Vesiculobullous diseases PEMPHIGUS VULGARIS PEMPHIGUS FOLIACEUS BULLOUS PEMPHIGOID

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

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

PEMPHIGUS VULGARIS Autoimmune disease. Common in Ashkenazi and Mediterranean jews . Middle aged females. Other variants are: Pemphius vegetans Paraneoplastic pemphgus

PEMPHIGUS VULGARIS CLINICAL FEATURES: Painful ulcers or bulla are formed which are fluid filled. They can be formed any where in the oral cavity . The bulla is rapidly ruptured leaving a collapsed roof of grayish membrane with a red ulcerated base.The ulcer may look like an apthous ulcer or may be large map shaped. Nikolsky sign is positive.

PEMPHIGUS VULGARIS Sometimes 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

PEMPHIGUS VULGARIS PATHOGENESIS: 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 path.cont…d

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 Inflammatory cells are very scanty however eosinophils may be seen. Acantholytic statum 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 TZANK CELLS.

PEMPHIGUS VULGARIS histology

PEMPHIGUS VULGARIS tzank cells

DIAGNOSIS Skin biopsy Electron microscopy has shown that widening of the intercellular space is followed by splitting of the desmosome junctions. Direct & indirect immunofluorescence ELISA

Direct immunofluorescence

Indirect immunofluorescence

PEMPHIGUS VULGARIS DIFFRENTIAL DIAGNOSIS: Pemphegoid Erthema multiforme Bullous lichen plannus

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

Pemphigus foliaceus

Definition: Blistering in this group of autoimmune diseases is high in the epidermis, either in the granular layer or just beneath the stratum corneum. Antibody binding may have a direct effect on the function of the desmosomal cadherins in the upper epidermis, causing detachment of keratinocytes. Desmoglein-l is present but only weakly expressed in mucosae accounting for the lack of mucosal involvement in pemphigus foliaceus.

Clinical feature The onset is usually insidious with scattered, scaly lesions involving the 'seborrhoeic' areas: scalp, face, chest and upper back. Blistering may not be obvious because the cleavage is superficial and the small flaccid blisters rupture easily. Oral lesions are uncommon. Pemphigus foliaceus is generally regarded as a benign disease which responds well to treatment and may remit.

Pemphigus foliaceus

Pemphigus foliaceus histology

TREATMENT Potent topical or intralesional steroids or, if control is inadequate, prednisolone 20-40 mg/ day. Azathioprine or cyclophosphamide are effective adjuncts to oral steroids in severe cases. Hydroxychloroquine 200/mg twice per day has also been recommended as adjuvant therapy. Intravenous Ig has been reported as effective in resistant cases.

BULLOUS PEMPHIGOID Bullous pemphigoid is an affliction of elderly people,with onset usually after 60 years of age. The blister in bullous pemphigoid is subepidermal with an intact and often viable epidermis forming the roof. Bullous pemphigoid commonly starts with itching and a non-specific rash on the limbs that may be either urticaria-like or occasionally eczematous and rarely may simulate vesicular eczema.

PEMPHGOID Blisters may arise on erythematous and on normal skin and may be associated with dermal edema. The blisters are tense and dome shaped, obtaining a diameter of many centimeteres. The blisters are tough and may remain intact for several days, the contents often becoming jelly-like with coagulated fibrin. Mucosal lesions occur less frequently and are less severe than in pemphigus vulgaris and are usually confined to the mouth.

BULLOUS PEMPHGOID

BULLOUS PEMPHIGOID HISTOLOGY

PEMPHGOID Untreated bullous pemphigoid runs a chronic, self limiting course over a number of months or years. The disease duration is usually 3-6 years, with most patients achieving complete remission off treatment.

TREATMENT Topical and systemic steroids are the mainstay of treatment. For localized BP, very potent topical steroids are often sufficient. Corticosteroid therapy has lowered the morbidity from the disease considerably and most patients achieve remission off all therapy, but significant mortality of bullous pemphigoid still remains at 15-40%, and is nearly always treatment related or related to the general condition and age of the patients.

DERMATITIS HERPETIFORMIS Definition. 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.

PATHOGENESIS The 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.

PATHOLOGY Diagnostic 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 HERPETIFIRMIS HISTHOLOGY

CLINICAL FEATURES Dermatitis 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 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.

TREATMENT Dapsone 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 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.