Bullous pemphigoid treatment. Pemphigodes bullosa is a disease that requires surgical treatment.

Bullous pemphigoid is a chronic autoimmune lesion of the skin that occurs most often in older people.

The clinical picture of this disease resembles the usual symptoms. The main manifestation is the formation of tense blisters (mainly on the skin of the arms, legs and front abdominal wall). In this case, pathological foci are distributed symmetrically. In addition to local symptoms, a disturbance in the general condition of the body occurs, which in the elderly can lead to death.

The diagnosis is made on the basis of patient complaints, examination, histological examination of the skin in the affected areas, as well as the results of immunological diagnostics.

Therapeutic measures consist of the use of immunosuppressive and cytotoxic (suppressing the growth of certain cells) drugs.

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Bullous pemphigoid is one of the chronic recurrent skin diseases that are autoimmune in nature - this means that the body perceives its own tissues as foreign and begins to fight them.

The disease is similar to pemphigus, as it produces the same blisters. But unlike pemphigus, with bullous pemphigoid, acantholysis does not occur - destruction of intercellular connections, while the formation of blisters in the epidermis develops as a secondary process. For the first time, such signs of the described disease were studied in the middle of the last century by the scientist Lever - he identified bullous pemphigoid as a separate nosological unit (before that, all types of blistering rashes were called pemphigoid).

The disease is most often diagnosed in people over 60 years of age, and males predominate among patients.

note

The older a person is, the higher the chances of developing bullous pemphigoid. Thus, the risk of developing the described pathology at 90 years of age is more than 300 times higher than at 60.

Also dermatologists in different years described about 100 clinical cases bullous pemphigoid in children and adolescents - it was named accordingly infantile And adolescent bullous pemphigoid.

There is evidence indicating a relationship between bullous pemphigoid and a number of oncological diseases. Therefore, some clinicians suggest considering this pathology as an oncological process. There is a reason for this - bullous pemphigoid is often detected against the background of other organs and tissues.

The pathology has other names - parapemphigus and senile herpetiformis.

Causes

The causes of bullous pemphigoid are quite controversial and this moment are a source of debate in scientific circles. Several main hypotheses have been formed with the help of which they try to explain the reasons for the development of the described pathology. The main theories are:

• genetic;
• medicinal;
• traumatic;
• age.

The most reliable explanation for the development of this pathology is the occurrence of mutations that affect tissue compatibility, and tissues from the category of “self” become foreign.

The theory has the following confirmation: among patients who were diagnosed with bullous pemphigoid, a large number of individuals had mutated genes with the long MHC marking DQB1 0301. But a direct connection of the pathology with the presence of this type of disorder has not yet been established.

Proponents of the drug theory argue that the development of bullous pemphigoid is triggered by taking certain medications. Confirmation that this theory is not without meaning is that bullous pemphigoid often develops in patients who undergo long-term drug treatment– in particular, such drugs as:

• furosemide (diuretic);
• potassium iodide (used in the treatment of a number of thyroid pathologies);
• amoxicillin (one of the representatives of broad-spectrum antibiotics).

note

The traumatic theory explains the development of bullous pemphigoid by a traumatic effect on the skin, which triggers the body’s reaction in the form of skin disorders.

Proponents of the age-related theory argue that bullous pemphigoid develops against the background of age-related changes in the human skin.

Actually, confirmation of their correctness is that the described disease is more often diagnosed in old age, moreover, further aging increases the chances of developing bullous pemphigoid. But the age theory does not explain what reasons led to the development of this disease in children and adolescents.

Contributing factors have also been identified - those against which bullous pemphigoid develops more “readily”. This:

Often such factors can influence throughout the patient's life, but be ignored - nevertheless, in old age their effect on human skin becomes apparent.

Development of pathology

Although the causes of bullous pemphigoid are still questionable, the development of the disease is better understood.

The bottom line is this: proteins human body They begin to be recognized by him as alien, and therefore are subjected to a natural attack in order to be neutralized. Specifically, these are two skin proteins that are functionally related - they are both:

• take part in the formation of intercellular connections;
• maintain the normal structure of stratified epithelium.

In all patients who have been diagnosed with bullous pemphigoid, certain antibodies are found in the blood plasma, designed to fight the above proteins. Also involved in the development of the process are T-lymphocytes - cells of the immune system, which:

• responsible for the cellular immune response;
• activate B-lymphocytes that produce antibodies, which are responsible for the so-called humoral immunity.

The body directs T-lymphocytes and antibodies, which literally behave aggressively, to its own proteins in the skin and mucous membranes, and a kind of “cell war” begins. Next, other cells penetrate into the pathological focus, designed to fight foreign agents - neutrophils and eosinophils. Some patients with bullous pemphigoid also have an increase in the number of so-called mast cells, a type of immune cell.

When skin cells cannot withstand the attack, they begin to change. First, vacuoles—microcavities—are formed in them. There are so many of them that when they begin to merge, bubbles filled with liquid are formed as a result of this process. Moreover, such blisters can be covered from above by an unchanged exfoliated epidermis, but as the pathology progresses, it undergoes necrosis (dies).

Since the restorative properties of tissues are not affected, the bottom of the bubble is covered with a layer of new cells. It is at this stage that the disease resembles ordinary pemphigus.

With bullous pemphigoid, an inflammatory (and often infectious-inflammatory) lesion can also occur. But this process is expressed differently in different patients - in some it is intense, and in others it is not detected at all. However, at the tissue level, signs of at least minimal infiltration (permeation) of the skin with lymphocytes, neutrophils and eosinophils are always present. Inflammation can affect both individual and all layers of the skin.

Symptoms of bullous pemphigoid

Most often, the first manifestations of the described pathology begin to appear in people after 60 years of age. There are two basic stages of the disease:

• prevesical;
• bubble

In the prevesicular stage, the symptoms of bullous pemphigoid are mild and very often nonspecific, and therefore do not indicate the presence of this particular disease. The clinical picture consists of symptoms:

• local;
• general

Typical local signs of bullous pemphigoid are:

• redness;
• minor rashes;
• erosion.

Characteristics of itching:

• by location - most often on the skin of the arms, legs and lower abdomen;
• in terms of severity - varying intensity (this indicator is very unstable).

The rashes are often erythematous in nature - they appear as small red dots.

note

Erosions occur in approximately a third of patients diagnosed with bullous pemphigoid. Most often they are found on the mucous membranes of the mouth and vagina.

With further progression of the pathology, blisters form on compromised areas of the skin. Their characteristics are as follows:

• in shape – hemispherical;
• in size - on average 1-3 cm in diameter;
• by consistency – tense.

The shell of such bubbles is quite durable, so they are not so easily injured. Inside the blisters there is serous content, in some cases mixed with blood. When an infectious agent is attached, the contents of such a bubble may be purulent.

When the blisters are opened, erosions form on the skin, but they differ from those erosions that occurred in the early stages of the development of the pathology. They are red in color and their surface is moist and tender. Such erosions heal quite quickly due to the fact that the epidermis over them “grows” quickly. At the same time, the marks after healing are not expressed.

But blisters are not the only type of rash that can appear with bullous pemphigoid. Patients often complain of the appearance of rashes in the form - they are also called urticarial. The morphological elements of such a rash can be of different sizes and severity.

General symptoms of bullous pemphigoid are signs of deterioration in the general condition of the body. This:

• fever – simultaneously observed hyperthermia (increased body temperature) and chills. Hyperthermia can reach 38.5-39.0 degrees Celsius. Sometimes there is only an increase in body temperature without chills;
• deterioration of appetite until it completely disappears;
• significant weight loss to the point of exhaustion;
• general malaise;
• weakness;
• brokenness.

Most often, a violation of the general condition with bullous pemphigoid is observed in weakened patients - for example, due to a concomitant disease. It is not as harmless as it may seem - for example, progressive exhaustion can be fatal.

Bullous pemphigoid is characterized by a protracted course with regularly alternating periods of exacerbation and weakening - while general symptoms and skin manifestations weaken and become active again.

In some patients (according to various sources - from 15 to 30%), cases of spontaneous recovery were recorded.

Diagnostics

The diagnosis is made based on the patient’s characteristic complaints, medical history, results additional methods studies (physical, immunological and histological).

A physical examination reveals the following:

• upon examination - its results depend on the stage of bullous pemphigoid. An erythematous rash, blisters, urticarial rashes, healing erosions, sometimes covered with a dried crust, may be detected;
• upon palpation (palpation) - pain around the affected area is noted. When you try to remove the crusts, a bleeding surface appears underneath.

Instrumental research methods in the diagnosis of bullous pemphigoid are not decisive - their use is indicated for assessing the general condition in case of its deterioration. Thus, an (ECG) can be performed to assess the cardiovascular activity of elderly patients, violations of which are the direct cause of death.

Of the laboratory research methods, the most informative are:

• – half of the patients show a moderate increase in the number of eosinophils (eosinophilia), which signals increased sensitivity of the body. It is also possible to increase the number of white blood cells (leukocytosis);
• immunoprecipitation reaction - with its help, immunoglobulin is isolated, which appears in autoimmune pathology of the body;
• simple light microscopy - the condition of the affected areas of the skin is assessed under a microscope. Its tissues are literally saturated with cells of the immune system;
• Immunofluorescence microscopy is a more advanced method than simple light microscopy. It is used to determine the accumulation of immunoglobulins and some other organic compounds, an increased number of which indicates the development of an autoimmune process.

Bacterioscopic and bacteriological research methods are auxiliary - they help to identify pathogenic microflora that have infested erosive surfaces. In the first case, erosion smears are studied under a microscope, identifying pathogens in them. In the second case, the erosion scrapings are inoculated onto nutrient media, colonies are expected to grow, and the type of pathogen is determined from them.

Differential diagnosis

Differential (distinctive) diagnosis of bullous pemphigoid is most often carried out with such diseases and pathological conditions as:

Complications

The most common complications of bullous pemphigoid are:

• pyoderma – pustular lesion of the superficial layers of the skin;
• – limited abscess;
• – diffuse purulent lesion;
• – spread of infection throughout the body through the bloodstream.

