Vesiculobullous diseases

Vesiculobullous Vesiculobullous diseasesdiseases

PEMPHIGUS VULGARISPEMPHIGUS VULGARISPEMPHIGUS FOLIACEUSPEMPHIGUS FOLIACEUSBULLOUS PEMPHIGOIDBULLOUS PEMPHIGOID

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 vegetansPemphius vegetans

Paraneoplastic pemphgusParaneoplastic pemphgus


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.


Sometimes the ulcers are joined together to make a Sometimes 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

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 layerInflammatory 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 TZANK contain hyper chromatic nuclei called the TZANK CELLS.CELLS.

PEMPHIGUS VULGARISPEMPHIGUS VULGARIShistologyhistology

PEMPHIGUS VULGARISPEMPHIGUS VULGARIStzank cellstzank cells

DIAGNOSISDIAGNOSIS

Skin biopsySkin biopsy

Electron microscopy has shown that Electron microscopy has shown that widening of the intercellular space is widening of the intercellular space is followed by splitting of the desmosome followed by splitting of the desmosome junctions.junctions.

Direct & indirect immunofluorescenceDirect & indirect immunofluorescence

ELISAELISA

Direct immunofluorescence Direct immunofluorescence

Indirect immunofluorescence Indirect immunofluorescence


DIFFRENTIAL DIAGNOSIS:DIFFRENTIAL DIAGNOSIS:

Pemphegoid Pemphegoid

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 cyclophosphamide in methotrexate and cyclophosphamide in progressed or advanced cases. progressed or advanced cases.

Pemphigus Pemphigus foliaceusfoliaceus

DefinitionDefinition: Blistering in this group of : Blistering in this group of autoimmune diseases is high in the autoimmune diseases is high in the epidermis, either in the granular layer or just epidermis, either in the granular layer or just beneath the stratum corneum.beneath the stratum corneum.

Antibody binding may have a direct effect on Antibody binding may have a direct effect on the function of the desmosomal cadherins in the function of the desmosomal cadherins in the upper epidermis, causing detachment of the upper epidermis, causing detachment of keratinocytes.keratinocytes.

Desmoglein-l is present but only weakly Desmoglein-l is present but only weakly expressed in mucosae accounting for the expressed in mucosae accounting for the lack of mucosal involvement in pemphigus lack of mucosal involvement in pemphigus foliaceus.foliaceus.

Clinical featureClinical featureThe onset is usually insidious with scattered, scaly The onset is usually insidious with scattered, scaly lesions involving the 'seborrhoeic' areas: scalp, lesions involving the 'seborrhoeic' areas: scalp, face, chest and upper back. Blistering may not be face, chest and upper back. Blistering may not be obvious because the cleavage is superficial and the obvious because the cleavage is superficial and the small flaccid blisters rupture easily.small flaccid blisters rupture easily.

Oral lesions are uncommon.Oral lesions are uncommon.

Pemphigus foliaceus is generally regarded as a Pemphigus foliaceus is generally regarded as a benign disease which responds well to treatment benign disease which responds well to treatment and may remit. and may remit.

Pemphigus foliaceusPemphigus foliaceus

Pemphigus foliaceusPemphigus foliaceushistologyhistology

TREATMENTTREATMENTPotent topical or intralesional steroids or, if Potent topical or intralesional steroids or, if control is inadequate, prednisolone 20-40 control is inadequate, prednisolone 20-40 mg/ day.mg/ day.

Azathioprine or cyclophosphamide are Azathioprine or cyclophosphamide are effective adjuncts to oral steroids in severe effective adjuncts to oral steroids in severe cases. Hydroxychloroquine 200/mg twice cases. Hydroxychloroquine 200/mg twice per day has also been recommended as per day has also been recommended as adjuvant therapy. Intravenous Ig has been adjuvant therapy. Intravenous Ig has been reported as effective in resistant cases.reported as effective in resistant cases.

BULLOUS PEMPHIGOIDBULLOUS PEMPHIGOIDBullous pemphigoid is an affliction of elderly Bullous pemphigoid is an affliction of elderly people,with onset usually after 60 years of people,with onset usually after 60 years of age.age.

The blister in bullous pemphigoid is The blister in bullous pemphigoid is subepidermal with an intact and often viable subepidermal with an intact and often viable epidermis forming the roof.epidermis forming the roof.

Bullous pemphigoid commonly starts with Bullous pemphigoid commonly starts with itching and a non-specific rash on the limbs itching and a non-specific rash on the limbs that may be either urticaria-like or that may be either urticaria-like or occasionally eczematous and rarely may occasionally eczematous and rarely may simulate vesicular eczema. simulate vesicular eczema.

PEMPHGOIDPEMPHGOIDBlisters may arise on erythematous and on Blisters may arise on erythematous and on normal skin and may be associated with dermal normal skin and may be associated with dermal edema. The blisters are tense and dome edema. The blisters are tense and dome shaped, obtaining a diameter of many shaped, obtaining a diameter of many centimeteres.centimeteres.

The blisters are tough and may remain intact for The blisters are tough and may remain intact for several days, the contents often becoming jelly-several days, the contents often becoming jelly-like with coagulated fibrin.like with coagulated fibrin.

Mucosal lesions occur less frequently and are Mucosal lesions occur less frequently and are less severe than in pemphigus vulgaris and are less severe than in pemphigus vulgaris and are usually confined to the mouth.usually confined to the mouth.

BULLOUS PEMPHGOIDBULLOUS PEMPHGOID

BULLOUS PEMPHIGOIDBULLOUS PEMPHIGOIDHISTOLOGYHISTOLOGY

PEMPHGOIDPEMPHGOID

Untreated bullous pemphigoid runs a Untreated bullous pemphigoid runs a chronic, self limiting course over a number chronic, self limiting course over a number of months or years.of months or years.

