimplex Autosomal dominant Intraepithelial Autosomal dominant Intraepithelial linking proteinslinking proteinsJunctionalJunctional autosomal recessive lamina lucidaautosomal recessive lamina lucida anchoring filamentsanchoring filamentsDystrophicDystrophic autosomal dominant sublamina densa autosomal dominant sublamina densa type VII collagentype VII collagen

AcquiredAcquiredAcquisitaAcquisita None/autoimmune sublamina densaNone/autoimmune sublamina densa type VII collagentype VII collagen


HEREDITARY TYPES:HEREDITARY TYPES:

Congenital absence of componentsCongenital absence of components

ACQUIRED TYPES:ACQUIRED TYPES:

Autoantibodies (IgG; sometimes IgA) to Autoantibodies (IgG; sometimes IgA) to type VII collagen.type VII collagen.



CLINICAL FEATURESCLINICAL FEATURES1.1.Epidermolysis Bullosa SimplexEpidermolysis Bullosa Simplex

Mild form; autosomal dominantMild form; autosomal dominantSites of trauma/frictionSites of trauma/frictionInvolve hands, feet and neck; occ. knees Involve hands, feet and neck; occ. knees and elbowsand elbowsTeeth not affected; intraoral blisters seenTeeth not affected; intraoral blisters seenAppears during infancyAppears during infancy



2.2. Junctional Epidermolysis BullosaJunctional Epidermolysis BullosaSevere form; autosomal recessiveSevere form; autosomal recessiveHaemorrhagic blisters; loss of nails, large Haemorrhagic blisters; loss of nails, large blisters of face, trunk and extremitiesblisters of face, trunk and extremitiesGeneralized scarring and atrophyGeneralized scarring and atrophyIntraorally-haemorrhagic blisters of palate, Intraorally-haemorrhagic blisters of palate, perioral and perinasal areasperioral and perinasal areasErupted teeth exhibit hypoplastic and severely Erupted teeth exhibit hypoplastic and severely pitted enamel prone to cariespitted enamel prone to caries


3.3. Dystrophic Epidermolysis BullosaDystrophic Epidermolysis BullosaBoth autosomal dominant and recessive; recessive is Both autosomal dominant and recessive; recessive is severesevereLesions are birth; arise at pressure sitesLesions are birth; arise at pressure sitesBlisters rupture leaving painful ulcers which heal with Blisters rupture leaving painful ulcers which heal with large scars that undergo contractures, leading to loss of large scars that undergo contractures, leading to loss of motility and claw-like hands (Mitten Deformity)motility and claw-like hands (Mitten Deformity)Teeth exhibit delayed eruption and enamel hypoplasia Teeth exhibit delayed eruption and enamel hypoplasia with rapid caries developmentwith rapid caries developmentScarring around mouth leads to diminished opening, Scarring around mouth leads to diminished opening, ankyloglossiaankyloglossia


Epidermolysis Bullosa AcquisitaEpidermolysis Bullosa Acquisita

Non-hereditary form; appears in adulthoodNon-hereditary form; appears in adulthood

Clinically resembles autosomal dominant Clinically resembles autosomal dominant type of JEB-type VII collagentype of JEB-type VII collagen

Trauma/friction induced blisters of knees, Trauma/friction induced blisters of knees, elbows, hands and feet- heal with scarselbows, hands and feet- heal with scars

Intraoral blisters rare- when present same Intraoral blisters rare- when present same picture same picture as JEBpicture same picture as JEB


HISTOPATHOLOGYHISTOPATHOLOGY

Simplex type exhibits zone of cleavage Simplex type exhibits zone of cleavage (intra-epithelial) above basal cell layer.(intra-epithelial) above basal cell layer.

Remaining types have sub-epithelial Remaining types have sub-epithelial separationseparation



MANAGEMENTMANAGEMENTNo specific treatment available for hereditary No specific treatment available for hereditary typestypesAcquired form maybe treated with Acquired form maybe treated with corticosteroids and immuno-suppressantscorticosteroids and immuno-suppressantsMaintenance of pt’s nutritional and oral hygiene Maintenance of pt’s nutritional and oral hygiene statusstatusWound healing techniquesWound healing techniquesPrevention of infectionsPrevention of infectionsSystemic use of Phenytoin (also acts as a Systemic use of Phenytoin (also acts as a collagenase inhibitor)collagenase inhibitor)

Technology

Vesiculobullous diseases