Treatment of bullous pemphigoid

Treatment of bullous pemphigoid is conservative. It can be general and local.

At the core general treatment– the following purposes:

• immunosuppressive drugs;
• cytostatic agents.

From steroid drugs Prednisolone, methylprednisolone and others are used. They are prescribed for a long time, the first dosages are high, then they are gradually reduced over 6-9 months. But such treatment is not complete - the patients are mainly elderly people, in whom glucocorticosteroids cause a lot of side effects. The way out of the situation is to prescribe a reduced dose of steroid drugs orally and local use ointments made on the basis of steroids.

Cyclosporine has proven itself well as an immunosuppressive agent, and methotrexate and cyclophosphamide are among cytostatic drugs.

From non-medicinal common methods Plasmapheresis with double filtration is used - blood purification using special equipment. Plasmapheresis significantly enhances the effect of drug therapy and helps to significantly speed up recovery.

For local treatment the following are used:

• ointments made on the basis of glucocorticosteroids;
• antiseptic drugs - in particular, aniline dyes. They are used to prevent secondary infections.

note

Treatment of bullous pemphigoid is very long (at least one and a half years), and requires the patience of both the patient and the doctor. But even with adequate prescriptions and the patient’s scrupulous implementation of all medical prescriptions, relapses may occur in 15-20% of victims.

Prevention

Since the true causes of the development of bullous pemphigoid have not been established, specific methods of prevention have not been developed. Based on assumptions about the etiology (causal factors) of this disease, the risk of its development can be reduced by following the following recommendations:

• Take medications only as prescribed by a doctor and under his supervision;
• avoid situations (domestic, industrial, etc.) that can lead to injury to the skin;
• monitor the condition of the skin in youth, prevent the occurrence of skin diseases, and when they appear, promptly diagnose and treat them. Compliance with such recommendations will help slow down the aging process of the skin, which means its tendency to develop this pathology.

Patients who suffer from bullous pemphigoid or have already undergone successful treatment should avoid exposing the skin to traumatic factors. First of all this:

• ultraviolet irradiation;
• exposure to high and low temperatures;
• even minor mechanical injury.

Otherwise, relapses of the disease may occur.

Forecast

The prognosis for bullous pemphigoid in most cases remains uncertain. It is not always possible to predict the course of development of this disease due to its chronic specific course, and also due to the fact that most patients are elderly people who, moreover, at the end of their lives already have a number of concomitant pathologies that worsen the course of the described diseases.

According to various sources, the mortality rate from bullous pemphigoid ranges from 10 to 40%. But such statistical indicators are considered incorrect, since the direct cause of death of an elderly person may be age-related critical changes and disorders due to concomitant diseases, so it cannot be said reliably whether they were the cause of death or whether it was bullous pemphigoid.

The prognosis for childhood and adolescent forms of this disease is much better - in most cases they are successfully cured.

Kovtonyuk Oksana Vladimirovna, medical observer, surgeon, consultant doctor

Bullous pemphigoid is a relatively common skin disease, which externally resembles that it occurs in a chronic form and, in the absence of timely diagnosis and treatment, can lead to unpleasant consequences. So what causes the development of such a disease? What symptoms does it manifest? What treatment options can modern medicine offer? The answers to these questions are of interest to many readers.

What is the disease?

Bullous pemphigoid in modern medicine is known by many names - this is Lever's disease, and senile pemphigus, and senile dermatitis herpetiformis. This is a chronic condition that is accompanied by the appearance of a large blistering rash on the skin (external symptoms sometimes resemble true pemphigus).

It is worth noting that the vast majority of patients with this diagnosis are people aged 65 years and older. Naturally, medicine also knows exceptions, since the disease is sometimes found in children and middle-aged patients. This disease is characterized by a benign course, but can sometimes lead to complications. In the clinical picture, periods of relative well-being alternate with exacerbations. Of course, for many people the question of what constitutes bullous pemphigoid is interesting. Symptoms and treatment of the disease, the causes of its occurrence - this information should be read more carefully.

Some similar diseases

It is worth noting that bullous pemphigoid belongs to the group of so-called blistering dermatoses. These ailments differ from true pemphigus because they are not accompanied by acantholysis. Group skin lesions includes several other ailments, the clinical picture of which is quite similar:

• Benign non-acantholytic pemphigus, in which the disease affects exclusively the mucous membrane of the mouth, without causing a rash in other areas. The disease is also characterized by a benign course. By the way, it was first described in 1959.
• Scarring pemphigoid - quite dangerous disease, which affects the mucous membrane of the eyes and conjunctiva, causing its atrophy. Rashes on the body are possible, but are observed relatively rarely. The main risk group is women over 50 years of age, although sometimes the disease is also registered among male patients.

Causes and pathogenesis of bullous pemphigoid

Unfortunately, the mechanism of occurrence of this disease has not yet been fully studied. Nevertheless, scientists were able to find out that the disease is autoimmune in nature. For one reason or another, malfunctions in the functioning of the immune system occur, as a result of which the produced antibodies attack not only foreign, but also the body’s own cells.

There is evidence for this theory. During studies, specific antibodies were found in the patient’s blood serum, as well as in the fluid taken from the blisters, which damage the basement membrane of the skin and mucous membranes. It was also possible to establish that the more actively the disease develops, the higher the titer of these antibodies.

Autoimmune diseases are believed to be genetically determined. However, a factor capable of activating the disease is required. It could be:

• vaccination against certain diseases;
• damage or severe skin irritation;
• exposure to ultraviolet radiation (prolonged sunbathing, abuse of solarium, etc.);
• thermal skin burns;
• frequent use of certain medications, for example, Furosemide, Captopril, Phenacetin, Amoxicillin and some others;
• sometimes the disease is activated after the patient undergoes a course of radiation therapy;
• kidney transplant rejection, repeated organ transplants.

Bullous pemphigoid: photos and symptoms

Of course, first of all, it is important to familiarize yourself with the symptoms, because the sooner the patient pays attention to the presence of disorders and consults a doctor, the easier the treatment process will be. The formation of intense blistering rashes on the skin is the main symptom that accompanies bullous pemphigoid (the photo shows what the rash looks like). The skin of the extremities and torso is most often affected. Rashes can occur in the area of ​​large natural folds, on the skin of the face and scalp, but this occurs less frequently.

The main elements of the rash are vesicles and blisters with tense covers. They contain liquid inside, usually transparent, but sometimes blood can be seen. Often the skin around the blisters turns red.

The “life” of the formations is several days. After this, they spontaneously open. At the site of the rash, areas of erosion and small ulcers form. Crusts practically do not form on the surface, since the eroded areas quickly epithelialize.

The first stages of the development of the disease in 20% of patients begin with the appearance of blisters on the oral mucosa, and only then the rash spreads to the skin. Blisters on the mucous membrane of the nose, pharynx, genitals, and eyes appear extremely rarely.

Patients complain of itching, and after opening the blisters, some pain. A rise in temperature is possible, although this is rare. Elderly patients, whose body is exhausted by frequent relapses, also experience decreased appetite, weight loss, and progressive weakness.

Histogenesis, histopathology and pathomorphology

The pathomorphology of bullous pemphigoid is quite interesting. First, numerous vacuoles form between the cytoplasmic processes of the basal cells. Gradually, these formations merge with each other, forming larger structures. Along with this, there is also a sharp swelling of the dermal tissue.

The lining of the bladder is epidermal tissue. Its cells are stretched, but the bridges between them are not damaged. As the disease progresses, epidermal cells gradually die. At the same time, new epidermal tissue advances from the edges of the vesicle, capturing its bottom - thus, the vesicle moves into the epidermis, and sometimes into the substratum.

Inside the bladder there is a liquid that contains lymphocytes mixed with neutrophils. Fibrin strands are present protein molecules and some other compounds.

If we consider the histogenesis of bullous pemphigoid, then it is first worth remembering that the disease is autoimmune. When examining tissues using electron microscope It can be seen that the so-called BPAg1 antigens, which are released during the immune reaction, are located in the basal layer, namely in the attachment sites of keratinocyte hemidesmosomes. Another antigen, BPAg2, is also located in the hemidesmosome region. It is believed to be formed by type XII collagen.

Also during the research, it was discovered that macrophages and eosinophils in this disease first accumulate near the basal membrane, after which they migrate through it and begin to accumulate inside the bladder and between the basal cells. There is also significant degranulation of mast cells.

Histologically, the disease causes detachment of the epidermis from the dermis, between which a subepidermal bubble is formed. The vessels in the skin tissues are also dilated, and swelling of their inner layers (endothelium) is observed.

Modern diagnostic methods

As a rule, there are no difficulties in diagnosing a disease such as bullous pemphigoid: the symptoms here are very characteristic, and therefore the doctor may suspect the disease already during a standard examination. Tense blisters form on the patient's skin, and the process of epithelization of erosions proceeds quickly.

The epidermal peeling test is negative. Additionally, the internal contents of the blisters are collected for further histological examination. During laboratory tests, vacuoles, histiocytic elements, eosinophils and lymphocytes can be detected in the liquid.

On the other hand, differential diagnosis is sometimes difficult, since the clinical picture is slightly reminiscent of other skin diseases, including true pemphigus and herpetiformis

What treatment is considered effective?

What to do if you are diagnosed with bullous pemphigoid? Treatment in in this case complex is required. Moreover, the selection of health measures and medications depends on many factors, including the severity of the disease, the age and general health of the patient, and the presence of concomitant pathologies. In any case, the treatment regimen can only be drawn up by the attending physician.

The basis of therapy is steroidal anti-inflammatory drugs containing glucocorticosteroids. Prednisolone is most often used for this purpose. The medicine is administered intravenously, and the dose is gradually reduced as symptoms disappear.

Also, cytostatics and immunosuppressants have a good effect, which help normalize the functioning of the immune system. Quite often, patients are prescribed drugs such as Cyclosporin A, Cyclophosphamide, Azathioprine.

Naturally, an important point is the treatment of rashes, erosions and ulcers on the skin. You need to keep your skin clean. Patients are prescribed solutions with (for example, Furcocin), which act as antiseptics, drying the skin. In more severe cases, steroid ointments are also required.

