Pemphigoid bullous

Pemphigoid bullous (synonyms: pemphigoid, parapemphigus, senile pemphigus, senile herpetiform dermatitis) is an autoimmune disease that usually develops in people over 60 years of age, including paraneoplasia. May occur in children. Pemphigoid is a benign chronic disease, the clinical picture of which is very similar to vulgar pemphigus, and histological - with herpetiform dermatitis.

[1], [2], [3], [4], [5], [6], [7], [8],

Causes and pathogenesis of bullous pemphigoid

In recent years, studies have shown that autoimmune processes play an important role in the pathogenesis of dermatosis. In patients with bullous pemphigoid in serum and vesicidal fluid, LgG antibodies, lgA antibodies to the basal membrane, IgG deposition, and less often IgA and C3 complement components in the basal membrane region of both skin and mucosa were detected. It has been established that the antibody titer and circulating immune complexes in the pemphigoid correlate with the activity of the disease.

[9], [10], [11], [12], [13], [14], [15]

Pathomorphology of bullous pemphigoid

In the process test, numerous vacuoles form between the cytoplasmic processes of the basal cells, which then merge and form larger subepidermal blisters against the background of the sharp edema of the dermis. Bubble cover is an unchanged epidermis, the cells of which are stretched, but the intercellular bridges are not damaged. In the future, necrosis of epidermal cells occurs. The regenerating epidermis, coming from the edges of the bubble, gradually seizes its bottom, as a result of which the bladder becomes intraepidermal, sometimes subthreshold. Inflammation in the dermis is expressed in different ways. If the blisters develop on unchanged skin, the infiltrates are arranged perivascularly. If the blisters are formed against the background of the inflammatory process, infiltrates in the dermis are very massive. The composition of the infiltrate is polymorphic, but mainly lymphocytes with an admixture of neutrophilic and especially eosinophilic granulocytes predominate, which may also be present in the contents of the bladder among the fibrin filaments. When immunomorphological study of infiltrates MS Nester and co-workers. (1987) found a large number of T-lymphocytes in lesions. Including T-helpers and T-suppressors, macrophages and intra-epidermal macrophies. A similar composition of the infiltrate testifies to the role of cellular immune responses in the formation of blisters with the involvement of macrophages in the process. An electron microscopic study of lesions in different stages of the process showed that in the earliest stages edema of the upper dermis is observed, and between basal cells within the basal membrane zone small vacuoles. Later, there is an expansion of the space between the base cell plasmolemma and the basal plate, which is the base of the bladder. Then it is partially condensed and destroyed. The processes of the basal cells contact the cells of the iliac (the filtrate of the dermis, the eosinophilic granulocytes penetrate the epidermis and defanulate in it, 40% of cases there is eosinophilic spongiosis with the presence of a chemotactic factor in the vesicle fluid.) In 50% of cases in the basal membrane zone, globular bodies are identified that are histologically , ultrastructurally and immunologically do not differ from those with red flat lice, lupus erythematosus, dermatomyositis and other dermatoses .The method of direct immunofluorescence J. Horiguchi et al. (1985) uzhili therein immunoglobulins G and M, the C3 component of complement and fibrin. The origin of these cells involved destructively altered epithelial tire bladder.

Differentiation of this disease from ordinary pemphigus is not difficult even with intraepidermal localization of blisters. Pemphigus is characterized by primary changes in the epidermis, where acantholytic blisters are formed, while in pemphigoid acantholysis is absent, and changes in the epidermis are secondary. To distinguish bullous pemphigoid from diseases with subepidermal localization of blisters is very difficult, often impossible. Bubbles that develop on a non-inflammatory basis may not contain zosinophilic granulocytes, then they are difficult to differentiate from blisters in bullous epidermolysis or late cutaneous porphyria. Bubbles that have arisen on an inflammatory basis are very difficult to distinguish from blisters in benign pemphigoid mucous membranes and herpetiform dermatitis. With a benign pemphigoid of the mucous membranes, a more intense bubble eruption is observed on them than with a pemphigoid. Unlike herpetiform dermatitis with bullous pemphigoid there are no papillary microabscesses, which subsequently form multi-chambered blisters. The bullous pemphigoid differs from the multiform exudative species by the absence of perivascularly located eosinophil granulonites located near the papillae of the dermis, the mononuclear character of the infiltrate near the dermoepidermal compound and early epilormal changes in the form of spongiosus, exocytosis, and necrobiosis. In all cases of difficulty, immunofluorescence diagnosis is necessary.

Histogenesis of bullous pemphigoid

Pemphigoid, like pemphigus, refers to autoimmune dermatoses. Antibodies in this disease are directed against two antigens - BPAg1 and BPAg2. The BPAg1 antigen is located at the sites of hemidesmosome attachment in the keratinocytes of the basal layer, the antigen of BPAg2 is also located in the hemodesmic region and is presumably formed by type XII collagen.

