Bullous – the chronic autoimmune disease of skin affecting generally senior citizens. Its symptoms are similar to those at a puzyrchatka and come down to formation of intense bubbles on integuments of hands, legs, and also a stomach; distribution of the pathological centers, as a rule, symmetric. Diagnostics of a bullous pemfigoid is made by means of survey of the patient, histologic studying of tissues of skin on affected areas, immunological researches. Treatment of a disease includes immunosupressivny and cytotoxic therapy with use of glyukokortikosteroidny and cytostatic means.
Bullous (, senile gerpetiformny dermatitis) – the chronic recurrent disease of autoimmune character which is characterized by defeat of subepidermalny layers of skin with development of intense bubbles and other pathological changes. Unlike an ordinary puzyrchatka, at this disease there is no akantoliz, and formation of bubbles in epidermis is secondary process. For the first time Lever who allocated bullous in separate nosological unit paid attention to it in 1953 – before the term "pemfigus" united all types of bubbly rash. Pathologies are subject generally persons 60 years are more senior, but in dermatology about 100 cases when bullous developed at children's or teenage age are described. Such forms of a disease received the name of an infantile and teenage bullous pemfigoid respectively.
Also are available the instruction on interrelation between this bullous dermatosis and some oncological diseases that allows to consider it as paraneoplastic process. Patients with this pathology developing against the background of cancer of a stomach, lungs, a bladder are described. In certain cases bullous it can be provoked by reception of medicines (furosemide, potassium iodide, amoxicillin), a skin injury. Occurrence of a disease makes about 1-13 cases on 1 million population, among patients men of advanced age prevail. The risk of development of a bullous pemfigoid very strongly increases with age – is counted that probability to ache with this pathology in 90 years more than 300 times higher, than in 60.
Reasons of a bullous pemfigoid
The etiology of a bullous pemfigoid at the moment remains a subject of a scientific discussion, researches in this area helped to create several main hypotheses explaining the reasons of this state. The opinion is most widespread that this autoimmune disease develops because of existence of the certain mutations changing the main complex of a gistosovmestimost. It partly is confirmed by the fact that among patients with a bullous pemfigoid the number of the persons having as an allele of the second class GKGS DQB1 0301 is increased. However mutations or other genetic disorders which could be connected with this skin disease unambiguously are not revealed today.
The pathogenesis of a bullous pemfigoid is studied slightly better than an etiology that allows to claim authentically about the autoimmune nature of this state. The main object for the attack by immune system are two proteins of epidermis – one of them, BP180, is a transmembrane protein and is associated at the moment with collagen of the 17th type. The second anti-gene participating in development of a bullous pemfigoid, BP230 settles down in cytoplasm of cells of epidermis and, presumably, concerns to group of plakin. These both proteins are connected on the function – they participate in formation of semi-desmosomes and support the ordered structure of a multilayered epithelium.
Class G antibodies which have ability to communicate autoantigenam of BP180 and BP230 are found in all patients with a bullous pemfigoid in plasma of blood. Their emergence is connected with development in an organism of autoreaktivny T-lymphocytes against the above-stated proteins of cages of an epithelium. T-lymphocytes are responsible for the cellular immune answer, in passing activating the V-lymphocytes making antibodies. Linkng of T-lymphocytes and antibodies with own proteins of skin and mucous membranes activates system of a complement that attracts in the pathological center other immunocompetent cages, mainly neutrophils and eosinophils. At some patients with a bullous pemfigoid considerable participation of labrotsit (corpulent cages) in pathogenesis of a disease is revealed.
Originally semi-desmosomes in a basal layer of epidermis are surprised, between shoots of cages there are numerous vacuoles. Their merge among themselves leads to formation of the subepidermalny bubble filled with exudate, from above it is covered with not changed epidermis at which intercellular communications are kept. However then it is exposed to a necrosis, and regeneration of a basal layer leads to a bubble bottom covering a layer of neogenic cages, and the center to become vnutriepidermalny. Thus, at this stage of development of a bullous pemfigoid, it bears to an ordinary puzyrchatka, behind that exception most a strong resemblance that development of bubbles was not the result of an akantoliz, and destructions of intercellular bridges only in a basal layer with its subsequent regeneration.
Inflammatory processes at a bullous pemfigoid are unequally expressed at different patients, however signs at least to the minimum infiltration of skin by lymphocytes, neutrophils and eosinophils is present always. The centers can settle down perivaskulyarno in case of an insignificant inflammation and fill all thickness of skin at the expressed inflammatory processes, sometimes attendants bullous .