Treatment with folk remedies

Bullous pemphigoid, or Lever's disease, is a pathology that requires competent, qualified treatment. The use of various homemade medications is possible, but only with the permission of a specialist. Before using any product, be sure to consult with your doctor. In folk medicine, many different medicines are used.

• It is believed that tincture of Eleutherococcus will have a positive effect on the patient’s health. You need to take it twice a day, 30 drops.
• For external treatment of rashes, juice from aloe leaves is used, which helps relieve itching and soreness, prevents the development of the inflammatory process, and accelerates regeneration processes. Moisten the bandage with the juice, then apply it to the damaged area of ​​skin and secure with a bandage. To achieve maximum effect, you can cover the compress with plastic wrap.
• For the same purpose, fresh juice or decoction of nettle leaves can be used. The compress is made according to the scheme described above.
• Bullous pemphigoid, or rather, its symptoms can be mitigated with the help of a special herbal decoction. To prepare it, take an equal amount (50 g each) of eucalyptus leaves, serpentine rhizomes, Japanese sophora fruits, birch buds, yarrow grass, shepherd's purse and nettle. Pour two tablespoons of the prepared herbal mixture into a glass of boiling water in the evening and leave overnight. In the morning, the infusion should be filtered and divided into three portions - they are taken throughout the day.

It is worth understanding that herbal medicines may act differently for each patient. Even if the drug has a positive effect, you should never give up drug therapy.

Prognosis for patients

Pemphigoid is a benign skin disease, and therefore in most cases it is not too severe. Moreover, in almost any hospital large city held successful treatment a disease under such a complex name - bullous pemphigoid. In Orenburg, Moscow and any other city you will definitely find good specialist. The cost of therapy will depend on the place of residence, since the prices for certain medications at different pharmacies vary.

With proper treatment, stable remission can be achieved. From time to time, some patients experience relapses, which, of course, is unpleasant, but not fatal. On the other hand, in the absence of therapy, the site of rash formation can become a gateway for infection, which, accordingly, ends in a more massive inflammatory process, suppuration of wounds, and penetration of pathogenic bacteria into the deeper layers of the skin.

Are there any means of prevention?

Unfortunately, there is no specific remedy for the prevention of such a disease as Lever's bullous pemphigoid. Naturally, it is extremely important to seek help in a timely manner, and since the disease is chronic, even during periods of relative well-being, you need to carefully monitor your health.

We should not forget that the disease is regarded in medicine as a possible marker of oncology. Therefore, if there is an illness, the patient must undergo a comprehensive examination to confirm or exclude an oncological diagnosis. Remember that any disease is much easier to cope with if you start therapy at an early stage.

Bullous pemphigoid- a rare, relatively benign bullous dermatosis that usually has a chronic course. Persistent, tense blisters form under the epidermis due to delamination of the basement membrane. Bullous pemphigoid is less common than true (acantholytic) pemphigus and usually affects older people (about 60-70 years), although it can sometimes occur in children - juvenile pemphigoid .

Etiology and pathogenesis of bullous pemphigoid

The etiology of bullous pemphigoid has not been established. The pathogenesis of the disease is autoimmune. It is based on an autoimmune reaction with the formation of autoantibodies to the proteins BP230 (BPAG1) and BP180 (BPAG2), with molecular weights of 230 and 180 kDa, respectively.

Protein BP230 Desmoplakin is an intracellular component of the hemidesmosome. Antibodies to BP230 are detected in 30-60% of patients with bullous pemphigoid and less frequently in other clinical variants.

Protein BP180- a transmembrane component of the basement membrane, consisting of type XVII collagen. Antibodies to BP180 are detected in 40-90% of patients with typical bullous pemphigoid, as well as in more rare clinical variants of pemphigoid.

It is known that autoantibodies fixed in a stripe pattern on the basement membrane activate the complement factor, which leads to the release of leukotriene B4 from mast cells and determines the chemotaxis of eosinophilic, neutrophilic granulocytes and macrophages. The proteolytic enzymes they release lead to destruction upper layers basement membrane, separation of the epidermis and dermis, formation of a subepithelial bladder. In some patients, bullous pemphigoid occurs as a paraneoplastic disease.

Clinical picture of bullous pemphigoid

Bullous pemphigoid is manifested by the development of tense blisters of varying sizes: from a few millimeters to 5-10 cm in diameter or more. Elements skin rash occur on apparently unchanged skin or against the background of edematous erythema and are accompanied by severe itching. The blisters have serous or serosanguineous contents due to damage to the superficial capillaries of the dermis during subepidermal detachment. When grouped, they sometimes form foci of bizarre shape, are located against a background of erythema and resemble manifestations of dermatosis herpetiformis. In some cases, blisters and erythematous patches may precede the appearance of blisters.

The rashes are usually widespread, symmetrically located, although localized variants of bullous pemphigoid are also occasionally found. Common sites of injury are the lateral surfaces of the neck, axillary areas, inguinal folds, flexor surfaces of the limbs and the upper abdomen. Sometimes bullous pemphigoid begins with blisters on the palms and soles and resembles manifestations of erythema multiforme.

When the blisters are opened, erosions are formed without a tendency to peripheral growth, which are covered with serous and serous-sanguineous crusts, epithelialize relatively quickly, leaving pigmentation. Thus, with bullous pemphigoid, there is both true and evolutionary polymorphism of the rash.

The appearance of numerous fresh rashes is accompanied by an increase in body temperature, loss of appetite, increased itching, and a deterioration in the patient’s general well-being. The marginal Nikolsky sign can be weakly positive, while on unchanged skin near the lesion the Nikolsky symptom is usually negative.

The oral mucosa is affected relatively rarely (about 10-20% of cases), usually with widespread skin rashes. Small tense blisters with serous or serous-hemorrhagic contents are found on the mucous membrane of the hard palate, cheeks or gums.

Unlike pemphigus vulgaris. blisters with bullous pemphigoid persist on the oral mucosa for several days due to the great depth of occurrence and thick tire. When they are opened, painful, clearly demarcated erosions without fibrinous plaque are formed, which epithelialize faster than with pemphigus. Very rarely, in addition to the skin, the mucous membrane of the pharynx, larynx, genitals, and eyes can be affected. The disease can be chronic with exacerbations and remissions of varying durations (months, years). If untreated, the mortality rate is lower than with pemphigus vulgaris (about 40%). Patients may die from secondary infection (bronchopneumonia, sepsis, etc.) or from decompensation of existing diseases. In patients with bullous pemphigoid, secondary anemia, leukocytosis with moderate eosinophilia develop, ESR increases, and the level of immunoglobulin E in the serum increases.

Diagnosis of bullous pemphigoid

In fingerprint smears from the bottom of fresh erosion, a large number of eosinophils (20-30% or more) are found; acantholytic cells are absent. Histological examination reveals a subepidermal cavity with numerous eosinophils. The basement membrane is split and can be traced both at the base of the bladder and in its operculum. In the dermis there is swelling of the papillae and an infiltrate consisting mainly of eosinophilic granulocytes.

Using PIF, a homogeneous strip-like deposition of immunoglobulins G and Cj-complement in the basement membrane zone is detected in biopsied areas of the affected skin of patients. Using indirect IF, IgG antibodies to a protein that is part of the basement membrane are detected in the blood serum and cystic fluid in 80-90% of patients. Their titers do not correlate with the severity of the disease. Differential diagnosis carried out with pemphigus vulgaris, bullous form of Dühring's dermatosis herpetiformis, bullous form of polymorphic exudative erythema and bullous toxicderma.

Treatment of bullous pemphigoid

In some cases, bullous pemphigoid can be a companion to cancer, so patients are examined in detail to identify malignant tumors and other concomitant diseases. Avoid medications and influences that can provoke bullous pemphigoid.

The basis of treatment for bullous pemphigoid is pathogenetic therapy with immunosuppressants: glucocorticoids alone or in combination with azathioprine or diaphenylsulfone (DDS). Prednisolone (or another GC in an equivalent dose) is prescribed in medium doses (40-60 mg per day) until a pronounced clinical effect is obtained (usually 2-3 weeks). Then the dose is gradually reduced to maintenance (10-15 mg of prednisolone per day). If no rash appears over the next 3-6 months of maintenance dose therapy, glucocorticosteroids can be completely discontinued. If there are contraindications to prednisone, treatment with azathioprine or DDS can be tried.

External treatment of bullous pemphigoid is similar to that for pemphigus. It is rational to use antimicrobial (if localized in folds - and antifungal) drugs that are astringent and have a local anesthetic effect.

Sources:

1. Sokolovsky E.V. Skin and venereal diseases. - St. Petersburg: Foliant, 2008.

2. Thoma-Uszynski S, Uter W, et al. BP230- and BP180-specific auto-antibodies in bullous pemphigoid. J Invest Dermatol. 2004 Jun.

3. Smolin G. Foster C.S. et al. Smolin and Thoft's The Cornea: Scientific Foundations and Clinical Practice. Lippincott Williams & Wilkins, 2005.

Pemphigoid: types of disease and its manifestations, principles of therapy

Pemphigoid is a chronic benign skin disease that occurs mainly in older people. The pathology is based on the detachment of areas of the epidermis without loss of intercellular connections in one of the widest ranges. This situation arises due to various reasons, in which antibodies to one’s own skin appear in the human body.

Diagnosis of pathology is carried out by a dermatologist using a combination of several instrumental techniques. Treatment includes both systemic immunosuppressive therapy and local agents. The disease responds well to therapy, but the drugs will have to be used for a long time to avoid relapse.

What is pemphigoid

This disease affects only the top layer of skin - the epidermis. To make the processes taking place clear, let us briefly consider the structure of this formation.

In structure, the epidermis resembles a house of 13-16 floors, lying on hills (the dermis creates such elevations and depressions) with a very wide roof. This layer consists of four, and on the palms and soles - of five anatomically different layers:

• those that make up the “building blocks” are the germ layers. There are two of them: basal (“bricks” lie in one or two layers) and spinous (there are 10 or more rows of cells);
• The “roof” is the remaining 2 or 3 layers. They come from germ layers, but with each row they look less and less like cells (the last layer is actually scales).