Immunoelectron microscopic study with the peroxidase-antiperoxidase method showed the localization of complement IgG, C3 and C4 components in the lamina lucida of the basal membrane and the lower surface of basal spiellocytes. In addition, the complement C3 component is found on the other side of the basal membrane - in the upper parts of the dermis. In some cases, IgM deposits are found. Circulating antibodies against the basal membrane zone are noted in 70-80% of cases, which is pathogmonic for the pemphigoid. There are a number of works showing the dynamics of immuno-morphological changes in the skin in places where blisters are formed. Thus, I. Carlo et al. (1979). Studying the skin in the vicinity of the lesion, beta-lobulin, a plasma protein regulating the biological activity of the complement C3-component, was detected in the basal membrane zone along with the complement C3 component of immunoglobulin G. T. Nishikawa et al. (1980) found antibodies against basal cells in intercellular spaces.

In the histogenesis of the bladder, enzymes released by the cells of the infiltrate also play a role. It was found that eosinophils and macrophages accumulate near the basal membrane, then migrate through it, accumulate in the lamina lucida and the spaces between the basal cells and the basal membrane zone. In addition, in response to the activation of complement there is a pronounced degranulation of the mast cells. Enzymes released by these cells cause tissue degradation and thereby participate in the formation of the bladder.

Histopathology

Histologically, exfoliation of the epidermis from the dermis is observed with the formation of a subepidermal bladder. Acantholysis is not noted. As a result of early regeneration of the bottom of the bladder and its peripheral part, the subepidermal bladder becomes, as it were, intra-epidermal. The contents of the bladder consists of histiocytes, lymphocytes with an admixture of eosinophils.

The bottom of the bladder is covered with a thick layer of leukocytes and fibrin. Dermis is edematic, diffusely infiltrated and consists of histiocytic elements, lymphocytes, the number of eosinophils varies.

Vessels are dilated, their endothelium is edematous. Because of the lack of acantholysis, Tzanck cells are missing in the smears-prints. The location of the IgG and the complementary C3 component is marked along the basal membrane.

Symptoms of bullous pemphigoid

The disease usually occurs in people of both sexes older than 60 years, but can be observed at any age. The main clinical sign is the presence of intense blisters arising on the erythematous-edematic background, less often on unchanged skin and predominantly localized on the abdomen, limbs, in the folds of the skin, in 1/3 of the cases on the oral mucosa. Local foci are observed. Nikolsky's symptom is negative, Ttsanka cells do not show. In some cases polymorphism of the rash may occur, scarring, mainly in benign pemphigoid mucous membranes and with local scarring pemphigoid. There are observations of a combination of scarring changes and common bullous eruptions in children with IgA deposition in the dermoepilemal zone against the background of low titers of IgA antibodies against the basal membrane, which is treated as a children's cicatrix pemphigoid with linear IgA deposits, if combinations of this process with other pathologies are excluded. The disease begins with the appearance of blisters on erythematous or erythematous-urticarial spots, rarely on externally unchanged skin. Bubbles are usually symmetrical, seldom there is a rashness of the rashes. Bubbles of 1 to 3 cm in size have a round or hemispherical shape, are filled with transparent serous contents, which can then turn into purulent or hemorrhagic. Due to a dense tire, they are very resistant to trauma and are clinically similar to herpetiform dermatitis. Large blisters sometimes are not so tense and outwardly very similar to those with an ordinary pemphigus. Simultaneously with the blisters appear small and large urtic rashes of pink-red or stagnant red color. This is especially evident at the time of the spread of the process, when the erythematous phenomena around the blisters regress or may completely disappear. After the opening of the blisters, slightly moist pinkish-red erosions are formed, which are quickly epithelized, sometimes even on their surface, crusts do not have time to form. The increase in the size of erosion, as a rule, is not observed, but sometimes their peripheral growth is noted. The favorite places for the localization of blisters are the folds of the skin, forearms, the inner surface of the shoulders, the trunk, the inner surface of the thighs. The defeat of the mucous membranes is not characteristic, but the erosion, on the mucous membrane of the oral cavity or vagina, is clinically similar to erosion in ordinary pemphigus.

Subjectively, rashes are accompanied by a slight itch, rarely - itching, pain and fever. In severe, widespread flow, and also with elderly and malnourished patients, loss of appetite, general weakness, weight loss, and sometimes - death are noted. The disease lasts for a long time, the periods of remission alternate with periods of relapse.

The course of the disease is chronic, the prognosis is much more favorable than with pemphigus.

Differential diagnosis

Bullous pemphigoid should be distinguished from the true pemphigus, During's herpetiform dermatitis, multi-form exudative erythema, etc.

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Treatment of bullous pemphigoid

Conducted therapy depends on the severity of the course and the prevalence of the process. Therapy should be comprehensive and individual. The main therapeutic agent - glucocorticosteroid drugs, which are prescribed at the rate of 40-80 mg of prednisolone per day with a gradual decrease. Perhaps the appointment of higher doses of the drug. Encouraging results are observed with the use of immunosuppressants (cyclosporin A) and cytostatics (methotrexate, azathioprine, cyclophosphamide). There are reports of high therapeutic efficacy in the combination of glucocorticosteroids with methotrexate, azathiprine, or plasmaphoresis. To increase the effectiveness of therapy, corticosteroids are prescribed concomitantly with systemic enzymes (phlogenzyme, vobenzyme). The dose depends on the severity of the disease and on average is 2 tablets 2-3 times a day. External apply aniline dyes, creams, ointments containing glucocorticosteroids.