The disease duration is usually 3-6 years, The disease duration is usually 3-6 years, with most patients achieving complete with most patients achieving complete remission off treatment.remission off treatment.

TREATMENTTREATMENTTopical and systemic steroids are the Topical and systemic steroids are the mainstay of treatment. For localized BP, very mainstay of treatment. For localized BP, very potent topical steroids are often sufficient.potent topical steroids are often sufficient.

Corticosteroid therapy has lowered the Corticosteroid therapy has lowered the morbidity from the disease considerably and morbidity from the disease considerably and most patients achieve remission off all most patients achieve remission off all therapy, but significant mortality of bullous therapy, but significant mortality of bullous pemphigoid still remains at 15-40%, and is pemphigoid still remains at 15-40%, and is nearly always treatment related or related to nearly always treatment related or related to the general condition and age of the the general condition and age of the patients.patients.

DERMATITIS HERPETIFORMISDefinition. Dermatitis herpetiformis (DH) is a rare, intensely pruritic,chronic, recurrent, papulovesicular disease.There is an underlying gluten-sensitive enteropathy that may be asymptomatic. The mechanism by which ingestion of gluten induces granular IgA deposition in the skin and blistering is still obscure.There is a family history of dermatitis herpetiformis or coeliac disease in 10.5% of patients and it has been reported to be both concordant and discordant in monozygotic twins.

PATHOGENESISThe IgA deposits are gluten dependent, and are slowly cleared from the skin once gluten is removed from the diet. The Ag within normal human skin to which IgA antibodies from DH sera bind is still unknown. One of the most exciting developments of recent years has been the recognition that autoantibodies and T-cell reactions to tissue transglutaminases, and in particular transglutaminase 2, are relevant to the pathogenesis of coeliac disease .These antibodies have been demonstrated in dermatitis herpetiformis.In addition, it is now clear that the previously recognized antireticulin and endomysial antibodies, in coeliac disease and dermatitis herpetiformis, are associated with these antibodies and require transglutaminase 2 to bind to tissues.

PATHOLOGYDiagnostic histological changes are best seen in the vicinity of early blisters or in lesions that have not yet blistered.Neutrophils and eosinophils accumulate within the dermal papillae and form microabscesses. The surrounding collagen is degraded, resulting in detachment of the epidermis and a subepidermal vesicle. Multilocular vesicles may coalesce to form blisters; Direct immunofluorescence is always positive. There are granular deposits of IgA in the dermal papillae There may also be C3 and IgG.

DERMATITIS HERPETIFIRMISHISTHOLOGY

CLINICAL FEATURESDermatitis herpetiformis presents mainly between the ages of 20 and 55 years, but can present both in childhood and old age. The onset may be acute or gradual, and pruritus is usually the first and predominant symptom. Early lesions on the skin are erythematous papules, urticarial weals or groups of small vesicles often excoriated so rapidly that it may be impossible to find one intact. The vesicles are usually grouped together on plaques of erythema, and rarely blisters 1-2 cm in diameter occur.The distribution of the lesions is characteristic. The extensor aspects of the limbs, especially the knees, just below the point of the elbows, buttocks and the natal cleft, are affected in the majority of patients The axillary folds, shoulders, trunk, face and scalp are all frequently involved.

There may be a feeling of malaise with the acutely active disease. In addition, constitutional symptoms due to the glutensensitive enteropathy can be present. The patient may experience bouts of abdominal pain, constipation and diarrhoea, and be undernourished. Associated diseases. There are often associated autoimmune diseases, particularly thyroid disease, pernicious anaemia and diabetes.There is an association with thyroid disease in up to 30% of patients. Lymphoma is a well-recognized complication of dermatitis herpetiformis, as are other malignancies although a recent study contradicts this . Moreover, the protective role of a gluten-free diet for the lymphomas has been established.

Differential diagnosis The diagnosis should be suspected when any persistent, pruritic, symmetrical eruption resists topical treatment. In view of the pruritus and involvement of the axillary folds and buttocks, many patients are thought to have scabies, but the absence of burrows or of contact cases should help with the diagnosis. The most difficult diagnostic problem is the group of patients with chronic exudative eczema, papular urticaria and chronic prurigo, some of whom may be dapsone responsive. The histology and the lack of IgA deposition should help establish the correct diagnosis.

TREATMENTDapsone is the most widely used treatment for dermatitis herpetiformis. The dose needed for the average case is 100-200 mg/ day but a few may require 400 mg/ day. Patients at risk of glucose-6-phosphate dehydrogenase deficiency should be screened prior to treatment. Methaemoglobinaemia is common, reaching a steady state after about 2 weeks, and may cause cyanosis, breathlessness and angina. Hepatitis, the dapsone syndrome (lymphadenopathy and hepatitis) and agranulocytosis are serious, usually early complications. Motor neuropathy may occur. Although systemic corticosteroids are in the main ineffective and not indicated, topical steroids may be helpful in lessening symptoms.

A gluten-free diet is the treatment of choice in the long term. It has been shown not only to improve the enteropathy, but also to allow discontinuation of drug therapy. It is usually many months and sometimes years before patients are able to reduce their dapsone requirements. Often dapsone can be discontinued altogether after 2-3 years on a strict gluten-free diet, but some patients take much longer . Reintroduction of gluten in selected patients produced a relapse in skin lesions .The gluten-free diet after 5-10 years protects patients from lymphoma, and this is an additional reason to recommend a gluten-free diet.

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Vesiculobullous diseases