The stratum spinosum is special: it is multilayered, and its cells are equipped with projections - “spines”. They are connected. In true pemphigus (pemphigus), the connection between these spines is destroyed as a result of the inflammatory process. With pemphigoid (the suffix “-oid” means “similar,” that is, “pemphigus-like” pathology), the relationship between the cells of the spinous layer remains “in force.” This is the main difference between the two pathologies, manifested by the appearance of blisters on the skin.

Under the influence of the reasons described below, immunoglobulin antibodies are formed to the membrane on which the basal layer of the epidermis lies. It is, in fact, a separator between the epidermis and dermis; it contains factors that stimulate the growth of the upper skin layer. When areas of the basement membrane come under “attack” of antibodies, a cascade is activated immune reactions, neutrophil cells enter here. Various enzymes are released from them, which destroy the “threads” connecting the epidermis to the dermis. The same thing happens with pemphigus, only with it there is a connection with the main tissue compatibility antigens localized on leukocytes, which does not happen with pemphigoid.

Bubbles (bullas) with bullous pemphigoid are formed as follows:

• between the processes of the cells of the lowest layer, with the help of which they communicate with each other, as a result of the autoimmune process, bubbles filled with liquid appear - vacuoles;
• In addition, swelling of the lower layer of skin - the dermis - occurs;
• the gradual fusion of vacuoles, together with dermal edema, leads to the formation of large fluid cavities. The bladder cover is stretched epidermal cells, the bridges between which are preserved;
• then the epidermal cells die;
• At the same time, regenerative processes are launched in the epidermis: new cells creep from the edges of the bubble and gradually capture its bottom. This makes the blister intraepidermal.

Bullae can be located on non-inflamed skin, then they occupy a position around the vessels. If the surrounding skin becomes inflamed, pronounced infiltrates form in the dermis. The fluid filling the bullae contains many lymphocytes, histiocytes (tissue immune cells), a small number of eosinophils (a type of white blood cell responsible for allergic manifestations).

But still, no matter what processes occur, the ligaments between the cells of the spinous layer are preserved, that is, acantholysis (their destruction) does not occur. Therefore, the disease is called a non-acantholytic process. Its second name is Lever's bullous pemphigoid.

Classification of the disease

There are several forms of this pathology:

• Actually bullous pemphigoid, also known as Lever's non-acantholytic pemphigoid. Its symptoms will be described below.
• Cicatricial pemphigoid, also called mucosynechial bullous dermatitis. The elderly age group (people over 50 years old), more often women, are susceptible to pathology. The appearance of blisters on the conjunctival membrane and oral mucosa is characteristic; Some patients experience skin rashes.
• Non-acantholytic benign pemphigus of the oral mucosa only. As the name suggests, blisters only appear in the mouth.

There are also separate species pemphigoid - pyococcal pemphigoid. This is an infectious disease caused by Staphylococcus aureus, which develops in children on the 3-10th day of their life. It is highly contagious. The source of infection can be the medical staff of the maternity hospital or the mother of the child who has recently been ill staphylococcal infection or is a carrier Staphylococcus aureus in the nasopharynx.

It is characterized by the rapid appearance of blisters on the baby's reddened or healthy-looking skin. Initially they appear on the torso and abdomen. The blisters initially have the size of a large pea, then they grow and can reach several centimeters in diameter and fester; they are surrounded by a pink corolla. In addition, the temperature rises and the general condition of the child may be affected. Staphylococcal pemphigoid can lead to blood poisoning, which can be fatal in severe cases.

Causes of pemphigoid

Why this disease develops is not known exactly. It is believed that pathology can occur due to:

• ultraviolet irradiation;
• taking certain medications: Penicillin, Furosemide, 5-fluorouracil, Salazopyridazine, Phenacetin, Potassium iodide, Ciprofloxacin, Amoxicillin or even Captopril;
• tumor process of any localization (therefore, when making a diagnosis of “Bullous pemphigoid”, doctors search for cancer in all possible localizations).

Symptoms of pathology

The disease has a chronic course, when a period of absence of symptoms (remission) is interspersed with a period of resumption of symptoms (exacerbation), and with each new exacerbation the pathology can spread.

Symptoms of bullous pemphigoid

The range of symptoms is quite wide. Usually this:

• the appearance of tense blisters measuring 0.5-3 cm on reddened and swollen skin, less often on normal skin;
• a lot;
• itchy, less often – itchy and painful;
• localized mainly: in the folds of the skin, on the abdomen, inner thighs and shoulders, forearms. In a third of cases, they appear in the size of 0.5-2 cm on the oral mucosa: on the cheeks, on the border between the hard and soft palate, on the gums;
• most often the bubbles are located symmetrically;
• have transparent contents, which over time can become purulent (yellow or white) or bloody;
• at the same time, like the bullae, urticaria-like elements of the rash appear, having a red or pink-red color. Such blisters are especially noticeable when the redness of the skin on which the blisters are located subsides;
• after the blister opens, a moist area of ​​pink-red color remains, which quickly heals with or without the formation of crusts;
• the general condition of most people does not suffer: consciousness is not depressed, there is no fever, weakness, nausea or vomiting. Depleted patients and the elderly may experience loss of appetite and weakness; they may lose weight.

In the initial stages of the disease there may be no blisters, only crusts, eczema-like polymorphic elements or blisters like urticaria. The rash may be accompanied by itching of varying intensity, which is difficult to treat. Subsequent exacerbation occurs already with usual symptoms, if this is the classic form of pemphigoid, or with repetition of the same symptoms, with atypical forms.

Manifestations of cicatricial pemphigoid

The rash can be found on the soft palate, buccal mucosa, uvula and tonsils, while the oral mucosa is red and swollen, but may not be changed. Sometimes eruptive elements appear on the lips, on the conjunctiva of the eyes, and, developing on the skin, are localized on the face, in folds (especially on the thigh), and scalp. The disease can also affect internal organs.

The rash is tense blisters, the contents of which are clear or bloody. After opening them, deep red erosions are visible.

A characteristic sign of cicatrizing pemphigoid is the appearance of blisters constantly in the same places, which contributes to the development of scars there. This scarring in the lip area makes it difficult to open the mouth. Activated on the conjunctival membrane of the eye, the cicatricial process leads to its wrinkling, restriction of movements of the eyeball, and impaired patency tear ducts. Ocular localization can also cause ulcers to appear on the cornea, causing it to become cloudy and only allow a person to perceive light.

The cutaneous localization of this form of pathology causes the appearance of scars located below the level of the underlying skin. Developing on the internal organs, the disease can be complicated by deterioration of the patency of the larynx, esophagus, urethra, vagina or anus.

Diagnostics

The diagnosis of Bullous Pemphigoid or Cicatricial Pemphigoid is made on the following grounds.

1. Inspection: pemphigoid has a characteristic localization and a typical high density of blisters.

2. Skin biopsy, according to which the following is carried out:

• conventional microscopy: acantholysis is excluded (loss of communications between the spines of cells of the spinous layer);
• immunofluorescence microscopy, which allows the dermatologist to see the glow of the skin in the area not of the spinous layer, but of the basement membrane;
• immunoelectron microscopy: gold labeling of immunoglobulins is used, after which its location is studied;
• method of immunoblotting and immunoprecipitation.

Therapy

Treatment of bullous pemphigoid consists of introducing drugs into the body that will block the functioning of the immune system - these are:

1. Glucocorticoid hormones: prednisolone, dexamethasone, starting with small doses (30-40 mg of prednisolone per day).
2. Cytostatics (similar drugs are also used in chemotherapy cancerous tumors): Azathioprine, Cytoxan, Methotrexate.

In case of severe pathology, the simultaneous use of both glucocorticosteroid and cytostatic drugs is recommended for the first 2 weeks.

To increase the effectiveness of the above means, the following are used:

3. systemic enzymes: Phlogenzyme, Wobenzym;
4. vitamins necessary to strengthen the vascular wall: vitamin P, C, nicotinamide;
5. immunotherapy drugs: Rituximab.

If it is proven that bullous pemphigoid has arisen as a result of the development of a malignant tumor in the body, antitumor therapy is carried out. It will depend on the location of the tumor, its degree of malignancy, and the stage of the disease. Can be surgical, radiation, medication (chemotherapy, targeted therapy).

Local treatment depends on the location of the lesions:

6. If they are on the skin, they are treated with ointments based on glucocorticoid hormones: prednisolone, hydrocortisone, Aklovate, Afloderm, Topicort, Oxycort.
7. When the blisters are located in the eye, local therapy is prescribed by an ophthalmologist. This eye drops with glucocorticoids (dexamethasone drops), antibacterial and antiseptic agents (Ocomistin, chloramphenicol drops) - for the prevention of purulent complications. If, after damage to the blisters, erosions on the conjunctival membrane do not epithelialize, the drug Korneregel is prescribed.
8. If the eruptive elements are located on the oral mucosa, rinses with antiseptics are prescribed: an aqueous solution of furatsilin, chlorhexidine, miramistin.

Skin care for bullous pemphigoid includes treating the blisters with antiseptics such as brilliant green solution, methylene blue or fucorcin. These medications will dry out the bullae and prevent them from becoming infected. If you have a blistering rash, swimming is not recommended. Hygiene is carried out with gauze wipes soaked in aqueous solutions of antiseptics: chlorhexidine, furatsillin. This should be done with blotting movements.

What to do with non-healing erosions with pemphigoid?

This happens either due to infection or poor regenerative abilities. In the first case, instead of single-component ointments containing only glucocorticoids, combined agents with hormones and antibiotics: Pimafucort, Imakort, Aurobin.

Poor regenerative abilities require further clarification of the reasons: it could be diabetes mellitus or vascular pathology. Then, if appropriate treatment is prescribed, the erosions will heal. Until the etiology is clarified or if it remains unknown, and in addition to treatment of the causative disease, dexpanthenol in the form of Bepanten cream or methyluracil in the form of a gel-like drug Levomekol is prescribed.

Do you need a diet?