Symptoms of a bullous pemfigoid
In most cases the first displays of a disease arise at persons is more senior than 60 years. Originally, before formation of bubbles (a prevesiculate stage), symptoms of a bullous pemfigoid are expressed poorly and are not specific enough – patients complain of the itch of various intensity which is localized on skin of hands and legs or the lower part of a stomach. Reddening of skin, insignificant eritematozny rashes can sometimes be observed. Over time on affected areas the intense bubbles having the hemispherical form and diameter of 1-3 centimeters are formed. Approximately in a third of cases of a bullous pemfigoid erosion on mucous membranes of an oral cavity and a vagina are formed. The "cover" of bubbles consisting of epidermis rather strong therefore these educations possess a certain travmoustoychivost. Contents of bubbles at a bullous pemfigoid have serous character, but in certain cases can change on hemorrhagic or even purulent.
When opening bubbles on the surface of skin there are erosion of red color with a gentle and damp surface. Restoration of epidermis over them happens quickly enough, traces after healing are insignificant. Besides bubbles at a bullous pemfigoid urtikarny rashes of the different sizes and intensity often develop. From other symptoms, except a skin itch and rashes, at patients fever, appetite loss, weight loss can be observed. Especially often such manifestations arise at the weakened and exhausted faces, at the same time bullous can even become the reason of a lethal outcome. The disease has a long and chronic current, symptoms and skin manifestations can weaken and again become more active over time. Before development of effective methods of treatment of a bullous pemfigoid it was found out that in 15-30% of cases there can occur spontaneous recovery.
Diagnostics of a bullous pemfigoid
Definition of such disease as bullous it is made on the basis of the given survey by the dermatologist, immunological researches and histologic studying of fabrics of the pathological centers. At survey, depending on a stage of development of pathology, the eritematozny rash, the created bubbles symmetrized, urtikarny rashes of various intensity, the healing erosion sometimes covered with a crust can be observed. The general blood test approximately in half of cases of a bullous pemfigoid shows a moderate eozinofiliya, sometimes . Also in peripheral blood by means of reaction of an immunopretsipitation it is possible to find IgG having ability to contact anti-genes of BP180 and BP230.
Histologic researches at a bullous pemfigoid include simple light microscopy and immunofluorescent microscopy. At survey under a microscope at various stages of formation of bubbles it is possible to find an epidermalny crack, then a subepidermalny bubble which turns into vnutriepidermalny. Derma under the pathological center is sharply edematous, the leykotsitarny infiltration consisting generally of lymphocytes, eosinophils and neutrophils can be expressed differently. The immunofluorescent microscopy reveals a congestion of immunoglobulins of a class G and fractions of a complement (most often C3) along a basal membrane of epidermis. At a bullous pemfigoid these molecules are mainly concentrated from the outer side of a basal membrane. Differential diagnostics should be carried out with an ordinary puzyrchatka, mnogoformny ekssudativny eritemy and a bullous epidermoliz.
Treatment of a bullous pemfigoid
The medicines of the first line used for treatment of a bullous pemfigoid are glucocorticosteroids – Prednisolonum, methylprednisolonum and others. Long-term treatment, therapy are begun with high dosages of steroids, gradually lowering a dose for 6-9 months. Considering that many patients with a bullous pemfigoid represent elderly people, it is not possible to carry out full therapy by glucocorticosteroids because of considerable side effects. Quite often in such situation treatment is made a combination of the reduced dose of steroids inside and local use of ointments on their basis.
Therapy of a bullous pemfigoid immunosuppressants – for example, tsiklosporiny has quite good results. Similarly apply cytostatic means – a methotrexate, . It is considerable can accelerate recovery and increase efficiency of therapy at a bullous pemfigoid a plasma exchange with a double filtration. Outwardly, besides ointments with glucocorticosteroids, use antiseptics (for example, aniline dyes) for prevention of complications like a secondary infection. However anyway treatment of this disease very long also takes not less than one and a half years, and even at the same time 15-20% of patients then have recurrence.
Forecast and prevention of a bullous pemfigoid
Forecast of a classical bullous pemfigoid in most cases uncertain. This results from the fact that the disease has the chronic and hardly predicted character, and most of patients – the elderly persons which often have other accompanying pathologies. An early appreciation of mortality from a bullous pemfigoid (from 10 to 40%%) nowadays is considered a little incorrect as at calculation the age, existence of other diseases and other factors was not considered. Children's and teenage forms of this pathology in most cases successfully recover. The persons who are suffering from a bullous pemfigoid or successfully underwent treatment should avoid impact on skin of the injuring factors – Ural federal district, high or low temperatures, mechanical injuries. It can provoke development of a recurrence of a disease.