A diet for bullous pemphigoid is needed in order not to expose the body, in which the immune system is strained, to additional allergenic influences. It consists of observing the following rules:

9. there should be enough vegetables in the diet;
10. replace meat with fish;
11. dairy products – minimum;
12. You should try to completely eliminate sugar;
13. trans fats - margarine, mayonnaise, sauces, fried foods, lard, ham, sausages - should be excluded.

What can you eat?

Greens, vegetables, fruits, sea fish, liver, whole grain bread, cereals, green tea, boiled or baked lean meat (chicken, veal), soups with a second broth or vegetarian.

Bullous pemphigoid: causes, symptoms, treatment

Bullous pemphigoid is an autoimmune skin disease that causes chronic blistering in older patients. Diagnosis is made using a biopsy. First of all, glucocorticoids are used in treatment. Many patients require long-term maintenance therapy, during which various medications may be used.

In bullous pemphigoid, antibodies are directed against the basement membrane and cause separation of the epidermis from the dermis. Bullous pemphigoid must be distinguished from pemphigus vulgaris, which is a more serious disease.

Symptoms and signs

Characteristic tense blisters appear on normal or reddened skin. Nikolsky's symptom is negative. Swollen or ring-shaped, dark red lesions with or without blistering may appear. There is often itching without any other symptoms. Lesions of the oral mucosa occur in 1/3 of patients, but usually heal quickly.

It is necessary to distinguish ordinary pemphigus from pemphigoid, IgA linear dermatosis, erythema multiforme, rashes caused by the use of drugs, benign pemphigoid of the mucous membranes, dermatosis herpetiformis, congenital epidermolysis bullosa. Diagnosis requires a skin biopsy and determination of antibody titers in the blood serum.

Prognosis and treatment

The prognosis is usually good and the disease usually resolves within a few months or years, but may lead to fatal outcome, especially in elderly patients.

For mild forms of the disease, local glucocorticoids can be used in treatment. Patients with a more severe form of the disease are prescribed prednisone 60-80 mg orally once a day, after a few weeks reducing the dose to a maintenance dose of 10-20 mg once a day. In most patients, remission occurs within 2-10 months. The occurrence of isolated new rashes in elderly patients does not require an increase in dosage.

The disease is sometimes treatable with tetracycline and nicotinamide. Dapsone, sulfapyridine, erythromycin and tetracycline may also be used as they have anti-inflammatory effects. Most patients do not require immunosuppressants, but azathioprine, cyclophosphamide, cyclosporine, or plasmapheresis may be used.

PEMFIGOID

O. L. Ivanov, A. N. Lvov

"Dermatologist's Handbook"

PEMPHIGOID (synonym: non-acantholytic pemphigus) is a benign chronic skin disease, the primary element of which is a bubble that forms subepidermally without signs of acantholysis.

Nikolsky's symptom is negative in all modifications. The blisters usually regress without a trace and are much less likely to leave scars. This circumstance gave grounds to distinguish between two variants of pemphigoid - bullous and cicatricial.

Etiology pemphigoid is unknown. In some cases it may be paraneoplastic in nature. The autoallergic nature of the disease is most substantiated: autoantibodies to the basement membrane of the epidermis (usually IgG, less often IgA and other classes) were detected.

Histologically on early stages pemphigoid, the formation of subepidermal microvacuoles is detected. Their fusion leads to the formation of blisters that separate the epidermis from the dermis. Subsequently, the epidermis, which makes up the covering of the bladder, becomes necrotic and destroyed, with the exception of the stratum corneum. After the formation of blisters, re-epithelialization of their bottom occurs, and they can be located in the dermis up to the subcorneal localization. There are no signs of acantholysis. With cicatricial pemphigoid, fibrosis of the upper layers of the dermis and a decrease in elastic tissue are noted.

Pemphigoid bullous has many synonyms:

14. chronic pemphigus vulgaris,
15. pemphigus vulgaris benign,
16. parapemphigus,
17. senile dermatitis herpetiformis,
18. dermatitis herpetiformis bullous.

They reflect the similarity of bullous pemphigoid with true (acantholytic) pemphigus and dermatitis herpetiformis. Moreover, the similarity with pemphigus is clinical due to blistering rashes, and with dermatitis herpetiformis - pathohistological due to the subepidermal formation of blisters.

It is distinguished from pemphigus by a benign chronic course and subepidermal formation of blisters, and from dermatitis herpetiformis by a monomorphic bullous rash; The predominant affection of elderly people (over 60 years of age) distinguishes bullous pemphigoid from pemphigus. and from dermatitis herpetiformis. Damage to the mucous membranes, unlike true pemphigus, is not inevitable, although it is not exceptionally rare.

The disease begins with the appearance of blisters against the background of erythematous-edematous spots, less often on apparently unchanged skin. Bubbles of medium size (from a pea to a bean), hemispherical in shape, with a dense, smooth and tense tire, serous or serous-hemorrhagic contents. Due to the dense covering, they are more persistent than the blisters of true pemphigus.

Erosions after their opening do not tend to grow peripherally and quickly epithelialize. When the contents of the blisters and erosion discharge dry out, yellowish-brown crusts of various sizes and thicknesses are formed. When they are rejected, pink-red spots covered with scales are exposed. The predominant localization is the lower half of the abdomen, inguinal folds, axillary fossae and flexor surfaces of the arms and legs. Damage to the mucous membranes is observed in approximately 20-40% of patients with bullous pemphigoid and occurs, with rare exceptions, secondarily. As the process progresses, and sometimes from the very beginning, blisters spread across the skin until a generalized and even universal rash forms. Subjectively - often itching of varying intensity, burning and soreness.

Relapses of pemphigoid are often caused by UV rays, both natural and artificial.

Over time, the severity of the disease gradually weakens, but bullous pemphigoid is a potentially serious disease that cannot exclude death.

Pemphigoid cicatricial. like bullous, it has many synonyms:

19. benign pemphigoid of the mucous membranes,
20. chronic mucocutaneous pemphigoid dermatitis,
21. pemphigus eye (conjunctiva),
22. pemphigoid mucosynechial.

The essence of the disease is most fully reflected by the term “bullous atrophying mucosynechial dermatitis,” emphasizing its main clinical feature - the outcome of blisters into scars, adhesions, and atrophy. Occurs 2 times more often in women than in men; older people get sick.

Cicatricial pemphigoid is a disease of the mucous membranes: in about a third of patients, the process is secondarily involved skin covering. The mucous membranes of the mouth and conjunctiva of the eyes are most often affected. In the oral cavity, tense blisters with a diameter of 0.2 to 1.5 cm appear on an externally unchanged mucous membrane or on an erythematous background; their contents are serous, rarely hemorrhagic. Erosion that occurs when the covering of the blisters ruptures is not prone to peripheral growth, does not bleed, their surface is free from any layers, they are not bordered by exfoliating epithelium; low pain. Salivation and swelling of the mucous membranes are insignificant.

Cicatricial adhesive and atrophic changes occur within 3 years after the onset of the disease.

It is distinguished by great originality cicatricial pemphigoid in the eye area. Already in the early stages, signs of scarring may appear in the form of small adhesions between the conjunctiva of the eyelids and the eyeball or between the upper and lower eyelids. As scarring increases, the vaults of the conjunctival cavity decrease until complete obliteration. A peculiar consequence of long-term scarring pemphigoid is the so-called sculpted eyes, in which the cornea is completely covered with a cloudy membrane, allowing only the perception of light.

On the skin there are single blisters, rarely generalized; occur on apparently healthy or erythematous skin and are persistent; erosions after them slowly heal with the formation of atrophic scars, leading to baldness on the scalp. With cicatricial pemphigoid, various functional and morphological disorders of the trachea and larynx, esophagus, vagina and anus, urethra, etc. can also occur.

Diagnosis of bullous and cicatricial pemphigoid It is based on:

23. clinical and histological data
24. results of indirect and direct immunofluorescence studies.

Differentiate pemphigoid especially difficult from pemphigus vulgaris. especially in its initial stages, when acantholytic cells are often not detected and Nikolsky’s symptom is negative. The final diagnosis is helped by the results of histological (subepidermal rather than intraepidermal location of the bladder) and immunofluorescence (luminescence in the area of ​​the basement membrane, and not in the area of ​​the spinous layer) studies.

Pemphigoid is also differentiated from:

Scarring pemphigoid is also differentiated from:

Corticosteroid hormones. The initial dose is 40-80 mg of prednisolone per day; for cicatricial pemphigoid with eye damage, higher doses may be required.

The duration of treatment and the rate of reduction in the daily dose are determined by the severity of the disease.

Cytostatics are also used, as in true pemphigus, and sulfone drugs, as in dermatitis herpetiformis.

If the disease is paraneoplastic, antitumor therapy is used.

Bullous pemphigoid is an autoimmune skin disease caused by the production of autoantibodies to hemidesmosomal components (antigens BP180 and BP230) and characterized by the formation of subepidermal blisters.

Etiology and epidemiology

In most cases, the development of bullous pemphigoid is not associated with any provoking factor. In some patients with bullous pemphigoid, the appearance of rashes is caused by taking medications, exposure to physical factors, and viral infections.

Drugs that may be associated with the development of bullous pemphigoid are penicillamine, penicillins and cephalosporins, captopril and other angiotensin-converting enzyme inhibitors; furosemide, aspirin and other non-steroidal anti-inflammatory drugs, nifedipine. There are known cases of the development of bullous pemphigoid after the administration of a flu vaccine or antitetanus toxoid. The development of bullous pemphigoid after exposure to physical factors - ultraviolet irradiation, radiation therapy, thermal and electrical burns, after surgical procedures. It is assumed that the development of bullous pemphigoid can be facilitated by viral infections (hepatitis B and C viruses, cytomegalovirus, Epstein-Barr virus).

The development of bullous pemphigoid is caused by the production of IgG autoantibodies to the proteins BP180 (type XVII collagen) and BP230, which are part of hemidesmosomes, which are a structural component of the basement membrane of the skin.
According to the Federal statistical observation incidence of bullous pemphigoid in Russian Federation in 2014 was 1.1 cases per 100,000 adults (aged 18 years and older), and the prevalence was 2.6 cases per 100,000 adults. Mostly elderly people are affected. Among people over the age of 80 years, the incidence of bullous pemphigoid reaches 15–33 cases per 100,000 of the corresponding population per year.

Classification

There is no generally accepted classification.

Symptoms of bullous pemphigoid

Skin lesions in bullous pemphigoid can be localized or generalized. The rashes are most often localized on the extremities, abdomen, inguinal-femoral folds, and on the inner thighs.
Rashes in patients with bullous pemphigoid can be polymorphic. The disease usually begins with the appearance of erythematous, papular and/or urticarial rashes accompanied by itching. These rashes can last for several months, after which blisters appear. The blisters have a tense, dense covering, round or oval shape, serous or serous-hemorrhagic contents, located on an erythematous background or on apparently unchanged skin. Erosion formed at the site of blisters, in the absence of secondary infection, quickly epithelializes and is not prone to peripheral growth. Nikolsky's symptom is negative. The mucous membranes are affected in 10–25% of patients. The disease is characterized by a chronic relapsing course.

The severity of bullous pemphigoid is determined by the number of vesicular elements that appear. Bullous pemphigoid is defined as severe when more than 10 blisters appear per day for 3 consecutive days, and mild when 10 or fewer blisters appear per day.

Diagnosis of bullous pemphigoid

Diagnosis of bullous pemphigoid is based on identifying clinical signs of the disease and detection of IgG antibodies to proteins of the basement membrane components of the skin:
Histological examination of a skin biopsy with a fresh blister reveals a subepidermal cavity with a superficial infiltrate in the dermis consisting of lymphocytes, histiocytes and eosinophils, which does not always make it possible to distinguish bullous pemphigoid from other diseases with a subepidermal location of the blister (Dühring's dermatitis herpetiformis, acquired epidermolysis bullosa).

To identify IgG to the proteins components of the basement membrane of the skin, an immunohistochemical study of a biopsy sample of apparently unaffected skin of the patient is performed, which reveals a linear deposition of IgG and/or C3 complement component in the area of ​​the basement membrane. If differential diagnosis with acquired epidermolysis bullosa is necessary, an additional immunofluorescent study of a skin biopsy sample, previously digested by keeping it in a 1M sodium chloride solution for 1 day, is carried out. This study reveals the deposition of IgG in the upper part (cover) of the cavity formed in the area of ​​the dermal-epidermal junction.

Differential diagnosis

The disease should be differentiated from the bullous form of Dühring's dermatitis herpetiformis, exudative erythema multiforme, pemphigus vulgaris, bullous toxiderma, acquired epidermolysis bullosa.

Treatment of bullous pemphigoid

Goal of treatment

• achieving remission.

General notes on therapy

When prescribing and carrying out therapy for patients with bullous pemphigoid, the following should be taken into account:

• Restrictions on the use of certain drugs in elderly patients.
• Possible concomitant diseases of the patient (diabetes mellitus, arterial hypertension, coronary heart disease, neurological diseases).
• Adverse events associated with systemic therapy and topical therapy.

During treatment with systemic glucocorticosteroids, blood pressure measurements should be taken to monitor the condition. of cardio-vascular system and blood glucose control.

During therapy with cytostatics, the content of hemoglobin and red blood cells, leukocytes and platelets in the peripheral blood, indicators of liver and kidney function, and indicators of a general urine test should be monitored. When carrying out therapy with systemic glucocorticosteroid drugs and immunosuppressants, it is also necessary to promptly identify signs infectious diseases and complications.

Treatment regimens

For mild bullous pemphigoid:

In the absence of clinical effect from therapy with a topical glucocorticosteroid drug for 1–3 weeks:

• prednisolone

For severe bullous pemphigoid:

• clobetasol dipropionate 0.05%
• prednisolone In case of relapse, the dose of the corticosteroid drug is increased to the original level.

If it is necessary to reduce the dose of systemic corticosteroids, the following are prescribed:

• plasmapheresis
• azathioprine
• mycophenolate mofetil
• methotrexate
• cyclophosphamide

In addition to prescribing topical corticosteroid drugs, large blisters and erosions are treated:

• the bubbles are opened with a puncture and drained, leaving the tire
• erosive lesions are treated with an antiseptic solution: chlorhexidine 0.05–0.2% solution, miramistin 0.01% solution, brilliant green 1% alcohol solution

Indications for hospitalization

• severe course of bullous pemphigoid, requiring systemic therapy;
• lack of effect from treatment with topical corticosteroids on an outpatient basis;
• the presence of secondary infection in the lesions.

Requirements for treatment results

• stopping the progression of the disease;
• reduction of itching;
• epithelization of erosions.

Tactics in the absence of treatment effect

If there is no effect from therapy with systemic and topical glucocorticosteroid drugs, immunosuppressive drugs or plasmapheresis are additionally prescribed for several weeks.

Prevention

There are no methods of prevention.

If you have any questions about this disease, please contact dermatovenerologist Adaev Kh.M:

WhatsApp 8 989 933 87 34

Email: [email protected]

Instagram @dermatolog_95

For quotation: Grigoriev D.V. Lever's bullous pemphigoid // Breast cancer. 2014. No. 8. P. 598

Main characteristics

1. Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease; it predominantly affects older people.

2. In most cases, this is a chronic disease with spontaneous exacerbations and remissions, which can be accompanied by a significant degree of spread of the disease.

3. PD is associated with tissue-fixed and circulating antibodies directed against BP180 antigen (BP180 or type XVII collagen) or BP230 antigen, components of junctional adhesion complexes called hemidesmosomes that support the epidermal junction.

4. The range of clinical manifestations is very wide. In typical cases, PD presents with an intensely itchy rash with widespread blistering. In the initial stages or with atypical variants of this disease, only excoriated, eczematous or urticarial lesions (localized or generalized) are present.

5. The diagnosis is based on immunopathological studies, especially direct and indirect immunofluorescence microscopy, as well as enzyme immunoassay of antibodies to BP180/BP230 antigens.

Introduction

PD is the most common autoimmune subepidermal blistering skin disease. This disease typically occurs in older adults as a widespread, pruritic, blistering rash and is potentially associated with a significant mortality rate. The clinical picture can be quite polymorphic, especially in the early stages of the disease or with atypical variants, in which fully developed bullous lesions may be absent. In these cases, establishing a diagnosis of PD requires a high degree of suspicion. PD is a pattern of organ-specific autoimmune disease. The antigens targeted by patients' antibodies are two components of hemidesmosomes, junctional adhesion complexes found in the skin and mucous membranes.

Story

During the 18th century, the term pemphigus was often used to describe any type of blistering rash. It was only in 1953 that Lever, based on specific clinical and histological features, recognized PD as a disorder distinct from the various types of “true” pemphigus. A decade later, Jordon, Beutner and colleagues demonstrated that PD patients have tissue-bound and circulating antibodies directed against the basement membrane zone of the skin. This observation led to the idea that epidermal detachment is caused by antibodies directed against skin structures that support the dermoepidermal junction. The next milestones in our understanding of PD included the immunochemical characterization of target proteins, cloning of their genes, and the creation of animal models of this disease.

Epidemiology

PD is typically a disease of older people with onset after 60 years of age. It is estimated that the annual incidence is at least 6-13 new cases per 1 million population (with a rapid increase after 60 years); however, these figures require further refinement (eg using age-matched individuals as the denominator). The relative risk for a patient over 90 years of age appears to be approximately 300 times higher than for a patient 60 years of age or younger, with a clear higher predominance in men than in women.

This disease also occurs in children, but is rare. Currently, there are data on fewer than 100 cases of juvenile PD. Cases of PD have been reported in the first few months of postnatal life, but transplacental transmission has not been described. Triggering factors for juvenile PD have not been clearly identified; Temporary associations with vaccinations, repeat organ transplantation, hyper-IgE syndrome, and chronic renal transplant rejection have been reported.

Some MHC class 2 alleles are more common in PD patients than in the general population. In Caucasians, a significant association was found with the DQB1*0301 allele, while an increased frequency of the DRB1*04, DRB1*1101 and DQB1*0302 alleles was observed in Japanese patients.

Pathogenesis

PD is an example of an immune system-mediated disease that is associated with a humoral and cellular response directed against two well-studied autoantigens: PD antigen 180 (BP180, BPAG2, or type XVII collagen) or BP antigen 230 (BP230, or BPAG1). While the former is a transmembrane protein with a large collagenous extracellular domain, the latter is a cytoplasmic protein belonging to the plakin family. These two antigens are components of hemidesmosomes, which are adhesion complexes that maintain the epithelial-stromal junction in stratified and other complex epithelia. Figure 1 demonstrates the location and interaction of the BPAG1 and BPAG2 molecules in the basement membrane of the epidermis.

In vitro studies and in vivo animal models have provided strong evidence for the pathogenetic role of antibodies in PD. In addition, in herpes pregnancy, a disease closely associated with PD, transplacental transfer of antibodies to HPAH2 from mother to fetus can lead to a transient bullous rash. Finally, the autoimmune etiology of PD is indirectly supported by its association with certain major histocompatibility complex class 2 haplotypes and its response to immunosuppressive therapy.

Humoral and cellular responses

Almost all patients with PD have circulating IgG antibodies that bind to PAH2. More precisely, it is the non-collagenous NC16A domain, a region of BPAG2 localized extracellularly but close to the transmembrane domain, that forms the immunodominant region (Fig. 2). However, additional antigenic sites exist within both the extracellular and intracellular domains of PAH2, and they are recognized by the sera of up to 70% of PD patients. Patients with PD also exhibit significant autoreactivity to intracellular PAH1. BP230-reactive antibodies bind predominantly, but not exclusively, to the C-terminal region of this autoantigen. The presence of multiple antigenic sites along the entire length of BP180 and BP230 is most likely the result of a phenomenon known as “epitope spreading.” This phenomenon may also explain the study's finding that patient serum rarely contains antibodies directed at additional components of the basement membrane zone.

Patients with PD exhibit an autoreactive T cell response to PAH2 and PAH1, and this may be critical for stimulating B cells to produce antibodies. This autoreactivity of anti-PD180 autoreactive T cells is limited to certain MHC2 alleles (eg, HLA-DQB1*0301) that are common in PD patients. These T lymphocytes, whose significant constituents are mostly epitopes, appear to be hidden within the NC16 domain, have a CD4+ phenotype and secrete both Th1- (e.g., interferon-γ) and Th2-cytokines (e.g., interleukins 4, 5 and 13). Th2 cytokines may be extremely important in the pathophysiology of PD; they predominate in the lesions and serum of patients. In addition, the IgG4 subclass, the secretion of which is regulated by Th2 cytokines, is one of the constituent isotypes of anti-BP180 antibodies.

Following antibody binding to antigenic targets, subepidermal blister formation occurs through a cascade of events that includes complement activation, recruitment of inflammatory cells (mainly neutrophils and eosinophils), and release of various chemokines and proteases such as matrix metalloproteinase-9 and neutrophil elastase. These proteinases proteolytically degrade various extracellular matrix proteins as well as BP180. Infiltrating mast cells and eosinophils (which can be activated by specific IgE anti-BP180 antibodies) are also significantly involved in causing tissue damage through the secretion of proteases and proinflammatory mediators, such as IL-5 and eotaxin. Antibodies to BP180 may also possibly enhance the inflammatory response by directly stimulating keratinocytes to produce various cytokines (eg, IL-6 and IL-8). Finally, IgG antibodies reduce the content of BP180 in hemidesmosomes and in this way can cause a weakening of the dermoepidermal cohesion. Figure 3 shows the mechanisms of bubble formation in PD.

Several animal models have provided strong evidence that antibodies against BP180 are pathogenic. When human antibodies against the NC16A domain (the immunodominant determinant of human PD180) were transferred into newborn mice (in which PD180 had been fully or partially humanized by genetic engineering), they were able to induce a cystic disease that reproduced all the core symptoms of PD. In contrast, antibodies against BP230 caused inflammatory reaction in rabbits only after additional trauma to their epidermis; however, recent evidence suggests that anti-BP230 antibodies may induce an inflammatory response and subepidermal blister formation in a mouse model. Together, these studies have led to the theory that antibodies to the ectodomain of BP180 are pathophysiologically important, while the production of antibodies against BP230 is a secondary phenomenon that contributes to tissue damage.

Clinical signs

Prevesical (nonbullous) phase

The cutaneous manifestations of PD can be extremely polymorphic. In the prodromal, nonbullous phase of this disease, signs and symptoms are often nonspecific with intractable moderate to severe pruritus or associated with excoriated, eczematous, papular, and/or urticarial eruptions that may persist for weeks or months. These nonspecific skin symptoms may remain the only signs of the disease.

Cystic (bullous) phase

The bullous stage is characterized by the development of vesicles and blisters on visually healthy or reddened skin along with urticarial or infiltrated nodules and plaques, which sometimes become ring-shaped. These blisters are tense, up to 1-4 cm in diameter, contain clear fluid and can persist for several days, leaving eroded or crusted areas. Sometimes the bladder fluid becomes bloody. The lesions often have a symmetrical distribution pattern and predominate on the flexor surfaces of the limbs and the lower part of the torso, including the abdomen. Vegetating plaques may be observed in intertriginous areas. Residual post-inflammatory changes include hyper- and hypopigmentation and, extremely rarely, milia. Oral involvement occurs in 10-30% of patients. The mucous membranes of the eyes, nose, pharynx, esophagus and anogenital area are affected less frequently. Approximately 50% of patients have eosinophilia in the peripheral blood.

Clinical options

Several clinical variants of PD are described and outlined in Table 1. Herpes gravidarum is also a variant of PD that typically occurs during pregnancy.

While individual foci of PD in children younger age and adolescents (infantile and adolescent PD) are similar to the lesions observed in the elderly, the localization of the lesions may differ. In young children, blisters often first appear on the acral areas and then spread to other areas, including the face. Lesions of the genital organs (for example, vulvar adolescent pemphigoid), as well as other areas of the mucous membranes, have been observed in adolescents.

Relationship with other diseases

The association of malignant tumors of internal organs with PD probably correlates with the older age of these patients. Although many reports have suggested an increased incidence of certain cancers (eg, gastrointestinal, bladder, lung) as well as lymphoproliferative diseases, in 3 case-control studies there was a trend towards an increased risk of malignancy. apparently was minimal. However, patients with PD should be screened using modern cancer screening tests recommended for the general population.

Rarely, PD has been described in patients with inflammatory disease intestines and other autoimmune diseases such as rheumatoid arthritis, Hashimoto's thyroiditis, dermatomyositis, systemic lupus erythematosus and autoimmune thrombocytopenia. It is believed that these connections are not accidental, but indicate a genetically predetermined increased susceptibility to the development of autoimmune diseases. However, one case-control study did not find any increased risk of autoimmune diseases for patients with PD.

In a few patients, PD appears to be initiated by trauma, burns, radiation therapy or ultraviolet radiation (including PUVA). PD has also been identified in association with certain dermatoses, such as psoriasis and lichen planus, and blisters may be located on psoriatic plaques. It has been suggested that a chronic inflammatory process in the dermoepidermal junction leads to the effect of antigens on autoreactive T lymphocytes, causing a secondary immune response (epitope expansion phenomenon).

It should be emphasized that PD is often associated with neurological diseases, such as Parkinson's disease, dementia, psychiatric diseases (unipolar and bipolar disorders) and paralysis. A strong relationship was also observed with multiple sclerosis in one population study. It should be noted that neural variants of BP230 are expressed in the central and peripheral nervous systems.

Drug-induced PD

Some patients have systemic medicines may lead to the development of PD. Drug culprits are numerous, including diuretics (eg, furosemide), analgesics (phenacetin), D-penicillamine, antibiotics (amoxicillin, ciprofloxacin), potassium iodide, gold, and captopril. Reproduction of PD rashes after repeated drug administration has been observed with some drugs (eg, furosemide), but for others the association is based on lesser evidence. One case-control study evaluating medications used on a long-term basis prior to the onset of the disease found that two classes of these medications, diuretics and antipsychotics, were used more often by PD patients than by control subjects. Among diuretics, the risk was associated with aldosterone antagonists. Therefore, a detailed drug history is required for all patients in order to exclude the triggering effect of any drug, since immediate withdrawal can lead to rapid improvement.

The mechanism by which drugs promote the development of PD remains to be elucidated. It is likely that these drugs act as a trigger in patients with underlying genetic susceptibility by either modifying the immune response or altering the antigenic properties of the epidermal basement membrane.

Diagnosis

The diagnosis of PD is based on the typical clinical presentation, histological features and, most importantly, positive microscopic findings of direct and indirect immunofluorescence or PD180 enzyme-linked immunosorbent assay (ELISA). In most cases, immunofluorescence microscopy provides criteria that are necessary and sufficient for the correct classification of patients. However, especially in patients who are negative by indirect immunofluorescence microscopy, additional immunochemical studies (eg, ELISA) are used and required to demonstrate an antibody response to the disease targets BP180 and/or BP230. In the absence of fully developed bullous eruptions, for example in the early stages or in atypical variants of this disease, the diagnosis of PD clearly depends on positive results direct immunofluorescence microscopy and characterization of antigenic targets.

Light microscopy and electron microscopy

In the nonbullous phase or in atypical PD, light microscopy may provide less specific information because only the epidermal cleft, eosinophilic spongiosis, and/or dermal eosinophil infiltrates may be detected (Fig. 4). Biopsy specimens of the blister typically show a subepidermal blister at an early stage of development, accompanied by a dermal inflammatory infiltrate consisting of eosinophils and mononuclear cells (Fig. 5). The infiltrate is most often found in the uppermost layers of the dermis, and the bladder cavity contains a fibrin network with a variable inflammatory infiltrate. Electron microscopic studies have demonstrated that the formation of a subepidermal bladder is observed at the level of the lamina lucida.

Immunofluorescence microscopy

In almost all patients, direct immunofluorescence microscopic examinations of uninvolved skin adjacent to the lesions usually characteristically demonstrate the presence of thin, linear, continuous deposits of IgG and/or C3 (and, less commonly, other classes of immunoglobulins) along the epidermal basement membrane (Fig. 6). ). IgG4 and IgG1 are the predominant IgG subclasses. Detailed analysis Linear fluorescence patterns in the basement membrane area, as well as examination of skin near lesions after treatment with 1 M NaCl (referred to as “salt-split skin”) can be used to distinguish PD from other autoimmune blistering diseases. In PD, immune deposits are found on the epidermal side (tegmentum) or on both the epidermal and dermal sides of the cleft layers (Fig. 7). Despite the fact that there is no antigenic mapping method in everyday practice, the nature of fluorescence allows one to more accurately determine the localization of deposited immunoreactants.

In 60-80% of patients, circulating antibodies to the basement membrane of the IgG class and, less commonly, the IgA and IgE classes can be detected. These antibodies typically bind to the epidermal side, or less commonly, both the epidermal and dermal sides of salt-split normal human skin. For indirect immunofluorescence studies, salt-digested normal human skin is the substrate of choice. Finally, when available, testing of circulating antibodies against skin substrates or keratinocyte cell lines that are absent from specific basement membrane proteins, such as BP180 or type VII collagen, provides an easy method for determining their precise pattern of reactivity.

Immunoelectron microscopy

Although less commonly used today, immunoelectron microscopy studies using gold labeling demonstrate that in vivo deposited IgG antibodies are predominantly localized to the outer basement membrane of the cell beneath the hemidesmosomes, with a distribution consistent with that of the extracellular domain of BP180. Using indirect immunoelectron microscopy, circulating antibodies to BP180 and BP230 can be seen in association with hemidesmosomal plaques and at the level of the lamina lucida beneath the hemidesmosomes, respectively.

Immunochemical studies

When studied by immunoblotting and immunoprecipitation of keratinocyte extracts, the serum of 60-100% of patients contains IgG antibodies that bind to BP180 and BP230, respectively. Also, patient serum often contains specific IgA and IgE antibodies. Recombinant forms of BP180 and BP230 expressed on pro- and eukaryotic systems are increasingly being used to detect autoantibodies.

It has been established that solid phase linked immunosorbent assay(ELISA) using recombinant proteins that include specific regions of PD antigens (eg, the NC16A domain of PD180 or the C terminus of PD180 or PD230) is highly specific (>90%). Sometimes, at low titres, false-positive results are observed in healthy individuals or elderly patients with itchy skin rashes. Overall, the sensitivity of the NC16A PD180 ELISA is likely to be comparable to that of indirect immunofluorescence (with saline-digested skin as substrate) when the test is performed in unselected PD patients. To increase overall sensitivity, different ELISAs for BP180 and BP230 proteins must be combined. Unlike immunoblotting, ELISA antigens are tested using natural conditions, and as a result, binding activity to conformational antigens is not lost. These tests are now commercially produced and provide a rapid description of the reactivity of a patient's serum.

Differential diagnosis

Because Clinical signs in the prevesical stage may be nonspecific, they may resemble a number of dermatoses, including drug reactions, contact dermatitis, prurigo, urticaria, reactions to arthropod bites and scabies. These diseases are usually distinguished based on history and general context, pathological features, and negative immunofluorescence microscopy results. The presence of blisters increases the likelihood of bullous reactions to arthropod bites, allergic contact dermatitis, Stevens-Johnson syndrome, bullous drug eruptions, dyshidrotic eczema, pseudoporphyria, and porphyria cutanea tarda. In children, it is necessary to consider bullous impetigo, congenital epidermolysis bullosa and the bullous form of mastocytosis.

Pemphigoid group, paraneoplastic pemphigus, and Dühring's dermatitis herpetiformis can be differentiated based on characteristic immunopathological findings and clinical context. One recent study suggests that in patients with subepidermal blistering disease associated with linear deposition of IgG or C3 along the epidermal basement membrane, the presence of the following four clinical criteria is highly suggestive of a diagnosis of PD:

1) absence of skin atrophy;

2) absence of damage to the mucous membranes;

3) absence of damage to the head and neck;

4) age over 70 years.

However, distinguishing PD from the following autoimmune subepidermal diseases can sometimes be difficult:

• Epidermolysis bullosa acquisita has a wide range of clinical manifestations. While the classic non-inflammatory form of epidermolysis bullosa acquisita is quite characteristic, the inflammatory form bears close resemblance to PD. As with PD, mucosal involvement may be present;
• linear IgA bullous dermatosis represents a group of subepidermal blistering diseases and not a separate entity. While the features of linear IgA bullous dermatosis are polymorphic in adults, in childhood the condition is often associated with annular or polycyclic lesions, as well as involvement of the genital and perioral area. However, the same features are also observed in juvenile PD;
• Mucosal pemphigoid (scarring) is a heterogeneous group of diseases that together have a predominant lesion of the mucous membranes, a chronic course and a tendency to scarring. Skin lesions are found in only 25-30% of patients, and they are usually located on the head and upper torso. In patients with both oral and cutaneous lesions, differentiation of mucosal pemphigoid from PD is difficult and classification depends on the presence of a clear tendency for scarring of the involved mucosal areas and limited skin involvement and sometimes on the results of immunological tests;
• incipient pemphigoid. Difficult question is how to categorize a group of elderly patients with generalized pruritus (with or without skin rash) who have circulating epidermal basement membrane antibodies and reactivity to BP180 and/or BP230 but remain negative on routine immunofluorescence microscopy. Some of these patients with initially negative findings of direct immunofluorescence microscopy actually develop PD over time and can be considered to have incipient pemphigoid;
• anti-p200 pemphigoid. A small group of patients has been described with features identical to those seen in PD, i.e., vesicles and tense blisters, as well as eczematous and urticarial papules and plaques. Sometimes grouped papulovesicles are present with a pattern similar to dermatitis herpetiformis. Damage to the mucous membranes may also occur. These patients have circulating antibodies that specifically bind to the dermal side of the split salt of human skin. This 200 kDa basement membrane protein target is laminin gamma 1 chain.

PD is a chronic disease characterized by spontaneous exacerbations and remissions. Observations in the pre-corticosteroid era indicate that the disease is self-limited in 30% of patients and self-limitation in adults is usually observed within 5-6 years. Due to intractable itching, blistering, eroded and infected lesions, this disease is often accompanied by significant skin damage with a profound impact on quality of life. Although most patients eventually achieve remission with treatment, mortality is significant among older patients. The estimated mortality rate during the first year ranges between 10 and 40%, depending on patient groups. It has been established that age and a Karnofsky score (scale from 0 to 100), which is less than 40, significantly affect the prognosis. It is likely that comorbid conditions and treatment regimens (use of corticosteroids and/or immunosuppressive drugs) also influence overall morbidity and mortality.

The prognosis of juvenile PD is good, and most reported cases have had a disease duration of 1 year or less, although sometimes the course of the disease can be more protracted.

ELISA-based studies have recently found that serum levels of IgG and IgE antibodies to PD180 correlated with disease severity. Moreover, IgG reactivity to both the NC16A domain and the C terminus of PD180 has been associated with a distinct clinical phenotype of PD, with a predominant mucosal involvement. While the practical use of ELISA results as a treatment guide remains to be established, one recent study found that a high BP180-NC16A ELISA (and to a lesser extent, positive direct immunofluorescence findings before the end of treatment are reliable indicators of future PD relapse).

Treatment

Treatment of PD is based more on clinical experience than on controlled studies.

The recommended initial dose of prednisolone is 20 mg/day, or 0.3 mg/kg/day - for localized or mild disease, 40 mg/day, or 0.6 mg/kg/day - for moderate disease and 50- 70 mg/day, or 0.75-1.0 mg/kg/day - for severe illness. Control over the course of the disease is usually achieved within 1-2 weeks, sometimes within 28 days.

This dose is then gradually reduced over a period of 6-9 months. or sometimes longer. Exist various schemes reducing the dose of prednisolone. When the appearance of blisters stops and complete epithelization of erosions occurs, the following option can be proposed: reduce prednisolone in increments of 20 mg once a week at doses of more than 60 mg/day, in increments of 10 mg once a week between doses of prednisolone 30 and 60 mg /day and in increments of 5 mg once a week between the dose of prednisolone 30 mg/day and the physiological dose level. There is an opinion that when the dose of prednisolone reaches 10-15 mg/week. it must be stored for at least 6 months. and in the absence of signs of disease activity, prednisolone reduction can be continued until complete discontinuation. When the prednisolone dose reaches below 10 mg/week. It is recommended to reduce it in increments of 1-2.5 mg/week. to restore the function of the adrenal cortex.

The second way to reduce the dose of prednisolone in PD is to start reducing it when no blisters have appeared within a week and erosions have healed by 80%, then the reduction is made by 20% of the original dose every 2 weeks. until a new bubble appears.

The use of corticosteroids in the elderly, however, is associated with significant side effects. Recent large controlled trials have highlighted the role of potent topical steroids, which appear to control even generalized PD with the same effectiveness as oral corticosteroids and, more significantly, with fewer systemic side effects. However, these studies did not determine the patient's ability to achieve complete disease-free remission compared with systemic corticosteroids. Sometimes pulse therapy with methylprednisolone at a dose of 15 mg/kg for 3 consecutive days is required to quickly control this disease.

The use of immunosuppressive drugs remains a matter of debate. Some clinicians prefer to use them exclusively as second-line therapy when corticosteroids alone do not control the disease or are contraindicated, or when the maintenance dose of corticosteroids is unacceptably high. Approximately half of patients require concomitant immunosuppressive therapy. The most commonly used drugs are azathioprine, mycophenolate mofetil (1.5-3 g/day), methotrexate, chlorambucil (0.1 mg/kg/day, often 4-6 mg/day) and cyclophosphamide (1-3 mg/day). kg/day). The dosage of azathioprine (0.5-2.5 mg/kg/day) should be adjusted according to thiopurine methyltransferase levels in order to increase efficacy and reduce toxicity. The choice of a specific immunosuppressive drug depends on the side effect profile, the general condition of the patient and the experience of the physician. Low-dose methotrexate may be an effective alternative in patients with generalized PD.

The combination of nicotinamide (500–2000 mg/day) and minocycline or tetracycline has been used with some success in a small group of patients and may be a therapeutic choice for mild disease when there are clear contraindications to corticosteroids. If there is no deficiency of glucose-6-phosphate dehydrogenase, the use of dapsone may also be justified, especially in the presence of mucosal lesions. The benefit of topical immunomodulators such as tacrolimus remains to be confirmed. For treatment-resistant cases, intravenous immunoglobulin, plasmapheresis, or anti-CD20 immunotherapy (rituximab) can be used.

Double-filtered plasmapheresis may be more effective than standard plasmapheresis, possibly because it removes pathogenic cytokines. Double-filtration plasmapheresis reduces the concentration of a number of cytokines, including interleukin 8, tumor necrosis factor α, or interleukin 2.

While the optimal duration of treatment has not been established, patients with PD should be treated for approximately 12–18 months. This time includes a maintenance phase in which low doses of oral prednisolone (<10 мг/сут) или топического клобетазона пропионата (10 мг/нед.) вводятся в течение 3-6 мес. после любого признака/прекращения клинически активного заболевания. После прекращения терапии рецидив наблюдается у 10-15% пациентов.

In conclusion, in all patients with PD it is important to minimize complications of both skin lesions and systemic treatment, including osteoporosis prevention, gastroprotection and assessment of cardiovascular function and risk of infection.

Literature

1. Rook's Textbook of dermatology, eighth edition, edited by Tony Burns, Stephen Breathnach, Neil Cox and Christopher Griffiths in four volumes. Willey-Blackwell, 2010.
2. Comprehensive dermatologic drug therapy, second edition. Stephen E. Wolverton. Saunders, 2007.
3. Clinical dermatology, fifth edition. Thomas P. Habif. Mosby, 2010.
4. Dermatology, third edition, 2-volume set, edited by Jean L. Bolognia, Joseph L. Jorizzo, Julie V Schaffer, Elsevier, 2012.
5. Pediatric dermatology, fourth edition, 2-volume set, edited by Lawrence A. Schachner, Ronald C. Hansen.Mosby, 2011.